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)

Viral and bacterial infection in the central nervous system can induce nitric oxide production, which serves as a major host defense against invading microorganisms. Glucocorticoids secretion is enhanced and immune responses are diminished in stressed animals or in patients suffering depression. Using N9 microglial cells, this study tested the hypothesis that glucocorticoids and their precursors caused an impaired immune defense in animals because these compounds could inhibit microglial nitric oxide production. Results indicated that both hydrocortisone and the synthetic glucocorticoid, dexamethasone, were potent inhibitors of the microglial nitric oxide production. While glucocorticoid precursors were not as potent as hydrocortisone, the potency of these precursors increased linearly as they advanced on the biosynthesis pathway. Northern and Western blot analyses indicated that hydrocortisone and dexamethasone might interfere with the inducible nitric oxide synthase at either the transcription or at the post-translational level, depending on the concentrations used. These results suggest that glucocorticoids have the ability to block nitric oxide production by microgila, which could partially explain the impaired immune protection against infection in the central nervous system in stressed animals.
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PMID:Inhibition of microglial nitric oxide production by hydrocortisone and glucocorticoid precursors. 1095 85

We examined the effects of lipopolysaccharide, a bacterial endotoxin, on synaptic plasticity in the rat hippocampal CA1 area in vitro. Lipopolysaccharide suppressed the induction of long-term potentiation elicited by tetanic stimulation and long-term depression, elicited by low-frequency stimulation of Schaffer collateral-commissural fibres at 10 and 50 microg/ml, respectively. Lipid A (1 microg/ml), the biologically active component of lipopolysaccharide, mimicked the effects of 10 microg/ml lipopolysaccharide on long-term potentiation and depression. Nifedipine, an L-type voltage-sensitive Ca(2+) channel antagonist, did not influence the induction of long-term potentiation and depression, whereas a high concentration of extracellular calcium enabled long-term potentiation induction in the presence of 10 microg/ml lipopolysaccharide. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 50 microM), nifedipine (10 microM) or lipopolysaccharide (10 or 50 microg/ml) partially reduced the magnitude of tetraethylammonium-induced long-term potentiation. Nifedipine combined with lipopolysaccharide completely blocked tetraethylammonium-induced long-term potentiation. Whole-cell voltage clamp recordings showed that lipopolysaccharide suppressed NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). Our results indicate that lipopolysaccharide acutely modifies synaptic plasticity by blocking Ca(2+) entry through NMDA receptors, suggesting a possible mechanism for the amnesic action of bacterial infection.
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PMID:Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area. 1143 Sep 15

Bacterial infection is a common complication in cirrhotic patients. The portal hypertension as well as the immune depression observed in these patients can explain this high incidence of bacterial infection. Because of the high probability of cirrhotic patients to develop infections, antibiotic prophylaxis is warranted in some conditions, such as upper gastrointestinal bleeding or after spontaneous bacterial peritonitis. Nevertheless, antibiotic prophylaxis is not widely recommended for cirrhotic patients.
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PMID:Current aspects of antibiotic prophylaxis for upper gastrointestinal bleeding in cirrhosis patients. 1249 10

Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 microm) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca2+ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.
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PMID:Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. 1271 4

