Cytotoxicity of Mouthrinses on Epithelial Cells by Micronucleus Test

Objectives To determine the cytotoxicity of three commercial mouthrinses Klorhex, Andorex and Tanflex on buccal epithelial cells using micronucleus (MN) test. Materials and Methods 28 patients with aged 16–24 undergone three mouthrinses’ application were analyzed before and after one week exposure. Physiologic saline was used for the control group. The MN incidence was scored in the buccal epithelial of each participants. The difference in pre- and post-treatment after one week incidence of MN and plaque (PI) and gingival indices (GI) was compared by non-parametric statistical tests. Results The micronuclei incidence increased in Klorhex, Tanflex and Andorex groups after exposure to mouth rinses (P<.05). But when compared with the control group, there was not any difference between Andorex and control group (P>.05). In the other study groups, MN incidence was significantly increased after 7 days treatment (P<.05). GI scores of all groups were decreased significantly (P<.05). PI scores were decreased only in the Klorhex group (P<.05). Conclusions Our primary findings support the presence of possible cytotoxic effects of the mouthrinses on gingival epithelial cells.

Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation.

Effects of a Topically Applied Bioadhesive Berry Gel on Loss of Heterozygosity Indices in Premalignant Oral Lesions

Purpose The aim of this study was to assess the effects of topical application of a 10% (w/w) freeze-dried black raspberry (FBR) gel on oral intraepithelial neoplasia (IEN) variables that included histologic diagnoses and loss of heterozygosity (LOH) indices. Microsatellite instability and/or LOH at tumor suppressor gene – associated chromosomal loci have been associated with a higher risk for oral IEN progression to oral squamous cell carcinoma. Previously, our laboratories have shown that FBRs are well tolerated and possess potent antioxidant, apoptotic, and differentiation-inducing properties. Experimental Design Each participant with IEN served as their own internal control. Before treatment, all lesions were photographed, and lesional tissue was hemisected to obtain a pretreatment diagnosis and baseline biochemical and molecular variables. Gel dosing (0.5 g applied four times daily for 6 weeks) was initiated 1 week after the initial biopsy. Genomic DNA was isolated from laser-captured basilar and suprabasilar surface epithelial cells followed by PCR amplification using primer sets that targeted known and presumed tumor suppressor gene loci associated with INK4a/ARF, p53, and FHIT. Allelic imbalance was determined by sequence analysis using normal participant tissues to establish microsatellite marker peak patterns and allele sizes. Results Confirming earlier phase I data, none of the 27 participants developed FBR gel – associated toxicities. Furthermore, our results show histologic regression in a subset of patients as well as statistically significant reduction in LOH at tumor suppressor gene – associated loci. Conclusions These preliminary data suggest that further evaluation of berry gels for oral IEN chemoprevention is warranted.

Influence of drinking patterns of carbonated beverages on dental erosion.

As a hard tissue dental disease, dental erosion has a multifactorial etiology. The majority of dental erosion that originates from extrinsic sources is the result of dietary intake, particularly acidic beverages. Several preventive means have been proposed to minimize the damage to the dentition, including a reduction in the consumption of causative beverages and the adoption of a specific method of drinking, utilizing a straw instead of a cup. This article presents two cases involving the clinical and radiographic features of erosion lesions associated with chronic and excessive intake of acidic carbonated beverages. These examples embody how drinking patterns influence the formation of erosion lesions in various anatomic locations within the dentition. The clinical and radiographic evidence presented in this report cautions against the use of nonspecific terms, such as "cup versus straw," and instead suggests implementing a more precise description of the suggested method. In view of the extensive damage inflicted by the chronic, excessive intake of carbonated beverages, preventive measures are considered to be the only effective course of management. This article offers illustrative examples of erosion lesions associated with long-term excessive intake of carbonated beverages. The influence of the drinking method--that is, a straw positioned into the labial vestibule versus a cup--on the anatomic location of the erosion lesions will be demonstrated through clinical and radiographic evidence.

Esophageal cancer: epidemiology, pathogenesis and prevention.

Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.

Bitter melon extract impairs prostate cancer cell cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anti-cancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle, and modulate cyclin D1, cyclin E and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression, and induced poly(ADP-ribose) polymerase cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high grade prostatic intraepithelial neoplasia (PIN) in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed ~51% reduction of PCNA expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell cycle progression and proliferation.

Monitoring of buccal epithelial cells by alkaline comet assay (single cell gel electrophoresis technique) in cytogenetic evaluation of chlorhexidine.

During the last few years, there has been increasing interest in buccal epithelial cells for cytogenetic evaluation of different materials. In the present study, the use of these cells and peripheral lymphocytes for cytogenetic evaluation of chlorhexidine digluconate (CHX) with comet assay (single cell gel electrophoresis, or SCGE) is reported. This technique detects DNA strand breaks in individual cells in alkaline conditions. Thirteen volunteers were requested to rinse their mouths with 0.12% CHX solution for 18 days. Buccal epithelial cells and peripheral blood lymphocytes were obtained from all participants at baseline and the end of the experimental period. One hundred cells per subject were analysed for the DNA damage. A statistical increase was observed in the damaged buccal and blood cells after the CHX application. The mean grade of damage in buccal cells was statistically different from that in blood cells. Due to minimal absorption of chlorhexidine into the tissues and low concentrations of free chlorhexidine in the oral cavity, the DNA damage produced by chlorhexidine in lymphocytes was lower than in buccal epithelial cells. As chlorhexidine does not accumulate in the body, the frequencies of DNA damage could be transient. Detected DNA damage after CHX use might be the indication of an earlier effect, before DNA repair begins, and could be reversible.

The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash.

Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite. In a cross-over designed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate (10mg/kg dissolved in water). In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load. Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite. We conclude that the acute increase in plasma nitrite seen after a nitrate load is critically dependent on nitrate reduction in the oral cavity by commensal bacteria. The removal of these bacteria with an antibacterial mouthwash will very likely attenuate the NO-dependent biological effects of dietary nitrate.

Surgical management of bisphosphonate-related osteonecrosis of the jaw in oncologic patients: a challenging problem.

AIM: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious oral complication of supportive cancer therapy and the best method of treatment is still unclear. The purpose of this article is to analyze the type of treatment and outcome in a large patient cohort with BRONJ. PATIENTS AND METHODS: A total of 142 patients suffering from BRONJ at different sites were studied. All patients had been treated with intravenous bisphosphonates for various oncological disease. A descriptive analysis of all relevant patient data was performed with particular emphasis on surgical outcome. RESULTS: The mandible was affected in 58% of the patients. All but two patients had previous invasive dental procedures. The mean duration of bisphosphonate treatment was 37.1 months. A total of 86% of the patients were treated surgically, including sequestrectomies and mandibular resections. Soft-tissue reconstruction was achieved by local closure, myofascial flap using the mylohyoid muscle, and a vascularized fasciocutaneous flap in one patient. No bony reconstruction was performed. CONCLUSION: Surgical treatment of BRONJ remains challenging. There is only limited evidence that oncologic patients with BRONJ are candidates for vascularized bone reconstruction.

Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells.

Carrageenan is a high molecular weight sulfated polygalactan used to improve the texture of commercial food products. Its use increased markedly during the last half century, although carrageenan is known to induce inflammation in rheumatological models and in intestinal models of colitis. We performed studies to determine its direct effects on human intestinal cells, including normal human intestinal epithelial cells from colonic surgeries, the normal intestinal epithelial cell line NCM460, and normal rat ileal epithelial cells. Cells were treated with high molecular weight lambda-carrageenan at a concentration of 1 mug/ml for 1-96 h. IL-8, IL-8 promoter activity, total and nuclear NF-kappaB, IkappaBalpha, phospho-IkappaBalpha, and Bcl10 were assessed by immunohistochemistry, Western blot, ELISA, and cDNA microarray. Increased Bcl10, nuclear and cytoplasmic NF-kappaB, IL-8 promoter activation, and IL-8 secretion were detected following carrageenan exposure. Knockdown of Bcl10 by siRNA markedly reduced the increase in IL-8 that followed carrageenan exposure in the NCM460 cells. These results show, for the first time, that exposure of human intestinal epithelial cells to carrageenan triggers a distinct inflammatory pathway via activation of Bcl10 with NF-kappaB activation and upregulation of IL-8 secretion. Since Bcl10 contains a caspase-recruitment domain, similar to that found in NOD2/CARD15 and associated with genetic predisposition to Crohn's disease, the study findings may represent a link between genetic and environmental etiologies of inflammatory bowel disease. Because of the high use of carrageenan as a food additive in the diet, the findings may have clinical significance.

Diet and prevention of oral cancer: strategies for clinical practice.

BACKGROUND: Oral health care professionals can play an important role in preventing oral cancer by performing oral mucosal examinations to detect pre-cancerous changes and by educating patients about oral cancer prevention strategies, including dietary approaches. CONCLUSIONS: Current evidence supports a diet high in fruits, vegetables and plant-based foods for prevention of oral cancer. Dietary supplements-including vitamins and minerals-have not been shown to be effective as substitutes for a diet high in fruits and vegetables. CLINICAL IMPLICATIONS: In addition to discussing tobacco and alcohol use with patients (and, if relevant, betel nut and gutka consumption), as well as the risk of sexual transmission of human papillo-mavirus, clinicians should provide dietary advice for the prevention of oral cancer as part of routine patient education practices.

