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Biomedical subjects

D Pawlak

Publications and source records attributed to D Pawlak.

At least 19 recordsLinked to original sources
PubMed2006

[Fundus flavimaculatus and choroidal neovascularization].

OBJECTIVE: Fundus flavimaculatus is an aspect of Stargardt disease, which is characterized by juvenile onset, rapidly progressive deterioration, and poor visual outcome due to atrophic areas or flecks. Recently, a late-onset form has been described, on the borderline with AMD. However, choroidal neovascular complications are not frequent and rarely described in Stargardt's disease. CASE REPORT: Late discovery of FFM in a patient over 50 years old. During her follow-up, she presented a decrease in visual acuity due to juxtafoveal choroidal neovascularization. In spite of laser treatment, a retrofoveal recurrence appeared, which was treated with perifoveal laser. DISCUSSION: Confusion between AMD and a late-onset Stargardt may occur because of their many clinical similarities. The population and the fundus results can be similar to AMD and an examiner may be confused. In the literature, choroidal neovascular complications appear in patients over 50 years of age who may suffer from AMD. In fundus flavimaculatus, pigmentary epithelium alterations are due to progressive lipoproteic scrap storage that predisposes to Bruch's membrane rupture and choroidal neovascularization. This physiopathology resembles the that of AMD. CONCLUSION: Choroidal neovascular complications are possible in late-onset Stargardt disease. Their appearance together may be greater than previously believed.

Choroidal Neovascularization↗
PubMed2005

Anthranilic acid-uraemic toxin damaged red cell's membrane.

Normocytic normochromic anaemia is a common syndrome present in patients with chronic renal insufficiency (CRI). Simultaneously in these patients the increase in L-tryptophan (TRP) degradation via kynurenine pathway is observed. On the basis of these observations we tried to examine whether one of the TRP metabolites, anthranilic acid (AA), shows interaction with membranes of erythrocytes and because of that it may contribute to anaemia development. In patients with CRI we have observed changes characteristic for normocytic normochromic anaemia, such as the decrease in erythrocyte count, haemoglobin concentration, haematocrit and the decrease in erythrocyte osmotic resistance as well as the increase in AA concentration in plasma in comparison to healthy subjects. We have also noticed the existence of a positive correlation between anthranilic acid concentration and creatinine and urea concentrations and also negative relationships between anthranilic acid concentration and haematological parameters. Moreover, incubation of healthy erythrocytes with 10 and 100 microM AA caused haemolysis curve movement to the right, which shows decrease in osmotic resistance. In conclusion, the increase in plasma AA concentration might be one of many factors, which damage erythrocyte membrane, and thereby contributes to anaemia development in patients with CRI.

Aged↗
PubMed2004

[Results of limited macular translocation in subfoveal choroidal neovascularization in age-related macular degeneration].

PURPOSE: Age-related macular degeneration (AMD) is the major cause of legal blindness in industrialized countries. The exudative form could be responsible for severe visual loss. Recent therapeutic approaches are now available for treating subfoveal neovascularization. The purpose of this study was to evaluate the visual results obtained with macular translocation (MT) in subfoveal choroidal neovascularization due to AMD. METHODS: A prospective nonrandomized review of 29 consecutive patients with subfoveal neovascularization attributable to AMD. Limited macular translocation with chorioscleral infolding based on the De Juan technique was performed. The mean follow-up was 14 months. RESULTS: The mean age of the patients studied was 75 years. The mean initial visual acuity was 20/200, with of 59% of patients having worse than 20/200. The mean displacement of the fovea after translocation was 1,274 microm, and at 1 year, vision was grossly unchanged in comparison to baseline (mean final gain of 0.7 line). Postoperative complications observed were retinal detachment (17.2%), macular hole (13%) and macular fold (14%). No complication was seen in 55.2% of the operated eyes, which had a mean final gain of 3.25 ETDRS lines at 14 months of follow-up. In comparison to the photodynamic therapy (PDT) group of the TAP study, 48% of the MT group had a gain of 1 line or more versus 16% of the PDT group. CONCLUSION: MT may lead to a significant improvement in visual acuity. Further larger and controlled studies are required to evaluate MT in the treatment of subfoveal neovascularization.

Aged↗
PubMed2004

Histomorphometry of marrow megakaryocytes in experimental uraemia in rats.

