Association of vascular endothelial growth factor a gene (VEGFA) polymorphisms, rs699947 and rs1570360, with diabetic retinopathy and altered VEGF secretion in the Pakistani patients with type 2 diabetes mellitus: a casecontrol study.

OBJECTIVE: To investigate the association of vascular endothelial growth factor A gene polymorphisms 2578C/A (rs699947) and 1154G/A (rs1570360) with type 2 diabetes mellitus, diabetic retinopathy and serum vascular endothelial growth factor levels in Pakistani patients. METHODS: The case-control study was conducted from Jan 2017 to Dec 2018 after approval from the ethics review board of Riphah International University, Islamabad, Pakistan, and comprised type 2 diabetes mellitus patients of either gender with diabetic retinopathy in group A, and without diabetic retinopathy in group B. Non-diabetic healthy individuals were enrolled in control group C. Genotyping was done by amplification refractory mutation system-polymerase chain reaction and serum vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. RESULTS: Of the 450 subjects, 150(33.3%) were in each of the 3 groups. The mean age in group A was 58.16±9.42, in group B 56.25±8.5 years and in group C it was 55.90±10.90. The proportion of Punjabi ethnicity was significantly high in group B compared to other groups (p<0.05). There was no significant association of rs699947 and rs1570360 genotypic and allelic frequencies in group B compared to group A. Further, rs699947 AA genotype was significantly associated with proliferative diabetic retinopathy compared to group A (p<0.05). Minor allele A showed significant association in groups A and B compared to group C (p<0.05). Significantly raised serum vascular endothelial growth factor levels were found in group B compared to group A (p<0.05), and were associated with rs699947 and rs1570360 heterozygosity in group A (p<0.05). Also, rs699947 genotype showed significant association with groups A and B in Punjabi and Pathan ethnicities (p<0.05) and with Kashmiri ethnicity in group B (p<0.05). CONCLUSIONS: There was a strong association of vascular endothelial growth factor 2578C/A (rs699947) gene polymorphism with proliferative diabetic retinopathy in type 2 diabetic Pakistani patients, suggesting its role in the pathogenesis of this condition.

Association of Pro-Inflammatory Cytokines with Vitamin D in Hashimoto's Thyroid Autoimmune Disease.

Background and objectives: Hashimoto's thyroiditis is an important autoimmune thyroid condition. It is characterized by lymphocytic congestion of the thyroid gland followed by progressive deterioration and fibrous substitution of the thyroid in the parenchymal structure. This study has provided insight into the variations of blood pro-inflammatory cytokine levels in patients with Hashimoto's disease and the key role of vitamin D levels among selected patients. Materials and Methods: A total of 144 participants including healthy controls and patients were studied in the current study in which 118 were female and 26 were male. The thyroid profile was evaluated in patients with Hashimoto's thyroiditis and healthy controls. Results: The mean ± SD Free T4 in the patients was recorded as 14.0 ± 4.9 pg/mL, and TSH was 7.6 ± 2.5 IU/L, whereas the median ± IQR thyroglobulin antibodies (anti-TG) were 285 ± 142. Thyroid peroxidase antibodies (anti-TPO) were 160 ± 63.5, whereas in the healthy controls, the mean ± SD Free T4 was recorded as 17.2 ± 2.1 pg/mL, and TSH was 2.1 ± 1.4 IU/L, whereas the median ± IQR anti-TGs were 56.30 ± 46.06, and anti-TPO was 5.6 ± 5.12. The assessment of pro-inflammatory cytokines (pg/mL) and total Vitamin D levels (nmol/L) in patients with Hashimoto's thyroiditis was recorded with values IL-1B 6.2 ± 0.8, IL-6 9.4 ± 0.4, IL-8 7.5 ± 0.5, IL-10 4.3 ± 0.1, IL-12 3.8 ± 0.5, TNF-α 7.6 ± 1.1, and total vitamin D 21.89 ± 3.5, whereas in healthy controls the mean ± SD IL-1B was 0.6 ± 0.1, IL-6 2.6 ± 0.5, IL-8 3.0 ± 1.2, IL-10 3.3 ± 1.3, IL-12 3.4 ± 0.4, TNF-α 1.4 ± 0.3 and total vitamin D was 42.26 ± 5.5. Conclusions: It was found that individuals with Hashimoto's thyroiditis had raised serum levels of IL-1B, IL-6, IL-8, IL-10, IL-12, and TNF-α as compared to the healthy controls, whereas the total vitamin D levels were remarkably low as compared to health controls. Serum TSH, anti-TG, and anti-TPO levels were typically lower in controls and much higher in individuals with Hashimoto's thyroiditis. The current study's findings might aid in future studies and in the diagnosis and management of autoimmune thyroid disease.

