Search

Gene therapy is an experimental treatment being investigated to correct defective genes that are responsible for disease development. To treat cancer and genetic illnesses, researchers are looking into a variety of gene therapy techniques. Finding a proper vector to transfer DNA into tissues is one of the most difficult aspects of gene therapy. Some gene therapy vectors have issues with infecting both quiescent and dividing cells, provoking an immunological response, lack of indefinite expression, and reproducible high titre. The adenovirus, retrovirus, and recombinant modified adeno-associated virus are top contenders for gene therapy vectors (rAAV). The issues with gene therapy may be resolved by the adeno associated virus (AAV). Hemophilia is a condition which may be benefited by the gene therapy using AAV as vector. Aim of this review is to emphasize on the role of adeno associated virus receptors(AAVR) and co-receptors in tropism and transduction of adeno associated virus(AAV) in the gene therapy of hemophilia In Vitro as well as In Vivo.

Osteocalcin (OC) and bone mineral density (BMD) measurements determine the bone mass and microarchitecture of bone. Both are used for diagnosing osteoporosis and their role as a biomarker in postmenopausal osteoporosis (PMO) remains controversial. To determine the relationship between serum OC and PMO and compare BMD vs OC, a metaanalysis was carried forward with case-control studies. Studies reporting mean/median and standard deviation of osteocalcin in post-menopausal women with and without osteoporosis were included. From the same studies, BMD measurements in both groups were included. Fifteen studies were included with 1864 postmenopausal women. We found significant increase in serum OC (Standardized Mean Difference of 0.918 and SE of 0.476 (p=0.054), confidence interval (CI) (-0.015 to 1.852) and significant decrease in BMD values (SMD of -2.321 and SE of 0.345 (p= 0 and significantly low BMD/t score levels with SMD 0 serum osteocalcin solely can be implemented as a promising marker for diagnosing osteoporosis.

NIL

Objective: The objective of the study is to compare three techniques, routinely used rapid diagnostic tests (lateral flow immune chromatography) versus nucleic acid amplification test (NAT) versus Paper-based microfluidics for DNA diagnostics of Malaria, in terms of their sensitivity and specificity as diagnostic tests in detecting malarial infection among febrile illnesses, suspected of malaria, as well as to compare their cost-effectiveness. Methodology: Three seventy febrile cases suspected of malaria with negative results with RDT will be screened by real-time PCR and DNA microfluidics techniques, sensitivity and specificity of these as screening tests will be compared. The number of extra positive cases detected by NAT gives us the yield. Cost-effectiveness analysis will be done by calculating the incremental cost-effectiveness ratio (ICER) and average cost-effectiveness ratio (ACER) for the tests. Statistical Analysis: Statistical analysis will be done using SPSS version 21. Sensitivity, specificity, Positive predictive values will be computed. Comparison of sensitivity and specificity of NAT, a paper microfluidic technique for DNA diagnostics and RDT will be carried out using McNemar’s test. Receiver operating curves will be generated separately to assess the utility of the NAT. Conclusion: The Implications of this study from the patient's perspective would mean early diagnosis which forms the tenet of control of the disease by increasing the yield. Early diagnosis at the community level would translate into the application of efficient prevention mechanisms to spread the infection. The cost-effectiveness analysis would provide a scientific basis for the adoption of the best test for the diagnosis, given the economic feasibility of the study.

BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes. METHODS In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3. RESULTS Hardy-Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively). CONCLUSION Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.

To evaluate the pattern of UGT1A6 and UGT2B7 gene polymorphism in pediatric epileptic patients and to compare the sodium valproate concentration in different patterns of UGT gene polymorphism. In this cross-sectional study, 99 pediatric epileptic patients aged 2–18 y receiving Sodium valproate monotherapy for the past one month were included from JusticeK S Hegde Charitable hospital, Mangalore after obtaining informed consent. Genetic polymorphism patterns were evaluated by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Trough level serum valproate concentration was estimated by high-performance liquid chromatography (HPLC). Sodium valproate concentration in different UGT genotypes was compared by Analysis of Variance (ANOVA). P value

