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Biomedical subjects

C Horvath

Publications and source records attributed to C Horvath.

At least 55 records · Page 3Linked to original sources
PubMed1980

Teratogenic effect of an inhibitor of cholesterol synthesis (AY 9944) in rats: correlation with maternal cholesterolemia.

The teratogenic action of AY 9944, an inhibitor of cholesterol synthesis, was previously shown. Its prevention by simultaneous administration of cholesterol led to the hypothesis that this action is correlated with the decrease in cholesterol. The present investigation demonstrates that there is an inverse correlation between holoprosencephalic type of malformations and maternal cholesterolemia and that, in Wistar rats, 0.30 g/liter of cholesterolemia is a threshold under which these malformations can be observed.

Abnormalities, Drug-Induced↗
PubMed1979

Teratogenic action and embryo lethality of AY 9944R. Prevention by a hypercholesterolemia-provoking diet.

Embryomortality and teratogenesis provoked by inhibitors of cholesterol synthesis are well demonstrated. Teratogenic action is particularly reflected by holoprosencephalies, but also by uro-genital abnormalities. A hypercholesterolemia-provoking diet has been shown to be completely effective for preventing holoprosencephaly, but only partially so for preventing the uro-genital malformations and fetal mortality. It is thus possible that the two types of abnormalities are governed by different mechanisms. In addition, the diet itself, whose hypercholesterolemic effect is considerable, has certain disadvantages. It seems to have a certain effect on fetal mortality and could be responsible for several uro-genital malformations. This deserves further study.

Abnormalities, Drug-Induced↗
PubMed1979

Interpretation of isolated agenesis of the pituitary.

Cholesterol synthesis inhibitors administered to rats caused more or less complete forms of the holoprosencephalic syndrome, consisting of severe abnormalities of the brain, sense organs and pituitary. The absence of the pituitary was also observed in fetuses without externally visible cephalic abnormalities. These observations suggest that the isolated absence of the pituitary is the lesser form of the holoprosencephalic syndrome. This interpretation is also valid for cases of isolated absence of the pituitary observed in humans.

Abnormalities, Drug-Induced↗
PubMed1978

Phenylalanine depletion for the management of phenylketonuria: use of enzyme reactors with immobilized enzymes.

Multitubular enzyme reactors with immobilized phenylalanine ammonia lyase were tested in vitro and in vivo for depletion of phenylalanine in circulating blood. Sustained reduction of phenylalanine was achieved in less than 30 minutes. A 50% decrease of phenylalanine was obtained with a 2-hour application of enzyme reactors and was maintained for more than 2 days. Similar enzyme reactors have therapeutic potential for temporary management of phenylketonuric patients when their circulating phenylalanine becomes exceedingly high because of infection, fever, or pregnancy.

Ammonia-Lyases↗
PubMed1978

Immobilized carboxypeptidase G1 in methotrexate removal.

Carboxypeptidase G1, and enzyme capable of cleaving the glutamate moiety from a variety of folate analogs, has been immobilized on nylon tubes and hollow fibers for use in extracorporeal enzyme reactors for methotrexate (MTX) removal from blood. The stability and reactor parameters of the system have been investigated with the use of single tubes and a multitubular arrangement. The results are used to predict their MTX-removing capacity at flow rates and MTX concentrations of clinical interest. In vivo experiments with dogs demonstrate the potential applications of such extracorporeal shunts in "rescue" after administration of large doses of MTX. For dogs a carboxypeptidase G1 reactor with a clearance value of about 150 ml/min would be required in such application.

Animals↗
PubMed1978

Preparation of immobilized L-phenylalanine ammonia-lyase in tubular form for depletion of L-phenylalanine.

The enzyme L-phenylalanine ammonia-lyase (EC 4.3.1.5), which catalyzes the conversion of L-phenylalanine into trans-cinnamic acid, was adsorbed in the walls of asymmetric hollow fibers and covalently bound to the innerwall of small bore nylon tubing. Multi-tubular enzyme reactor cartridges were constructed both from hollow fibers and nylon tubes and the capacity of the reactors to degrade phenylalanine at physiological concentrations was evaluated in perfusion studies at different flow rates ranging from 30 to 80 ml/min. Hollow fiber enzyme reactors showed significantly higher activity than nylon tube reactors of commensurable dimensions and this finding is attributed to the difficulties in immobilizing L-phenylalanine ammonia-lyase via covalent linkages. The results suggest that extracorporeal use of such multi-tubular enzyme reactors offer a promising approach to deplete serum phenylalanine levels.

Ammonia-Lyases↗
PubMed1977

Continuous-flow analysis for glucose, triglycerides, and ATP with immobilized enzymes in tubular form.

