Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Women using oral contraceptives (OCs) have been found to excrete increased amounts of several metabolites arising from tryptophan catabolism, the most pronounced change being in xanthurenic acid and kynurenic acid excretion. The abnormality is largely corrected by the administration of pyridoxine, suggesting an increased need for vitamin B6 in OC users. Although a majority of malnourished and well-nourished women show the abnormality in tryptophan metabolism following OC use, investigators differ in their assessment of vitamin B6 status using other tests. The question of vitamin B6 deficiency in OC users is controversial. 2 types of multiparameter assessment approaches have been used to elucidate the vitamin B6 requirement of OC users. In a study of malnourished India women, it was observed that daily supplements of 10 mg pyridoxine from the day of starting contraception largely prevented the development of the abnormality in tryptophan metabolism. This level of supplementation also prevented the OC-mediated deterioration in vitamin B6 status as determined byerythrocyte aspartate aminotransferase activation. In another type of multiparametric approach Brown et al. and Laklem et al. measured the pyridoxine status of OC users on known intakes of the vitamin in a depletion followed by repletion study. Despite the current controversy, it might be advisable to supplement women using OC with pyridoxine to ensure a daily intake of at least 5 mg vitamin B6.
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PMID:The vitamin B6 requirement in oral contraceptive users. 39 35

Cyclosporine metabolites (CM) were compared with cyclosporine for their in vitro and in vivo immunosuppressive, nephrotoxic, and hepatotoxic effects using (A) in vitro mixed lymphocyte induction of monocyte/macrophage procoagulant activity (PCA), an accurate marker of allograft rejection; (B) in vitro toxic effects on renal cells in culture; and (C) a unidirectional rejection model of rat small intestinal transplantation (SIT). CM were composed of OL1, OL17, OL18, and two additional peaks C and H, (peak C: mass = 1235, 15.3% of total CM, peak H: mass = 1205, 6.3% of total CM). In vitro, CM fully suppressed the one-way mixed lymphocyte culture-induced PCA from 52.5 +/- 8.2 mU/10(6) PBM to the basal level 22.3 +/- 6.6 mU/10(6) PBM (P less than 0.01), which was comparable to CsA (21.3 +/- 5.5 mU/10(6) PBM). Lewis rats that had received Lewis-Brown Norway F1 hybrid intestinal allografts when treated with CM, demonstrated near-normal histology with minimal signs of rejection as compared with the fulminant clinical and histological rejection observed in the control (untreated and Cremaphor/NaCl treated) animals. PCA was markedly elevated in the control animals, 278 +/- 172 (untreated) and 160 +/- 98 mU/10(6) PBM (Cremaphor/normal saline treated), whereas CsA-treated allogeneic transplants expressed only basal levels of PCA (14.0 +/- 4 mU/10(6) PBM) (P less than 0.01), associated with normal histology. CM-treated animals expressed PCA levels of 27.0 +/- 10 mU/10(6) PBM, which was significantly different from both control and CsA-treated animals (P less than 0.01). In contrast to CsA-treated animals, CM-treated allogeneic transplants demonstrated no apparent renal or hepatic toxicity, as measured by blood urea nitrogen (25.3 +/- 9.5 vs. 10.0 +/- 5.3 mg/dl), alkaline phosphatase (160.7 +/- 29.3 vs. 100.3 +/- 19.5 U/L), and aspartate transaminase (96.7 +/- 23.7 vs. 61.7 +/- 11.7 U/L) (P less than 0.01). Similarly, in contrast to CsA, CM had minimal or no toxicity in renal epithelial and mesangial cells in culture, as measured by minimal or no inhibition of DNA, RNA, and protein synthesis. These results suggest that CM have potent immunosuppressive properties with no apparent nephrotoxicity and hepatotoxicity in vitro and in vivo.
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PMID:The effects of cyclosporine and cyclosporine metabolites in experimental small intestinal transplantation. 236 Feb 47

