Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects?

Background: A gabaergic antiepileptic drug, vigabatrin (VGB), is known to induce bilateral concentric visual field defects (VFD) in 30-40% of treated patients. Although the clinical and electrophysiological features of VFDs are well documented, the mechanism of retinal toxicity is still unclear.

Purpose: To determine if low basal ornithine-δ-aminotranspherase (OAT) activity is implicated in the etiology of VGB retinotoxicity, resulting in a phenotype of a mild form of gyrate atrophy.

Hippurate metabolism as a hydroxyl radical trapping mechanism in the rat kidney.

Hippurate (Hip) is considered to be the end product of benzoate (BA) metabolism. However, the kidney is able to metabolize Hip. Although only Hip but no BA is present in the blood, rat urine contains under normal conditions less Hip (about 0.

Fast method for the simultaneous determination of 2-oxo acids in biological fluids by high-performance liquid chromatography.

A fast and sensitive method for the single-run quantification of various 2-oxo acids including 2-ketoglutarate, glyoxylate and pyruvate is described. It ensures good separation of peaks with minor interference by other substances. The 2-oxo acid derivatives are measured photometrically at 324 nm after derivatization with phenylhydrazine and subsequent isocratic separation with ethanolic phosphate buffer on a C18 reversed-phase HPLC column.

Ammonia production from hippurate by the rat kidney in vitro.

Hippurate is known to be synthesized from benzoate and glycine in the liver and kidney. It takes part in renal ammoniagenesis by modulating the activity of gamma-glutamyl transpeptidase (gamma GT). Due to its chemical structure, however, hippurate might also serve as a substrate of renal ammoniagenesis.

Improved determination of small amounts of free hydroxyproline in biological fluids.

A fast, reliable, and sensitive (< 20 pmol) method for the quantification of 4-hydroxyproline is described. It ensures good separation of imino acid peaks, eliminates interference by primary amino acids, and guarantees full (96-105%) recovery of hydroxyproline (HYP). Interfering primary amino acids are derivatized by o-phthaldialdehyde and removed from the sample by use of a discardable C18 column.

Support of hypoxic renal cell volume regulation by glycine.

PO2 declines to less than 10 mm Hg in local regions of the renal cortex. Amino acids seem to modify the hypoxic tolerance of renal cells. It was suggested that glycine may support renal function in hypoxia.

Differences in the renal handling of pancreatic and salivary amylase in the rat.

Plasma activity and excretion of pancreatic (P) amylase in the rat was found to be negligible. In contrast, the excretion rate of salivary (S) amylase was substantial and variable, depending on diuresis. P-amylase had a higher isoelectric point, a greater sieving coefficient, and a shorter half-life than S-amylase.

Renal handling of 125I-labelled homologous pancreatic lipase and amylase in the rat.

Experiments were carried out in vivo on rats and in vitro on tubular brush border vesicles in order to study the renal mechanisms of the elimination of pancreatic lipase and amylase from the circulation. Highly purified 125I-labelled homologous lipase, amylase or 125I-labelled di-iodo-tyrosine was injected intravenously in a single dose. The sieving coefficients of lipase and amylase were found to be 0.

[Enzymuria following administration of contrast media in hypertensive rats].

Renal complications may occur in risk patients with pre-existing kidney damage if x-ray contrast media are administered. Nothing is known of the exact mechanisms of these reactions. We examined in rats with long-term renovascular hypertension and resulting nephrosclerosis the low osmolar contrast media ioxaglate, iohexol and iopamidol in respect of their renal tolerance compared with an osmotically equivalent mannite solution.

The role of the kidney in the elimination of pancreatic lipase and amylase from blood.

Two clinical observations indicate that the kidney plays the main role in the elimination of lipase and amylase from the circulation: 1. in patients with uncomplicated acute pancreatitis the decrease of the activity of both enzymes in the serum ran almost in parallel. The half life for lipase was found to be 6.

