Biomedical subjects

G Inselmann

Publications and source records attributed to G Inselmann.

32 records · Page 2Linked to original sources

PubMed1994

[Pericardial lipoma as the cause of extensive mediastinal space-occupying lesion].

Lipomas of the heart are benign neoplasias and have rarely been described. Due to the fact that they normally cause no symptoms, diagnosis is often purely accidental. In the current report, the case of a 55-year-old patient is described in whom serial chest x-rays showed massive, progressive cardiac enlargement. Echocardiography and NMR showed a large pericardial mass confirmed by subsequent surgery which revealed a giant pericardial lipoma.

Diagnosis, Differential↗

PubMed1993

Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria.

OBJECTIVE: Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. METHODS: The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. RESULTS: The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. CONCLUSIONS: Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria.

Animals↗

PubMed1993

[Correlation between Doppler echocardiography and invasive determination of left ventricular hemodynamic valve parameters. A comparative study under routine conditions in a cardiology center].

UNLABELLED: Simultaneously performed combined Doppler/catheter studies have shown excellent correlations regarding the comparison of invasively and non-invasively obtained valve gradients. To reflect daily clinical life the current study compared the valve parameters obtained by Doppler echocardiography to those obtained later by catheterization in all consecutive patients who underwent invasive procedure between October 1988 and December 1990. A total of 113 patients was included in the study, 76 with aortic and 37 with mitral stenosis. Regarding the mean aortic valve gradient the following correlations were obtained: all patients: r = .79, patients with an ejection fraction > 50% (n = 59): r = .81, patients with an ejection fraction < 50% (n = 17): r = .67, patients with additional aortic insufficiency (n = 21): r = .77. When the mean mitral valve gradient was compared the correlation was r = .71 for all patients and r = .44 when additional mitral regurgitation was present (n = 10). The comparison of the mitral valve orifice area (n = 30) showed a correlation of r = .58. CONCLUSION: Non-simultaneously performed combined Doppler/catheter studies in unselected patients do reflect daily clinical life, however, correlations are not as good as in corresponding simultaneously performed investigations, thus emphasizing the impact of the study conditions on the final results.

Adult↗

PubMed1992

Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat.

The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentrations and glucose-6-phosphatase activity. Intravenous amphotericin B (3 mg/kg) given daily for 3 days decreased antipyrine clearance from control values of 1.24 +/- 0.24 ml/min to 0.67 +/- 0.12 ml/min (p less than 0.001); whereas antipyrine clearance was unchanged by sodium deoxycholate. The P-450 concentration on the third day was reduced from 0.74 +/- 0.14 nmol/mg protein in control rats to 0.33 +/- 0.09 nmol/mg protein in rats treated with amphotericin B (p less than 0.001). Sodium deoxycholate had no effect on P-450 concentration. In contrast, amphotericin B had no effect on either antipyrine clearance or P-450 concentration following enzyme induction by phenobarbital. Amphotericin B had no effect on microsomal glucose-6-phosphatase activity in vivo. Neither amphotericin B nor sodium deoxycholate induced lipid peroxidation, measured as malondialdehyde production. These results show that amphotericin B decreases hepatic cytochrome P-450 content and function in the rat. These effects can not be observed in the enzyme induced state. Amphotericin B has no effect on glucose-6-phosphatase in vivo, the key enzyme of the gluconeogenesis, indicating selective effects on hepatic microsomal function.

Amphotericin B↗

PubMed1992

Amphotericin B and sodium deoxycholate induced impairment of renal p-aminohippurate accumulation (PAH) and effect on lipid peroxidation in the rat kidney.