Pro-inflammatory NF-κB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epi...

The widely used food additive carrageenan (CGN) has been shown to induce intestinal inflammation, ulcerative colitis-like symptoms, or neoplasm in the gut epithelia in animal models, which are also clinical features of human inflammatory bowel disease. In this study, the effects of CGN on pro-inflammatory transcription factors NF-κB and early growth response gene 1 product (EGR-1) were evaluated in terms of human intestinal epithelial barrier integrity. Both pro-inflammatory transcription factors were elevated by CGN and only NF-κB activation was shown to be involved in the induction of pro-inflammatory cytokine interleukin-8. Moreover, the integrity of the in vitro epithelial monolayer under the CGN insult was maintained by both activated pro-inflammatory transcription factors NF-κB and EGR-1. Suppression of NF-κB or EGR-1 aggravated barrier disruption by CGN, which was associated with the reduced gene expression of tight junction component zonula occludens 1 and its irregular localization in the epithelial monolayer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A CASE OF MULTIPLE MYELOMA PRESENTING AS A BULLOUS DERMATOSIS

Multiple myeloma is a malignant plasma cell proliferative disorder that produces a monoclonal immunoglobulin protein. The skin involvement and the development of bullous disease are rarely seen features in multiple myeloma. We present a 55-year-old man with a longstanding, large, tense bullous eruption and hypertrophic scars over his body accompanied recently with weight loss and fatique. He had no response to the previous treatments, which included oral glucocorticoids and dapsone. Histologic examination of the lesions revealed subepidermal bullae, while no immunoflourescence staining was observed. In a further detailed labarotory examination, multiple myeloma was detected. After the treatment of multiple myeloma with chemotherapy, the lesions regressed. Patients with longstanding, recurrent, unusual bullous eruption should be investigated for the development of multiple myeloma.

Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease

Background Epithelial barrier function is impaired in Crohn's disease. Aim To define the underlying cellular mechanisms with special attention to tight junctions. Methods Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn's disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction proteins were investigated immunohistochemically by confocal laser scanning microscopy and quantified in immunoblots. Epithelial apoptosis was analysed in terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling and 4′,6‐diamidino‐2‐phenylindole staining. Results Patients with active Crohn's disease showed an impaired intestinal barrier function as indicated by a distinct reduction in epithelial resistance. As distribution of conductivity was even, focal epithelial lesions (eg, microerosions) did not contribute to barrier dysfunction. Instead, freeze fracture electron microscopy analysis showed reduced and discontinuous tight junction strands. Occludin and the sealing tight junction proteins claudin 5 and claudin 8 were downregulated and redistributed off the tight junction, whereas the pore‐forming tight junctions protein claudin 2 was strongly upregulated, which constitute the molecular basis of tight junction changes. Other claudins were unchanged (claudins 1, 4 and 7) or not detectable in sigmoid colon (claudins 11, 12, 14, 15 and 16). Claudin 2 upregulation was less pronounced in active Crohn's disease compared with active ulcerative colitis and was inducible by tumour necrosis factor α. As a second source of impaired barrier function, epithelial apoptosis was distinctly increased in active Crohn's disease (mean (SD) 5.2 (0.5)% v 1.9 (0.2)% in control). By contrast, barrier function, tight junction proteins and apoptosis were unaffected in Crohn's disease in remission. Conclusion Upregulation of pore‐forming claudin 2 and downregulation and redistribution of sealing claudins 5 and 8 lead to altered tight junction structure and pronounced barrier dysfunction already in mild to moderately active Crohn's disease.

Dietary factors and oral and pharyngeal cancer risk.

We reviewed data from six cohort studies and approximately 40 case-control studies on the relation between selected aspects of diet and the risk of oral and pharyngeal cancer. Fruit and vegetables were inversely related to the risk: the pooled relative risk (RR) for high vegetable consumption was 0.65 from three cohort studies on upper aerodigestive tract cancers and 0.52 from 18 case-control studies of oral and pharyngeal cancer; corresponding RRs for high fruit consumption were 0.78 and 0.55. beta-carotene, vitamin C and selected flavonoids have been inversely related to the risk, but it is difficult to disentangle their potential effect from that of fruit and vegetables. Whole grain, but not refined grain, intake was also favorably related to oral cancer risk. The results were not consistent with reference to other foods beverages, and nutrients, but it is now possible to exclude a strong relation between these foods and oral and pharyngeal cancer risk. In western countries, selected aspects of diet may account for 20-25% of oral and pharyngeal cancer, and the population attributable risk increases to 85-95% when tobacco and alcohol consumption are also considered.

Fiber intake and the risk of oral, pharyngeal and esophageal cancer.

The relation between various types of fiber and oral, pharyngeal and esophageal cancer was investigated using data from a case-control study conducted between 1992 and 1997 in Italy. Cases were 271 hospital patients with incident, histologically confirmed oral cancer, 327 with pharyngeal cancer and 304 with esophageal cancer. Controls were 1,950 subjects admitted to the same network of hospitals as the cases for acute, nonneoplastic diseases. Cases and controls were interviewed during their hospital stay using a validated food frequency questionnaire. Odds ratios (OR) were computed after allowance for age, sex, and other potential confounding factors, including alcohol, tobacco consumption, and energy intake. The ORs for the highest vs. the lowest quintile of intake of oral, pharyngeal and esophageal cancer combined were 0.40 for total (Englyst) fiber, 0.37 for soluble fiber, 0.52 for cellulose, 0.48 for insoluble non cellulose polysaccharide, 0.33 for total insoluble fiber and 0.38 for lignin. The inverse relation were similar for vegetable fiber (OR = 0.51), fruit fiber (OR = 0.60) and grain fiber (OR = 0.56), and were somewhat stronger for oral and pharyngeal cancer than for esophageal cancer. The ORs were similar for the two sexes and strata of age, education, alcohol and tobacco consumption, and total non-alcohol energy intake. Our study indicates that fiber intake may have a protective role on oral, pharyngeal and esophageal cancer.

Salivary acetaldehyde increase due to alcohol-containing mouthwash use: a risk factor for oral cancer.

Increasing evidence suggests that acetaldehyde, the first and genotoxic metabolite of ethanol, mediates the carcinogenicity of alcoholic beverages. Ethanol is also contained in a number of ready-to-use mouthwashes typically between 5 and 27% vol. An increased risk of oral cancer has been discussed for users of such mouthwashes; however, epidemiological evidence had remained inconclusive. This study is the first to investigate acetaldehyde levels in saliva after use of alcohol-containing mouthwashes. Ready-to-use mouthwashes and mouthrinses (n = 13) were rinsed in the mouth by healthy, nonsmoking volunteers (n = 4) as intended by the manufacturers (20 ml for 30 sec). Saliva was collected at 0.5, 2, 5 and 10 min after mouthwash use and analyzed using headspace gas chromatography. The acetaldehyde content in the saliva was 41 +/- 15 microM, range 9-85 microM (0.5 min), 52 +/- 14 microM, range 11-105 microM (2 min), 32 +/- 7 microM, range 9-67 microM (5 min) and 15 +/- 7 microM, range 0-37 microM (10 min). The contents were significantly above endogenous levels and corresponding to concentrations normally found after alcoholic beverage consumption. A twice-daily use of alcohol-containing mouthwashes leads to a systemic acetaldehyde exposure of 0.26 microg/kg bodyweight/day on average, which corresponds to a lifetime cancer risk of 3E-6. The margin of exposure was calculated to be 217,604, which would be seen as a low public health concern. However, the local acetaldehyde contents in the saliva are reaching concentrations associated with DNA adduct formation and sister chromatid exchange in vitro, so that concerns for local carcinogenic effects in the oral cavity remain.

Ductal carcinoma in situ: terminology, classification, and natural history.

Ductal carcinoma in situ (DCIS) refers to breast epithelial cells that have become "cancerous" but still reside in their normal place in the ducts and lobules. In this setting, cancerous means that there is an abnormal increase in the growth of the epithelial cells, which accumulate within and greatly expand the ducts and lobules. DCIS is a nonlethal type of cancer because it stays in its normal place. However, DCIS is very important because it is the immediate precursor of invasive breast cancers, which are potentially lethal. This article provides a general overview of DCIS, including historical perspective, methods of classification, current perspective, and future goals.

Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans

There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.

Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism.

