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Biomedical subjects

A Urbanowicz

Publications and source records attributed to A Urbanowicz.

10 recordsLinked to original sources
PubMed2006

Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant.

OBJECTIVE: The aim of this study was to investigate the effect of time on pharmacokinetic (PK) parameters of mycophenolic acid (MPA) in the early post-transplant period in kidney recipients. MPA is the active metabolite of mycophenolate mofetil (MMF), which was introduced into clinical practice ten years ago. METHOD: Mycophenolate mofetil was co-administered with cyclosporin (CsA) in a subgroup of 23 patients and with tacrolimus (Tac) in a subgroup of 10 patients. MPA plasma concentration profiles were measured by a validated high performance liquid chromatography method 1 week, 2 and 3 months after transplantation. RESULTS: Despite a comparable MMF dose, a large inter-patient variability in both MPA area under the curve (AUC) from 0 to 12 h (range 10.03-135.4 microg h/mL) and in predose concentrations (0.31-6.09 microg/mL) was observed. Patients with AUC > 35 microg h/mL showed better (P < 0.1) renal function than patients with AUC < 20 microg h/mL (mean creatinine concentration 1.48 +/- 0.12 vs. 3.35 +/- 0.4 mg/dL respectively). The total MPA trough and AUC did not correlate with biochemical parameters: leucocyte cell count and haematocrit. A higher trough level of the metabolite MPA glucuronide (MPAG) in the 1 week after transplantation was found when compared with the 3-month level (mean 150.1 +/- 146.7; range 17.1 to 560 vs. 75.8 +/- 40.0; range 27.3 to 174.2 microg/mL). The concentration of MPA, and MPA AUC values were significantly lower in patients receiving MMF and CsA than those receiving MMF and Tac during all three periods studied (P < 0.02). The influence of C(0) and MPA AUC values on the risk of graft rejection was investigated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for AUC was 0.847, whereas that of C(0) was 0.632. CONCLUSIONS: The MPA AUC(0-12h) appeared to be the more effective PK parameter for predicting acute rejection. We recommend that routine MPA and MPAG therapeutic drug level monitoring should be an important part of MMF therapy.

Adolescent↗
PubMed2005

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

Antibodies, Monoclonal↗
PubMed2005

Tubular and glomerular proteinuria in diagnosing chronic allograft nephropathy with relevance to the degree of urinary albumin excretion.

The diagnosis of chronic allograft nephropathy (CAN) is based on pathological examination according to Banff 97 schema. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria for noninvasive recognition of CAN. One hundred and thirty renal allograft recipients (at least 90 days after transplantation) who had undergone diagnostic allograft biopsy were included in the study. Beta2-microglobulin, alpha1-microglobulin, albumin, immunoglobulin G, total protein, and creatinine concentrations were obtained from the second morning urine specimen. Raw data and values calculated per 1 g of creatinine excreted in urine along with time after transplantation, serum creatinine, and its change over a period of 2 months prior to biopsy were taken for analysis. Urine proteins were measured using a nephelometric method. Statistical calculations were performed using MANOVA and stepwise discriminant analysis (SDA). Statistical diagnosis and staging of CAN matched the pathological method in 68% of a preliminary SDA. Therefore patients were divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. There was no significant differences between protein excretion, except alpha1-microglobulinuria (CAN 0 vs 2, P = .018; CAN 1 vs 2, P = .041), beta2-microglobulinuria (CAN 0 vs 2, P = .026; CAN 1 vs 2, P = .0033), and total proteinuria (CAN 0 vs 2, P = .042) in the normoalbuminuric group. Nevertheless, diagnoses obtained using SDA were 89%, 91%, and 92% identical to the results of pathological examinations, for normoalbuminuric, microalbuminuric, and macroalbuminuric groups, respectively. In conclusion, tubular and glomerular proteinuria measurements may be useful for a noninvasive CAN diagnosis and staging only with regard to degree of urinary albumin excretion.

Albuminuria↗
PubMed2003

Assessment of some porcine strains as donors of islets of Langerhans.