The influence of amphotericin B on PAH transport as well as on lipid peroxidation in rat renal cortical slices was studied in vitro and ex vivo. In vitro, renal cortical slices were incubated with different amphotericin B (AmB) concentrations (2-60 micrograms/mL) or with the corresponding vehicle concentrations of sodium deoxycholate (NaDo) (1.64-49.2 micrograms/mL) and time dependently (15-30-60 min) with 30 micrograms/mL AmB or 24.6 micrograms/mL NaDo. Ex vivo, PAH transport of renal cortical slices was investigated following a 3-day intravenous AmB administration with 3 mg/kg per day or 2.46 mg/kg/day NaDo, respectively. In vitro AmB as well as NaDo decreased PAH transport dose and time dependently. At the highest AmB concentration of 60 micrograms/mL, PAH uptake decreased to 17.6%. The corresponding NaDo concentration (49.2 micrograms/mL) decreased PAH uptake to 33.3%. Time dependently AmB decreased PAH uptake to 25% after 60 min. NaDo caused a decrease to 69%. Administration of AmB for 3 days resulted in a PAH decline to 81%; NaDO decreased PAH uptake to 77%. In vitro as well as in vivo, AmB or its vehicle did not induce lipid peroxidation in renal cortical tissue. In summary, the results show that AmB and its vehicle, NaDo, decrease PAH uptake by renal cortical cells, reflecting a direct effect of AmB on tubular function. The impairment of the PAH transport is not due to enhanced lipid peroxidation.

Amphotericin B↗

PubMed1991

Influences of Ginkgo biloba on cyclosporin A induced lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and N-acetylcysteine.

The in vitro effect of cyclosporin A (CsA) on lipid peroxidation in human liver microsomes was investigated, and efforts were made to prevent the resulting toxic effect of CsA. Microsomes were prepared from human liver resection material and incubated with CsA (0, 10, 30, 100, 300, 1000 micrograms/mL) for one hour (pH 7.4, 37 degrees, 95% O2, 5% CO2). Subsequently the resulting concentrations of malondialdehyde equivalents (MDA) were determined, a breakdown product of lipid peroxidation. Furthermore the duration of incubation was varied (0, 15, 30, 60, 90 min) using a CsA concentration of 300 micrograms/mL. CsA was shown to stimulate MDA-formation to up to 10-fold of the control value in both a time and concentration dependent manner. The dosage dependent experiment stated above was repeated, adding alpha-tocopherol (vitamin E, 1 mM), reduced glutathione (GSH, 1 mM), N-acetylcysteine (0.1, 0.3, 1, 3 mM), and Ginkgo biloba extract (Gbe, 15, 50, 150 micrograms/mL), respectively, to the medium of incubation. Vitamin E, a potent radical scavenger, proved to inhibit lipid peroxidation almost totally. Both GSH and N-acetylcysteine were also able to prevent lipid peroxidation, suggesting that the antioxidant effect of GSH might be caused by its thiol group and does not depend on the integrity of the whole molecule. Gbe inhibited CsA induced lipid peroxidation in a concentration dependent manner. This effect of Gbe was diminished yet not totally abolished when FeCl3 was added to the medium of incubation, whereas N-acetylcysteine even slightly enhanced CsA stimulated lipid peroxidation in the presence of iron. These results suggest that Gbe might be able to prevent radical mediated damage to human membranes caused by CsA.

Acetylcysteine↗

PubMed1991

Cyclosporin-A-induced lipid peroxidation in human liver microsomes and its influence on cytochrome P-450.

The present in vitro study using human liver tissue was performed to investigate the effect of cyclosporin A on lipid peroxidation and cytochrome P-450 concentration in isolated liver microsomes. Incubations were either carried out with cyclosporin A concentrations of 10, 30, 100 and 300 micrograms ml-1 for 1 h or for different time periods (15, 30, 60 and 90 min) with cyclosporin A 300 micrograms ml-1. Lipid peroxidation was monitored measuring the amount of malondialdehyde. In additional experiments the effect of reduced and oxidized glutathione (1 mM) on cyclosporin-A-induced lipid peroxidation in human liver microsomes was studied. Cyclosporin A caused a significant dose and time-dependent increase of the lipid peroxidation product malondialdehyde. At the highest cyclosporin A concentration (300 micrograms ml-1) malondialdehyde production increased 5-fold in comparison to corresponding control values. Incubations for different time periods resulted in a 5-fold net increase of malondialdehyde formation after 90 min. In the presence of reduced glutathione, cyclosporin-A-induced lipid peroxidation was significantly inhibited. Furthermore, cyclosporin-A-induced microsomal lipid peroxidation was accompanied by a significant dose-dependent decline of the microsomal cytochrome P-450 content. At a cyclosporin A concentration of 300 micrograms ml-1, cytochrome P-450 content was decreased to 49% in comparison to control values. In the presence of reduced glutathione, cyclosporin A decreased the cytochrome P-450 concentration only to 79% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗

PubMed1991

Effect of chronic theophylline administration on amphotericin B nephrotoxicity in rats.

