Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.
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PMID:Visceral leishmaniasis: a model for infection-induced cachexia. 163 76

Deterioration in nutritional status occurs late in the progress of cancers at certain sites, but at all stages in patients with gastrointestinal cancer. Weight loss with decrease in body fat and muscle wastage, occurs to a varying degree. Superficially, the clinical condition resembles simple food deprivation. However, the derangements in metabolism are often and some patients show an elevated resting energy expenditure, disturbances of carbohydrate, fat and protein metabolism and generally, a failure to adapt to reduced food intake, which is characteristic of cachexia. Cancer cachexia then becomes characterized by signs of marked negative energy and protein balance, including hypoalbuminemia, weight loss, and anemia. On the other hand, toxohormone extracted from tumor tissues was considered as the main cause to produce cancer cachexia. However, it has become clearer that cytokines, e.g. cachectin/TNF, IL-1, LT and IFN gamma play an important role to produce cachexia. Patients who are malnourished have an incidence of postoperative complications double that seen in adequately nourished patients. The effectiveness of cancer-chemotherapy is also different in nutritional status of patients. Although in patients requiring hyperalimentation, enteral nutritional support may feasible and enteral feeding has a distinct metabolic advantage compared with parenteral feeding, there is a definite role for total parenteral nutrition in patients who have severe chronic radiation enteritis, side effect of chemotherapy, weight loss and malabsorption. Tentative weight gain and correction of hypoalbuminemia without improving patient survival may be expected by this intravenous hyperalimentation.
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PMID:[Palliative therapy in cancer 2. Nutrition control]. 169 91

Cachectin/tumor necrosis factor (TNF-alpha) is a macrophage-secreted cytokine initially found to be a lipoprotein lipase-suppressing serum factor in cachectic, parasite-infected animals. Cloning of the cDNA encoding the gene for cachectin enabled biosynthesis of recombinant human cachectin and proof that the protein is identical to TNF-alpha. Numerous biological activities have subsequently been attributed to this pluripotent cytokine. In addition to suppressing LPL, cachectin/TNF mediates decreased lipogenic enzyme synthesis in adipocytes, causing a state of "cellular cachexia" in vitro. Similarly, catabolic cellular energy responses are induced by cachectin/TNF in cultured skeletal muscle cells which exhibit accelerated glycogenolysis, enhanced lactate production, and increased expression of hexose transporters. Persistent cachectin/TNF production occurs in chronic infection and malignancy, and chronic exposure induces a cachexia syndrome characterized by anorexia, weight loss, and anemia. Acute systemic appearance of cachectin/TNF is capable of inducing a state of lethal shock, disseminated hemorrhagic necrosis, catabolic hormone release, and multiple organ injury. Inhibiting the toxic effects of cachectin/TNF with monoclonal anti-cachectin antibodies during overwhelming Gram-negative bacteremia confers protection against septic shock. In these studies, the unprotected controls succumbed within hours, but baboons immunized against cachectin/TNF did not develop the characteristic increases of IL-1, IL-6, or catabolic stress hormones and did not die, suggesting that cachectin/TNF is a pivotal, proximal factor in the humoral cascade mediating septic shock syndrome. Recent evidence indicates that when produced in lesser quantities, cachectin/TNF may participate in the degradative and reparative mechanisms of physiological tissue remodelling and homeostasis. Future studies of the immunological and metabolic effects of cachectin/TNF should lead to a better understanding of the pathogenesis of infection and inflammation.
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PMID:Metabolic responses to cachectin/TNF. A brief review. 219 78

We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
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PMID:Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. 225 57

C57BL/6 mice bearing either a transplantable methylcholanthrene-induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor-alpha. Mice bearing methylcholanthrene-induced sarcoma developed tumor-associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor-bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anticachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor-bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.
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PMID:Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models. 272 56

