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Biomedical subjects

K Baumann

Publications and source records attributed to K Baumann.

At least 19 recordsLinked to original sources
PubMed1992

Nephrotoxicity of acyclovir and cis-diamminedichloroplatinum(II)--effect of co-administration in rats.

The effect of co-administration of acyclovir and cis-diamminedichloroplatinum(II) (cisplatin) on nephrotoxicity in male Wistar rats was investigated. Animals received acyclovir (15 mg/kg body weight, s.c., three times per day for 5 days) or cisplatin (5 mg/kg body weight, i.p., one single injection) or a combination of both drugs. Acyclovir plasma levels were determined after one single acyclovir s.c. injection. Urines were monitored for volume, pH, osmolality and excretion of N-acetyl-beta-D-glucosaminidase (NAG), lysozyme and total protein. Concentrations of blood urea nitrogen and plasma creatinine were determined on day 6. Renal cortical slices were monitored to assess the accumulation of weak organic bases (tetraethylammonium) and acids (p-aminohippurate). Cisplatin induced a marked increase in the excretion of NAG, lysozyme and total protein and an increase in urine volume, plasma creatinine and blood urea nitrogen. Urine osmolality and accumulation of p-aminohippurate were depressed by cisplatin. Acyclovir treatment alone caused no significant symptoms of nephrotoxicity. Co-administration did not impair renal function more than cisplatin treatment alone, excepting a slight rise in lysozyme excretion on day 6. Short-term antiviral therapy with acyclovir, concomitant to cisplatin treatment, may bring, if at all, a slightly increased nephrotoxic risk.

Acyclovir↗
PubMed1992

Active autoimmune gastritis without total atrophy of the glands.

To date, autoimmune gastritis has been diagnosed for the most part only when total atrophy of the oxyntic glands is detected. On the basis of 40 patients without total atrophy of the glands, and with parietal cell antibodies in the serum, we show that the diagnosis of type A gastritis is also possible in the pre-atrophic stage. The histological criteria for the diagnosis of active autoimmune gastritis without total atrophy of the glands are 1. usually dense, diffuse locally emphasized lymphocytic infiltration of the lamina propria between the glands in the oxyntic mucosa, 2. focal destruction of individual glands in the corpus of the stomach by lymphocytes, and 3. reactive pseudohypertrophy of the parietal cells. A comparison with a group of patients with autoimmune gastritis and total atrophy of the glands shows that in active autoimmune gastritis, too, women are more frequently affected than men (in both groups, the sex ratio is approximately 3:1). Patients without atrophy of the glands are, on average, about 12 years younger than those with "burnt out" type A gastritis (average age 69.98:57.80 years). While in the case of burnt out type A gastritis, no colonisation with Helicobacter pylori was to be found, such colonisation was demonstrated for the corpus mucosa in 22.5%, and for the antral mucosa in 15.0%. In 27.5% a minimal or low-grade inactive superficial gastritis, as may be seen after eradication of Helicobacter pylori, was additionally diagnosed in the antrum. A knowledge of the histological appearance of the pre-atrophic stage of type A gastritis might be of importance for the possible prevention of pernicious anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Iron- and ascorbic acid-induced lipid peroxidation in renal microsomes isolated from rats treated with platinum compounds.

Renal microsomes isolated on day 3 from cisplatin (CDDP, single i.p. injection, 4 or 6 mg/kg)-treated rats were monitored for their susceptibility to lipid peroxidation as compared with microsomes from rats treated with carboplatin (CBDCA, 30 mg/kg), transplatin (TDDP, 6 mg/kg) or CDDP hydrolysis products (4 or 6 mg/kg) or from control animals. Cephaloridine (1 g/kg daily for 4 days, i.p. injection) was used as a positive control. The effect of CDDP on renal microsomal glucose-6-phosphatase activity was investigated in vivo and in vitro. Following treatment with CDDP and CDDP hydrolysis products vs CBDCA and TDDP treatment, microsomes revealed an enhanced susceptibility to lipid peroxidation in a Fe2+ and/or ascorbic acid stimulation system. Increased lipid peroxidation, expressed as an increase in malondialdehyde (MDA) generation, paralleled the alterations in body and kidney weight and the elevations of plasma creatinine and blood urea nitrogen concentrations. Injection of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD, 0.5 g/kg, i.p.) at 24 h prior to CDDP treatment abolished the increased vulnerability of renal microsomes to lipid peroxidation. In vivo, only CDDP hydrolysis products exhibited a significant inhibitory effect on renal glucose-6-phosphatase activity. In vitro, rat renal and hepatic microsomal glucose-6-phosphatase activity was decreased by CDDP both time- and concentration-dependently. Nephrotoxicity induced by CDDP and CDDP hydrolysis products might be attributable to iron-dependent lipid peroxidation and microsomes might represent target organelles on a subcellular level.

