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Boleslaw Rutkowski

Publications and source records attributed to Boleslaw Rutkowski.

48 records · Page 3Linked to original sources
PubMed2003

Contribution of increased HMG-CoA reductase gene expression to hypercholesterolemia in experimental chronic renal failure.

The aim of the present study was to examine hypothesis that the enhanced cholesterologenesis, found in rats with experimental chronic renal failure (CRF) resulted from the increased gene expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase--the rate limiting enzyme in the cholesterologenesis pathway, responsible for mevalonate synthesis. Wistar rats were used and experimental CRF was achieved by 5/6 nephrectomy model. We examined: (a) the changes in the rat liver microsomal HMG-CoA reductase activity, (b) the rat liver HMG-CoA reductase mRNA abundance in various times of day. Obtained data indicates that the increased activity of HMG-CoA reductase in the liver of rats with experimental CRF parallel enhanced mRNA level and suggests that enhanced cholesterol biosynthesis, observed in experimental CRF is at least in part due to the increased HMG-CoA reductase gene expression. The results also indicate that the physiological diurnal rhythm of HMG-CoA reductase activity is preserved in the course of experimental CRF.

Animals↗
PubMed2002

Accumulation of plasma N-methyl-2-pyridone-5-carboxamide in patients with chronic renal failure.

Intracellular catabolism of NAD in mammalian cells occurs mainly via reaction catalyzed by poly(ADP-ribose) polymerase (PARP) with the release of nicotinamide, which is then metabolized predominantly to N-methyl-2-pyridone-5-carboxamide (2PY). PARP could be activated by binding to broken DNA and is known to be involved in DNA repair mechanisms, cell stress response and regulation of apoptosis. 2PY may accumulate under disease conditions resulting in accelerated DNA damage and retention of catabolic products. Our hypothesis was that chronic renal failure would lead to elevation of 2PY and potentially to inhibition of PARP and related physiological mechanisms. In the present study we: (a) compared plasma 2PY concentration in healthy subjects and in patients with chronic renal failure (CRF); (b) evaluated the relationship between plasma 2PY concentration and the severity of CRF; (c) evaluated the effect of hemodialysis treatment and kidney transplantation on 2PY concentration. We found that the plasma 2PY concentration in healthy subjects is 0.83+/-0.18 microM but it could increase up to 40 microM in patients with CRF. A significant correlation was found in CRF between plasma 2PY and creatinine concentration. A single hemodialysis treatment was associated with significant reduction of plasma 2PY concentration after the hemodialysis, but it increased rapidly 48 h after the end of treatment. Successful kidney transplantation was associated with return of 2PY concentration to the normal range. In conclusion, our results indicated significant production of 2PY in humans. In healthy subjects 2PY is cleared from the plasma by excretion in the urine. Altered excretion by the kidney leads to increase in plasma concentration of 2PY. It is possible that 2PY may play a significant role in the development of uremic toxemia, especially as an inhibitor of poly(ADP-ribose)polymerase.

Adult↗
PubMed2002

Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis: pilot study.

OBJECTIVE: There is evidence that angiotensin II, the main effector of renin-angiotensin system, plays a crucial role in the pathogenesis of chronic renal injury. Angiotensin II type 1 (AT-1) receptor blockers reduce renin-angiotensin system activity by blocking the receptor, the activation of which is responsible for the majority of deleterious angiotensin II effects. The aim of the present study was to investigate renal and metabolic effects of specific AT-1 receptor blocker-losartan in patients with primary glomerulonephritis. DESIGN: Pilot clinical study. SETTING: Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland. PARTICIPANTS: Fifteen patients aged 43.3 +/- 11.3 years with primary glomerulonephritis confirmed by renal biopsy were studied. INTERVENTION: Creatinine clearance, urinary excretion of protein and uric acid, urinary activity of N-acetyl-beta-D-glucosaminidase, and serum concentrations of lipids, protein, and uric acid were evaluated before and after 3 months of losartan (Cozaar; Merck Sharp & Dohme, Harlow, Essex, United Kingdom) treatment at a dose of 25 mg daily. RESULTS: We found a significant reduction of urinary excretion of protein (P <.008; average, 32%). Results also revealed a decrease of serum uric acid level (P <.01), probably as a consequence of elevated uric acid urinary excretion (P <.09). No significant changes in creatinine clearance, N-acetyl-beta-D-glucosaminidase activity, protein, or lipid levels were observed. CONCLUSION: We concluded that losartan treatment at a small dose of 25 mg daily produces antiproteinuric effect without adverse effects, notably with no decrease of glomerular filtration, and simultaneously induces beneficial changes in purine metabolism.

Adult↗
PubMed2002

Upregulation of fatty acid synthase gene expression in experimental chronic renal failure.

