UMLS:C0011570 - FACTA Search

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)

In many forms of cardiomyopathic left ventricular (LV) dysfunction, there is a rapid myocardial expression of pro-inflammatory cytokines such as interleukin 1, interleukin 6 and tumour necrosis factor-alpha (TNF-alpha) which mediate, via specific receptors, various processes such as gene expression, cell growth or apoptosis. In the initial stages of myocarditis, the myocardial expression of proinflammatory cytokines appears to be part of an inflammatory process. In many other conditions such as ischaemic cardiomyopathy and chronic LV pressure or volume overload, myocardial expression of proinflammatory cytokines is triggered by an elevation of LV wall stress. Myocardial expression of cytokines contributes to depression of contractile performance and adverse LV remodelling. Cytokine-induced depression of contractile performance appears to result from sphingosine production, which interferes with myocardial calcium handling. In transgenic mice, the rate of progression of LV dilatation appears to correlate with the intensity of myocardial TNF-alpha overexpression. In heart failure patients, cytokine concentrations are elevated not only in the myocardium but also in plasma. Cytokines are, therefore, responsible not only for autocrine and paracrine signalling within the myocardium but also for endocrine signalling throughout the body, especially affecting striated muscle mass with induction of muscle wasting and cachexia. The source of cytokine production in heart failure remains uncertain and several mechanisms have been proposed including endotoxin-induced immune activation due to bowel oedema, myocardial production due to haemodynamic overload and peripheral extramyocardial production due to tissue hypoperfusion and hypoxia. The latter seems to be the most likely mechanism, possibly modulated by the presence of bacterial endotoxins released from the gut. Numerous drugs have meanwhile been shown to influence this cardioinflammatory response to heart failure either by reducing basal levels of cytokines (e.g. amlodipine, pentoxifylline, beta-blockers) or by reducing endotoxin-induced cytokine gene expression (e.g. ouabain, amiodarone, adenosine, angiotensin converting enzyme inhibitors, angiotensin II-receptor blockers). Direct blockade of the deleterious actions of elevated plasma levels of cytokines recently became possible through intravenous infusion of a soluble TNF-alpha receptor fusion protein, which resulted in an increase in exercise tolerance and LV performance.
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PMID:Cytokines and heart failure. 1263 74

Based upon a case report, the hypothesis is proposed that a virus infection could be responsible for remission of affective disease by causing gene silencing. A farmer of 59 had been suffering from a therapy resistant depressive episode over many months. His depressive illness seemed primarily biogenetically determined. Because of acute suicidality clinical treatment and observation became necessary. After six weeks of unsuccessful psychiatric treatment the patient caught a severe virus infection causing pneumonia and myocarditis. The physical treatment showed up to be difficult, but finally managed to cope with the virus infection. Remarkably, parallel to the decrease of physical symptoms also the mood was markedly elevated towards a full remission. At that time the patient was no longer under antidepressant medication. Many viruses have a genetic blueprint made from RNA, rather than DNA. When they infect a cell, double-stranded copies (double-stranded RNA, dsRNA) of their genetic material are produced. In response, the RNA interference (RNAi) pathway of the infected cell is activated. The enzyme Dicer first chops viral dsRNA into small segments of 21-25 basepairs in length, termed short interfering RNAs (siRNAs) and these siRNAs are used to identify intact viral RNA and to mark it for destruction. When an endogenous gene is activated, its sequence is read to produce messenger RNA (mRNA), which contains the information necessary to produce a particular protein, and improper expression of an endogenous gene could cause affective disorder in a patient. Therefore one would expect that if such a patient were infected by a virus that contained a sequence similar to the improperly expressed endogenous gene, the patient's anti-viral response would inadvertently reduce expression of the gene causing affective disorder. If mutations in genes responsible for affective disorders are identified and they turn out to cause over-expression of a particular gene, gene silencing could be an alternative therapeutic tool, especially for therapy-resistant severe depression. The therapy could involve introducing dsRNA either as synthetic RNA, or by infecting the patient with a recombinant virus containing sequence from the gene whose expression must be reduced.
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PMID:Gene silencing: a possible molecular mechanism in remission of affective disorder. 1514 45

The bird examined was a 10-week-old female Gouldian finch (Chloebia gouldiae) from an aviary that had housed about 100 Gouldian finches, which had nasal discharge, dyspnoea, anorexia, depression and a very high mortality (50%) in both adult and young birds. Gross and histopathology revealed moderate to severe lymphoid depletion in the bursa of Fabricius and thymus, and sinusitis/rhinitis, tracheitis, bronchopneumonia, myocarditis, nephritis and splenitis. Circovirus infection was diagnosed in the Gouldian finch based on finding characteristic globular intracytoplasmic inclusion bodies containing 15 to 18 nm virus particles in the mononuclear cells of the bursa of Fabricius by transmission electron microscopy and by demonstrating circovirus DNA in the cytoplasm of mononuclear cells of the bursa of Fabricius by in situ hybridization using a circovirus-specific DNA probe. The Gouldian finch was also affected by concurrent bacterial and adenovirus infections. This is the first report of circovirus infection in a Gouldian finch.
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PMID:Circovirus infection in a Gouldian finch (Chloebia gouldiae). 1554 33

