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1. Amaç: Çalışmamızda, Sitokrom p450 enzimlerini kodlayan CYP ve vitamin K epoksit redüktaz kompleks subünit1 enzimini kodlayan VKORC1 genlerinin alt gruplarındaki tek nükleotit polimorfizmlerinin muhtemel bireysel ve ortak etkilerini prostat kanseri hastalarında araştırmayı amaçladık. Çalışma sonuçları aynı zamanda bu iki gen ile ilgili henüz ortaya konmamış olan bizim populasyonumuza özgü genotip dağılımını da kısmen ortaya koyacaktır. 2. Gereç ve Yöntem: Çalışmamıza 48 prostat kanseri tanılı erkek hasta ve 48 sağlıklı erkek birey dâhil edildi. Hasta grubu prostat tanısı almış yaş aralığı 49-86 olan gönüllü bireylerden seçildi. Kontrol grubu prostat kanseri olmadığı belirlenmiş, 51-86 yaş grubundaki gönüllü bireylerden seçildi. Hasta ve kontrol grubu bireylerinin venöz kanları alınarak genomik DNA izolasyonları yapıldı. İzole edilen DNA’ların ilgili gen bölgeleri polimeraz zincir reaksiyonu (PCR) ile çoğaltıldı. Sonrasında PCR ürünleri mikroarray cihazında özel problar yardımıyla çalışıldı. CYP2C9 ve VKORC1 gen bölgelerine ait alt grupların polimorfizmleri tanımlandı ve EpiInfo 3.5.1 istatistik programı ile anlamlılıkları hesaplandı. 3. Bulgular: Sonuçlarımızda CYP2C9 ve VKORC1 enzimlerini kodlayan genlerin alt gruplarının polimorfizmleri karşılaştırıldığında hasta ve kontrol grubu arasında yüzde olarak önemli farklar görüldü. Örneğin VKORC1 6853 G>C polimorfizmi için kontrol grubunda CC alleli %25 iken hasta grubunda %34,5 olarak tespit edildi. CYP2C9 *3 A>C değişimi için kontrol grubunda CC alleli %79,16 iken hasta grubunda %87,5 olarak tespit edildi. 4. Sonuç: Çalışmamızda sayı ve yüzde olarak hasta ve kontrol grubunda önemli farklar görüldü. CYP2C9 ve VKORC1 geninin alt gruplarının analizleri sonucunda istatistiksel anlamlılık tespit edilmedi. Bunun sebebinin örnek sayısı azlığı ile alakalı olduğu düşünüldü ve ileri çalışmaların konuyu aydınlatacağı düşünüldü.

Aim: Polycystic ovary syndrome (PCOS) is a multifactorial, endocrine, and metabolic disorder seen in 10%-20% of women of reproductive age. Due to the close relationshipobserved between the increased risk of type 2 diabetes and insulin resistance and the polymorphism of the fatty acid binding protein 1 (FABP1) gene rs2197076 single nucleotide polymorphism (SNP), we investigated the frequency of the FABP1 gene rs2197076 SNP in patients with PCOS. Methods: This is a prospective case-control study. The study included 151 women—75 patients with PCOS and 76 healthy women. A real-time polymerase chain reaction was performed for the FABP1 rs2197076 polymorphism. Additionally, biochemical and hormonal levels of the patients were studied. Results: Menstrual irregularities, the body mass index (BMI), hirsutism scores, the luteinizing hormone / follicular stimulating hormone ratio, dehydroepiandrosterone sulfate and testosterone levels were significantly higher in the PCOS group than in the control. There was no significant difference between the PCOS and control groups in terms of FABP1 rs2197076 genotype distribution and FABP1 rs2197076 allele frequency distribution. Conclusion: There was no increase in the genotype distribution and allelic frequency of the FABP1 gene rs2197076 SNP in PCOS patients. Further studies are needed on this subject.

Poland syndrome has been reported to be associated with true dextrocardia, but not with true situs inversus. In this report, we describe the first patient with total situs inversus in medical literature and try to highlight the syndrome's probable etiology and pathogenetic mechanisms in utero.

Human apolipoprotein E (apo E) alleles are polymorphic with significantly different frequencies among different ethnic groups and have been associated with increased risk of coronary heart disease, and postulated as a major genetic susceptibility locus for Alzheimer's disease. Studies undertaken in different populations have shown different association patterns between apo E genotype and stroke. The aim of this study was to determine the risk of apo E genotype in stroke patients living in the eastern part of Turkey. The apo E genotypes and allele frequencies of 229 individuals from the same geographic area were determined by polymerase chain reaction and restriction fragment length polymorphism, of which 103 were patients with a documented history of stroke without other apparent dementia and 126 age-matched healthy subjects as a control group. A reduced E3/4 genotype frequency was found in subjects with stroke and the E2/3 genotype frequency was elevated in patients with previous stroke. There was no association between apo E epsilon4 allele and stroke. The APOE alleles had divergent effects in this population. Association between APOE (the gene) alleles and stroke in this population may be altered due to interaction with other genetic effects. The effects of APOE alleles and genotypes require further study in different populations.

Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathological processes such as cancer. In this study, the association between TIMP-2 (-418 G/C) and MMP-2 (-1306 C/T) polymorphisms and prostate cancer in the Turkish population was investigated.Sixty-one prostate cancer patients and 46 healthy subjects were included in the study. DNA was isolated from 2 mL of peripheral blood taken from subjects, and genotypes were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method.The TIMP-2 -418 (GC) genotype was found in 15 cases (32.6%) in the control group and in 9 cases (14.8%) in the patients group, and statistical significance was determined (P = 0.037, OR = 0.346). The MMP-2 -1306 (CT) genotype was found 2.17 times more in the patient group than in the control group (P = 0.149, OR = 2.17).Our results show that the TIMP-2 -418 (GC) genotype had a putative protective effect against prostate cancer.

Methylxanthines (theophylline, theobromine and caffeine) are widely used as central nervous system stimulants and caffeine is used in the treatment of apnea in newborns. Plasma therapeutic concentration of caffeine is around 110 microM. Caffeine diffuses the blood brain barrier easily, increasing oxygen consumption in neurones and leading to cell death. In the present study, 4-7-day-old rats were used to obtain cerebellar granular cell cultures. Caffeine was used 50, 150, 250 and 350 microM concentrations and the most toxic dose for it was found to be 350 microM. Death cell scores were 0.9+/-0.63 for control, 1.1+/-0.63 for 50 microM, 0.89+/-0.47 for 150 microM (P0.05 for both), 3.84+/-0.8 for 250 microM (P=0.024) and 6.2+/-0. 86 for 350 microM (P=0.001) caffeine concentrations. The role of voltage-dependent calcium channels in caffeine-induced neurotoxicity was tested with the doses of 100 and 200 microM nimodipine 45 min before or after the 350 microM caffeine. Both doses of nimodipine after caffeine administration were found to be ineffective in blocking neurotoxicity. Doses administered 45 min prior to caffeine, reduced death cell score to 0.89+/-0.23 (P=0.000) for 100 microM nimodipine and 2.35+/-0.96 (P=0.000) for 200 microM nimodipine administration into the cultures. A dose-dependent manner of nimodipine in ischemic states is well-known. In the light of these results, nimodipine may be used in the treatment of newborn apneas together with caffeine to prevent neurotoxic side effects of high or repeated doses of it.

In this study, norepinephrine was tested in 0.1, 1, 10, 25 and 50 microM doses in 100 microM NMDA toxicity on cerebellar granular cell culture of rats. NMDA in 100 microM concentration induced cell death significantly with respect to controls. Death cell population was 1.08 +/- 0.44% in control and 22.15 +/- 2.46% in 100 microM NMDA (P0.0001). None of the norepinephrine concentrations administrated 15 min prior to NMDA was able to reduce death cell scores to control levels. Results were 8.75 +/- 0.83% in 0.1 microM, 7.0 +/- 1.01% in 1 microM, 17.25 +/- 1.31% in 10 microM, 35.5 +/- 1.38% in 25 microM and 17.9 +/- 1.72% in 50 microM norepinephrine plus 100 microM NMDA administrated groups (P0.0001 for all with respect to control). Labetalol, as an alpha and beta blocker in 0.5 microM concentration which was given 15 min prior to norepinephrine was able to block the effects of it. In comparison with 100 microM NMDA administered group, only low doses of norepinephrine reduced the death cell scores significantly (for 0.1 and 1 microM norepinephrine plus NMDA groups; P0.0001). For 10 and 50 microM norepinephrine plus NMDA groups, death cell scores were found statistically insignificant from the NMDA-administered group (P0.05 for both) while for the 25 microM norepinephrine plus NMDA group, the death cell score was found to be statistically increased (P0.0001).

The neuroprotective role of nimodipine was tested in kainic acid (50 and 100 microM) induced neurotoxicity in cerebellar granular cell cultures of 4 to 7 day-old rat pups. Nimodipine was applied in 50, 100 and 200 microM concentrations. Kainate, in either dose, induced cerebellar granular cell death in respect to controls and the results were statistically significant (P = 0.000 for both doses). However, kainic acid in 100 microM concentration led to higher rates of cell death than 50 microM (P = 0.017). The neuroprotective role of nimodipine in kainate induced neurotoxicity was dose dependent. Kainate toxicity in 50 microM concentration was blocked by 50 and 100 microM nimodipine concentrations (P = 0.006 and P = 0.002, respectively) while 200 microM nimodipine was found ineffective. The most effective nimodipine dose for 100 microM kainic acid neurotoxicity was 200 microM (P = 0.000) while 50 and 100 microM concentrations of nimodipine were found ineffective. In this study, we have proven the dose-dependent neuroprotective role of nimodipine in kainate induced neurotoxicity in cerebellar granular cell cultures of rat pups.

