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Biomedical subjects

I Rychlík

Publications and source records attributed to I Rychlík.

At least 37 records · Page 2Linked to original sources

Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study.

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.

Adult↗

Optimizing antihypertensive therapy in patients with diabetic nephropathy.

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.

Angiotensin Receptor Antagonists↗

[Cytokines and adhesion molecules in renal vasculitis and lupus nephritis].

BACKGROUND: Plasma levels and urinary excretion of proinflammatory cytokines and soluble adhesion molecules may be useful parameters of the activity of ANCA-positive renal vasculitis and lupus nephritis. METHODS AND RESULTS: Plasma levels and urinary excretion of TNF alpha, IL-6, IL-8, ICAM-1 and VCAM-1 were measured by ELISA in 14 patients (pts) with ANCA-positive renal vasculitis (8 active-ANCA-A, 6 in remission ANCA-R), 6 pts with active lupus nephritis (L.N), 15 pts with IgA nephropathy (IgAN) 10 pts with autosomal dominant polycystic kidney disease and 9 healthy subjects (Co). Fractional excretion (FE) of selected cytokines and adhesion molecules was also calculated. Pts with LN had in comparison with controls increased plasma levels of ICAM-1, VCAM-1, IL-6, IL-8 and TNF alpha, increased urinary excretion of VCAM-1, IL-8 and TNF alpha and increased fractional excretion of VCAM-1 and IL-8. Patients with ANCA-A had in comparison with controls increased plasma concentrations of ICAM-1 and VCAM-1, increased urinary excretion of VCAM-1, IL-6 and TNF alpha and increased fractional excretion of VCAM-1, IL-6, IL-8 and TNF alpha. Patients with ANCA-R had in comparison with controls higher plasma levels of ICAM-1, VCAM-1, IL-6 and TNF alpha, increased urinary excretion of VCAM-1 and TNF alpha and increased fractional excretion of VCAM-1, IL-6 and TNF alpha. CONCLUSIONS: Patients with ANCA-positive renal vasculitis had in contradistinction to pts with active LN increased fractional excretion of IL-6 and TNF alpha. Both cytokines are probably produced in renal vasculitis locally in the kidney. Increased plasma levels of soluble adhesion molecules and increased plasma levels and fractional excretion of proinflammatory cytokines in patients with ANCA-positive renal vasculitis in clinical remission may explain the strong propensity of these patients to develop relapses of the diseases on withdrawal of immunosuppressive treatment.

Adult↗

[Controlled clinical study of Consupren versus cyclophosphamide in chronic glomerulonephritis. II. Adverse effects].

BACKGROUND: The second part of the study was designed to assess Consupren side effects. METHODS AND RESULTS: The groups of patients studied were described in Part I. Side affects typical of Cy-A were evaluated only in the CS group. Gastrointestinal intolerance, only mild and temporary, was observed in 31%, neurotoxicity in 44%, hypertrichosis in 37%, nephrotoxicity in 25%, and gingival hypertrophy in 19%. Mean values of systolic and diastolic blood pressure did not change significantly in the course of treatment. When changes in blood pressure were individually investigated in particular patients, they were found in 31% in the CS group and in none in the K group. Mean values of uric acid non-significantly increased in the CS group and, on individual investigation, hyperuricaemia was observed in 31%. Mean values of serum potassium did not alter significantly. Signs of possible hepatotoxicity were found in 37% patients of the CS group. In this group, there was a significant decrease in haemoglobin mean values and a decrease in haemoglobin of more than 25 g/l was observed in 44% of CS group patients. In the K group significant decrease in mean leukocyte count was noted, but no patient developed real leukopenia. CONCLUSIONS: The occurrence of side effects was comparable to data known from the literature.

Chronic Disease↗

[Clinical spectrum of the antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is characterized by multiple arterial and venous thromboses, repeated spontaneous abortions and thrombocytopenia, together with the presence of antiphospholipid antibodies in serum. We present three patients, two men and a woman, at the age of 43, 24 and 23 years respectively. The younger man and the woman had secondary APS and systemic lupus erythematosus, the older man had primary APS. The symptoms and course of the disease were different. The older man lives 17 years after the onset of first symptoms with multiple neurologic disorders, the younger man is symptomless. The woman died several months after the acute onset of the disease.