Hypertriglyceridemia associated with chronic renal failure (CRF) and elevated plasma concentration of very-low-density lipoprotein (VLDL) are thought to be a consequence of the depressed lipoprotein lipase and hepatic lipase activities and impaired clearance of lipoproteins. However, there is some evidence that the lipoproteins overproduction might also contribute to hypertriglyceridemia in CRF. This study was performed to test the hypothesis that the increased rate of lipogenesis consequent to upregulation of fatty acid synthase (FAS), a key lipogenic enzyme, gene expression could contribute to overproduction of triacylglycerols and to hypertriglyceridemia in CRF. FAS activity, FAS protein mass (Western blot analysis), and FAS mRNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) were measured in male Wistar rats 6 weeks after subtotal (5 of 6) nephrectomy or sham operation. Moreover, the rate of lipogenesis in WAT was determined. The CRF group showed significant increase in FAS gene expression (measured as activity, mRNA, and protein abundance) in both liver and WAT. This was associated with the increase in the lipogenesis rate and with the increase in plasma triacylglycerol and VLDL concentrations. Our results suggest that not only decreased removal, but also an increase of triacylglycerol production could contribute, in part, to the CRF-associated hyperlipidemia. Upregulation of FAS gene expression, shown in this report for the first time, reveals another factor involved in disturbed lipid metabolism in CRF. It seems that elevated plasma insulin and cytokine concentration could play an important role in the mechanism responsible for the increased FAS gene expression in CRF.

Adipose Tissue↗
PubMed2002

High plasma adenine concentration in chronic renal failure and its relation to erythrocyte ATP.

BACKGROUND: Concentration of plasma adenine has been found to increase in chronic renal failure (CRF). The aim of the present study was to evaluate whether high plasma adenine concentration contributes to the elevated ATP in erythrocytes of patients with CRF. METHODS: Three groups of patients with CRF were studied: (A) 30 patients with different degree of CRF; (B) 11 patients on hemodialysis, and (C) 12 patients after successful renal transplantation. Concentrations of plasma adenine and erythrocyte adenine nucleotides were measured in groups A, B and C. Furthermore, adenine incorporation into erythrocyte adenine nucleotide pool was measured in group A. RESULTS: A positive correlation between plasma adenine and creatinine concentrations was found in CRF as well as between plasma adenine and erythrocyte ATP. Furthermore, positive correlation was evident between the rate of adenine incorporation into erythrocyte adenine nucleotide pool and the severity of CRF. A significant reduction in both plasma adenine and erythrocyte ATP was observed immediately following hemodalysis, but 2 days later, high predialysis plasma adenine and erythrocyte ATP concentrations were restored. Following successful renal transplantation erythrocyte ATP and plasma adenine concentrations reached control values. CONCLUSION: Our results provide evidence that plasma adenine concentration increases in parallel to the progress of the disease and that it could be responsible for the increase in erythrocyte ATP of patients with CRF.

Adenine↗
PubMed2002

Multifactorial determination of hypertensive nephroangiosclerosis.

Essential hypertension causes renal injury. Hypertensive nephroangiosclerosis (HN) or hypertensive nephropathy are terms most commonly used to describe this renal pathology. Although specific histological lesions occurring in affected kidneys are well known, pathogenesis of hypertension-related renal scarring is not completely understood. Evidence exists to support the theory that other factors such as aging, black race or smoking, beside blood pressure, contribute to the development and progression of HN. Metabolic disturbances, cocaine and nonsteroidal anti-inflammatory drug abuse, ochratoxin A exposure, dietary salt intake, heavy metal toxicity, hantavirus infection and perinatal programming are also considered risk factors. Renal susceptibility genes may determine whether hypertension-induced progressive renal damage occurs and how severe it is. Determination of all risk factors may identify patients at high risk of renal failure and help tailor an appropriate management. In the present paper, the knowledge available on this clinically important objective is discussed.

Humans↗
PubMed2002

[Epidemiology of end stage renal disease in Poland].

Development of end stage renal disease for many years was in Poland "signum maliominis" for patients with this syndrome. Situation dramatically changed as a consequence of dramatic development of renal replacement therapy. This progress was observed not only in basic forms of dialysis therapy (hemodialysis and peritoneal dialysis) but also renal transplantation. Increased availability of renal replacement therapy influenced both on the increment total number of treated patients (by 250% during period 1991-2001) and an qualification criteria. These changes caused substantial increase of patients with diabetic and hypertensive nephropathy. Such phenomenon is observed in whole the world and one can conclude that situation in this matter is normalizing in Poland. Similar situation is observed taking into account age of treated patients together with described above changes in primary diseases leading to end stage renal disease will cause more and more significant problem for health care system in Poland and many other countries.

Adolescent↗
PubMedDate not supplied

Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation.

BACKGROUND: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. METHODS: Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. RESULTS: Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. CONCLUSIONS: These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy.

Adult↗
PubMedDate not supplied

Generation of TNFalpha and interleukin-6 by peritoneal macrophages after overnight dwells with bicarbonate- or lactate-buffered dialysis fluid.