Two hundred twenty four dairy cattle (6 mo to second calving) representing four breeds (169 Holstein, 24 Guernsey, 19 Jersey, 12 Brown Swiss) were used to determine effects of age, temperature-season, and breed on blood characteristics. A total of 1183 blood samples were collected by jugular venipuncture in the middle of each temperature-season. Covariate age affected blood profile except for hemoglobin, oxyhemoglobin, glutamic-oxalacetic transaminase, and albumin. Temperature-season increased or decreased all measures except enzyme creatine phosphokinase, total creatine phosphokinase, calcium and phosphorus. Years differed for all measures except hemoglobin and oxyhemoglobin. Except for enzyme creatine phosphokinase, total creatine phosphokinase, and phosphorus, breeds differed in other measures. There were interactions between temperature-season and year, temperature-season and breed, and year and breed. Differences among temperature-seasons were not consistent from year to year. Breed differences were not consistent from temperature-season to temperature-season for calcium or protein-bound iodine. Breed differences were not consistent from year to year for glutamic-oxaloacetic transaminase, total protein, albumin, or calcium.
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PMID:Effects of age, temperature-season, and breed on blood characteristics of dairy cattle. 726 21

Leflunomide is a compound recently shown to reduce T and B cell-mediated responses in a number of experimental rat, mouse, and human systems. To explore its potential as an immunosuppressant, we studied leflunomide in 128 Brown-Norway/Lewis cardiac transplants and in 48 unoperated Lewis rats. At doses ranging from 0.63 mg/kg to 10 mg/kg given for 7 days, leflunomide significantly prolonged graft survival compared with controls. When cyclosporine or leflunomide was given for 21 days at a dose of 5 mg/kg, indefinite graft survival occurred in 3/6 animals receiving leflunomide but in none of the 21-day cyclosporine-treated animals. When acute rejection was allowed to develop for four days in untreated rats, leflunomide but not cyclosporine reversed the rejection, returning histology to a normal appearance by seven days. Alloantibody responses measured in microcytoxicity assays as well as total allospecific IgG and IgM in the rejecting animals also were returned to baseline levels by leflunomide but not cyclosporine. When both drugs were used together, a synergistic effect was observed at low doses of both drugs. Pharmacokinetics studies showed that their combined use for up to 28 days did not affect the trough levels of cyclosporine or cyclosporine elimination, suggesting that the synergistic effect was not caused by reduced elimination. The toxicity of each drug was negligible in a group of 32 rats receiving the drugs alone or in combination as measured by serial observation of general appearance, testing of serum ALT, AST, bilirubin, creatinine, white blood cell counts, hemoglobin, and gross necropsy appearance. Weight gain was slightly reduced by both drugs but combined drug use did not alter the pattern. The results of these experiments show leflunomide to be a potent, well-tolerated immunosuppressant, synergistic in its activity with cyclosporine, and would seem to encourage a closer look at this drug for potential use in man.
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PMID:Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine. 817 50

In liver transplantation, the quality of the liver is determined by a number of factors including donor nutritional status. Livers from fasted donors appear to tolerate long-term preservation better than livers from fed donors. In this study we repeated earlier results and obtained 31% (4/13) survival after 40-hr preservation of livers from fed donor Brown Norway rats and 67% (8/12) survivors with donor livers from 4-day-fasted rats (P = 0.154). The explanation for this improvement is not known but may be due to inactivation of Kupffer cells due to nutritional depletion of the liver. Kupffer cell activation has been one explanation advanced to explain how cold storage injuries livers during reperfusion (transplantation). In this study, we have measured how donor fasting affects Kupffer cell function (phagocytosis of colloidal carbon) after preservation of the rat liver. In addition, we measured how enhancing liver glycogen by feeding glucose to the rat donors affected outcome and liver functions tested by isolated perfusion after 24- and 40-hr cold storage of the liver. Preservation did not cause inactivation or activation of Kupffer cell phagocytosis of colloidal carbon. In livers with 0-hr preservation, colloidal carbon uptake was 3.1 +/- 0.2 mg/g/hr, after 40-hr preservation uptake was 3.8 mg/g/hr (P < 0.05 vs. 0 hr) (fed) and 2.7 +/- 0.3 mg/g/hr (fasted, P, 0.05 vs. 0-hr and 40-hr-fed). Thus, the improved survival obtained with livers from fasted donors does not appear related to inactivation of Kupffer cell phagocytosis. Although livers from fasted donors showed improved survival, there was extensive hepatocellular injury as indicated by large LDH release from the livers after 40-hr cold storage as tested by isolated perfusion. LDH released into the perfusate increased from 35.8 +/- 10.1 U/L (fed, 40-hr CS) to 301 +/- 65 U/L (fasted, 40-hr CS) after 1-hr reperfusion. AST release showed a similar pattern and bile production was suppressed more in livers from fasted donors than fed donors. Feeding rats glucose elevated liver glycogen and significantly reduced hepatocellular injury as measured by LDH release and AST release in the isolated perfused liver after 40-hr cold storage. Feeding rats glucose (40% in drinking water for 4 days) also improved survival: fed+glucose = 85% survival versus 31% survival with no glucose and fasted+glucose = 92% survival versus 67% survival with no glucose. These results show that both extensive donor fasting and glucose feeding enhanced outcome in orthotopic liver transplantation. This dilemma (both fasting and feeding improved survival) are discussed in terms of how the interactions between Kupffer cells and hepatocytes affect liver viability. Donor fasting is probably impractical clinically as a method to improve the donor liver, but elevating liver glycogen by glucose supplementation is possible and may lead to improved preservation and outcome in liver transplantation.
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PMID:Donor nutritional status--a determinant of liver preservation injury. 860 Jun 31

