Biomedical subjects

Leszek Domański

Publications and source records attributed to Leszek Domański.

15 recordsLinked to original sources

PubMed2007

Oxypurine and purine nucleoside concentrations in renal vein of allograft are potential markers of energy status of renal tissue.

BACKGROUND: Impairment of organ function derived from ischemia-reperfusion injury is an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage that occurs during the reperfusion phase. Purine nucleosides and oxypurines are products of adenine nucleotides degradation. Reperfusion and reoxygenation are accompanied by production of reactive oxygen species and free radicals, which lead to damage of graft tissue. The aim of this study was to measure concentrations of adenine nucleotides and their metabolites in renal allograft vein as well as in recipient's peripheral veins during the reperfusion period and to evaluate their usefulness as markers of tissue metabolism in kidney allografts. METHODS: The study enrolled 20 renal transplant recipients. The first blood sample was taken from the recipient's ulnar vein before anastomosing of the kidney graft's vessels with recipient's iliac vessels. Samples were then taken from the renal allograft and ulnar veins 5 min after total graft reperfusion measured with an infrared camera. High-performance liquid chromatography (HPLC) was performed to measure whole blood and plasma concentrations of adenosine triphosphate (ATP), adenosine monophosphate (AMP), guanosine (Guo), inosine (Ino), hypoxanthine (Hyp), xanthine (Xan), uric acid (UA), and uridine (Urd). RESULTS: Hyp and Xan concentrations were significantly increased in renal allograft vein after reperfusion as compared with peripheral vein during the pre- and post-reperfusion periods. CONCLUSIONS: The results of the present study suggest that differences in Hyp and Xan concentrations between renal and peripheral veins reflect metabolic alterations in renal tissue during reperfusion and may be useful for graft function monitoring during reperfusion.

Adult↗

PubMed2006

Peripheral blood lymphocytes P-glycoprotein (P-gp, gp-170) expression in allogenic kidney transplant patients.

AIM AND METHODS: P-glycoprotein (gp-170, P-gp) is a transmembrane transporter involved in drug, for example cyclosporine A, efflux from the cells thus limiting their intracellular concentration. Expression of the transporter on the surface of immune competent cells may be associated with poor prognosis in kidney transplant patients. The aim of the present study was to evaluate P-gp expression on the surface of CD4(+), CD8(+), CD19(+) and CD56(+) cells in kidney transplant patients treated with cyclosporine A as a main immunosuppressant, using flow cytometry. RESULTS: It was found that P-gp expression in kidney transplant patients with acute rejection did not differ significantly from transplanted patients without rejection studied in the same period after transplantation, as well as from the healthy controls. Administration of 3-day course of 1,000 mg/24 h methylprednisolone did not affect the expression of P-gp in the studied cells, except for significant elevation in CD56(+) cells, which disappeared at 2 weeks after cessation of steroid administration. CONCLUSION: Based on the results from the present study it can be concluded that P-gp expression is not a prognostic factor of acute kidney graft rejection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Early phase of reperfusion of human kidney allograft does not affect an erythrocyte anti-oxidative system.

BACKGROUND: Generation of reactive oxygen specimens is the basic mechanism leading to ischaemia/reperfusion injury of the kidney graft. Oxygen burst is a trigger for sophisticated biochemical changes leading to generation of oxygenated lipids and changes in microcirculation, which recruit recipient's neutrophils and contribute to delayed graft function. It has been shown that the free radicals generation correlates with the activity of anti-oxidative system. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) are involved in protection against free radicals. AIM: To examine the activity of erythrocyte anti-oxidative system during reperfusion of the transplanted kidney allograft. METHODS: The study included 40 renal transplant recipients. Blood was taken from the iliac vein before transplantation and from the graft's renal vein immediately, as well as 2 and 4 min after total reperfusion. The authors assessed the process of reperfusion using ThermaCAM SC500 termovision camera. Spectrophotometric methods were used to measure superoxide dismutase, glutathione peroxidase and catalase activity as well as glutathione concentrations in erythrocytes. RESULTS: There were no statistically significant differences in the activities of superoxide dismutase, catalase and glutathione peroxidase as well as glutathione concentrations during the first 4 min after total graft reperfusion. Nevertheless, there was a positive correlation between the activity of superoxide dismutase and glutathione peroxidase. CONCLUSION: The results suggest that the erythrocyte anti-oxidative system is stable during the early phase after reperfusion. An association between some anti-oxidative enzymes was noted.