Uraemic patients frequently demonstrate tendencies towards life-threatening bleeding. Reduced platelet counts and their functional immaturity seem to be caused, among other things, by disorders in the system of marrow megakaryocytes. The aim of the study was a histomorphometric evaluation of marrow megakaryocytes in the course of experimental uraemia in rats. Uraemia was induced by means of right nephrectomy and a partial removal of the left kidney cortex in rats. Morphometric analysis was conducted, using the Microlmage program set. The number of MK, MK area, N/C, CDMK, CDNMK and MK cluster formation were analysed. Uraemic rats showed a reduction in the MK count and their area and an increase in the N/C ratio, CDMK, CDNMK and in the incidence of MK clusters. The results indicate that platelet disorders, observed in uraemia, can also be conditioned by disturbed maturation of MK.

Animals↗
PubMed2003

Peripheral distribution of kynurenine metabolites and activity of kynurenine pathway enzymes in renal failure.

We investigated L-kynurenine distribution and metabolism in rats with experimental chronic renal failure of various severity, induced by unilateral nephrectomy and partial removal of contralateral kidney cortex. In animals with renal insufficiency the plasma concentration and the content of L-tryptophan in homogenates of kidney, liver, lung, intestine and spleen were significantly decreased. These changes were accompanied by increase activity of liver tryptophan 2,3-dioxygenase, the rate-limiting enzyme of kynurenine pathway in rats, while indoleamine 2,3-dioxygenase activity was unchanged. Conversely, the plasma concentration and tissue content of L-kynurenine, 3-hydroxykynurenine, and anthranilic, kynurenic, xanthurenic and quinolinic acids in the kidney, liver, lung, intestine, spleen and muscles were increased. The accumulation of L-kynurenine and the products of its degradation was proportional to the severity of renal failure and correlated with the concentration of renal insufficiency marker, creatinine. Kynurenine aminotransferase, kynureninase and 3-hydroxyanthranilate-3,4-dioxygenase activity was diminished or unchanged, while the activity of kynurenine 3-hydroxylase was significantly increased. We conclude that chronic renal failure is associated with the accumulation of L-kynurenine metabolites, which may be involved in the pathogenesis of certain uremic syndromes.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed2002

R-134a emissions from vehicles.

We report the first study of R-134a (also known as HFC-134a and CF3CFH2) refrigerant leakage from air conditioning (AC) systems of modern vehicles. Twenty-eight light duty vehicles from five manufacturers (Ford, Toyota, Daimler Chrysler, General Motors, and Honda) were tested according to the USEPA (Federal) extended diurnal test procedure using the Sealed Housing for Evaporative Determination (SHED) apparatus. All tests were conducted using stationary vehicles with the motor and air conditioning system turned off. R-134a was measured using gas chromatography (GC) with a flame ionization detector (FID). All vehicles exhibited measurable R-134a leakage over the 2-day diurnal test. Leak rates of R-134a ranged from 0.01 to 0.36 g/day with an average of 0.07+/-0.07 g/day. When combined with leakage associated with vehicle operation, servicing, and disposal we estimate that the lifetime average R-134a emission rate from an AC equipped vehicle is 0.41+/-0.27 g/day (the majority of emissions are associated with vehicle servicing and disposal). Assuming that the average vehicle travels 10 000 miles per year we estimate that the global warming impact of R-134a leakage from an AC equipped vehicle is approximately 4-5% of that of the CO2 emitted by the vehicle. The results are discussed with respect to the contribution of vehicle emissions to global climate change.

Aerosol Propellants↗
PubMed2002

Tryptophan metabolism via the kynurenine pathway in experimental chronic renal failure.

BACKGROUND: Kidneys are involved in tryptophan (TRP) metabolism in two ways. They eliminate TRP derivatives on the one hand, and they produce several enzymes taking part in TRP metabolism mainly via the kynurenine pathway on the other. The aim of the present study was to examine the time-course of changes in the peripheral kynurenine products degradation during experimental chronic renal failure in rats. METHODS: Tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, anthranilic acid and quinolinic acid were determined in plasma using high-performance liquid chromatography technique with UV, fluorescence and electrochemical detection. RESULTS: A decreased TRP level and significant increase in kynurenine pathway metabolite concentrations in plasma of uremic rats were found. CONCLUSIONS: Substantial disturbances in the peripheral kynurenic pathway were observed in experimental chronic renal failure. They may contribute to several symptoms of uremia.