Avocados have a high content of phytochemicals with potential chemopreventive activity. Previously we reported that phytochemicals extracted from avocado meat into a chloroform partition (D003) selectively induced apoptosis in cancer but not normal, human oral epithelial cell lines. In the present study, we observed that treatment of human oral cancer cell lines containing high levels of reactive oxygen (ROS) with D003 increased ROS levels twofold to threefold and induced apoptosis. In contrast, ROS levels increased only 1.3-fold, and apoptosis was not induced in the normal cell lines containing much lower levels of basal ROS. When cellular ROS levels in the malignant cell lines were reduced by N-acetyl-l-cysteine (NAC), cells were resistant to D003 induced apoptosis. NAC also delayed the induction of apoptosis in dominant negative FADD-expressing malignant cell lines. D003 increased ROS levels via mitochondrial complex I in the electron transport chain to induce apoptosis. Normal human oral epithelial cell lines transformed with HPV16 E6 or E7 expressed higher basal levels of ROS and became sensitive to D003. These data suggest that perturbing the ROS levels in human oral cancer cell lines may be a key factor in selective apoptosis and molecular targeting for chemoprevention by phytochemicals.

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.

Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem.

Escherichia coli is probably the best-known bacterial species and one of the most frequently isolated organisms from clinical specimens. Despite this, underappreciation and misunderstandings exist among medical professionals and the lay public alike regarding E. coli as an extraintestinal pathogen. Underappreciated features include (i) the wide variety of extraintestinal infections E. coli can cause, (ii) the high incidence and associated morbidity, mortality, and costs of these diverse clinical syndromes, (iii) the pathogenic potential of different groups of E. coli strains for causing intestinal versus extraintestinal disease, and (iv) increasing antimicrobial resistance. In this era in which health news often sensationalizes uncommon infection syndromes or pathogens, the strains of E. coli that cause extraintestinal infection are an increasingly important endemic problem and underappreciated "killers". Billions of health care dollars, millions of work days, and hundreds of thousands of lives are lost each year to extraintestinal infections due to E. coli. New treatments and prevention measures will be needed for improved outcomes and a diminished disease burden.

Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial.

BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.

Postprandial plasma lipid hydroperoxides: a possible link between diet and atherosclerosis.

There is increasing evidence implicating a dietary source of plasma lipid peroxides that become elevated in the postprandial state. This phenomenon may be a contributing factor to the correlation found between postprandial hyperlipidemia and increased risk of cardiovascular disease. Using a newly developed method for measuring lipid hydroperoxides directly in plasma, a pilot study was performed which revealed that lipid hydroperoxides are indeed elevated following a fatty meal. Lipid hydroperoxides increased within 2-4 h after the meal and returned to basal levels, corresponding to the usual postprandial hyperlipidemia. A marked suppression of postprandial hydroperoxides was found when a meal was consumed with wine, suggesting that these hydroperoxides can be formed and then absorbed during the digestive process.

Oral sex, cancer and death: sexually transmitted cancers

We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor.

Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici...

Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.

Side-effect profile of cyclosporin A in patients treated for psoriasis.

This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.

Dietary behavior and knowledge of dental erosion among Chinese adults

Objectives To study the dietary behavior and knowledge about dental erosion and self-reported symptoms that can be related to dental erosion among Chinese adults in Hong Kong. Methods Chinese adults aged 25-45 years were randomly selected from a list of registered telephone numbers generated by computer. A telephone survey was administered to obtain information on demographic characteristics, dietary habits, dental visits, and knowledge of and presence of self-reported symptoms that can be related to dental erosion. Results A total of 520 participants were interviewed (response rate, 75%; sampling error, ± 4.4%) and their mean age was 37. Most respondents (79%) had ever had caries, and about two thirds (64%) attended dental check-ups at least once a year. Respondents had a mean of 5.4 meals per day and 36% had at least 6 meals per day. Fruit (89%) and lemon tea/water (41%) were the most commonly consumed acidic food and beverage. When asked if they ever noticed changes in their teeth, most respondents (92%) said they had experienced change that can be related to erosion. However, many (71%) had never heard about dental erosion and 53% mixed up dental erosion with dental caries. Conclusion Hong Kong Chinese adults have frequent intake of food and many have experienced symptoms that can be related to dental erosion. Their level of awareness of and knowledge about dental erosion is generally low, despite most of them have regular dental check-ups. Dental health education is essential to help the public understand dental erosion and its damaging effects.

Novel anti-microbial therapies for dental plaque-related diseases.

Control of dental plaque-related diseases has traditionally relied on non-specific removal of plaque by mechanical means. As our knowledge of oral disease mechanisms increases, future treatment is likely to be more targeted, for example at small groups of organisms, single species or at key virulence factors they produce. The aim of this review is to consider the current status as regards novel treatment approaches. Maintenance of oral hygiene often includes use of chemical agents; however, increasing problems of resistance to synthetic antimicrobials have encouraged the search for alternative natural products. Plants are the source of more than 25% of prescription and over-the-counter preparations, and the potential of natural agents for oral prophylaxis will therefore be considered. Targeted approaches may be directed at the black-pigmented anaerobes associated with periodontitis. Such pigments provide an opportunity for targeted phototherapy with high-intensity monochromatic light. Studies to date have demonstrated selective killing of Porphyromonas gingivalis and Prevotella intermedia in biofilms. Functional inhibition approaches, including the use of protease inhibitors, are also being explored to control periodontitis. Replacement therapy by which a resident pathogen is replaced with a non-pathogenic bacteriocin-producing variant is currently under development with respect to Streptococcus mutans and dental caries.

Light alcohol drinking and cancer: a meta-analysis.

BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Brachial artery ultrasound: a noninvasive tool in the assessment of triglyceride-rich lipoproteins.

In recent years, endothelial dysfunction has been identified as an early feature of atherosclerosis. Endothelial function can be measured noninvasively by using brachial artery ultrasound. A variety of factors associated with atherosclerosis also impair endothelial function. Some of these factors are lipoproteins such as various forms of low-density lipoproteins, postprandial chylomicron remnants, fasting triglyceride-rich particles, and free fatty acids. A high-fat diet also has an adverse effect on endothelial function. Several interventions can improve endothelial function and, at the same time, reduce cardiovascular events. Measuring endothelial function may eventually serve as a useful index to determine an individual's risk for coronary artery disease.

Chlorhexidine (CHX) in dentistry: state of the art.

Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.

Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus.

Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.

Chemoprevention in Barrett's oesophagus.

Barrett's oesophagus normally affects the distal oesophagus when metaplastic columnar lined epithelium replaces stratified squamous epithelium which predisposes to cancer development. This develops as a consequence of chronic gastroesophageal reflux (GORD). Those with Barrett's have a 40 fold increased risk of oesophageal adenocarcinoma [1]. There are is still a lack of understanding of the natural history of the cell of origin. This does hamper research into this area. We accept that there is a limitation in testing of the pathogenesis of Barrett's oesophagus due to a lack of a universally accepted animal model. The major questions surrounding Barrett's oesophagus include validity of surveillance strategies, the optimal treatment and more importantly an agent that can prevent progression to cancer without unacceptable side effects. The main chemopreventative agents that show promise are aspirin and proton pump inhibitors (PPIs). There are other agents such as green tea, berries and antioxidants and diet that have been suggested; we discuss the evidence available for these strategies. We hope for continued improvement in the clinical trial infrastructure to facilitate testing of new pharmacological and endoscopic interventions for Barrett's oesophagus. Copyright © 2011 Elsevier Ltd. All rights reserved.

Associations of dietary dark-green and deep-yellow vegetables and fruits with cervical intraepithelial neoplasia: modification by smoking.

Smoking has been positively and fruit and vegetable intake has been negatively associated with cervical cancer, the second most common cancer among women worldwide. However, a lower consumption of fruits and reduced serum carotenoids have been observed among smokers. It is not known whether the smoking effect on the risk of cervical neoplasia is modified by a low intake of fruits and vegetables. The present study examined the combined effects of tobacco smoking and diet using a validated FFQ and serum carotenoid and tocopherol levels on cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case-control study conducted in São Paulo, Brazil, between 2003 and 2005. The sample comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls. A low intake ( ≤ 39 g) of dark-green and deep-yellow vegetables and fruits without tobacco smoking had a lesser effect on CIN3 (OR 1·14; 95 % CI 0·49, 2·65) than among smokers with higher intake ( ≥ 40 g; OR 1·83; 95 % CI 0·73, 4·62) after adjusting for confounders. The OR for the joint exposure of tobacco smoking and low intake of vegetables and fruits was greater (3·86; 95 % CI 1·74, 8·57; P for trend < 0·001) compared with non-smokers with higher intake after adjusting for confounding variables and human papillomavirus status. Similar results were observed for total fruit, serum total carotene (including β-, α- and γ-carotene) and tocopherols. These findings suggest that the effect of nutritional factors on CIN3 is modified by smoking.

Diet, nutrition and the prevention of dental diseases.

