PubMed Health⌕ Search

Biomedical subjects

Boleslaw Rutkowski

Publications and source records attributed to Boleslaw Rutkowski.

At least 37 records · Page 2Linked to original sources
PubMed2004

Upregulation of lipogenic enzymes genes expression in white adipose tissue of rats with chronic renal failure is associated with higher level of sterol regulatory element binding protein-1.

Chronic renal failure (CRF) frequently results in hypertriglyceridemia and elevated plasma concentration of very-low-density lipoprotein (VLDL). These abnormalities are thought to be primarily due to depressed lipoprotein lipase and hepatic lipase activities, as well as impaired clearance of plasma lipoproteins. Some results suggest that not only lipoproteins catabolism but also their overproduction might contribute to hypertriglyceridemia in CRF. Because sterol regulatory element binding protein (SREBP) plays an important role in the regulation of lipid homeostasis, increased level of this transcription factor might be involved in modulating lipid metabolism in CRF. The purpose of the present study is to determine whether there is an altered regulation of the SREBP-1 in CRF rats and whether the altered regulation of SREBP-1 is associated with the upregulation of lipogenic enzymes genes expression in CRF rats. In the white adipose tissue (WAT) of CRF rats, marked increases in the microsomal (precursor) and nuclear (mature) forms of SREBP-1 have been found. The increase in SREBP-1 was associated with an increased level of lipogenic enzymes (acetyl-coenzyme A [CoA] carboxylase [ACC], adenosine triphosphate-citrate lyase [ACL], fatty acid synthase [FAS], glucose 6-phosphate dehydrogenase [G6PDH], 6-phosphogluconate dehydrogenase [6PGDH], and malic enzyme [ME]) genes expression. In turn, this was associated with an increased rate of fatty acids synthesis in WAT and a significant increase in plasma triacylglycerol (TAG) and VLDL concentration. Our study indicates that WAT SREBP-1 expression is increased in CRF rats and that SREBP-1 may play an important role in the increased fatty acid synthesis. These results reveal another facet of disturbed lipid metabolism in CRF.

Adipose Tissue↗
PubMed2004

The age-related increase in N-methyl-2-pyridone-5-carboxamide (NAD catabolite) in human plasma.

N-Methyl-2-pyridone-5-carboxamide (2PY) is a major catabolite of NAD, which is excreted in the urine. Assay of plasma concentration and urine exrection of 2PY is of interest for monitoring niacin nutritional state and NAD catabolism. Aging has major impact on number of metabolic processes, but its effect on plasma and tissue 2PY concentration has not been studied so far. The present study was undertaken to investigate the effect of aging on human plasma 2PY concentration. Blood samples were collected from 78 (56 females and 22 males) healthy subjects at different age ranging from 5 to 90 years. Plasma ultrafiltrates were analyzed with liquid chromatography/mass spectrometry (LC/MS) for 2PY concentration. 2PY concentration was also evaluated in plasma and liver of young (2 month) and old (24 month) rats. The mean plasma 2PY concentration in young (5-16 years old) healthy subjects was 0.39 +/- 0.22 micromol/l while in old healthy subjects (50-90 years old) it was approximately 2.6-fold higher. No gender differences was found in plasma 2PY concentration. Univariate regression analysis displayed positive correlation between age and human plasma 2PY concentration (r = 0.57, p < 0.01) and between age and 2PY/creatinine ratio (r = 0.4, p < 0.01). Multivariate regression analysis indicates that both age and plasma creatinine concentrations were independently correlated with the increase in plasma 2PY concentration. Daily 2PY excretion with urine corrected for weight was approximately 30% lower in old subjects than in young humans. 2PY concentrations in liver and plasma of 2-month-old rats were lower than in 24-month-old rats. In conclusion, our results demonstrated that human plasma 2PY concentration increases with age. This could be a consequence of both decreased renal excretion and increased production in the the liver or other organs. Our results indicate that age should be taken into consideration in the interpretation of plasma 2PY concentration.

