human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The aim of this study was to evaluate the efficacy of low-level laser therapy ( LLLT ) and alpha-lipoic acid ( ALA ) in the treatment of  burning mouth syndrome ( BMS ) and secondary oral burning ( SOB ) by unstimulated sialometry , symptom assessment , and measurement of salivary TNF-α levels . Forty-four patients were r and omized into four treatment groups : BMS/laser ( n = 10 ) , BMS/ALA ( n = 5 ) , SOB/laser ( n = 15 ) , and SOB/ALA ( n = 14 ) . The control group consisted of eight healthy female subjects . Unstimulated salivary flow was measured before and after treatment , and the collected saliva was stored at − 20 ° C for the analysis of TNF-α . Symptoms were evaluated before and after treatment using a pain visual analog scale . Most patients were women ( 81.8 % ) during menopause ( 72.2 % ) . LLLT and ALA were efficient in increasing salivary flow only in BMS but provided symptom relief in both conditions . TNF-α levels did not differ between patients with BMS and SOB or between those patients and the control group . No differences were observed in posttreatment TNF-α levels in either condition . The results of this study suggest that LLLT and ALA are efficient therapies in reducing burning mouth symptoms , with LLLT being more efficient than ALA Background : A limited amount of data exists regarding the effect of lipoic acid ( LA ) , an oral antioxidant supplement , on cytokine profiles among multiple sclerosis ( MS ) patients . Objective : We aim ed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients . Methods : In this double-blind , placebo-controlled , r and omized clinical trial , 52 relapsing-remitting MS patients with an age range of 18 - 50 years were recruited into 2 groups : LA consumption ( 1,200 mg/day ) or placebo . Patients followed their prescribed supplements for 12 weeks  . Fasting blood sample s for cytokine profile measurement were collected at baseline and after the intervention . Anthropometric parameters were measured based on the st and ard guidelines . Results : INF-γ , ICAM-1 , TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [ ( INF-γ : 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml , p < 0.0001 ) , ( ICAM-1 : 20.2 ± 9.4 vs. 8 ± 10 ng/ml , p = 0.0001 ) , ( TGF-β : 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml , p < 0.0001 ) and ( IL-4 : 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml , p = 0.0112 ) ] . No significant changes in TNF-α , IL-6 , EDSS and MMP-9 were found between the LA and placebo groups ( p = 0.6 , p = 0.8 , p = 0.09 and p = 0.8 , respectively ) . Conclusion : The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ , ICAM-1 TGF-β and IL-4 . Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients OBJECTIVE To examine whether 3 months of lipoic acid ( LA ) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease ( PAD ) . DESIGN R and omized , double-blind , controlled study . SETTING General Clinical Research Center . SUBJECTS Twenty-eight ( 28 ) participants ( 15 men , 13 women ) with PAD ( ankle brachial index range 0.9 - 0.4 , mean age 73.2 + /- 1.6 years ) . INTERVENTION LA ( 600 mg/day ) or placebo for 3 months . OUTCOME MEASURES Walking tolerance was assessed by 6-minute walk test distance , 4-meter walk time , initial claudication pain time ( ICT ) and distance ( ICD ) , and peak claudication pain . Serum was assessed for inflammation ( C-reactive protein [ CRP ] ) and oxidative stress ( lipid hydroperoxides ) as potential mechanisms for changes in walking tolerance . RESULTS ICT increased 34.4 % and 15 % , ICD was reduced by 40.5 % and 18 % , and peak claudication pain ratings were reduced by 93 % and 7 % in LA and placebo groups , respectively . Although the improvements in peak pain and ICT achieved significance within the LA group ( both p<0.05 ) , the interactions of group by time were not found to be significant ( p>0.05 ) . Oxidative stress and CRP measures were not different between groups by month 3 ( p>0.05 ) . There were no serious side-effects associated with the LA . CONCLUSIONS LA may confer pain relief during exercise . However , longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms Several studies showed that impairment of endothelium-dependent arterial dilation ( EDAD ) exists in subjects with impaired fasting glucose ( IFG ) . The crucial mechanism of this endothelial dysfunction remains unclear . We hypothesized that oxidative stress may be