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)

This is a case report of lepromatous infection diagnosed at necropsy, with cardiac alterations directly caused by mycobacteria, in a 34-year-old black male with the cardiac form of Chagas' disease. The possible role of inflammatory mediators on cardiac dysfunction, and the possibility that immune depression may be due to factors associated with heart failure, as congestive splenomegaly and splenic infarctions, are emphasized.
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PMID:[Hanseniasis virchowiana in Chagas cardiopathy: an autopsy report]. 966 66

Visceral leishmaniasis (VL) is characterized by a depression of the T helper cell type 1 immune response. Although mRNA expression for interleukin-4 (IL-4) is observed, evidence of the role of this cytokine in the pathogenesis of VL has been lacking. Since IL-4 is involved in IgE synthesis, we measured the total IgE and Leishmania antigen-specific IgE antibody levels in sera from patients with VL. Specific IgE antibodies detected by an ELISA technique after absorbing the sera with purified sheep IgG anti-human IgG were found in all 23 patients with VL and were not detected in subjects with subclinical Leishmania chagasi infection (n = 10), Chagas' disease (n = 10), atopic patients (n = 10), and healthy controls (n = 10). Levels of Leishmania-specific IgE (optical density values) before and after treatment were 0.100 +/- 0.03 (mean +/- SD) and 0.028 +/- 0.002, respectively (P < 0.05). These results indicate that a specific IgE response is useful in the diagnosis of active disease and to evaluate response to treatment.
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PMID:Anti-leishmanial IgE antibodies: a marker of active disease in visceral leishmaniasis. 974 38

Global left ventricular (LV) systolic dysfunction is the strongest predictor of morbidity and mortality in Chagas disease. Echocardiography is considered the gold standard for the detection of LV dysfunction, but not always available in endemic areas where chagasic cardiomyopathy is most common. Brain natriuretic peptide (BNP) is a neurohormone that has been recently described as a simple and inexpensive diagnostic and prognostic marker for patients with congestive heart failure. Chagasic patients (n = 63) and non-infected healthy individuals (n = 18) were recruited prospectively and underwent complete clinical examination, echocardiography and 24-h Holter monitoring. BNP was measured from thawed plasma samples using the Triage BNP test. We observed high levels of BNP in association with depression of LV ejection fraction, with increase of LV end-diastolic diameter and with LV premature complexes. An elevated concentration of BNP, defined as a concentration of 60 pg/ml or more, had a sensitivity of 91.7%, specificity of 82.8%, positive predictive value of 52.4%, and negative predictive value of 98% for detecting LV dysfunction (LV ejection fraction < 40%).BNP measurement using a simple, relatively inexpensive and rapid test has a promising role in identifying LV dysfunction associated with chagasic cardiomyopathy. Equally important, patients with Trypanosoma cruzi infection who have low levels of BNP level in plasma have a very low likelihood of severe cardiac involvement, and echocardiography is probably not necessary.
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PMID:Brain natriuretic peptide and left ventricular dysfunction in chagasic cardiomyopathy. 1555 79

Young children spend more than 90% of their time in the household environment--a likely place of exposure to hazardous substances. In the developing world, childhood diarrheal disease and acute lower respiratory infections represent a large portion of the global burden of disease and are strongly related to housing conditions. In the developed world, allergies and asthma are also strongly linked to housing conditions. Therefore, intervention to improve housing is essential to improve and maintain children's health. This paper will review several factors that have been shown to mediate housing and health relations, including psychosocial, environmental, socioeconomic, behavior-cultural, and physiological factors, and will provide examples of intervention to improve child health, with housing as a focus. Environmental contaminants found in the household include biological (for example, vector-borne diseases, dustmites, mold, water- and sanitation-related), chemical (for example, lead, volatile organic compounds, asbestos) or physical (for example, radon, electric and magnetic fields). Socioeconomic factors include household income, the ability to obtain adequate and appropriate housing, and the ability to implement ongoing preventative maintenance. Housing tenure has been used as a proxy for socioeconomic status and shown some relation with health outcome. Socioeconomic factors can be relevant to the ability of households to create social networks that affect health. Psychosocial factors, including stress and depression, can also be related to housing type or design. Behavioral-cultural factors include practices that might influence exposure to chemical, biological, or radiation hazards like time-activity patterns, including gender relations and household decision-making patterns. Physiological factors include genetics or the nutritional and immune status of household members, which can influence the extent to which other housing factors like biological or chemical contaminants adversely affect children. Examples of intersectoral interventions and strategies to improve child health globally, with housing and health as a focus, include integrated pest-management programs to control vector-borne diseases like malaria and Chagas disease and energy-efficiency programs to improve thermal comfort and to reduce the presence of allergens like mold and dustmites. Other interventions include housing and health policy, regulation and standard setting, education, training, and participation.
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PMID:Interventions to improve children's health by improving the housing environment. 1574 71

