Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium

We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ~500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene.     

Resistance to macrolide, lincosamide and streptogramin antibiotics in staphylococci isolated in Istanbul, Turkey

The purpose of this study was to investigate the prevalence and genetic mechanisms of erythromycin resistance in staphylococci. A total of 102 erythromycin resistant non-duplicate clinical isolates of staphylococci [78 coagulase negative stapylococci (CNS), 24 Staphylococcus aureus] were collected between October 2003 and August 2004 in Istanbul Faculty of Medicine in Turkey. The majority of the isolates were from blood and urine specimens. Antimicrobial susceptibilities were determined by the agar dilution procedure and the resistance phenotypes by the double disk induction test. A multiplex PCR was performed, using primers specific for erm(A), erm(B), erm(C), and msrA genes. Among the 78 CNS isolates, 57.8% expressed the MLSB-constitutive, 20.6% the MLSB-inducible, and 21.6% the MSB phenotypes. By PCR, 78.2% of these isolates harbored the erm(C) gene, 8.9% erm(A), 6.4% erm(B), and 11.5% msrA genes. In S. aureus, the constitutive MLSB (58.3%) was more common than the inducible phenotype (20.8%). erm(A) was detected in 50% and erm(C) in 62.5% of the isolates, while 37.5% contained both erm(A) and erm(C). erm(C)-associated macrolide resistance was the most prevalent in CNS, while erm(C) and erm(A, C) was the most prevalent in S. aureus.     

Should chronic obstructive pulmonary disease outpatients be routinely evaluated for trace elements?

We searched for serum concentrations of trace elements and correlated them to malondialdehyde (MDA), which is an indirect marker of oxidative stress, in order to clarify if routine evaluation is necessary in chronic obstructive pulmonary disease (COPD) outpatients. Serum concentrations of copper (Cu), zinc (Zn), and magnesium (Mg) were determined by atomic absorption spectrophotometry and iron (Fe) by a ILLab 1800 autoanalyzer with ILLab test kits. Serum MDA concentrations were detected in terms of TBARS (thiobarbituric acid reactive substances) spectrophotometrically. Serum Cu, Zn, Mg, Fe, and MDA concentrations in patient and control groups were all in the normal reference range. The results respectively were as follows: Cu:123±29.2 and 122.2±23.4 μg/dL; Zn: 87.8±17.8 and 96.9 ± 12.9 μg/dL; Mg: 2.3±0,5 and 2.04±0.28 mg/dL; Fe: 73.8±35.5 and 80.7±51.2 μg/dL; MDA: 1.09±0.11 and 0.95±0.06 nmol/L. MDA was not correlated to Cu, Zn, Mg, or Fe (p>0.05 for all). The serum Zn concentration of COPD group was lower than the control group (p=0.042), whereas the Mg concentration was higher (p=0.021). There was no statistical difference in other study parameters. Oxidative stress was not increased in clinically stable, regularly treated COPD patients. Although there was no deficiency in trace elements (Cu, Fe, Mg, and Zn), serum Zn was close to the lower limit of the reference value. There is no need for routine evaluation of trace elements in clinically stable, regularly treated COPD outpatients.     

“Robin Hood” of Techno-Turkey or Organ Trafficking in the State of Ethical Beings

Dr S. is a famous transplant surgeon in the Middle East. He operates "underground" on wealthy patients in different countries, from Israel to Turkey to Russia. The media refer to him as the "Organ Mafia doctor," and patients diagnosed with renal failure speak of him sardonically as "Robin Hood," acknowledging that he takes organs from the poor to give to the rich. But ethical issues of organ trafficking are not limited to marginal private clinics and "Mafia" doctors. All-living related organ transplants in Turkey involve similar ethical dilemmas: many related or nonrelated organ recipients pay their donors, and demand continues to rise. This paper explores practices in state and university hospitals and the ethical dilemmas doctors encounter to understand where and how judicial, cultural, and social categories of "human rights" and "crime" are constructed in our high-tech world.     

Effects of garlic extract consumption on plasma and erythrocyte antioxidant parameters in atherosclerotic patients

Effects of ingesting garlic extract on plasma and erythrocyte antioxidant parameters of atherosclerotic patients were investigated in this study. Eleven patients with atherosclerosis participated in the study. They ingested a dose of 1 ml/kg body weight of garlic extract daily for 6 months (study period). Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde, MDA and xanthine oxidase, XO) and antioxidant (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) parameters were studied in plasma and erythrocytes obtained from the patients. Blood samples obtained from 11 healthy subjects served as the controls. Plasma XO activity and MDA levels were higher, but plasma and erythrocyte GSH-Px activities were lower, in patients with atherosclerosis relative to those of the control group. Our results showed that ingestion of garlic extract leads to significantly lowered plasma and erythrocyte MDA levels in the patients even in the absence of changes in antioxidant enzyme activities. Our results also demonstrated the presence of oxidant stress in blood samples from patients with atherosclerosis, but ingesting garlic extract prevented oxidation reactions by eliminating this oxidant stress. Thus, it is possible that reduced peroxidation processes may play a part in some of the beneficial effects of garlic in atherosclerotic diseases.     