Oral health is related to diet in many ways, for example, nutritional influences on craniofacial development, oral cancer and oral infectious diseases. Dental diseases impact considerably on self-esteem and quality of life and are expensive to treat. The objective of this paper is to review the evidence for an association between nutrition, diet and dental diseases and to present dietary recommendations for their prevention. Nutrition affects the teeth during development and malnutrition may exacerbate periodontal and oral infectious diseases. However, the most significant effect of nutrition on teeth is the local action of diet in the mouth on the development of dental caries and enamel erosion. Dental erosion is increasing and is associated with dietary acids, a major source of which is soft drinks. Despite improved trends in levels of dental caries in developed countries, dental caries remains prevalent and is increasing in some developing countries undergoing nutrition transition. There is convincing evidence, collectively from human intervention studies, epidemiological studies, animal studies and experimental studies, for an association between the amount and frequency of free sugars intake and dental caries. Although other fermentable carbohydrates may not be totally blameless, epidemiological studies show that consumption of starchy staple foods and fresh fruit are associated with low levels of dental caries. Fluoride reduces caries risk but has not eliminated dental caries and many countries do not have adequate exposure to fluoride. It is important that countries with a low intake of free sugars do not increase intake, as the available evidence shows that when free sugars consumption is <15-20 kg/yr ( approximately 6-10% energy intake), dental caries is low. For countries with high consumption levels it is recommended that national health authorities and decision-makers formulate country-specific and community-specific goals for reducing the amount of free sugars aiming towards the recommended maximum of no more than 10% of energy intake. In addition, the frequency of consumption of foods containing free sugars should be limited to a maximum of 4 times per day. It is the responsibility of national authorities to ensure implementation of feasible fluoride programmes for their country.

Rheumatic fever: from sore throat to autoimmune heart lesions.

Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients. Copyright 2004 S. Karger AG, Basel

Mortality from malignant diseases-update of the Baltimore union poultry cohort.

We previously studied mortality up to 1989 in 2,639 members of a local union who had ever worked in poultry slaughtering and processing plants, because they were exposed to oncogenic viruses present in poultry. In this report, cancer mortality was updated to the year 2003 for 2,580 of the 2,639 subjects who worked exclusively in poultry plants. Mortality in poultry workers was compared with that in the US general population through the estimation of proportional mortality and standardized mortality ratios separately for each race/sex group and for the whole cohort. Compared to the US general population, an excess of cancers of the buccal and nasal cavities and pharynx (base of the tongue, palate and other unspecified mouth, tonsil and oropharynx, nasal cavity/middle ear/accessory sinus), esophagus, recto-sigmoid/rectum/anus, liver and intrabiliary system, myelofibrosis, lymphoid leukemia and multiple myeloma was observed in particular subgroups or in the entire poultry cohort. We hypothesize that oncogenic viruses present in poultry, and exposure to fumes, are candidates for an etiologic role to explain the excess occurrence of at least some of these cancers in the poultry workers. Larger studies which can control for confounding factors are urgently needed to determine the significance of these findings.

Differences in microbiological composition of saliva and dental plaque in subjects with different drinking habits.

Several foods have been shown to contain natural components (especially polyphenols) which display anti-adhesive properties against Streptococcus mutans, the aetiological agent responsible for dental crown caries, as well as inhibition of glucosyltransferases, which are the S. mutans enzymes involved in the synthesis of an adherent, water-insoluble glucan from sucrose. Other studies have demonstrated an in vitro action on oral plaque biofilm formation and desorption. This study evaluated whether the activity displayed in vitro by food compounds could affect the microbiological composition of saliva and dental plaque of subjects with a diet rich in these foods, comparing the results with those obtained from subjects with a different diet. The foods considered were: coffee, barley coffee, tea and wine. A total of 93 subjects were recruited into the study. Six samples of both plaque and saliva were collected from each subject at roughly one-monthly intervals. Total bacteria, total streptococci, S. mutans and lactobacilli counts were determined by culture in both saliva and dental plaque. The highest bacterial titres were recorded for the control population, while each drinking habit subgroup showed counts roughly one log lower than the controls. These differences in bacterial counts proved statistically significant (P<0.05). As far as dental plaque was concerned, while total counts did not significantly vary per mg of plaque in the subjects belonging to the different drinking habit subgroups, a significant decrease (P<0.05) was observed in those subjects drinking coffee, tea, barley coffee and wine when mutans streptococci and lactobacilli were evaluated. In several cases a more than one log decrease was observed. Plaque indices were also determined, and a significant (P<0.05) reduction in values was recorded in the subjects belonging the specific drinking habit subgroups compared to the control group. This study indicates that there is a correlation between consumption of specific foods and oral health in terms of reduced plaque deposition and lower counts of odontopathogens.

Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro.

Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1-10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1-8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6-8 d of CGN exposure, the percentage of cells reentering G0-G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology.

Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection.

Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for cervical neoplasia, although infection alone is insufficient to produce disease. Cofactors such as nutritional factors may be necessary for viral progression to neoplasia. Results from previous studies have suggested that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical neoplasia. This study evaluated the role of vitamin A and carotenoids on HPV persistence comparing women with intermittent and persistent infections. As determined by the Hybrid Capture II system, oncogenic HPV infections were assessed at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the risk of persistent HPV infection associated with each tertile of dietary and circulating micronutrients. Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01). These data suggest that vegetable consumption and circulating cis-lycopene may be protective against HPV persistence.

Do endodontic compounds induce genetic damage? A comprehensive review.

Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.

Cellulite: nature and aetiopathogenesis.

Only a limited number of studies on cellulite have been published in the international literature and many of them reach somewhat antithetical conclusions. Consequently, it is not yet possible to reconcile the extreme differences of opinion which have lingered on for years concerning the nature of this disorder, as well as its origin and even the most basic aspects of its histopathological classification. It does not even have a recognized name: in fact, the term 'cellulitis' is used in scientific English to indicate a spreading gangrenous infection of the subcutaneous cellular tissue. The other terms used from time to time [panniculitis, lipodystrophy, edematofibrosclerotic panniculitis (EFP), liposclerosis, lipoedema, etc.] have quite different morphological and pathogenetic connotations in general. Over the last few decades, three major conflicting theories have emerged in relation to the ethiopathogenesis of cellulite. These indicate, respectively, the following causes: 1. Oedema caused by excessive hydrophilia of the intercellular matrix. 2. A homeostatic alteration on a regional microcirculatory level; this pathogenetic theory is summarized in a synthetic and self-explanatory denomination: EFP. 3. A peculiar anatomical conformation of the subcutaneous tissue of women, different from male morphology. These theories must all now be updated in the light of recent advances on the sophisticated and composite physiopathology of the adipose organ - which acts not only as a control device which regulates the systematic equilibrium of energy and modulates the food intake and the metabolism of other tissue substrate through a multiple glandular secretion of hormones and parahormones.

Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China.

OBJECTIVE: To evaluate the prevalence of benign prostatic hyperplasia (BPH) and prostatic cancer (CaP) in the mainland of China. METHODS: The incidence of BPH and CaP in urological hospital was investigated in 1997 in 26 provinces and 4 metropolises scattered over the mainland of China. The change of hospital incidences of BPH and CaP in the Institute of Urology, Beijing Medical University from 1951 to 1997 was also reviewed. RESULTS: The incidence of BPH and CaP in 1997 in 187 hospitals scattered over the mainland of China was 16.1% (15,459/95,749) and 1.5% (1389/95,749), respectively. The incidence of BPH and CaP in the Institute of Urology, Beijing University from 1951 to 1960 was 7.6% and 0.6%, respectively, while it was 18.5% and 3.4% from 1991 to 1997. CONCLUSION: The hospital incidence of BPH and CaP is rising rapidly in China, but CaP is still not a common disease in China.

Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin

Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells. HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including JNK, ERK, and p38. The synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was not seen in normal cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.

Migrating fish bone presenting as acute onset of neck lump.

We encountered a 62-year-old woman with a progressively worsening sore throat and a sharp lump located in her left upper neck, which appeared several hours before admission. After questioning, she underwent rigid esophagoscopy at a local hospital for suspected fish bone impaction but this gave a negative result. Unusual signs caused us to arrange a computed tomography scan, which showed that a foreign body had penetrated the left sternocleidomastoid muscle to the subcutaneous layer, with extensive emphysema in the neck. We extracted the foreign body with a 1-cm horizontal incision of the neck under general anesthesia. The patient returned to a normal diet and was discharged on day 5 of hospitalization without further morbidity. This is another rare case of a migrating foreign body presenting as a neck lump. On reviewing the literature, most cases involving subcutaneously migrating fish bones show development of a neck lump several weeks to months after ingestion, with relatively stable conditions. However, our case showed a neck lump 1 day after ingestion with acute toxic symptoms.

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish (‘fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.

Brushing abrasion of softened and remineralised dentin: an in situ study.