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Chronic hyperglycemia induces reactive oxygen species and increases oxidative stress. Human serum paraoxonase-1 (PON-1) is an enzyme synthesized in the liver, and it is an antioxidant enzyme with a beneficial role in fighting oxidative stress. The objective of the study was to compare PON-1 activity in type 2 diabetes mellitus (T2DM) and nondiabetics, as well as to find the association between PON-1 activity and different insulin resistance (IR) models in diabetics.The cross-sectional study recruited 100 diabetic and 100 age and gender-matched controls. Fasting blood glucose, insulin, and C-peptide, were assayed. PON-1 activity was measured by the spectrophotometric method. Various insulin resistance models based on insulin and C-peptide were constructed using appropriate formulae. Receiver operating characteristic was constructed to find if PON-1 can be a good marker for diabetes.PON-1 activity was found to be significantly higher (p0.0001) in diabetics compared to controls. Highly significant hyperinsulinemia (p0.0001) was noted in diabetics. C-peptide levels were significantly lower in cases (p = 0.0215) as compared to controls. Homeostasis model assessment (HOMA)-IR C was insignificantly higher in cases. HOMA B cell, HOMA 1% B cell, and C-peptide-based IR (CIR) were significantly lower in cases (p0.0001 and p = 0.002), respectively, as compared to controls. An odds ratio of 3.15 was obtained, which suggests that the risk of T2DM is 3 times higher in subjects with elevated PON-1 levels. Chi-square showed a significant association (p = 0.0001) between DM and PON-1 levels; the chi-square statistic value (with Yates correction) was 14.49. Correlation data showed that PON-1 activity had a significant negative correlation with quantitative insulin sensitivity check index (r = -0.265, p = 0.019). A significant negative correlation (r = -0.22, p = 0.016) was also seen between PON-1 and CIR (HOMA-IR C). There was no significant correlation seen between PON-1 and other IR models.It can be concluded from our study that PON-1 activity is elevated in T2DM patients, which can be a beneficial marker.

Background: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Methods: Hundred GDM patients and an equal number of BMI and gestational age matched normal glucose tolerant pregnant women were recruited as cases and controls. Five milliliters of venous blood was drawn for biochemical and genetic analysis. Genotyping of LEPR (Gln223Arg) was performed by PCR-RFLP. Fasting blood sugar, leptin, insulin, C-peptide, and lipid profile estimations were done. Various insulin resistance models were constructed using suitable formulae. The statistical analysis was performed using SPSS 23.0 software. Results: There was no significant association found between LEPR gene polymorphism with leptin levels and insulin resistance in GDM. However, Odd’s ratio showed that individuals with the “A” allele were at 1.25 times higher risk of developing GDM. HOMA B-cell significantly varied among LEPR genotypes (p

Aims of the study were to compare liver markers in T2DM patients with that in non-diabetic healthy volunteers and also to find the correlation between insulin resistance(IR) and liver markers. The objective of the study was also to find out whether PON1 can be an alternative liver marker. The cross-sectional study was conducted in the Clinical Biochemistry laboratory. 114 type 2 DM patients in the age group 18-65 years, diagnosed as per ADA guidelines were recruited in the study.100 age and gender-matched non-diabetics, healthy volunteers or those having health packages were taken as controls. The blood sample was collected and fasting blood glucose, transaminases and Alkaline phosphatase, bilirubin (total and direct), total protein, albumin, and insulin were assayed. HOMA-IR was calculated. Statistical analysis was done by using SPSS 16. A significant elevation was seen in AST, ALT, ALP, GGT, TB, DB, TP, A: G ratio in diabetics. A lowered albumin and A: G ratio were observed in diabetics as compared to controls. Fasting insulin levels were 1.7 times higher in diabetics compared controls, suggesting hyperinsulinemia in cases. Homeostatic model for assessment of insulin resistance (insulin based) was 2.7 times greater in T2DM compared to controls. A significant positive correlation was found between insulin levels and total and direct bilirubin, (r=0.279, P=0.003, and r=0.233, P=0.014 respectively). ALP, total and direct bilirubin had a significant positive correlation with HOMA-IR (r=0.228,P=0.033,; r=0.231,P=0.030 ; r=0.242. P=0.023 respectively).A very significant negative correlation was found between albumin and HOMA- IR (r= -0.306, P=0.004). A significant positive correlation was observed between PON1 and HOMA-IR (P=0.000), PON and insulin (P=0.015). It can be concluded from that diabetics had high liver enzymes as compared to non-diabetics. An association was found between T2DM, liver markers, and IR. It was observed that PON1 was not a good liver marker in T2DM.