Toxicology and carcinogenesis studies of pentachloronitrobenzene (99% pure), a fungicide, were conducted by administering diets containing 0, 2,500, or 5,000 ppm pentachloronitrobenzene to groups of 50 B6C3F1 mice of each sex for 103 weeks. These doses were selected because, in 13-week studies in which the chemical was administered in feed at doses up to 20,000 ppm in male mice and up to 40,000 ppm in female mice, body weight gain depression was observed at 10,000 ppm and above in males and female and deaths occurred at 40,000 ppm in females. The National Cancer Institute had conducted 2-year (diet) studies in B6C3F1 mice and Osborne-Mendel rats (See TR-61 reported in 1978). Survival among male mice was low, not all livers were examined from dosed female mice, and the size of the control group was considered to be small. For these reasons, the NCI decided to conduct additional 13-week and 2-year studies in B6C3F1 mice. Under the conditions of the NCI studies, pentachloronitrobenzene was not carcinogenic in either Osborne-Mendel rats or B6C3F1 mice. In the studies reported in this Technical Report, the survival of male mice was comparable among control and dosed groups (control, 35/50; low dose, 31/50; high dose, 32/50). Final mean body weights of low dose and high dose male mice were 96% and 90% that of the controls. All groups of female mice showed evidence of bacterial infection. At week 84, survival in dosed and control female mice was 38/50; 34/50; 30/50; after week 84, survival in dosed groups decreased, with the final survival being 30/50; 20/50; 15/50. The mean body weight of high dose female mice was more than 10% lower than that of the control group after week 20 and was 21% lower than controls at week 104. The mean body weight of low dose female mice was within 10% that of the control group until week 88 and was 18% lower than controls at week 104. No compound-related neoplastic lesions were seen in either male or female mice. The nonneoplastic lesions observed in female mice were considered to be secondary to bacterial infection (primarily Klebsiella) and included hematopoiesis of the liver (9/50; 21/50; 23/50) and spleen (14/50; 23/48; 27/50), plasma cell hyperplasia of the mediastinal lymph nodes (1/44; 4/47; 9/45), and ovarian abscesses (12/49; 22/50; 29/50). Pentachloronitrobenzene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of Aroclor 1254-induced male Syrian hamster or male Sprague-Dawley rat liver S9 when tested according to the preincubational protocol. Pentachloronitrobenzene was not mutagenic at the TK+/- locus of L5178Y mouse lymphoma cells in the presence or absence of Aroclor 1254-induced F344/N rat liver S9. In cultured Chinese hamster ovary cells, pentachloronitrobenzene did not induce sister-chromatid exchanges but did induce chromosomal aberrations both with and without Aroclor 1254-induced male Sprague-Dawley rat liver S9. An audit of the experimental data was conducted for the 2-year studies of pentachloronitrobenzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenicity for either male or female B6C3F1 mice receiving 2,500 or 5,000 ppm of pentachloronitrobenzene. Infection is considered to have decreased survival of the female mice and thus reduced the sensitivity for determining the presence or absence of a carcinogenic response. Synonyms or Trade Names: Avicolreg.; PCNB; quintozene; Botrilexreg.; Brassicolreg.;Folosanreg.; PKhNB; Tilcarexreg.; Terraclorreg.; Tritosanreg.
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PMID:NTP Toxicology and Carcinogenesis Studies of Pentachloronitrobenzene (CAS No. 82-68-8) in B6C3F1 Mice (Feed Studies). 1274 28