Animals↗
PubMed1990

[Diabetic neuropathy].

Neuropathy is a frequent late complication of diabetes. The severity and duration of hyperglycaemia are probably the principal causal factor. The consequences of the effects of neuropathy on the lower-limb and the autonomic nervous system are major causes of morbidity. Apart from glycaemic control, no specific treatment is yet available, but measures for symptomatic alleviation of certain painful and visceral manifestations of diabetic neuropathy exist and are outlined in these guidelines. The guidelines also describe simple diagnostic strategies for detecting potentially threatening neurological signs, notably reduction or loss of lower-limb sensation which expose the patient to the risk of ulceration, unnoticed trauma and amputation. The guidelines also summarize the preventive educational measures required to minimize these risks.

Diabetic Neuropathies↗
PubMed1990

Nephrotoxicity of cisplatin, carboplatin and transplatin. A comparative in vitro study.

The present study was designed to compare the nephrotoxicity induced by the three platinum compounds cisplatin (CDDP), carboplatin (CBDCA) and transplatin (TDDP) in vitro and to obtain information to elucidate the mechanism of platinum compound-induced nephrotoxicity. Rat or rabbit renal cortical slices were incubated for different periods of time in platinum compound-containing media (0.42 or 1.67 mM) and thereafter monitored for platinum content, tetraethylammonium(TEA) and paraaminohippurate(PAH) accumulation and gluconeogenesis. Malondialdehyde(MDA) content of slices was determined as a parameter of lipid peroxidation. Activity of glucose-6-phosphatase of rat renal microsomes was investigated after platinum-compound exposure. In all series of experiments the effect of the antioxidant N,N'diphenyl-p-phenylenediamine (DPPD) was tested. CBDCA showed no effects on all parameters of renal cell function at all concentrations and all time points investigated, except for the activity of glucose-6-phosphatase, which was slightly affected by CBDCA. CBDCA-induced MDA production was lower, compared to CDDP, which showed marked toxic effects on TEA and PAH accumulation, gluconeogenesis and glucose-6-phosphatase activity. The onset of CDDP-induced alterations was dependent on drug concentration. MDA production was reduced by DPPD. Protection against the platinum compound-induced decrease in TEA and PAH accumulation was observed after the use of DPPD. DPPD had no protective effect on CDDP-induced inhibition of gluconeogenesis and glucose-6-phosphatase, which might indicate an effect on gluconeogenesis by direct inhibition of glucose-6-phosphatase. DPPD did not alter uptake of platinum compounds in rat renal cortical slices. TDDP showed different in vitro properties compared to in vivo conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of cyclosporine A on accumulation of tetraethylammonium and p-aminohippurate, and on lipid peroxidation in rat renal microsomes and cortical slices.

The effect of cyclosporine A (CsA) on lipid peroxidation (LPO) was assessed in renal cortical slices and renal microsomes. Cortical slices were incubated with 1500 micrograms/ml CsA and microsomes with 0.5-20 micrograms/ml under identical conditions (pH 7.4, 37 degrees C) for 3 hours, and LPO monitored by the formation of malondialdehyde (MDA). CsA at concentrations of 3 micrograms/ml and higher caused a significant increase MDA in microsomes and renal cortical slices showed a time dependent release of MDA into the incubation medium. The influence of CsA on tetraethammonium (TEA) and p-aminohippurate (PAH) accumulation in renal cortical slices was investigated for up to 3 hours with concentration of CsA from 10 to 1000 micrograms/ml. CsA caused a time- and concentration-dependent decrease of TEA accumulation and higher concentrations of CsA decreased PAH accumulation in renal cortical slices. The results add further evidence to the suggestion that lipid peroxidation participate in CsA-induced impairment of kidney function.

Animals↗
PubMed1990

Cyclosporine A induced lipid peroxidation and influence on glucose-6-phosphatase in rat hepatic and renal microsomes.

