Identification and Molecular Simulation of Genetic Variants in ABCA1 Gene Associated with Susceptibility to Dyslipidemia in Type 2 Diabetes.

Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by ABCA1 is involved in transporting cholesterol across the cell membrane. Genetic variations in the ABCA1 gene are well documented; however, their role in the development of diabetic dyslipidemia still needs to be explored. This study aimed to identify the associations of rs757194699 (K1587Q) and rs2066714 (I883M) with dyslipidemia in type 2 diabetes and performed molecular simulations. In our case-control study, 330 individuals were divided equally into a diabetic dyslipidemia cases and a healthy controls. Allele-specific polymerase chain reaction and restriction fragment length polymorphism were performed to screen selected variants of the ABCA1 gene. Sanger sequencing was also performed to find genetic mutations in exon 5 of the ABCA1 gene. The C allele of rs757194699 was observed at a high frequency in cases compared to controls and followed the overdominant genetic model (p < 0.0001, OR:3.84; CI:1.67-8.82). The frequency of G allele of rs2066714 was significantly higher in cases compared to controls and followed the genetic model of codominant (p< 0.0001, OR: 39.61; CI:9.97-157.32), dominant (p < 0.0001,OR:59.59; CI:15.19-233.81), overdominant (p< 0.0001, OR:9.75; CI:3.16-30.11), and log-additive (p< 0.0001, OR:42.15; CI:11.08-160.40). In silico modeling and docking revealed that rs2066714 and rs757194699 produced deleterious conformational changes in the ABCA1 protein, resulting in alterations in the binding of the apoA1 protein. There were no genetic variations found in exon-5 in Sanger sequencing. The G allele of rs2066714 and C allele of rs757194699 in the ABCA1 gene were found to be risk alleles in the development of dyslipidemia in type 2 diabetes. These polymorphisms could alter the binding site of ABCA1 with apoA1 thus disturbs the reverse cholesterol transport.

Demographic analysis of hearing impairment based on various parameters in patients with cochlear implant.

Objectives: To analyse the demographic and clinical variables in children having undergone cochlear implant surgery because of deafness. METHODS: The cross-sectional study was conducted from January to November 2022 at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Ear, Nose and Throat Department of Combined Military Hospital, Rawalpindi, and comprised children of eith gender aged up to 10 years who had received cochlear implant. Data was collected through questionnaire-based detailed interviews. Syndromic Hearing Loss, Non-Syndromic Hearing Loss, and Acquired Hearing Loss were identified among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 250 cases, 147(58.8%) were boys, 146(58.4%) were aged 0-5 years, 219(87.6%) had prelingual onset of disease, and 202(80.8%) had a non-progressive disease course. In 203(81.2%) cases, normal developmental milestones were seen. Parental consanguinity was observed in 219(87.6%) cases. However, 63(25.2%) patients had a first-degree relative who had a history of deafness. In 170(68%) cases, hearing loss was hereditary, whereas in 80(32%) it was acquired. Meningitis was the most commonly identified risk factor 55(68.75%). Acquired risk factors and family history had significant association with hearing loss (p<0.05). Speech perception significantly improved in all 219(100%) patients with prelingual hearing loss who underwent cochlear implantation. CONCLUSIONS: Majority of the cases were found to be male, had a prelingual disease onset and a non-progressive disease course. Family history was a significant factor, while meningitis was the most common acquired cause of hearing loss.

Significance of serum ferritin and De Ritis ratio in non-alcoholic fatty liver disease as diagnostic markers.

