Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.37 (malate dehydrogenase)
 4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simian virus 40 infection of the CV-1 line of green monkey kidney cells results in the release of mitochondrial malic dehydrogenase as early as 24 h. Released malic dehydrogenase is detected in the cytoplasm prior to its appearance in the overlay medium. Infected cells lose the ability to consume oxygen between 48 and 56 h, and damage to the elctron transport system is indicated. Nevertheless, cellular ATP levels remain high as late as 72 h. Infection leads to a stimulation of membrane phospholipid synthesis, which reaches a peak at about 32 h. This is followed by a severe decline in new membrane synthesis, which correlates in time with the release of cytoplasmic lactic dehydrogenase into the overlay media. Lactic dehydrogenase release precedes the accumulation of trypan blue-stainable cells by about 6 h. Infection had no effect on the turnover of prelabeled membrane phospholipids. An early simian virus 40 mutant, tsA58, and a late mutant, tsB11, are both less effective than wild-type virus at causing reduced levels of phospholipid synthesis, enzyme release, and the accumulation of trypan blue-stainable cells. Another late mutant, tsB8, is similar to wild-type virus in these respects. At 64 h, there is no detectable cell-associated lactic dehydrogenase and nearly all the cells are trypan blue stainable. Nevertheless, at concentrations of deoxyglucose in the medium below the transport Km, deoxyglucose uptake was similar in infected and control cultures. With higher concentrations of deoxyglucose in the medium, uptake by the infected cultures exceeded that by the control cultures.
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PMID:Cell killing by simian virus 40: impairment of membrane formation and function. 19 51

The potential renal tolerance of cefuroxime was investigated in 80 female albino Wistar rats and compared with that of cephacetrile. The drugs were administered i.m. in different dosages (1000, 2000, 3000 and 5000 mg/kg/day; dosage interval: 12 h) over a period of five days. The excretion of tubular cells and urinary malic dehydrogenase was assessed before, during and after administration of the antibiotics. In addition, the concentration of serum urea was analysed and the renal histology was examined. The following toxic threshold doses were estimated: cefuroxime 5000 mg/kg/day, cephacetrile 3000 mg/kg/day. In comparison with other cephalosporines cefuroxime belongs to those antibiotics with which a high degree of renal tolerance is demonstrated.
Infection 1977
PMID:[Experimental studies on the renal tolerance of cefuroxime (author's transl)]. 88 Dec 67

The possible nephrotoxity of cephalothin and the antibiotic combinations cephalotin-gentamicin and cephalothin-tobramycin was investigated in standardized animal experiments. Toxicity parameters were blood-urea concentration, the urinary enzymes GOT, LDH, MDH and the cell excretion rate, supplemented by histological investigations of the kidneys. Compared with other cephalosporine derivates, the antibiotic cephalothin in a toxic threshold-dose of 3000 mg/kg/day proved to be realtively well tolerated by the kidneys. On comparison with the respective monotherapy, the renal tolerance for cephalothin-aminoglycoside combinations was reduced. The clinical value of these findings is discussed.
Infection 1975
PMID:[Experimental study in rats on the renal compatibility of cephalothin and cephalothin-aminoglycoside combinations (author's transl)]. 118 95

An Onchocerca sp. was isolated from the nuchal ligaments of 78 out of 79 naturally infected cattle in Southern Mexico. Infections were moderate to heavy, averaging 20-30 parasites per nuchal ligament. Microfilariae were concentrated in the skin of the head and neck, although small numbers were found in the skin of the withers, brisket and medial abdomen. High numbers of microfilariae were found in the skin around the eye, but not in the ocular tissues themselves a situation dissimilar to that found in human onchocerciasis. Morphologically, adult females, males and microfilariae were identified as being O. gutturosa. Analysis of the isoenzyme patterns of LDH, MDH, PGM, GPI, PGD and ES of adult female worms, showed the Mexican parasite to be the same as O. gutturosa from England and Australia.
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PMID:Morphological characteristics and isoenzyme patterns of an Onchocerca sp. found in cattle in Southern Mexico. 621 51