Effect of castration on the experimental renal hypertension of the rat. Blood pressure, nephrosclerosis, long-chain fatty acids, and N-acetylation of PAH in the kidney.

Rats were rendered hypertensive by clamping one renal artery. Both kidneys remained in situ ('two-kidney one-clip Goldblatt hypertension'). Half of the animals were simultaneously castrated.

Effect of castration and testosterone substitution on the urinary output of gamma-glutamyl transpeptidase and of N-acetyl-beta-D-glucosaminidase of male rats with renovascular hypertension.

The effect of castration of male rats with experimental renal hypertension ('two-kidney Goldblatt hypertension') was studied on the height of the hypertension and on the urinary output of gamma-glutamyl transpeptidase (gamma GT) and of N-acetyl-beta-D-glucosaminidase (NAG). Castration was carried out immediately after clamping one renal artery. Some of the castrates received testosterone substitution from the 3rd postoperative week onwards.

Interdependence of O2 consumption, renal NEFA pattern and N-acetylation of PAH in the isolated perfused rat kidney. Effect of long-chain NEFA and of PGF2 alpha on the renal N-acetyltransferase activity.

Tissue concentration of nonesterified fatty acids (NEFA) exerting an inhibitory effect on renal N-acetyltransferase activity was determined in the isolated perfused rat kidney. Concurrently, O2 consumption and the N-acetylation rate of p-aminohippurate (PAH) were measured. In a second series of experiments, the mode of inhibition of NEFA on acetylating enzyme(s) was studied.

[On the etiology of water excretion inhibition in Addison's disease].

Micropuncture experiments, performed on adrenalectomized rats disclosed an impairment of the hypertonic sodium chloride transport of the thick ascending limb of Henle's loop (the diluting segment). This transport inhibition was documented by a delayed time course of NaCl-concentration decrease within the diluting segment. Assuming a pump leak model of the hypertonic NaCl-transport, we calculated a 50% inhibition of the NaCl-transport velocity compared with controls.

Enzymuria (the output of gamma-glutamyl-transpeptidase and of N-acetyl-beta-D-glucosaminidase) in the course of experimental renovascular hypertension.

The urinary output of gamma-glutamyl-transpeptidase (gamma GT) and of N-acetyl-beta-D-glucosaminidase (NAG) was studied with "two-kidney Goldblatt hypertension' 3-6, 16-19 and 30-33 weeks after eliciting high blood pressure. gamma GT excretion rate of normotensive males was higher than that of females, while the activity of the renal tissue was on the same level. gamma GT output of hypertensive males was elevated in the early and in the middle stages of the disease, it was subnormal in the late stage.

Quantitative structure-pharmacokinetic relationships derived on antibacterial sulfonamides in rats and its comparison to quantitative structure-activity relationships.

Quantitative structure-pharmacokinetic relationships have been derived for a series of substituted 2-sulfapyridines. Pharmacokinetic parameters, such as elimination rate constant (ke), clearance (Cl), and protein-binding constant (Kassoc), have been determined in rats. The observed variation is statistically significant, explained by changes in the lipophilic (deltaRm), electronic (pKa), and steric effects (I, ES) of the substituents.

Improved sodium and PAH transport in the isolated fluorocarbon-perfused rat kidney.

The effect of an artificial O2 carrier (emulsion of the perfluorochemical FC43 with Pluronic-F-108) on the functional capability of the isolated perfused rat kidney was tested. In control series hydroxyethyl starch (HES) instead of fluorocarbon was used. Improving O2 supply in FC 43 experiments raised Na reabsorption to 149 mumol/g x min compared to 84.

Interdependence of Na-excretion, plasma electrolytes, plasma volume and renal Na-K-ATPase-activity in hypertensive rats.

Hypertensive Goldblatt-rats have higher than normal Na-appetite and an enhanced Na-output. They have normal plasma Na- and K-concentration and kidney weight but a significantly reduced plasma volume. The amount of renal membrane protein and the renal Na-K-ATPase-activity of hypertensive rats was found to be significantly below that of controls.