BACKGROUND Epilepsy is a chronic neurological disease characterized by recurrent unprovoked seizures. Therapeutic drug monitoring (TDM) has often been performed during the pharmacological treatment of epilepsy, but the plasma levels of some AEDs do not correlate well with the doses and/or the therapeutic or toxic effects of the drugs. OBJECTIVE Objective of the study is to evaluate the pattern of polymorphism in UGT1A3 in pediatric epileptics on valproate. It also aims to find the association between gene polymorphism and plasma concentration of valproate, its clinical effectiveness and its adverse effect profile. METHODS One hundred children aged 2-18 years with a diagnosis of epilepsy and treated with sodium valproate mono therapy will be included in the study. Their demographic profile, type of seizure, dose and frequency of sodium valproate will be recorded. Five ml of venous blood will be collected after 30 days of starting the regimen,3ml EDTA blood will be utilized for genotyping by PCR-RFLP method and for platelet count, 2 ml plain blood will be used for estimating serum drug concentration by HPLC and for biochemical tests. The patient will be followed up quarterly or more frequently (as deemed by the clinician) for clinical evaluation. Statistical analysis: Hardy-Weinberg equilibrium (HWE) analysis will be performed on UGT1A3 polymorphisms. ANOVA will be used to investigate the association between genotypes distribution and serum concentration of VPA. A p-value RESULTS The study is funded by Indian council of Medical research, sanction letter dated 19.08.2019 No.5/4-5/187/Neuro/2019-NCD-I. The university ethical approval was obtained, ref NU/CEC/2019/0223.A total of thirty samples are collected at the end of six months.PCR-RFLP and HPLC methods are standardized and results will be available on completion of the study. CONCLUSIONS Genetic polymorphisms of UGTs may influence VPA metabolism and hence the steady-state concentration of the drug in plasma may be altered. This may demand an increased or reduced dose of VPA in epileptics so as to maintain the therapeutic levels. The study may be useful in optimizing the anti-epileptic dosage. CLINICALTRIAL NOt applicable.

Introduction: Type 2 diabetes mellitus is a metabolic disease characterized by insulin resistance and defective insulin secretion. Quantification of insulin resistance is essential as it may guide treatment options. The aim of the study was to compare HOMA-IR (both insulin and C-peptide based) and QUICKI in type 2 diabetes mellitus patients. Methodology: The cross-sectional study included a hundred and fourteen type 2 DM patients diagnosed as per the American Diabetic Association 2017 guidelines. Fasting blood glucose, insulin and C-peptide were assayed. Insulin resistance and beta cell functioning were calculated by HOMA for insulin and Cpeptide using suitable formulas. Linear regression analysis was done to correlate insulin and C-peptide based HOMA.ROC curves were constructed to compare different insulin sensitivity indices. Results: There was a significant correlation (p=0.007) between insulin and C-peptide based HOMA-IR (r=0.3654. r2=0.1335). Insulin and C-peptide based HOMA1% B also had a significant correlation, p=0.0066 (r=0.2975. r2=0.08850). Insulin and C-peptide based HOMA-B cell also had a significant correlation, p=0.0019 (r=0.3223. r2=0.1039). A linear negative correlation was observed between QUICKI and HOMA-IR (p=0.0001) and HOMA-C (p=0.0004) respectively. ROC curve showed that Cpeptide based HOMA model had the highest area under the curve, 0.836 with better sensitivity and specificity compared to other insulin resistance/sensitivity models. Conclusion: Insulin and C-peptide based HOMA-IR are positively correlated. C-peptide based HOMA is a more sensitive and specific marker of insulin resistance compared to insulin based HOMA-IR and QUICKI.

Objective: Aim of the study , was to compare the efficacy of regimens containing zidovudine, stavudine and tinofovir by comparing CD4 counts of patients at the end of 2 years .We also aim to evaluate their efficacy, by comparing basal CD4 count and CD4 count at 2 years in patients on these three regimens. Methodology: A retrospective observational study was conducted on 128 HIV patients, receiving various antiretroviral regimens in a teaching hospital in coastal Karnataka. Data of patients who were diagnosed to be HIV positive, receiving HAART and were attending the hospital for regular follow up once in six months was collected in data extraction form. Regimens containing zidovudine, stavudine and tinofovir were evaluated by comparing 2 year CD4s of patients. Effectiveness of each regimen was evaluated by comparing basal CD4 count with CD4 count at the end of 2 years. Results: We did not find any significant difference in basal CD4 counts in 3 regimens. CD4 count at the end of 2 years differed significantly (P

Introduction: Inspite of HAART, it has been found that viral replication persists even when viral load is undetectable. Adherence has been reported to be positively associated with CD4 count in various settings. Objectives of our study were comparison of basal CD4 count of HIV patients on various ART regimens with that at six months and one year as well as finding correlation between percentage adherence to ART and CD4 counts at six months and one year. We also aimed to compare percentage adherence and CD4 counts of patients on various ART regimens. Methodology: A retrospective observational study was conducted on 63 HIV patients, receiving four antiretroviral regimens (AZT/3TC/NVP, AZT/3TC/EFV, d4T/3TC/NVP and d4T / 3TC / EFV). Patient demography, drug regimen, baseline CD4 counts, serial CD4 counts (every six months), and adherence to ART (monthly) were recorded. Comparison of basal CD4 counts with that at six months and one year was done. Comparison of CD4 count and adherence were done between the groups. Results: An extremely significant elevation was seen in CD4 counts at six months and at one year (p < 0.0001). Linear regression showed a significant positive correlation (p = 0.037) between adherence and CD4 counts at one year. There was no significant difference in percentage adherence and CD4 counts between four groups. Conclusion: We conclude that optimal CD4 levels were obtained in patients on all four different regimens. However percentage adherence was suboptimal in all groups which caution to take appropriate measures to achieve optimal drug adherence.

