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)

Hyperhomocysteinemia (HHCY) is a consequence of disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological and clinical studies have proven HHCY to be an independent risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Trials in progress may clarify the "causality" of high homocysteine (HCY) concentrations and will assess the value of HCY lowering therapy. HHCY is also seen as a risk factor for neurodegenerative diseases such as cognitive impairment, dementia, Alzheimer's disease, and also for depression. There is a high prevalence of HHCY as a syndrome of vitamin shortage in elderly subjects, which strongly increases with advancing age. Elderly people have a high frequency of vitamin B12 deficiency which is more reliably diagnosed by measurement of serum methylmalonic acid and holotranscobalamin II, the metabolically active B12 fraction, than by total serum vitamin B12. Subjects who follow a strict vegetarian diet also have a high prevalence of HHCY caused by vitamin B12 deficiency. For prevention of neurological damages an early diagnosis of vitamin B12 deficiency is important. Furthermore, HHCY is a factor in the pathogenesis of neural tube defects and preeclampsia. HCY should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in adipose subjects, in elderly people, in vegetarians, in postmenopausal women, and in early pregnancy.
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PMID:Hyperhomocysteinemia: a new risk factor for degenerative diseases. 1238 6

Autonomic functions, such as increased sympathetic and parasympathetic activity and the brain's suprachiasmatic nucleus, higher nervous centres, depression, hostility and aggression appear to be important determinants of heart rate variability (HRV), which is, itself, an important risk factor of myocardial infarction, arrhythmias, sudden death, heart failure and atherosclerosis. The circadian rhythm of these complications with an increased occurrence in the second quarter of the day may be due to autonomic dysfunction as well as to the presence of excitatory brain and heart tissues. While increased sympathetic activity is associated with increased levels of cortisol, catecholamines, serotonin, renin, aldosterone, angiotensin and free radicals; increased parasympathetic activity may be associated with greater levels of acetylecholine, dopamine, nitric oxide, endorphins, coenzyme Q10, antioxidants and other protective factors. Recent studies indicate that hyperglycemia, diabetes, hyperlipidemia, ambient pollution, insulin resistance and mental stress can increase the risk of low HRV. These risk factors, which are known to favour cardiovascular disease, seem to act by decreasing HRV. There is evidence that regular fasting may modulate HRV and other risk factors of heart attack. While exercise is known to decrease HRV, exercise training may not have any adverse effect on HRV. In a recent study among 202 patients with acute myocardial infarction (AMI), the incidence of onset of chest pain was highest in the second quarter of the day (41.0%), mainly between 4.0-8.0 AM, followed by the fourth quarter, usually after large meals (28.2%). Emotion was the second most common trigger (43.5%). Cold weather was a predisposing factor in 29.2% and hot temperature (> 40 degrees celsius) was common in 24.7% of the patients. Dietary n-3 fatty acids and coenzyme Q10 have been found to prevent the increased circadian occurrence of cardiac events in our randomized controlled trials, possibly by increasing HRV. We have also found that n-3 fatty acids plus CoQ can decrease TNF-alpha and IL-6 in AMI which are pro-inflammatory agents. There is evidence that dietary n-3 fatty acids canenhance hippocampal acetylecholine levels, which may be protective. Similarly, the stimulation of the vagus nerve may inhibit TNF synthesis in the liver and acetylecholine, the principal vagal neurotransmitter, significantly attenuates the release of pro-inflammatory cytokines TNF-alpha, interleukin 1,6 and 18, but not the anti-inflammatory cytokine IL-10 in experiments. Therefore, any agent which can enhance brain acetylecholine levels, may be used as a therapeutic agent in protecting the suprachiasmatic nucleus, higher nervous centres, vagal activity and sympathetic nerve activity which are known to regulate the body clock and HRV and the risk of SCD and heart attack.
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PMID:Brain-heart connection and the risk of heart attack. 1265 78

