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Biomedical subjects

M Bohdanecká

Publications and source records attributed to M Bohdanecká.

At least 19 recordsLinked to original sources

[Charge interactions of immune deposits in glomeruli (experimental study)].

An i.v. injection of 8-40 mg (kg cationized and heat-aggregated rabbit or human Ig (cat-aggr RIg,-HuIg; pI 9.5) elicited a strong diffuse linear fixation in rat glomerular capillaries revealed by one-step immunofluorescence or immunoenzyme histochemistry 1 and 2 h post-injection. Preferential binding to the lamina rara externa (LRE) was documented in ultrastructure by preembedding and postembedding assays (HRP-coupled antibody and protein A-colloidal gold, respectively). After 24 and 48 h the glomeruli were negative. Polyethylenimine (PEI)-reactive polyanion of LRE was significantly reduced 1 h after cat-aggr-Ig; depletion persisted even after 48 h. Non-cationized Ig aggregates did not bind to the glomerular capillaries. A subsequent i.p. injection of swine anti-rabbit-Ig antibody (SwAR, 15 mg i.p. after 4 h) produced the same linear binding of both two antigens which, however, persisted after 10 days and assumed a granular pattern. After presensitization with RIg (1-2 mg i.p. or s.c.; 4 days before cat-aggr RIg) the early linear fixation underwent a gradual transformation into the granular pattern and deposits of mesangial, rarely of epimembranous type were found 1 week after cat-aggr RIg and later. RIg and SwIg were proved in both types of deposits. After 2 weeks both rat Ig and C 3 were present, too. Rarefaction of deposits and their concentration in the vascular poles took place during 3 months, and deposits also appeared in the media of vas afferens. The antigen load did not produce an acute glomerulonephritis or significant proteinuria; slight focal mesangial sclerosis and a discrete increase in serum creatinine were noted after 2-3 months. To sum up: The one-shot charge interaction is prompt but short-lived whereas the local binding of additional proteins, especially after a specific preimmunization, significantly prolongs the contamination of glomeruli and promotes the build-up of immune complex-type deposits which gradually retreat to the mesangial stalk and vascular pole.

Animals

Effect of chronic renal insufficiency on the function and metabolic parameters of the isolated rat heart.

Chronic renal insufficiency (CRI) is often associated with cardiovascular disease; however, its underlying mechanisms are not completely understood. Therefore, in the present study, myocardial functions and metabolic changes were investigated using an animal model of CRI in subtotally nephrectomized rats. In addition, some other parameters, considered risk factors of cardiovascular diseases, were determined. Subtotal nephrectomy led to an elevation in blood pressure (144 +/- 2.8 vs 114 +/- 2.5 mm Hg), left ventricular hypertrophy (290 +/- 12 vs 200 +/- 40 mg/100 g b.w.), hypertriglyceridaemia (2.96 +/- 0.31 vs 0.77 +/- 0.07 mmol/l), and impaired glucose tolerance (AUC 836 +/- 12.4 vs 804 +/- 10.4 mmol x l(-1) x 120 min). Isolated perfused hearts of uraemic rats exhibited diminished basal functions (coronary and aortic flow, stroke volume) by 20-30% compared with the controls. Interestingly, the tolerance of isolated heart to global 20-min no-flow ischaemia was improved in uraemic rats. The most marked differences in heart function recovery during reperfusion concerned aortic flow (90 +/- 2.3 vs 66 +/- 10%) and stroke volume (97 +/- 2.7 vs 68 +/- 5.6% of pre-ischaemic values). Pre-ischaemic myocardial glycogen content was distinctly increased (by 50%) in uraemic rats compared with the controls.

Adenosine Triphosphate

[Comparison of experimental models of renal ischemia. Morphologic study].

