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Predisposition to diabetes is attributed to a large number of genes. TCF7L2 is one of the most significant candidate genes among them, and it is crucial for beta-cell activity and blood glucose regulation. According to previous research, TCF7L2 has been implicated in T2DM in various Indian tribes. Many studies have discovered a link between TCF7L2 gene variations and vulnerability to T2DM. These results suggest that changes in TCF7L2 expression are not only associated with insulin resistance but also with risk for genotypes connected to poor beta cell activity. TCF7L2 drives the conventional Wnt signalling pathway and functions as a nuclear ligand for beta catenin. Wnt signalling is necessary for intestinal endocrine L-cells to emit GLP-1 (glucagon-like peptide-1). As a result, a blockage in this route would cause less GLP-1 to be released, which might have an impact on the release of insulin after meals contributing to T2DM as a result. The molecular processes through which the TCF7L2 gene increases the susceptibility of T2DM will therefore be of significant interest, as will the identification of possible therapeutic targets that may be employed to treat and prevent the illness as a result of the gene variations.

Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p

Diabetic nephropathy (DN) is a chronic complication of both type 1 and type 2 diabetes. However, there is still inadequate understanding of the exact mechanism related to progressive diabetic renal disease. The GLUT-1 XbaI gene polymorphism in the glucose transporter has been suggested in the development of DN. However, its association with T2DM and DN is controversial and has not been established in different ethnic populations. To enhance the understanding of GLUT-1 XbaI gene polymorphism in the context of T2DM and DN. We investigated the possible genetic association of GLUT-1 XbaI polymorphism with T2DM and DN in North Indian population. 100 T2DM patients and 100 patients of DN with 100 healthy controls were included in the study. GLUT-1 XbaI polymorphism was determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). The obtained data showed no significant association between GLUT-1 XbaI gene polymorphism with T2DM and DN leading us to conclude that GLUT-1 XbaI gene polymorphism may not have major effects on T2DM and DN in North Indian population.

Diabetes in combination with abdominal obesity and hypertension is the leading cause of cardiovascular diseases (CVD) and death. Type 2 diabetes (T2DM) increases CVD risk in two- to fourfold. The prevalence of CVD is constantly rising in India and is higher in urban areas. In addition, more than 50% of diabetic patients are still undiagnosed in the general population. The Madras Diabetes Research Foundation-Indian Diabetes Risk Score (MDRF-IDRS) is a cost-effective and very simple tool, which can be used at a primary health care center routinely. It is observed that people with increasing age, sedentary lifestyle, greater abdominal obesity, and family history of diabetes are at a high risk for diabetes and its complications. MDRF-IDRS is helpful for mass screening of diabetes and its complications in North Indian population to prevent the incidence of diabetes and with lifestyle interventions, knowledge, and awareness, it helps to reduce and revert the complications of diabetes. It is suggested that regular practice of MDRF-IDRS-based screening at primary health care center may also reduce the burden at the critical care center in North India.

Background and objectives Pulmonary hypertension (PH) is an independent risk factor for increased mortality, especially in patients undergoing hemodialysis (HD), but the mechanism of its development is unknown. This study aimed at evaluating volume overload and inflammation as potential variables to cause its development in patients undergoing maintenance hemodialysis. Materials and methods This was an observational cross-sectional study conducted on patients undergoing hemodialysis at a tertiary hospital in northern India. Patients of end-stage renal disease, aged 18 years or more, on maintenance hemodialysis for over two months were included in the study. The patients were divided into two groups based on the presence or absence of PH, determined by measuring systolic pulmonary arterial pressure (SPAP). The severity of PH was defined as: mild (SPAP 35-45 mmHg), moderate (SPAP 46-55 mmHg), and severe (SPAP> 55mmHg). The two groups were evaluated for demographic variables, type of vascular access, biochemical parameters, and markers of inflammation and fluid overload. Data between the two groups were compared statistically. Results This study included a total of 82 patients showing the prevalence of PH to be 25.6% with a men-to-women ratio of 2:1. Out of 21 cases of PH, mild PH was found in seven (33.3%) cases, moderate in 14 (66.7%), and cases with severe PH were none. The two groups differed significantly in ejection fraction and markers of inflammation and volume status. Laboratory data associated with PH were alpha-1-acid glycoprotein (p