Adolescent↗
PubMed2004

Mycophenolate mofetil treatment following renal transplantation decreases GTP concentrations in mononuclear leucocytes.

MMF (mycophenolate mofetil) has been proven to provide an effective immunosuppression by non-competitive selective reversible inhibition of IMPDH (inosine monophosphate dehydrogenase), the enzyme playing a crucial role in GTP biosynthesis. However, the exact metabolic changes induced by inhibition of IMPDH in target cells of the immune system have been the subject of recent debate. The aim of the present study was to evaluate whether MMF treatment produced sustained changes in the guanosine nucleotide pool of MNLs (mononuclear leucocytes) in vivo. Sixty-two renal failure patients were divided into three groups: chronic renal failure patients undergoing haemodialysis (CRF-HD; n=20) and two groups of patients after renal transplantation, the first on AZA (azathioprine; TN-AZA; n=23) and the second treated with MMF (TN-MMF; n=19). In addition, MNLs from 25 healthy subjects were analysed as controls. Anion-exchange HPLC was used to quantify purine and pyrimidine nucleotides in MNLs. We report a significant decrease in GTP and the total MNL guanine nucleotide pool in the TN-MMF group (P<0.05) compared with control, CRF-HD and TN-AZA groups, although no significant differences were found between any of the other groups. Adenine nucleotide concentrations in MNLs were decreased in the TN-AZA group, but not in the TN-MMF group compared with the CRF-HD group and controls. There were no differences in CTP concentrations, but UTP concentrations were decreased in the CRF-HD, TN-AZA and TN-MMF groups compared with controls. MMF caused a significant and sustained decrease in the guanine nucleotide pool in MNLs from renal transplant recipients. This decrease contrasts with the elevation in GTP reported in erythrocytes of MMF-treated patients.

Adolescent↗
PubMed2004

Low-dose dual blockade of the renin-angiotensin system in patients with primary glomerulonephritis.

BACKGROUND: Treatment with agents interfering with the renin-angiotensin system retards the progressive course of proteinuric chronic renal disease. However, because of unwanted effects associated with such therapy, some patients cannot be treated with these drugs at all or may be administered only very small doses. To find an optimal nephroprotective strategy for these patients, we compared antiproteinuric effects of combination therapy with an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist in very small doses with treatment with either agent alone at greater, but not maximal, doses. We compared the concomitant use of benazepril, 5 mg, and losartan, 25 mg, and monotherapy with these agents in doses 2-fold greater. METHODS: This is a randomized, open, crossover study of 3 treatments in 3 periods of 4 months each. Twenty-four patients with primary glomerulonephritis and nonnephrotic proteinuria, recognized previously as not able to be administered high doses of drugs from these classes, completed the protocol. RESULTS: Combined therapy decreased 24-hour proteinuria (-45.54% versus baseline) more effectively than either losartan (-28.17%; analysis of variance, P < 0.01) or benazepril (-20.19%; analysis of variance, P < 0.001) alone. Subgroup analysis showed that antiproteinuric effects of combination therapy, as well as losartan or benazepril alone, were significantly greater in patients with basal proteinuria greater than 2 g/24 h than in those with proteinuria less than this value (P < 0.001, P < 0.01, and P < 0.05, respectively). All therapies significantly decreased blood pressure (BP) compared with baseline, but there were no differences between treatments in BP changes. CONCLUSION: The study shows that combination therapy with very small doses of losartan and benazepril was more effective in reducing proteinuria than greater doses of either agent in monotherapy, and this greater antiproteinuric efficacy was independent of changes in BP.

Adult↗
PubMed2004

Low-dose angiotensin II receptor antagonists and angiotensin II-converting enzyme inhibitors alone or in combination for treatment of primary glomerulonephritis.