partially responsible for the impairment in EDAD in subjects with IFG . Thus , the present study was design ed to assess whether the antioxidant α-lipoic acid can improve endothelial dysfunction in subjects with IFG . Sixty subjects with newly diagnosed IFG and 32 healthy individuals with normal glucose tolerance were enrolled . Subjects were r and omized into 2 groups : untreated experimental group ( n = 30 ) and α-lipoic acid treatment group ( n = 30 , α-lipoic acid 600 mg via intravenous infusion once a day for 3 weeks ) . We measured EDAD at baseline and after 3 weeks of intervention . At baseline , EDADs in α-lipoic acid and untreated experimental groups were 4.03 % and 4.14 % , respectively , which were significantly lower than that in controls ( 5.72 % ) ( P < .001 ) . After 3 weeks of intervention , there was a remarkable increase in EDAD ( reaching 5.10 % ; ΔEDAD , 26.5 % ) ( P < .01 ) and a significant decrease in plasma thiobarbituric acid reactive substances ( TBARS ) ( 29.1 % ) ( P < .05 ) in IFG subjects treated with α-lipoic acid . Endothelium-dependent arterial dilation and TBARS remained unchanged before and after intervention in the untreated experimental group . The absolute changes in EDAD showed a significant negative correlation with the changes in TBARS ( r = -0.444 , P = .014 ) . Our data showed that IFG subjects have impaired endothelial function  and that antioxidant α-lipoic acid can improve endothelial function through a decrease of oxygen-derived free radicals BACKGROUND Takotsubo syndrome is a stress cardiomyopathy , characterized by reversible left ventricle ( LV ) apical ballooning in the absence of significant angiographic coronary artery stenosis . The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement . We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance . METHODS From January 2010 to June 2012 , 886 patients were consecutively evaluated at Cardarelli Hospital , Naples , Italy . Among these , 48 patients met takotsubo cardiomyopathy ( TCM ) criteria . Each patient was assessed with history and physical examination , 12-lead electrocardiogram , serum troponin , coronary arteriography , and left ventricular angiogram , perfusion myocardial scintigraphy with technetium 99 m , with echocardiography and 123I-metaiodobenzylguanidine ( MIBG ) myocardial scintigraphy . At discharge , the surviving patients were r and omly assigned to α-lipoic acid ( ALA ) treatment ( 600 mg once daily ) or placebo . Following discharge , after the initial TCM event , patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months . Routine analysis , myocardial damage serum markers , oxidative stress serum markers , pro-inflammatory cytokines , and sympathetic tone activity were evaluated in all patients . RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo . CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction . ALA treatment improves the adrenergic cardiac innervation . This study evaluates whether sympatho-vagal alterations are TCM event-related Background Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes , Alzheimer 's disease and multiple sclerosis ( MS ) . Lipoic acid ( LA ) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases . We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases . LA also suppressed NK cell activation and cytotoxicity . In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade . Additionally , we show that LA oral administration elevates cAMP levels in MS subjects . Methodology /Principal Findings We determined the effects of LA on IL-6 , IL-17 and IL-10 secretion using ELISAs . Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34 % , respectively , in T cell enriched P BMC s. IL-17 levels were also reduced by 35 and 50 % , respectively . Though not significant , LA appeared to have a biphasic effect on IL-10 production . Thymidine incorporation studies showed LA inhibited T cell proliferation by 90 % . T-cell activation was reduced by 50 % as measured by IL-2 secretion . Western blot analysis showed that LA treatment increased phosphorylation of Lck , a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA , PKI , blocked LA inhibition of IL-2 and IFN gamma production , indicating that PKA mediates these responses . Oral administration of 1200 mg LA to MS subjects result ed in increased cAMP levels in P BMC s four hours after ingestion . Average cAMP levels in 20 subjects were 43 % higher than baseline . Conclusions / Significance Oral administration of LA in vivo result ed in significant increases in cAMP concentration . The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade . These novel findings enhance our underst and ing of the mechanisms of action of LA OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity . We investigated whether α-lipoic acid ( ALA ) has any effect on platelet reactivity in these patients . RESEARCH DESIGN AND METHODS We r and omly assigned 51 type 1 diabetic patients to ALA  ( 600 mg once daily ) or placebo for 5 weeks . Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression . C-reactive protein ( CRP ) and 8-iso-prostagl and in F2α serum levels also were measured . RESULTS Baseline variables were similar in the two groups . After treatment , closure time was longer ( P = 0.006 ) and CD62P platelet expression was lower , both before ( P = 0.002 ) and after ( P = 0.009 ) ADP stimulation in the ALA group compared with the placebo group . CRP and 8-iso-prostagl and in F2α levels showed no differences between the two groups . CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients , independently of antioxidant or anti-inflammatory effects Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and re sources . This study investigates the role of alpha-lipoic acid ( ALA ) in end stage renal disease patients undergoing hemodialysis . By the virtue of its antioxidative effects , ALA is expected to act as an erythropoietin ( EPO ) adjuvant , and also has extended beneficial effects on endothelial dysfunction . Methods Forty-four patients undergoing hemodialysis and receiving EPO  were r and omized into two groups : the first group received ALA 600 mg once daily for 3 months ; while the other group represented the control group . Parameters measured at baseline and at end of study were hemoglobin , EPO doses , EPO resistance index ( ERI ) , iron store indices , malondialdehyde , oxidized low-density lipoprotein ( ox-LDL ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and asymmetric dimethylarginine ( ADMA ) , as well as routine laboratory follow-up . Results EPO doses and ERI were significantly decreased in the treatment group , while they did not change 
    Output:
    
agent
Our results indicated possible decreasing effect of ALA on inflammatory mediators especially in high dose .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The aim of this study was to evaluate the efficacy of low-level laser therapy ( LLLT ) and alpha-lipoic acid ( ALA ) in the treatment of  burning mouth syndrome ( BMS ) and secondary oral burning ( SOB ) by unstimulated sialometry , symptom assessment , and measurement of salivary TNF-α levels . Forty-four patients were r and omized into four treatment groups : BMS/laser ( n = 10 ) , BMS/ALA ( n = 5 ) , SOB/laser ( n = 15 ) , and SOB/ALA ( n = 14 ) . The control group consisted of eight healthy female subjects . Unstimulated salivary flow was measured before and after treatment , and the collected saliva was stored at − 20 ° C for the analysis of TNF-α . Symptoms were evaluated before and after treatment using a pain visual analog scale . Most patients were women ( 81.8 % ) during menopause ( 72.2 % ) . LLLT and ALA were efficient in increasing salivary flow only in BMS but provided symptom relief in both conditions . TNF-α levels did not differ between patients with BMS and SOB or between those patients and the control group . No differences were observed in posttreatment TNF-α levels in either condition . The results of this study suggest that LLLT and ALA are efficient therapies in reducing burning mouth symptoms , with LLLT being more efficient than ALA Background : A limited amount of data exists regarding the effect of lipoic acid ( LA ) , an oral antioxidant supplement , on cytokine profiles among multiple sclerosis ( MS ) patients . Objective : We aim ed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients . Methods : In this double-blind , placebo-controlled , r and omized clinical trial , 52 relapsing-remitting MS patients with an age range of 18 - 50 years were recruited into 2 groups : LA consumption ( 1,200 mg/day ) or placebo . Patients followed their prescribed supplements for 12 weeks  . Fasting blood sample s for cytokine profile measurement were collected at baseline and after the intervention . Anthropometric parameters were measured based on the st and ard guidelines . Results : INF-γ , ICAM-1 , TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [ ( INF-γ : 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml , p < 0.0001 ) , ( ICAM-1 : 20.2 ± 9.4 vs. 8 ± 10 ng/ml , p = 0.0001 ) , ( TGF-β : 103.1 ± 20.2 vs. 54.9 ± 26 ng/ml , p < 0.0001 ) and ( IL-4 : 0.1 ± 0.1 vs. 1.02 ± 1.7 ng/ml , p = 0.0112 ) ] . No significant changes in TNF-α , IL-6 , EDSS and MMP-9 were found between the LA and placebo groups ( p = 0.6 , p = 0.8 , p = 0.09 and p = 0.8 , respectively ) . Conclusion : The results suggested that consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ , ICAM-1 TGF-β and IL-4 . Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients OBJECTIVE To examine whether 3 months of lipoic acid ( LA ) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease ( PAD ) . DESIGN R and omized , double-blind , controlled study . SETTING General Clinical Research Center . SUBJECTS Twenty-eight ( 28 ) participants ( 15 men , 13 women ) with PAD ( ankle brachial index range 0.9 - 0.4 , mean age 73.2 + /- 1.6 years ) . INTERVENTION LA ( 600 mg/day ) or placebo for 3 months . OUTCOME MEASURES Walking tolerance was assessed by 6-minute walk test distance , 4-meter walk time , initial claudication pain time ( ICT ) and distance ( ICD ) , and peak claudication pain . Serum was assessed for inflammation ( C-reactive protein [ CRP ] ) and oxidative stress ( lipid hydroperoxides ) as potential mechanisms for changes in walking tolerance . RESULTS ICT increased 34.4 % and 15 % , ICD was reduced by 40.5 % and 18 % , and peak claudication pain ratings were reduced by 93 % and 7 % in LA and placebo groups , respectively . Although the improvements in peak pain and ICT achieved significance within the LA group ( both p<0.05 ) , the interactions of group by time were not found to be significant ( p>0.05 ) . Oxidative stress and CRP measures were not different between groups by month 3 ( p>0.05 ) . There were no serious side-effects associated with the LA . CONCLUSIONS LA may confer pain relief during exercise . However , longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms Several studies showed that impairment of endothelium-dependent arterial dilation ( EDAD ) exists in subjects with impaired fasting glucose ( IFG ) . The crucial mechanism of this endothelial dysfunction remains unclear . We hypothesized that oxidative stress may be partially responsible for the impairment in EDAD in subjects with IFG . Thus , the present study was design ed to assess whether the antioxidant α-lipoic acid can improve endothelial dysfunction in subjects with IFG . Sixty subjects with newly diagnosed IFG and 32 healthy individuals with normal glucose tolerance were enrolled . Subjects were r and omized into 2 groups : untreated experimental group ( n = 30 ) and α-lipoic acid treatment group ( n = 30 , α-lipoic acid 600 mg via intravenous infusion once a day for 3 weeks ) . We measured EDAD at baseline and after 3 weeks of intervention . At baseline , EDADs in α-lipoic acid and untreated experimental groups were 4.03 % and 4.14 % , respectively , which were significantly lower than that in controls ( 5.72 % ) ( P < .001 ) . After 3 weeks of intervention , there was a remarkable increase in EDAD ( reaching 5.10 % ; ΔEDAD , 26.5 % ) ( P < .01 ) and a significant decrease in plasma thiobarbituric acid reactive substances ( TBARS ) ( 29.1 % ) ( P < .05 ) in IFG subjects treated with α-lipoic acid . Endothelium-dependent arterial dilation and TBARS remained unchanged before and after intervention in the untreated experimental group . The absolute changes in EDAD showed a significant negative correlation with the changes in TBARS ( r = -0.444 , P = .014 ) . Our data showed that IFG subjects have impaired endothelial function  and that antioxidant α-lipoic acid can improve endothelial function through a decrease of oxygen-derived free radicals BACKGROUND Takotsubo syndrome is a stress cardiomyopathy , characterized by reversible left ventricle ( LV ) apical ballooning in the absence of significant angiographic coronary artery stenosis . The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement . We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance . METHODS From January 2010 to June 2012 , 886 patients were consecutively evaluated at Cardarelli Hospital , Naples , Italy . Among these , 48 patients met takotsubo cardiomyopathy ( TCM ) criteria . Each patient was assessed with history and physical examination , 12-lead electrocardiogram , serum troponin , coronary arteriography , and left ventricular angiogram , perfusion myocardial scintigraphy with technetium 99 m , with echocardiography and 123I-metaiodobenzylguanidine ( MIBG ) myocardial scintigraphy . At discharge , the surviving patients were r and omly assigned to α-lipoic acid ( ALA ) treatment ( 600 mg once daily ) or placebo . Following discharge , after the initial TCM event , patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months . Routine analysis , myocardial damage serum markers , oxidative stress serum markers , pro-inflammatory cytokines , and sympathetic tone activity were evaluated in all patients . RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo . CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction . ALA treatment improves the adrenergic cardiac innervation . This study evaluates whether sympatho-vagal alterations are TCM event-related Background Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes , Alzheimer 's disease and multiple sclerosis ( MS ) . Lipoic acid ( LA ) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases . We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases . LA also suppressed NK cell activation and cytotoxicity . In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade . Additionally , we show that LA oral administration elevates cAMP levels in MS subjects . Methodology /Principal Findings We determined the effects of LA on IL-6 , IL-17 and IL-10 secretion using ELISAs . Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34 % , respectively , in T cell enriched P BMC s. IL-17 levels were also reduced by 35 and 50 % , respectively . Though not significant , LA appeared to have a biphasic effect on IL-10 production . Thymidine incorporation studies showed LA inhibited T cell proliferation by 90 % . T-cell activation was reduced by 50 % as measured by IL-2 secretion . Western blot analysis showed that LA treatment increased phosphorylation of Lck , a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA , PKI , blocked LA inhibition of IL-2 and IFN gamma production , indicating that PKA mediates these responses . Oral administration of 1200 mg LA to MS subjects result ed in increased cAMP levels in P BMC s four hours after ingestion . Average cAMP levels in 20 subjects were 43 % higher than baseline . Conclusions / Significance Oral administration of LA in vivo result ed in significant increases in cAMP concentration . The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade . These novel findings enhance our underst and ing of the mechanisms of action of LA OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity . We investigated whether α-lipoic acid ( ALA ) has any effect on platelet reactivity in these patients . RESEARCH DESIGN AND METHODS We r and omly assigned 51 type 1 diabetic patients to ALA  ( 600 mg once daily ) or placebo for 5 weeks . Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression . C-reactive protein ( CRP ) and 8-iso-prostagl and in F2α serum levels also were measured . RESULTS Baseline variables were similar in the two groups . After treatment , closure time was longer ( P = 0.006 ) and CD62P platelet expression was lower , both before ( P = 0.002 ) and after ( P = 0.009 ) ADP stimulation in the ALA group compared with the placebo group . CRP and 8-iso-prostagl and in F2α levels showed no differences between the two groups . CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients , independently of antioxidant or anti-inflammatory effects Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and re sources . This study investigates the role of alpha-lipoic acid ( ALA ) in end stage renal disease patients undergoing hemodialysis . By the virtue of its antioxidative effects , ALA is expected to act as an erythropoietin ( EPO ) adjuvant , and also has extended beneficial effects on endothelial dysfunction . Methods Forty-four patients undergoing hemodialysis and receiving EPO  were r and omized into two groups : the first group received ALA 600 mg once daily for 3 months ; while the other group represented the control group . Parameters measured at baseline and at end of study were hemoglobin , EPO doses , EPO resistance index ( ERI ) , iron store indices , malondialdehyde , oxidized low-density lipoprotein ( ox-LDL ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and asymmetric dimethylarginine ( ADMA ) , as well as routine laboratory follow-up . Results EPO doses and ERI were significantly decreased in the treatment group , while they did not change 
    Output:
    