Eight-week-old Wistar female rats were treated intramuscularly with 300, 1,000 and 3,000 mg/kg/day of cefotiam for five days. The nephrotoxicity of cefotiam was determined on the basis of the number of tubular epithelial cells excreted, the malate dehydrogenase activity in the urine and the histological examination of the kidneys. Cephalothin (3,000 mg/kg/day) was used as a reference compound. There were slight increases in the number of tubular epithelial cells excreted and in the malate dehydrogenase activity in the urine of some animals receiving 3,000 mg/kg/day of cefotiam or cephalothin. All of these changes disappeared within a few days after the dosing period. The histological examination of the kidneys at the end of both the dosing (5 days) and the recovery (7 days) periods revealed no pathological changes indicating nephrotoxicity. It was concluded that the nephrotoxicity of cefotiam was comparable to that of cephalothin; the urinary changes in animals receiving the highest dose were considered to be an early sign of nephrotoxicity. The maximum non-toxic dose of cefotiam was 1,000 mg/kg/day under the present experimental conditions.
Infection
PMID:Nephrotoxicity of cefotiam in rats. 631 96

We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did not impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of beta-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.
Infection
PMID:Animal studies on the reduction of aminoglycoside-induced nephrotoxicity by D-glucaro-1,5-lactam. 688 75

Chickens aged 6 weeks were inoculated intravenously with two strains of Newcastle disease virus: a mesogenic strain (MAJ) with relatively high neurotropism and a lentogenic strain (V5K7E1). The levels of several enzymes were determined in serum and in various tissues of the infected birds. A marked increase in lactic dehydrogenase (LDH) level in skeletal muscles and a decrease of LDH activity in liver were found in chickens infected with the MAJ strain. Differentiation of LDH isoenzymes by either heating or electrophoresis indicated a significant elevation of LDH 5 iso-enzyme in breast muscle and of LDH 1 in leg muscle, while the activity of LDH 1 in liver decreased. Similar changes were found in the activity of hydroxy butyrate dehydrogenase. Infection with the MAJ strain caused an increase of acid phosphatase activity in breast muscle, a marked decrease of alkaline phosphatase and malate dehydrogenase and an increase of glutamate-oxaloacetate transaminase activities in the intestine. These findings indicate the origin of the changes in enzyme levels found in serum. The possibility of metabolic changes in muscles and liver resulting from damage to the central nervous system is discussed. Inoculation of chickens with the lentogenic strain produced no significant change in the enzyme profile of tissues and serum.
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PMID:Enzymatic changes in serum and tissues in fowl infected with a neurotropic-mesogenic strain of Newcastle disease virus. 1877 Feb 5

Infections with the microaerophilic parasite Trichomonas vaginalis are treated with the 5-nitroimidazole drug metronidazole, which is also in use against Entamoeba histolytica, Giardia intestinalis and microaerophilic/anaerobic bacteria. Here we report that in T. vaginalis the flavin enzyme thioredoxin reductase displays nitroreductase activity with nitroimidazoles, including metronidazole, and with the nitrofuran drug furazolidone. Reactive metabolites of metronidazole and other nitroimidazoles form covalent adducts with several proteins that are known or assumed to be associated with thioredoxin-mediated redox regulation, including thioredoxin reductase itself, ribonucleotide reductase, thioredoxin peroxidase and cytosolic malate dehydrogenase. Disulphide reducing activity of thioredoxin reductase was greatly diminished in extracts of metronidazole-treated cells and intracellular non-protein thiol levels were sharply decreased. We generated a highly metronidazole-resistant cell line that displayed only minimal thioredoxin reductase activity, not due to diminished expression of the enzyme but due to the lack of its FAD cofactor. Reduction of free flavins, readily observed in metronidazole-susceptible cells, was also absent in the resistant cells. On the other hand, iron-depleted T. vaginalis cells, expressing only minimal amounts of PFOR and hydrogenosomal malate dehydrogenase, remained fully susceptible to metronidazole. Thus, taken together, our data suggest a flavin-based mechanism of metronidazole activation and thereby challenge the current model of hydrogenosomal activation of nitroimidazole drugs.
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PMID:Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. 1941 1

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.
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PMID:Induction of systemic immunity through nasal-associated lymphoid tissue (NALT) of mice intranasally immunized with Brucella abortus malate dehydrogenase-loaded chitosan nanoparticles. 3202 89