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in hepatic and renal microsomes (male Wistar rats) were investigated either with different CsA concentrations (0.3-1000 micrograms/ml), incubation time 3 h or for different periods of time (0.5-3.0 h) at a CsA concentration of 1000 micrograms/ml. LPO was monitored by measuring the formation of malondialdehyde (MDA) using the thiobarbituric acid assay. Furthermore the influence of CsA on the microsomal enzyme glucose-6-phosphatase was investigated. CsA caused a time- and concentration-dependent increase of LPO in hepatic and renal microsomes. The lowest CsA concentration which produced a significant increase in MDA production amounted to 1 microgram/ml for hepatic microsomes and 3 micrograms/ml for renal microsomes. Under identical experimental conditions, the MDA production by hepatic microsomes was 3 to 5 fold higher than by renal microsomes. Addition of the radical scavenger alpha-tocopherol (1 mM) to the incubation medium decreased the CsA-caused microsomal MDA production. Regarding the microsomal enzyme, CsA decreased the specific activity of glucose-6-phosphatase in a time- and concentration-dependent fashion. Compared to microsomal MDA production, higher CsA concentrations were necessary to effect on specific enzyme activity. The results suggest, that production of free radicals and subsequently lipid peroxidation could participate in cyclosporine A induced hepato- and nephrotoxicity.

Animals↗
PubMed1989

Sex differences in nephrotoxic and gastrointestinal effects of phenylbutazone.

Male and female Wistar rats were used to study the sex differences in nephrotoxic, ulcerogenic and lethal effects of phenylbutazone (PBZ). In one series of experiments, male and female rats were given daily oral doses of 25, 125, 250, 400 and 500 mg PBZ/kg for 7 days to assess mortality, gross and microscopic lesions of the stomach, intestine and kidneys and to determine the PBZ effects on renal protein and glucose excretion. In another series of experiments, PBZ effects on renal gluconeogenesis and p-aminohippurate (PAH) accumulation in renal cortical slices were measured 12 h after administration of the same PBZ doses to male and female rats. Reduced glutathione (GSH) depletion and malondialdehyde (MDA) content in kidney cortex and liver were determined 2 h after a single administration of 250 mg PBZ/kg to male and female rats. To measure the effects of PBZ on blood urea nitrogen (BUN), male and female rats were given a single dose of PBZ (125 mg/kg) and were sacrificed at different time intervals, from 0 to 48 h. Gross and microscopic examination of the kidneys and gastrointestinal tract showed more pronounced renal and gastrointestinal lesions in surviving female than in male rats at the same doses. In PBZ treated male rats, BUN did not differ from control rats 48 h after PBZ administration. In female rats, BUN increased from 18 to 96 mg/100 ml 48 h after PBZ administration. After 7 days of PBZ treatment there was a greater increase of protein excretion in female than in male rats, but there were almost no sex differences in glucose excretion. Twelve hours after PBZ administration, renal PAH accumulation and gluconeogenesis were not different from controls in male rats but decreased in a dose-dependent fashion in females. A significant depletion of GSH and a significant increase in MDA content in liver and renal cortex occurred in female but not in male rats. In conclusion, the PBZ treatment was associated with nephrotoxic and gastrointestinal effects which could be detected earlier and were greater in female than in male rats.

Animals↗
PubMed1989

Computer analysis reveals changes in renal Na+-glucose cotransporter in diabetic rats.

A novel, computer-assisted program was developed to analyze the time course of Na+-glucose cotransport by rat renal cortical brush-border membrane vesicles (BBMV). Transporter characteristics can be measured, which routine kinetic analyses fail to distinguish: cotransporter membrane density is derived from the picomoles of D-glucose bound per milligram of protein. Binding is stereospecific, blocked by phlorizin, and supported equally well by Na+ or K+ (but not Cs+). Quasi-first-order influx and efflux rate constants for the composite Na+-driven influx and the (presumed) Na+-independent efflux processes were highly dependent on glucose concentration. Either two Na+-glucose transporters exist in proximal tubules or a single mechanism abruptly changes rate when glucose falls to low levels. The major operation mode is slow, has a high capacity but low affinity, and may have a 2 Na+:2 glucose stoichiometry (Hill coefficient is unity). The minor system is a fast, smaller-capacity, higher-affinity operation with a 2 Na+:1 glucose stoichiometry that was not distinguishable when the same data were analyzed in conventional kinetic plots. Results with streptozocin-induced diabetic rats illustrate the method's utility. Low-glucose-affinity cotransporters were upregulated in hyperglycemic, but not in cachectic, ketoacidotic animals. Rate constants, especially for efflux, were decreased in diabetes.