Differential expression of cancer associated plasma miRNAs in the ordnance factory workers, exposed to 2,4,6-Trinitrotoluene.

Objectives: To determine differential expression of microRNAs (miRNAs) in plasma of 2, 4, 6-Trinitrotoluene (TNT) exposed ordnance factory workers. Methods: A case control study was conducted at the Department of Toxicology, Armed Forces Institute of Pathology, Rawalpindi from July to December 2020. A total 30 subjects were recruited from an ordnance factory that were directly exposed to TNT and 120 non-exposed individuals from non-factory healthy population. Plasma levels of five miRNAs including miRNA-let-7a-2, miRNA-34a-1, miRNA-21-2, miRNA-106b-1, miRNA-122a-1 were measured by quantitative real-time polymerase chain reaction (RT-PCR). Results: Micro RNAs showed a wide range of Ct (cycle threshold) values ranging from 23.48 to 41.94. Among the five miRNAs let-7a-2 and miRNA-122a-1 displayed relatively high expression with Ct values ranging from 26.58 ± 2.25 to 27.18 ± 0.80 respectively. Relative fold change expression for all five miRNAs of exposed individuals were found high (p <0.0001) vs non-exposed. Dividing fold change expression of exposed individuals into two groups as ≤ 10 and > 10, the individuals having ≤ 10-fold change expression were19 (63.3%) in miRNA-let-7a-2, 30 (100%) in miRNA-34a-1 and 23 (76.7%) in miRNA-122a-1 while in miRNA-21-2 and miR-106b-1, 23 (76.7%) and 18(60%) individuals had > 10-fold change expression respectively. Among the five miRNAs in exposed individuals, miRNA-let-7a-2, miR-21-2, miR-106b-1 and miR-122a-1 were found highly expressed with fold change expression > 10 (p <0.0001). No significant association was found between miRNAs expression levels with age and working duration. Conclusion: The study shows upregulation of all five miRNAs in TNT exposed subjects with no significant association of expression levels with age and working duration.

Association analysis of -429T/C receptor for advanced glycation end products (RAGE) gene polymorphism with type 2 diabetic retinopathy and serum soluble RAGE levels in Pakistani patients.

OBJECTIVE: To investigate the association of receptor for advanced glycation end products gene polymorphism 429T/C (rs1800625) with diabetic retinopathy and serum soluble receptor for advanced glycation end products levels in patients with type 2 diabetes. METHODS: The case-control study was conducted from January 2017 to December 2018 at Pakistan Railway Hospital, Rawalpindi, and the Multidisciplinary Laboratories of Islamic International Medical College, Riphah International University (RIU), Islamabad, Pakistan. Those included were healthy controls in group A, diabetics without retinopathy in group B and patients having diabetic retinopathy in group C. Genotyping for 429T/C was done by tetra-primer amplification refractory mutation system-polymerase chain reaction. Serum soluble receptor for advanced glycation end products levels were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. RESULTS: Of the 450 subjects, 150(33.3%) were in each of the three groups. The frequency of TT, TC and CC genotypes of 429T/C polymorphism were 137(91.3%), 10(6.7%) and 3(2%) in group A; 133(88.6%), 13(8.7%) and 4(2.7%) in group B; and 127(84.7%), 18(12%) and 5(3.3%) in group C. No significant association of 429T/C genotypic and allelic frequencies were found with groups B and C (p>0.05). Serum soluble receptor for advanced glycation end products levels were significantly high in patients with proliferative diabetic retinopathy and were positively correlated with fasting plasma glucose in group C (p<0.05). TC and CC genotypes were significantly associated with raised serum soluble receptor for advanced glycation end products, and TC with raised fasting plasma glucose in group C. CONCLUSIONS: The 429T/C receptor for advanced glycation end products gene polymorphism was found to be associated with severe non-proliferative diabetic retinopathy, and serum soluble receptor for advanced glycation end products levels had a positive correlation with severity of diabetic retinopathy.

Association of miR-146α gene polymorphism and expression levels of its target protein RhoA in Pakistani breast cancer patients.

