Levent Kayrin

Effects of apolipoprotein E genotypes and other risk factors on the development of coronary artery disease in Southern Turkey.

BACKGROUND Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism and lipid transport. Associations between apoE genotypes, coronary artery disease (CAD) and other risk factors have been described by many investigators. The aim of this study was to investigate the role of apoE gene polymorphism and other risk factors in the development of CAD in subjects whose coronary arteries were evaluated by means of coronary angiography. METHODS The study population consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD. The apoE gene was amplified by polymerase chain reaction (PCR) and then digested by CfoI restriction enzyme. The plasma lipid levels and other risk factors were also determined in all subjects. RESULTS The epsilon2 and epsilon4 allele frequencies and genotypes carrying epsilon4 allele were significantly higher in CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+) cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were the independent predictors of CAD. There was no association between apoE alleles and lipids. CONCLUSION We conclude that apoE polymorphism (presence of epsilon4 allele) is associated with the development of CAD in Southern Turkey. In our study, we did not observe any effect of apoE alleles on lipid levels.

Asymptomatic hyperammonemia in children treated with valproic acid.

It was also reported that therapy with valproic acid led to the decreased plasma free carnitine concentration associated with hyperammonemia .6,1 Ohtani et all reported that there was a negative correlation between plasma ammonia and carnitine levels in patients taking valproic acid, and after giving L-carnitine (50 mg/kg/day) for 4 weeks, both hyperammonemia and carnitine deficiency were improved. We planned this study in patients without hepatic dysfunction and taking valproic acid to evaluate: (1) whether or not hyperammonemia rises; (2) if it is symptomatic; (3) if it rises, to what extent; (4) which variables affect it; and (5) if it is responsive to oral L-carrdtine, and if so, how long carnitine therapy should be given to these patients.

effects of L-carnitine and niacin supplied by drinking water on fattening performance, carcass quality and plasma L-carnitine concentration of broiler chicks

The present study was initiated to determine whether dietary supplemental L-carnitine and niacin affect growth performance, carcass yield, abdominal fat and plasma L-carnitine concentration of broiler chicks. One-day-old broiler chicks (COB500) were used in the experiment. A two by two factorial arrangement was employed with two levels (0 and 50 mg/l) of supplemental L-carnitine and two levels (0 or 50 mg/l) of supplemental niacin in drinking water as main effects. Body weight gain was significantly improved by L-carnitine, or L-carnitine + niacin supplementation during the first 3 weeks. However, supplemental L-carnitine and niacin did not change body weight gain during the last 3 weeks of the experimental period. Supplemental L-carnitine significantly improved feed intake during the first 3 weeks. Supplemental L-carnitine or niacin did not influence carcass weight, carcass yield and abdominal fat weight. L-carnitine content in the plasma was significantly higher in the groups receiving supplemental L-carnitine and L-carnitine + niacin. It is concluded that dietary supplemental L-carnitine or L-carnitine + niacin could have positive effects on body weight gain and feed intake during the early stages of growing. However, supplemental L-carnitine or L-carnitine + niacin were not of benefit regarding the complete growth period.

Oxidative-antioxidative system in peripartum acute renal failure and preeclampsia-eclampsia.

Background: Preeclampsia‐eclampsia and acute renal failure in peripartum women can be the cause of mortality and morbidity. There are many different reports about oxidative–antioxidative systems in preeclampsia‐eclampsia. Until now, products of activated oxidative–antioxidative systems were not evaluated in peripartum women with acute renal failure. In this study, our aim was to evaluate the oxidative–antioxidative systems in peripartum women with acute renal failure and/or preeclampsia‐eclampsia. Methods: The study groups consisted of 17 peripartum women (first week of delivery) with acute renal failure (G I), 11 preeclamptic (G II), 11 healthy pregnancy (≥ 30 weeks of pregnancy) (G III), and 11 healthy women (G IV) aged between 18–38 years. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) in erythrocytes, and plasma malondialdehyde (MDA) levels were measured in all groups. SOD, GSHPx, and MDA levels were also measured at the onset of acute renal failure (G IA), regression of renal dysfunction (G IB) and recovery of renal functions (G IC). Results: MDA levels were 11.95 ± 4.25, 9.22 ± 3.62, 5.10 ± 3.65, 3.40 ± 1.27, 4.91 ± 2.06, 4.24 ± 1.67 mmol/mL in G IA, G IB, G IC, G II, G III, and G IV, respectively. SOD activity in erythrocyte were 3269.23 ± 1437.83, 2641.35 ± 1411.13, 2056.35 ± 1143.11, 924 ± 160.04, 1057.91 ± 257.03, 861.63 ± 243.28 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. GSHPx activity in erythrocyte was 70.17 ± 23.52, 58.27 ± 23.75, 45.44 ± 17.60, 24.48 ± 6.77, 26.28 ± 7.27, 32.95 ± 8.24 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. MDA levels and activities of SOD, GSHPx in erythrocytes were highest in GIA The values of MDA, SOD, and GSH‐Px in G IA, G IB, and G IC were significantly different from each other and decreased while regaining of renal functions. Preeclampsia‐eclampsia or normal pregnancy did not cause elevation of plasma MDA levels and GSHPx, SOD in erythrocyte. Conclusion: Although SOD and GSHPx in erythrocytes and plasma MDA level were found to be similar in healthy women, pregnant women, and preeclamptic women; SOD, GSHPx, and MDA increased at the beginning and decreased during recovery of renal functions in peripartum women with acute renal failure.