The mechanism(s) of rejection or tolerance induction is a competitive, complex process that presumably involves interactions between multiple subpopulations of T lymphocytes. We investigated the roles of CD8+ cytolytic and CD4+ helper T cells in rat strains that tolerate liver allografts and that differ at both the major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes. Orthotopic liver transplantation (OLT) with arterial reconstruction was performed with Brown Norway (BN) (RT1n) donors and Lewis (RT1(1)) recipients, some of which were untreated, others treated with anti-CD8 antibody, and still others treated with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2) liver biopsies at weekly intervals and at the time of sacrifice at the end of the study period. In the untreated control group, an elevation of AST was found to peak at day 6 after grafting, and it remained elevated until day 28 (AST 542 +/- 72 U/l). Histologically, signs of severe rejection were first observed on day 9; these changed to moderate rejection about day 21 and to mild rejection by day 28, when the animals were sacrificed. Recipients pre-treated with anti-CD8 demonstrated a significant elevation of AST within 6 days that, unlike in the control recipients, continued to rise sharply through the observation period (AST 1127 +/- 181 U/l, P = 0.009 vs control group). Liver biopsies showed mild rejection at day 9 and moderate rejection at days 21 through 28. Recipients pretreated with anti-CD4 showed a time course of enzyme elevation and severity of rejection that was not significantly different from that observed in the control group. However, anti-CD4 treatment resulted in only 75% depletion of CD4+ cells in peripheral blood as compared to complete elimination of CD8+ cells following anti-CD8 treatment. Functional studies of spleen and liver-infiltrating lymphocytes obtained after 28 days showed low proliferative response in mixed lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells. These results suggest that in this donor/recipient combination, removal of CD8+ cells increases the severity of rejection as demonstrated by a progressive rise in AST and histology. Moreover, OLT in this combination results in a profound, nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.
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PMID:Liver allograft rejection in rats depleted of CD8+ cells. 887 94

Liver transplantation (Ltx) has become a routine procedure for patients with end-stage liver disease. Despite ongoing progress on short- and long-term graft survival, primary dysfunction (PDF) remains a major problem. PDF is significantly associated with the duration of cold ischemia- and, possibly, with reperfusion-related injury. Nitric oxide (NO) has many physiological functions and plays an important role in modulating tissue injury. However, the mechanism of NO action in ischemia/reperfusion injury after Ltx is thus far unknown. In this study we investigated the role of inducable NO synthase (iNOS) in the liver after preservation with UW solution using the orthotopic Ltx model in the rat. Male Brown Norway rats were used for the Ltx procedure. After donor hepatectomy, livers were stored on ice-cold UW solution for 24 or 40 h and subsequently transplanted. A control group consisted of rats with Ltx after less than 1 h storage. Post-transplant blood samples were taken at 48 h to determine standard parameters for liver injury (aspartate transaminase, lactate dehydrogenase). Liver biopsies were obtained for detection of expression of iNOS (western blot) 24 and 48 h post-transplant. We observed that a preservation time of 24 h in UW solution presents no problem for graft survival after Ltx in rats with some brain function and in healthy animals. After 40 h preservation, liver damage is obvious and graft survival reduced, indicating the limits of cold storage may be within reach. With longer preservation times, more NOs was detected in liver tissue. This finding suggests that NO has a role in ischemia/reperfusion-related injury. Current intervention with NOS inhibitors will reveal whether NO has a negative or a positive effect on graft survival after Ltx.
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PMID:Extended preservation and effect of nitric oxide production in liver transplantation. 966 72

