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)

A role for interleukin-6 (IL-6) in malignant mesothelioma has been suggested by the clinically presenting symptoms of mesothelioma patients, which include fever, weight loss and thrombocytosis. A murine model of malignant mesothelioma was therefore used to examine the potential role of IL-6 in this cancer type and whether the effect of interferon alpha (IFN alpha) therapy on mesothelioma might be mediated, in part, by regulating IL-6 levels and/or IL-6-induced pathobiology. A panel of human and murine mesothelioma cell lines was assayed for endogenous IL-6 production in a bioassay, and for IL-6-mRNA expression. Four out of 5 human and 5 out of 15 murine mesothelioma cell lines produced moderate to high levels of bioactive IL-6 in vitro. This result was corroborated by mRNA detection. One of the representative murine cell lines, AB22, was chosen for further in vivo studies in the murine mesothelioma model. In AB22-inoculated mice detectable serum IL-6 levels were found to precede macroscopically detectable tumour growth, clinical signs (cachexia, abdominal distension, diarrhoea) and changes in the peripheral lymphoid organs (cell depletion and functional depression). Treatment with anti-IL-6 antibody curtailed the clinical symptoms (P < 0.001), as did treatment with recombinant human (rhu) IFN alpha (P < 0.001). Neither anti-IL-6 antibody nor rhuIFN alpha had a direct growth-inhibitory effect on the AB22 mesothelioma cell line in vitro, however, in vivo rhuIFN alpha treatment of mice inoculated with AB22 cells attenuated both IL-6 mRNA expression in the tumours and serum IL-6 levels, ameliorated the depression of lymphocyte activities, and enhanced the number of tumour-infiltrating lymphocytes and macrophages. On the basis of these results it is suggested that IL-6 mediates some of these effects, directly or indirectly, and that a combination therapy of rhuIFN alpha and anti-IL-6 antibody may be an improved palliative treatment for patients with malignant mesothelioma.
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PMID:Interleukin-6 involvement in mesothelioma pathobiology: inhibition by interferon alpha immunotherapy. 775 Jan 22

Pregnant Fischer 344 rats were given fluoxetine orally at dose levels of 0, 2, 5, or 12.5 mg/kg on Gestation Days (GD) 6-15; pregnant Dutch Belted rabbits were given 0, 2.5, 7.5, or 15 mg/kg orally on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated at 12.5 mg/kg by depression of weight gain and food consumption. Fetal viability, weight, and morphology were not affected at any dose level. Maternal and developmental No Observed Adverse Effect Levels (NOAELs) in the rat were 5 and 12.5 mg/kg, respectively. In rabbits, weight loss occurred at 2.5, 7.5, and 15 mg/kg. Food consumption was also depressed at 7.5 and 15 mg/kg; abortions and maternal mortality occurred secondarily to anorexia and cachexia at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. A NOAEL for maternal effects was not established in the rabbit; the NOAEL for developmental effects in the rabbit was 15 mg/kg. Based on these data, fluoxetine did not exhibit any toxicity toward the developing rat or rabbit conceptus at doses that were maternally toxic.
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PMID:Developmental toxicology studies of fluoxetine hydrochloride administered orally to rats and rabbits. 805 99

In common with any medical problem, careful assessment and an analytical approach are the keystones to effective symptom control in advanced cancer. When dealing with such symptoms the multi-faceted pathophysiology must be considered, and due attention paid to the affective component of pain and other symptoms. Adequate care given to history taking and a knowledge of the likely pathogenesis of symptoms in advanced cancer can prevent unnecessary investigations and fruitless trials of inappropriate symptomatic remedies. The treatment chosen should be the simplest effective regimen tailored to the individual patient. The importance of explanation to the patient cannot be overstated and is an integral part of any treatment and the sole component of many. This paper reviews the management of common symptoms in advanced cancer (dyspnoea, nausea and vomiting, constipation, anorexia-cachexia syndrome, hypercalcaemia, confusion, insomnia and depression.
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PMID:Control of common symptoms in advanced cancer. 808 Feb 22

Transforming growth factor beta is a known inhibitor of the proliferation and differentiation of early haematopoietic progenitors but has no effect on mature erythroid cells in vitro. Mice injected with rhTGF beta 1 exhibited severe and progressive suppression of erythropoiesis manifested by a decline of reticulocyte count, marrow erythroblasts and marrow and spleen CFU-E, which could be prevented by administration of erythropoietin. This suppression of erythropoiesis was associated with the appearance of tumour necrosis factor in the blood, development of pronounced cachexia and depression of serum erythropoietin levels. TGF beta induces TNF in vivo that leads to cachexia, decrease of serum erythropoietin levels and suppression of erythropoietin dependent erythropoiesis.
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PMID:Chronic administration of transforming growth factor-beta suppresses erythropoietin-dependent erythropoiesis and induces tumour necrosis factor in vivo. 821 88

