Investigation on two polymorphisms effective on HDL-C concentration in patients with coronary artery disease using restriction fragment length polymorphism

Background and aim: High density lipoprotein cholesterol (HDL-C) is a known inverse predictor of coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are key proteins in HDL-C metabolism so that decreased CETP or HL activity is associated with high HDL-C. -629C/A polymorphism in promoter of CETP gene and-514C/T in promoter of HL gene were previously reported to reduce related protein level in plasma. In this study association of these polymorphisms with CHD related to HDL-C level were investigated. Methods: In this analytical-descriptive study 321 subjects underwent coronary angiography and divided in two groups base on angiogram (non CAD = 135 and CAD = 186). Serum lipids profile was measured by standard procedure and genotype was detected using PCR-RFLP method. Results: Overall the CETP genotype frequencies were in CAD patients: 58.8% (n=110), 28.9% (n=54) and 12.3% (n=23) and in non CAD patients: 45.2% (n=61), 41.5% (n=56) and 13.3% (n=18) for AA, CA and CC respectively. HL genotype frequencies were in CAD patients: 61.6% (n=114), 33.5% (n=62) and 4.9% (n=9) and in non CAD patients: 65.9% (n=89), 27.4% (n=37) and 6.7% (n=9) for CC, CT and TT respectively. In control group HDL-C concentration was higher for AA than CC genotype in -629C/A, and also for TT than CC genotype in -514C/T. Allele A in all subjects and T allele in woman were higher in CAD than non CAD group. A high increase in HDL-C level (10. mg/dl) was observed in individuals with CETP-AA/LIPC-TT and CETP-CA/LIPC-TT relative to CETP-CC/LIPC-CC across all subjects (P< 0.001) but there was no difference in CAD prevalence. Conclusion: Allele A from -629C/A, and T from -514C/T even with the increasing of HDL-C concentration had higher frequency in CAD than non CAD group. Therefore, it seems that HDL-C didn’t protect coronary artery when CETP or HL activity was reduced by these polymorphisms

I405V and -629C/A polymorphisms of the cholesteryl ester transfer protein gene in patients with coronary artery disease

Background: Cholesteryl ester transfer protein (CETP) plays a main role in high-density lipoprotein metabolism. CETP gene possesses several single nucleotide polymorphisms which have been associated with plasma high-density lipoprotein cholesterol (HDL-C) concentrations. The aim of this study was to determine the association of CETP -629C/A and I405V polymorphisms with coronary artery disease (CAD) in Iranian population. Methods: The presence of two CETP gene polymorphisms -629C/A and I405V were studied in 187 unrelated CAD cases and 136 controls. All the samples were clinically examined and lipid profile was estimated. Genotyping was performed using polymerase chain reaction/restriction fragment length polymorphism method. Results: The frequency of -629C/A and I405V allelic variants were found to be 0.732 and 0.366 in cases and 0.658 and 0.348 in controls, respectively. The frequency of A allele of -629C/A polymorphism in cases was significantly higher than that of controls. HDL-C in AA genotype was higher than CA and CC genotypes in controls. No significant effect of II, IV and VV genotypes was found in lipid profiles. Conclusion: No significant association was found between CETP I405V polymorphism and increased risk of CAD in Azeri population studied. AA genotype of -629C/A increased HDL but the risk of CAD in this genotype might be higher than CC genotype

Digenic inheritance in autosomal recessive non-syndromic hearing loss cases carrying GJB2 heterozygote mutations: Assessment of GJB4, GJA1, and GJC3

Objective: Autosomal recessive non-syndromic hearing loss (ARNSHL) can be caused by many genes. However, mutations in the GJB2 gene, which encodes the gap-junction (GJ) protein connexin (Cx) 26, constitute a considerable proportion differing among population. Between 10 and 42 percent of patients with recessive GJB2 mutations carry only one mutant allele. Mutations in GJB4, GJA1, and GJC3 encoding Cx30.3, Cx43, and Cx29, respectively, can lead to HL Combination of different connexins in heteromeric and heterotypic GJ assemblies is possible. This study aims to determine whether variations in any of the genes GJB4, GJA1 or GJC3 can be the second mutant allele causing the disease in the digenic mode of inheritance in the studied GJB2 heterozygous cases. Methods: We examined 34 unrelated GJB2 heterozygous ARNSHL subjects from different geographic and ethnic areas in Iran, using polymerase chain reaction (PCR) followed by direct DNA sequencing to identify any sequence variations in these genes. Restriction fragment length polymorphism (RFLP) assays were performed on 400 normal hearing individuals. Results: Sequence analysis of GJB4 showed five heterozygous variations including cA51C>A, c.219C>T, c.507C>G, c.155_158delTCTG and c.542C>T, with only the latter variation not being detected in any of control samples. There were three heterozygous variations including c.758C>T, c.717G>A and c.3*dupA in GJA1 in four cases. We found no variations in GJC3 gene sequence. Conclusion: Our data suggest that GJB4 c.542C>T variant and less likely some variations of GJB4 and GJA1, but not possibly GJC3, can be assigned to ARNSHL in GJB2 heterozygous mutation carriers providing clues of the digenic pattern. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Therapeutic Effects of Laser on Partial Osteotomy in the Rat Model of Hypothyroidism

