Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72) polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia), and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg) = 0.69 and P (Pro) = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.
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PMID:TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population. 1793 43

--Obesity is an important healthcare issue. --Recent research has led to insights into the role of the endocannabinoid system in the regulation of body weight. --Rimonabant is a CB1-endocannabinoid-receptor antagonist. --Four trials were published recently on the efficacy and safety of rimonabant in the treatment of people with obesity. --When combined with a hypocaloric diet, rimonabant 20 mg/day was more effective than placebo in achieving and maintaining weight loss. In addition, treatment with rimonabant had beneficial effects on insulin resistance, HDL-cholesterol and hypertriglyceridaemia. --There is concern regarding the increased incidence of depression during treatment. --Whether the beneficial effects of rimonabant on weight reduction and cardiovascular risk factors translate into a reduction in cardiovascular morbidity and mortality remains to be established in large phase III trials.
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PMID:[The endocannabinoid system, overweight, and the CB1-endocannabinoid-receptor antagonist rimonabant]. 1816 Dec 63

Eating disorders (ED) are a group of important psychiatric disorders that affect young men and women, and can have serious consequences. Among all ED, anorexia nervosa (AN) is the most typical but also the most severe. The pathogenesis of AN is multifactorial and a great variety of cognitive deficits may contribute to its pathogenesis. The present study is aimed to measure NO and peroxynitrite production, iNOS and nNOS expression by Western immunoblot after incubation of AN lipoproteins at different times with human astrocytoma cells. The AN-HDL treated cells showed an increased production of NO at 3 h versus control-HDL treated cells and a decreased production at 24 h. Regarding LDL, a significant increase of NO production was obtained both at 3 and 24 h. The AN-HDL and AN-LDL treated cells showed an increased production of peroxynitrite both at 3 and 24 h compared to control lipoproteins. Densitometric analysis of bands indicated that both iNOS and nNOS protein levels were significantly higher in the cells incubated with AN lipoproteins compared to cells incubated with control lipoproteins both at 3 and 24 h. Although the pathogenesis of AN remains uncertain, evidence exists that modifications to the lipoprotein profile and cholesterol, structural alterations of phospholipids and integral constituents of myelin and synaptosomes may be related to psychotic disorders and body image distortion common to AN. Thus, a relevant pathophysiological association between NO and depression is certainly a possibility, as well as a central role played by NO in the pathogenesis.
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PMID:Lipoproteins obtained from anorexia nervosa patients induce higher oxidative stress in U373MG astrocytes through nitric oxide production. 1829 74

Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. Clinical trials showed that, compared to placebo, rimonabant 20 mg/ day consistently increases weight loss, reduces waist circumference, improves atherogenic dyslipidaemia (low HDL cholesterol, high triglycerides, high small dense LDL), diminishes insulin resistance, reduces HbA1c levels, and contributes to lower blood pressure and C-reactive protein levels. Almost half of the most important metabolic effects occur beyond weight loss, suggesting direct peripheral effects of rimonabant, especially in visceral adipose tissue as suggested by the increase in adiponectin levels. Rimonabant at a daily dose of 20 mg is indicated as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s) such as type 2 diabetes or dyslipidaemia. Adverse effects concern digestive tract (nausea, mostly transient) and psychological disorders (depressed mood, anxiety), in relation to the mechanism of action of the drug. Therefore, rimonabant is contra-indicated in case of depression and/or in patients receiving antidepressants.
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PMID:[Medication of the month. Rimonabant (Acomplia): first CB1 receptor antagonist of the endocannabinoid system]. 1830 86

Long-term depression may increase the risk for adverse coronary events. Low levels of high-density lipoprotein cholesterol (HDL-C) have in particular been suggested to underlie this connection. A total of 124 participants with a recorded seven-year history of depressive symptoms (depressed, n=63) or euthymic state (controls, n=61) underwent a Structured Clinical Interview for DSM-IV to confirm their psychiatric diagnosis. Total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) levels, triglycerides, non-HDL-C and atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were assessed. The HDL-C levels were lower and atherogenic indices higher in the depressed group compared with the controls. Furthermore, those with HDL-C level below the gender-adjusted median (<1.54 mmol/l in women, <1.16 mmol/l in men) were 2.4-fold more likely to be depressed in a model adjusting for age and non-HDL-C (p=0.019). After further adjustment for educational level, marital status, alcohol use, daily smoking and overweight this association remained significant (p=0.049). These findings suggest that compared with the healthy controls, those with long-term depression may have lower HDL-C values and higher atherogenic indices.
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PMID:Low HDL cholesterol associates with major depression in a sample with a 7-year history of depressive symptoms. 1858 11

The aim of the study was to analyse psychological characteristics and medical parameters in obese and overweight to identify the possible psychosocial consequences of obesity that may occur along with the numerous medical problems associated with excess body weight. Analysis was made on 296 patients (103 males and 193 females, median age 50, range 16-81) divided in three groups, depending on their Body mass index (BMI). Group I included 41 patients with BMI ranging from 25 to 29.9, group II included 170 patients with BMI from 30 to 34.9, and group III 85 patients with BM > or =35. We compared medical (glucose, cholesterol, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, body fat percentage) and psychological parameters (anxiety, depression, pros and cons of losing weight, self efficacy and four stages of change) in the patients included in the study. Univariate analysis has shown statistically significant difference among obese and overweight patients in goal weight, systolic and diastolic blood pressure, body fat percentage, glucose and cholesterol serum level. People with higher BMI (>30) found more advantages (pros) over disadvantages (cons) of weight loss but the level of anxiety and depression did not differ significantly among those 3 groups of patients. The results have shown that overweight and obese people have serious medical problems. They also differ in some psychological characteristics which have to be taken into consideration. Therefore, approach to these patients should be multidisciplinary, including dietary care, physical activity, psychological and medical care.
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PMID:Medical and psychological parameters in overweight and obese persons seeking treatment. 1875 17