Small-bore ("Autozyme") tubes with immobilized enzymes at the inner wall have been developed and studied for application in the Technicon "SMAC" high-speed continuous-flow biochemical analyzer. Tubes coated with glucose oxidase (D-glucose:oxygen oxidoreductase, EC 1.1.3.4) have been prepared for the assay of glucose, with colorimetric assay of the hydrogen peroxide produced; tubes coated with glycerol kinase (ATP:glycerol phosphotransferase, EC 2.7.1.30) for the enzymatic assay of triglycerides; tubes coated with hexokinase (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1) and glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NAD+ oxidoreductase EC 1.1.1.49) for the measurement of ATP, an intermediate product in assays for creatine kinase. With use of 10-15 cm lengths of Autozyme tube and SMAC hydraulics (150 samples per hour), assay sensitivity and carryover were similar to values for the corresponding free-enzyme methods. These immobilized enzymes were sufficiently stable for one to eight weeks of continuous use before replacemnt. We conclude that suitable bound-enzyme tubes can replace either single or multiple free-enzyme reagents in many continuous-flow assays at high sampling rates.

Adenosine Triphosphate↗
PubMed1976

Preventive effect of riboflavin and ATP on the teratogenic effects of the phenothiazine derivative T-82.

To examine the hypothesis that the teratogenic effects of the phenothiazine derivative T-82 are due to its causing a riboflavin deficiency day 11 or 12 pregnant CB Wistar rats were each given 2,000 mg/kg T-82 po plus 100 mg/kg riboflavin ip, 12.4 mg/kg ATP ip, or both. The rates of fetal mortality and external malformations were significantly decreased in all supplementation experiments. The frequencies of cleft palate, micrognathia, and micromelia were unchanged but those of ectopic testis and hydrops fetalis were significantly increased in the group treated with T-82 and ATP on day 12.

Abnormalities, Drug-Induced↗
PubMed1976

Immobilized glucose oxidase used in the continuous-flow determination of serum glucose.

We used a tubular glucose-oxidase wall reactor in the "AutoAnalyzer II" continuous-flow analytical system to determine glucose in blood serum. Sensitivity was high and wash characteristics were satisfactory with use of a 30-cm tube containing immobilized glucose oxidase. Results compared favorably with those of the conventional free-enzyme method. More than 25000 such assays can be performed with a single enzyme tube, which also shows long-term storage stability. Because of the steady-state chemistry 60 samples can be analyzed per hour. The linearity of the method is excellent and sample interaction from 5.0 to 1.0 g/liter is less than 5%. Results correlate well (greater than 0.993) with those obtained with both the neocuproine method used in the "SMA 12/60" multichannel analytical system and the free glucose oxidase method used in the AutoAnalyzer.

Autoanalysis↗
PubMed1975

Behavior of soluble and immobilized acid phosphatase in hydro-organic media.

The hydrolysis of p-nitrophenyl phosphate by wheat germ acid phosphatase (orthophosphoric monoester phosphohydrolase, EC 3.1.3.2) has been investigated in mixtures of aqueous buffers with acetone, dioxane and acetonitrile. The enzyme was either in free solution or immobilized on a pellicular support which consisted of a porous carbonaceous layer on solid glass beads. The highest enzyme activity was obtained in acetone and acetonitrile mixed with citrate buffer over a wide range of organic solvent concentration. In 50% (v/v) acetone both V and Km of the immobilized enzyme were about half of the values in the neat aqueous buffer, but the Ki for inorganic phosphate was unchanged. In 50% (v/v) mixtures of various solvents and citrate buffers of different pH, the enzymic activity was found to depend on the pH of the aqueous buffer component rather than the pH of the hydro-organic mixture as measured with the glass-calomel electrode. The relatively high rates of p-nitrophenol liberation in the presence of glucose even at high organic solvent concentrations suggest that transphosphorylation is facilitated at low water activity.

Acid Phosphatase↗
PubMed1975

Action of the phenothiazine derivative methophenazine on prenatal development in rats.

Single doses of 100-400 mg/kg or multiple doses of 10 or 50 mg/kg of the phenothiazine derivative methophenzaine were given per osto Wistar rats at various times on the 7th-14th days fo gestation and the fetuses examined near term. Results indicated that methophenazine was mainly embryolethal when administered on the 8th-11th days, and was teratogenic at later times, producing types of malformations that depended on the day of treatment, the most susceptible period being the 13th and 14th days of gestation. Teratogenicity occurred only when the dosages were highly toxic to the pregnant rats. Ribovlavin given ip on the 14th day significantly reduced the embryolethal but not the teratogenic action of methophenazine.

Abnormalities, Drug-Induced↗
PubMed1975

Electrostatic effects on the kinetics of bound enzymes.

1. The effect of the interaction between the charged matrix and substrate on the kinetic behaviour of bound enzymes was investigated theoretically. 2. Simple expression is derived for the apparent Km. 3. The apparent Km can only be used for the characterization of the electrostatic effect of the ionic strength does not vary with the substrate concentration. 4. The deviations from Michaelis-Menton kinetics are graphically illustrated for cases when the ionic strength varies with the substrate concentration. 5. The inhibition of the bound enzyme by a charged inhibitor at constant ionic strength is characterized by an apparent Ki. 6. When both the inhibitor concentration and the ionic strength change there is no apparent Ki, and the inhibition profile is graphically illustrated for this case. 7. Under certain conditions the electrostatic effects manifest thenselves in a sigmoidal dependence of the enzyme activity on the concentration of the substrate or inhibitor.

Binding Sites↗