Objectives: To ascertain the significance of serum ferritin and De Ritis ratio as diagnostic markers in patients of nonalcoholic fatty liver disease with and without type 2 diabetes mellitus. METHODS: The comparative cross-sectional study was conducted from February to October 2022 at the Radiology Department of Combined Military Hospital, Rawalpindi, Pakistan, and comprised individuals aged 30-65 who were divided into 3 groups. Healthy controls formed group I, non-alcoholic fatty liver disease patients without type 2 diabetes mellitus formed group II and non-alcoholic fatty liver disease patients with type 2 diabetes mellitus were in group III. Blood 5ml was withdrawn and assessed for alkaline phosphatase, aspartate transaminase, alanine transaminase and ferritin. De Ritis ratio was calculated and subjected to intergroup comparison. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 110(52.4%) were males and 100(47.6%) were females, with 70(33.3%) in each of the three groups. Group I had 38(54.3%) females and 32(45.7%) males with mean age 37.50±4.513. In group II, there were 27(38.6%) females and 43(61.4%) males with mean age 45.86±9.646, while in group III there were 35(50%) females and 35(50%) males with mean age 54.01±9.243 years. Serum ferritin levels were significantly increased in patient groups II and III compared to control group I (p<0.05). De Ritis ratio was markedly raised in groups II and III compared to group I (p<0.05). Ferritin was significantly correlated to age, weight, height, fasting blood glucose, haemoglobin, alkaline phosphatase, aspartate aminotransferase, alanine transaminase and bilirubin (p<0.05). De Ritis ratio had a significant correlation with body mass index and fasting blood glucose (p<0.05). CONCLUSIONS: Serum ferritin and De Ritis ratio were found to be useful diagnostic indicators for non-alcoholic fatty liver disease, highlighting their importance in improving disease screening.

Association of serum IL12 with clinical and biochemical parameters in a cohort of diagnosed rheumatoid arthritis patients on oral conventional synthetic disease modifying anti-rheumatic drugs.

Objective: To determine the association of serum interleukin-12 levels with disease progression in active rheumatoid arthritis patients on oral conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: The case-control study was conducted at the Army Medical College, Rawalpindi, in collaboration with the Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2022, and comprised rheumatoid arthritis patients or either gender aged 18-75 years who were placed in group I, while group II comprised healthy controls. Demographic and clinical data was noted, and 2ml blood samples were drawn from each subject. The serum was separated and analysed using sandwich enzyme-linked immunosorbent assay to quantify serum interleukin-12 levels. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, 75(50%) were in group I; 27(36%) males and 48(64%) females with overall mean age 45.70±11.70 years. There were 75(50%) subjects in group II; 37(49.3%) males and 38(50.7%) females with overall mean age 31.70±7.70 years. Serum interleukin-12, erythrocyte sedimentation rate and C-reactive proteinquantitative levels were significantly higher in group I compared to group II (p<0.05). Smoking, positive family history of rheumatoid arthritis in a first-degree relative and history of consanguinity were identified as risk factors though they were not statistically significant (p>0.05). In group I (n=75), out of total study subjects, only 55(73.3%) cases belonged to the predominant castes, namely Awan, Rajput, Pathan, Araeen, Bhatti, Malik, Mughal, Sudhan, Chaudary, and Jutt. These individuals showed significantly higher mean serum interleukin-12 levels compared to patients of other castes in the same group. Conclusion: Mean serum interleukin-12 levels were higher in rheumatoid arthritis patients despite being on oral conventional synthetic disease-modifying anti-rheumatic drugs.

Comparison of oxidative stress, lipid peroxidation and inflammatory markers between rheumatoid arthritis and ankylosing spondylitis patients.

Objectives: To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis and ankylosing spondylitis. METHODS: The comparative, cross-sectional study was conducted from February 2 to December 30, 2022, at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi. The sample comprised healthy controls in group 1, patients of rheumatoid arthritis in group 2 and patients of ankylosing spondylitis in group 3. Blood samples were assessed for levels of superoxide dismutase, malondialdehyde, erythrocyte sedimentation rate and C-reactive protein. Data was analysed using SPSS 25. RESULTS: Of the 180 subjects, 60(33.3%) were in group 1; 32(53.3%) females and 28(46.7%) males with mean age 34.9±6.4 years. There were 60(33.3%) patients in group 2; 35(58.3%) females and 25(41.7%) males with mean age 46.0±11.1 years. There were 60(33.3%) patients in group 3, and all 60(100%) were males with mean age 35.9±6.9 years. Superoxide dismutase level was significantly low and malondialdehyde level was significantly high in groups 2 and 3 compared to group 1 (p<0.05). Erythrocyte sedimentation rate was the highest in group 2, followed by group 3 (p<0.05). C-reactive protein levels were the highest in group 2 and the lowest in group 3 (p<0.05). A significantly negative correlation (p<0.001) was found between superoxide dismutase and malondialdehyde. CONCLUSIONS: Oxidative stress played a pivotal role in chronic inflammatory rheumatic diseases, like rheumatoid arthritis and ankylosing spondylitis.

Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy.

Objective: To determine the association of diabetic nephropathy with glyoxalase-1 enzyme levels and a genetic missense variation (SNP rs4746) in its gene (GLO-1). Methods: This cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi from November 2020 to December 2022. One hundred patients and one hundred and thirteen healthy controls were enrolled using the nonprobability convenience sampling method. Medical history and 10ml blood were obtained from each individual after written informed consent. Blood samples were subjected to biochemical tests and DNA extraction which was later used for single nucleotide polymorphism (SNP) analysis (C332C variant of rs4741 GLO-1 gene) using Tetra primer ARMS PCR and gel electrophoresis. Glyoxalase-1 enzyme activity in serum was measured using ELISA. Results: There was a significant difference in serum glyoxalase-1 levels in the two groups (p-value< 0.001). The patient group had lower levels (16.24 ± 22.51mg/dl) of glyoxalase-1 as compared to the control group (48.70 ± 42.54mg/dl). In genotypic analysis, 98 out of 100 control individuals had AA genotype-while only one had CC and another AC genotype. In the patient group, 94 out of 100 patients showed AA genotype, three AC, and three CC genotypes. As the statistical significance (p-value) was 0.37, there was no significant association found between AC or CC genotype and diabetic nephropathy. Conclusion: Glyoxalase-1 levels are linked to the development of diabetic nephropathy in our patients while a known missense variant rs4746 in the GLO-1 gene is not associated with increased risk.

Association of single nucleotide polymorphism rs3213119 variant of IL-12B gene in diagnosed Rheumatoid Arthritis patients.

Objective: To identify the IL12B gene variant (rs3213119) and to find its association in Pakistani clinical population of Rheumatoid Arthritis. Methods: It was a population association (unrelated) case control study, performed from January - December 2022 at Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi. Blood samples were collected from all 150 study participants, followed by DNA extraction and Allele-specific polymerase chain reaction performed at Center for Research in Experimental and Applied Medicine (CREAM) Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' (version-22), followed by gene analysis on 'SNPstat'. Results: About 28.0% of RA patients were smokers, 38.7% had history of RA in a first degree relative and 70.7% had positive history of consanguinity. Considering rs3213119 variant of IL12B gene, frequency of major allele C was 100%, minor allele A was 21%, genotype C/C was 79% and C/A was 21%. Applying the log additive model, the odds ratio of the genotype C/C was 1.00 (adjusted by age and gender with 95 % CI) and the odds ratio of the genotype C/A was 0.00, 52.0% of RA patients originated from four predominant ethnic groups, namely Awaans (18.7%), Rajputs (14.7%), Pathans (12.0%) and Araeens (6.7%). Conclusion: The study findings suggest the role of minor allele 'A' as risk allele in our clinical population. CA genotype confers susceptibility towards the RA development.

An insight into genetic landscape of inflammatory bowel disease.

Inflammatory bowel disease has been regarded to be chronic intestinal inflammation characterised by a dsyregulatory immune response. The disease pathophysiology is known to be complex. Growing pieces of evidences underpin the involvement of various environmental and genetic determinants in the disease onset. The current narrative review was planned to manifest the contribution of genetic drivers for disease onset and to target signalling pathways that might present a therapeutic potential for further research. The factors of the disease that provide the genetic nature and understanding of the pathways involved have been researched in recent times. Also, numerous diseasedeveloping factors have been studied and assessed. Among them genetic determinants of disease onset have further improved the understanding of disease development. Genetic contributors to the onset of disease as well as important therapeutic targets need to be understood as predictive genetic risk factors have a potential implication for personalised treatment.

Aldose reductase gene polymorphism rs752010122 and retinopathy in type 2 diabetics.