Adult↗

[A controlled clinical trial of Consupren versus cyclophosphamide in chronic glomerulonephritis].

BACKGROUND: Experience gained from recent studies shows, that Cyclosporine-A (Cy-A) may decrease proteinuria (PU) in some forms of chronic glomerulonephritis (GN) with the nephrotic syndrome. The aim of this study was to test the efficacy of Czech-made Cy-A, Consupren. METHODS AND RESULTS: 30 patients with chronic GN, confirmed by biopsy and PU higher than 3 g/d, corticodependent or corticoresistant, were randomized according to the month of birth to either therapy with Consupren at an initial dose of 5 mg/kg/d (CS group, after dropout of 3 patients who did not finish the treatment, n = 16) or Cyclophosphamide at a dose of 1.5 mg/kg/d (K group, n = 11), and prednisone maintained at the original dose in both groups. The treatment was stopped after six months or after achieving remission. The main criterion of efficacy was PU. The decrease in mean values, statistically evaluated by Holm's procedure was highly significant in the CS group and non-significant in the K group. A similar evaluation of PU corrected by glomerular filtration rate was significant in both groups. Partial or complete remission was reached in 50% of CS group patients and in 34% of K group patients (NS). In the CS group a significant increase in the mean values of albumin and gama-globulin, and a decrease in cholesterol levels were observed. In the K group, these changes were non-significant. CONCLUSIONS: In patients with chronic GN and the nephrotic syndrome, the efficacy of Consupren treatment gives comparable, or even better results versus treatment with Cyclophosphamide.

Adult↗

The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats.

Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric acid) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin. Rats with nephrotic syndrome treated from the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.

Animals↗

Identification of enterotoxin-producing strains of Escherichia coli by PCR and biological methods.

The polymerase chain reaction (PCR) and biological methods for detection of enterotoxigenic strains of Escherichia coli were compared. The tests for LT, STa and STb were done in the cell line Y1, suckling mice, and ligated piglet intestinal loops, respectively. The production of STb was tested only in strains negative for LT and STa. The polymerase chain reaction has proved to be specific and reliable method than the biological methods. Unlike the latter, PCR allows the detection of strains producing in vitro only low quantities of the toxin. On the other hand, PCR fails to identify strains producing toxic substances with a different structure but the same or similar biological properties.

Animals↗

[Use of molecular genetics for identification and differentiation of various strains and species of bacteria].

The aim of the paper is to inform on methods and practical application of DNA fingerprinting in typing of living organisms. Methods discussed in the review include standard DNA fingerprinting, plasmid profile analysis, RAPD PCR and direct sequencing of selected parts of genomes. In each method molecular basis together with its advantages and limitations is explained. All described methods are supplemented with selected cases of their practical application.

Bacteria↗

[Long-term administration of cyclosporine A in patients with IgA nephropathy].