The aim of this study was to examine the long-term effect of lung transplantation on Health Related Quality of Life by studying 28 patients who survived at least 55 months after lung transplantation. Measures included the Nottingham Health Profile, questions concerning lung-specific problems, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-Being, the Karnofsky performance index, and questions concerning activities of daily life. Furthermore, comorbid conditions were measured. Before transplantation patients reported restrictions on almost all quality of life measures. Until approximately 43 months after transplantation there were significant improvements on most dimensions of the Nottingham Health Profile and more patients could walk without dyspnea. Significant improvements occurred with regard to the levels of anxiety, depression, and well being, and the scores on the Karnofsky performance index improved. Activities of daily life could be performed without help by most patients. After approximately 43 months patients experienced more dyspnea, anxiety, depression, and a lower level of well being. The number of patients suffering from a decrease of kidney function, drug treated hyperlipidemia, insulin dependent diabetes mellitus and bronchiolitis obliterans syndrome increased. It may be concluded that patients experience a stable and better overall quality of life after transplantation. Long-term after lung transplantation patients experience a decline on several dimensions of quality of life, which may be explained by an increase of comorbid conditions and Bronchiolitis Obliterans Syndrome.
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PMID:Long-term quality of life in patients surviving at least 55 months after lung transplantation. 1267 22

Approximately half of patients with schizophrenia have at least one comorbid psychiatric or medical condition, worsening prognosis and contributing to the high rate of morbidity and mortality. Depression is associated with suicide, the leading cause of premature death in patients with schizophrenia; obsessive-compulsive symptoms may worsen prognosis; alcohol and substance use disorders are associated with a poor outcome; and comorbid medical conditions, including cardiac and pulmonary disease, infectious diseases, diabetes, hyperlipidemia, hypogonadism, and osteoporosis, are often underrecognized and undertreated. The new generation of antipsychotic medications has improved the potential outcome of patients with schizophrenia. Providing optimal treatment for patients and fully realizing the potential of these new agents require focused attention on detection, recognition, and treatment of comorbid psychiatric and medical conditions in patients with schizophrenia.
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PMID:Detection and management of comorbidity in patients with schizophrenia. 1268 63

Endogenous thyroid receptor hormones 3,5,3',5'-tetraiodo-l-thyronine (T(4), 1) and 3,5,3'-triiodo-l-thyronine (T(3), 2) exert a significant effects on growth, development, and homeostasis in mammals. They regulate important genes in intestinal, skeletal, and cardiac muscles, the liver, and the central nervous system, influence overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood and overall sense of well being. The literature suggests many or most effects of thyroid hormones on the heart, in particular on the heart rate and rhythm, are mediated through the TRalpha(1) isoform, while most actions of the hormones on the liver and other tissues are mediated more through the TRbeta(1) isoform of the receptor. Some effects of thyroid hormones may be therapeutically useful in nonthyroid disorders if adverse effects can be minimized or eliminated. These potentially useful features include weight reduction for the treatment of obesity, cholesterol lowering for treating hyperlipidemia, amelioration of depression, and stimulation of bone formation in osteoporosis. Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism and, in particular, cardiovascular toxicity. Consequently, development of thyroid hormone receptor agonists that are selective for the beta-isoform could lead to safe therapies for these common disorders while avoiding cardiotoxicity. We describe here the synthesis and evaluation of a series of novel TR ligands, which are selective for TRbeta(1) over TRalpha(1). These ligands could potentially be useful for treatment of various disorders as outlined above. From a series of homologous R(1)-substituted carboxylic acid derivatives, increasing chain length was found to have a profound effect on affinity and selectivity in a radioreceptor binding assay for the human thyroid hormone receptors alpha(1) and beta(1) (TRalpha(1) and TRbeta(2)) as well as a reporter cell assay employing CHOK1-cells (Chinese hamster ovary cells) stably transfected with hTRalpha(1) or hTRbeta(1) and an alkaline phosphatase reporter-gene downstream thyroid response element (TRAFalpha(1) and TRAFbeta(1)). Affinity increases in the order formic, acetic, and propionic acid, while beta-selectivity is highest when the R(1) position is substituted with acetic acid. Within this series 3,5-dibromo-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (11a) and 3,5-dichloro-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (15) were found to reveal the most promising in vitro data based on isoform selectivity and were selected for further in vivo studies. The effect of 2, 11a, and 15 in a cholesterol-fed rat model was monitored including potencies for heart rate (ED(15)), cholesterol (ED(50)), and TSH (ED(50)). Potency for tachycardia was significantly reduced for the TRbeta selective compounds 11a and 15 compared with 2, while both 11a and 15 retained the cholesterol-lowering potency of 2. This left an approximately 10-fold therapeutic window between heart rate and cholesterol, which is consistent with the action of ligands that are approximately 10-fold more selective for TRbeta(1). We also report the X-ray crystallographic structures of the ligand binding domains of TRalpha and TRbeta in complex with 15. These structures reveal that the single amino acid difference in the ligand binding pocket (Ser277 in TRalpha or Asn331 in TRbeta) results in a slightly different hydrogen bonding pattern that may explain the increased beta-selectivity of 15.
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PMID:Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. 1269 76