Animals↗
PubMed2001

Highly potent side-chain to side-chain cyclized enkephalin analogues containing a carbonyl bridge: synthesis, biology and conformation.

Six novel cyclic enkephalin analogues have been synthesized. Cyclization of the linear peptides containing basic amino acid residues in position 2 and 5 was achieved by treatment with bis(4-nitrophenyl)carbonate. It was found that some of the compounds exibit unusually high mu-opioid activity in the guinea pig ileum (GPI) assay. The 18-membered analogue cyclo(N(epsilon),N(beta)-carbonyl-D-Lys2,Dap5)-enkephalinamide turned out to be one of the most potent mu-agonists reported so far. NMR spectra of the peptides were recorded and structural parameters were determined. The conformational space was exhaustively examined for each of them using the electrostatically driven Monte Carlo method. Each peptide was finally described as an ensemble of conformations. A model of the bioactive conformation of this class of opioid peptides was proposed.

Animals↗
PubMed2001

Accumulation of toxic products degradation of kynurenine in hemodialyzed patients.

In patients that developed a chronic renal failure the augmentation in tryptophan degradation is reflected in the increase in plasma metabolites of kynurenine pathway. Hemodialysis is one of therapeutic approaches that significantly reduce all plasma kynurenine metabolites in uremic patients. In spite of haemodialysis, plasma concentration of kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid and quinolinic acid were still elevated in uremic patients in comparison with healthy volunteers. These data shows significant disturbances in kynurenine metabolism in uremic patients. Accumulation of these substances in uremic blood is capable to account for certain uremic symptoms.

Female↗
PubMed2001

Kynurenine and its metabolites in the rat with experimental renal insufficiency.

In uremia a great number of the endogenous metabolites that are ordinarily excreted in urine accumulate in the blood. Among these are the products of KYN degradation. In the present study we evaluated the peripheral KYN metabolism in the various stages of the rat experimental chronic renal insufficiency. Our results showed significant disturbances in peripheral kynurenic pathway, which resulted in the significant decrease of TRP plasma level and augmentation of concentration of its metabolites. The high concentrations of 3-hydroxykynurenine, xanthurenic acid, kynurenic acid, anthranilic acid and quinolinic acid positively correlated with degree of the renal insufficiency. Talking into account the biological properties of KYN metabolites, their accumulation in the blood, may be at least partially, responsible for severity of uremia as well as for uremic symptoms such as neuropathy, increased susceptibility to infections, hypertension, lipid disturbances and anemia.

Animals↗
PubMed2001

[Enzymes of the kynurenine pathway].

In this review, the role of kynurenine pathway enzymes (tryptophan 2,3-dioxygenase, indoleamine 2,3-dioxygenase, formamidase, kynurenine aminotransferase, kynurenine 3-hydroxylase, kynureninase, 3-hydroxyanthranilic acid oxygenase, picolinic carboxylase, quinolinic acid phosphoribosyltransferase) in the synthesis of tryptophan products degradation was described. Taking into account the importance of disorders, in which kynurenine metabolites may play pathogenic role. It was been postulated that kynurenine metabolites may be involved in pathogenesis of many diseases of clinical importance. Therefore evaluation of correlations between kynurenine metabolites and other variables, both clinical and biochemical, would be of interest. Attention was paid to the potential use of those biochemical parameter as biomarkers of many disease activity.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed2000

Platelet serotonergic mechanisms in patients with cancer of the urinary bladder.

Platelet reactivity of hypertensive patients and patients with cancer of the urinary bladder was examined in vitro in comparison with normotensive patients. A significant increase in free serotonin in the plasma of patients with cancer of the bladder and a less pronounced increase in hypertensive subjects was observed. The platelets in neoplastic disease and hypertension showed a significant reduction in the kinetics of serotonin uptake. However, the release reaction was markedly higher, compared with healthy volunteers. Enhancement of platelet aggregation with serotonin was much greater in patients with cancer of the bladder than in control groups and in hypertensive patients. These data indicate increased sensitivity to serotonin within the platelets of patients with cancer of the urinary bladder.

Adenosine Diphosphate↗
PubMed2000

Serotonergic and kynurenic pathways in rats exposed to foot shock.