The present study reports the clinical, virological and pathological findings observed in a natural outbreak of highly pathogenic avian influenza in farmed commercial ducks. The ducks developed clinical signs, including mild respiratory distress, depression, mild diarrhoea, loss of appetite and increasing mortality (up to 12%). At necropsy, multifocal mottled necrosis was commonly found in the pancreas with splenomegaly, hepatomegaly, and swollen kidneys. Microscopically, there was necrotized pancreatitis and hepatitis, and lymphocytic meningoencephalitis and myocarditis. Influenza viral antigen was demonstrated in areas closely associated with histopathological lesion. Avian influenza virus was isolated from the caecal tonsil, faeces, and kidney of the domestic ducks. The isolated virus was identified as a highly pathogenic H5N1, with a haemagglutinin proteolytic cleavage site deduced amino acid sequence of ... QREKRKKR/GLFGAIAG ... In order to determine the pathogenicity of the isolate, eight 6-week-old specific pathogen free chickens were inoculated intravenously with the virus, and all birds died within 24 h after inoculation. This is the first report of an outbreak of highly pathogenic avian influenza with clinical signs in commercial domestic ducks in South Korea.
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PMID:Highly pathogenic avian influenza (H5N1) in the commercial domestic ducks of South Korea. 1614 75

Pro-inflammatory factors such as the adipokine leptin and cytokine tumor necrosis factor-alpha (TNFalpha) have been implicated in the onset of myocardial dysfunction in ischemia-reperfusion injury, sepsis, heart failure, viral myocarditis and cardiac allograft rejection. Although circulating TNFalpha and leptin levels are both elevated under a variety of inflammatory conditions, it remains unknown whether TNFalpha and leptin depress cardiac contractile function independently or synergistically. We examined the effect of acute (30 min) and short-term (24h) exposure of TNFalpha, leptin or both on cardiac contractile function in adult rat ventricular myocytes. Contractile properties were evaluated using an Ionoptix Softedge system including peak shortening (PS), maximal velocity of shortening/relengthening (+/-L/t), time-to-PS (TPS) and time-to-90% relengthening (TR(90)). Both TNFalpha (0.5-500 pg/ml) and leptin (1-100 nm) exerted concentration-dependent inhibitions in PS and +/-L/t following a 30-min exposure. TNFalpha but not leptin prolonged TR(90). Interestingly, TNFalpha-induced depression of cell shortening was masked by leptin and vice versa. Following a 24-h incubation, both TNFalpha and leptin significantly inhibited PS and +/-L/t without affecting TPS and TR(90). There was no additive or synergistic response by the two pro-inflammatory factors. The nitric oxide synthase inhibitor l-NMMA abolished depression of myocyte shortening elicited by TNFalpha, leptin or both. In summary, this study demonstrated that the inhibitory effect on cardiac contraction by TNFalpha and leptin may mask each other and share a common mechanism(s), probably dependent on NO.
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PMID:Interaction between tumor necrosis factor-alpha and leptin-induced inhibition of cardiac contractile function in isolated ventricular myocytes. 1629 37

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive depression of myocardial contractile function and ventricular dilatation. Thirty percent of DCM patients belong to the inherited genetic form; the rest may be idiopathic, viral, autoimmune, or immune-mediated associated with a viral infection. Disturbances in humoral and cellular immunity have been described in cases of myocarditis and DCM. A number of autoantibodies against cardiac cell proteins have been identified in DCM. In this study, we have profiled the autoantibody repertoire of plasma from DCM patients against a human protein array consisting of 37,200 redundant, recombinant human proteins and performed qualitative and quantitative validation of these putative autoantigens on protein microarrays to identify novel putative DCM specific autoantigens. In addition to analyzing the whole IgG autoantibody repertoire, we have also analyzed the IgG3 antibody repertoire in the plasma samples to study the characteristics of IgG3 subclass antibodies. By combining screening of a protein expression library with protein microarray technology, we have detected 26 proteins identified by the IgG antibody repertoire and 6 proteins bound by the IgG3 subclass. Several of these autoantibodies found in plasma of DCM patients, such as the autoantibody against the Kv channel-interacting protein, are associated with heart failure.
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PMID:Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease-associated protein chip. 1641 13