The aim of the present in situ study was to evaluate the effect of different periods of intra-oral remineralisation on the susceptibility of softened dentin to toothbrushing abrasion. Groups of 6 human dentin specimens (A-F) were recessed in the buccal aspects of intra-oral appliances which were worn for 21 days by 11 volunteers. The samples were demineralised twice a day extra-orally in the acidic beverage Sprite Light (pH 2.9) for 90 s. Subsequently, the dentin specimens were brushed at different times. Specimen A was brushed immediately after demineralisation. Specimens B-E were brushed after the intra-oral appliances had been worn for various periods in the mouth: specimen B for 10 min, C for 20 min, D for 30 min and E for 60 min. Specimen F was not brushed (control). After 21 days, dentin wear was measured with a profilometer. The following values (means +/- standard deviation) were recorded (microm): A, 23.6 +/- 16.7; B, 37.9 +/- 29.7; C, 31.8 +/- 26.5; D, 18.5 +/- 10.5; E, 15.3 +/- 11.6; F, 12.6 +/- 6.7. There was a statistically significantly increased dentin loss for groups A, B and C as compared to the controls (U test: p < 0.05). However, after intra-oral periods of 30 and 60 min, wear was not significantly higher than in unbrushed controls. It is concluded that for protection of dentin surfaces at least 30 min should elapse before toothbrushing after an erosive attack. Copyright 2004 S. Karger AG, Basel

Effects of intestinal microflora and the environment on the development of asthma and allergy.

The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.

Obesity as a Major Risk Factor for Cancer

The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

A possible role for the alpha 1-->3 galactosyl epitope and the natural anti-gal antibody in oncogenesis.

Glycoconjugates and their antibodies are vital components of host-tumor interaction. This review concentrates on the oncological implications of research concerning the alpha gal triad; the alpha 1-->3 galactosyl epitope (alpha Gal), the enzyme responsible for its construction, alpha 1,3 galactosyl transferase (alpha 1-3GT), and its associated antibody: anti-gal. Alpha gal epitopes, previously assumed to be absent from human tissue, have been demonstrated on several human cancer cell lines, senescent red blood cells, and Graves' disease thyrocytes. Alpha-gal presence on neoplastic lines is correlated with increased metastatic formation in animal models. The mechanisms of human response to these neoantigens are complex, as natural anti-gal antibodies exist in high titers in normal sera, thus predicting immunological recognition of cells expressing alpha gal epitopes. Hypotheses vary regarding the pathogenic contributions of metastasis-associated phenomena such as de novo expression of alpha gal and its unmasking by desialylation. The means by which alpha gal is sporadically expressed in human tissue remain unknown, as the galactosyl transferase which produces this epitope in constitutively expressive animals has undergone significant mutation at the genomic level in humans. Pathological re-expression is presumed to require permissive changes at a cellular level. Detailing these alterations is a prerequisite to the comprehension of the metastatic phenotype. In this context, the possibility of therapeutic strategies affecting alpha gal expression are also discussed.

Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.

Radioprotective effects of Zingiber officinale Roscoe (ginger): past, present and future.

Radiation is an important modality in treating people with cancer especially when surgical intervention is impracticable or might debilitate the patient. However, effective use of ionizing radiation is compromised by the side effects that result from radiation-induced damage to normal tissue. The use of radioprotective compounds, which can selectively protect normal tissues against radiation injury is of immense use because in addition to association with protecting the normal tissue, it will also permits use of higher doses of radiation to obtain better cancer control and possible cure. However, till date no ideal radioprotectors are available as most synthetic compounds are toxic at their optimal concentrations. Plants commonly used as dietary and or therapeutic agents have recently been the focus of attention since in most cases they are non-toxic and are easily accepted for human use. Ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has widely been used as both culinary and medicinal agent. Preclinical studies carried out in the last decade has shown that ginger and its phytochemicals dehydrozingerone, zingerone possess radioprotective effects in laboratory animals and in cultured cells in vitro. The hydroalcoholic extract of ginger rhizome when administered either through intraperitoneal or oral route was effective in protecting against gamma radiation-induced sickness and mortality. The phytochemicals dehydrogingerone and zingerone present in ginger are also shown to protect mice against radiation-induced sickness and mortality. Mechanistic studies have indicated that the free radical scavenging, antioxidant affects, anti-inflammatory and anti-clastogenic effects may contribute towards the observed protection. Additionally, studies with tumor bearing mice have also shown that zingerone selectively protects the normal tissues against the tumoricidal effects of radiation. This review for the first time summarizes the results related to the radioprotective properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a radioprotective agent.

Epithelial barrier biology: good fences make good neighbours

The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.

Dietary clues to the pathogenesis of Crohn's disease.

Crohn's disease is a complex inherited disorder of unknown pathogenesis with environmental, genetic and microbial factors involved in the development of the disease. A remarkable feature of this disease in childhood is the effective response to exclusive enteral nutrition (EEN) therapy and the need for complete exclusion of normal diet required for success (principle of exclusivity). EEN or dietary interventions might act through removal of dietary components, which affect microbial composition, decrease a proinflammatory response and promote restitution of the epithelial barrier, likewise allowing termination of this vicious disease-forming cycle before a critical threshold is reached. Multiple traditional and nontraditional dietary components may affect the microbiome, mucous layer, intestinal permeability, or adherence and translocation of pathobionts. We review the epidemiological data, as well as data from animal models and cell lines, and propose a model for pathogenesis we have termed the 'bacterial penetration cycle', whereby dietary components such as animal fat, high sugar intake and gliadin, and consumption of emulsifiers, maltodextrin as well as low-fiber diets may be able to cause a localized acquired bacterial clearance defect, leading to bacterial adhesion and penetration, and subsequently inflammation in the gut. © 2014 S. Karger AG, Basel.

Nutritional intervention in patients with periodontal disease: clinical, immunological and microbiological variables during 12 months.

The role of nutrition in onset, progression and treatment of periodontitis has not been thoroughly evaluated. In the present prospective clinical study, we investigated the influence of a nutritional intervention on changes in clinical, microbiological and immunological periodontal variables during a period of 12 months in patients with the metabolic syndrome and chronic periodontitis. Twenty female subjects with the metabolic syndrome and mild to moderate chronic periodontitis participated in a guided nutritional intervention programme. Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after intervention. Clinical measurements included probing depth, Löe and Silness gingival index and Quigley-Hein plaque index. In gingival crevicular fluid, periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of granulocyte elastase were determined. In stimulated saliva, antioxidative and oxidative variables were measured. After 12 months the following significant changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm; P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P < 0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P < 0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival crevicular fluid. Bacterial counts in gingival crevicular fluid as well as oxidative and antioxidative variables in saliva showed no significant changes. Only salivary catalase showed a tendency to lower values. These findings indicate that in patients with the metabolic syndrome wholesome nutrition might reduce inflammatory variables of periodontal disease and promote periodontal health.

CT evaluation of cervical cancer: spectrum of disease.

Invasive cervical cancer is the third most common gynecologic malignancy. The prognosis is based on the stage, size, and histologic grade of the primary tumor and the status of the lymph nodes. Assessment of the stage of disease is important in determining whether the patient may benefit from surgery or will receive radiation therapy. The official clinical staging system of the International Federation of Gynecology and Obstetrics has led to errors of 65%-90% in stage III and IV disease; the result has been unofficial extended staging with cross-sectional imaging modalities such as computed tomography (CT). CT is useful in staging advanced disease and in monitoring patients for recurrence. The primary tumor is heterogeneous and hypoattenuating relative to normal stroma on contrast material-enhanced scans. Obliteration of the periureteral fat plane and a soft-tissue mass are the most reliable signs of parametrial extension. Less than 3 mm separation of the tumor from the pelvic muscles and vascular encasement are signs of pelvic side wall invasion. Lymphatic spread is along the external and internal iliac nodal chains and the presacral route to the paraaortic nodes. Distant metastases are seen with primary or recurrent disease and can involve the liver, lung, and bone.

Curcumin: the story so far.

Curcumin is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. Apart from curcumin's potent antioxidant capacity at neutral and acidic pH, its mechanisms of action include inhibition of several cell signalling pathways at multiple levels, effects on cellular enzymes such as cyclooxygenase and glutathione S-transferases, immuno-modulation and effects on angiogenesis and cell-cell adhesion. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. Although curcumin's low systemic bioavailability following oral dosing may limit access of sufficient concentrations for pharmacological effect in certain tissues, the attainment of biologically active levels in the gastrointestinal tract has been demonstrated in animals and humans. Sufficient data currently exist to advocate phase II clinical evaluation of oral curcumin in patients with invasive malignancy or pre-invasive lesions of the gastrointestinal tract, particularly the colon and rectum.

Atherogenesis: a postprandial phenomenon.

The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.

Inhibition of the growth of premalignant and malignant human oral cell lines by extracts and components of black raspberries.

Black raspberries are a rich natural source of chemopreventive phytochemicals. Recent studies have shown that freeze-dried black raspberries inhibit the development of oral, esophageal, and colon cancer in rodents, and extracts of black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster embryo fibroblasts. However, the molecular mechanisms and the active components responsible for black raspberry chemoprevention are unclear. In this study, we found that 2 major chemopreventive components of black raspberries, ferulic acid and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica column chromatography of the organic extract of freeze-dried black raspberries inhibit the growth of premalignant and malignant but not normal human oral epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and ellagic acid inhibited the growth of normal as well as premalignant and malignant human oral cell lines. We investigated the molecular mechanisms by which ferulic acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth of premalignant and malignant oral cells using flow cytometry and Western blotting of cell cycle regulatory proteins. There was no discernable change in the cell cycle distribution following treatment of cells with the RO-ET fraction. Premalignant and malignant cells redistributed to the G2/M phase of the cell cycle following incubation with ferulic acid. beta-sitosterol treated premalignant and malignant cells accumulated in the G0/G1 and G2/M phases, respectively. The RO-ET fraction reduced the levels of cyclin A and cell division cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1 in the malignant cell line. Ferulic acid treatment led to increased levels of cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2 while increasing p21waf1/cip1 in both the premalignant and malignant cell lines. These results show for the first time that the growth inhibitory effects of black raspberries on premalignant and malignant human oral cells may reside in specific components that target aberrant signaling pathways regulating cell cycle progression.