Attitude toward genetic testing for cancer risk in Istanbul

To identify attitudes toward genetic testing, and the effects of this information on decisions regarding issues such as pregnancy, abortion, and prophylactic surgery, several subsets of the Turkish population were surveyed in hospital settings. Individuals (n = 179) chosen arbitrarily from four different subsets of a Turkish population were asked to participate in a confidential 23-question survey. Survey participants were familiar with the concept of cancer being a familial disease (85.5%), and 84.7% of them expressed interest in genetic testing to determine cancer risk, 83.9% would have their fetuses tested for such cancer risk, 65.1% would terminate their pregnancies, 92.2% would have their children tested if they were determined to have an increased cancer risk, 71.9% would agree to undergo prophylactic oophorectomy or orchiectomy and 67.6% would have mastectomy/prostatectomy should there be an increased cancer risk to these organs. It appears that at least the sampled segment of a Turkish population is willing to undergo genetic testing to determine if they are at increased risk for cancer. The feasibility and acceptance of genetic testing and the influence of education and genetic counseling in the Turkish people should further be evaluated with a larger stratified sample of the population.     

Solubilizing poorly soluble antimycotic agents by emulsification via a solvent-free process

The purpose of this study was to formulate itraconazole and ketoconazole as oil/water emulsions for parenteral delivery by using a solvent-free homogenization process, namely SolEmuls (solubilization by emulsification) technology. The drugs were incorporated in the commercial emulsion Lipofundin MCT 20%, composed of a medium-chain triglyceride/long-chain triglyceride (MCT/LCT) oil phase (1:1) and stabilized with 1.2% lecithin. Different parameters such as drug-loading capacity, long-term physical stability, and completeness of drug dissolution were investigated. Up to 10.0 mg/mL complete drug dissolution was achieved with itraconazole; at 20 mg/mL hybrid dispersion was obtained. Itraconazole-loaded emulsions were physically stable for 9 months (data up to now). Ketoconazole showed physical instability in the Lipofundin emulsion, which was stabilized with only 1.2% lecithin. Stabilization of ketoconazole-loaded emulsions was achieved using additionally Tween 80 as steric stabilizer. Higher concentrations of ketoconazole (ie, 10.0 mg/mL concentrated ketoconazole emulsions) were also produced with additional 2.0% Tween 80. Ketoconazole-loaded emulsions, 1 mg/mL, which were stabilized with 2.0% Tween 80, were stable for a period of 6 months. It can be concluded, after formulating amphotericin B and carbamazepine with SolEmuls technology, that SolEmuls was also applicable to the antimycotic agents itraconazole and ketoconazole, yielding IV-applicable emulsions with cost-effective production technologies.     

ATXN2 and Its Neighbouring Gene SH2B3 Are Associated with Increased ALS Risk in the Turkish Population

Expansions of the polyglutamine (polyQ) domain (≥34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1–4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In accordance with other studies, our results confirmed that 31–32 polyQ repeats in the ATXN2 gene are associated with risk of developing ALS in 1.7% of the Turkish ALS cohort (p = 0.0172). Additionally, a significant association of a 136 kb haplotype block across the ATXN2 and SH2B3 genes was found in 19.4% of a subset of our ALS cohort and in 10.1% of the controls (p = 0.0057, OR: 2.23). ATXN2 and SH2B3 encode proteins that both interact with growth receptor tyrosine kinases. Our novel observations suggest that genotyping of SNPs at this locus may be useful for the study of ALS risk in a high percentage of individuals and that ATXN2 and SH2B3 variants may interact in modulating the disease pathway.     

Selenium Inhibits Proliferation Signaling and Restores Sodium/Potassium Pump Function of Diabetic Rat Aorta

Diabetes is characterized with increased oxidant stress, vasculopathy, and neuropathy. In diabetic vasculopathy, the observed thickening of the media and intima is not only a result of vascular smooth muscle cell proliferation but also due to modification of the extracellular matrix by these cells. Also, there is hampered membrane function and a reduction in sodium pump expression in the vessels of the diabetic animals. Selenium, being a trace element, has both insulinomimetic and antioxidant effects. Thus, we hypothesized that selenium treatment will reduce proliferation, restore physiology, and correct increased proliferation signaling of diabetic aorta. Diabetes was induced by streptozotocin (50 mg/kg body weight), and rats were then treated with sodium selenate (15 mumol/kg body weight/day) for 4 weeks. Our data from diabetic rats showed an increase in proliferation rate and matrix metalloproteinase activity in aortic cell cultures. We observed marked increases in MAPK phosphorylation and caveolin 1 expression but a decrease in Na(+)/K(+) ATPase activity in diabetic rat aorta homogenates. Selenium treatment resulted in complete normalization of the above parameters to control level, while it increased Na(+)/K(+) pump activity by 40%. Our results suggest that selenium treatment of diabetics can play beneficial role in protecting vascular architecture and function against diabetes-induced pathology.