OBJECTIVE: To assess the association of miR-146a and its target protein RhoA expression levels in breast cancer. METHODS: The case-control study was conducted at Riphah International University, Islamabad, Pakistan, from March 2017 to November 2018, and comprised confirmed breast cancer cases and controls who were matched for age and ethnicity. Genotyping and expression profiling of archived samples was performed. Data was analysed using SPSS 22. RESULTS: Of the 590 subjects, 295(50%) each were cases and controls. Among the cases, there were 195(66%) Punjabis, 59(20%) Pathans and 41(14%) Kashmiris. The corresponding numbers among the controls were 198(67%), 58(19.7%) and 39(13.2%). The association between genotypes of the cases and controls was significant (p<0.05). Strong association was seen in dominant, recessive and allelic models (p=0.05). In Punjabi group the association was (p<0.00) significant, but this association was not significant in Kashmiri and Pathan groups (p>0.05). No association was found with the receptor status and miR-146a polymorphism. CONCLUSIONS: The miR-146a gene polymorphism rs2910164 G/C was found to have increased susceptibility to breast cancer at genotype and allelic levels.

Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients.

OBJECTIVES: to determine the relationship of 374T/A (rs1800624) polymorphism in the gene encoding RAGE with Type-2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) level in Pakistani patients. METHODS: A case-control study, conducted from January 2017 to December 2018, involving 150 healthy controls (HC), 150 T2DM patients with no retinopathy (DNR) and 150 DR patients diagnosed by coloured fundus photography. Tetra-primer amplification refractory mutation system - polymerase chain reaction (T-ARMS-PCR) was used for genotyping. Serum sRAGE levels were measured by enzyme-linked immunosorbent assays (ELIZA). RESULTS: The frequency of TT, TA and AA genotypes of rs1800624 polymorphism were: 92.7%, 6%, 1.3% in HC, 80%, 17.3%, 2.7% in DNR and 76.7%, 19.3%, 4.3% in DR groups. Heterozygous TA genotype and mutant A allele showed significant association with diabetes and DR vs HC. In dominant model, mutant allele showed significant association with DNR and DR vs HC. No significant association of rs1800624 was detected with DR and its sub-groups, non-proliferative DR (NPDR) and proliferative DR (PDR) vs DNR. Dividing NPDR into mild, moderate and severe, heterozygous TA genotype showed significant association with moderate and severe NPDR vs DNR. In DNR and DR groups, TA genotype was significantly associated with raised sRAGE. CONCLUSION: rs1800624 RAGE gene polymorphism might be a risk factor for T2DM and NPDR in Pakistani patients. Raised sRAGE levels have a positive correlation with PDR and are associated with heterozygosity of rs1800624 polymorphism in DNR and DR groups.

Association of single nucleotide polymorphism of transforming growth factor ß1 (T29C) in breast cancer patients: a case control study in Rawalpindi.

OBJECTIVE: To determine the association of single nucleotide polymorphism in three CC, TT and TC genotypes of transforming growth factor ß1 T29C in breast cancer patients. METHODS: The case-control study was conducted from April 2017 to April 2018 at the Islamic International Medical College, Rawalpindi, Pakistan, in collaboration with Nuclear Oncology Medicine and Radiotherapy Institute and Holy Family Hospital, Rawalpindi. Using convenience sampling, breast cancer cases and healthy controls were enrolled. All investigations were done using standardized laboratory protocols. The outcomes were determined in terms of association of single nucleotide polymorphism of transforming growth factor ß1with breast cancer. Data was analysed using SPSS 21. RESULTS: Of the 150 subjects, 80(53.3%) were cases and 70(47.7%) were healthy controls. Among the cases, the most frequent genotype was CC 38(47.5%) followed by TC 26(32.5%) and TT 16(20%). Among the controls, the corrsesponding values were 50(71.42%), 13(18.5%) and 7(10%). Transforming growth factor ß1 TC genotype was strongly associated with the increased risk of developing breast cancer (odds ratio: 3.79). CONCLUSIONS: The incidence of breast cancer was markedly lower among women with CC genotype compared to those with CT or TT genotypes.

Genetic polymorphism of miRNA-196a and its target gene annexin-A1 expression based on ethnicity in Pakistani female breast cancer patients.