Antioxidants↗

PubMed2006

[Influence of gastric juice pH on the metabolism of vitamin C in gastric mucosa and juice].

UNLABELLED: Vitamin C is present as ascorbic acid (Asc) with antioxidative properties and as its oxidation product dehydroascorbic acid (dAsc). Asc is actively transported from blood to gastric juice where it prevents formation of carcinogenic nitrosamines and protects mucosa from reactive oxygen species. Another important function of gastric mucosa is proton pump-dependent secretion of hydrochloric acid. The pump maintains high pH gradient between gastric juice and plasma. The aim of the work was to analyse relations between gastric juice pH and concentrations of Asc and dAsc in plasma, gastric mucosa and juice as well as other factors modifying metabolism of vitamin C and function of gastric mucosa. MATERIALS AND METHODS: 31 patients were subjected to diagnostic endoscopy due to dyspepsia. Concentrations of Asc and dAsc were measured in plasma, gastric mucosa and juice with HPLC method. pH of gastric juice was determined. Histopathology examination of mucosa and urease test for Helicobacter pylori were performed. Data concerning dyspeptic symptoms and used drugs, including vitamin C preparations, were collected. RESULTS: Patients taking vitamin C preparations had significantly lower gastric juice pH values than the others (median 2.2 vs 5.4; p < 0.01). Treatment with vitamin C preparations was also associated with higher Asc concentrations in gastric juice (median 16.6 vs. 1.8 micromol/L; p < 0.09); the difference was statistically significant in the subgroup of patients with gastritis (median 16.6 vs. 0.1 micromol/L; p < 0.04). Strong negative correlations of pH with Asc (Rs = -0.67; p < 0.001) and dAsc (Rs = -0.48; p < 0.01) concentrations were observed in gastric juice. Positive correlation of pH and relative dAsc content expressed as percent of total vitamin C concentration in gastric juice was also statistically significant (Rs = +0.48; p < 0.05). CONCLUSIONS: Performance of the proton pump and vitamin C metabolism in the stomach are closely mutually connected. Modification of hydrochloric acid secretion may affect gastric juice vitamin C concentration. Potentially disadvantageous influence of antisecretory drugs on the mechanisms of antioxidative protection in the stomach needs further investigation.

Ascorbic Acid↗

PubMed2005

Elements of Mediterranean diet improve oxidative status in blood of kidney graft recipients.

Patients were fully informed as to the study objectives and benefits, and provided written consent prior to enrolment. The study protocol was approved by the Committee on Human Research at the Pomeranian Medical University, Szczecin, Poland. An intensification of free-radical reactions may contribute to accelerated atherosclerosis in kidney graft recipients. We examined the effect of a Mediterranean-type diet (MD) on the oxidative status of the plasma and erythrocytes of kidney graft recipients. Two patient groups were formed: a study group consuming the MD diet and a control group with a low-fat diet. C-reactive protein levels in plasma, oleic acid C18 : 1n-9 and linoleic acid C18 : 2n-6 concentrations in triacylglycerols were determined. To determine the oxidative status, we measured the concentrations of alpha-tocopherol in plasma, the content of thiobarbituric acid-reactive species (TBARS) in plasma and erythrocytes, and the activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes. In the MD group, the activities of erythrocyte enzymes changed significantly: those of superoxide dismutase increased (P<0.001 after 6 months), catalase decreased (P<0.001 after 6 months) and glutathione peroxidase decreased (P<0.05 after 2 months). The oleic acid content of triacylglycerols was increased (P<0.006) whereas that of linoleic acid was decreased (P<0.00005), alpha-tocopherol levels remaining unchanged. TBARS in plasma were decreased after 6 months of MD (P<0.05). No significant correlations were observed between TBARS, oleic acid, linoleic acid and alpha-tocopherol levels in plasma. MD appears to protect the erythrocytes against the action of free radicals, as reflected in the modified activities of some enzymes regulating the oxidative status of these blood cells.

