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OBJECTIVE: There are limited data on nutritional management of infants with intrauterine growth restriction (IUGR). Postnatal protein supplementation for promoting growth is a common clinical practice in neonatology. The present study aims to investigate the consequences of protein supplementation on long-term growth, brain and body weight, brain histology and behavioral outcome in a rat model of IUGR. MATERIALS AND METHODS: Twenty-four IUGR-formed rat puppies and 12 healthy puppies were included in the study. IUGR model was established by low (10%) protein diet throughout pregnancy together with intraperitoneal injection of lipopolysaccharide (LPS). Pups were started to be fed with either standard protein (SP), or high protein (HP) diet until postnatal day (PN) 35. Puppies in the control group were given SP diet for 35 days. Six pups from each group were sacrificed at PN7, remaining six were evaluated by Morris water maze test between PN 30 to 35 days and then sacrificed at PN35. Histologic evaluation of brain tissue was performed at PN7 and PN35. RESULTS: IUGR group displayed lower body and brain weights at PN7 when compared with control. At PN35, SP group achieved similar brain/body weight ratios with control, whereas HP group displayed lowest brain/body weight ratio. The number of TUNEL positive cells was significantly higher and myelin basic protein and oligodendrocyte marker O4 immunoreactivity were significantly lower in HP group when compared with SP at PN35. Neuronal density in prefrontal cortex and hippocampus at PN7 were similar among SP and HP groups, but significantly lower in HP group when compared with SP at PN35. SP group displayed better results in the Morris water maze test when compared with HP group. CONCLUSIONS: Although postnatal HP support is associated with increase in body weight at PN35, it did not result in better brain/body weight ratios in the rat model of IUGR. In IUGR rats, HP diet was associated with increased apoptosis in brain tissue with lower neuronal density and decreased myelination when compared to SP. Furthermore, better neurodevelopmental scores were achieved by SP diet rather than HP support in IUGR. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus. MATERIALS AND METHODS: A total of 60 Wistar albino rat puppies with experimental kernicterus model were included in the study. The Kernicterus was established administering a bilirubin injection via a cisterna magna puncture 30 minutes after ip drug injection. The puppies were divided into five groups with 12 in each group as shown below: a control group, bilirubin group, darbepoetin alpha group, topiramate group and darbepoetin alpha+ topiramate group. Darbepoetin alpha and/or topiramate were administered on day 5 intraperitoneally (ip). At the 6th and 24th hours, bilirubin induced neurological dysfunction (BIND) score was used to assess behavioral changes. Hearing functions were evaluated on days 10 and 28. On day 30, the Water Maze water tank test was implemented to evaluate spatial memory. The rats were sacrificed on days 6 and 34 and apoptosis in the globus pallidus and hippocampus was examined. RESULTS: The BIND score was improved following darbepoetin alpha treatment. Neither darbepoetin alpha nor topiramate therapy ameliorate spatial memory. There were no significant differences between groups in terms of the auditory brainstem response (ABR). The combined use of darbepoetin alpha and topiramate lead to slight decrease in apoptosis. CONCLUSIONS: Darbepoetin alpha or topiramate administration ameliorates bilirubin induced neurological dysfunction in experimental model of kernicterus. [ABSTRACT FROM AUTHOR]

Helicobacter pyloriinfection is one of the most prevalent infections in humans. The high prevalence and the association with peptic ulceration and gastric cancer require simple and non-invasive methods for the diagnosis of the infection. Detection of salivary anti-H. pyloriIgG antibodies has advantages compared with those on serum. In this study, salivary immunoglobulin G response toH. pyloriwas evaluated in 100 consecutive dyspeptic patients by enzyme-linked immunosorbent assay (ELISA), in comparison with culture and histopathologic examination of gastric biopsy specimens obtained at endoscopic procedures and assessed the accuracy of salivary diagnosis of the infection. The overall sensitivity and specificity of the test were 87 and 73%, respectively. These results suggest that saliva testing forH. pyloriantibodies could be used reliably for screening dyspeptic patients in general practice, especially in children in whom venesection is more difficult. [ABSTRACT FROM AUTHOR]

Presents an experiment which examined the electrical properties in metal polyimide silicon (MIS). What polyimides are; Materials and synthesis of the experiment; Results of the experiment; Discussion on the findings; Conclusions on the experiment.