OBJECTIVE: To evaluate the association of miR-196a rs11614913 C/T genetic variation and its target gene annexin A1 mRNA expression with breast cancer risk in Pakistani female ethnicities. METHODS: This case control study, conducted from March 2017 to November 2018 included 295 breast cancer patients, 295 controls of three Pakistani ethnicities and archived 100 samples of cohort group for genotyping and expression profiling. Genotyping of miR-196a (rs11614913 C/T) was done by ARMS PCR technique. Annexin-A1 (ANXA1) mRNA expression was measured with qRT-PCR and detection of protein expression of ANXA1 was done by immunohistochemistry. RESULTS: CC homozygous genotype of miR-196a rs11614913 was present in 81.4% of cases and 73.9% controls. C/T polymorphism was found to be significantly associated with decrease risk of breast cancer (OR=0.25 (0.11- 0.58, p <0.05). Similar trend was seen with the minor T allele (OR=0.55 (0.39-0.77, p <0.05, and both dominant and recessive models (OR=0.64; p=0.02 and OR=0.26, p=0.00). In the KPK ethnic group significant decrease association with breast cancer risk was observed (OR= 0.22 (0.09-0.53, p < 0.05). Immunohistochemical staining showed loss of ANXA1 protein expression in 72 samples, and significant association was observed with pathological type p=0. 00 and triple negative receptor status p=0.03 and with genotypes of miR-196a p=0.00. Increase relative expression of 2.81± .88 by qPCR analysis of ANXA1 mRNA was noted with TT genotype. CONCLUSIONS: Our results demonstrate that miR-196a rs11614913 C/T polymorphism is associated with a decreased risk and loss of protein expression in breast cancer in the Pakistani population.

Relationship of S/R warfarin ratio with CYP2C9 genotypes in Pakistani population.

Warfarin is administered as a racemic preparation of R- and S-enantiomers. S-warfarin is more potent than R-warfarin, so changes in blood levels of S-warfarin affect the anticoagulant response. This study was carried out to determine the effect of CYP2C9*2 and CYP2C9*3 polymorphisms on S/R warfarin ratio. A single blood sample was collected 12-16 hours after drug administration from 170 stable patients fulfilling the criteria. Genotyping of the CYP2C9 polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. S- and R-warfarin enantiomers extraction from plasma was accomplished by a validated HPLC method. The concentration of S-warfarin was significantly different among CYP2C9 genotypes (p =0.018) whereas there was no effect on R-warfarin (p =0.134). There was statistically significant effect of different CYP2C9 genotypes on S/R warfarin ratio (p=0.000). It is concluded that CYP2C9 polymorphisms influence CYP2C9 enzymatic activity in turn affecting S-warfari levels but not R-warfarin, thus leading to different S/R warfarin enantiomers ratio among different CYP2C9 genotypes.

Association of RETN C-420G single nucleotide polymorphism with type 2 diabetes mellitus in Pakistani Punjabi Rajput population.

OBJECTIVE: To determine the association of human resistin gene RETN C-420G single nucleotide polymorphism with type 2 diabetes mellitus in a specific ethnic population.. METHODS: The controlled study was conducted from June 2012 to January 2015 at Military Hospital, Rawalpindi, Army Medical College, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan. Patients with type 2 diabetes and healthy controls belonging to Pakistani Punjabi Rajput ethnic group were genotyped for human resistin gene RETNC-420G single nucleotide polymorphism. Serum resistin, serum insulin, fasting blood sugar, lipid profile, body mass index and insulin resistance was determined and correlated with genotypes. SPSS 18 was used for data analysis. RESULTS: Of the 789 subjects, 539(68%) were diabetics and 250(32%) were controls. Serum resistin levels were significantly higher in diabetics than controls (p<0.05). The frequency of GG, GC and CC was 15(2.8%), 322(59.75%) and 202(37.5%) in diabtics. This single nucleotide polymorphism was associated with diabetes (p<0.02).Human resistin gene RETN C-420G single nucleotide polymorphism was not associated with serum resistin, insulin, body mass index, insulin resistance and dyslipidaemia in both groups (p<0.05 each). CONCLUSIONS: Human resistin gene RETN C-420G single nucleotide polymorphism was found to be a risk factor for type 2 diabetes in Pakistani Punjabi Rajput population..

Influence of cytokine gene polymorphisms on proinflammatory/anti-inflammatory cytokine imbalance in premature coronary artery disease.

BACKGROUND: Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (IL) 18, tumour necrosis factor-α (TNFA), IL6 and IL10 single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10). MATERIAL AND METHODS: The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN assay. RESULTS: The risk allele frequencies (RAFs) of rs1800795 (IL6) and rs187238 (IL18) cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the IL6 rs1800795 CC genotype. IL18 SNP rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by TNFA SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios. CONCLUSIONS: The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD.

Association of IL-6 C-174G (rs 1800795) single nucleotide polymorphism with type 2 diabetes mellitus in Pakistani population.