The Vascular Endothelium and Human Diseases

Alterations of endothelial cells and the vasculature play a central role in the pathogenesis of a broad spectrum of the most dreadful of human diseases, as endothelial cells have the key function of participating in the maintenance of patent and functional capillaries. The endothelium is directly involved in peripheral vascular disease, stroke, heart disease, diabetes, insulin resistance, chronic kidney failure, tumor growth, metastasis, venous thrombosis, and severe viral infectious diseases. Dysfunction of the vascular endothelium is thus a hallmark of human diseases. In this review the main endothelial abnormalities found in various human diseases such as cancer, diabetes mellitus, atherosclerosis, and viral infections are addressed.

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

Dental X-rays and Risk of Meningioma

Context Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, the most frequently reported primary brain tumor in the United States. Objective To examine the association between dental x-rays, the most common artificial source of ionizing radiation, and risk of intra-cranial meningioma. Design and Setting Population-based case-control study design. Participants The study includes 1433 intra-cranial meningioma cases aged 29-79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Houston, Texas counties between May 1, 2006 and April 28, 2011 and 1350 controls that were frequency-matched on age, sex and geography. Main Outcome Measure The association of intra-cranial meningioma diagnosis with self-report of bitewing, full-mouth, and panorex dental x-rays. Results Over a lifetime, cases were more than twice (Odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.4-2.9) as likely as controls to report having ever had a bitewing exam. Regardless of the age at which the films were received, persons who reported receiving bitewing films on a yearly or greater frequency had an elevated risk with odds ratios of 1.4 (95%CI: 1.0-1.8), 1.6 (95%CI: 1.2-2.0), 1.9 (95%CI: 1.4-2.6), and 1.5 (95%CI: 1.1-2.0) for ages <10, 10-19, 20-49, and 50+ years, respectively. Increased risk of meningioma was also associated with panorex films taken at a young age or on a yearly or greater frequency with persons reporting receiving such films under the age of 10 years at 4.9 times (95%CI: 1.8-13.2) increased risk of meningioma. No association was appreciated with location of tumor above or below the tentorium. Conclusion Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with increased risk of intra-cranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.

Carcinogenesis in the GI tract: from morphology to genetics and back again.

The genetic alterations in colorectal cancer progression are determined by one of two separate and distinct underlying pathways of genomic instability. The first pathway, chromosomal instability, is characterized by allelic losses and aneuploidy. The second pathway, microsatellite instability, is characterized by an abundance of subtle DNA mutations and diploidy. Although the genes causing chromosomal instability remain unknown, microsatellite instability is caused by inactivation of a DNA mismatch repair gene (predominantly MLH1 or MSH2). Microsatellite instability is present in 15% of colorectal cancers, and is diagnosed by analysis of tumor DNA from paraffin blocks and by demonstration of loss of mismatch repair protein expression in cancers. In addition to the unique profile of genetic alterations, colorectal cancers with microsatellite instability have distinct pathologic features and improved survival. Finally, cancers from most patients with hereditary non-polyposis colorectal cancer (or Lynch syndrome) have microsatellite instability due to germline mutations in the DNA mismatch repair genes. Identification of the microsatellite instability pathway has enormous implications for the clinical investigation and management of colorectal cancer patients.

Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil.

OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.

Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium

Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (≥30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (≥50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (≥40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

Is oral sex really a dangerous carcinogen? Let's take a closer look.

INTRODUCTION: Questions have recently arisen in the popular press about the association between specific sexual behaviors, namely, fellatio and cunnilingus, with head and neck cancers. Although there has been an overall decline in the incidence of head and neck cancers over the past 25 years, there has been a shift in the distribution of these cancers toward a particular type known as oral squamous cell carcinomas (OSCCs), and a younger demographic. These particular cancers, OSCCs, have been shown to be associated with the human papillomavirus (HPV). Several researchers have suggested that this shift in the epidemiology of head and neck cancers might be attributable to changing sexual practices. While this speculation has caught on in the popular press, there are several interesting contradictions in the existing evidence that suggest this conclusion might be premature and overreached. AIM: The intent of this article is to help clarify the issues so that sexual medicine professionals can give accurate and up-to-date information to their patients. MAIN OUTCOME MEASURES: This is a review article; no outcome data are reported. This is a review article; no measures were collected. METHODS: Pubmed search on HPV, oral sex, oral cancers, and OSCCs. RESULTS: One hundred ninety-six articles on HPV were found; 63 articles on oral sex, 55 on oral cancer, and 5 articles on OSCCs were identified as relevant. CONCLUSIONS: HPV infections occur commonly and are usually cleared within 18 months, thus HPV infection should not be a cause for concern among monogamous couples with a rich and varied sex life as long as the sexual system remains closed and other immune compromising factors are not present. HPV becomes a concern in the context of immune system compromise and infection persistence. Factors contributing to immune system compromise, HPV persistence, and oncogenesis are reviewed. © 2012 International Society for Sexual Medicine.

Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation.

Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque. Copyright Blackwell Munksgaard, 2004.

Disseminated chlorellosis in a dog.

An adult dog with ataxia and a lingual mass, previously diagnosed as protothecosis, was euthanized. At the postmortem examination, the lingual mass, regions of the lungs and hilar lymph nodes, liver, mesenteric and sublumbar lymph nodes, and spinal meninges had pronounced green discoloration. Histologically, pyogranulomatous inflammation and algal organisms were found in the tongue, spinal meninges, hilar and mesenteric lymph nodes, liver, and lung. The algae had cell walls positive for periodic acid-Schiff and cytoplasmic granules. Ultrastructurally, the algae had a well-defined cell wall, stacks of grana and thylakoid membrane, and dense bodies, typical of starch granules. The organisms were identified as Chlorella, a green alga, based on the results of histochemistical and electron microscopic examination. To the author's knowledge this is the first report of disseminated Chlorella infection and the first report in a companion animal.

Dietary Phosphorus Acutely Impairs Endothelial Function

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa. MATERIALS AND METHODS: Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay. RESULTS: Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB. CONCLUSION: Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.

Melanomas in renal transplant recipients.

BACKGROUND: It is well documented that renal transplant recipients are at increased risk of developing skin cancers, in particular squamous cell carcinomas. Less extensively reviewed in the literature is the increased incidence of malignant melanoma. We have reviewed 10 patients in the Oxford renal transplant population who developed 12 melanomas following transplantation. OBJECTIVES: To determine the incidence and characteristics of melanoma in renal transplant recipients. METHODS: We reviewed the case notes and pathology of all patients who developed melanoma within the Oxford Renal Transplant Unit. The clinical details were recorded including date of transplant, immunosuppressive therapy, interval between transplant and melanoma, site of occurrence, history of sun exposure, type of clinician diagnosing the melanoma, history of other skin malignancies and outcome. From the histopathology we documented various prognostic factors. RESULTS: Ten patients developed 12 melanomas (one patient had three melanomas) from a population of 1874 transplanted patients. The total number of transplant years was 11 942.2. The incidence of melanoma in our population was 12 per 11 942.2 transplant years, which is approximately 8 times greater than the standardized rate for this region. We found that the mean interval between transplant and melanoma was approximately 11 years (median 8.5). A dermatologist was the diagnosing clinician in at least 67% of cases. Melanomas occurred on the trunk in the majority of cases (58%), followed by the upper limb (25%). All patients apart from one are alive with no recurrence of their melanoma. One patient died as a result of metastatic melanoma. The mean follow-up period following melanoma was 3.7 years. In all patients apart from the patient who died, the melanomas were < 1 mm Breslow thickness. That patient's melanoma was 4.5 mm thick. There was no precursor naevus in eight of the 12 melanomas. In two there was a precursor dysplastic naevus. In the cases in vertical growth phase the tumour-infiltrating lymphocyte response was absent in four cases and nonbrisk in one patient. CONCLUSIONS: In the Oxford transplant population studied melanomas occurred at approximately 8 times the rate in the general population. This is the highest rate reported in the literature. The patients had a better outcome than reported previously. This may be due to detection at a relatively early stage. Renal transplant recipients attend dedicated dermatology clinics in Oxford, which may have contributed to the early diagnosis and good outcome.

Oral implications of the vegan diet: observational study.