Chronic inflammatory diseases are often associated with decreased red blood cell (RBC) mass. The cytokines cachectin/tumor necrosis factor-alpha (TNF) and interleukin 1 (IL 1) are produced by monocytes/macrophages in response to many inflammatory stimuli and have been implicated in the anemia of chronic disease. This study was undertaken to evaluate the mechanisms by which cachectin/TNF, IL 1, or endotoxin induce anemia. Hematologic parameters and RBC kinetics were quantitated in rats given chronic sublethal quantities of either recombinant human cachectin/TNF, recombinant human IL 1 alpha, or Salmonella endotoxin for 7 days. Cachectin/TNF or endotoxin treatment resulted in a 25 or 31% decrease, respectively, in total RBC mass, whereas RBC mass was unchanged by IL 1 administration. Anemia associated with either chronic cachectin or endotoxin administration was characterized by normal mean corpuscular volume, mean corpuscular hemoglobin content, and reticulocyte numbers. [59Fe]RBC survival was significantly shortened in animals given cachectin, IL 1 or endotoxin, but the magnitude of the response was greatest in cachectin/TNF-or endotoxin-treated rats. Although cachectin/TNF-IL 1-, or endotoxin treatment resulted in similar hypoferremia and shortened plasma iron half-life, endotoxin or cachectin/TNF treatment (but not IL 1) significantly reduced the incorporation of plasma 59Fe into newly synthesized RBCs. We conclude that chronic cachectin/TNF administration produces anemia by decreasing RBC synthesis and reducing the life span of circulating RBCs. An endogenous cachectin/TNF response during inflammatory disease may contribute to an associated anemic state, whereas the modestly reduced red cell life span induced by IL 1 does not lead to a net reduction in RBC mass, presumably owing to a preserved RBC synthetic rate.
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PMID:Cachectin/tumor necrosis factor-alpha alters red blood cell kinetics and induces anemia in vivo. 278 16

Septic shock and invasive infection are diseases caused by humoral mediators of both exogenous and endogenous origin. The search for and identification of these factors has led to the discovery and molecular cloning of cachectin. This pyrogenic cytokine is identical to tumor necrosis factor (TNF) and, when released into the circulation, causes profound shock and multiple organ injury. Cachectin antibodies protect against the lethal effects of mice given endotoxin and baboons given E. coli, a result suggesting that this mediator is both necessary and sufficient to provoke septic shock. Cachectin is produced in humans after endotoxin infusion; the infusion of small doses of TNF is associated with fever, rigors, headache, and hypotension. Septicemic patients also produce cachectin, and during meningococcal infection, patients with the highest serum levels of cachectin die. Chronic cachectin production causes a potentially lethal syndrome of cachexia, anemia, and protein and lipid wasting. Future investigation is being directed toward the development of cachectin antibodies for use in treating the humorally mediated systemic complications of infectious disease.
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PMID:Cachectin: a hormone that triggers acute shock and chronic cachexia. 327 61

Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.
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PMID:Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone. 328 90

Cachexia is a potentially lethal syndrome of unknown etiology characterized by anorexia, weight loss, and protein wasting that frequently complicates the treatment of chronic inflammation and cancer. Cachectin/TNF was isolated during the search for a humoral mediator of cachexia and found to stimulate the breakdown of energy stores from adipocytes and myocytes in vitro, but the chronic effects of the monokine in vivo are not known. Sublethal doses of recombinant human cachectin administered twice daily for 7-10 d caused cachexia in rats, as evidenced by reduced food intake, weight loss, and depletion of whole-body lipid and protein stores. Significant anemia is also observed and found to be the result of decreased red blood cell mass, not expanded plasma volume. Leukocytosis and histopathological evidence of tissue injury and inflammation are observed in several organs, including omentum, liver, spleen, and heart. These data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.
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PMID:Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. 335 36

Although the role of systemic proinflammatory cytokines, IL-1beta and TNF-alpha, and their up-regulation of adhesion molecules, ICAM-1, VCAM-1 and E-Selectin, in the pathogenesis of cerebral malaria (CM) is well established, the role of local cytokine release remain unclear. Immunohistochemistry (IHC) was used to compare the expression of ICAM-1, VCAM-1, E-Selectin, IL-1beta, TNF-a and TGF-beta at light microscopic level in cerebral, cerebellar and brainstem postmortem cryostat sections from 10 CM, 5 severe malarial anemia (SMA), 1 purulent bacterial meningitis (PBM), 2 non-central nervous system infections (NCNSI) and 3 non-infections (NI) deaths in Ghanaian children. Fatal malaria and Salmonella sepsis showed significantly higher vascular expression of all 3 adhesion molecules, with highly significant co-localization with sequestration in the malaria cases. However, there was negligible difference between CM and SMA. TGF-beta showed intravascular and perivascular distribution in all cases, but expression was most intense in the PBM case and CM group. TNF-alpha and IL-1beta showed prominent brain parenchymal staining, in addition to intravascular and perivascular staining, in only the PBM case and CM group. The maximal expression of all 6 antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation is a feature of fatal malaria and Salmonella sepsis, with adhesion molecule expression being highly correlated with sequestration. IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases. Both cytokines and adhesion molecules were maximally upregulated in the cerebellar sections of the malaria cases.
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PMID:Cytokines and adhesion molecules expression in the brain in human cerebral malaria. 1670 10


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