BACKGROUND: IgA nephropathy is the most common glomerulonephritis all over the world and a considerable proportion of the patients reaches end-stage renal failure. Yet the standard treatment for the patients with progressive course and/or great proteinuria is currently lacking. All suggested treatment protocols, including short-term treatment with cyclosporine A had equivocal results. Therefore we decided to try long-term cyclosporine treatment. METHODS AND RESULTS: We treated 6 patients (4 males, 2 females, age 21-31 years) with bioptically proven IgA nephropathy and proteinuria over 3.5 g/24 hrs with or without nephrotic syndrome non responding to corticosteroid therapy administered for at least 3 months. Patients with serum creatinine greater than 200 mumol/l and/or glomerulosclerosis in more than 50% of glomeruli in renal biopsy were excluded. Pts were given cyclosporine A in initial dose 5 mg/kg bw/day then titrated aiming to the serum concentration of 70-150 ng/ml. Prednisone 5-10 mg on alternate days was given with cyclosporine. Proteinuria decreased during first month of therapy from 4.66 +/- 0.43 g/day to 1.38 +/- 0.29 g/day (p < 0.01) and remained low after one year of treatment (0.59 +/- 0.14 g/day, p < 0.001). Glomerular filtration rate (creatinine clearance) did not change during first month of therapy (1.25 +/- 0.21 ml/s vs. 1.38 +/- 0.29 ml/s), but slightly decreased after one year of treatment (1.05 +/- 0.14 ml/s, p < 0.05). We also calculated ratio of proteinuria to glomerular filtration rate (g/l) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80.10(-3) +/- 15.20.10(-3) before cyclosporin therapy, it decreased significantly after one month (11.56.10(-3) +/- 3.24.10(-3), p < 0.05) and achieved the lowest value after one year of therapy (6.78.10(-3) +/- 4.25 .10(-3) +/- 4.25.10(-3), p < 0.01). Serum cholesterol also significantly decreased after 12 months of therapy (6.21 +/- 0.62 vs. 5.41 +/- 0.45 mmol/l, p < 0.05). CONCLUSIONS: CyA significantly lowered moderate to high proteinuria with much less decrease of glomerular filtration rate in 6 patients with IgA. Significant decrease of proteinuria/GFR ratio strongly suggests some non-hemodynamic mechanisms of cyclosporine action in these patients. Therapy was well tolerated and side-effects were not so severe to require cyclosporine withdrawal.

Adult↗

[Renal vasculitis and glomerulonephritis with anti-neutrophil cytoplasmic antibody positivity].

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) define pathogenetically related group of renal vasculitides and glomerulonephritides mostly with serious prognosis. If unrecognized, these life-threatening diseases may cause loss of independent renal function and other dangerous extrarenal complications (e. g. pulmonary haemorrhage). We concentrated on the diagnosis, treatment and log-term follow-up of these patients. METHODS AND RESULTS: Renal biopsy was performed in 46 ANCA-positive patients. Age and sex distribution, type of ANCA, organ involvement, renal biopsy findings, renal function and effect of therapy were analyzed in these patients. Twenty three patients suffered from renal vasculitis, most commonly Wegener's granulomatosis (14 patients) and microscopic polyarthritis (7 patients). IgA nephropathy (7 patients) and idiopathic necrotizing/crescentic glomerulonephritis (8 patients) prevailed in patients with limited renal involvement. Renal morphology and function was most seriously impaired in patients with Wegener's granulomatosis. Immunosuppressive treatment was able to control the activity of the disease with the negativization of ANCA and improvement or stabilization of renal function in more than 90% of patients.CONCLUSIONS. ANCA-positive renal vasculitis and glomerulonephritis is relatively common. Clinical signs of extrarenal involvement are present in about 50% of patients with ANCA-positive glomerulonephritis. Rapidly introduced immunosuppressive treatment effectively controls renal and extrarenal manifestations of the disease.

Adult↗

The influence of pefloxacine on experimental adriamycin-induced nephrotic syndrome in rats.

Initial reports on antiproteinuric effect of pefloxacine in small groups of patients with minimal-change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS) have not been confirmed in other papers. To assess its antiproteinuric effect in experimental animals we administered pefloxacine to rats with adriamycin nephropathy showing morphological changes resembling human minimal-change disease or focal segmental glomerulosclerosis, and clinically with full-blown nephrotic syndrome. Pefloxacine treatment was at least partially effective in preventing further increase of proteinuria in rats with adriamycin nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on the glomerular cytokine network and glomerular production of reactive oxygen species.

Animals↗

[Lipid metabolism in the nephrotic syndrome].