OBJECTIVE: To determine the association of interleukin-6 C-174G single nucleotide polymorphism with type 2 diabetes mellitus and metabolic parameters. METHODS: This case-control study was conducted from June 2012 to December 2013 at the Military Hospital Rawalpindi, the Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan. Two cohorts of subjects were genotyped for the single nucleotide polymorphism. One cohort comprised type 2 diabetics and other included healthy subjects. In these groups, serum interleukin-6, serum insulin, blood sugar fasting, lipid profile, body mass index and insulin resistance was determined and correlated with genotypes. RESULTS: Of the 789 participants, 539(68.3%) were in the study group and 250(31.7%) in the control group. Serum interleukin-6 was significantly higher in diabetics than healthy controls (p<0.0001). The frequency of GG, GC and CC was 267(49.5%), 235(43.6%) and 37(6.9%) in diabetic patients and 128(51.2%), 74(29.6%) and 48(19.2%) in healthy controls, respectively. Interleukin-6 C-174G single nucleotide polymorphism was significantly associated with diabetes [odds ratio = 3.22 (95% confidence interval: 2.04-5.1; p<0.0001). Genotypes were within Hardy-Weinberg equilibrium. Interleukin-6 C-174G single nucleotide polymorphism was significantly associated with serum interleukin-6 in the order of GC>GG>CC but was not associated with body mass index, insulin resistance, serum insulin and dyslipidaemia in diabetic patients (p>0.05 each). CONCLUSIONS: Interleukin-6 C-174G single nucleotide polymorphism was a risk factor in type 2 diabetes and contributed to higher serum interleukin-6 levels among the participants.

Effects of two functionally important SLCO1B1 gene polymorphisms on pharmacokinetics of atorvastatin.

Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by (SLCO1B1) gene, an uptake transporter involved in the transport of drugs and endogenous compounds and located in hepatocyte sinusoidal membrane. Objective of study was to investigate the effects of two functionally significant SNPs (388A>G and 521T>C) and their respective genotypes of SLCO1B1 gene encoding OATP1B1 on the pharmacokinetics of atorvastatin. A total of 100 subjects divided into 6 groups as per their genotype profile were recruited. A single dose of 80mg atorvastatin was orally administered and plasma concentration measured up to 48 hours. The 388A>G and 521T>C genotypes were significantly associated with each other when compared for AUC and Cmax but exhibited no significant variations in Tmax and t1/2. 521 SNP is rather more strongly associated with altered pharmacokinetics of atorvastatin when compared with the 388 SNP, though the homozygous bi-allelic variant of 388 SNP also exhibited a fairly significant variation along with homozygous bi-allelic variant of 521 SNP. The inter-individual variation in pharmacokinetics can be explained by SLCO1B1 polymorphism.

Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

Effects of oral vanadium on glycaemic and lipid profile in rats.

OBJECTIVE: Vanadyl sulphate, an inorganic tetravalent salt of transition metal vanadium is conventionally used to treat diabetes and by athletes as body-building supplement. Vanadyl sulphate is a constituent of many supplements and herbal preparations available over the counter in many parts of the world. In this study the efficacy of the salt as hypoglycaemic agent and its effects on lipid profile were determined when administered in therapeutic dose range (in humans) to healthy Sprague Dawley rats for a considerable duration. METHODS: One hundred and five rats were randomly divided into three groups of 35 rats each. Animals of all three groups were provided normal rodent diet and water ad libitum. Group I animals were administered 0.5 ml plain water through oral gavage while group II and group III rats, 0.25mg/Kg/day and 1.2mg/Kg/day vanadyl sulphate respectively for 24 weeks. At the end of 24 weeks intra-cardiac blood sampling was done and blood glucose, insulin and lipid profile were measured. RESULTS: There was significant decrease in plasma glucose, insulin and HDL-c levels while LDL-c, TGs and TC levels were significantly increased in a dose dependent manner in treated groups. CONCLUSIONS: Our study showed that vanadyl sulphate possesses hypoglycaemic effect in healthy rats while insulin levels are also decreased which may be secondary to hypoglycaemia. Moreover it causes unfavorable derangement of lipid parameters in treated rats. In conclusion vanadyl sulphate though contains significant hypoglycaemic effects; its use in humans may be re-evaluated to establish its safety in relation to lipid profile.

Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

OBJECTIVE: To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. METHODS: The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. RESULTS: Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). CONCLUSIONS: Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

Comparison Of Protective Effect Of Green Tea And Vitamin C Against Cypermethrin Induce Nephrotoxicity In Mice.