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

To assess cardiovascular magnetic resonance (CMR) findings in Takotsubo cardiomyopathy (TTC), 17 consecutive patients (15 women) with TTC who underwent left heart catheterization and gadolinium-enhanced CMR were evaluated. All patients had an abnormal electrocardiogram consisting of ST-segment elevation (n=8) and/or ST-segment depression (n=4) and/or T-wave inversion (n=14). One patient presented with left-bundle branch block. Left ventricular apical segments were involved in 10 patients (classical TTC), while they were not affected in 7 (variant form). Mean time delay between presentation and CMR was 9+/-7 days (range 3-24 days). CMR demonstrated complete resolution (n=4) or significant improvement of initial WMA in all cases. WMA were confined to basal and mid-ventricular segments (segments 1-12 in the 17-segment model) in the variant form, while they were virtually confined to the mid and apical left ventricle (segments 7-17) in classical TTC. Upon presentation ejection fraction by ventriculography was lower in classical TTC (36+/-7% vs. 58 +/-8%, p=0.0001). However, upon follow up ejection fraction by CMR was not different between classical and variant TTC (49+/-9% vs. 56+/-11%, p=0.23). Delayed hyperenhancement was absent in all but one patient. This finding may help differentiate TTC from entities with similar clinical presentations such as myocarditis and myocardial infarction, as the latter typically exhibits a subendocardial pattern of delayed hyperenhancement while the former usually displays a patchy subepicardial pattern.
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PMID:Cardiovascular magnetic resonance findings in typical versus atypical forms of the acute apical ballooning syndrome (Takotsubo cardiomyopathy). 1717 45

Despite clinical evidence of myocardial dysfunction, there is no pathological evidence of myocardial injury in hantavirus pulmonary syndrome (HPS). The dominant opinion is that the primary cardiac lesion is functional rather than structural. The present study describes hantaviral antigen and particles in the cardiac endothelium and interstitial macrophages in association with a typical myocarditis in HPS. Human hearts from 14 individuals who died of HPS were compared with hearts from 14 individuals who died of acute necrotizing pancreatitis associated with acute lung injury and 4 individuals who died accidental deaths without thoracic injury (as controls); all cases were selected from autopsies. Transmural blocks of myocardial tissue were excised from the middle portion of the left-ventricular free wall and fixed in formalin. Small samples of myocardial tissue from 4 HPS cases and 4 non-HPS controls were fixed in glutaraldehyde for electron microscopic study. Histomorphometric, immunohistochemical, and ultrastructural methods were employed to detect the presence of hantavirus in the myocardium and to evaluate interstitial edema and the minor diameter of myocytes, to characterize the immunophenotype, and to estimate the number of inflammatory cells and in situ cytokine-producing cells and the T helper cell subset 1 and 2 immune responses (tumor necrosis factor [TNF]-alpha, interferon-gamma, interleukin [IL]-10, and IL-4). Cardiac remodeling; hantaviral antigen and particles in the endothelium and macrophages; scattered foci of myofiber necrosis; greater interstitial cellular infiltration, mainly composed of macrophages and memory T lymphocytes and a significant number of T helper and B lymphocytes; and TNF-alpha protein expression in macrophage-type cells and cardiomyocytes were observed to a greater extent in HPS myocardium than in normal and acute pancreatitis control myocardium. These findings give support to the opinion that structural changes could be responsible for myocardial depression and shock in HPS, and it should be properly named as "hantavirus cardiopulmonary syndrome" (HCPS).
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PMID:Hantavirus infection induces a typical myocarditis that may be responsible for myocardial depression and shock in hantavirus pulmonary syndrome. 1743 35

Cardiac manifestations of Lyme Borreliosis are relatively infrequent, occurring within weeks after the infectious tick bite (median of 21 days), and resulting at this stage from a direct borrelial infection of the myocardium, as indicated by reports of spirochete isolation from pericardium and myocardium. They may persist or appear in the late, tertiary phase of the illness, being then more likely due to infection-triggered autoimmunity. Lyme carditis typically presents with a fluctuating degree of atrioventricular block that spontaneously resolves in several days. Rarely, myocarditis may occur with or without pericardial involvement, in patients presenting with chest pain, ST depression or T wave inversion, mimicking an acute myocardial infarction, and various arrhythmias are reported, as well as pericardial effusion or heart failure. A complete recovery is usually observed, spontaneous or after antibiotherapy. Severe myocarditis or Pericarditis leading to death is exceptional. The diagnosis of Lyme carditis is based on the same association of clinical and laboratory features as in Lyme disease without cardiac involvement. But the occurrence of conduction disturbances in healthy young people suggests screening for other criteria of Lyme disease. The management of Lyme carditis does not differ from the treatment of Lyme disease without carditis and is mainly based upon the use of doxycycline or ceftriaxone.
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PMID:[Cardiac involvement in Lyme disease]. 1762 49

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