Abdullah Tuli

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.

Antioxidant enzyme levels in cases with gastrointesinal cancer

UNLABELLED The aim is to evaluate the antioxidant enzyme levels in tumoral tissues and accompanying normal tissues in gastrointestinal cancer; and compare the colorectal cancer (CRC) with gastric cancer (GC). METHOD Antioxidant enzymes including glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA) and glucose 6 phosphate dehyrogenase (G6PD) which are important for anti-oxidant functions were evaluated in fresh tumor tissues and adjacent normal tissues obtained from a total of 58 patients. RESULTS All the enzyme levels were higher in tumoral tissues compared to normal tissue from non-cancerous disease. There was not a significant difference for enzyme levels between CRC and GC groups except GPx. GPx activity tended to be higher in cases without serosal involvement (SI), and this activity was higher in cases without lymph node (LN) involvement in normal tissue (p=0.012). MDA activity was higher in cases without serosal involvement compared to with SI groups in tumor tissue (p=0.050). G6PD activity in normal tissue was higher in cases with serosal involvement and LN involvement (p=0.064, 0.046, respectively). GR activity was higher in signet ring cell cancer (SRC) than adeno cancer. In GC, G6PD activity in tumor was tended to be higher in undifferentiated cancer (p=0.071). CONCLUSION The antioxidant enzymes activities such as GPX, SOD, G6PD, MDA and GR were found to be related with malignant phenotype in gastrointestinal cancers. We need further studies to understand the biologic and clinical importance of these enzymes in GI cancers.

The effect of edaravone on ischemia-reperfusion injury in rat ovary.

OBJECTIVE The aim of this study was to investigate the effect of edaravone on experimentally induced ovarian torsion/detorsion ischemia/reperfusion (I/R) injury. STUDY DESIGN Forty-six female adult Wistar-Albino rats were utilized to create five groups: In group 1, only 5 mg/kg edaravone was given and ovary torsion was not performed. In group 2, torsion was not performed and no drug was given. In group 3, vehicle was given and torsion/detorsion was performed. In group 4, 1 mg/kg edaravone was given and torsion/detorsion was performed. In group 5, edaravone; 5 mg/kg drug was administered and torsion/detorsion was performed. Right ovarian torsion was simulated for a 3-h period of ischemia and a 1-h reperfusion period. Right ovaries were then surgically extirpated in all groups. In ovarian tissue samples malondialdehyde (MDA) levels and activity of superoxide dismutase were studied. Microscopic ovarian tissue damage was scored by histologic and electron microscopic findings. RESULTS The MDA level in the group 5 was significantly lower than group 3 (p<0.001). Superoxide dismutase activity in the group 5 was significantly higher than group 3 (p<0.001). Histopathological ovarian tissue damage in the group 5 were significantly lower than group 3 (p<0.001). CONCLUSION These results indicate that edaravone could be an effective agent in the short-term treatment and prevention of ovarian ischemia and reperfusion damage.

Studies on Red Cell Glucose-6-Phosphate Dehydrogenase: Evaluation of Reference Values

The analytical, intra-individual, inter-individual variation and reference values were determined for red cell glucose-6-phosphate dehydrogenase (G6PD). Different procedures for the conditions for storage of red blood cells and the preparation of haemolysates were investigated. A total of 2170 samples of blood were taken from apparently healthy persons—1212 males and 958 females—from randomly selected villages and city centres in the southern part of Turkey. Analytical variation, intra-individual variation and inter-individual variation were 8·67%, 32·8% and 31·8%, respectively. The mean (SD) for G6PD was 8·6 (3·3) IU/gHb. The index of individuality, 1·03, showed that the reference intervals could be used for diagnostic purposes. Whole blood or a red cell pellet could be stored in physiological saline for one week at 4°C or −20° with little loss of activity. Two of three different procedures for the preparation of haemolysate gave data that showed no statistical difference and were equally satisfactory.