Adult↗

PubMed2005

The impact of thiopurine s-methyltransferase polymorphism on azathioprine-induced myelotoxicity in renal transplant recipients.

Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TMPT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. It has previously been reported that 3 variant alleles: TPMT*2, *3A, and *3C are responsible for over 95% cases of low enzyme activity. The purpose of this study was to explore the association between these polymorphisms and the occurrence of azathioprine adverse effects in 112 renal transplant recipients undergoing triple immunosuppressive therapy including azathioprine, cyclosporine, and prednisone. TPMT genetic polymorphism was determined using PCR-RFLP and allele-specific PCR methods. Azathioprine dose, leukocyte, erythrocyte, and platelet counts, graft rejection episodes, as well as cyclosporine levels were analyzed throughout the first year after organ transplantation. We found the frequency of leukopenia episodes (WBC < 4.0 x 10(9)/L) significantly higher in heterozygous patients (53.8%) compared with those with TPMT wild-type genotype (23.5%). One patient, who was a compound homozygote (3A/*3C), experienced severe azathioprine-related myelotoxicity each time after receiving the standard drug dose. Our results suggest that polymorphisms in TPMT gene may be responsible for approximately 12.5% of all leukopenia episodes in renal transplant recipients treated with azathioprine. Genotyping for the major TPMT variant alleles may be a valuable tool in preventing AZA toxicity and optimization of immunosuppressive therapy.

Adolescent↗

PubMed2005

[Kidney sponge--treatment--case report].

Medullary sponge kidney (MSK) is a benign asymptomatic developmental anomaly of the kidney mostly seen in adult females. Typical for this morphological abnormality is dilation of the collecting ducts. Intravenosus pyelogram shows accumulation of contrast in dilated ducts giving to the papillae the appearance of a bouquet flowers, characteristic for MSK. Urinary tract infections, nephrolithiasis, hematuria and hyperkalciuria are the common complications of the kidney sponge. We present a case of a 29-year-old female who suffers from recurrent urinary tract infection, nephrolithiasis and distal tubular acidosis. This kind of tubular acidosis is specific for kidney sponge clinical picture.

Acidosis, Renal Tubular↗

PubMed2004

Methods of GFR determination--creatinine clearance after cimetidine administration in clinical practice.

Determination of clearance of endogenous creatinine using its plasma and urinary concentration (standard clearance) or Cockroft and Gault equation (estimated clearance) is commonly performed for assessment of glomerular filtration rate. Although evaluation of renal function in this way is useful, it is biased with an error resulting from secretion of creatinine in tubules. This error can be reduced by determining the clearance after administration of cimetidine. This study enrolled 40 patients who were divided into two groups--the first group consisted of 12 healthy subjects and the second group joined healthy subjects and patients with chronic renal failure. The second group was divided into three subgroups in relation to creatinine serum concentration (intervals: creatinine < 1 mg/dL - 9 subjects, creatinine 1-2 mg/dL - 7 subjects, creatinine > 2 mg/dL - 10 subjects). Estimated and standard creatinine clearance, clearance after cimetidine administration and inulin clearance were assessed. Analysis of mean percentage differences between clearance value after cimetidine administration and estimated or standard clearance shows increasing contribution of tubular creatinine secretion with increase in plasma creatinine concentration. This study suggests that determination of creatinine clearance after cimetidine administration can be used in precise evaluation of renal function.

Aged↗

PubMed2003

Influence of glucose in dialyzing fluid on purine concentrations in hemodialyzed patients with chronic renal failure.