AIM: The aim of this study was to investigate oral changes in subjects who have assumed a vegan diet for a long time (at least 18 months), that is to say, a diet completely lacking in meat and animal derivatives. METHODS: A sample of 15 subjects was analyzed, all from northern Italy and aged 24 to 60 year, composed of 11 men and 4 women who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years. In parallel with the study sample, a control group (15 subjects) with the same criteria of age, sex, and place of origin all following an omnivorous diet was chosen. The sample answered a questionnaire that investigated their eating habits, the frequency with which they eat meals, the main foodstuffs assumed, oral hygiene habits, and any painful symptomatology of the teeth or more general problems in the oral cavity. The sample was then subject to objective examination in which the saliva pH was measured and the teeth were checked for demineralization of the enamel, white spots, and caries (using KaVo DIAGNOdent) with particular attention being paid to the localization of these lesions, and lastly, sounding was carried out to detect any osseous defects and periodontal pockets. RESULTS: The study revealed greater incidence of demineralization and white spots in the vegan subjects compared to the omnivorous ones localized at the neck of the teeth and on the vestibular surfaces of dental elements (with the exception of the lower anterior group). The saliva pH, more acid in the omnivorous patients, ranged between four and six. Changes in oral conditions in both groups of subjects were observed. CONCLUSION: In order to research into the cause-effect relationship of the vegan diet on the oral cavity effectively, the sample needs to be studied for a longer period of time and the results re-evaluated.

A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells.

OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.

Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms.

PURPOSE OF REVIEW: Although age, genetics, and sex steroid hormones play prominent roles in the cause of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS), recent epidemiological studies suggest that modifiable lifestyle factors also contribute substantially to the pathogenesis of these conditions. RECENT FINDINGS: Lifestyle and metabolic factors associated with significantly increased risks of benign prostatic hyperplasia and lower urinary tract symptoms include obesity, diabetes, and meat and fat consumption. Factors associated with decreased risks include physical activity, moderate alcohol intake, and vegetable consumption. Factors for which no clear risk patterns have emerged include lipids and smoking. Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of benign prostatic hyperplasia and lower urinary tract symptoms have yet to be performed. SUMMARY: Lifestyle factors present a novel opportunity for the prevention and treatment of benign prostatic hyperplasia and lower urinary tract symptoms. Although clinical trials of lifestyle modifications have not yet been undertaken, promotion of healthy lifestyle alternatives within the context of standard benign prostatic hyperplasia and lower urinary tract symptoms treatment algorithms is potentially beneficial.

Saturated fatty acid metabolism is key link between cell division, cancer, and senescence in cellular and whole organism aging

Cellular senescence is an in vivo and in vitro phenomenon, accompanied by physiological changes including cessation of division and disturbances of organelle structure and function. Review of the literature was undertaken to determine whether there is evidence that whole organism aging and cell senescence share a common initiation pathway. In vivo aged cells of different lineages, including aged T lymphocytes, show high expression of the INK4A-p16 gene. In cell culture when telomeres are shortened past a key length or state, the Arf/Ink gene system (p16/p14 humans, p16/p19 mice) switches on and activates p53, which suppresses further cell division. The p53 gene is a key tumor suppressor and its deletion or mutation allows cancerous growth. The switching on of p53 also causes changes in fatty acid metabolism, especially down-regulation of both fatty acid synthase and stearoyl-CoA (delta-9) desaturase. The co-suppression of these genes together with enhanced uptake of extracellular fatty acids, leads to raised levels of cellular palmitate and induction of either apoptosis or senescence. In senescent cells, the fatty acid composition of the cellular membranes alters and leads to changes in both structure and function of organelles, especially mitochondria. Animal models of accelerated aging exhibit repression of stearoyl-CoA desaturase activity while anti-aging calorie restriction stimulates the same enzyme system. It is concluded that aging in cells and whole organisms share a common initiation pathway and that cellular senescence is protective against cancer. Healthy longevity is likely to be most enhanced by factors that actively suppress excessive cell division.

Methionine as methyl-group donor in the synthesis of Mycobacterium avium envelope lipids, and its inhibition by DL-ethionine, D-norleucine and DL-n...

The radioactivity from 3H-methyl methionine was rapidly incorporated into the surface lipids of Mycobacterium avium. The transmethylation reaction was efficiently inhibited by DL-ethionine, D-norleucine and DL-norleucine. The structure of the outerlayer of the M. avium envelope was profoundly altered in the bacteria treated with DL-norleucine.

Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells.

Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.

Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients.

OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.

Review of harmful gastrointestinal effects of carrageenan in animal experiments.

In this article I review the association between exposure to carrageenan and the occurrence of colonic ulcerations and gastrointestinal neoplasms in animal models. Although the International Agency for Research on Cancer in 1982 identified sufficient evidence for the carcinogenicity of degraded carrageenan in animals to regard it as posing a carcinogenic risk to humans, carrageenan is still used widely as a thickener, stabilizer, and texturizer in a variety of processed foods prevalent in the Western diet. I reviewed experimental data pertaining to carrageenan's effects with particular attention to the occurrence of ulcerations and neoplasms in association with exposure to carrageenan. In addition, I reviewed from established sources mechanisms for production of degraded carrageenan from undegraded or native carrageenan and data with regard to carrageenan intake. Review of these data demonstrated that exposure to undegraded as well as to degraded carrageenan was associated with the occurrence of intestinal ulcerations and neoplasms. This association may be attributed to contamination of undegraded carrageenan by components of low molecular weight, spontaneous metabolism of undegraded carrageenan by acid hydrolysis under conditions of normal digestion, or the interactions with intestinal bacteria. Although in 1972, the U.S. Food and Drug Administration considered restricting dietary carrageenan to an average molecular weight > 100,000, this resolution did not prevail, and no subsequent regulation has restricted use. Because of the acknowledged carcinogenic properties of degraded carrageenan in animal models and the cancer-promoting effects of undegraded carrageenan in experimental models, the widespread use of carrageenan in the Western diet should be reconsidered.

The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomav...

The definition of cervical neoplasia as a sexually determined disease caused by some types of human papillomavirus has been widely accepted. Recent epidemiologic studies, however, have failed to identify a correlation between sexual activity and human papillomavirus infection. Moreover, sexual activity has also been shown to be independent of human papillomavirus infection in increasing cervical cancer risk. These incoherences are analyzed with respect to etiologic models for cervical neoplasia and by considering the role of misclassification of human papillomavirus infection in interpreting the relations assumed under these models. Even small levels of misclassification can considerably distort (1) the presumed prevalence of viral infection, (2) the association between sexual activity and human papillomavirus infection, and (3) the ability to control the relation between sexual activity and cancer by human papillomavirus infection. In field surveys, the presumed rates of human papillomavirus infection based on a DNA assay such as the filter in situ hybridization may be a gross overestimation of the true viral prevalence. Use of moderately misclassified human papillomavirus infection test results for effect estimation and covariate adjustment in data analysis may seriously distort the underlying relations. Consequently, considering these conditions, the apparent incoherence of recent epidemiologic findings should not be construed as evidence against the role of human papillomavirus in the etiology of cervical cancer or the validity of the sexually transmitted disease model.

Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study.

OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.

Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation, no imaging modality is recommended as standard of care for screening or diagnosis. Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings. Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes, increased hepatorenal echogenicity, vascular blurring of portal or hepatic vein and subcutaneous tissue thickness. These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD. While sonographic findings such as attenuation of image, diffuse echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged liver filling of the entire field could be identified by clinicians from bedside ultrasound. The accessibility, ease of use, and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis. When used with appropriate clinical risk factors and steatosis involves greater than 33% of the liver, ultrasound can reliably diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The purpose of this review is to examine the diagnostic accuracy, utility, and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.

Cytotoxic response of breast cancer cell lines, MCF 7 and T 47 D to triphala and its modification by antioxidants.

The cytotoxic effects of Triphala (TPL), an Indian Ayurvedic formulation with known anti-cancer properties, has been investigated on two human breast cancer cell lines differing in their p53 status. In vitro studies showed that MCF 7 with wild type p53 was more sensitive to TPL than T 47 D, which is p53 negative. TPL induced loss of cell viability was determined by MTT assay. After 72h incubation, the IC 50 values for MCF 7 was found to be approximately 8microg/ml and that for T 47 D was approximately 26microg/ml. Moreover, TPL inhibited the clonogenic growth of MCF 7 cells, which was significantly recovered by pifithrin-alpha, the p53 inhibitor. However, pifithrin-alpha, did not modify TPL induced cytotoxicity in T 47 D cells. Exogenous addition of antioxidants, glutathione (GSH) and N-Acetyl-Cysteine (NAC) inhibited the anti-proliferative ability of TPL in both MCF 7 and T47 D. Annexin-V and propidium iodide double staining of cells treated with TPL for 2h revealed that TPL induced significant apoptosis in both the cell lines in a dose dependant manner but magnitude of apoptosis was significantly higher in MCF 7 than in T 47-D cells. TPL was also found to induce dose and time dependent increase in intracellular reactive oxygen species in both the cell lines. Present results have demonstrated that MCF 7 and T 47 D cells exhibited differential sensitivity to TPL, which seems to be dependant on their p53 status. Inhibition of anti-proliferative ability of TPL by antioxidants suggests a role for TPL induced ROS in the induction of apoptosis. It is concluded that p53 status of cancer cells formed an important factor in predicting the response of cancer cells to prooxidant drugs.