Objectives: To investigate the association of polymorphism in rs752010122 in aldose reductase gene with the pathogenesis of diabetic retinopathy, and to determine the association and allelic frequency between the variant and the disease. METHODS: The cross-sectional study was conducted from June 2021 to March 2022 at Centre for Research in Experimental and Applied Medicine (CREAM) Laboratory, Department of Biochemistry and Molecular Biology, Army Medical College, in collaboration with the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, and comprised blood samples from subjects of either gender aged 40-70 years. The samples were divided into group I having diabetic retinopathy patients, group II having diabetics without retinopathy, and group III having healthy controls matched for age and gender. The samples were subjected to molecular analysis. Gene sequence was downloaded from the Human Genome Database and Ensemble. Data was analysed using SPSS 22. RESULTS: Of the 150 subjects, there were 50(33.3%) in each of the 3 groups. Variants of aldose reductase rs752010122 polymorphism were significantly associated with a lower risk of diabetic retinopathy (p<0.05). An odds ratio of 1 was noted for both heterozygous and homozygous genotypes (95% confidence interval: 1). CONCLUSIONS: Aldose reductase was associated with lower risk of the disease.

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects.

Objective: To find possible association of R1939W and P1987R variants of OTOF gene with severe to profound NSSHL in cochlear implant subjects. Methods: It was a case control study, conducted from June 2021 to February 2022, comprising 50 cases of severe to profound NSSHL who had received cochlear implant from ENT Department, CMH Rawalpindi and 50 age-matched healthy controls from PEMH Rawalpindi. Blood samples were collected from all the subjects, followed by DNA extraction and allele-specific polymerase chain reaction, performed at Multi-disciplinary Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using 'SPSS' and 'XLSTAT', followed by genetic analysis using 'SNPstat'. Results: Mean age of the cases was 5.96 ± 4.62 years (N=50), comprising 58% males and 42% females. All had bilateral and prelingual HL. Parental consanguinity was 72%, whereas 62% cases had a positive family history of deafness. Alleles of R1939W and P1987R were not associated with NSSHL, as shown by their p values of 0.56 and 0.89 respectively. For R1939W ORs were 0.71 (dominant model) and 0.80 (overdominant model), indicating negative association with NSSHL. Regarding P1987R OR was 0.96 (log-additive model). Genotypes of both variants were not in HW Equilibrium (p <0.0001), whereas their alleles showed high LD (D'=0.92). Conclusion: High percentage of parental consanguinity was observed among cochlear implant candidates. The OTOF variants R1939W and P1987R were found to have protective roles against NSSHL in study population.

Peroxisome Proliferator-Activated Receptor-α (PPARα) Expression in a Clinical Population of Pakistani Patients with Type 2 Diabetes and Dyslipidemia.

Poor glycemic control and dyslipidemia are hallmarks of type 2 diabetes mellitus (T2DM), which predispose to cardiovascular diseases. Peroxisome proliferator-activated receptor-α (PPARα) has been associated with atherosclerosis, but its role in T2DM is less clear. Previously, we studied PPARα expression levels in diabetics with and without dyslipidemia (DD). In this study we described the association with fasting blood glucose, HbA1c levels and lipid levels of the study population. Patient demography and biochemical data were collected from hospitals in Islamabad, Pakistan, and RT-PCR data of PPARα expression were retrieved from our previous study from the same cohort. We performed t-tests and regression analysis to evaluate the relationships between PPARα expression and demographic and clinical variables. As expected, body mass index and HbA1c were elevated in T2DM and DD patients compared to controls. Blood lipids (total cholesterol, triglycerides, LDL and HDL) were significantly higher in the DD group compared to the other two groups. In the T2DM and DD groups, the PPARα expression was not associated with any of the physical and biochemical parameters measured in this study. Expression of the PPARα gene was independent of blood lipids and glycemic control in this study. Further research is necessary to better understand the biological parameters of PPARα expression.

Association of C-262 polymorphism in catalase gene with rheumatoid arthritis.

OBJECTIVE: To evaluate the association of C-262 polymorphism in Catalase gene (CAT) with Rheumatoid Arthritis. METHODS: The comparative cross-sectional study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, in collaboration with the Rheumatology Department, Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2020, and comprised Deoxyribonucleic acid extraction of samples. Samples in group I belonged to diagnosed rheumatoid arthritis patients of either gender aged 30-60 years who were on disease-modifying anti-rheumatic drugs. Group II had an equal number of healthy controls. The promoter region of the CAT gene having the polymorphic segment was amplified through polymerase chain reaction, and its products were then subjected to restriction fragment length polymorphism for the analysis of polymorphic region of the CAT gene. Genotypic frequency equilibrium and the association of polymorphism with rheumatoid arthritis was checked. Also, association between fasting lipid profile and haemoglobin was assessed. Data was analysed using SPSSS 22. RESULTS: Of the 60 samples, 30(50%) belonged to each of the two groups. The mean age was 44.90±10.50 years (range: 30-60 years). Overall, there were 34(56.7%) males and 26(43.3%) were females. Two alleles and three genotypes of the polymorphism was detected. The frequency of CC genotype was higher in group I 23(76.6%), but no association of any of the genotype of polymorphism was found significant (p <0.05). Haemoglobin and lipid profile levels were significantly different in the two groups (p≤0.05). CONCLUSIONS: There was no significant association found between C-262 polymorphism in CAT gene and rheumatoid arthritis.