Introduction: Several experimental studies have displayed positive result for laser radiation on stimulating bone regeneration in recent years. The purpose of this experimental study was to determine low-level laser (LLL) effects on partial bone defects in hypothyroidism male rat.Methods: Forty male Wistar rats were randomly distributed as below groups: hypothyroidism + laser (Hypo + laser), hypothyroidism (Hypo), and control. Four weeks after surgery, the tibia bone was removed. Biomechanical and histological examinations were performed immediately.Results: Our results showed significant reduction in the absorption of energy, resistance in bending deformation (bending stiffness), maximum force, high stress load, trabecular bone volume, and number of osteocytes, osteoblasts and osteoclasts in the osteotomy site in hypothyroidism rats compared to hypothyroidism + laser group (P &lt; 0.05).Conclusion: The results indicated that using laser may improve fracture regeneration and it may accelerate bone healing in hypothyroidism rat

Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss

Background: Hearing loss (HL) is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB) have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. Methods: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with >= 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. Results: Sixteen families were found to be linked to seven different known loci, including DFNB I (6 families), DFNB4 (3 families +1 family with Pendred syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1 family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. Conclusion: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families

Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with autosomal recessive non-syndromic hearing loss

Background and aim: The incidence of prelingual hearing loss (HL) is about 1 in 1000 neonates of which, more than 60% of cases are inherited. Non-syndromic HL (NSHL) is extremely heterogeneous: more than 100 loci have been identified. The most common form of NSHL is the autosomal recessive form (ARNSHL). Here, we have investigated CX26 (GJB2) and CX30 (GJB6) gene mutation and linkage analysis of 3 known loci in Iranian families. Methods: A cohort of 36 big ARNSHL pedigrees from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations using direct sequencing and multiplex PCR, respectively. The negative mutations pedigrees for the above- mentioned mutations, were then tested for the linkage to the 3 known loci, including DFNB3(MYO7A), DFNB4(SLC26A4) and DFNB7/11(TMC1), using STR markers and conventional PCR and PAGE. Results: Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4 and 1 family was linked to DFNB7/11. Conclusion: DFNB1 (GJB2) and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian populatio

Mutation analysis of GJB2 and GJB6 genes and the genetic linkage analysis of five common DFNB loci in the Iranian families with autosomal recessive non-syndrom

The incidence of pre-lingual hearing loss (HL) is about 1 in 1000 neonates. More than 60% of cases are inherited. Non-syndromic HL (NSHL) is extremely heterogeneous: more than 130 loci have been identified so far. The most common form of NSHL is the autosomal recessive form (ARNSHL). In this study, a cohort of 36 big ARNSHL pedigrees with 4 or more patients from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations using direct sequencing and multiplex PCR methods, respectively. The negative pedigrees for the above-named genes were then tested for the linkage to 5 known loci including DFNB3 (MYO7A), DFNB4 (SLC26A4), DFNB7/11 (TMC1), DFNB21 (TECTA) and DFNB59 (PJVK) by genotyping the corresponding STR markers using PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4, 1 family to DFNB7/11 and 1 family to DFNB21. No family was linked to DFNB59. GJB2 included 16.6% of the causes of ARNSHL in our study. In the remaining negative families, DFNB4 accounted for 10% of the causes. Other loci including DFNB7/11 and DFNB21 were each responsible for 3.3% of the etiology. Thus, DFNB1(GJB2) and DFNB4 are the main causes of ARNSHL in our study and GJB6 mutations (del D13S1830, del D13S1854), DFNB3 and DFNB59 were absent. Totally, 30.5% of the ARNSHL etiology was found in this study

Anisotropic Properties of Articular Cartilage in an Accelerated In Vitro Wear Test