Abstract Background Ovarian cancer (OvCa) most often derives from ovarian surface epithelial (OSE) cells. Several lines of evidence strongly suggest that increased exposure to progesterone (P4) protects women against developing OvCa. However, the underlying mechanisms of this protection are incompletely understood. Methods To determine downstream gene targets of P4, we established short term in vitro cultures of non-neoplastic OSE cells from six subjects, exposed the cells to P4 (10-6 M) for five days and performed transcriptional profiling with oligonucleotide microarrays containing over 22,000 transcripts. Results We identified concordant but modest gene expression changes in cholesterol/lipid homeostasis genes in three of six samples (responders), whereas the other three samples (non-responders) showed no expressional response to P4. The most up-regulated gene was TMEM97 which encodes a transmembrane protein of unknown function (MAC30). Analyses of outlier transcripts, whose expression levels changed most significantly upon P4 exposure, uncovered coordinate up-regulation of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density lipoprotein receptor, ABCG1, endothelial lipase, stearoyl- CoA and fatty acid desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic acute regulatory protein and ABCC6. Highly correlated tissue-specific expression patterns of TMEM97 and the cholesterol biosynthesis genes were confirmed by analysis of the GNF Atlas 2 universal gene expression database. Real-time quantitative RT-PCR analyses revealed 2.4-fold suppression of the TMEM97 gene expression in short-term cultures of OvCa relative to the normal OSE cells. Conclusion These findings suggest that a co-regulated transcript network of cholesterol/lipid homeostasis genes and TMEM97 are downstream targets of P4 in normal OSE cells and that TMEM97 plays a role in cholesterol and lipid metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE cells might play a role in conferring protection against OvCa.

Abstract Background Balancing selection operating for long evolutionary periods at a locus is characterized by the maintenance of distinct alleles because of a heterozygote or rare-allele advantage. The loci under balancing selection are distinguished by their unusually high polymorphism levels. In this report, we provide statistical and comparative genetic evidence suggesting that the SDHA gene is under long-term balancing selection. SDHA encodes the major catalytical subunit (flavoprotein, Fp) of the succinate dehydrogenase enzyme complex (SDH; mitochondrial complex II). The inhibition of Fp by homozygous SDHA mutations or by 3-nitropropionic acid poisoning causes central nervous system pathologies. In contrast, heterozygous mutations in SDHB, SDHC, and SDHD, the other SDH subunit genes, cause hereditary paraganglioma (PGL) tumors, which show constitutive activation of pathways induced by oxygen deprivation (hypoxia). Results We sequenced the four SDH subunit genes (10.8 kb) in 24 African American and 24 European American samples. We also sequenced the SDHA gene (2.8 kb) in 18 chimpanzees. Increased nucleotide diversity distinguished the human SDHA gene from its chimpanzee ortholog and from the PGL genes. Sequence analysis uncovered two common SDHA missense variants and refuted the previous suggestions that these variants originate from different genetic loci. Two highly dissimilar SDHA haplotype clusters were present in intermediate frequencies in both racial groups. The SDHA variation pattern showed statistically significant deviations from neutrality by the Tajima, Fu and Li, Hudson-Kreitman-Aguadé, and Depaulis haplotype number tests. Empirically, the elevated values of the nucleotide diversity (% π = 0.231) and the Tajima statistics (D = 1.954) in the SDHA gene were comparable with the most outstanding cases for balancing selection in the African American population. Conclusion The SDHA gene has a strong signature of balancing selection. The SDHA variants that have increased in frequency during human evolution might, by influencing the regulation of cellular oxygen homeostasis, confer protection against certain environmental toxins or pathogens that are prevalent in Africa.

Abstract Background A mannosyltransferase gene (ALG9, DIBD1) at chromosome band 11q23 was previously identified to be disrupted by a balanced chromosomal translocation t(9;11)(p24;q23) co-segregating with bipolar affective disorder in a small family. Inborn ALG9 deficiency (congenital disorders of glycosylation type IL) is associated with progressive microcephaly, seizures, developmental delay, and hepatomegaly. It is unknown whether common variations of ALG9 predispose to bipolar affective disorder. Methods We tested five polymorphic markers spanning ALG9 (three intragenic and one upstream microsatellite repeats and one common missense variation, V289I (rs10502151) for their association with bipolar I disorder in two pedigree series. The NIMH (National Institute of Mental Health) pedigrees had a total of 166 families showing transmissions to 250 affected offspring, whereas The PITT (The University of Pittsburgh) pedigrees had a total of 129 families showing transmissions to 135 cases. We used transmission disequilibrium test for the association analyses. Results We identified three common and distinct haplotypes spanning the ALG9 gene. We found no statistically-significant evidence of transmission disequilibrium of marker alleles or multi-marker haplotypes to the affected offspring with bipolar I disorder. Conclusion These results suggest that common variations in ALG9 do not play a major role in predisposition to bipolar affective disorder.