Association of Pro198Leu polymorphism in glutathione peroxidase one (GPX1) gene with peripheral neuropathy in type 2 diabetic patients.

OBJECTIVE: To evaluate the association of Pro198Leu polymorphism in glutathione peroxidase 1 gene in type 2 diabetic patients with neuropathy. METHODS: The comparative cross-sectional study was conducted from February 2 to November 30, 2018, at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Neurology, Military Hospital, Rawalpindi. Diagnosed type 2 diabetics of either genders aged 40-70 years were divided into two equal groups of neuropathy and non- neuropathy subjects. Deoxyribonucleic acid was subjected to restriction fragment length polymorphism for glutathione peroxidase 1gene analysis. Hardy Weinberg equation was used to check the genotype frequency equilibrium. RESULTS: Of the 60 patients, there were 30(50%) each in the two groups. Age, fasting glucose level and diabetes duration were significantly different between the groups (p<0.05). Even though the frequency of TT genotype was higher, no association of the polymorphism and any of the genotypes was found with diabetic neuropathy (p>0.05). CONCLUSIONS: There was no association found between Pro198 Lue polymorphism in glutathione peroxidase 1 and diabetic neuropathy.

Evaluation of correlation between expression of P53 and Malondialdehyde levels in prostate cancer patients.

The analytical study was conducted at the National University of Sciences and Technology, Islamabad, Pakistan from Nov 2012 to Nov 2013 to find out, correlate and assess negative correlation of serum malondialdehyde (MDA) with expression of p53 gene, and comprised 32 samples. Expression of p53 and MDA levels were determined by real time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) technique respectively. Mean value of MDA in prostate carcinoma (CaP) and control group were compared, and the difference was statistically significant (p=0.002). Mean cycle threshold (CT) value of CaP was compared with control group, and the difference was statistically significant (p<0.05). Expression of p53 was 0.18 folds decreased in CaP compared to control group. MDA may be used as marker to determine prognosis of CaP. Expression of p53 may be helpful in the diagnosis of CaP.

Report-Model studies of transmembrane interaction of FcεRIα/FcRγ reveal novel strategies to inhibit allergic responses.

The high-affinity IgE receptor complex plays an essential part in allergic responses and involved in downstream signaling, released inflammatory mediators that cause allergic responses. The transmembrane region of the high-affinity IgE has a conserved motif (LFAVDTGL) where a polar aspartate (D194) is important for the ligand binding. This modeling study proposes novel potential binding sites between high affinity immunoglobulin E receptor α subunit (FcεRIα) and FcRγ and as a consequence, we propose a new model of FcεRIα and FcRγ interaction (T194) which can mediate downstream signaling in allergic response. The docking of FcRγ with wild-type (D194) and mutant human high affinity immunoglobulin E receptor α subunit (D194T, D194I, D194L, D194A, D194V, D194E, D194S and D194R) has been performed on Autodock Vina. This modeling study is based on lab data obtained by carrying out site-directed mutagenesis done at residue D194 of FcεRIα to assess its functional importance for the mediation of intracellular signal cascade. HuFcεRIα D194 residue was replaced with threonine, leucine, serine, arginine, alanine, asparagine and glutamic acid. FcRγ docking on mutated huFcεRIα (D194T) indicated a new site of interaction and emphasizes the significance of the charge and size of an amino acid at position 194 in huFcεRIα subunit. Amino acids D & T at position 194 are important for cell surface localization, interactions, distribution and downstream signaling of IgE receptor subunit. These proposed models may herald in better therapeutic interventions to combat unfavorably allergic diseases.