The authors investigated in rats after unilateral nephrectomy morphological changes in the remaining kidney where the blood flow was arrested for 20, 30, 45 or 60 min. The investigation period was 24 hours, 3, 7, 14, 21 and 28 days after ischaemization. After short-term ischaemia monocellular necroses of the cortex epithelium in the canals occurs and rapid regeneration. In the initial stages after 20 min. ischaemia and in all periods after 30 min. ischaemia the authors observed slight hyperplasia of the juxtaglomerular apparatus manifested by fine granulations. After ischaemia persisting for 45 min. in addition to necroses of the tubules regressive arterial changes are observed with subsequent regeneration from the deep cortex to the surface. After discontinuation of the blood flow for 60 min. the animals die after 7 days with diffuse damage of the cortical parenchyma and regression of smooth muscle cells of the arterial walls with subsequent insudates of the media.

Animals

[Nephrotoxicity of Sandimmune and Consupren in an experiment].

Cyclosporin A is a basic immunosuppresive drug after organ transplantation. Morphological and functional features of Cyclosporin A nephrotoxicity caused by Sandimmune (Sandoz) and Consupren (of the Czech origin) were investigated in male Wistar rats. Rats were subjected to a right side nephrectomy followed by 45-minute- ischemia of remaining left kidney. Sandimmune was administered to one group of animals, Consupren to another group, both in the amount of 10 mg/kg/day. The second part of the experiment was performed in animals with right side nephrectomy only (without ischemia of the left side kidney) followed by the same administration of drugs. Changes were checked the 3rd and 21st day after nephrectomy. Ischemic arterial insudation lasted in the 3rd day set of animals with nephrectomy and left kidney ischemia treated by Consupren and was lacking after Sandimmune. Microvascularization of tubular epithelial cells was observed in significant frequency in the 21st day set of animals with unilateral nephrectomy without ischemia after Consupren and not after Sandimmune. The finding correlated with significantly higher blood level of Consupren and higher creatinine concentrations in serum than those of Sandimmune in rats with unilateral nephrectomy only.

Animals

[An experimental model of the effect of uremia on cyclosporin A availability].

BACKGROUND: The aim of the study was to determine whether or not uraemia has an effect on cyclosporine A intestinal resorption. METHODS AND RESULTS: Model experiments were conducted in rats to monitor the effect of acute uraemia (bilateral nephrectomy) on the kinetics of cyclosporine A. Using intragastric tube, Cyclosporine A was administered to one group of rats in the form of Consupren (Galena, Czech Republic) and to another group in the form of Sandimmune (Sandoz, Switzerland), at a dose of 10 mg/kg/24 h either case. Blood levels of cyclosporine A were determined using RIA and specific and non-specific antibodies (cyclosporine and its metabolites). Cyclosporine A kinetics in nephrectomized rats was compared with that in control rats and in rats undergoing sham nephrectomy. The blood levels of cyclosporine A were significantly lower, and the area under the curve (AUC) of blood cyclosporine A in nephrectomized rats significantly smaller than in control rats. No significant differences in the evaluated parameters after Consupren or Sandimmune were observed. CONCLUSIONS: Our findings support the hypothesis that uraemia decreases cyclosporine A availability. The results suggest that the changes in cyclosporine A kinetics in nephrectomized rats following Consupren and Sandimmune administration are of the same character.

Acute Disease

[Comparison of the effects of 2 preparations of cyclosporin A-- Consupren and Sandimmune--from the aspect of functional and morphologic changes in rats with renal ischemia].

BACKGROUND: Cyclosporine A is in transplantology an irreplaceable immunosuppressive agent. Its only manufacturer preparation Sandimmune--was the Swiss firm Sandoz. In 1990 the Czech firm Galena introduced cyclosporine A with the name Consupren on the market. The objective of the present investigation was to assess whether the nephrotoxic effect of the two preparations is comparable, or whether it differs. METHODS AND RESULTS: In a group of 65 rats after unilateral nephrectomy and 45-minute ischaemia of the remaining kidney the nephrotoxic action of cyclosporine preparations Sandimmune (Sandoz) and Consupren (Galena, CZ) administered in doses of 10 mg/kg body weight/24 hours throughout the experiment was investigated. The functional and morphological examination was made 3 or 21 days following nephrectomy. After three days the serum levels of creatinine, urea, sodium, osmolality and their urinary excretion as well as the intensity of proteinuria and morphological findings using light and electron microscopy did not differ in the two groups. The same was found during follow-up after 21 days; the small difference in the serum creatinine level only (Sandimmune 96.0 +/- 9.7 mumol/l, Consupren 111.4 +/- 11.2 mumol/l; p < 0.005) may be associated with the significantly higher cyclosporin levels following Consupren administration. CONCLUSIONS: The findings of the investigation support the idea that even after ischaemic kidney damage the nephrotoxicity of Consupren is not higher than that of Sandimmune.