1. The aim of this study was to examine the effects of roxarsone (3-nitro-4-hydroxyphenylarsonic acid) inclusion in the diet on the performance, liver function and lipid metabolism in the liver of laying Brown Tsaiya ducks. 2. Sixty 36-week-old laying ducks were selected and allocated at random into 4 dietary treatments with 3 replications for each treatment. Feeding was for 7 weeks with 3 weeks of experimental diets followed by a 4 week withdrawal period. The experimental diets were supplemented with 0, 50, 100 and 300 mg/kg roxarsone, respectively 3. Dietary inclusion of 50 or 100 mg/kg roxarsone did not significantly promote performance. Inclusion of 300 mg/kg significantly depressed (P<0.05) performance, liver weight and content, serum triacylglycerol (TG), serum nonesterified fatty acid (NEFA) and increased (P<0.05) cholesterol, creatine kinase (CK) and aspartate aminotransferase (AST) in the serum at the end of 3 weeks on the experimental diet. 4. Laying characteristics returned to normal 4 weeks after withdrawal of roxarsone. The liver weight, fat and TG in the liver and serum concentrations of TG, NEFA, high density lipoprotein (HDL) and AST increased significantly (P<0.05), while the level of very low density lipoprotein (VLDL) decreased (P<0.05) at the end of the withdrawal period. More prominent vacuolised hepatic fatty cells were observed in laying ducks treated with 300 mg/kg of roxarsone.
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PMID:Effect of roxarsone inclusion in the diet on the performance and hepatic lipid metabolism of laying Tsaiya duck. 1108 32

This study was designed to test the effects of feed withdrawal and darkening on the performance, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and some blood serum metabolite and mineral concentrations of laying hens reared at high ambient temperatures ranging from 25 to 35 degrees C. Ninety, 16-week-old hens (Ross Brown) were divided into 3 groups, 30 hens each. The first group was used as control. Hens in the second group (feed withdrawal) were subjected to feed removal from 14:00 to 18:00, and hens in the third group (darkening) were subjected to light restriction from 14:00 to 18:00 using black curtains. Liveweight, feed intake, and egg production were higher (P < 0.01) in the feed withdrawal and darkening groups, particularly in the darkening group, than in the control. Water intake was higher in the control group compared with the feed withdrawal and darkening groups (P < 0.01). T3, T4, and TSH concentrations in the serum were higher (P < 0.01), whereas ACTH serum concentration was lower (P < 0.01) in the feed withdrawal and darkening groups compared with the control. The haematocrit was higher in the feed withdrawal and darkening groups compared with the control (P < 0.01). Darkening and feed withdrawal treatments increased serum glucose, urea-N, uric acid, albumin, triglyceride, cholesterol, Ca, P, Na, and K concentrations, also the activities of amylase and alkaline phosphatase, but did not influence the activities of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). The present study found that feed withdrawal and darkening, particularly darkening, at high temperatures during the summer months offer a good management practice to reduce heat stress related depression in feed intake and egg production in laying hens.
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PMID:A simple way to reduce heat stress in laying hens as judged by egg laying, body weight gain and biochemical parameters. 1194 21

The influence of dietary boron (B) supplementation on some serum parameters and egg-yolk cholesterol was studied in laying hens. A total of 224 eighteen-week-old hens of the Hyline Brown 98 strain were assigned to 7 groups with 4 replicates of 8 hens each after 10 days of adaptation, and they were fed commercial diets supplemented with 0, 5, 10, 50, 100, 200 or 400 mg/kg (diet) B (H3BO3) for 8 weeks. Serum gamma-glutamyl transpeptidase (GGT) activity, albumin, glucose, total cholesterol, HDL- and LDL-cholesterol levels were decreased with all B levels. Except in the group receiving 5 mg/kg B supplementation, decreases were found in serum triglycerides in all groups. Serum aspartate aminotransferase (AST) activity was decreased in the groups receiving 100 mg/kg or higher levels of B. All levels of B supplementation increased lactate dehydrogenase (LDH) activity at weeks 21 and 22, while 10 mg/kg or higher levels of B increased serum globulin, urea and egg-yolk cholesterol levels. The results demonstrate that B supplementation at levels exceeding 5 mg/kg affects serum biochemical parameters and increases egg-yolk cholesterol in laying hens.
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PMID:Influence of dietary boron supplementation on some serum metabolites and egg-yolk cholesterol in laying hens. 1738 54


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