OBJECTIVE: The renin-angiotensin system is thought to be involved in the progression of chronic renal diseases of both diabetic and non-diabetic origin. It has been confirmed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) reduce urinary protein excretion and attenuate the development of renal injury. Clinical data comparing the renal effects of ACEIs and ARBs, either singly or in combination, are scarce and usually concern the use of standard or high doses. MATERIAL AND METHODS: This was a prospective, randomized, 9-month study of the effects of low doses of losartan (25 mg; n = 18) versus enalapril (10 mg; n = 18) versus the combination of losartan (25 mg) and enalapril (10 mg) (n = 16) on proteinuria, kidney function and metabolic profile in 54 patients with biopsy-proven chronic glomerulonephritis, hypertension and normal or slightly impaired kidney function. The clinical evaluation and laboratory tests were performed before treatment (baseline) and after 3 and 9 months of therapy. RESULTS: After 3 months, significant decreases in proteinuria were observed in all groups: losartan, 22.6% (p = 0.02); enalapril, 43% (p = 0.012); and combined therapy, 63% (p = 0.001). This anti-proteinuric effect was even greater after 9 months of therapy: losartan, 44.2% (p = 0.02); enalapril, 49.6% (p = 0.02); and combined therapy, 51% (p = 0.003). There was no significant difference between losartan and enalapril with respect to their impact on proteinuria level. Proteinuria reduction was significantly greater in patients receiving combined therapy in comparison with losartan treatment after 3 months of therapy (p = 0.02). Creatinine clearance and serum creatinine were stable during the entire study period in all patients. No significant changes in lipids, serum uric acid or protein levels were observed. CONCLUSIONS: These results indicate that proteinuria is reduced by low doses of losartan or enalapril. The combination of these drugs seems to be beneficial and may offer an additional renoprotective effect. This needs to be confirmed in a study with a larger sample size.

Adult↗
PubMed2004

No effects of ozonated autohemotherapy on inflammation response in hemodialyzed patients.

BACKGROUND: Ozone as a strong oxidant may induce an inflammatory response. AIM: The hypothesis was verified as to whether ozonated autohemotherapy using an ozone dose in therapeutic range changes the plasma concentration of C-reactive protein and interleukin-6, markers of inflammation. METHODS: In a controlled, single-blind, cross-over study, 12 chronically hemodialyzed patients with peripheral arterial disease were exposed to nine sessions of autohemotherapy with blood exposure to oxygen as a control followed by nine sessions of ozonated autohemotherapy with an ozone concentration of 50 microg/ml. RESULTS: There was no statistical difference between C-reactive protein levels at baseline (1.53 +/- 1.01 mg/l), after nine sessions of control autohemotherapy (1.48 +/- 0.96 mg/l), and after nine sessions of ozonated autohemotherapy (1.55 +/- 0.84 mg/l). There was also no statistical difference between the interleukin-6 serum concentration at baseline (438 +/- 118 pg/ml), after nine sessions of control autohemotherapy (444 +/- 120 pg/ml), and after nine sessions of ozonated autohemotherapy (466 +/- 152 pg/ml). CONCLUSION: The results of this study suggest that ozonated autohemotherapy using an ozone concentration of 50 microg/ml does not induce an inflammatory response.

C-Reactive Protein↗
PubMed2004

Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells.