OBJECTIVE: In order to evaluate the biocompatibility profile of a newly designed peritoneal dialysis fluid (PDF), we evaluated peritoneal leukocyte (PMphi) cytokine release following overnight in vivo dwells using standard, lactate-buffered, single-chamber bag PDF (Lac-PDF) and purely bicarbonate-buffered, double-chamber bag PDF containing 34 (Bic-PDF) or 39 (Bic Hi-PDF) mmol/L bicarbonate. DESIGN: A randomized, open, crossover clinical trial with single weekly test dwells was performed in stable, long-term continuous ambulatory PD patients (n = 8). During 8-hour overnight dwells, PMphi were exposed to different PDF containing 1.5% glucose. After drainage, peritoneal cells were isolated and incubated with RPMI 1640 medium for 2 or 3 hours, with and without stimulation by lipopolysaccharide (LPS). Ex vivo release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was measured by specific ELISA technique. RESULTS: After pre-exposure to Lac-PDF, PMphi generated 242 +/- 279 pg TNFalpha/10(6) cells and 157 +/- 105 pg IL-6/10(6) cells. When pre-exposed to Bic-PDF and Bic Hi-PDF, TNFa and IL-6 production of PMphi was not significantly different from Lac-PDF. After LPS stimulation (100 ng/mL), PMD secretion of TNFalpha and IL-6 pre-exposed to three PDF revealed no significant differences between groups: TNFalpha was 2,864 +/- 1,216, 2,910 +/- 1,202, and 3,291 +/- 558 pg/10(6) cells after overnight dwells with Lac-PDF, Bic-PDF, and Bic Hi-PDF, respectively. Comparably, LPS-stimulated (100 pg/ mL) PMphi showed IL-6 secretion of 891 +/- 335, 1,380 +/- 1,149, and 1,442 +/- 966 pg/10(6) cells for Lac-PDF, Bic-PDF, and Bic Hi-PDF. CONCLUSION: After long-term overnight dwells, initial pH, the different buffers, and varying glucose degradation product levels of PDF do not strongly affect PMphi function with respect to cytokine release. The lack of significant differences between fluids may result from the complete dialysate equilibration achieved during the overnight intraperitoneal dwell.

Adult↗
PubMedDate not supplied

Transmigration of blood leukocytes into the peritoneal cavity is related to the upregulation of ICAM-1 (CD54) and Mac-1 (CD11b/CD18) adhesion molecules.

BACKGROUND: Migration of blood leukocytes into the peritoneal cavity of patients treated with peritoneal dialysis appears to be an important mechanism to prevent and fight peritonitis. To study the role of adhesion molecules in the process of leukocyte transmigration, we compared the expression of several adhesion receptors between peripheral blood monocytes and macrophages isolated from overnight dwell effluents. METHODS: The study was performed in 12, stable, infection-free patients treated with continuous ambulatory peritoneal dialysis (CAPD) and in 9 patients during peritonitis. In another set of experiments, we analyzed the expression of these molecules on blood leukocytes in 10 predialysis chronic renal failure (CRF) patients and 9 healthy controls. Peritoneal cells from an 8-hour dwell were isolated by centrifugation. Expression of adhesion receptors CD11a, CD11b, CD18, CD49d, and CD54 on blood and peritoneal leukocytes was measured using flow cytometry. RESULTS: In macrophages from the uninfected effluents, expression of both subunits of Mac-1 integrin receptor (CD11b and CD18) and intercellular adhesion molecule (ICAM)-1 receptor (CD54) was upregulated compared to peripheral blood monocytes from the same patients. The median value of mean fluorescence intensity in blood and effluent was 760.3 versus 1085.8 for CD11b (p = 0.013), 288.8 versus 448.6 for CD18 (p = 0.003), and 186.1 versus 365.7 for CD54 (p = 0.001). The same adhesion receptors were also significantly upregulated on peritoneal macrophages and neutrophils during peritonitis compared to blood leukocytes. Blood leukocytes from CAPD and CRF patients showed higher expression of CD54 and CD49d molecules compared to leukocytes from healthy controls. CONCLUSIONS: These data suggest that transmigration of blood leukocytes into the peritoneal cavity during uncomplicated dialysis and in peritonitis is related to selective upregulation of ICAM-1 (CD54) and Mac-1 (CD18/CD11b) receptors.

Adult↗
PubMedDate not supplied

Jakub Penson and his studies on acute renal failure during typhus epidemics in Warsaw Ghetto.

In the Warsaw Ghetto established by the German Nazis as a special district for Polish Jews in 1940 there were two typhus epidemics. Many patients affected by this disease (1500 during the first and 6500 during second epidemic) were treated at The Department of Infectious Disease of Czyste Hospital headed by Dr Jakub Penson--a Polish physician of Jewish origin. A heroic group of 20 physicians not only treated patients in these tragic circumstances, but also performed in defiance of Nazi prohibition, scientific studies on the clinical course of typhus with special attention on hyperazotemia and renal complication. The results of their observations were presented in 1941-42 during clinical meetings in Czyste Hospital and later published by Penson in 1946 in the Polish Physicians Weekly. Among other clinical statements a description of acute renal failure of extrarenal origin, caused by dehydration and toxic influence of primary disease seems the most important one. It has to be taken into account that acute renal failure appearing during Crush Syndrome was described by Bywaters in 1941. Jakub Penson survived the German Nazi occupation and later become a head of the Internal Medicine Department in Gdansk Medical University and one of the precursors of clinical nephrology in Poland.

Acute Kidney Injury↗