The effect of acute topiramate administration on morphine withdrawal syndrome and brain-derived neurotrophic factor in central nervous system.

OBJECTIVES: Nucleus accumbens plays an important role in opioid addiction. Topiramate, increases postsynaptic gamma-aminobutyric acid receptor activity and antagonizes glutamatergic activity. Brain-derived neurotrophic factor (BDNF), which plays a key role in synaptic plasticity, is produced from proBDNF. The aim of this study is to investigate the effects of 100 µM topiramate applied into the lateral ventricle or nucleus accumbens on naloxone-induced morphine withdrawal and the BDNF/proBDNF ratio in the frontal cortex. METHODS: In the study, 36 adult male Wistar rats weighing 250-350 g were used. Morphine dependence was created with morphine pellets following guide cannula implantations. Withdrawal findings were evaluated in naloxone-induced morphine withdrawal syndrome following topiramate administration, and locomotor activity measurements were performed simultaneously. The brains of sacrificed animals were removed for determination of BDNF/proBDNF ratio. RESULTS: Topiramate administered by either route significantly suppressed the number of jumps in morphine withdrawal. Topiramate applied into the nucleus accumbens significantly reduced stereotypical behavior in morphine withdrawal, but did not cause any changes in other locomotor activity behaviors. Topiramate applied into the lateral ventricle significantly decreased the BDNF/proBDNF ratio, whereas administered into the nucleus accumbens significantly increased this ratio. CONCLUSION: The findings of this study indicate that topiramate administered into the lateral ventricle and nucleus accumbens reduces naloxone-induced morphine withdrawal symptoms, stereotypical locomotor activity, and changes the BDNF/proBDNF ratio.

Propensities of Some Amino Acid Pairings in α-Helices Vary with Length.

The results of secondary structure prediction methods are widely used in applications in biotechnology and bioinformatics. However, the accuracy limit of these methods could be improved up to 92%. One approach to achieve this goal is to harvest information from the primary structure of the peptide. This study aims to contribute to this goal by investigating the variations in propensity of amino acid pairings to α-helices in globular proteins depending on helix length. (n):(n + 4) residue pairings were determined using a comprehensive peptide data set according to backbone hydrogen bond criterion which states that backbone hydrogen bond is the dominant driving force of protein folding. Helix length is limited to 13 to 26 residues. Findings of this study show that propensities of ALA:GLY and GLY:GLU pairings to α-helix in globular protein increase with increasing helix length but of ALA:ALA and ALA:VAL decrease. While the frequencies of ILE:ALA, LEU:ALA, LEU:GLN, LEU:GLU, LEU:LEU, MET:ILE and VAL:LEU pairings remain roughly constant with length, the 25 residue pairings have varying propensities in narrow helix lengths. The remaining pairings have no prominent propensity to α-helices.

Correction to: Propensities of Amino Acid Pairings in Secondary Structure of Globular Proteins.

In the original version of this article, under the Introduction section in paragraph starting "Some findings of this study..." the "Sect. 10" should be changed to "Sect. 3".

Propensities of Amino Acid Pairings in Secondary Structure of Globular Proteins.

A class of secondary structure prediction algorithms use the information from the statistics of the residue pairs found in secondary structural elements. Because the protein folding process is dominated by backbone hydrogen bonding, an approach based on backbone hydrogen-bonded residue pairings would improve the predicting capabilities of these class algorithms. The reliability of the prediction algorithms depends on the quality of the statistics, therefore, of the data set. In this study, it was aimed to determine the propensities of the backbone hydrogen-bonded residue pairings for secondary structural elements of α-helix and ß-sheet in globular proteins using a new and comprehensive data set created from the peptides deposited in Worldwide Protein Data Bank. A master data set including 4882 globular peptide chains with resolution better than 2.5 Å, sequence identity smaller than 25% and length of no shorter than 100 residues were created. Separate data sub sets also were created for helix and sheet structures from master set and each sub set includes 4594 and 4483 chains, respectively. Backbone hydrogen-bonded residue pairings in helices and sheets were detected and the propensities of them were represented as odds ratios (observed/[random or expected]) in matrices. Propensities assigned by this study to the residue pairings in secondary structural elements (as helix, overall strands, parallel strands and antiparallel strands) differ from the previous studies by 19 to 34%. These dissimilarities are important and they would cause further improvements in secondary structure prediction algorithms.

Sex hormone binding globulin gene polymorphisms and metabolic syndrome in postmenopausal Turkish women.

