Molecular characterization of autosomal recessive non syndromic hearing loss in selected families from district Mardan, Pakistan

Deafness is the most common sensory disorder, which affects 1/1000 neonates globally. Genetic factors are major contributors for hearing impairment. This study was conducted to explore the linkage of DFNB loci and their mutations with NSHL in selected Pakistani families. We included 10 families with history of deafness from district Mardan, Pakistan. Blood sample [5ml] along with personal and clinical information was collected from the available family members including both diseased and un-affected individuals. Genomic DNA was amplified using loci specific STR markers to investigate the linkage of DFNB loci. Family found linked with DFNB4 locus was screened for SLC26A4 mutations. One out of the ten explored families was found linked with DFNB4 locus which was further investigated for SLC26A4 gene mutation through direct DNA sequencing. Two novel mutations were observed in the studied family, one at splice donor site [164+2T>G] and the other at position 164+5C>G only in the affected members of the linked family. DFNB4 locus was found linked in the present study which harbors SLC26A4 gene. The novel mutation of SLC26A4 gene at the splice donor site results in skipping of the first coding exon and thus can lead to loss of expression of SLC26A4 product in the inner ear

Association of ADIPOQ C-11377G [rs266729], TNF-alpha G-308A [rs1800629] and TNF-alpha G-238A [rs361525] single nucleotide polymorphisms with type 2 diabetes mellitus in Pakistani population

Objective: to determine the frequencies of adiponectin [ADIPOQ] C-11377G, tumor necrosis factor-alpha [TNF-alpha] G-308A and TNF-alpha G-238A single nucleotide polymorphisms [SNP] and their association with serum levels in Pakistani T2DM and healthy population

Study Design: Case control study

Place and Duration of Study: Military Hospital, Rawalpindi, Army Medical College and Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan, from June 2012 till 2014

Methodology: cases [n=539] and controls [n=250] comprising of T2DM and healthy subjects, respectively, belonging to Pakistani Punjabi Rajput ethnicity were genotyped for SNPs. Serum adiponectin, TNF-alpha, insulin, blood sugar fasting [BSF], lipid profile, body mass index [BMI], and insulin resistance [IR] was determined and correlated with genotypes

Results: serum TNF-alpha was significantly higher and adiponectin was lower in T2DM than healthy controls [p < 0.003 and 0.0001, respectively, Mann-Whitney U-test]. The frequency of ADIPOQ CC, GC and GG was 340 [63.1%], 167 [31%] and 32 [5.9%] in T2DM patients. ADIPOQ -11377 SNP was not significantly associated with T2DM [OR = 1.116 [95% CI 0.81- 1.53], p = 0.27- Fisher's exact test]. Genotypes deviated from Hardy-Weinberg equilibrium. Minor alleles of TNF-alpha G-308A and TNF-alpha G-238A were not found in either groups

Conclusion: frequency of ADIPOQ -11377 risk allele is low and does not functionally affect the serum adiponectin levels; hence, ADIPOQ C-11377G SNP is not a risk factor for T2DM in Pakistani Punjabi Rajput patients. Moreover, TNF-alpha G-308A and TNF-alpha G-238A SNPs are not prevalent in this ethnic group

Polymorphisms of the ABCB1 gene in the pakistani population

To investigate the frequency of the single nucleotide polymorphism C1236T in exon 12 of the ABCB1 gene in Pakistani population and to compare it with published data on Asian and Caucasian populations. A cross-sectional observational study. Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering [IBGE], Islamabad, from August 2012 to May 2013. C1236T polymorphism was investigated in 426 Pakistani subjects. The frequency was compared with the published data on other Asian and Caucasian populations. The frequencies of ABCB1 C1236T were 16.4% for CC, 44.1% for CT and 39.4% for TT. Pakistanis differed significantly from all the European populations compared in the distribution of the TT genotype of C1236T ABCB1 [p < 0.05]. The Pakistani population also differed significantly from some of the European populations in the distribution of CC and CT genotype [p < 0.05]. There was significant difference in the genotype frequency of the ABCB1 gene compared to other populations. This study has provided a framework for future pharmacogenetic and pharmacokinetic studies on this polymorphic variant of ABCB1 gene in the Pakistani population

Association of anti-emetic efficacy of ondansetron with G2677T polymorphism in a drug transporter gene ABCB1 in Pakistani population

To determine the association of ABCB1polymorphism G2677T with anti-emetic efficacy in patients treated with ondansetron for preventing postoperative nausea and vomiting. A clinical trial. Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering, Islamabad, from 2012 to 2013. Four mg ondansetron was administered intravenously 30 minutes before the end of surgery. A total of 246 patients with the complaints of nausea and vomiting and 244 patients without nausea and vomiting were analyzed for G2677T polymorphism using PCR-RFLP method. Results were described as frequency percentages and chi-square test with significance at p < 0.05. The patients with TT genotype had significantly lower incidence of postoperative nausea and vomiting during the first 2 hours [p < 0.001] and between 2 - 24 hours after surgery as compared to other genotypes [p < 0.001]. The patients with GG genotypes had significantly higher incidence of this complaint [p=0.014]. Polymorphism of ABCB1 has an association with responsiveness for ondansetron. There is a role for genetics in the management of PONV

Prevalence of cyp2d6*4 genotype and its association with tamoxifen induced hot flashes in Pakistani female breast cancer patients