GENETIC HETEROGENEITY OF β-THALASSEMIA AT ÇUKUROVA IN SOUTHERN TURKEY

β-Thalassemia is the most common genetic abnormality causing health problems worldwide.Ç ukurova, in the southern part of Turkey, being on the Mediterranean, is in the thalassemic belt. Since there is no cure for the disease at present, the frequency of the mutation types of β-thalassemia must first be identified to aid in clinical follow-up and prenatal diagnosis. Carriers identified during a screening survey and patients referred to our laboratory were studied for this purpose. After routine hematological analysis molecular screening was performed by the amplification refractory mutation system and DNA sequencing. The frequency of the common mutations were: IVS-I-110 (G→A) 57.3%, IVS-I-1 (G→A) 8.3%, codon 39 (C→T) 6.4%, IVS-I-6 (T→C) 5.7%, frameshift codon 8 (–AA) 5.7%, –30 (T→A) 4.7%, IVS-II-1 (G→A) 3.4%, IVS-II-745 (G→C) 2.8%, and frameshift codon 5 (–CT) 1.1%. Some rare mutations (1%) such as frameshift codon 44 (–C) 0.7%, frameshift codons 74/75 (–C) 0.7%, IVS-I-5 (G→C) 0.7%, frameshift codons 8/9 (+G) 0.4%, frameshift codons 36/37 (–T) 0.4%, frameshift codons 22/23/24 (–AAGTTGG) 0.4%, IVS-I-130 (G→C) 0.4%, IVS-I-5 (G→T) 0.2%, –28 (A→C) 0.2%, codon 15 (TGG→TGA) 0.2%, and frameshift codons 82/83 (–G) 0.2%, were detected by sequence analysis. The codon 15 (TGG→TGA) and frameshift codons 82/83 (–G) mutations were seen in Turkey for the first time.

Evaluation of reference values for erythrocyte glutathione

The analytical, intra-individual and inter-individual variations as well as the best storage conditions were determined for erythrocyte glutathione, and the reference values were established. A total of 396 apparently healthy people, 206 male, and 190 female, were randomly selected from villages and cities of the southern part of Turkey. The distribution was Gaussian and no significant difference was observed between the male and the female subjects. The mean (standard deviation) of the population investigated for glutathione was 6.9 (1.0) mumol/gHb. The analytical, intra-individual and inter-individual variations were assessed in 20 apparently healthy subjects and were found to be 4.63%, 13.67% and 11.16%, respectively. Whole blood stored at -70 degrees C for up to 10 days was shown to be the best storage condition for erythrocyte glutathione determination. The results of the index of individuality showed that glutathione reference values could be used for diagnostic purposes.

Ultrastructural evaluation of the effect of N-acetylcysteine on methotrexate nephrotoxicity in rats.

The aim of this study is to investigate the possible protective effect of N-Acetylcysteine (NAC) against the likely methotrexate (MTX) toxicity on the kidney using ultrastructural together with biochemical data. Moreover, the immunohistochemical detection of Ki67 nuclear antigen is to be evaluated. Fifteen male Wistar albino rats, weighing 240-290 g, were divided into three equal groups: Rats receiving MTX alone, rats receiving MTX plus NAC treatment, and rats comprising the control group. MTX (18 mg/kg/day, body weight) in dissolved physiologic saline was administered intraperitoneally to rats during 3 days. For the MTX plus NAC group, N-Acetylcysteine (300 mg/kg/day, body weight) was administered together with MTX. At the end of the third day, all the rats were killed with cervical dislocation to obtain blood and tissue samples. Application of MTX principally induced prominent large vacuolization in the proximal convoluted tubule cells, and focal thickening in the glomerular basal lamina of some glomeruli. A decrease in tissue SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase), and an increase in serum urea nitrogen and creatinine and in tissue MDA (malondialdehyde) levels were also seen in the MTX group. These changes were significantly reversed in the MTX-plus-NAC-treated group. Most of the vacuoles in the proximal convoluted tubule cells disappeared. Furthermore, an increase in antioxidant enzyme activities, a decrease in serum urea nitrogen and creatinine, and tissue MDA levels were all significant. Additionally, an increase in the number of Ki67 positive-stained cells in proximal tubules was also noted. In conclusion, NAC may be a promising substance against MTX-induced renal damage. It might be useful to use NAC supplementally to minimize MTX-induced nephrotoxicity.