Animals

[Preclinical models of the effect of acute renal ischemia on creatinine plasma levels].

The effect of temporary and complete renal artery clamping on the plasma concentrations of creatinine (Pcr) and morphologic alterations was studied in the remaining kidney of unilaterally nephrectomized rats. It was demonstrated that 20-minute ischaemia did not entail a significant increase in Pcr although histologic changes were already detectable in the kidney. Thirty-minute ischaemia was associated with appreciable histologic changes in the kidney even though the rise in Pcr was mild and transient. Forty-five and sixty-minute ischaemia was found to be associated with severe histologic changes and a distinct increase in Pcr. Seen from the perspective of transplantation requiring evaluation of the functional status of cadaverous donors, the experimental findings show that normal levels of Pcr do not exclude the possible presence of morphologic changes, and that even major histologic change may manifest themselves in an insignificant increase in Pcr.

Animals

[Comparison of functional and morphologic changes after administration of Consupren and Sandimmune in rats with a 5/6 nephrectomy].

Rats with 5/6 nephrectomy were used to compare the nephrotoxic effects of Consupren (cyclosporine A by Galena, Czech Republic) and Sandimmun (Sandoz, Switzerland). Twenty-one days after the administration of the same dosage, 10 mg/kg 24 hr, the blood levels of cyclosporine A were statistically significantly higher (P < 0.025) in rats given Consupren than in rats receiving Sandimmun. The serum concentrations of creatinine, urea, electrolytes, and osmolality did not differ after Consupren and Sandimmun. No significant difference between the two drugs was found in urinary excretion or proteinuria. The increase in the weight of residual renal parenchyma at 21 days after 5/6 nephrectomy did not differ significantly between rats administered Consupren or Sandimmun. Histology revealed gross hypergranularities in the juxtaglomerular apparatus equally present in both studied groups. Results show no significant differences in any of the evaluated parameters of the functional capacity of residual renal parenchyma or in the nephrotoxic effect as demonstrated in the histologic picture.

Animals

Experimental adriamycin nephropathy. Fine structure, morphometry, glomerular polyanion, and cell membrane antigens.

Two doses of adriamycin (2 mg/kg i.v.) were administered to young adult rats with a 22-day interval and the kidneys were examined 51, 79, and 107 days after the first injection. Light microscopy showed early prominent intraglomerular microcystic spaces and progressive, though not severe, segmental glomerulosclerosis with focal interstitial scarring and round-cell infiltration. The main features of the ultrastructure were widespread fusion of foot processes, focal cytoplasmic rarefaction of podocytes, and non-specific sclerosis of the mesangium without signs of severe degenerative changes or mesangiolysis. The segmental microcystic structures corresponded to agglomerated intrapodocytic vacuoles. The scatter of glomerular polyanion sites visualized by polyethylenimine-phosphotungstic acid resembled that of control animals but the quantitative assessment revealed a significant reduction. CD4-positive cells were the predominant element of the interstitial infiltrates. Most of the infiltrating cells expressed Ia antigens, whereas Ia-positive intraglomerular resident mononuclear cells were depleted. The adriamycin lesion resembles the post-five-sixths nephrectomy ablation nephropathy in the subpopulations of the interstitial infiltrate but differs from it in the reduction of intraglomerular resident macrophages, the absence of destructive mesangial damage, and reduced segmental glomerulosclerosis. The main feature is the prolonged damage of podocytes, especially of their cytoskeletal system.