Is dementia reversible in patients with neurocysticercosis?

Methods: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. Results: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. Conclusions: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.

Molecular mechanisms of alcohol-mediated carcinogenesis.

Approximately 3.6% of cancers worldwide derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, most recent research has focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Ethanol may also stimulate carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Alcohol-related carcinogenesis may interact with other factors such as smoking, diet and comorbidities, and depends on genetic susceptibility.

Left subclavian arterioesophageal fistula induced by chicken bone with upper gastrointestinal hemorrhage and unexpected death: report of a case.

Left subclavian arterioesophageal fistula resulting from chicken bone ingestion is a rare occurrence. The authors report the death of a 42-year-old Thai female with mental retardation who presented to the hospital with severe hematemesis and arrested Death occurred about 24 hours after laparotomy due to hypovolemic shock Postmortem examination revealed a chicken bone embedded in middle part of esophagus with fistula between the esophagus and the left subclavian artery.

Transurethral electrovaporization of the prostate in benign prostatic hyperplasia. Evaluation of results using different urodynamic parameters.

We studied the obstruction-relieving capabilities of transurethral electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were performed before and 6 months after treatment. All 32 patients showed significant improvement of both subjective and objective obstruction parameters. There were few postoperative irritative symptoms and one patient required recatheterization. In conclusion, TVP is a promising modification of performing transurethral resection of the prostate, and it is indeed capable of relieving bladder outflow obstruction.

The use of dental radiographs: update and recommendations.

BACKGROUND AND OVERVIEW: The National Council on Radiation Protection & Measurements updated its recommendations on radiation protection in dentistry in 2003, the Centers for Disease Control and Prevention published its Guidelines for Infection Control in Dental Health-Care Settings in 2003, and the U.S. Food and Drug Administration updated its selection criteria for dental radiographs in 2004. This report summarizes the recommendations presented in these documents and addresses additional topics such as patient selection criteria, film selection for conventional radiographs, collimation, beam filtration, patient protective equipment, film holders, operator protection, film exposure and processing, infection control, quality assurance, image viewing, direct digital radiography and continuing education of dental health care workers who expose radiographs. CONCLUSIONS: This report discusses implementation of proper radiographic practices. In addition to these guidelines, dentists should be aware of, and comply with, applicable federal and state regulations. CLINICAL IMPLICATIONS: Dentists should weigh the benefits of dental radiographs against the consequences of increasing a patient's exposure to radiation and implement appropriate radiation control procedures.

Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world and its incidence is increasing rapidly. NAFLD is a spectrum ranging from simple steatosis, which is relatively benign hepatically, to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia are the most important risk factors for NAFLD. Due to heavy enrichment with metabolic risk factors, individuals with NAFLD are at significantly higher risk for cardiovascular disease. Individuals with NAFLD have higher incidence of type 2 diabetes. The diagnosis of NAFLD requires imaging evidence of hepatic steatosis in the absence of competing etiologies including significant alcohol consumption. Liver biopsy remains the gold standard for diagnosing NASH and for determining prognosis. Weight loss remains a cornerstone of treatment. Weight loss of ∼5% is believed to improve steatosis, whereas ∼10% weight loss is necessary to improve steatohepatitis. A number of pharmacologic therapies have been investigated to treat NASH, and agents such as vitamin E and thiazolidinediones have shown promise in select patient subgroups.

Acne, dairy and cancer

A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.

BRCA1-methylated sporadic breast cancers are BRCA-like in showing a basal phenotype and absence of ER expression.

BRCA1 mutations have been associated with hereditary breast cancer only. Recent studies indicate that a subgroup of sporadic breast cancer might also be associated with reduction in BRCA1 mRNA levels and protein expression. However, the mechanism of reduced mRNA and protein expression is yet not fully elucidated. This study aims to assess BRCA1 protein expression and the role of BRCA1 promoter methylation in sporadic breast cancer in North Indian population and to correlate these with known prognostic factors and molecular profiles of breast cancer. BRCA1 protein expression was normal (>50 % tumour cells) in 41 (43 %) cases, reduced (20-50 % tumour cells) in 33 (35 %) cases and absent/markedly reduced (<20 % tumour cells) in 21 (22.1 %) cases. Cases which were negative for BRCA1 protein were more frequently positive for basal markers (29 versus 5 %) and were more often ER-negative (62 versus 39 %) than BRCA1-positive tumours. Methylation of BRCA1 promoter region was seen in 11/45 cases (24 %). All 11 cases showing BRCA1 methylation had absent (eight cases) or reduced (three cases) BRCA1 protein expression. BRCA1 protein-negative tumours were more frequently basal marker-positive and ER-negative, highlighting the 'BRCAness' of sporadic breast cancer with loss of BRCA1 protein expression through promoter hypermethylation similar to hereditary breast cancer with BRCA1 mutations. Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.

The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells

Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.

Neurocysticercosis and oncogenesis.

Recent studies suggest that neurocysticercosis may be a risk factor for human cancer. Pathogenetic mechanisms explaining possible oncogenic effects of cysticerci include the following: (a) parasite-induced modulation of the host immune response that may be associated with loss of regulatory mechanisms implicated in the immunological surveillance against cancer; (b) transfer of genetic material from the parasite to the host, causing DNA damage and malignant transformation of host cells, and (c) chronic inflammation with liberation of nitric oxide and inhibition of tumor suppressor genes. Further research is needed to confirm the potential role of cysticercosis in the development of cancer. These studies should determine the presence of cysticercotic factors responsible for the transfer of genetic material and potential mutations in the tumor suppressor genes in proliferating astrocytes surrounding cysticercotic lesions. Additionally, the complex interaction between the immune state of the host with variable cytokine release and the presence of inflammatory cells releasing nitric oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be investigated.

Emerging science in the dietary control and prevention of dental caries.

The key environmental factor involved in caries incidence is fermentable carbohydrates. Because of the high costs of caries treatment, researchers continue to explore dietary control as a promising preventive method. While dietary change has been demonstrated to reduce Streptococcus mutans, a preventive role is expected for "functional foods" and dietary habit alterations. The authors consider how recent advances in the understanding of caries pathology can reveal dietary control as a valuable method in promoting a healthy dentition.

Pediatrician's role in screening and treatment: bullying, prediabetes, oral health.

PURPOSE OF REVIEW: To review recent literature on important topics in pediatric office practice: bullying, screening for the prediabetic state, and pediatric oral health. RECENT FINDINGS: Recent literature shows that bullying behaviors are common in children as young as kindergarten age, that there is a strong association between being a bully or victim and a range of psychosomatic and depressive symptoms in children, and that interventions including family therapy and school-based programs are effective for bullies and victims. Recent studies have further delineated glucose and insulin metabolism. Recent work has provided new models to help practitioners screen for the prediabetic state in hope of providing earlier opportunities to intervene and avoid the morbidities associated with type 2 diabetes mellitus. Recent literature emphasizes continued gaps in dental healthcare for patients who are most at risk. Recent studies emphasize the important role that diet and sealants have in preventing dental caries. SUMMARY: Recent literature emphasizes the important role that office-based pediatricians have in identifying patients who are involved in bullying, at risk of developing type 2 diabetes mellitus, or have poor dental health. Future research will help delineate these problems and provide us with refined primary prevention and treatment guidelines.

Growth Factors and their receptors in cancer metastases.

Metastatic, rather than primary tumours are responsible for ninety percent cancer deaths. Despite significant advances in the understanding of molecular and cellular mechanisms in tumour metastases, there are limitations in preventive treatment of metastatic tumours. Much evidence arising from laboratory and clinical studies suggests that growth factors and their receptors are implicated in cancer metastases development. We review the origin and production of growth factors and their receptors in all stages of cancer metastases including epithelial-mesenchymal transition, cancer cell invasion and migration, survival within the circulation, seeding at distant organs and metastatic tumour angiogenesis. The functions of growth factors and their receptors are also discussed. This review presents the efforts made in understanding this challenge to aid in the development of new treatment strategies for cancer metastases.

Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer.

The human serum Sex Hormone-Binding Globulin (SHBG) plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. We here summarize data reported over the years concerning the involvement of SHBG and SHBG polymorphisms in the definition of breast cancer risk. We also report what is known about the direct action of SHBG in breast cancer cells, illustrating its interaction with these cells and the subsequent initiation of a specific intracellular pathway leading to cross-talk with the estradiol-activated pathway and, finally, to the inhibition of several effects of estradiol in breast cancer cells. In conclusion, as a result of its unique property of regulating the estrogen free fraction and cross-talking with the estradiol pathways, by inhibiting estradiol-induced breast cancer cell growth and proliferation, SHBG is associated with a reduced risk of developing the neoplasm after estrogen exposure. 2009 Elsevier Ireland Ltd. All rights reserved.

mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ...

Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation.

OBJECTIVE: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. METHODS AND RESULTS: We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). CONCLUSIONS: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.