To investigate the frequency of CYP2D6*4 in Pakistani breast cancer patients for the first time and also investigate its association with tamoxifen induced hot flashes. A retrospective study carried out in Nuclear Medicine, Oncology and Radiotherapy Institute [NORI] Islamabad and Combined Military Hospital Rawalpindi [CMH]. Pre and postmenopausal breast cancer women who were advised 20mg/day of tamoxifen as adjuvant therapy were recruited for the study. The data from January 2000 to September 2013 was collected from the medical records of the outpatient breast cancer clinics. 232 women who fulfilled the eligibility criteria were initially recruited and their peripheral whole blood samples were taken. CYP2D6*4 was determined by using PCR-RFLP, allele*4 was not identified in 9 women and study was conducted on 223 women. None of the women died during the study period. Data of 223 women was analysed and the allele frequency of CYP2D6*1 was 86% and that of CYP2D6*4 was 14%. Women with CYP2D6*4/*4 did not experience mild to moderate or severe hot flashes as compared to women heterozygous or homozygous for wild type allele *1. The frequency of CYP2D6*4 allele in Pakistani breast cancer women is 14% which is comparable to the Caucasians moreover CYP2D6*4/*4 genotypes have lower incidence of hot flashes, but the results are not statistically significant

case control study of risk factors associated with female breast cancer

To find the association of various risk factors with breast cancer. It was a case-control study. The study was carried out in NORI Hospital Islamabad and Combined Military Hospital Rawalpindi between August, 2013 and February, 2014. Two hundred breast cancer patients and 200 control subjects were inducted. A short approved and planned questionnaire was used to collect data regarding basic demographic, menstrual and reproductive characteristics of participating females. Cases and controls were then interviewed after taking written consent. Breast cancer patients and control subjects did not differ regarding age [p = 0.15], early menarche [OR for menarche at <13 years vs. >/=13=1.3, 95% CI = 0.84 - 2.02], and history of breast cancer in 1st degree relatives did not increase breast cancer risk [OR = 1.0, 95% CI = 0.57- 1.74]. Nulliparous women had significantly higher risk than parous women [OR = 2.43, 95% CI = 1.22 - 4.84] and women with late menopause compared to women with early onset of menopause were also at higher risk for breast cancer [OR for menopause at >/= 50 vs. < 50 = 5.16, 95% CI = 2.59 - 10.29]. Nulliparity and menopausal age of more than 50 years was associated with increased breast cancer risk. Breastfeeding and age less than 25 years at first live birth was not protective against breast cancer

Effect of smoking on nausea, vomiting and pain in the post-operative period

Objective: To determine the effect of smoking on the post-operative nausea and vomiting [PONV] as well as severity of pain in the post-operative period

Methodology: A total of 147 patients undergoing elective laparoscopic cholecystectomy under general anesthesia were divided into 2 groups of non-smokers [n=75] and smokers [n=72]. In the first 24 hours after surgery the frequency of PONV and the severity of pain on Visual Analogue Score were assessed

Results: The group of non-smokers had statistically more nausea and vomiting [n=59, 78.6%] as compared to that of smokers [n=20, 27.7%] [p<0.05]. However there was no significant difference in the maximum pain scores in both the groups [p>0.05]

Conclusion: We conclude that frequency of PONV is less in smokers as compared to non-smokers

P-glycoprotein in blood brain barrier

The endothelial cells of the blood brain barrier prevent the transport of enormous number of substances into the brain. An important component of this barrier is the P-glycoprotein [P-gp]. It is an efflux protein that is ATP dependent and thus rightly called the "traffic ATPase" involved in extrusion of compounds, using the energy of ATP hydrolysis to move the variety of structurally unrelated compounds and preventing their accumulation within the brain. Understanding of structure and function of the drug transporter P-gp in the blood brain barrier will pave the way to more tailored and targeted therapies for complex diseases

Antibacterial activity of local herbs collected from Murree [Pakistan] against multi-drug resistant klebsiella pneumonae, E. coli and methyciline resistant Staphylococcus aureus

Exploring healing power in plants emerged in prehistory of human civilization. Sustaining good health has been achieved over the millions of years by use of plant products in various traditional sockets. A major contribution of medicinal plants to health care systems is their limitless possession of bioactive components that stimulate explicit physiological actions. Luckily Pakistan is blessed with huge reservoir of plants with medicinal potential and some of them; we focused in this study for their medicinal importance. In this study we checked the antibacterial activity inherent in Ricinus communis, Solanum nigrum, Dodonaea viscose and Berberis lyceum extracts for multidrug resistance bacterial strains Klebsiella pneumonae, E. coli and methyciline resistant Staphylococcus aureus. MRSA showed sensitivity for Ricinus communis. Multidrug resistant Klebsiella pneumonae was sensitive with Pine roxburgii and Ricinus communis but weakly susceptible for Solanum nigrum. Multidrug resistant E. coli was resistant to all plant extracts. Treatment of severe infections caused by the bacterial strains used in this study with Ricinus communis, Pine roxburgii and Solanum nigrum can lower the undesired side effects of synthetic medicine and also reduce the economic burden

Making personalized prostate cancer medicine a reality: challenges and opportunities in the re-establishment of gold standards

Prostate cancer is a serious multidimensional disorder that arises because of misrepresentation of signaling cascades and acquired resistance against apoptosis. It is progressively becoming more insurmountable because of rheostat like switching of oncogenic signaling in androgen dependent and androgen depleted microenvironment. Additionally, oncogenic fusion proteins have been explored in prostate cancer tissues thus adding another layer of complexity to the targeting of protein network in cancer cell and generate hurdles in the standardization of therapy. In this review we briefly describe identified oncogenic fusion transcripts in prostate cancer and suggest utilization of this biomarker for prostate cancer diagnosis along with standard PSA and immunohistochemistry analysis in Pakistan. We also provide overview of animal model studies to interpret the efficacy of vitamins