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: Obesity , the global epidemic health problem , results in chronic disorders . Melatonin supplementation may prevent the adverse health consequences of obesity . The aim of this study was to assess the effects of melatonin supplementation on inflammatory and oxidative stress parameters in obese women . In r and omized , double-blind , placebo-controlled trial , 44 obese women were r and omly assigned to melatonin ( n=22 ) and placebo ( n=22 ) groups . Subjects were supplemented with a daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days . Serum TNF-α , IL-6 , hsCRP , TAC , and MDA levels were assessed before and after intervention . In the melatonin group , mean serum TNF-α , IL-6 , hsCRP , and MDA levels decreased significantly ( p<0.05 ) from 3.52±0.72 pg/ml , 27.12±6.32 pg/ml , 2.54±0.49 mg/l , and 3.81±0.29 nmol/l to 1.73±0.07 , 16.34±6.32 , 1.67±0.27 , and 2.79±0.29 , respectively . Whilst in the placebo group the decrease in values were not statistically significant . Mean TAC level increased slightly ( from 1.11±0.30 to 1.14±0.45 mmol/l ) in the melatonin group whereas it decreased slightly ( from 1.13±0.15 to 1.08±0.21 nmol/l ) in the placebo group . Significant differences were observed only for TNF-α ( p=0.02 ) and IL-6 ( p=0.03 ) between the 2 study groups . Considering the improvements in inflammatory and oxidative stress factors in obese women , it seems that melatonin supplementation may provide beneficial effects in obesity treatment by ameliorating some of its complications . However , further studies are needed to make concise conclusions The objective of the present study was to assess the toxicology of melatonin ( 10 mg ) , administered for 28 days to 40 volunteers r and omly assigned to groups receiving either melatonin ( N = 30 ) or placebo  ( N = 10 ) in a double-blind fashion . The following measurements were performed : polysomnography ( PSG ) , laboratory examinations , including complete blood count , urinalysis , sodium , potassium and calcium levels , total protein levels , albumin , blood glucose , triglycerides , total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and very low-density lipoprotein ( VLDL ) , urea , creatinine , uric acid , glutamic-oxalacetic transaminase ( GOT ) , glutamic-pyruvate transaminase ( GPT ) , bilirubin , alkaline phosphatase , gama-glutamic transaminase ( GGT ) , T3 , T4 , TSH , LH/FSH , cortisol , and melatonin serum concentrations . In addition , the Epworth Somnolence Scale ( ESS ) and a sleep diary ( SD ) were also applied to the volunteers 1 wk before each PSG . In addition , the volunteers were asked about possible side effects ( SE ) that appeared during the treatment . The study was carried out according to the following timetable : Visit 0 , filling out the term of consent and inclusion criteria ; Visit 1 , PSG , laboratory examinations , ESS , SD ,  melatonin serum concentrations ; Visit 2 , SD ,  melatonin serum concentrations , SE ; Visit 3 ,  melatonin serum concentrations , PSG , ESS , SE ; Visit 4 , laboratory examinations , SE , melatonin serum concentrations , SD ; and Visit 5 , PSG , ESS , SE . Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group . No other differences between the placebo and melatonin groups were obtained . In the present study we did not observe , according to the parameters analyzed , any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study Nonalcoholic fatty liver disease is the most common chronic liver disease and nonalcocholic steatohepatitis ( NASH ) is its advanced form . Oxidative stress and hepatocyte apoptosis may be involved in pathogenesis of NASH and particularly in progress of NASH to liver fibrosis and cirrhosis , which are initiated by the inflammation and which promote the progress of the disease . The aim of this study was to evaluate the effects of melatonin and L-tryptophan on selected biochemical parameters of blood in patients with NASH . Forty five patients with NASH , confirmed by histopathological examination of liver biopsy sample s , were admitted to the study . They were divided into three groups ( I , II and III ) . The first group ( group I , n=15 ) received preparation Essentiale forte 3 times a day and tryptophan 500 mg twice daily for 4 weeks . In the second group ( group II , n=15 ) , Essentiale forte three times a day was administered with melatonin 5 mg applied twice a day for 4 weeks . The third group ( group III , n=15 ) received only Essentiale forte with placebo three times a day for 4 weeks . After four-week treatment we found statistically significant reduction in GGTP , triglycerides and proinflammatory cytokine levels in the melatonin-treated ( group I ) and the L-tryptophan-treated patients ( group II ) . Plasma level of melatonin was significantly elevated in groups treated with tryptophan ( group I ) and melatonin ( group II ) , but remained unchanged in placebo-treated group ( group III ) . Among patients from the third group ( treated with placebo ) no statistically significant differences in the measured biochemical parameters were observed . The present study suggests that melatonin and tryptophan have the significant impact on the reduction in plasma levels of proinflammatory cytokines and may be useful in the treatment of patients with NASH Background : In this study , we investigated the effect of melatonin administration on four markers of endothelial cell function including intercellular adhesion molecule ( ICAM ) , vascular cell adhesion molecule ( VCAM ) , C-reactive protein ( CRP ) , and nitric oxide ( NO ) on patients with three vessels coronary disease . Material s and Methods : This double-blind , r and omized , controlled trial study was conducted on 39 patients ( 32 men and 7 women ) with three vessels coronary disease . The case group included 20 patients who received 10 mg oral melatonin 1 h before sleeping for 1 month . The control group included 19 patients who received placebo 1 h before sleeping for 1 month . The serum levels of CRP , ICAM , VCAM , and NO were compared after 1 month treatment . Results : After 1 month of melatonin treatment , the mean level of ICAM , VCAM , and CRP showed a statistically significant decrease in the case group . On the other h and , the mean level of VCAM increased significantly in the control group . The mean levels of CRP and ICAM were also increased in the control group , but the difference did not reach the significant threshold . With respect to NO , there was a statistically significant increase in the case group , while there was a statistically significant decrease in serum NO in the control group . Conclusions : The results of this study suggested that melatonin may have beneficial effects on endothelial oxidative stress even in patient with severe and advanced atherosclerosis It is known that neoplastic cachexia shows metabolic characteristics different from other common causes of malnutrition , and that it is mainly due to an abnormal secretion of TNF , whose levels are often high in patients with advanced neoplasia . Previous clinical studies have suggested that the pineal hormone melatonin ( MLT ) , which plays an essential role in the neuroendocrine regulation of biological systems , may improve the clinical status of advanced cancer patients and inhibit TNF secretion . To investigate the relationship between MLT , TNF and cancer-related weight loss , 100 untreatable metastatic solid tumour patients entered this study to receive either supportive care alone , or supportive care plus MLT ( 20 mg/day orally in the evening ) . Patients were observed for 3 months , and were considered evaluable when they were observed for at least 2 months . There were 86 evaluable patients , the other 14 patients having died from rapid progression of disease . The per cent of weight loss greater than 10 % was significantly higher in patients treated by supportive care alone than in those concomitantly treated by MLT , with no difference in food intake ( P < 0.01 ) . Mean serum levels of TNF progressively increased in the supportive care group , but to levels that were not significantly different from pretreatment values . In contrast , TNF mean concentrations significantly decreased ( P < 0.05 ) in patients concomitantly treated by MLT . These results suggest that the pineal hormone MLT may be effective in the treatment of the neoplastic cachexia by decreasing TNF blood concentrations BACKGROUND The aim of this clinical trial was to determine the effects of melatonin administration on disease severity and sleep quality in children diagnosed with atopic dermatitis ( AD ) . METHODS This r and omized , double-blinded , placebo-controlled trial was conducted by recruiting 70 patients , aged 6 - 12 years , who had been diagnosed with AD . Study participants were r and omly allocated into two intervention groups to receive either 6 mg/d melatonin supplements or placebo ( n = 35 each group ) for 6 weeks . Severity of disease was assessed using the scoring atopic dermatitis ( SCORAD ) and objective SCORAD indices . Sleep quality was evaluated by completing the Children 's Sleep Habits Question naire ( CSHQ ) . RESULTS Following 6 weeks of intervention , melatonin supplementation significantly improved SCORAD index ( β -3.55 ; 95 % CI , -6.11 , -0.98 ; P = 0.007 ) , objective SCORAD index ( β -3.23 ; 95 % CI , -5.08 , -1.38 ; P = 0.001 ) , serum total IgE levels ( β -153.94 ku/L ; 95 % CI , -260.39 , -47.49 ; P = 0.005 ) , and CSHQ scores ( β -2.55 ; 95 % CI , -4.34 , -0.75 ; P = 0.006 ) . However , melatonin had no significant impact on pruritus scores , high-sensitivity C-reactive protein ( hs-CRP ) , sleep-onset latency , total sleep time , weight , and BMI  compared