Electric foot shock was applied to rats and levels of tryptophan and its metabolites were measured in the plasma, central nervous system and peripheral tissues. Metabolites of tryptophan are the results of the enhancement of serotonergic and kynurenine pathways. Plasma levels of tryptophan increased significantly immediately after the foot shock and returned to normal values within 24 h. Tryptophan levels also increased in all the brain areas immediately after stress application and returned to normal values within 24 h. Foot shock elevated the levels of kynurenine in the plasma, liver, kidney and every parts of the brain. 3-Hydroxykynurenine and kynurenic acid levels were increased in the brain. The present observations suggest that stress activates not only serotonergic pathway but also kynurenine pathway in the central nervous system and periphery. Some metabolites of kynurenine pathway, such as 3-hydroxykynurenine, are neurotoxic while other metabolite, such as kynurenic acid, may be neuroprotective. Increase in serotonin level in the hypothalamus and midbrain stabilises emotion and prevents mood disorders. Therefore, some brain dysfunction resulting from stress may be prevented by the metabolites of tryptophan. The balance of these functions may be important in the maintenance of nerve integrity under stress conditions.

Animals↗
PubMed2000

Importance of serotonergic mechanisms in the thrombotic complications in hemodialyzed patients treated with erythropoietin.

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.

Adult↗
PubMed2000

In vivo and in vitro suppression by leptin of glucose-stimulated insulin hypersecretion in high glucose-fed rats.

OBJECTIVES: Chronic feeding to rats of high glycaemic index (GI) diets results in the hypersecretion of insulin in response to an i.v. glucose load. The first aim of this study was to see if this exaggerated insulin response was accompanied by a hypersensitivity to glucose stimulation in isolated islets in vitro. The second aim was to see if the adipocyte factor, leptin, was able to alter insulin secretion in this model both in vivo and in vitro. DESIGN AND METHODS: Rats were fed for 6 weeks either a high GI diet in which the carbohydrate component was mostly glucose (GLUC diet) or a low GI diet containing mostly amylose (AMOSE diet). Rats then underwent an i.v. glucose tolerance test (ivGTT) (1g/kg) with and without a prior infusion of leptin (133 microg/kg perh). Islets were then isolated from these rats and basal and glucose-stimulated insulin secretion (GSIS) measured in both the absence and presence (100ng/ml) of leptin. RESULTS AND CONCLUSIONS: Peak insulin response during the ivGTT was 3-fold greater in GLUC rats (P<0.001). Leptin had no effect on AMOSE rat insulin response but lowered the GLUC rat response to AMOSE rat levels. In vitro, basal insulin secretion was 4-fold greater in GLUC rats (P<0.05). At 20mmol/l glucose, there was no further increase in insulin secretion in GLUC rats but a 2-fold increase in AMOSE rats. Leptin had no effect on basal insulin secretion or GSIS in AMOSE rats but reduced basal insulin secretion and GSIS in GLUC rats. These results show insulin hypersecretion in high GI-fed rats may be reduced by leptin.

Animals↗
PubMed2000

The involvement of AT(2)-receptor in the antithrombotic effect of losartan in renal hypertensive rats.

In previous studies, we have shown that losartan possesses nitric oxide-dependent antithrombotic properties in various models of hypertension in rats. It was demonstrated that stimulation of AT2-receptors plays an important role in the pharmacological effects of AT1-receptor antagonists. Thus, in this study, we examine the participation of AT2-receptors in the antithrombotic action of losartan in renal hypertensive rats on venous thrombosis induced by a two-hour ligation of the vena cava. Losartan administration(30 mg/kg, p.o.) resulted in a marked decrease in thrombus weight (by 85%, p<0.001). PD123319, an AT2-receptor antagonist (10 mg/kg, i.v.), administered concomitantly with losartan, abolished its antithrombotic effect, whilst it had no influence on thrombus weight when given alone. A significant decrease in systolic blood pressure was observed in animals given losartan. PD123319 administration didnot abolish this action of losartan and did not alter blood pressure when given alone. No changes in prothrombin time, activated partial thromboplastin time, or euglobulin clot lysis time were observed in animals administered losartan and/or PD123319.Similarly, primary haemostatics evaluated by bleeding time and platelet count did not change in any group of rats. In conclusion, we have shown that AT2-receptor stimulation is involved in the antithrombotic action of losartan in renal hypertensive rats.

Animals↗