Shosaikoto, a Kampo medicine used clinically to treat patients with chronic hepatitis or cirrhosis in Japan, displays immunoregulatory effects, especially on macrophage functions. Oral administration of shosaikoto influences the synthesis of humoral factors such as the interleukins, nitric oxide and prostaglandins in macrophages. In addition, phagocytic activity is enhanced by treatment with shosaikoto, resulting in an antigen that is effectively presented to T lymphocytes to produce more antibodies. The role of macrophages in the pathogenesis of atherosclerosis is well recognized, although a therapeutic agent targeted at macrophages has not yet been developed. When shosaikoto was administered to atherosclerotic rabbits, it did not exhibit antihyperlipidemic effects but did reduce the formation of atherosclerotic lesions. In addition, treatment with shosaikoto suppressed intimal hyperplasia in apoE-deficient mice fed a cholesterol-enriched diet for nine weeks. Biochemical studies demonstrated that the mechanism of the antiatherosclerotic effect was partly due to the increase of oxidized low-density lipoprotein (oxLDL) elimination by macrophages, resulting from stimulation of oxLDL uptake through scavenger receptors, activation of acyl-CoA:cholesterol acyltransferase and neutral cholesteryl ester hydrolase, and increase of cholesterol elimination by high-density lipoprotein. Furthermore, shosaikoto is able to reverse the depression of macrophage functions caused by hyperlipidemia. These results indicate the potential of this medicine as a new type of preventive or therapeutic agent for atherosclerosis.
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PMID:Shosaikoto as a potential antiatherosclerotic agent. 1293 13

Elevated cortisol in a subset of depressed patients is an enduring and well-replicated finding. Much interest has focused on the possible effects of depression on the hippocampus; however, an emerging body of evidence suggests an association between depression and non-central nervous system illnesses. In this review, data on the effects of depression on the brain and other organ systems sensitive to elevated cortisol are discussed. From searches of the MEDLINE, PSYCHINFO, and Current Contents databases, and other sources, articles were found specifically related to depression and physical changes or medical conditions associated with corticosteroid excess in patients with Cushing's disease, including cognitive impairment, hippocampal atrophy, increased waist-to-hip ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density. Some evidence suggests an association between depression and hypertension, peptic ulcers, and diabetes. Depression does not appear to be associated with hyperlipidemia. The data provide some support for similar health effects in depressed patients and patients with Cushing's disease or the metabolic syndrome; however, additional studies are needed relating systemic effects of depression to cortisol. Limitations of the current literature, treatment implications, and possible directions for future research are discussed.
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PMID:Association of depression with medical illness: does cortisol play a role? 1470 19