Dimethylvinyl chloride is a clear colorless liquid, which, because of its volatility and flammability at room temperature, is a significant fire hazard. It has a boiling point of 68.1 degrees C (155 degrees F) and a density at 20 degrees C of 0.919 g/ml. Dimethylvinyl chloride is a byproduct in the production of 3-chloro-2-methylpropene by the chlorination of isobutene. It is not known to be produced in the United States for other than laboratory purposes. This chemical was nominated for toxicologic studies because of its reported presence in ambient air in the Baltimore area and was selected for toxicologic characterization because of its structural similarity to the known animal and human carcinogen, vinyl chloride monomer. Toxicology and carcinogenesis studies of dimethylvinyl chloride (96%-98% pure), a structural analog of vinyl chloride monomer, a known human carcinogen, by administered dimethylvinyl chloride in corn oil by gavage to groups of 50 male and 50 female F344/N rats and B6C3F1 mice at doses of 0, 100, or 200 mg/kg body weight 5 days per week for 102 or 103 weeks. The selection of these doses was based on results of 13-week studies, which included depression of body weight at doses of 500 mg/kg or above in rats as well as histopathologic changes intestinal epithelium, bone marrow, hepatocytes, and the testes at doses of 250 mg/kg and above; doses in mice were selected on the basis of histopathologic changes in lymphopoietic cells, liver, pancreatic islets, ovary, testis, and spleen, with changes being most prominent at doses of 500 mg/kg and above. In the 2-year studies, body weights of rats and mice given 100 mg/kg were comparable to those of the vehicle controls except for the last few weeks in mice when body weights were markedly lower than those for the vehicle controls. At 200 mg/kg, the mean body weights of rats and mice were progressively decreased relative to those of vehicle controls, with the significant departure from vehicle controls occurring somewhat earlier in males than in females. Survival of vehicle control rats and mice was comparable to historical values; however, survival of dosed male and female rats was significantly lower than that of vehicle controls, with the incidence of mortality being more severe at the high dose than at the low dose. There were no survivors in the high dose group of male rats after week 85 or in the high dose group of female rats after week 97. Survival was significantly lower among dosed male and female mice compared with vehicle controls. In the absence of toxicological findings that would explain the early deaths, it is assumed that the high incidence of tumors and chemical-related toxicity contributed to the decreased survival of dosed rats and mice. In rats, the severity and incidence of nonneoplastic lesions were minimal; these lesions included necrosis of the duodenum and epithelial hyperplasia at the sites of tumor formation--the nasal cavity, esophagus, and forestomach. In mice, the severity of nonneoplastic lesions was also minimal; the lesions included necrosis of the liver, bone marrow granulocytic hyperplasia, and inflammation of the nasal cavity (small number, females only.) Several types of neoplastic lesions occurred with significantly increased incidences in dosed animals as shown in the following table (see page 11 of Technical Report). Among rats, these lesions included malignant epithelial tumors of the nasal cavity and squamous cell tumors of the oral cavity, esophagus, and forestomach in males and females. The increased number of fibroadenomas of the mammary gland in female rats may have been related to dimethylvinyl chloride administration. The lack of a clear dose-response relationship for certain tumors in rats is considered to be related to the increased number of early deaths observed in the high dose groups. Among dosed mice, there were significantly increased incidences of squamous cell carcinomas of the forestomach (both sexes), squamous cell papillomas of the forestomach (males), and squamous cell carcinomas of the preputial gla preputial gland (males). The increased incidence of papillary adenomas of the harderian gland and alveolar/bronchiolar adenomas or carcinomas in female mice may have been related to administration of dimethylvinyl chloride. Limited metabolism studies of 14C-labeled dimethylvinyl chloride were conducted in male F344/N rats and B6C3F1 mice. Single doses of 150 mg/kg were administered to rats for 1, 2, or 4 consecutive days. About 25% of the administered doses was exhaled as carbon dioxide; this amount was independent of the number of doses administered. Another 25%-35% of the administered dose was exhaled; 96% of this parent was material. Approximately 35% and 6% were excreted in the urine and feces, respectively. The elimination half-life of radioactive label was 3-4 days for the liver and kidney, the two organs containing the greatest amounts of the administered dose. In mice, a much smaller fraction of the dose was exhaled and a larger proportion was excreted in urine compared with rats. Dimethylvinyl chloride was not mutagenic in four strains ofSalmonella typhimurium with or without metabolic activation, but it was mutagenic in the mouse lymphoma L5178Y/TK± assay in the absence of metabolic activation. Sister-chromatid exchanges were induced in Chinese hamster ovary cells with and without metabolic activation, but there was no increase in chromosomal aberrations. When fed to Drosophila, dimethylvinyl chloride induced significant increases in the frequencies of both sex-linked recessive lethal mutations and reciprocal translocations. Studies of the immunotoxicity of dimethylvinyl chloride were conducted in which female B6C3F1 mice received daily oral doses of 0, 50, 100, 200, or 400 mg dimethylvinyl chloride per kilogram body weight. Compound-related increases in susceptibility to bacterial infection and decreases in macrophage cytostasis were observed at all doses. At the highest dose, the decreased resistance to bacterial and viral challenge could be related to alterations in specific immune function. However, the increased mortality in rats and mice in the 2-year studies was not relatable to infectious processes. An audit of the experimental data was conducted for these2-year toxicology and carcinogenesis studies on dimethylvinyl chloride. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of dimethylvinyl chloride for both sexes of F344/N rats and B6C3F1 mice. This was based on increased incidences of neoplasms of the nasal cavity, oral cavity, esophagus, and forestomach of male and female F344/N rats. B6C3F1 mice showed increased incidences of squamous cell neoplasms of the forestomach in males and females and squamous cell carcinomas of the preputial gland in males. Synonym: 1-chloro-2-methylpropene
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PMID:NTP Toxicology and Carcinogenesis Studies of Dimethylvinyl Chloride (1-Chloro-2-Methylpropene) (CAS No. 513-37-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1274 37

