Dimethylarginine – biomarkers in progression of kidney disease / Dimetilarginini – biomarkeri u progresiji bubrežnih oboljenja

Summary Decreased nitric oxide (NO) production and/or impaired NO bioavailability may occur in patients with the chronic kidney disease (CKD), and could contribute to elevation of blood pressure, cardiovascular disease (CVD) and progression of renal injury in these patients. Free guanidinomethylated arginine residues occur endogenously as a result of proteolysis of post-translational methylated tissue proteins. The asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of the nitric oxide synthase (NOS) enzymes. The kidney has a predominant role in ADMA elimination by combining two mechanisms; urinary excretion and metabolization of ADMA The degradation of ADMA is accomplished intracellularly by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). ADMA is not only a uremic toxin, but also a strong marker of the endothelial dysfunction and atherosclerosis and a stronger independent predictor of all-cause mortality and cardiovascular outcome in patients with the chronic renal failure. There are at least four mechanisms that may explain the accumulation of ADMA in CKD: increased methylation of proteins, increased protein turnover, decreased metabolism by DDAH and impaired renal excretion. A strong positive correlation between symmetric dimethyl arginine (SDMA) and creatinine suggests that SDMA might be of value as a marker of the renal function. Reduced NO elaboration secondary to accumulation of ADMA and elevated inflammation may be important pathogenic factors for endothelial dysfunction in patients with the renal disease. Elevation of ADMA may be a missing link between CVD and CKD

EFFECTS OF INHALATED GLUCOCORTICOSTEROIDS TREATMENT ON CLINICAL AND EOSINOPHILIC INFLAMMATORY PARAMETERS IN PATIENTS WITH BRONCHIAL ASTHMA

Inhaled glucocorticosteroids are the most efficient anti-inflamatory drugs used in asthma treatment that can bring the improvement of clinical symptoms as well as lung function. Eosinophils (Eo) are the key efector cells in asthmatic inflammation, and determination of their number and concentration of mediators which can bring about eosinophilic activation- interleukin-5 (IL-5) would contribute to the evaluation of anti-inflammatory treatment effects in asthma patients.The aim of this study was to compare clinical parameters and eosinophilic inflammation parameters in patients with asthma, after 4-week treatment with fluticasone-propionate (FP) in a daily dose of 500 μg.The study involved 39 patients with bronchial asthma as well as 17 healthy subjects (controls). Asthma symptom scores, FEV1, FEV1/FVC, total number of Eo in peripheral blood and IL-5 concentracion in serum were measured in all subjects, before and after FP 500 treatment. There was a significant decrease in asthma symptom scores (p<0.001) and improvement of FEV1 and FEV1/FVC (p<0.05) after FP 500 treatment.There was also a statistically significant negative correlation beetwen asthma symptom score and FEV1 before and after the treatment (r=-0,415, p<0,01; r=-0,346, p<0,05). The concentration of eosinophilic inflammatory parameters (Eo, IL-5) was significantly reduced after the treatment (p<0.05) in groups of patients with larger number of eosinophiles prior to the therapy.Besides lung function normalisation and improvement of disease symptoms after the treatment, there were higher concentrations of eosinophilic inflammatory parameters that point to persistant inflammation of airways during well-controlled asthma. It is necessary to constantly compare the symptoms of desease, lung function, severity of desease and level of inflammation parameters in order to assess the treatment effects of inhaled glycocortico-steroids

Age-related changes of superoxide dismutase activity in patients with schizophrenia

Background/Aim: Superoxide dismutase (SOD) is the critical enzyme in the detoxification of superoxide radicals because those are the first species produced in the majority of biological free radical producing reactions. Inconsistent data are present about SOD activity in patients with schizophrenia. Numerous studies have shown that SOD has been elevated in chronic schizophrenic patients. However, decreased SOD activity was found in neuroleptic naïve, first episode schizophrenic patients, in chronic-medicated patients and in chronic-unmedicated patients. The aim of this study was to examine which of the following factors including age, gender, the onset of the disease, the duration, the number of episodes, heredity, psychopathologic symptoms and drug treatment could affect erythrocyte SOD activity in patients with schizophrenia. Methods: This study included 68 consecutive patients with schizophrenia (29 males and 39 females) ranging in age from 18 to 61 years, divided into two age groups (34 years). SOD activity was measured in erythrocyte hemolyzates by Ransod commercially available test. Results: In the group of patients younger than 34 years SOD levels were significantly higher (1381±273 U/gHb, p=0.038) compared to the levels of the older group (1231±206 U/gHb). Gender and heredity did not induce any significant difference in SOD activity between younger and older subgroups. A significant difference in enzyme activity was found between the younger and older subgroups having the onset of the disease after 24 years of age (1408±217 U/gHb vs. 1252±213 U/gHb, p=0.031). The patients of the younger group who had more than one psychotic episode had significantly higher SOD activity (1492±298 U/gHb; p=0.009) than those who had only one episode (1256±177 U/gHb), as well as than the older subgroup with more than one episode (1253±231 U/gHb; p=0.014). Although the duration of the disease did not induce any significant difference in enzyme activity between younger and older subgroups, a significant negative correlation was obtained between SOD activity and the duration of the disease (r=-0.511, p<0.01). No significant differences were found in SOD activity between the subgroups with different PANSS scores. First generation antipsychotics were associated with elevated enzyme activity in both groups. Simultaneous treatment of patients with first generation antipsychotics and second generation antipsychotics induced a significant decrease in SOD activity in the younger group. Conclusion: Our results show that erythrocyte SOD activity is increased in the early phase of schizophrenia and that depends on age of onset of the disease, the number of psychotic episodes, the duration of the disease and medical treatment