The challenges of the epidemic are not limited to concerns about bulk and weight. The disabilities caused by obesity are physiologic and psychosocial. The increased waist to hip girth is associated with increased risk of cardiovascular disease, hyperlipidemia, hypertension, and diabetes. Obesity also has been related directly to increased risk of sleep apnea, cancer, gallbladder disease, musculoskeletal disorders, severe pancreatitis, bacterial panniculitis, diverticulitis, infertility, urinary incontinence, and idiopathic intracranial hypertension. The psychosocial factors and quality of life in the obese population also have been documented. Although there is some debate, the obese have been found to be twice as likely to suffer from anxiety, impaired social interaction,and depression when compared with the nonobese population. Although advances in obesity surgery have resulted in long-term, lasting treatment of this disease and some of its comorbidities (ie, diabetes, hypertension, sleep apnea), There is a pressing need to develop a comprehensive medical and nutrition plan to reduce the prevalence of this newly identified disease state. Some draw parallels to tobacco and the morbidity and mortality associated with its use. Perhaps there are similarities in these two epidemics. Both start with education of the population as to the morbidities and mortality associated with the disease. As with tobacco, this education is especially important for youth. Without a plan of education to promote nutrition and increased physical activity, and continued research into the causes of obesity, the prevalence of obesity will continue to rise in the United States.
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PMID:Epidemiology of obesity in the United States. 1582 34

More than 30 million men are estimated to have erectile dysfunction (ED) in the United States. Worldwide, ED is estimated to affect more than 150 million men, and that number is expected to exceed 300 million men by the year 2025. The prevalence of ED ranges from 7% in men aged 18-29 years to 85% in men aged 76-85 years. In addition, a recent report showed that 68% of patients with ED aged 18 years and older have at least one comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression, and research suggests that ED may be an early indicator of systemic vascular disease. Viagra (sildenafil citrate), the first-in-class phosphodiesterase type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED. In the 7 years since its market launch, more than 750,000 physicians have prescribed sildenafil to more than 23 million men, helping establish an excellent safety and efficacy record. Clinical studies have demonstrated that sildenafil successfully treats ED of varied organic, psychogenic or mixed aetiology, and is effective in men with ED and comorbidities such as hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a breakthrough medication that addressed a previously unfulfilled medical need. The impact of sildenafil has stimulated academic, clinical and industrial research to better understand the nature of sexual function and develop better treatment and management for sexual dysfunctions such as ED. With the advent of other erectogenic therapies for the treatment of ED, this 7-year update will focus on the unique history and development of sildenafil, its current use and applications and its future directions and indications. Special emphasis is placed on the impact of sildenafil on our understanding of sexual health and on the extensive safety and efficacy data that have been amassed from numerous clinical trials.
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PMID:Past, present, and future: a 7-year update of Viagra (sildenafil citrate). 1592 97

Despite the established benefit of drug-eluting stents (DESs) in improving clinical and angiographic outcomes in pivotal, randomized trials, relatively little is known regarding the frequency and patterns of DES use in clinical practice. To characterize DES use in a broad, unselected high-risk non-ST-segment elevation acute coronary syndrome population, we evaluated the frequency, patterns, and predictors of DES use among patients in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Quality Improvement Initiative who were selected to undergo percutaneous coronary intervention. Of 8,852 patients with high-risk non-ST-segment elevation acute coronary syndromes who underwent percutaneous revascularization at 262 hospitals between October 2003 and June 2004, 5,858 (66.2%) were treated with DESs and 2,994 (33.8%) were not. During a 9-month period, DES use increased considerably from 52.6% of cases in October 2003 to 78.5% in June 2004. Compared with the bare metal stent cohort, patients receiving DESs were more likely to be women and to have private insurance, but were less likely to present with positive cardiac markers or ST-segment depression. In adjusted analysis, death and recurrent infarction were significantly lower among the patients with a DES, yet early revascularization and treatment with guideline-recommended therapies were less frequent. In a multivariate model, significant (p <0.05) predictors of DES use included hyperlipidemia, elevated systolic blood pressure, private insurance, and treatment at a larger hospital. In conclusion, these findings not only identified differences in the selection and treatment of patients receiving bare metal stents versus DESs, but also demonstrated the increasing use of DESs in higher risk patients who have previously been excluded from randomized, pivotal trials.
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PMID:Frequency, predictors, and outcomes of drug-eluting stent utilization in patients with high-risk non-ST-segment elevation acute coronary syndromes. 1616 52


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