Mustafa Calapoglu

The novel ischemia marker ‘ischemia-modified albumin’ is increased in normal pregnancies

The aim of this prospective case‐control study was to determine the change in serum maternal ischemia‐modified albumin (IMA) during normal pregnancies. A total of 117 pregnant (first trimester (n = 24), second trimester (n = 34), and third trimester (n = 35)) and non‐pregnant healthy women (n = 23) were included. Maternal serum IMA, Malondialdehyde (MDA), and albumin levels were measured. Compared with non‐pregnant women, the cross‐sectional mean IMA levels in pregnant women were significantly increased, while the mean serum MDA and albumin levels were significantly decreased throughout pregnancy. Furthermore, a significant negative correlation between serum IMA and albumin levels (r = −0.354, p<0.001) was found, and there was a weak positive correlation between serum albumin and MDA levels (r = 0.334, p<0.001). Serum IMA, which has recently been developed as a clinical marker of ongoing myocardial ischemia, appears to be elevated in normal pregnancy. This may be due to the physiologic oxidative stress state of pregnancy.

Effects of misoprostol on cisplatin-induced renal damage in rats

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CPs side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.

Plasma fibronectin level and its relationships with lipids, lipoproteins and C-reactive protein in patients with dyslipidaemia during lipid-lowering therapy

Objectives — The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. Methods — Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. Results — After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43,6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=–0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57±0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57±0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45±0.11 g/l). During the lipidlowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. Conclusions — It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.OBJECTIVES The purpose of this study is to determine plasma fibronectin level and its relationships with plasma lipids, lipoproteins and C-reactive protein (CRP) levels in patients with dyslipidaemia during lipid-lowering therapy. METHODS Plasma levels of fibronectin, CRP, fibrinogen, lipids and lipoproteins in 38 patients with dyslipidaemia were determined before and after lipid-lowering therapy by using atorvastatin, 10 mg/day. RESULTS After lipid-lowering therapy, serum levels of fibronectin and CRP were found to be significantly decreased by 30.4% and 43.6%, respectively, while fibrinogen levels were increased 11.7% in patients with dyslipidaemia. Before the treatment, fibronectin was found to be positively correlated with CRP and total cholesterol (r=0.38, p<0.05 and r=0.33, p<0.05, respectively) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=-0.42, p<0.01) in patients with dyslipidaemia. High fibronectin levels (0.57 +/- 0.17 g/l) were found in patients with HDL-C below 35 mg/dl (0.57 +/- 0.09 g/l), compared to patients with HDL-C above 35 mg/dl (0.45 +/- 0.11 g/l). During the lipid-lowering therapy, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and apo B levels were reduced while HDL-C and apo AI levels were increased. CONCLUSIONS It was found that plasma fibronectin and CRP levels were decreased by lipid lowering therapy. Plasma fibronectin levels were associated with lipids, lipoproteins, CRP levels before treatment and these relationships disappeared after treatment. Consequently, it was suggested that reduction of plasma fibronectin levels, together with lipids and loss of its relationship with CRP, may play a role on the antiatherogenic effects of lipid-lowering therapy.

Novel GDAP1 Mutation in a Turkish Family with CMT2K (CMT2K with Novel GDAP1 Mutation)

Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot–Marie–Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes. It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins. Here, we report a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant (c.102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2.

Clinical Case Study: CONNEXIN 32 MUTATION IN A TURKISH FAMILY WITH X-LINKED CHARCOT-MARIE-TOOTH DISEASE

In the present work, we describe a large Turkish family (N = 39) with Charcot-Marie-Tooth disease, which is the most commonly inherited peripheral neuropathy. The subjects were from four generations, including six hemizygote patients and nine heterozygote carrier females. Symptoms appeared in late childhood in males (mean age = 13.5) but later in carrier females (mean age = 33.5). The peripheral nerve conduction was more severely affected in males than females. Genomic DNA was isolated from peripheral white blood cells. Using SSCP technique (single strand conformation polymorphism analysis), abnormal patterns of migration were observed in 15 subjects: 6 of them were hemizygote males and 9 were heterozygote carrier females. We identified a mutation of the Cx32 gene, consisting of a guanine to adenine transition at position 271 (271G-A). The results suggested relations between degenerative processes and position of Cx32 mutations.

A Case-Control Association Study of RANTES (-28C>G) Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinsons disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86–347.24 and 1.74–591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01–0.63], p = 0.019). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk.