Pyruvate kinase activity in cerebral hemispheres and cerebellum-brainstem of normal and hypoxic-ischemic newborn rats

Energy metabolism is affected in hypoxia-ischemia. Changes in the tissue concentrations of the high-energy phosphate reserves occur early during the course of the metabolic insult and with concurrent increases in cellular ADP and AMP leading glycolysis. It has been shown that enzymes of glycolysis tend to be regulated in hypoxia and ischemia. In this study we determined pyruvate kinase (PK) activity, one of the main enzymes in glycolysis, in brain tissues of healthy (n = 15) and hypoxic-ischemic (n = 18) 7-day-old newborn rats. Left common carotid artery was ligated in the hypoxic-ischemic group and after 2 hours rats were exposed to hypoxia in a chamber at 34–36 °C with 8% oxygen in nitrogen. The rats were decapitated after 2 hours of hypoxia and right and left cerebral hemispheres (CH) and cerebellum-brain stem (C-BS) were removed. Pyruvate kinase activity was significantly higher in C-BSs than CHs in both groups (p.< 0.00005). There was no significant difference in enzyme activities of either CHs or C-BS of hypoxic-ischemic group compared to control healthy group (p > 0.05). In conclusion, brain pyruvate kinase activity did not change in hypoxia-ischemia and suggests that PK of brain differs from other tissues where it usually increases in hypoxiaischemia.

THE ACTIVITY AND KINETICS OF PYRUVATE KINASE IN HYPOXIC NEWBORNS

Pyruvate kinase (PK) plays a key role in erythrocytes, which obtain most of their energy from glycolysis. This study investigated erythrocyte energy metabolism in hypoxic newborns, measuring pyruvate kinase activity, kinetic, and ATP levels in hypoxia. Forty-nine babies who had cord pH value lower than 7.2 and Apgar scores lower than 7 in the first minute were accepted as the hypoxic group, and 48 babies who had cord pH value higher than 7.2 and an Apgar score higher than 7 in the first minute were taken as controls. The erythrocyte mean PK activity was found to be lower (16.9 ± 8.5 [5.8−47.9] EU/gHb) in the hypoxic group than the control group (21.3 ± 10.9 [3.9−44.3] EU/gHb) (p <. 05). The mean ATP value of hypoxic group was higher (19.2 ± 11.3 [3.9−37.6] mM) compared to control group (13.8 ± 7.16 [3.9−28.7] mM). In the kinetic study, with different ADP concentrations in the control group, the substrate amount (Km) that is needed to reach the half-maximum of enzyme activity (Vmax = 27.7 Eu/gHb) was found to be 2.70 mM, but it was 1.47 mM to reach Vmax (22.7 Eu/gHb) in the hypoxic group. Vmax was 41.67 Eu/gHb and Km was 8.33 mM in the control group at different PEP concentrations, whereas Vmax was 21.7 Eu/gHb and Km was 0.89 mM in the hypoxic group. Increase in the ATP level while ePK activity decreases, suggesting that glycolysis increases in hypoxia. In the kinetic study, the substrate amount needed for reaching the half-maximum of enzyme activity was less in the hypoxic group, probably suggests that pyruvate kinase increases glycolysis by increasing its affinity to the substrates. In this way, erythrocytes may gain the energy required for oxygen delivery to tissues and maintaining ion gradient. This arrangement possibly proceeds from sygmoidal structure of pyruvate kinase.