BACKGROUND: Insulin resistance is associated with obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, and cardiovascular disease. Constellation of these risk factors iscalled metabolic syndrome (MetS). MetS is common among postmenopausal women. Low sex hormone binding globulin (SHBG) levels associate with an increased risk of MetS in postmenopausal women. Variations in SHBG gene associate with low levels of circulating SHBG levels. We aim to study the association between SHBG gene polymorphisms - rs1799941 (A/G) and rs6257 (T/C) - with MetS among postmenopausal women. METHODS: The study population consisted of 182 postmenopausal women with MetS and 119 control subjects. We analyzed the allele frequencies of SHBG gene polymorphisms in relation to the risk components of MetS. RESULTS: MetS patients displayed significantly lower SHBG levels compared to the lean control subjects (p = 0.036). rs1799941 A allele was associated with high SHBG levels (p = 0.031), low blood pressure, body mass index and waist circumference. The number of 'high risk' alleles (G allele of the rs1799941 and T allele of rs6257) correlated positively with waist circumference (r = 0.203, p = 0.006) and negatively with SHBG levels (r = -0.291, p = 0.024). CONCLUSIONS: SHBG gene polymorphisms associate with SHBG levels and MetS risk components among postmenopausal women. Hence, A allele (rs1799941) may have a protective effect for MetS through its association with high SHBG levels among postmenopausal women.

Investigation of the association between dopamine D1 receptor gene polymorphisms and essential hypertension in a group of Turkish subjects.

Dopamine has been shown to influence blood pressure by regulating renal sodium excretion through direct interaction with the dopamine receptors, especially with the Dopamine D1 receptor (DRD1). To better understand the role of polymorphisms in those effects, we investigated the association between two polymorphic sites in the DRD1 promoter region (A-48G, G-94A) and essential hypertension in the Turkish population. The DRD1 variants were genotyped by restriction fragment length polymorphism (RFLP) analysis. A total of 205 unrelated individuals were enrolled in the study. We found that genotype distributions and allele frequencies of the control and hypertensive subjects were very similar and did not show any significant difference with respect to blood pressure (BP) and hypertension. Contribution of the gene variances in BP or hypertension by sex differences and dependence on body mass index (BMI) were also evaluated. Distribution of genotypes and allele frequencies were found to be in line with previous reports. However, increments detected in hypertensive subjects were far from being statistically significant.

The role of G protein ß3 subunit polymorphisms C825T, C1429T, and G5177A in Turkish subjects with essential hypertension.

Hypertension is a multifactorial disorder that constitutes a major risk factor for the cardiovascular system. Heterotrimeric G-proteins, which couple receptors for diverse extracellular enzymes or ion channels, are correlated with disease mechanisms. Several studies have demonstrated an association between G protein polymorphisms and essential hypertension in some populations, although contradictive results also exist. In this study, we have investigated the potential role of the C825T, C1429T, and G5177A polymorphisms of the ß3 subunit of G-proteins in essential hypertension in a group of Turkish subjects. Genomic DNA from 106 normotensive individuals (117.4 ± 13.1, 75.2 ± 10.5; systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels, respectively) and 101 hypertensive subjects (152.3 ± 18.0, 92.5 ± 11.6; SBP and DBP levels, respectively) were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods for these polymorphisms. Allele frequencies of the polymorphisms were consistent with Hardy Weinberg equilibrium, except for the C825T polymorphism (χ(2) = 7.8). The frequencies of the 825T and 1429T variants were higher in hypertensive subjects compared to those of controls. Differences between hypertensives and controls were not statistically significant, though difference was very close to significance for C825T (p = 0.056 and 0.099 for 825T and 1429T, respectively). T allele frequency in overall population showed significant association with hypertension for C825T (0.0134). The prevalence of the 5177A-variant was very low and all subjects carrying it were heterozygotes in both groups.

G protein mutations in pituitary tumors: a study on Turkish patients.

Activating mutations of the G proteins, Gsalpha (gsp) and Gi2alpha (gip) have been reported in subsets of pituitary tumors. The objective of the study was to assess the frequency of gsp and gip mutations in pituitary tumors from Turkish patients and to investigate the possibility of mutations of protein kinase A catalytic subunit (PKAC) that activates the downstream effectors of adenylyl cyclase. PCR-amplified genomic DNA was analyzed for the presence of mutations in codons 201 and 227 of Gsalpha, codon 179 and 205 of Gi2alpha and codon 196 of PKAC, by single strand conformation polymorphism analysis, allele-specific oligonucleotide hybridization and DNA sequencing. Twenty-two patients from Turkey, 15 females and 7 males were investigated; 7 somatotroph adenomas, 7 clinically non-functioning tumors, 7 prolactinomas and 1 corticotroph adenoma. G protein mutations were identified in 6 of 22 (27.3%) pituitary tumors. Four tumors (3/7 somatotroph adenomas, 43%, 1/7 clinically non-functioning tumor) demonstrated gsp mutations at codon 201 arginine to cysteine and one recurrent somatotroph adenoma demonstrated a mutation of the Gi2alpha gene at codon 193 lysine to arginine. One tumor exhibited a C to T variation in the intervening sequence between codons 179 and 205 of the Gi2alpha gene. No mutations at codon 227 of Gsalpha, codons 179 and 205 of Gi2alpha and codon 196 of the PKAC gene were identified.