Animals↗
PubMed1988

Nephrotoxic potential of first-, second-, and third-generation cephalosporins.

First-, second-, and third-generation cephalosporins were investigated for their peroidative and nephrotoxic potential. Renal cortical slices from male Wistar rats were incubated at 37 C for 1 h in a phosphate-buffered medium containing the cephalosporin (1.25, 2.5, 5 or 10 mg/ml). In another series of experiments 5 mg/ml cephalosporin was incubated under the same conditions for 30, 60, 90 and 120 min. Subsequently, slices were incubated for 60 or 90 min in a bicarbonate- or phosphate-buffered medium containing pyruvate or tetraethylammonium (TEA) to determine gluconeogenesis and TEA accumulation, respectively. The peroxidative potential was determined at the end of the first incubation by measuring the increase in the malondialdehyde (MDA) content in renal cortical slices. The nephrotoxic potential was determined at the end of the second incubation by measuring the decrease in accumulation of the organic ion (TEA) and decrease of pyruvate-stimulated gluconeogenesis in renal cortical slices. First-generation cephalosporins, cephaloridine and cephalothin showed a time- and concentration-dependent increase in MDA content and a decrease in TEA accumulation and gluconeogenesis by renal cortical slices. Cefazolin, another first generation cephalosporin, showed a weak peroxidative and practically no nephrotoxic potential. In the group of second-generation cephalosporins, cefotiam showed a weak peroxidative potential comparable to that of cefoxitin but had a much greater nephrotoxic potential which was similar to that of cephaloridine. The third-generation cephalosporins, cefotaxime and cefoperazone showed a low peroxidative and no nephrotoxic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cisplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: different effects of antioxidants and radical scavengers.

The present in vitro study was performed to investigate the effect of the nephrotoxic anticancer agent cisplatin (CP) on lipid peroxidation, on pyruvate-stimulated gluconeogenesis and on p-aminohippurate (PAH) accumulation in rat renal cortical slices. In addition, the inhibitory effects of the antioxidants and radical scavengers N,N'-diphenyl-p-phenylenediamine (DPPD), (+)-cyanidanol-3 or alpha-tocopherol on CP-induced lipid peroxidation and CP-induced decrease of gluconeogenesis and the inhibitory effect of DPPD on CP-induced decrease of PAH accumulation were evaluated. Slices were incubated in a CP-containing medium for different periods of time (7.5-300 min) and at different concentrations (0.025-1.5 mg/ml). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Accumulation of PAH was expressed as slice to medium concentration ratio. Pyruvate-stimulated gluconeogenesis, measured as glucose production, was determined after a subsequent 60- or 15-min incubation in a pyruvate-containing, CP-free medium. CP led to a time- and concentration-dependent increase in MDA production, a time- and concentration-dependent decrease of pyruvate-stimulated gluconeogenesis and a time-dependent decrease of PAH accumulation in renal cortical slices. Decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation. Antioxidants reduced CP-induced MDA production and CP-induced decrease of accumulation of PAH, but did not reverse CP-induced decrease of gluconeogenesis. This might indicate, that the generation of free radicals and subsequent lipid peroxidation may play a role, at least in part, in inducing CP nephrotoxicity. There could be more than one mechanism of CP-induced nephrotoxicity, since decrease of gluconeogenesis preceded MDA production and decrease of PAH accumulation and could not be inhibited by antioxidants and radical scavengers.

Animals↗
PubMed1988

Inhibition of lactate-dehydrogenase by cisplatin and other platinum-compounds: enzyme leakage of LDH is not a suitable method to measure platinum-compound-induced kidney cell damage in vitro.

The effects of three platinum-compounds on the activity of hog muscle lactate-dehydrogenase (LDH), cytosolic LDH released from rat renal cortical slices and cytosolic LDH isolated from rat kidney cells were investigated. In vitro, cisplatin inhibited the activity of LDH in a concentration-dependent manner. At a concentration of 0.25 mg/ml, cisplatin, transplatin and cisplatin-hydrolysis-products inhibited the activity of LDH time-dependently. These observations make it doubtful to use LDH-enzyme leakage experiments to demonstrate damage of kidney cells by platinum-compounds. The nonnephrotoxic compound transplatin had an enhanced inhibitory effect on the activity of LDH compared to the nephrotoxic compounds cisplatin or cisplatin-hydrolysis-products (transplatin greater than cisplatin greater than cisplatin-hydrolysis-products). Thus, LDH-enzyme inhibition seems not to be related to the nephrotoxicity of cisplatin.