Many material properties of articular cartilage are anisotropic, particularly in the superficial zone where collagen fibers have a preferential direction. However, the anisotropy of cartilage wear had not been previously investigated. The objective of this study was to evaluate the anisotropy of cartilage material behavior in an in vitro wear test. The wear and coefficient of friction of bovine condylar cartilage were measured with loading in directions parallel (longitudinal) and orthogonal (transverse) to the collagen fiber orientation at the articular surface. An accelerated cartilage wear test was performed against a T316 stainless-steel plate in a solution of phosphate buffered saline with protease inhibitors. A constant load of 160 N was maintained for 14000 cycles of reciprocal sliding motion at 4 mm/s velocity and a travel distance of 18 mm in each direction. The contact pressure during the wear test was approximately 2 MPa, which is in the range of that reported in the human knee and hip joint. Wear was measured by biochemically quantifying the glycosaminoglycans (GAGs) and collagen that was released from the tissue during the wear test. Collagen damage was evaluated with collagen hybridizing peptide (CHP), while visualization of the tissue composition after the wear test was provided with histologic analysis. Results demonstrated that wear in the transverse direction released about twice as many GAGs than in the longitudinal direction, but that no significant differences were seen in the amount of collagen released from the specimens. Specimens worn in the transverse direction had a higher intensity of CHP stain than those worn in the longitudinal direction, suggesting more collagen damage from wear in the transverse direction. No anisotropy in friction was detected at any point in the wear test. Histologic and CHP images demonstrate that the GAG loss and collagen damage extended through much of the depth of the cartilage tissue, particularly for wear in the transverse direction. These results highlight distinct differences between cartilage wear and the wear of traditional engineering materials, and suggest that further study on cartilage wear is warranted. A potential clinical implication of these results is that orienting osteochondral grafts such that the direction of wear is aligned with the primary fiber direction at the articular surface may optimize the life of the graft

Carbamazepine and the QTc interval: any association?

Abstract Objective: To determine whether carbamazepine monotherapy in epilepsy patients is or is not associated with prolongation of the QTc interval. Methods: This case-control study enrolled 100 consecutive patients with generalized tonic-clonic seizures. Fifty patients were already taking carbamazepine for a variable time, and the rest (n=50) were not on any antiepileptic drug. The QTc interval was calculated after doing a resting 12-lead ECG examination on a single occasion. Results: Of the 50 patients who had received carbamazepine, 11 patients displayed prolongation of their QTc interval, while 8 patients out of the 50 in the control group had QTc interval prolongation after correction for gender; p value =0.49, OR 1.36, 95% CI 0.54-3.29. Conclusion: This study demonstrated no statistically signifi cant association between carbamazepine monotherapy and prolongation of the QTc interval. Carbamazepine does not seem to prolong the QT interval when used as monotherapy for epilepsy. The presence of prolonged QTc interval in such patients should prompt a search for co-factors that prolong this interval, such as multiple medications, electrolytes disturbances, structural heart disease, and congenital long QT interval syndromes

Uncertainty quantification of granular computing‑neural network model for prediction of pollutant longitudinal dispersion coefficient in aquatic streams

Discharge of pollution loads into natural water systems remains a global challenge that threatens water and food supply, as well as endangering ecosystem services. Natural rehabilitation of contaminated streams is mainly influenced by the longitudinal dispersion coefficient, or the rate of longitudinal dispersion (Dx), a key parameter with large spatiotemporal fluctuations that characterizes pollution transport. The large uncertainty in estimation of Dx in streams limits the water quality assessment in natural streams and design of water quality enhancement strategies. This study develops an artificial intelligence-based predictive model, coupling granular computing and neural network models (GrC-ANN) to provide robust estimation of Dx and its uncertainty for a range of flow-geometric conditions with high spatiotemporal variability. Uncertainty analysis of Dx estimated from the proposed GrC-ANN model was performed by alteration of the training data used to tune the model. Modified bootstrap method was employed to generate different training patterns through resampling from a global database of tracer experiments in streams with 503 datapoints. Comparison between the Dx values estimated by GrC-ANN to those determined from tracer measurements shows the appropriateness and robustness of the proposed method in determining the rate of longitudinal dispersion. The GrC-ANN model with the narrowest bandwidth of estimated uncertainty (bandwidth-factor = 0.56) that brackets the highest percentage of true Dx data (i.e., 100%) is the best model to compute Dx in streams. Considering the significant inherent uncertainty reported in the previous Dx models, the GrC-ANN model developed in this study is shown to have a robust performance for evaluating pollutant mixing (Dx) in turbulent environmental flow systems