The effect of chronic theophylline administration on amphotericin B nephrotoxicity was investigated in rats. A 7-day treatment of amphotericin B (5 mg/kg/day i.p.) significantly reduced the glomerular filtration rate (GFR) measured as inuline clearance and creatinine clearance (0.74 +/- 0.29 and 0.16 +/- 0.04 ml/min, respectively) in comparison to vehicle-treated rats (2.04 +/- 0.23 and 1.29 +/- 0.19 ml/min, respectively). The reduced GFR led to evaluations in serum creatinine and BUN concentrations (0.94 +/- 0.09 and 78 +/- 11 mg/dl) in comparison to their own values before treatment (0.45 +/- 0.11 and 19 +/- 3 mg/dl). In addition amphotericin B induced an increase in sodium and a decrease in potassium excretion, the fractional sodium excretion was elevated 50-fold. The methylxanthine, theophylline, had a beneficial effect on the outcome of amphotericin-B-induced renal failure. The inuline clearance was 1.17 +/- 0.04 ml/min, the creatinine clearance 0.43 +/- 0.03 ml/min, the serum creatinine concentration 0.76 +/- 0.05 mg/dl and the BUN concentration 40 +/- 6 mg/dl. Theophylline had no effect on total sodium excretion and potassium excretion. The fractional sodium excretion, however, improved significantly. Theophylline as well as sodium deoxycholate, the detergent of amphotericin B, given alone had no effect on renal hemodynamics measured after 7 days.

Acute Kidney Injury↗

PubMed1990

Long-term effects of acetazolamide and sodium chloride loading on cisplatin nephrotoxicity in the rat.

The protective effect of acetazolamide or sodium chloride loading on cisplatin nephrotoxicity was investigated in rats. After a single dose of cisplatin (5 mg kg-1 i.p.) kidney function was studied after 5, 28 and 84 days. Acetazolamide (75 mg kg-1 i.p.) was administered as a single dose prior (30 min) to the cisplatin injection. By the time of cisplatin administration, the rats were sodium depleted except the sodium-loaded group. Five days after the cisplatin administration all rats received a regular rat chow for the rest of the experiment. Cisplatin alone caused renal failure that could be observed for up to 12 weeks (ClCr 0.32 +/- 0.13 vs. 0.62 +/- 0.06 ml min-1 x 100 g BW-1) with polyuria (UVol 41.2 +/- 4.5 vs. 18.4 +/- 4.6 ml 24 h-1). Pretreatment with acetazolamide was the most protective manoeuvre tested. Five days after cisplatin, kidney function was significantly better than in rats treated with cisplatin alone (ClCr 0.21 +/- 0.06 vs. 0.03 +/- 0.01 ml min-1 x 100 g BW-1), after 28 days the only sign of nephrotoxicity was polyuria (UVol 28.9 +/- 3.7 vs. 19.0 +/- 2.6 ml 24 h-1) after 84 days no differences could be observed at all. Sodium chloride loading was less protective on cisplatin nephrotoxicity. Impaired renal function could still be observed after 12 weeks (ClCr 0.41 +/- 0.05 vs. 0.62 +/- 0.06 ml min-1 x 100 g BW-1) with no difference in comparison with the rats treated with cisplatin alone. However, since 12 rats died in the group having received cisplatin alone and only one rat in the high-salt group, sodium chloride loading is regarded as being advantageous over sodium depletion on cisplatin nephrotoxicity.

Acetazolamide↗

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

Effect of 5-fluorocytosine and 5-fluorouracil on human and rat hepatic cytochrome P 450.

Hepatotoxicity is a well-known side effect of the antifungal drug 5-fluorocytosine. The underlying mechanisms of this toxicity are unknown. The present in vitro study was, therefore, designed to assess the influence of 5-fluorocytosine and 5-fluorouracil on the hepatic cytochrome P 450 concentration in human and rat liver microsomes. Incubation of human or rat hepatic microsomes for 1 h with 5-fluorocytosine up to 500 micrograms/ml or with 5-fluorouracil up to 200 micrograms/ml did not influence the cytochrome P 450 concentration. In comparison the amount of cytochrome P 450 in human liver, however, was lower than in rat liver microsomes and a more interindividual variation was observed.

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↗