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R N Zahlten

Publications and source records attributed to R N Zahlten.

At least 19 recordsLinked to original sources

[Summarized results of clinical phase II and III studies with ofloxacin (HOE 280) in Europe].

Ofloxacin is a new quinolone-carboxylic acid derivative with a broad spectrum of activity, excellent bioavailability after oral administration and insignificant metabolisation. The serum elimination half-life is six to eight hours. 879 patients were treated with ofloxacin in therapeutic comparative studies monitored by the Department of Clinical Research, Hoechst AG. Of the original isolates 91 to 100% were susceptible to ofloxacin, 67 to 84% to co-trimoxazole, 73 to 98% to a fixed combination of amoxycilline plus clavulanic acid (AMC), 74% to nalidixic acid, 77% to nitrofurantoin, and 79% to pipemidic acid in previous in vitro tests. In the therapeutic studies which included only patients with pathogens susceptible to the antimicrobial agent used, the following cure rates (clinical and bacteriological) were obtained for uncomplicated infections of the lower urinary tract: ofloxacin (single dose treatment) 78% and 83%, co-trimoxazole 62%, nalidixic acid 72%. A three-day course with ofloxacin compared to a three to four-day treatment with co-trimoxazole or seven-day treatment with the other comparative compounds resulted for lower urinary tract infections in the following cure rates: ofloxacin 89%, co-trimoxazole 84%; ofloxacin 71%, AMC 33%; ofloxacin 64%, nitrofurantoin 56%; ofloxacin 56%, pipemidic acid 36%. The unfavourable results after treatment with AMC or pipemidic acid were caused by a high rate of superinfections. The combined cure rate in infections of the upper urinary tract was 73% for ofloxacin and 65% for co-trimoxazole or 81% for ofloxacin and 57% for AMC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗

Isolated Kupffer cells, endothelial cells and hepatocytes as investigative tools for liver research.

The preparation and utilization of purified liver cell subpopulation is becoming an established tool for laboratory research in biological sciences. The various methods employed utilize cell separation based on differential sensitivity to enzymatic digestion, differences in cell size-density characteristics, and differential adherence of the various cell populations to a glass or plastic substrate. As detailed here, the choice of a technique for cell isolation is determined not only by whether parenchymal or nonparenchymal populations are to be used, but also by considerations relevant for the study of specific physiologic parameters. In this paper, techniques for the isolation and enrichment of hepatocytes and Kupffer cells are reviewed, with special attention to the utilization of counterflow elutriation in the preparation of these and other purified nonparenchymal cell populations. As examples of how isolated cells provide useful insights, studies on the properties of hepatocyte and nonparenchymal liver cell glycoprotein receptors, as well as observations on the immunologic functioned capabilities of isolated Kupffer cells, are presented.

Animals↗

Morphological characterization of Kupffer and endothelial cells of rat liver isolated by counterflow elutriation.

Kupffer and endothelial cells of rat liver were purified by recirculating collagenase perfusion, metrizamide gradient, and counterflow elutriation. Every step of the isolation procedure was followed by light microscopy and histochemistry. The final fractions of purified sinusoidal cells were examined in their isolated state by transmission and scanning electron microscopy. The scope of this manuscript is the detailed documentation and discussion of all technical aspects and problems of a rather new isolation technique, as well as the detailed description of the purified sinusoidal cells of the liver by scanning electron microscopy. Broader acceptance of this isolation procedure should lead to the specific characterization of biochemical and immunological functions of these cells and elucidate their pathophysiological significance.

Animals↗

Sulfhydryl group quantitation of hepatoma and liver microsomal fractions.

The relationship of sulfhydryl and disulfide groups to protein synthesis in normal and rapidly growing tissues was investigated by quantitation of sulfhydryl groups in endoplasmic reticulum and polyribosomes of normal liver and hepatomas. Stripping by ethylenediaminetetraacetate and potassium chloride of normal liver smooth and rough endoplasmic reticulum reduced by 15 percent and increased 30 percent, respectively, the sulfhydryl groups available for carboxamidemethylation by iodoacetamide. This could reflect the removal of ribosomes from rough endoplasmic reticulum with the subsequent exposure of sulfhydryl groups. Exposed sulfhydryl groups of normal mature female rat liver smooth endoplasmic reticulum were decreased to a similar degree by the stripping procedure with ethylenediaminetetra-acetate and potassium chloride when quantitated by either iodoacetamide or 4,4'-dithiodipyridine. This was not the case in young male and female rats, where the stripping procedure failed to decrease the exposed sulfhydryl groups of smooth endoplasmic reticulum. An increase in the quantity of exposed sulfhydryl groups of normal young and mature rat liver rough endoplasmic reticulum after stripping by ethylenediaminetetraacetate and potassium chloride was observed with iodoacetamide. However, when 4,4'-dithiodipyridine was used, no change could be detected. The hypothesis that smooth endoplasmic reticulum arises by degranulation of the rough endoplasmic reticulum in vivo is not supported by our sulfhydryl group quantitation of smooth endoplasmic reticulum and in vitro degranulated rough endoplasmic reticulum. A negative correlation between exposed sulfhydryl groups on the polyribosomes and the rate of growth of normal liver and of Morris hepatomas 6 and 38B suggests that the conformation of the free polyribosomal proteins could be a control factor for the rate of protein synthesis. Faster growing hepatomas also have greater quantities of sulfhydryls and disulfides.

Age Factors↗

Regulation of glucose synthesis in hormone-sensitive isolated rat hepatocytes.

A simplified procedure was developed for isolation of intact, hormone-sensitive liver cells in a high and reproducible yield. These cells produce glucose from various precursors at rates comparable to those achieved in isolated perfused liver. Glucagon enhanced glucose synthesis from pyruvate, dihydroxyacetone, fructose, or xylitol more effectively at low than at high substrate concentration. At high pyruvate concentrations (>2 mM), glucagon or adenosine 3':5'-cyclic monophosphate (0.1 mM) exerts a curious inhibition of gluconeogenesis that can be reverted to stimulation on addition of ethanol. It is suggested that glucagon and cyclic AMP inhibit pyruvate dehydrogenase and thus limit the supply of reducing equivalents needed for glucose formation. Supporting evidence for hormonal control of pyruvate dehydrogenase in isolated liver cells is provided by the fact that glucagon decreases and insulin increases decarboxylation of [1-(14)C]pyruvate. Calcium salts (1.3 mM) enhance glucose formation from pyruvate but greatly enhance the inhibition exerted by the divalent cationophore, A23187. Inhibition by glucagon of glucose synthesis from pyruvate is additive with the effects of A23187 + Ca(++). However, with dihydroxyacetone as substrate, glucagon partially reverses the inhibition exerted by A23187 + Ca(++). The results are consistent with glucagon effecting an inhibition of pyruvate dehydrogenase and a stimulation of hexosediphosphatase activities.

Acetone↗