Investigation of hypoxia-inducible factor-1alpha (HIF-1α) gene polymorphisms in individuals with high levels of hemoglobin / Hemoglobin seviyesi yüksek bireylerde hipoksi ile indüklenen faktör-1 alfa (HIF-1α) gen polimorfizminin araştırılması

Abstract Objective: A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate oxygen-sensing machinery and hypoxic cell metabolism. Recent works suggest that mutation of the HIF oxygen-sensing pathway plays a key role in the pathogenesis of the erythrocytosis. In the present study, the probable role of the polymorphic HIF-1α variants, C1772T (P582S) (rs11549465) and G1790A (A588T) (rs115494657), which are known to enhance transcriptional activity, were evaluated in the etiology of the polycythemia. Methods: A total of 284 subjects 97 with normal levels of hemoglobin (Hgb) 157 with high levels of Hgb, and 30 with polycythemia vera (PV)) were recruited for this study. Genomic DNA was extracted from peripheral blood lymphocytes of all subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for HIF-1α C1772T and G1790A single nucletide polymorphisms (SNP). A complete blood count was performed for all subjects. Results: There was a significant decrease in the frequency of the HIF-1α C1772T allele T in subjects with PV compared with those in the normal level Hgb group (OR 0.51; 95% CI 0.75−0.95; p=0.03). High level Hgb subjects had a significantly higher frequency of the HIF-1α G1790A allele A (OR 10.79; 95% CI 0.62-; 187.96; p=0.027) than the subjects in the normal level Hgb group. A significant difference was observed in genotype distribution of GG and combined GA+AA genotypes of HIF-1α G1790A in PV and normal Hgb level subjects (OR 17.11; 95% CI 0.80−366,61; p>0.05). Conclusion: Our results suggest that the HIF-1α C1772T and G1790A polymorphisms may be associated with PV in the study population. Özet Amaç: Sistemik hipoksiye karşı klasik fizyolojik cevap kırmızı kan hücresi üretimindeki artıştır. Hipoksi ile İnduklenebilir Faktorler (HIFs), oksijen-duyarlılık mekanizmasını ve hipoksik hücre metabolizmasını düzenlemektedirler. Son yıllardaki calışmalar, HIF oksijen- duyarlılık yolağındaki mutasyonların eritrositozun patogenezinde anahtar rol oynadığını göstermektedir. Bu çalışmada, transkripsiyonel aktiviteyi artırdığı bilinen, polimorfik HIF-1α varyantlarının, C1772T (P582S) (rs11549465) ve G1790A (A588T) (rs11549467), polisitemi etiyolojisindeki muhtemel rolü araştırıldı. Metod: Normal hemoglobin (Hgb) seviyeli 97 birey, yüksek Hgb seviyeli 157 birey ve polisitemi veralı (PV) 30 birey olmak uzere toplam 284 birey çalışmaya dahil edildi. Genomik DNA örnekleri periferal kan lökositlerinden standart yonteme gore izole edildi. HIF-1α C1772T ve G1790A tek nükleotid polimorfizmleri için polimeraz zincir reaksiyonu-parca uzunluk polimorfizmi (PCRRFLP) metodu uygulandı. Tum bireyler için tam kan sayımı yapıldı. Bulgular: PV’li ve normal Hgb seviyesine sahip guruplar karşılaştırıldığında PV’li gurupta HIF-1α C1772T için T allelinin anlamlı olarak artmış olduğu (OR 0,51; %95 CI 0,75-0,95; p=0,03), normal Hgb sahip gurupla yüksek Hgb sahip guruplar karşılaştırıldığında ise HIF-1α G1790A için A allelinin anlamlı olarak yuksek olduğunu bulundu (OR 10,79; %95 CI 0,62-; 187,96; p=0,027 ). HIF-1α G1790A polimorfizmi acısından PV ve normal Hgb seviyeli grupta GG ve kombine GA+AA genotiplerinde anlamlı farklılık gözlendi (OR 17,11; %95 CI 0,80-366,61; p<0,05). Sonuç: Çalışılan populasyonda, HIF-1α C1772T ve G1790A polimorfizmlerinin PV ile ilişkili olabileceği sonucuna varılmıştır.

Genetic Study of Demyelinating form of Autosomal-Recessive Charcot–Marie–Tooth Diseases in a Turkish Family

Charcot–Marie–Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited peripheral motor and sensory neuropathies characterized by distal muscle weakness atrophy predominantly in the lower extremities, diminished or absent deep tendon reflexes, distal sensory loss and skeletal deformities. Mode of inheritance could be either autosomal dominant, autosomal recessive, or X-linked. The autosomal-recessive subgroup of CMT (AR-CMT) neuropathies is heterogeneous as well. To date, nine demyelinating loci have been implicated in CMT4 and seven genes have been identified. It has been screened in this study for the presence of mutations in the coding region of GDAP1 and genetic linkage analyses of CMT4B1, CMT4B2, CMT4C, CMT4D, CMT4E, and CMT4F loci were tested in a Turkish family presenting recessively inherited form of CMT disease characterized by severe motor weakness. We did not find any mutations in GDAP1 and genetic linkage excluded for the six demyelinating genes loci (CMT4B1, CMT4B2, CMT4C, CMT4D, CMT4E, and CMT4F). Our findings indicate that another locus may be associated with AR-CMT disease.