The medical records of 53 horses with purpura haemorrhagica were reviewed. Seventeen of them had been exposed to or infected with Streptococcus equi, nine had been infected with Corynebacterium pseudotuberculosis, five had been vaccinated with S. equi M protein, five had had a respiratory infection of unknown aetiology, and two had open wounds; the other 15 cases had no history of recent viral or bacterial infection. The horses were between six months and 19 years of age (mean 8.4 years). The predominant clinical signs were well demarcated subcutaneous oedema of all four limbs and haemorrhages on the visible mucous membranes; other signs included depression, anorexia, fever, tachycardia, tachypnoea, reluctance to move, drainage from lymph nodes, exudation of serum from the skin, colic, epistaxis and weight loss. Haematological and biochemical abnormalities commonly detected were anaemia, neutrophilia, hyperproteinaemia, hyperfibrinogenaemia, hyperglobulinaemia and high activities of muscle enzymes. All of the horses were treated with corticosteroids; 42 also received non-steroidal anti-inflammatory drugs and 26 received antimicrobial drugs. Selected cases received special nursing care, including hydrotherapy and bandaging of the limbs. Most of the horses were treated for more than seven days and none of them relapsed. Forty-nine of the horses survived, one died and three were euthanased, either because their severe clinical disease failed to respond to treatment or because they developed secondary complications. Two of the four non-survivors had been vaccinated against S. equi with a product containing the M protein, one had a S. equi infection and the other had a respiratory infection of undetermined aetiology.
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PMID:Purpura haemorrhagica in 53 horses. 1291 29

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.
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PMID:A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors. 1599 Aug 68

Serum iron levels have been shown to decline both with fever and with strenuous exercise, leading to the supposition that the decrease might be the result of a rise in core body temperature. To evaluate this hypothesis, the serum iron response to an exercise-induced 1.5 degrees C rise in core body temperature was measured. To increase core temperature, five females and two males exercised in an environmental chamber heated to 41 degrees C with a relative humidity of 40%. Blood samples were taken before exercise and immediately after body temperature increased approximately 1.5 degrees C. Blood was also collected 1 h, 6 h, and 24 h postexercise. Results showed that the core body temperature significantly increased (p<0.001) from a mean baseline value of 36.5 +/- 0.1 degrees C to 38.1 +/- 0.1 degrees C following exercise. A one-way repeated measures analysis of variance was used to examine the effect of increased core body temperature on serum iron levels over the five time periods: preexercise, immediate postexercise, and 1 h, 6 h, and 24 h post exercise. The results indicated that there were no significant differences in serum iron levels among time periods. This suggests that the previously reported depression of serum iron levels that occurs with fever and after prolonged exercise is not the result of hyperthermia. Rather, the change in serum iron occurs in response to biological or physiological stressors, such as bacterial infection, muscle damage, or unusual trauma. Further studies are needed to explicate the mechanisms responsible for these changes.
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PMID:Effect of exercise-induced hyperthermia on serum iron concentration. 1632 60

Several cases of toxic shock-like syndrome (TSLS) have been reported in dogs but no inciting cause has been identified. TSLS associated with a closed-cervix pyometra was suspected in the reported bitch. The dog was evaluated for the complaint of generalized dermatopathy (erythema and oedema) and systemic signs with multiorganic involvement (depression, fever, immature neutrophilia, hypoalbuminaemia, renal disease, vomiting and diarrhoea). Histological features consistent with TSLS included superficial dermatitis with epidermal neutrophilic exocytosis and necrotic keratinocytes. The tentative diagnosis of TSLS was based on case history, clinical presentation, laboratory and histopathological findings, and the resolution of all clinical signs following surgical removal of the localized bacterial infection.
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PMID:Suspected toxic shock-like syndrome in a dog with closed-cervix pyometra. 1722 39


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