The evidence of increased cardiovascular disease (CVD) risk in posttraumatic stress disorder (PTSD) is accumulating. The present study aimed to determine whether chronic, combat-related PTSD is associated with serum lipid and homocysteine concentrations that could indicate higher CVD risk. The authors tested 66 war veterans with PTSD, 33 war veterans without PTSD, and 42 healthy volunteers for serum concentrations of homocysteine, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides. All the subjects were men and the analyses were adjusted for age, body mass index and smoking. Potential influences of depression, anxiety, and psychotic symptoms on the outcome measures were checked by introducing the scores from the Hamilton Depression Rating Scale (HAM-D-17), the Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) into the overall statistical model. No differences in total cholesterol, LDL-C, HDL-C and triglycerides were found between the groups. Non-smoking PTSD war veterans had higher homocysteine concentrations (mean=10.4 micromol/L, SD=1.7) when compared to non-smoking war veterans without PTSD (mean=8.2 micromol/L, SD=4.0, P=0.014) and both smoking (mean=8.7 micromol/L, SD=2.3, P=0.008) and non-smoking healthy volunteers (mean=8.8 micromol/L, SD=2.2, P=0.021). The results of our cross-sectional study are possibly confounded by many factors, especially behavioral and life-style related which are difficult to control comprehensively and might have influenced serum lipids and homocysteine concentration in a complex manner. An increase in the homocysteine concentration observed in the non-smoking PTSD patients needs further investigation with a carefully designed prospective study to confirm associated, possibly enhanced CVD risk.
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PMID:Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. 1903 3

A considerable literature has been published on the health benefits of fish, oil-rich fish and fish oils and their constituent long-chain (LC) n-3 PUFA. Evidence from epidemiological studies highlights the cardioprotective attributes of diets rich in fish, especially oil-rich fish. Data from intervention trials are consistent in suggesting that LC n-3 PUFA lower the risk of CVD, probably by the multiple mechanisms of lowering serum triacylglycerols, improving the LDL:HDL ratio, anti-arrhythmic effects on heart muscle, improved plaque stability, anti-thrombotic effects and reduced endothelial activation. Research indicates LC n-3 PUFA provision has an impact during development, and there is preliminary evidence that docosahexaenoic acid supplementation during pregnancy could optimise brain and retina development in the infant. LC n-3 PUFA are also postulated to ameliorate behavioural and mental health disturbances such as depression, schizophrenia, dementia and attention deficit hyperactivity disorder. However, despite some positive evidence in each of these areas, use of LC n-3 PUFA in these conditions remains at the experimental stage. In the case of immune function, there is little doubt that LC n-3 PUFA have a positive effect. Although intervention trials in rheumatoid arthritis show strong evidence of benefit, evidence for efficacy in other inflammatory conditions, including Crohn's disease, ulcerative colitis, psoriasis, lupus, multiple sclerosis, cystic fibrosis and asthma, is inconsistent or inadequate. More promising evidence in some conditions may come from studies which attempt to modify the fetal environment using LC n-3 PUFA supplementation during pregnancy.
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PMID:The impact of long-chain n-3 polyunsaturated fatty acids on human health. 1907 99

Abdominal obesity (high waist circumference) is more strongly associated with cardiovascular disease and type 2 diabetes than generalized adiposity (high body mass index). Recent research has highlighted the role of chronic overactivation of the endogenous endocannabinoid system, acting through its CB(1) receptor, as a key factor involved in the development of abdominal obesity and related cardiometabolic risk abnormalities such as insulin resistance, low HDL-cholesterol, hypertriglyceridemia, inflammation and low adiponectin. Evidence suggests that these cardiometabolic risk factors/markers are not optimally managed by current treatments. Improving the nutrition and physical activity/exercise habits of patients remains the cornerstone of management of elevated global cardiometabolic risk. Antagonism of the endocannabinoid system provides a novel strategy to target several unaddressed cardiometabolic risk markers/factors. Randomized trials of rimonabant in patients with overweight or obesity and/or type 2 diabetes have demonstrated marked and significant improvements in body weight, waist circumference, glycemic control (in patients with type 2 diabetes), features of atherogenic dyslipidemia, insulin resistance, adipose tissue-derived cytokines (leptin and adiponectin) and C-reactive protein (a marker of systemic inflammation). Further analyses suggested that about half of the improvements of several cardiometabolic risk markers were independent from concomitant weight loss. Blood pressure also improved with rimonabant treatment, this effect being consistent with the blood pressure lowering effect of weight loss. The tolerability and safety of rimonabant have been extensively studied and most transient side effects include some gastrointestinal side effects, anxiety, mood changes and incidence of depressive disorders, particularly in patients with previous history of depression. Rimonabant is a useful option for patients with abdominal obesity and with related cardiometabolic risk abnormalities such as an atherogenic dyslipidemia and/or type 2 diabetes.
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PMID:Pleiotropic effects of rimonabant: clinical implications. 1919 81

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.
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PMID:[Association of obesity and depression]. 1921 97


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