BACKGROUND: In vitro experiments point to a better biocompatibility profile of new pH-neutral peritoneal dialysis fluids (PDFs) containing low levels of glucose degradation products (GDPs). The present study examines the impact on human peritoneal mesothelial cells (HPMCs) of equilibrated dialysates obtained during dialysis with either conventional or new PDFs. METHODS: Peritoneal dialysate was collected from 17 patients participating in a randomized, controlled, cross-over trial comparing a pH-neutral low-GDP solution (Balance) to a conventional solution (S-PDF). All patients were treated sequentially for 3 months with both PDFs. At the end of each treatment phase, peritoneal effluent was drained after a timed 10 h dwell. Samples of dialysate were then mixed with standard culture medium and added to in vitro cultures of HPMCs from healthy donors. Cells were assessed for proliferation, viability and cytokine release. RESULTS: Proliferation and viability of HPMCs were better preserved in the presence of effluent obtained during dialysis with Balance (P<0.046 and P<0.035, respectively). The proliferative response of HPMCs correlated with the concentration of fibronectin in dialysates (P = 0.0024). Effluent drained following a 3 month dialysis with Balance contained significantly increased levels of fibronectin (P = 0.004) and CA125 antigen (P = 0.0004) compared with S-PDF. There was no significant difference in constitutive and stimulated cytokine (IL-6, MCP-1, VEGF) synthesis by HPMCs treated with either Balance- or S-PDF-derived effluents. CONCLUSIONS: These results suggest that therapy with new pH-neutral low-GDP solutions contribute to an intraperitoneal milieu that improves mesothelial cell proliferation and viability. It may positively impact on the preservation of the peritoneal membrane integrity during long-term dialysis.

Adult↗
PubMed2004

Platelet function unaffected by ozonated autohaemotherapy in chronically haemodialysed patients.

BACKGROUND: The therapeutic use of ozone is still a controversial medical strategy due to the potential toxicity of ozone, which is recognized as a highly reactive oxidant. The reactive oxygen species are known to induce platelet aggregation, the process involved in the development of atherosclerosis and cardiovascular events. In the present study, the influence of ozonated autohaemotherapy (O3-AHT) on the platelet function was evaluated in chronically haemodialysed patients with peripheral arterial disease. METHODS: This was an oxygen-controlled, cross-over study, in which nine sessions of autohaemotherapy with oxygen administration as a control were followed by nine sessions of O3-AHT. The platelet function was assessed by the extent of spontaneous aggregation (SPA) and agonist-induced aggregation (AIPA), where different concentrations of adenosine were used as an agonist. RESULTS: There were no differences between SPA and AIPA assessed after nine sessions of O3-AHT and after nine sessions of autohaemotherapy with oxygen administration. SPA and AIPA did not change after the first session of O3-AHT as compared with the levels before this procedure. CONCLUSION: O3-AHT with ozone concentration of 50 microg/ml and citrate as an anticoagulant does not induce platelet aggregation.

Aged↗
PubMed2004

Ozonated autohemotherapy in patients on maintenance hemodialysis: influence on lipid profile and endothelium.

Ozonated autohemotherapy (O3-AHT) is used in the treatment of atherosclerotic ischemia of lower limbs (AILL). The impact of ozone on serum lipids and endothelium injury is of particular interest since these factors are important in the development of atherosclerotic lesions. To evaluate this issue, a prospective, placebo-controlled study was designed. Twelve hemodialyzed subjects with AILL received autohemotherapy with oxygen as a control followed by O3-AHT with ozone concentration of 50 micro g/ml. Serum lipids and plasma activity of von Willebrand factor (vWF) were measured. After O3-AHT, total cholesterol significantly decreased compared to the baseline (-8.34%) [P < 0.01]. LDL cholesterol was also significantly lower than the initial value (-17.71%) [P < 0.001]. No significant changes in the activity of vWF were found after the first session of O3-AHT and after all nine sessions of O3-AHT. The study demonstrated that O3-AHT did not affect deleteriously the endothelium in patients with chronic renal failure on maintenance hemodialysis. It may stimulate beneficial changes in serum lipid profile manifesting as a decrease in the total- and LDL-cholesterol levels.

Aged↗
PubMed2004

Fistula function and dialysis adequacy during ozonotherapy in chronically hemodialyzed patients.