ERYTHROCYTE PYRUVATE KINASE ACTIVITY IN TERM AND PRETERM INFANTS

The activity of erythrocyte pyruvate kinase (PK), one of the most important enzymes in the anaerobic glycolytic pathway, was measured in a total of 57 healthy (22 term and 35 preterm) infants. The mean PK activity was 8.98 +/- 3.43 IU/gHb in term and 16.56 +/- 7.26 IU/gHb in preterm infants. The mean PK activity was significantly higher in preterm babies than term infants (16.56 +/- 7.26 IU/gHb and 8.98 +/- 3.43 IU/gHb, respectively) (P < .001). A significant negative correlation was found between gestational age, birth weight, and PK activity (r = 0.40, P < .05; r = -0.37, P < .05). No correlation was found between postnatal age and PK activity in both preterm and term infants. The increased PK activity in preterm babies was thought to be due to increased glycolytic activity and energy production in these infants.

A new biosensor for noninvasive determination of fetal RHD status in maternal blood of RhD negative pregnant women

Prenatal detection of the fetal RHD status can be useful in the management of RhD incompatibility to identify fetuses at risk of hemolytic disease. Hemolytic disease causes morbidity and mortality of the fetus in the neonatal period. The routine use of antenatal and postnatal anti-D prophylaxis has reduced the incidence of hemolytic disease of the fetus and newborn. This study describe the detection of fetal RhD antigens in blood of RhD negative pregnant women using a nanopolymer coated electrochemical biosensor for medical diagnosis. Cell free fetal DNA in maternal plasma was also used to genotyping fetal RHD status using multiplex real-time PCR. Twenty-six RhD negative pregnant women in different gestational ages were included in the study. RhD positive fetal antibodies detected with a developed biosensor in maternal blood of RhD negative mothers. The electrochemical measurements were performed on a PalmSens potentiostat, and corundum ceramic based screen printed gold electrode combined with the reference Ag/AgCl electrode, and the auxiliary Au/Pd (98/2%) electrode. Fetal RHD genotyping performed using fluorescence-based multiplex real-time PCR exons 5 and 7 of the RHD gene. The fetal RHD status of 26 RhD negative cases were detected 21 as RhD positive and 5 as RhD negative with electrochemical biosensor. Fetal RHD status confirmed with extracted fetal DNA in maternal plasma using multiplex real-time PCR RHD genotyping and by serological test after delivery. The new method for fetal RhD detection in early pregnancy is useful and can be carry out rapidly in clinical diagnosis. Using automated biosensors are reproducible, quick and results can be generated within a few minutes compared to noninvasive fetal RHD genotyping from maternal plasma with real-time PCR-based techniques. We suggest the biosensor techniques could become an alternative part of fetal RHD genotyping from maternal plasma as a prenatal screening in the management of RhD incompatibility.

Kanser Metabolizması ve Otofaji

Otofaji hasarli veya gereksiz protein ve organellerin temizlenmesi ve besinsel strese yanit olarak enerji kaynaklarini dengelemek amaciyla hucrenin kendini parcalama surecidir. Apoptozis mekanizmasi hasarli olan tumor hucrelerinde otofaji, hucrenin sag-kalim suresini uzatmaktadir. Bununla birlikte otofaji, tumor olusumunun erken evrelerinde tumor baskilanmasini saglayabilir. Bu durumda otofajinin uyarilmasi kanserin onlenmesinde yararli olabilir. Bu derlemede otofajinin onemi, normal dokulara kiyasla tumor dokusuna olan bagimliligina ve tumor olusumunda metabolizmaya olan etkisi tartisilarak genel bir bakis acisi ile sunulmustur.

Sirkadiyen Saatin Epigenetikle İlişkisi

Sirkadiyen saat organizmalarin biyokimyalarinin, fizyolojilerinin ve davranislarinin gunluk ritmlerini kontrol eder. Sirkadiyen ritmin bozulmasi, kanserler de dahil olmak uzere bircok uzun sureli hastaligi ve vucuttaki biyolojik surecleri etkilemektedir. Sirkadiyen duzenleyici yollar, sirkadiyen epigenomlarin olusumuna ve ritmik epigenetik degisikliklere neden olur. Sirkadiyenin bozulmasindan dolayi olusan hipermetilasyon gibi anormal epigenetik modifikasyonlar, normal hucrelerin kanser hucrelerine donusumune sebep olabilir. Bu derlemede sirkadiyen genler ve duzenleyici proteinler, sirkadiyen saatin bozulmasi sonucu olusan epigenetik degisikliklere iliskin guncel kanitlar ve sirkadiyen bozulmanin karsinojenik etkileri ve insanlardaki farkli kanserlerdeki potansiyel rolu tartisilacaktir.