Animals↗
PubMed1988

Cyclosporine A induced lipid peroxidation in microsomes and effect on active and passive glucose transport by brush border membrane vesicles of rat kidney.

The in vitro effect of cyclosporine A (CsA) on lipid peroxidation (LPO) in rat renal microsomes were investigated either with different CsA concentrations (0.001 to 1.5 mg/ml) or for different periods of time (0.5 to 3 h). Furthermore the influence of this drug on glucose uptake by rat renal brush border membrane vesicles (RBBMV) prepared from renal cortical slices which were preincubated with CsA for 1 or 3 h was studied. CsA caused a time- and concentration-dependent increase of malondialdehyde production in renal microsomes. LPO was inhibited by addition of the radical scavenger alpha-tocopherol. Regarding the CsA effect on the vesicular glucose uptake, an increase in the passive influx constants of L-glucose and a decrease in the maximal transport rates of the sodium-dependent D-glucose uptake were found as compared to the corresponding control values. The apparent affinities of D-glucose to the glucose transporter were slightly lowered after incubation of slices in a CsA containing medium. The results of the present study suggest that CsA causes LPO in renal microsomes and that this LPO is due to membrane damage by CsA as shown by alternations of active and passive glucose uptake by RBBMV.

Animals↗
PubMed1985

Inhibition of cephaloridine-induced lipid peroxidation.

The present study was designed to elucidate whether cephaloridine-induced lipid peroxidation is inhibited by probenecid, cobalt chloride and antioxidants such as alpha-tocopherol and N,N'-diphenyl-p-phenylenediamine (DPPD). Kidney slices obtained from the renal cortex of male Wistar rats were incubated for 1 h in a cephaloridine or cefotaxime (1.25-10 mg/ml) containing medium. In another series of experiments, kidney slices were incubated with cephaloridine or cefotaxime (5 mg/ml) for different periods of time (30-120 min). Lipid peroxidation was monitored by measuring the production of malondialdehyde (MDA). Subsequently, kidney slices were incubated in both series of experiments, in a cephalosporin free medium containing tetraethylammonium (TEA). Accumulation of TEA in renal cortical slices, expressed as slice to medium ratio (S/M), was used to measure changes in the transport capacity of the kidney cells. While cefotaxime had only a slight effect, cephaloridine induced a significant time- and concentration-dependent increase of MDA production and a significant time- and concentration-dependent decrease of TEA accumulation. Inhibition of the renal uptake of cephaloridine by probenecid induced a decrease in MDA production and complete recovery of TEA accumulation. The antioxidants DPPD and alpha-tocopherol inhibited cephaloridine-induced lipid peroxidation in a concentration-dependent manner. Recovery of TEA accumulation accompanied the decrease in lipid peroxidation. DPPD was a more potent inhibitor of lipid peroxidation than alpha-tocopherol. Cobalt chloride, known for its ability to decrease cellular concentration of cytochrome P-450, effectively decreased cephaloridine-induced lipid peroxidation. Thus, these findings support the concept that lipid peroxidation has an important role in the development of cephaloridine-induced nephrotoxicity.

Animals↗
PubMed1985

Cephaloridine-induced lipid peroxidation initiated by reactive oxygen species as a possible mechanism of cephaloridine nephrotoxicity.

Rat kidney microsomes reduced cephaloridine when incubated anaerobically with NADPH. Superoxide anion was generated in a concentration- and time-dependent manner when cephaloridine was incubated with rat kidney microsomes. Cephaloridine increased the in vitro peroxidation of rat kidney microsomal lipids in a concentration- and time-dependent manner. Cephaloridine-induced lipid peroxidation was inhibited by a combination of superoxide dismutase and catalase, by the hydroxyl radical scavengers, mannitol, (+)-cyanidanol-3 and by the singlet oxygen scavenger histidine in a concentration-dependent manner. It is proposed that cephaloridine nephrotoxicity may occur through the transfer of an electron from reduced cephaloridine to oxygen and subsequent formation of the superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These activated oxygen species then are very likely to react with membrane lipids to induce lipid peroxidation and nephrotoxicity.

Anaerobiosis↗