There are a variety of complications related to chronic hemodialysis treatment, including thrombosis in hemodialysis access leading to blood recirculation, and in turn to the deterioration in hemodialysis effectiveness. Given that ozone decreases blood viscosity, increases erythrocyte deformability, and inhibits coagulation, the periodic blood ozonation may be of benefit in the attenuation of these disturbances. To gain insight into this issue,we originally evaluated the impact of ozonated autohemotherapy on recirculation in arteriovenous fistula, hemodialysis adequacy, and the frequency of dialyzer reuse. Twelve chronically hemodialyzed patients with peripheral arterial disease were enrolled in the prospective, placebo-controlled study. Nine sessions of autohemotherapy with the exposure of blood to oxygen, as a control, and nine sessions of autohemotherapy where the blood is exposed to ozone in a concentration of 50 microg/mL are administered in a single-blind manner. Access recirculation is measured by means of spectral technology(Crit Line Monitor, HemaMetrics, Kaysville, UT, U.S.A.), and hemodialysis adequacy is calculated using the Daugirdas formula and expressed as the Kt/V index. The Kt/V index and the frequency of dialyzer reuse do not change after ozonated autohemotherapy. Recirculation decreases after ozonotherapy in the majority of patients.on average by 35.3%, but the change does not reach the level of statistical significance (P = 0.064). We demonstrate that ozonated autohemotherapy does not influence dialysis adequacy and the frequency of dialyzer reuse. The improvement of fistula function, expressed as a decrease in recirculation, is not significant, although seen in the majority of patients.

Aged↗
PubMed2004

Nutritional status and oxidative processes in diabetic and nondiabetic peritoneal dialysis patients.

OBJECTIVE: The purpose of our study was to compare the level of malonyldialdehyde (MDA) and carbonyl groups (GC) in diabetic and nondiabetic peritoneal dialysis patients. DESIGN/SETTING: Prospective, observational study on peritoneal dialysis patients in a teaching hospital dialysis unit. PATIENTS: A total of 21 diabetic and 66 nondiabetic patients treated with peritoneal dialysis were examined in the study. Main outcome measures The assessment of nutritional status was determined by clinical, anthropometric, and biochemical methods. The GC content was determined by the 2,4-dinitrophenylohydrazine assay using the Garibaldi method. The MDA was measured using the colorimetric method (LPO-586). RESULTS: The plasma content of the GC and the MDA of peritoneal dialysis patients was significantly higher than in the healthy group (2.0 +/- 1.3 versus 1.3 +/- 0.4 nmol/mg protein and 3.8 +/- 1.4 versus 3.0 +/- 1.2 micromol/L). Moreover, the tendency toward increased levels of MDA and GC in the diabetic group in comparison with the nondiabetic group was noticed. Also, the highest values of GC and MDA were observed in severely malnourished patients. CONCLUSION: The increase in oxidative stress may be related to a degree of malnutrition.

Adult↗
PubMed2003

N-methyl-2-pyridone-5-carboxamide: a novel uremic toxin?

BACKGROUND: N-methyl-2-pyridone-5-carboxamide (2PY) is one of the end products of nicotinamide-adenine dinucleotide (NAD) degradation. We recently found that serum 2PY concentrations in chronic renal failure (CRF) patients were enhanced to the values, which are potentially toxic. The aim of this study was to determine whether 2PY is an inhibitor of poly(ADP-ribose) polymerase, the nuclear enzyme that is highly involved in variety of physiologic events, including regulation of DNA replication and DNA repair. METHODS: High-performance liquid chromatography (HPLC) was used to determine 2PY and other NAD catabolite concentrations in serum of: nondialyzed patients; patients chronically hemodialyzed; patients after kidney transplantation; and healthy individuals (control group). Moreover, the effect of nicotinamide and 2PY on poly(ADP-ribose) polymerase (PARP-1) in vitro was studied. RESULTS: The serum nicotinamide, 2PY, and 4PY (N-methyl-4-pyridone-3-carboxamide) concentrations are many times elevated in nondialyzed CRF patients when compared with controls. The direct correlations were found between serum 2PY (as well as 4PY and nicotinamide) concentrations and serum creatinine concentration, and negative correlations between serum concentrations of these compounds and creatinine clearance. The concentration of 2PY decreases considerably after hemodialysis (HD) session, but elevates back 48 hours later. It permanently declines after kidney transplantation. Nicotinamide and 2PY significantly inhibit PARP-1 activity in vitro. CONCLUSIONS: Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.