Noninvasive prenatal diagnosis experience in the Çukurova Region of Southern Turkey: detecting paternal mutations of sickle cell anemia and β‐thalassemia in cell‐free fetal DNA using high‐resolution melting analysis

This study used a high‐resolution melting (HRM) technique to detect paternal mutations for the noninvasive prenatal diagnosis (NIPD) of β‐thalassemia and sickle cell anemia (HbS). We also determined the levels of cell‐free fetal DNA and total cell‐free DNA.

Protective Effects of Phosphodiesterase-4-specific Inhibitor Rolipram on Acute Ischemia-reperfusion Injury in Rat Kidney

OBJECTIVE To investigate the effect of Rolipram, a phosphodiesterase-4-inhibitor, on renal ischemia-reperfusion injury (IRI) in rats. METHODS Thirty rats were divided into 5 different groups of 6 rats. Nothing was done to the control group. In the second group, the renal pedicle was clamped for 30 minutes. In the third group, 1 mg/kg of Rolipram was given by intraperitoneal injection 30 minutes before clamping. The fourth group received the same injection when the clamp was placed, as did the fifth group 30 minutes after the clamp was opened. Clamping time was set at 30 minutes. Twenty-four hours later, nephrectomy was performed in all the groups. Half of each kidney was examined histopathologically. Levels of biochemical agents, such as malondialdehyde, superoxide dismutase, and catalase, were measured in the other half. RESULTS The malondialdehyde (MDA) levels significantly decreased and reached control levels in the group in which Rolipram was administered 30 minutes after reperfusion (P = .07). The catalase and superoxide dismutase activities obtained from renal homogentisates of the ischemia groups were evaluated; there were striking increases in tissue levels of these 2 enzymes in the groups in which Rolipram was administered during ischemia and 30 minutes after ischemia (P < .001). Histopathologically, there was no significant difference in inflammation between the Rolipram-administrated groups compared with group 1 (control) and group 2 (IRI). Tubular necrosis and apoptosis was significantly lower in group 5 than the other groups, except group 1 (P < .001). CONCLUSION We suggest that in surgical procedures that can lead to renal IRI, the administration of Rolipram can decrease oxidative renal tissue damage and the severe deterioration of renal function.

Polymorphism of the angiotensin-converting enzyme gene and angiotensin-converting enzyme activity in transient tachypnea of neonate and respiratory distress syndrome.

Background: Transient tachypnea of neonate (TTN) and respiratory distress syndrome (RDS) of the newborn are the most common cause of early respiratory distress in the immediate neonatal period. There is increasing evidence to support the role for the activation of the renin angiotensin system during acute lung injury. Objectives: The purpose of this study was to determine if there is a relationship between angiotensin-converting enzyme (ACE) I/D polymorphism, ACE activity and TTN and respiratory distress syndromes. Methods: Nineteen neonates with TTN, 20 neonates with RDS and 21 control infants are studied for ACE polymorphism and serum ACE activity. Results: Twenty six (43.3%) patients have DD polymorphism, 19 (31.7%) patients have ID polymorphism and 15 (25%) patients have II polymorphism. Serum ACE activity is 43.5 ± 1.8 (40–46) U/L in DD, 31.5 ± 2.3 (28–36) U/L in ID and 22.1± 2.1(19–46) U/L in II patient. Conclusions: The study could not find any difference in DD alleles and ACE activity between control group and TTN group. ACE polymorphism was not different between RDS group and control group in this study.