Mass isolation of viable porcine islets is a difficult task because of their fragility, and because of donor variability with respect to strain, age, sex, feeding, and methods of slaughtering. Not all strains are equally suitable for islet separation. The aim of this study was to evaluate porcine pancreata as an alternative source of islets for clinical transplantation. Pancreata were digested from pig strains available in Poland: 248 market weight slaughterhouse pigs and 42 pigs, belonging to the Polish Large White (WBP, 14 sows and 3 males), Polish White Pendant-Ears (PBZ; 16 sows), Pietrain (8 sows), and Yorkshire (1 sow) races. Prepurification data of recoverable islets/g and islet equivalents/g were considered as representative for the number of recoverable islets. Acceptable results namely, islet and/or islet-equivalent (IE) number of at least 1000/g, were obtained from only 56 of 248 slaughterhouse pigs, namely 2073 +/- 137.4 SE (median 1767/g) islets with values of IE of 2994 +/- 303 SE (median 1874/g). Our data support Krickhahn et al suggesting that only pancreata with an average islet size exceeding 199 microm should be digested and that only from 1 of 3 to 5 porcine pancreata is an adequate amount of islets generated.

Animals↗
PubMed1997

Distribution of compound potentials recorded from the surface of isolated stellate ganglia following stimulation of postganglionic branches, in rats and cats.

The experiments were performed on 9 cat and 18 rat isolated stellate ganglia. Rats and cats were anesthetized with alpha-glucochloralose or urethane, respectively. The ganglia, isolated with their branches, were transferred to a recording chamber and constantly superfused with artificial extracellular fluid bubbled with 95% O2 and 5% CO2. Branches of the ganglion were one by one placed in suction electrodes and stimulated. Antidromic evoked potentials were systematically recorded from numerous points on the ganglion surface. The area under the curve of the negative wave of each recorded potential was considered proportional to the number of neurons located in the vicinity of the recording electrode, projecting to the stimulated nerve. We have found that: (1) cardiac sympathetic neurons are located in the lower, caudal half of the ganglia; (2) vertebral sympathetic neurons occupy the cranial, upper half of the ganglia; (3) neurons with axons in the ansae are positioned near the point of exit of the respective ansa from the ganglion; (4) localization of neurons projecting to the same branches is very similar on both sides--right and left; (5) this localization is also similar in rats compared to cats.

Animals↗
PubMedDate not supplied

The weight of pharmacokinetic parameters for mycophenolic acid in prediction of rejection outcome: the receiver operating characteristic curve analysis.

Often the clinical researcher is confronted with the question of how accurate a particular laboratory test is to identify disease. To confirm the ability of pharmacokinetic (PK) parameters to discriminate between patients with or without acute rejection after kidney transplantation, an analysis of receiver operating characteristic (ROC) curves was performed in 51 adult patients, among whom nearly 50% experienced biopsy-proven acute rejection episodes during the first 90 days posttransplant. All patients received cyclosporine or tacrolimus, prednisone, and mycophenolate mofetil (MMF). The following PK variables were determined for mycophenolic acid, an active metabolite of MMF: predose (C(0)), maximum concentration (C(max)), and area under the concentration-time curve (AUC(0-12h)). ROC plots of sensitivity versus 1-specificity were generated to determine whether a particular PK parameter could discriminate renal transplant recipients with an acute rejection from those who experienced no rejection. Area under the ROC curves and the 95% confidence interval limits were calculated using the method of Hanley and McNeil. The C(0) and C(max) were less predictive values for acute rejection than AUC(0-12h). The AUC parameter appeared the most effective to discriminate an acute rejection episode during MMF therapy. This study indicated the utility of ROC curve analysis to select PK parameters to predict acute rejection episodes.

Adolescent↗
PubMedDate not supplied

Antagonistic effect of MR2266 and MR2267 on morphine or nalbuphine analgesia at the spinal levels in rats.

The aim of this paper was to study the effect of two benzomorphan derivatives MR2266 and MR2267 with predominant antagonism to kappa-opioid receptors administered intrathecally on the analgesic action of morphine and nalbuphine. Both compounds attenuated the analgesia elicited by examined opioid agonists. Our results support the hypothesis that the spinal opioid receptors take part in analgesic effect of morphine and nalbuphine. It was for the first time described that MR2267, considered as inactive enantiomer of MR2266, is an active opioid antagonist when administered intrathecally.

Analgesics, Opioid↗