with placebo . CONCLUSIONS Overall , melatonin supplementation had beneficial effects on disease severity , serum total IgE levels , and CSHQ among children diagnosed with AD Background Diabetes mellitus ( DM ) and periodontitis are two common chronic diseases with bidirectional relationship . Oxidative stress plays a key role in the pathogenesis of these two diseases . The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status , serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis ( CP ) . Material s and methods In this double-blind clinical trial study , 50 type 2 DM patients with CP were r and omly allocated to the intervention and control groups . The intervention and control groups received either 6 mg melatonin or placebo ( 2 tablets ) once a day . Serum levels of melatonin , tumor necrosis factor-alpha ( TNF-α ) , interleukin-6 ( IL-6 ) , hs-C-reactive protein ( hs-CRP ) , clinical attachment loss ( CAL ) , pocket depth ( PD ) , bleeding on probing ( BOP ) and plaque index were evaluated in all subjects pre- and post-intervention . Results Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention . The mean changes of melatonin were significantly higher in intervention group compared with control group . IL-6 and hs-CRP levels were significantly ( p = 0.008 and p = 0.017 , respectively ) reduced in the intervention group . The mean changes of IL-6 were significantly lower in the intervention group compared with the control group ( p = 0.04 ) . In the intervention group , PD and CAL were significantly decreased after intervention ( p < 0.001 ) . There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention ( p < 0.001 ) . Conclusions Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP Multiple sclerosis ( MS ) is a chronic inflammatory disease , which leads to focal plaques of demyelination and tissue injury in the central nervous system ( CNS ) . Neuroinflammation and oxidative stress are involved in the pathogenesis of MS , promoting tissue damage and demielinization . Current research findings suggest that melatonin has antioxidant and neuroprotective effects . The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis ( RRMS ) . 36 patients diagnose with RRMS treated with Interferon β-1b ( IFNβ-1b ) were enrolled in a double bind , r and omized , placebo controlled trial . The experimental group received orally 
    Output:
    
agent
The results of the present meta- analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators
***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: Obesity , the global epidemic health problem , results in chronic disorders . Melatonin supplementation may prevent the adverse health consequences of obesity . The aim of this study was to assess the effects of melatonin supplementation on inflammatory and oxidative stress parameters in obese women . In r and omized , double-blind , placebo-controlled trial , 44 obese women were r and omly assigned to melatonin ( n=22 ) and placebo ( n=22 ) groups . Subjects were supplemented with a daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days . Serum TNF-α , IL-6 , hsCRP , TAC , and MDA levels were assessed before and after intervention . In the melatonin group , mean serum TNF-α , IL-6 , hsCRP , and MDA levels decreased significantly ( p<0.05 ) from 3.52±0.72 pg/ml , 27.12±6.32 pg/ml , 2.54±0.49 mg/l , and 3.81±0.29 nmol/l to 1.73±0.07 , 16.34±6.32 , 1.67±0.27 , and 2.79±0.29 , respectively . Whilst in the placebo group the decrease in values were not statistically significant . Mean TAC level increased slightly ( from 1.11±0.30 to 1.14±0.45 mmol/l ) in the melatonin group whereas it decreased slightly ( from 1.13±0.15 to 1.08±0.21 nmol/l ) in the placebo group . Significant differences were observed only for TNF-α ( p=0.02 ) and IL-6 ( p=0.03 ) between the 2 study groups . Considering the improvements in inflammatory and oxidative stress factors in obese women , it seems that melatonin supplementation may provide beneficial effects in obesity treatment by ameliorating some of its complications . However , further studies are needed to make concise conclusions The objective of the present study was to assess the toxicology of melatonin ( 10 mg ) , administered for 28 days to 40 volunteers r and omly assigned to groups receiving either melatonin ( N = 30 ) or placebo  ( N = 10 ) in a double-blind fashion . The following measurements were performed : polysomnography ( PSG ) , laboratory examinations , including complete blood count , urinalysis , sodium , potassium and calcium levels , total protein levels , albumin , blood glucose , triglycerides , total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and very low-density lipoprotein ( VLDL ) , urea , creatinine , uric acid , glutamic-oxalacetic transaminase ( GOT ) , glutamic-pyruvate transaminase ( GPT ) , bilirubin , alkaline phosphatase , gama-glutamic