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)

Previous studies from this laboratory indicated that inorganic and organic anions inhibit the unidirectional influx and net transport of the folate analog methotrexate in mammalian cells. Studies were undertaken to establish whether anions retained in uremia might inhibit the membrane transport of folates. Methotrexate was utilized as a model folate compound and its transport was determined in the Ehrlich ascites tumor cell. Influx of methotrexate was inhibited when cells were suspended into sera or ultrafiltrates of sera (pH adjusted to 7.4 by regulation of PCO2) from uremic patients, an effect that was decreased after the patient underwent hemodialysis or peritoneal dialysis. The inhibitory effect of uremic sera correlated well with the level of retained anions as estimated from the "anion gap," but could not be related to changes in osmolality, blood urea nitrogen (BUN), sodium, potassium, calcium, or magnesium. While inhibiting the influx of methotrexate, inorganic anions did not displace methotrexate from albumin binding sites. Anionic inhibition of the membrane transport of 5-methyl [14C] tetrahydrofolate was also demonstrated and this was shown to be accompanied by a depression in the rate of incorporation of the labeled 14C moiety into nucleic acids and protein. The data suggested that transport of folates is impaired in uremia and raises the possibility that whatever the measured blood folate level in the uremic individual with retained anions, the rate of uptake of folates into folate-dependent tissues which this blood folate level will sustain may be reduced.
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PMID:Inhibition of the membrane transport of folates by anions retained in uremia. 118 41

The effects of p-aminohippurate (PAH) on electrolyte clearances were measured in 8 human volunteers. At plasma PAH levels used to measure renal plasm flow, the only significant increase was in sodium clearance, while with PAH levels used to measure maximum tubular secretion, the clearances of sodium, potassium and phosphorus were all significantly increased. The antriuresis combined with a depression of free water clearance and the absence of a chloruresis led to the conclusion that PAH- changed the anion composition of the filtrate delivered to the ascending limb, thus interfering with coupled Na+ reabsorption. This finding must be taken into account when electrolyte excretion is being measured during PAH infusion. A similar mechanism may operate in patients with chronic uremia whose endogenous hippurate level is increased.
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PMID:The natriuretic effect of p-aminohippurate in man. 124 77

The effect of uremia on the choroid plexus system responsible for transport of penicillin from cerebrospinal fluid (CSF) to blood was studied in vitro and in vivo. Uremia was induced in rabbits by injecting toxic doses of cephaloridine or by obstructing urine flow. Three days after the induction of uremia, isolated choroid plexuses from normal rabbits were unable to concentrate penicillin 14C normally when incubated in either CSF or ultrafiltrates of plasma from uremic rabbits. In vivo, a decrease in the disappearance of penicillin 14C from CSF was observed in uremic rabbits. However, the choroid plexus transport system for penicillin was only partially and reversibly depressed in uremia. The increased CSF levels of penicillin uremia are due to: decreased excretion of penicillin by the kidney, depression of active efflux of penicillin from the CSF, and decreased plasma binding of penicillin.
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PMID:The effect of uremia on penicillin flux between blood and cerebrospinal fluid. 127 Aug 86

A case of systemic lupus erythematosus (SLE) that developed 2 years after beginning hemodialysis is reported. The patient had not been given any drug implicated in the production of SLE. She had been treated with deferoxamine, an in vitro inhibitory of DNA synthesis. The difficulty of the diagnosis is emphasized. Clinical improvement after prednisone treatment was impressive. SLE may appear even in patients receiving hemodialysis, despite immunological depression derived from chronic uremia.
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PMID:Development of systemic lupus erythematosus in a patient on hemodialysis. 141 53

Red deer calves dying at 24 to 72 hours old were infected with cryptosporidia. The clinical signs were extreme depression and weakness, but they did not consistently have diarrhoea. One calf was severely uraemic, and evidence from subsequent cases suggested that cryptosporidium infection in very young red deer calves may result in terminal uraemia. The possibility of intrauterine infection is considered. The factors which could have predisposed to the outbreak of infection were investigated; the calves were deficient in vitamin E despite having received adequate colostrum.
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PMID:Cryptosporidiosis in newborn red deer (Cervus elaphus). 156 43

Thymus lymphocyte subsets in uraemic rats were studied using monoclonal antibodies. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the weight of the thymus decreased in uraemic rats. As for lymphocyte subsets, the frequency of W3/25+OX8+ decreased and those of W3/25-OX8-, W3/25+OX8- and W3/25- OX8+ relatively increased in uraemic rats. All these changes were more significant in severely uraemic than in moderately uraemic rats. When thymosin fraction 5 (TF5) was administered to severely uraemic rats, the weight of the thymus increased and the lymphocytes subsets normalized. These results suggest that uraemia may cause a maturational impairment of thymus lymphocytes by the depression of thymic hormone secretion.
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PMID:Thymus lymphocytes in uraemic rats and the effect of thymosin fraction 5 in vivo. 173 85