Humans↗
PubMed2003

Predialysis Survey on Anemia Management: patient referral.

BACKGROUND: The Predialysis Survey on Anemia Management was designed to assess the care given to predialysis patients within 3 months of the start of hemodialysis or peritoneal dialysis (PD) therapy. In this presentation, we focus on demographic data and patient referral practices of patients who enter kidney centers. METHODS: We conducted a retrospective chart review of patients who had started hemodialysis or PD therapy between August 1999 and April 2000. All patients (age, 16 to 99 years) who entered 1 of the 779 centers in 21 European countries, Israel, or South Africa were included, except those for whom dialysis therapy was only started during an acute episode. Demographic characteristics, referral to kidney centers, comorbidities, drug treatments, major clinical events, and use of epoetin were documented. RESULTS: Mean creatinine clearance rate at the first visit to the kidney center was 18.2 mL/min (0.303 mL/s). Of all patients, greater than 35% had a creatinine clearance less than 10.0 mL/min (<0.167 mL/s) at their first visit. Overall, 87% of patients were initiated on hemodialysis therapy, and 13% were started on PD therapy. PD was used more often the longer a patient was under the care of a nephrologist. Of 4,333 new dialysis patients, 68% had a hemoglobin concentration of 11.0 g/dL or less (< or =110 g/L) at the first visit. CONCLUSION: The majority of patients in the survey had been under the care of a nephrologist for more than 12 months before the start of dialysis therapy. Nevertheless, most of these patients were anemic, and only a minority were on epoetin treatment.

Adolescent↗
PubMed2003

The role of lipogenesis in the development of uremic hyperlipidemia.

BACKGROUND: It is well documented that hypertriglyceridemia in renal failure mostly is a result of impaired plasma triglyceride (TG) removal. However, the role of TG production in its development is obscure. Therefore, our attention was given to the gene expression of lipogenic enzymes participating in TG biosynthesis. METHODS: We measured some lipogenic enzyme activities, protein abundance (Western blot analysis), and messenger RNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) of rats with surgically induced renal failure (two-stage subtotal nephrectomy). Simultaneously, plasma TG and very low-density lipoprotein (VLDL) concentrations in uremic animals were determined. RESULTS: An increase in plasma TG and VLDL concentrations in rats with renal failure was observed. It was associated with an increase in fatty acid synthase and adenosine triphosphate-citrate lyase (ACL) gene expression in liver and WAT. Moreover, increased activities of malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were found. CONCLUSION: Results of the present study provide some evidence that the accumulation of TG-rich lipoproteins in renal insufficiency could be related in part to increased lipogenic enzyme gene expression and, consequently, TG overproduction.

ATP Citrate (pro-S)-Lyase↗
PubMed2003

PRE-dialysis survey on anaemia management.

BACKGROUND: The PRE-dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre-dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. METHODS: For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. RESULTS: A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration < or = 11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r = 0.43, P < 0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration < or = 11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. CONCLUSIONS: Few pre-dialysis patients met the EBPG target for Hb concentration, despite regular nephrology care.

Anemia↗
PubMed2003

Antioxidants: a possible role in kidney protection.

Oxidative stress contributes to the pathophysiology of kidney injury. Beneficial renal effects of some medications, such as angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor antagonists, calcium channel blockers, beta-blockers and lipid lowering agents depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in prevention and attenuation of renal scaring in numerous animal models of kidney diseases. These include vitamins, N-acetylcysteine, alpha-lipoic acid, melatonin, dietary flavonoids and phytoestrogens, and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen renal damage. To date, the evidence is insufficient to recommend antioxidant supplements in patients with kidney disease. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies are indispensable.

Animals↗