BACKGROUND: In chronic renal failure the accumulation of some purine nucleotides (in erythrocytes) develops both in patients undergoing conservative treatment and in hemodialyzed patients. The aim of the study was: (1) To find if hemodialysis (HD) sessions using dialyzing fluid containing glucose leads to an increase in ATP concentration and changes in the concentration of other nucleotides, nucleosides and oxypurines in erythrocytes. The potential consequence of such purine concentration changes is the increase of 2,3-DPG concentration and an improved transportation of oxygen in erythrocytes which are more resistant to hemolysis. (2) To compare blood concentrations of purine nucleotides, nucleosides and oxypurines in patients undergoing chronic HD with dialyzing fluid containing or lacking glucose. Significant differences could suggest the long-term influence of glucose in dialyzing fluid on erythrocyte energetic state. METHODS: Whole blood nucleotide concentrations were evaluated with the use of a high-performance liquid chromatography technique. RESULTS: Before the HD session the patients in the 'plus glucose' group had significantly higher concentrations of ATP, ADP, AMP, TAN, NAD, NADP, GTP + GDP, GMP, Urd and HYP than patients in the 'no glucose' group. After the HD the patients in the 'plus glucose' group had significantly higher concentrations of ADP, AMP, TAN, NAD, NADP, Urd and HYP than in the 'no glucose' group. Both before and after the HD session, the uric acid concentrations and AEC were significantly lower in the 'plus glucose' group than in the 'no glucose' group. A significant decrease in the whole blood hypoxanthine (p < 0.05) and uric acid (p < 0.001) concentrations after HD was found in the 'no glucose' group while a significant increase in ADP concentration (p < 0.05) was detected in the patients' erythrocytes in the 'plus glucose' group. In this group a significant decrease of GTP + GDP and GMP (p < 0.05), uric acid concentration (p < 0.001) and adenylate energy charge (p < 0.05) were observed after the dialysis. However, no significant differences in nucleotide concentrations before and after the HD were found in the 'no glucose' group. CONCLUSION: The presence of glucose in the dialyzing fluid causes a significant modification of the energetic state of cells which is reflected by the purines' and their metabolites' concentrations in the erythrocytes. Higher ATP concentrations in patients with renal failure who have been dialyzed with the fluid containing glucose can be considered as an organism adaptation to a decreased amount of RBC and hemoglobin concentration.

2,3-Diphosphoglycerate↗

PubMed2003

Oral iron absorption test: should it be performed before starting treatment with ferrous preparations?

The oral iron absorption test is sometimes used in the assessment of ferrous preparation efficacy before therapeutic use in the treatment of patients with anemia. Overdoses of Fe can cause the production of free radicals that are dangerous because of chemical modifications and damage of proteins, lipids, carbohydrates, and nucleotides. We suggest that this test should not be performed with the recommended dose of iron because of the potential threat to the patients. We assessed the serum concentration of iron and total iron-binding capacity during the test. Before and after the test, the concentration of malonyldialdehyde, an end product of lipid peroxidation, was determined in serum. In most patients, we found an increase in malonyldialdehyde concentration, suggesting the enhanced production of free radicals. This increase was particularly marked in patients with an overabsorption of iron. The administration of iron in the dose recommended for the oral iron absorption test causes increase in serum malonyldialdehyde concentration, proving an overproduction of free radicals. This test should not be performed because of the evidence proving detrimental effects of free-radical overproduction on the human body.

Administration, Oral↗

PubMed2003

[Acute renal failure after paracetamol (Acetaminophen) poisoning--report of two cases].

Two cases of paracetamol (acetaminophen) poisoning resulting in acute oliguric renal failure requiring dialysis in one case are described. There were signs of hepatotoxicity with no marked hepatic failure in either of cases. Neither was treated with N-acetylocystein due to late referral to a dialysis center. It is concluded that acute renal failure during paracetamol poisoning may not necessarily be followed by an evident hepatic failure.

Acetaminophen↗

PubMedDate not supplied

Impaired synthesis is not the reason for decreased activity of extracellular superoxide dismutase in patients with diabetes.

BACKGROUND: The aim of the study was to find the cause of decreased activity of extracellular superoxide dismutase (EC SOD) in patients with diabetes-is it the decreased synthesis or increased glycation? METHODS: Total EC SOD activity, the activity of its fractions (A, B, and C) and its glycated form were determined in basal state and 30 min after intravenous (i.v.) administration of 50 mg of heparin. Patients were given i.v. heparin at a dose of 10,000 IU (100 mg) each 6 h for at least 3 days, and the activity of EC SOD was determined before the first heparin administration, just before each subsequent administration, and 30 min after heparin administration. RESULTS: Pre- and postheparinic activities of EC SOD and its fraction C in the group of patients with diabetes were significantly lower (p <0.001) than in control group. Preheparinic activities of EC SOD did not differ between the examined groups of patients. The postheparinic activities were different during the first 18 h of treatment. They were significantly lower in the group of patients with diabetes. During the following hours, after subsequently administered doses, there were no differences in the activity of EC SOD between the examined groups. Decline of EC SOD activity was observed after administration of repeated doses of heparin both in the examined and in the control groups. CONCLUSIONS: The decrease of extracellular superoxide dismutase activity in diabetes develops due to excessive glycation but not due to impaired synthesis. Therefore, appropriate glycemic control can lead to normalization of EC SOD activity.