Systemic chemotherapy (SC) has a negative effect on ovarian functions. The aim of this study is to investigate the effect of SC on anti-müllerian hormone (AMH) levels, antral follicle counts (AFC) and ovarian volumes (MOV) in patients with BC. The demographic, clinical and pathological features of premenopausal breast cancer (BC) patients who were operated in the Istanbul Florence Nightingale Hospital were recorded. AMH levels, AFC and MOV measurements were performed before and after adjuvant SC in 3-month periods. The patients who did not have menstruel cycles for 6 months or longer had been classified as chemotherapy induced amenorrhea (CIA). The effects of different chemotherapy regimens on AMH, AFC and MOV in terms menstruel cycles resumption and CIA were investigated. Seventy one patients were eligible for the study, and median age of them was 38 years (ranged from 23 to 51 years). Median follow-up was 37 months (ranged from 20 to 51 months), CIA developed in 62% of patients. AMH, AFC, and MOV significantly decreased one year after SC (p < 0.0001). AMH before chemotherapy (median: 1,520 vs 0,755, p = 0.001), at the end of first year (median: 0,073 vs 0,010 ng/ml, p = 0.030) and pre-treatment AFC (median12 vs 4,50, p = 0.026) was lower in patients with CIA comparing those without CIA. In multivariate logistic regression analysis, AMH levels (OR:0.273, 95%: 0.102 – 0.733, p = 0.010) and AFC (OR: 1,180, 95% CI; 1,016-1,369, p = 0.030) before SC were the most valuable and earliest factors to predict CIA. There were no significant relationships between age of the patients (≤30vs>30), BMI (30vs> 30), SC regimen and number of cycles (4 vs > 4) and CIA (p > 0.05). Table 254P muitivariet analyses with logistic regrettion for CIA Table UNIVARIET MULTIVARIET OR 95% CI OR 95% CI ER 0,19 0,038 - 0,891 0,035 0,002 0,000 - 0,111 0,002 HER 2 0.80 0,435 - 2,936 1,130 ALND PERFORMED 1,75 0,653 - 4,702 0,265 AMH-1 0,64 0,454 - 0,914 0,014 0,273 0,102 - 0,733 0,010 AMH-5 0,23 0,063 - 0,812 0,023 0,009 0,000 - 0,754 0,037 AFC-1 0,87 0,780 - 0,961 0,007 0,735 0,572 - 0,944 0,016 AFC-5 0,93 0,741 - 1,165 0,527 MOV-1 1,00 0,987 - 1,021 0,686 MOV-5 0,98 0,854 - 1,158 0,790 TAXANE/W&İTHOUTTAXANE 0,71 0,267 - 1,910 0,503 TC/AC 0,85 0,209 - 3,491 0,825 AGE 35 4,66 1,613 - 13,498 0,004 CHEMONUMBER 0,24 0,080 - 0,766 0,017 BMI 25 2,57 0,929 - 7,118 0,069 SC significantly decreases AMH and AFC values independently of chemotherapeutic agents in patients with BC. The low AMH levels and less AFC before SC may predict CIA. İstanbul Demiroğlu Bilim University. Has not received any funding. All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Introduction. Identification of the gene involved with hereditary paragangliomas (PGL1) was the objective. At least 50% of all glomus tumours have a positive family history via an autosomal dominant inheritance with genomic imprinting linked to chromosome 11q 23. Methods. DNA sequences revealed the presence of the SDHD gene in the PGL1 gene-related glomus families. Results. In almost all PGL-1-related glomus families, four germline mutations were found in the SDHD gene (Succinate dehydrogenase, subunit D). This is a special (tumour-suppressor) gene, encoding a mitochondrial protein that takes part in the respiratory chain complex. Surprisingly, the SDHD mutation was found in 40% of non-familial cases. Conclusion. The discovery of the SDHD gene encoding for hereditary paragangliomas offers both clinical and scientific possibilities of presymptomatic DNA research for optimal genetic counselling, efficient clinical examination, radiodiagnostics and follow-up, insight into the mechanism of genomic imprinting and into the molecular process from mutation to tumour in extremely slow-growing paragangliomas. [ABSTRACT FROM AUTHOR]