The association of age with glycaemic and cholesterol control in patients with type 2 diabetes mellitus.

OBJECTIVE: To find the risk of dyslipidaemia in diabetic patients of different age groups. METHODS: This cross-sectional study was conducted at Holy Family Hospital, Rawalpindi, and Pakistan Ordnance Factories Hospital, Wah Cantonment, Pakistan, from February to July 2014, and comprised type 2 diabetic patients. Patients' body mass index was calculated and biochemical tests were performed for high-density lipoprotein, total cholesterol, low-density lipoprotein, triglyceride and glucose. Data was analysed using SPSS 20. RESULTS: Of the 40 patients, 17(42.5%) were men and 23(57.5%) women. The blood glucose control of younger age group (30-40 years) was 234±90.37mg/dl compared to older age group (60-70 years) with a mean of 173.4±54.2 mg/dl. Serum triglyceride levels of the youngest age group (30-40 years) were the highest with a mean value of 216±137 mg/dl. There was a significant association between age and triglyceride levels (p=0.03) , while the serum high-density lipoprotein level of this group was lowest with a mean of 29.6±13.4 mg/dl. CONCLUSIONS: There was a significant association between triglyceride levels in the youngest age group of patients with type 2 diabetes.

Association of Interferon Alpha Receptor 1 with sustained virological response in hepatitis C and B co-infected patients.

OBJECTIVE: To determine the association of interferon alpha receptor-1 with success rate of interferon therapy in patients co-infected with hepatitis C virus and hepatitis B virus. METHODS: The study was conducted at the Army Medical College, Rawalpindi, Pakistan, from December 2013 to November 2014, and comprised patients with hepatitis C and hepatitis B co-infection. The patients were treated with pegylated-interferon-2b plus ribavirin therapy for six months. With respect to interferon therapy, patients with undetectable hepatitis C virus-ribonucleic acid along with normal alanine aminotransferase were considered responders and patients with detectable hepatitis C virus-ribonucleic acid at week 48 were considered as non-responders. SPSS 20 was used for data analysis. RESULTS: Of the 86 patients, there were 50(58%) males and 36(42%) females. The presence of high pre-treatment interferon alpha receptors 1-messenger ribonucleic acid in peripheral blood mononuclear cells was significantly associated with sustained virological response (85.7% vs. 64.7%, P = 0.031). Multiple regression analysis showed that females (p < 0.001), lower hepatitis C virus-ribonucleic acid levels (p < 0.001) and lower hepatitis B virus-deoxyribonucleic acid levels (p < 0.001) were associated with expression level of interferon alpha receptors 1 in the co-infected patients. CONCLUSIONS: Interferon alpha receptors 1-messenger ribonucleic acid may be useful for predicting response to interferon plus ribavirin therapy in hepatitis C virus/ hepatitis B virus co-infected patients who were females with lower hepatitis C virus-ribonucleic acid and hepatitis B virus-deoxyribonucleic acid levels.

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.

Detection of Interferon Alpha Receptor 2 in Interferon Resistant HCV Patients.

BACKGROUND/AIMS: Hepatitis C virus infects more than 3% of the world's population and 4% of Pakistan's population. The virus multiplies in the host using novel methods, defending itself from the host's immune response, ultimately leading to liver cirrhosis and hepatocellular carcinoma. The approved therapy for the disease is interferon alpha combined with ribavirin. The disease is incurable, and often resistant, due to multiple viral and cellular factors. However, a strong host system can minimize the viral count to zero. This study was designed to detect the functional interferon alpha receptor 2 in liver biopsies of interferon resistant hepatitis C virus patients. METHODOLOGY: Total messenger ribonucleic acid was isolated from the liver biopsies of the interferon resistant hepatitis C virus patients and subjected to complementary deoxyribonucleic acid synthesis. Primers specific to interferon alpha receptor 2 were designed and used in polymerase chain reaction to detect interferon alpha receptor 2. RESULTS: Interferon alpha receptor 2 was detected in 90% of interferon resistant hepatitis C virus patients. CONCLUSION: Lack of expression of functional Interferon Alpha Receptor 2 does not seem to be the major cause of interferon resistance in hepatitis C virus patients receiving standard interferon therapy.