Pacemaker (PM)-related thrombosis is an infrequent complication of pacing. We present the case of a 58-year-old man with heart failure and atrial fibrillation who had recurrent episodes of PM lead thrombosis while undergoing anticoagulation therapy. The patient was admitted to the hospital with complaints of dyspnea and palpitation. Echocardiography revealed normal right ventricular dimensions and an enlarged left ventricle with poor contractility and an ejection fraction of 20%. Transesophageal echocardiography demonstrated a large, mobile thrombus in the right atrium that was attached to the PM lead. The patient was successfully treated with a thrombolytic agent. Genetic tests revealed that the patient was a heterozygous carrier of the methylenetetrahydrofolate reductase (MTHFR) gene mutation.

In the present study, melatonin was tested in subsequent doses in glutamate induced neurotoxicity in cerebellar granular cell culture of rat pups. Glutamate at 10(-7) M was found to induce neuronal cell death. The dead cell score was 2.75+/-0.7 in the control, while it was found to be 35.12+/-1.8 in the glutamate-administered group (P0.0001). Melatonin very potently blocked glutamate neurotoxicity at all doses tested, with 10(-3) M, the highest dose tested, being the most effective. Glutamate may exert a neuroprotective effect by blocking one or more steps of the oxidation cascade in neurons and this effect may be blocked by melatonin.

In the present study, dantrolene, nimodipine, basilen blue, and ruthenium red were tested in experimental bilirubin toxicity in cortical cell culture of rats. Neurotoxicity was induced by 10(-4) M bilirubin. Basilen blue in the highest concentration of 10(-4) M was determined as the most protective agent when applied alone. Dantrolene alone was found surprisingly ineffective in all doses tested. But it was found very protective both in double and triple combinations. Nimodipine, basilen blue, and ruthenim red neuroprotective potentials were enhanced by adding dantrolene into the media. Best double combination was determined as dantrolene plus ruthenium red. On the other hand, most useful triple combination was found as dantrolene plus nimodipine plus basilen blue. As a result, dantrolene wasn't found to be effective alone, while it seems most potential compound in combined application in bilirubin-induced neurotoxicity. The importance of calcium intrusion was confirmed in bilirubin-induced neurotoxicity.

WOS: 000229881900004 PubMed: 15896552 . In the present study, we used the L-type calcium channel blocker nimodipine, the endoplasmic reticulum (ER) calcium release blocker dantrolene and the calcium transport blocker in mitochondria ruthenium red (RuR), in NMDA induced neurotoxicity, to observe the. most suitable combination for neuroprotection in cerebellar granular cell culture of rat pups. In addition we tested the effect of RuR on intact neuronal cells without adding NMDA into the flask, in order to compare the effects. As was expected, NMDA induced neuronal cell death. In NMDA induced neurotoxicity, RuR was the most neuroprotective agent of all three compounds tested, but interestingly, RuR alone was found to be neurotoxic in non-NMDA treated cultures. RuR showed neuroprotectivity in a dose dependent manner in NMDA toxicity. Dantrolene and nimodipine were also found to have neuroprotective properties in NMDA induced cell death in rat cerebellum. On the other hand, the combined application of the compounds was not found as protective as ruthenium red applications alone. The present study revealed a neurotoxic feature of ruthenium red, however we also demonstrated a neuroprotective role for it in NMDA-mediated neuron culture. This could be interpreted as a result of the partial agonistic effect of ruthenium red. (c) 2005 Elsevier Ltd. All rights reserved.

Despite the existence of some positive and negative reports on dantrolene in ischemic states, combined application of an endoplasmic reticulum Ca2+ release inhibitor and a calcium channel blocker has not yet been elucidated. In the present study, we have investigated the role of dantrolene in subsequent doses alone or in coexistence with the dihydropyridine calcium antagonist nimodipine (10(-4) M concentration) in glutamate-induced (10(-7) M) neurotoxicity in cerebellar granular cell cultures of rat pups. Glutamate induced neuronal cell death at a concentration of 10(-7) M. Despite the fact that none of the groups tested were able to reverse cell death to control values, dantrolene was found to be effective in preventing glutamate toxicity in cerebellar cultures of rat pups. The protective effect of dantrolene potentialized in combination with nimodipine at all doses tested. The most effective dose of dantrolene was found to be 10(-4)M in combination with nimodipine. As a result, both extracellular and internal calcium stores play important roles in the genesis of neuronal cell death induced by glutamate.

Glutamate (10(-7)m) and one of its non-NMDA receptor agonists, kainic acid (10(-4)m), were administered to rat cerebellar granular cell cultures, and the neuroprotective role of salicylic acid was examined. Glutamate induced 38.58 +/- 1.45% neuronal cell death while kainic acid induced only 21.4 +/- 2.01% despite being 1000 times more concentrated. The most effective dose for the neuroprotective effect of salicylate in glutamate-induced neurotoxicity was 10(-5)m and it had no protective effect at 10(-7)m. With kainic acid-induced toxicity, 10(-6)m salicylate had no protective effect but 10(-5)m and. 10(-4)m salicylic acid were very effective against kainic acid-induced toxicity. As an OH-trapping agent, salicylate had a protective role in NMDA and non-NMDA receptor-activated neuronal cell death. The present study gives some important clues about oxygen free radical generation having an important role in glutamate- and kainic acid-induced neurotoxicity. On the other hand, the neuroprotective effects of salicylic acid in the present study may depend on the pH alterations in salicylic acid solutions.