Erythrocyte metabolism in insulin-induced hypoglycemia

Insulinomas are pancreatic tumors associated with hyperinsulinism and hypoglycaemia. The effects of long-term hypoglycaemia, caused by hyperinsulinism in insulinoma patients, on erythrocyte metabolism, were in­vestigated. The modifications of erythrocyte metabolism were studied in prolonged hypoglycaemia. “Fast” haemoglobin modifications were re-invcstigated and the activi­ties in some erythrocyte enzymes of carbohydrate metab­olism and oxidative defense system, were determined. On the basis of the results obtained the structural alterations of haemoglobin molecule and the physiological impor­ tance of these changes, were assumed.4th Meeting of the Balkan Clinical Laboratory Federation, Budva, Yugoslavi

Miokardno premošćavanje prednje međukomorne arterije (r. interventricularis anterior) i njenih grana u malog zelenog majmuna (Cercopithecus aethiops sabeus)

Myocardial bridges (MBs) are structures consisting of heart muscle fibers running above the subepicardially positioned coronary arteries. In the light of previous studies, MBs are most often associated with the ramus interventricularis anterior (RIA) which put this vessel into the focus of our research. The purpose of the present study was to determine the frequency of occurrence and quantitative analysis of myocardial bridges over the RIA and its lateral branches. The studied material consisted of 55 Cercopithecus aethiops hearts, of both sexes, preserved in formaldehyde solution. Standard anatomical methods were used in the analysis, with the help of a stereomicroscope. The presence of MBs over the RIA was confirmed in a total of 70.9% samples, with no statistically significant differences related to the gender. In 2 hearts (3.6%) multiple bridges were revealed. The length of the bridges varies in the range of 0.5 mm - 31.6 mm, the distance from the origin of RIA varies between 0.5 mm - 25 mm which makes the proximal third of the anterior (paraconal) interventricular groove most frequently tunneled. The lateral branches of RIA were overbridged in 5.4%, with a single muscular band. The lenght of MBs varied from 6.2 mm - 12.5 mm, and they were localized over the first lateral branch in all cases.Fenomen miokardnog premošćavanja subepikardnih koronarnih krvnih sudova je proučavan na 55 srca malog zelenog majmuna (Cercopithecus aethiops sabeus). Koristeći standardne metode disekcije, identifikovali smo prisustvo miokardnih mostova (MM) na prednjoj međukomornoj arteriji (RIA) na 39 od 55 srca (70.9%), od kojih su 25 (71.4%) bila srca ženki, a 14 (70%) srca mužjaka, što nije pretstavljalo statistički značajnu razliku vezanu za pol (p>0.05). U najvećem broju slučajeva, 96.4% zabeležili smo jedan MM nad RIA, a samo na 2 srca (3.6%) RIA je bila premošćena sa dva MM. Ukupan broj MM u našoj seriji je 41, a njihova najčešća lokalizacija je proksimalna trećina krvnog suda. Dužina MM je varirala između 0.5 mm i 31.6 mm, a češće smo nalazili kraće strukture (do 15 mm). Udaljenost MM od mesta nastanka RIA je varirala od 0.6 mm do 25 mm. MM nad (levim) bočnim granama RIA (r. laterales) smo uočili na 3 od 55 srca (5.4%), i to na 2 srca ženki (5.7%) i na 1 srcu mužjaka (5%), što nije predstavljalo statistički značajnu razliku u odnosu na pol (p>0.05). Dužina MM je varirala od 6.2 mm do 12.5 mm. U svim slučajevim smo našli po jedan MM nad prvom bočnom granom RIA

Polymorphisms of tumor-necrosis factor-alpha-7308 and lymphotoxin-alpha+250: Possible modulation of susceptibility to apoptosis in chronic lymphocytic leukemia and non-Hodgkin lymphoma mononuclear cells

Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) have been shown to play an important role in the pathogenesis of limphoproliferative disease. Both cytokines regulate cell-survival and cell-death in leukemic cells. TNF-alpha and LT-alpha are highly produced in chronic lymphotic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients. Genetic polymorphism within regulatory regions of these cytokine genes can alter their expression levels. This study investigates an influence of TNF-alpha - 308 and LT-alpha + 250 polymorphisms on the activity of alkaline DNase in mononuclear cells of both patient groups as a potent biochemical marker of DNA fragmentation in the terminal phase of apoptosis. Study was performed on mononuclear cells of CLL and NHL patients. SNP were obtained by PCR-RFLP method. The activity of alkaline DNase was measured by spectrophotometric method. The study provided evidence of the influence of TNFG/A genotype and A alleles in the susceptibility to NHL, since the association of LT-alpha G/G genotype with CLL was observed. High-producing TNF-alpha - 308/LT-alpha + 250 heterozygous haplotype is associated with high NHL incidence. The investigated SNP influence the activity of alkaline DNase in CLL and NHL patients. The observed polymorphisms may modulate susceptibility of leukemic cells to apoptosis by way of DNase activity