Patients with HIV-infection often exhibit progressive loss of weight and poor nutritional status. The problems, which may appear during all stages of the HIV-infection, may be explained by low intake of food or selected nutrients as a result of anorexia and eating problems, and by impaired gastro-intestinal function and increased metabolic rate following secondary to opportunistic infections or the HIV-infection itself. The extent of weight loss and depletion of body cell mass is discussed in relation to the possible effect on development of the disease and time of death in AIDS-patients. Compromising on nutritional status may have a negative effect on the outcome of treatment, and may lead to malnutrition-related immune depression and rates of infection. Nutrition issues are of vital importance to HIV-infected persons. Although nutrition does not promise of a "magic bullet", dietary counselling and nutritional intervention may prevent cachexia and alleviate some symptoms of the disease.
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PMID:[Nutritional counseling to patients with HIV infection. Can nutritional intervention prevent, expose or relieve symptoms in HIV-positive persons?]. 844 78

The effects of progressive cachexia on protein metabolism in skeletal muscle has been investigated in mice bearing the MAC16 adenocarcinoma which produces cachexia with tumour burdens of < 1% of the host weight. Weight loss was accompanied by loss of whole body nitrogen in proportion to the overall loss of body mass. Using L-[4-3H]phenylalanine to label proteins in gastrocnemius muscle, a significant depression (60%) in protein synthesis occurred in animals with a weight loss between 15 and 30% accompanied by an increase in protein degradation, which increased with increasing weight loss between 15 and 30%. Muscle degradation in vitro could be achieved by serum from cachectic animals, which appeared to contain a proteolysis-inducing factor. These results suggest that the increased degradation of skeletal muscle seen in this model of cachexia may be due to a circulating proteolysis-inducing factor.
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PMID:Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia. 847 25

This study was initiated to evaluate the in vivo infectivity and pathogenicity of a group of recombinant feline leukemia viruses (rFeLVs) previously generated by in vitro forced recombination between a FeLV subgroup A virus (FeLV-A) and an endogenous FeLV (enFeLV) envelope (env) element (Sheets et al., 1992, Virology 190, 849-855). To determine infectivity of rFeLVs, neonatal cats were inoculated with rFeLVs alone or in combination with FeLV-A. The recombinant viruses were able to replicate efficiently in vivo only when administered along with FeLV-A. Of six co-infected cats, three developed thymic lymphosarcomas, one severe aplastic anemia, and two cachexia and depression; all were viremic and seroconverted shortly after inoculation. While both virus types were detected in virtually all tissues examined from these tumor-bearing cats, there was a particularly noteworthy sequence reversion in the rFeLVs. It is known that exogenous FeLV isolates carry a conserved neutralizing MGPNL epitope in the middle of the surface glycoprotein domain of the env gene. In contrast, the parental recombinant viruses used to inoculate these cats harbored the enFeLV-derived MGPNP sequence at this position. However, all in vivo-propagated recombinants displayed the MGPNL sequence, while the env-encoded backbone flanking the MGPNL sequence was that of the parental recombinant virus. These results suggest that viruses with the MGPNL epitope have an in vivo proliferative advantage. The data also provide an explanation for the conservation of this epitope in exogenous FeLVs despite the existence of variant forms in enFeLV proviral elements with which they can recombine.
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PMID:Feline leukemia virus variants in experimentally induced thymic lymphosarcomas. 855 60

Anorexia is associated with disorders of all systems. Anorexia represents a consistent clinical manifestation during acute and chronic pathophysiological processes (infection, inflammation, injury, toxins, immunological reactions, malignancy and necrosis). Anorexia during disease can be beneficial or deleterious depending on the timing and duration. Temporary anorexia during acute disease may be beneficial to an organism since a restriction in the intake of micro- and macro-nutrients will inhibit bacterial growth. Long-term anorexia during chronic disease, however, is deleterious to an organism and may be associated with cachexia, which can ultimately result in death. Various mechanisms participate in the anorexia observed during disease, including cytokine action. Anorexia induced by cytokines is proposed to involve modulation of hypothalamic-feeding associated sites, prostaglandin-dependent mechanisms, modifications of neurotransmitter systems, gastrointestinal, metabolic, and endocrine factors. In addition, the anorexia-cachexia syndrome is multifactorial and may involve chronic pain, depression or anxiety, hypogeusia and hyposmia, chronic nausea, early satiety, malfunction of the gastrointestinal system, metabolic alterations, cytokine action, production of other anorexigenic substances and/or iatrogenic causes (chemotherapy, radiotherapy). Cachexia may result not only from anorexia and a decreased caloric intake, but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions), or a change in body metabolism. Research has focused on potential interventions to modify anorexia during disease and the anorexia-cachexia syndrome. Nutritional modifications and the use of specific steroids (such as megestrol acetate) are being tested in the clinical setting. Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexia (during a critical time in a specific disease), and to devise less toxic immunotherapeutic regimens using cytokines.
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PMID:Anorexia during acute and chronic disease. 905 54

The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.
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PMID:Serum cortisol and DHEA concentrations during HIV infection. 926 42

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophan-nicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cachexia.
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PMID:Cancer cachexia and depressive states: a neuro-endocrine-immunological disease? 928 72


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