BACKGROUND: Insecticide toxicity is the problem of every person in under developed countries. It is necessary to counteract its effect by natural and cheap remedies like green tea and vitamin C. In this manner common man can also enjoy blessings of life. The current research was performed to compare the protective function of green tea and vitamin C on experimental cypermethrin provoked nephrotoxicity. METHODS: Forty healthy Balb/C mice purchased from National Institute of Health, Islamabad, Pakistan and divided in to four groups (10 each). Group a was control which received only normal diet. Group B, group C and group D were experimental groups which were given Cypermethrin, Cypermethrin with green tea and Cypermethrin with vitamin C respectively. These groups were also given normal diet. After 1 month blood was drawn by intra-cardiac method to assess renal parameters. RESULTS: One month research showed increase in serum urea to 6.8±.48 m.mol/l (n=3.9±.44) while green tea and vitamin C normalize them to 4.0±.83m.mol/l and 3.4±.33m.mol/l respectively. Serum creatinine increased to 42.90±3.28m.mol/l (n=29.50±3.95) while green tea and vitamin C normalize them to 28.80±4.58m.mol/l and 22.60±2.06m.mol/l correspondingly. CONCLUSIONS: The results showed that green tea and vitamin C neutralized toxicity induced by Cypermethrin in mice and their effect is comparable.

Pattern of dyslipidaemia and impact of increasing age and duration of type 2 diabetes mellitus on dyslipidaemia, insulin levels and insulin resistance.

OBJECTIVE: To study the pattern of dyslipidaemia in Type 2 Diabetes Mellitus patients and to determine the correlation of increasing age and duration of the disease with dyslipidaemia, insulin level and insulin resistance in diabetic patients. METHODS: The cross-sectional case-control study was conducted at Combined Military Hospital, Rawalpindi, and Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi, Pakistan from June 2011 to June 2012, and comprised patients of type 2 diabetes mellitus and healthy controls. Serum levels of total cholesterol, triglycerides, low density lipoprotein, high-density lipoprotein and insulin in both the cases and the controls. Insulin resistance was calculated by Homeostatic Model of Assessment of insulin resistance. Correlation between increasing age and duration of the disease was determined using biochemical parameters. SPSS 17 was used for statistical analysis. RESULTS: Of the 112 subjects in the study, 72(64%) were patients and 40(36%) were healthy controls. Among the cases, hypertriglyceridaemia was the commonest in 44(61%) followed by low-density-lipoprotein-hypercholesterolaemia 36(50%). Among the controls, 20(50%) subjects had low-density-lipoprotein-hypercholesterolaemia, followed by hypertriglyceridaemia in 17(42.5%). Duration of the disease was not found to be correlated with dyslipidaemia or insulin resistance (p>0.05). There was strong negative correlation of duration of the disease with serum insulin levels (p=0.03). Age showed no significant correlation with dyslipidaemia, serum insulin levels or insulin resistance on regression analysis (p>0.05 each). CONCLUSIONS: In type diabetes mellitus, hypertriglyceridaemia was the commonest dyslipidaemia whereas hypercholesterolaemia was a risk factor in healthy individuals. Besides, the duration of disease was inversely correlated with serum insulin levels and positively correlated with dyslipidaemia.

Comparative evaluation of Nigella sativa (Kalonji) and simvastatin for the treatment of hyperlipidemia and in the induction of hepatotoxicity.

Hyperlipidemia is a major risk factor for incidence of coronary artery disease. Simvastatin is a synthetic lipid lowering drug and Nigella sativa seeds found helpful in controlling hyperlipidemia. The study performed to evaluate the efficacy of Nigella sativa in comparison to simvastatin to treat hyperlipidemia. Thirty Sprague Dawley rats fed on an ad libitum diet for 02 weeks, on cholesterol diet for 08 weeks. Then group II treated with simvastatin and group III with Nigella sativa for 06 weeks. Blood samples analyzed for serum cholesterol, serum triglycerides, HDL-C, LDL-C & serum ALT. The results evident that Nigella sativa (kalonji) and simvastatin showed significant improvement in the lipid profile of rats in respective groups after treatment. The p value <0.05 of group II and III documented that Nigella sativa (kalonji) affect the lipid profile in the same way as of simvastatin. However, ALT levels significantly raised in group II treated with simvastatin compared to group III. Nigella sativa and simvastatin showed comparable effects in the treatment of hyperlipidemia. Nigella sativa showed protective role in terms of hepatic dysfunction and can be used as a cholesterol lowering agent.