Introduction: Lipemia is represented as turbidity in the serum or plasma which becomes evident before the analytical process. It is mainly caused by large particles of lipoproteins such as chylomicrons or VLDL, the main lipid component of which is triglyceride. Lipemic interference is commonly found in routine clinical chemistry tests. It can, not only influence measurements of analytes, but can also cause false increase or decrease intheir levels. The aim was to use Lipemic index (LI) as an automated determinant of lipemia in venous blood specimens sent to our clinical chemistry laboratory and measure the extent of turbidity. Methods: The study was conducted in Clinical Biochemistry laboratory in the month of January 2016.Total of 809 samples were collected and lipemic index (LI) was estimated in autoanalyzer, transasia XL-640.LI values were categorized from L- to L++++.Percentage of sample in each category was calculated. Results: Most of our patients (68.23%) had LI

Objective: The aim of the study was to study the cost of illness of uncomplicated and complicated type 2 diabetes mellitus.Methods: The non-interventional retrospective study was carried out in K.S. Hegde Medical Academy. Annual laboratory costs, pharmacy cost, consultation charges, hospital bed charges, and surgical/intervention costs of 340 diabetic patients were obtained from the medical record section of the hospital. Patients were divided into six groups, uncomplicated, diabetic retinopathy (DR), nephropathy, neuropathy, diabetic foot (DF), and those with ischemic heart disease (IHD) and different costs were compared. Correlation of costs with duration of the study and glycemic control were studied.Results: Uncomplicated patients had significantly lower costs (p

Introduction: CD4 count can be used as marker to assess the effectiveness of antiretro viral treatment (ART), mortality and survival rates in HIV patients. It is an important guide to treatment as it reflects drug resistance, treatment failure and need to switch over to different regimen. Objective of the study was to assess the effectiveness of two regimens, Nevirapine (NVP) versus Efavirenz (EFV), both in combination with Zidovudine (AZT) and Lamivudine (3TC) in HIV patients. Methods: A retrospective observational study on 48 adult HIV patients, receiving AZT+3TC+NPV (ZLN) (group I) and 28 patients on AZT+3TC+EFV (ZLE) (group II) was carried out. Demographic profile, medication prescribed, baseline CD4 cell counts, serially monitored CD4 count values for 2 years and Hb% were recorded from patient's medical record.Basal and 2 yr CD4 counts were compared using suitable statistical tests. Results: A very highly significant (p=0.0001) increment in CD4 count was observed in both the groups after treatment. Mean CD4 count of 2 years was significantly high (p=0.038) in patients on EFV regimen as compared to those on NVP. Conclusion: We conclude that ART regimen containing EFV is superior to NVP. However further studies need to be done in this area, by taking adherence to treatment, concomitant infections, ADRs in to consideration. Key words: CD4 Count, Efavirenz, Nevirapine

BackgroundEpidemiologic studies demonstrate a relation between preeclampsia and an increased risk of future maternal coronary heart disease. The pathophysiology of the underlying mechanism is unknown. Disorders of lipoprotein metabolism may contribute to endothelial dysfunction. Oxidative stress and decreased antioxidant defense enhances free radical-mediated membrane lipid peroxidation and possibly vascular endothelial damage. The aim of this study was to elucidate the possible relation between lipidemic status, lipid peroxidation and albumin with total antioxidant activity (AOA) that may contribute to atherogenicity in preeclamptic women.MethodsTwenty-five women with preeclampsia and 25 normal pregnant women who were matched for maternal and gestational age were selected for the study. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), atherogenic index (AI), malondialdehyde (MDA), a marker of lipid peroxidation, AOA and albumin levels were measured.ResultsMDA, TC and AI were significantly elevated (p < 0.001), and HDL-C, AOA and albumin levels were significantly decreased (p < 0.001) in preeclamptic patients compared to the control group.ConclusionWe conclude that hypercholesterolemia leads to excessive lipid peroxidation. Coexistent diminution in antioxidant activity leads to an imbalance between prooxidants and antioxidants, resulting in oxidative stress. Oxidative stress and elevated AI may contribute to atherogenicity in preeclampsia.