BACKGROUNDS: Hyperlipidemia is a common and serious complication in patients with chronic nephrotic syndrome which unremitted may result in accelerated atherosclerosis. Accumulation of lipids in glomeruli may moreover contribute to the progression of renal insufficiency in these patients. METHODS: Total cholesterol, HDL-cholesterol and its HDL2 a HDL3 subfractions, LDL-cholesterol, triglycerides, free fatty acids, apoprotein B, apoprotein A1 and lipoprotein (a) were determined before any immunosuppressive and/or hypolipidemic therapy in 15 patients (pts) with nephrotic syndrome (8 pts with proteinuria higher than 10 g/24 hrs-NS-A, 7 with proteinuria between 5 and 10 g/24 hrs-NS-B), 7 pts with glomerulonephritis with low proteinuria (GN) and 6 pts with autosomal dominant polycystic kidney disease (PKD). All pts had normal glomerular filtration rate. RESULTS: Plasma cholesterol (10.26 +/- 2.22 vs. 4.75 +/- 0.66 mmol/1, p < 0.001), plasma triglycerides (4.03 +/- 1.64 vs. 2.17 +/- 0.12 mmol/1, p < 0.05), LDL-cholesterol (7.16 +/- 1.55 vs. 2.62 +/- 0.67 mmol/1, p < 0.001) and apoprotein B (1.92 +/- 0.47 vs. 1.11 +/- 0.31 g/1, p < 0.01) were significantly higher in NS-A than in PKD. There was no difference in total HDL-cholesterol and the ratio HDL2/HDL3 between investigated groups of pts. Lipoprotein (a) was higher in NS-A than in other investigated groups of pts. The differences between NS-B and PKD were less significant. CONCLUSIONS: Disorder of lipid metabolism is more serious in patients with more severe nephrotic syndrome than in nephrotic patients with milder proteinuria. Hypercholesterolemia is complicated in these subjects by hypertriglyceridemia and by the increase of apoprotein B and A1 and lipoprotein (a). Metabolic and renal consequences of these disorders depend undoubtedly on their duration and probably also on other factors (e.g. age, hypertension, long-term therapy with corticosteroids., etc.).

Female↗

Effect of long-term administration of stobadine to rats on selective variables of spontaneous behaviour of their offspring.

The present study investigated the effect of long-term administration of the cardioprotective drug stobadine (STB) to dams on selective variables of spontaneous behaviour of their offspring in open field (horizontal and vertical activities, frequency and duration of grooming, and duration of total activity and immobility) tested on day 60 of age. The treatment of dams with STB significantly increased horizontal activity of offspring in both sexes. The other variables studied were not affected, with the exception of a significant increase in the frequency and duration of grooming and in the duration of total activity in females compared to males from STB treated dams.

Animals↗

Rapid method for isolation of high molecular weight plasmids suitable for digestion with restriction endonucleases.

The described method is a modification of the hot alkaline method (Kado and Liu, 1981). The modification lies in replacement of SDS with Triton X- 100. The DNA purified by this method was readily digested with restriction endonucleases for a variety of applications, e. g. restriction analysis of plasmid DNA in epidemiological studies, restriction mapping and cloning of high molecular weight plasmids, and for identification of transpozon mutants.

DNA Restriction Enzymes↗

[The effect of pefloxacin on nephrotic syndrome in experimental adriamycin nephropathy].

BACKGROUND: Antiproteinuric effect of pefloxacine was demonstrated in a small group of patients with minimal change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS). This finding was not, however, confirmed by other papers. Adriamycine nephropathy is an experimental model of nephrotic syndrome with morphological changes resembling MCN and/or FSGS in patients. METHODS AND RESULTS: Nephrotic syndrome was induced in rats by the i.v. administration of adriamycine. One part of nephrotic animals was treated from the beginning of the 4th week by daily intraperitoneal application of pefloxacine. Administration of adriamycine led in experimental animals after 3 weeks to the development of full-blown nephrotic syndrome with further progression of proteinuria in the next 3 weeks (from 1.4 +/- 1.25 to 2.23 +/- 1.89 g of protein/mmol of urinary creatinine, p < 0.05). Proteinuria did not change in nephrotic rats treated by pefloxacine (from 1.04 +/- 0.97 to 1.26 +/- 1.11 g of protein/mmol of urinary creatinine, p = n.s.). The difference in proteinuria between both groups was also significant (0.83 +/- 0.73 vs. 0.23 +/- 0.67 g of protein/mmol of urinary creatinine, p < 0.05). CONCLUSIONS: Pefloxacine was antiproteinuric in experimental adriamycine nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on glomerular cytokine network and glomerular production of reactive oxygen species.

Animals↗