Animals

[Preclinical modeling of the possible effect of acute uremia on drug resorption in the gastrointestinal tract].

The authors investigated in experiments on rats the course of serum concentrations of sulfisoxazole (S) and acetylsulfisoxazole (AS) in normal rats and in rats after bilateral nephrectomy after intra gastric administration of S. Serum concentrations of S and AS during the first three hours following administration did not differ significantly or were very close. During the subsequent hours the serum concentrations of S and AS in uraemic animals were significantly higher than in controls. The value of the absorption constant in the uraemic animals was on average higher and the absorption half-life lower than in controls. The assembled results suggest that in acute uraemia in rats the intestinal reabsorption of S and its metabolism in the liver are not reduced. The findings support the idea that the model used could be useful in preclinical research of drugs used in the treatment of acute uraemia.

Acute Disease

Experimental ablation nephropathy. Fine structure, morphometry, cell membrane epitopes, glomerular polyanion and effect of subsequent transplantation.

The subtotal (5/6) nephrectomy performed in 23 adult female rats induced severe hypertrophy of residual parenchyma with interstitial fibrosis, tubular dilatation, and focal and segmental glomerulosclerosis (FSG). This ablation nephropathy (AbN) caused proteinuria, progressive renal failure, and hypertension. The extent of FSG was assessed by semiquantitative scoring. The ultrastructure revealed widespread foot process fusion, many dense cytoplasmic inclusions in podocytes, and degenerative changes or disruption of mesangium with glomerular "microcysts". Numerous granular deposits of rat Ig were seen in the glomeruli but a short praeterminal i.v. load by heat-aggregated human Ig did not alter the morphology of AbN and produced discrete and inconstant glomerular deposits. Similarly an i.v. injection of protamine and heparin generated protamine-heparin complexes seen in various layers of glomerular capillary wall, similar to those found previously in normal rats. AbN displayed a partial irregular depletion of polyanion sites reactive with polyethylenimine in lamina rara externa. A significant increase in both glomerular and interstitial Ia+ cells and a marked predominance of W3/25+ cells in the interstitial infiltrates were documented by immunohistochemistry in the remnant kidneys. Both AbN and FSG could be largely corrected (or prevented?) by subsequent syngeneic renal transplantation (TPL; 6 animals). On the other hand a severe AbN was found in two post-ablation residues after unsuccessful TPL with graft necrosis or sclerosis.--AbN has some analogies to various chronic human nephropathies (e.g. FSG) and may explain their progression to the terminal failure. Degenerative and finally destructive mesangial lesion seems to be of prime importance in AbN.

Animals

The influence of furosemide on intrarenal distribution of 2-sulphanilamido-5-methoxypyrimidine in rats with normal and reduced renal parenchyma.

Internal distribution of 2-sulphanilamido-5-methoxypyrimidine (SM) 100 mg/kg in rats is characterized by a corticopapillary gradient. The papilla/cortex ratio of SM concentration averaged 2.25 +/- 0.34. Furosemide (5 mg/kg) elicited a significant corticopapillary gradient decrease for SM. Corticopapillary gradients for SM and sodium showed a positive correlation (r = 0.45; p less than 0.001). After furosemide corticopapillary gradient for SM averaged 1.4 +/- 0.22. Unilateral nephrectomy alone induced no significant difference in the corticopapillary gradient for SM compared with controls. Corticopapillary gradient for SM was significantly lower in unilaterally nephrectomized rats than in controls when furosemide was given after 24 hours or 7 or 14 days. The results suggest that SM concentration was significantly higher in the medulla than in the cortex; furosemide led to a significant decrease of corticopapillary gradient for SM against controls; the corticopapillary gradient for SM did not significantly change after unilateral nephrectomy; the effect of furosemide on corticopapillary gradient for SM was more pronounced in rats after unilateral nephrectomy than in controls.

Animals