transaminase ( GGT ) , T3 , T4 , TSH , LH/FSH , cortisol , and melatonin serum concentrations . In addition , the Epworth Somnolence Scale ( ESS ) and a sleep diary ( SD ) were also applied to the volunteers 1 wk before each PSG . In addition , the volunteers were asked about possible side effects ( SE ) that appeared during the treatment . The study was carried out according to the following timetable : Visit 0 , filling out the term of consent and inclusion criteria ; Visit 1 , PSG , laboratory examinations , ESS , SD ,  melatonin serum concentrations ; Visit 2 , SD ,  melatonin serum concentrations , SE ; Visit 3 ,  melatonin serum concentrations , PSG , ESS , SE ; Visit 4 , laboratory examinations , SE , melatonin serum concentrations , SD ; and Visit 5 , PSG , ESS , SE . Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group . No other differences between the placebo and melatonin groups were obtained . In the present study we did not observe , according to the parameters analyzed , any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study Nonalcoholic fatty liver disease is the most common chronic liver disease and nonalcocholic steatohepatitis ( NASH ) is its advanced form . Oxidative stress and hepatocyte apoptosis may be involved in pathogenesis of NASH and particularly in progress of NASH to liver fibrosis and cirrhosis , which are initiated by the inflammation and which promote the progress of the disease . The aim of this study was to evaluate the effects of melatonin and L-tryptophan on selected biochemical parameters of blood in patients with NASH . Forty five patients with NASH , confirmed by histopathological examination of liver biopsy sample s , were admitted to the study . They were divided into three groups ( I , II and III ) . The first group ( group I , n=15 ) received preparation Essentiale forte 3 times a day and tryptophan 500 mg twice daily for 4 weeks . In the second group ( group II , n=15 ) , Essentiale forte three times a day was administered with melatonin 5 mg applied twice a day for 4 weeks . The third group ( group III , n=15 ) received only Essentiale forte with placebo three times a day for 4 weeks . After four-week treatment we found statistically significant reduction in GGTP , triglycerides and proinflammatory cytokine levels in the melatonin-treated ( group I ) and the L-tryptophan-treated patients ( group II ) . Plasma level of melatonin was significantly elevated in groups treated with tryptophan ( group I ) and melatonin ( group II ) , but remained unchanged in placebo-treated group ( group III ) . Among patients from the third group ( treated with placebo ) no statistically significant differences in the measured biochemical parameters were observed . The present study suggests that melatonin and tryptophan have the significant impact on the reduction in plasma levels of proinflammatory cytokines and may be useful in the treatment of patients with NASH Background : In this study , we investigated the effect of melatonin administration on four markers of endothelial cell function including intercellular adhesion molecule ( ICAM ) , vascular cell adhesion molecule ( VCAM ) , C-reactive protein ( CRP ) , and nitric oxide ( NO ) on patients with three vessels coronary disease . Material s and Methods : This double-blind , r and omized , controlled trial study was conducted on 39 patients ( 32 men and 7 women ) with three vessels coronary disease . The case group included 20 patients who received 10 mg oral melatonin 1 h before sleeping for 1 month . The control group included 19 patients who received placebo 1 h before sleeping for 1 month . The serum levels of CRP , ICAM , VCAM , and NO were compared after 1 month treatment . Results : After 1 month of melatonin treatment , the mean level of ICAM , VCAM , and CRP showed a statistically significant decrease in the case group . On the other h and , the mean level of VCAM increased significantly in the control group . The mean levels of CRP and ICAM were also increased in the control group , but the difference did not reach the significant threshold . With respect to NO , there was a statistically significant increase in the case group , while there was a statistically significant decrease in serum NO in the control group . Conclusions : The results of this study suggested that melatonin may have beneficial effects on endothelial oxidative stress even in patient with severe and advanced atherosclerosis It is known that neoplastic cachexia shows metabolic characteristics different from other common causes of malnutrition , and that it is mainly due to an abnormal secretion of TNF , whose levels are often high in patients with advanced neoplasia . Previous clinical studies have suggested that the pineal hormone melatonin ( MLT ) , which plays an essential role in the neuroendocrine regulation of biological systems , may improve the clinical status of advanced cancer patients and inhibit TNF secretion . To investigate the relationship between MLT , TNF and cancer-related weight loss , 100 untreatable metastatic solid tumour patients entered this study to receive either supportive care alone , or supportive care plus MLT ( 20 mg/day orally in the evening ) . Patients were observed for 3 months , and were considered evaluable when they were observed for at least 2 months . There were 86 evaluable patients , the other 14 patients having died from rapid progression of disease . The per cent of weight loss greater than 10 % was significantly higher in patients treated by supportive care alone than in those concomitantly treated by MLT , with no difference in food intake ( P < 0.01 ) . Mean serum levels of TNF progressively increased in the supportive care group , but to levels that were not significantly different from pretreatment values . In contrast , TNF mean concentrations significantly decreased ( P < 0.05 ) in patients concomitantly treated by MLT . These results suggest that the pineal hormone MLT may be effective in the treatment of the neoplastic cachexia by decreasing TNF blood concentrations BACKGROUND The aim of this clinical trial was to determine the effects of melatonin administration on disease severity and sleep quality in children diagnosed with atopic dermatitis ( AD ) . METHODS This r and omized , double-blinded , placebo-controlled trial was conducted by recruiting 70 patients , aged 6 - 12 years , who had been diagnosed with AD . Study participants were r and omly allocated into two intervention groups to receive either 6 mg/d melatonin supplements or placebo ( n = 35 each group ) for 6 weeks . Severity of disease was assessed using the scoring atopic dermatitis ( SCORAD ) and objective SCORAD indices . Sleep quality was evaluated by completing the Children 's Sleep Habits Question naire ( CSHQ ) . RESULTS Following 6 weeks of intervention , melatonin supplementation significantly improved SCORAD index ( β -3.55 ; 95 % CI , -6.11 , -0.98 ; P = 0.007 ) , objective SCORAD index ( β -3.23 ; 95 % CI , -5.08 , -1.38 ; P = 0.001 ) , serum total IgE levels ( β -153.94 ku/L ; 95 % CI , -260.39 , -47.49 ; P = 0.005 ) , and CSHQ scores ( β -2.55 ; 95 % CI , -4.34 , -0.75 ; P = 0.006 ) . However , melatonin had no significant impact on pruritus scores , high-sensitivity C-reactive protein ( hs-CRP ) , sleep-onset latency , total sleep time , weight , and BMI  compared with placebo . CONCLUSIONS Overall , melatonin supplementation had beneficial effects on disease severity , serum total IgE levels , and CSHQ among children diagnosed with AD Background Diabetes mellitus ( DM ) and periodontitis are two common chronic diseases with bidirectional relationship . Oxidative stress plays a key role in the pathogenesis of these two diseases . The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status , serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis ( CP ) . Material s and methods In this double-blind clinical trial study , 50 type 2 DM patients with CP were r and omly allocated to the intervention and control groups . The intervention and control groups received either 6 mg melatonin or placebo ( 2 tablets ) once a day . Serum levels of melatonin , tumor necrosis factor-alpha ( TNF-α ) , interleukin-6 ( IL-6 ) , hs-C-reactive protein ( hs-CRP ) , clinical attachment loss ( CAL ) , pocket depth ( PD ) , bleeding on probing ( BOP ) and plaque index were evaluated in all subjects pre- and post-intervention . Results Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention . The mean changes of melatonin were significantly higher in intervention group compared with control group . IL-6 and hs-CRP levels were significantly ( p = 0.008 and p = 0.017 , respectively ) reduced in the intervention group . The mean changes of IL-6 were significantly lower in the intervention group compared with the control group ( p = 0.04 ) . In the intervention group , PD and CAL were significantly decreased after intervention ( p < 0.001 ) . There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention ( p < 0.001 ) . Conclusions Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP Multiple sclerosis ( MS ) is a chronic inflammatory disease , which leads to focal plaques of demyelination and tissue injury in the central nervous system ( CNS ) . Neuroinflammation and oxidative stress are involved in the pathogenesis of MS , promoting tissue damage and demielinization . Current research findings suggest that melatonin has antioxidant and neuroprotective effects . The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis ( RRMS ) . 36 patients diagnose with RRMS treated with Interferon β-1b ( IFNβ-1b ) were enrolled in a double bind , r and omized , placebo controlled trial . The experimental group received orally 
    Output:
    