Adult↗

PubMedDate not supplied

Plasma prekallikrein as a risk factor for diabetic retinopathy.

BACKGROUND: The aim of the study was to verify the hypothesis that in diabetes there is an increased activation of coagulation system leading in consequence to diabetic retinopathy. METHODS: Thirty three healthy subjects (controls, 16 males and 17 females) and 35 patients with diabetes type 1 (15 males and 20 females) were examined. We monitored plasma prekallikrein (PPK), glycemia, fructosamine, glycosylated hemoglobin, activated partial thromboplastin time (PTT), INR, fibrinolysis in euglobulins time (FET), level of antithrombin III (AT III), fibrinogen (Fb) and fibrinogen degradation products (FDP). RESULTS: In diabetic patients without retinopathy, PKK concentration was 16% higher (p <0.005), in patients with background retinopathy 33% higher (p <0.001), and in patients with proliferative retinopathy PKK concentration was 50% higher (p <0.001) than in controls. In the subgroup of patients with proliferative retinopathy PTT was significantly shorter (p <0.001), and FET was significantly longer (p <0.001) than in control. In patients with diabetes higher FDP concentrations were found than in controls (p <0.05). Significant correlations were found between PPK and fructosamine levels in all diabetic patients (R(S)=+0.57 p <0.001), in diabetic patients without retinopathy (R(S)=+0.61, p <0.05), and in diabetic patients with retinopathy (R(S)=+0.62, p <0.005). We found negative correlation between PPK concentration and PTT (R(S)=-0.43, p <0.001) and positive correlation between PPK concentration and FET (R(S)=+0.59, p <0.00001) in the entire study group. CONCLUSIONS: The occurrence of diabetic retinopathy is connected with higher levels of plasma prekallikrein.

Adult↗

PubMedDate not supplied

MDR1 gene polymorphism in allogeenic kidney transplant patients with tremor.

P-glycoprotein (P-gp), an ATP-dependent efflux pump, is a membrane protein encoded by MDR1 gene, which demonstrates functional polymorphism. It is present in endothelial cells of the blood-brain barrier. P-gp pays a role in transmembrane transport of various xenobiotics, thus limiting their accumulation in the central nervous system. Cyclosporine A which is used as an immunosuppressive drug in patients with allogenic kidney grafts is a substrate for P-gp. Cyclosporine A may cause neurotoxic adverse effects, among them tremor. It was assumed that polymorphism of MDR1 gene which is associated with change in P-gp activity plays a role in induction of tremor in some patients with allogenic kidney graft treated with cyclosporine A. A total of 118 unrelated postransplant kidney patients were enrolled into the study. The tremor group included 23 cases and 95 randomly selected posttransplant individuals with no signs of tremor served as controls. No statistically significant correlation between MDR1 gene polymorphism C3435T and tremor was found. The tremor group and the control group were characterized by similar distribution of MDR1 genotypes, i.e. 3435CC, 3435CT, 3435TT.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Nephrotic syndrome and situs inversus viscerum: correlation or coincidence.

Asymmetric human internal organ organization has been a research topic for many years. Currently, although we know many mechanisms leading to the creation of specific internal organ organization, the problem requires further investigation. Transforming Growth Factor-beta superfamily (TGF-beta SF) molecules seem to play a major role in the process. They affect the cell by signaling through type I and II serine/threonine kinase receptors. Smad proteins seem vital in transmitting the signal between the receptor and the nucleus. We present the case of an 18-year-old female patient, who was admitted to the hospital because of steroid-sensitive nephrotic syndrome. Physical examination revealed that the patient also had a complete reversal of the intra-abdominal anatomy - situs inversus totalis. We suggest that disturbed TGF-beta and Smad signaling could be responsible for both nephrotic syndrome and situs inversus totalis.

Adolescent↗