A depression of the general immune response in uremia is well documented, and hemodialyzed (HD) patients present deficient interleukin-2 (IL2) secretion. Since soluble IL2 receptors (SIL2R) could affect the immune response through interaction with circulating immune cells, we studied the potential relationship between SIL2R concentration and lymphocyte subsets in 44 HD patients. HD patients present lymphopenia, higher CD4/CD8 ratio. CD16 counts and SIL2R concentrations than controls. A significant negative correlation was found between SIL2R concentration and lymphocyte count (p less than 0.01), and between SIL2R concentration and T4/T8 ratio (p less than 0.01). An increase of SIL2R concentration due to abnormal T cell preactivation in HD patients with nonreused cuprophan membranes could perhaps contribute to cell immunity impairment through IL2 binding and inhibition of T cell activation.
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PMID:Soluble interleukin-2 receptors in chronic renal failure. 179 84

The depression of immunity to various antigens in chronic uremia is a frequently encountered phenomenon. Zinc deficiency might well be an important factor in its genesis. The aim of this study was to investigate the role of zinc deficiency in this reduced immune response. Two groups of 7 patients on haemodialysis who had failed to respond with seroconversion to an earlier vaccination against hepatitis B were revaccinated. One group received zinc by the addition of zinc chloride to the dialysate. Before initiation of the study zinc in plasma and leucocytes was measured. No difference in plasma and leucocyte zinc was observed between the two groups. Zinc in leucocytes was lower in patients than in a group of healthy volunteers (61.5 pmol/10E6 cells +/- 4.6 versus 73.8 +/- 5.6, p less than 0.005). Plasma zinc showed no difference between patients and healthy volunteers. During zinc supplementation zinc in plasma rose in the patient group receiving zinc (10.4 mmol/L +/- 1.5 to 14.2 +/- 1.9, p less than 0.005). However, no rise in leucocyte zinc was seen. At the end of the trial seroconversion had occurred in 2 patients in each group. It is concluded that zinc supplementation in haemodialysis patients does not lead to the restoration of leucocyte zinc to normal levels. Neither did it lead to an enhanced antibody response in our population after revaccination of haemodialysis patients against hepatitis B.
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PMID:Effects of zinc supplementation on zinc status and immunity in haemodialysis patients. 182 9

We review the English-language literature on antibiotic-associated adverse reactions in patients with renal insufficiency in order to highlight this important but often overlooked clinical problem. Because many adverse reactions to antibiotics are not dependent on renal function, we have attempted to review only those reactions that are believed to be associated with renal insufficiency or that have been reported in patients with impaired renal function. Adverse effects of antibiotics in this setting can be divided into six major categories: neurologic toxicity, coagulopathy, nephrotoxicity, hypoglycemia, hematologic toxicity, and aminoglycoside inactivation by penicillins. Neurologic toxicity can be further divided into central nervous system toxicity consisting primarily of encephalopathy and seizures, ototoxicity, peripheral neuropathy, and neuromuscular blockade/respiratory depression. We explore the factors in uremia that may contribute to the susceptibility of patients with renal insufficiency to the adverse effects of antibiotics. Moreover, we make general recommendations regarding the use of the discussed antibiotics in patients with compromised renal function.
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PMID:Adverse antibiotic effects associated with renal insufficiency. 192 3

Antibody responses against pneumococcal capsular antigens and tetanus toxoid were measured in 14 patients with chronic renal failure who were managed by continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD) and in eight healthy controls. IgG antipneumococcal responses were predominantly of the IgG2 and to a lesser extent IgG1 subclasses, while the IgG response against tetanus toxoid was largely IgG1 with smaller amounts of IgG4 and IgG3. The post-immunisation serum levels of IgG1 and IgM antibody against both antigens were significantly reduced in the uraemic patients compared with controls (P less than 0.05). All the uraemic patients had normal levels of IgG, IgA and IgM in the serum, but elevated levels of IgG3 prior to immunisation. The mechanisms responsible for the asymmetric depression of antibody responses in uraemia are unclear and may account in part for the increased susceptibility to infection in these patients.
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PMID:T-cell-independent and T-cell-dependent antibody responses in patients with chronic renal failure. 249 80


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