After returning from the Beagle in 1836, Charles Darwin suffered for over 40 years from long bouts of vomiting, gut pain, headaches, severe tiredness, skin problems, and depression. Twenty doctors failed to treat him. Many books and papers have explained Darwin's mystery illness as organic or psychosomatic, including arsenic poisoning, Chagas' disease, multiple allergy, hypochondria, or bereavement syndrome. None stand up to full scrutiny. His medical history shows he had an organic problem, exacerbated by depression. Here we show that all Darwin's symptoms match systemic lactose intolerance. Vomiting and gut problems showed up two to three hours after a meal, the time it takes for lactose to reach the large intestine. His family history shows a major inherited component, as with genetically predisposed hypolactasia. Darwin only got better when, by chance, he stopped taking milk and cream. Darwin's illness highlights something else he missed--the importance of lactose in mammalian and human evolution.
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PMID:Darwin's illness revealed. 1581 89

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
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PMID:Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). 1693 19

The presence of mutilations in the form of tattooing and body piercing is becoming increasingly common in adolescents, a practice that is not free of risk. Reported complications include local infections, bleeding, tearing, hypersensitivity reactions, transfusion-transmitted diseases (hepatitis B virus, hepatitis C virus, HIV, syphilis), Chagas' disease and infective endocarditis. On the other hand, several studies have demonstrated an association between body modifications and high-risk behavior in adolescents, as alcohol or drug abuse, cigarette smoking, violence and schooling problems. There is also an association with depression, suicide, eating disorders and other psychophysiologic disorders. This is a review of body modifications in adolescents, emphasizing in the risks, complications and motivations of this practice.
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PMID:[Tattooing and piercing in teenagers]. 1718 6

The biology of natural selection is an enduring mystery, as is the nature of Charles Darwin's chronic illness. Of the theories advanced to explain the latter, Oedipal conflicts and Chagas' disease are preeminent. Hypomania, however, propelled Darwin to the pinnacle of scientific achievement and good health, the depression that followed condemning him to intellectual stagnation, lethargy, impaired memory and concentration, and incapacitating gastrointestinal disorders. Examples of natural selection in humans are much sought after when, ironically, one need look no further than Darwin himself.
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PMID:The paradoxical advantages and disadvantages of natural selection: the case history of Charles Darwin. 1749 50

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.
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PMID:Chagas disease as a mechanistic model for testing a novel hypothesis. 1836 74

Trypanosoma cruzi phosphodiesterase (PDE) C (TcrPDEC), a novel and rather unusual PDE in which, unlike all other class I PDEs, the catalytic domain is localized in the middle of the polypeptide chain, is able to hydrolyze cyclic GMP (cGMP), although it prefers cyclic AMP (cAMP), and has a FYVE-type domain in its N-terminal region (S. Kunz et al., FEBS J. 272:6412-6422, 2005). TcrPDEC shows homology to the mammalian PDE4 family members. PDE4 inhibitors are currently under development for the treatment of inflammatory diseases, such as asthma, chronic pulmonary diseases, and psoriasis, and for treating depression and serving as cognitive enhancers. We therefore tested a number of compounds originally synthesized as potential PDE4 inhibitors on T. cruzi amastigote growth, and we obtained several useful hits. We then conducted homology modeling of T. cruzi PDEC and identified other compounds as potential inhibitors through virtual screening. Testing of these compounds against amastigote growth and recombinant TcrPDEC activity resulted in several potent inhibitors. The most-potent inhibitors were found to increase the cellular concentration of cAMP. Preincubation of cells in the presence of one of these compounds stimulated volume recovery after hyposmotic stress, in agreement with their TcrPDEC inhibitory activity in vitro, providing chemical validation of this target. The compounds found could be useful tools in the study of osmoregulation in T. cruzi. In addition, their further optimization could result in the development of new drugs against Chagas' disease and other trypanosomiases.
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PMID:Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cruzi, the etiological agent of Chagas' disease. 2062 48


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