Introduction: Anemia is common in Chronic Kidney Disease (CKD) and diabetes is a major leading risk factor for it. In Diabetic Kidney Disease (DKD), it worsens more, which further increases cardiovascular morbidity and mortality. Despite of adequate iron stores anemia persist, which may be due to impaired iron release from body stores that is unable to meet the demand for erythropoiesis (also called reticuloendothelial cell iron blockade). High parathyroid hormone (PTH) along with vitamin D, may be attributable for anemia. Methods: A cross-sectional study of 150 advanced (Stage 4 & 5) pre dialyzed DKD patients (GFR

Diabetic kidney disease is one of the most serious microvascular complications and among the leading causes of end stage renal disease. Persistently increasing albuminuria has been considered to be the central hallmark of nephropathy. However, albuminuria can indicate kidney damage for clinicians; it is not a specific biomarker for prediction of diabetic kidney disease prior to the onset of this devastating complication, and in fact all individuals with microalbuminuria do not progress to overt nephropathy. Controlled glycemia is unable to prevent nephropathy in all diabetic individuals indicating the role of other factors in progression of diabetic kidney disease. There are numerous cellular and molecular defects persisting prior to appearance of clinical symptoms. So, there is an urgent need to look for easy, novel, and accurate way to detect diabetic kidney disease prior to its beginning or at the infancy stage so that its progression can be slowed or arrested. It is now accepted that initiation and progression of diabetic kidney disease are a result of complex interactions between genetic and environmental factors. Environmental signals can alter the intracellular pathways by chromatin modifiers and regulate gene expression patterns leading to diabetes and its complications. In the present review, we have discussed a possible link between aberrant DNA methylation and altered gene expression in diabetic kidney disease. Drugs targeting to reverse epigenetic alteration can retard or stop the development of this devastating disease, just by breaking the chain of events occurring prior to the development of this microvascular complication in patients with diabetes.

Background and Objectives: Insulin action of reducing blood glucose has been found to be enhanced by trace elements. Material and Methods: This was a cross sectional study including 150 patients with Type 2 Diabetes Mellitus (T2DM) and 50 controls. Serum concentrations of zinc, copper, chromium, selenium and magnesium was measured by colorimetric kit. Fasting Blood Glucose and Glycated Haemoglobin (HbA1c) were assayed using the standard kit. Results: Out of 150 patients, 85.4% (n = 128) of the cases had uncontrolled blood sugar with HbA1c ≥7 and only 14.6% (n = 22) had good control of blood sugar with HbA1c

Introduction: Anaemia contributes significantly to the morbidity and mortality in Chronic Kidney Diseases (CKD). Erythropoietin Stimulating Agents (ESA) have revolutionised the management of the anaemia in CKD patients. However, over 50% of the patients do not reach the target haemoglobin level. Hepcidin which plays important role in iron metabolism and inflammation may be the cause of this hyporesponsiveness to ESA. Aim: The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy with special attention to hyporesponsive anaemia in advanced kidney disease. Materials and Methods: In this cross sectional study, total of 81 clinically stable patients from Department of Medicine and Nephrology, King George’s Medical University, Lucknow of advanced CKD on ESA for past 12 weeks were enrolled. Patients whose haemoglobin rose more than 2 gm/dL or were above 10 gm/dL were classified as responders while below 10 gm/dL were classified as poor responders. Results: In present study, majority 54 patients (66.7%) were poor responders to ESA. We found significant higher level of hepcidin in poor responders (p=0.01) while no significant variation in serum iron, Transferrin Saturation (TSAT) and ferritin. High sensitivity C-Reactive Protein (hsCRP) was markedly elevated with median value 3.13 mg/L and Interquartile Range (IQR) (1.14-13.78) in all patients. Conclusion: Hepcidin may be one of the causes of hyporesponsiveness to ESA due to reticulo-endothelial blockade of iron.

Metabolism is a delicately coordinated entity of chemical reactions. Inborn Errors of Metabolism (IEM) are rare congenital disorders that are mainly due to gene defect of enzymes or cofactors participating in a metabolic pathway or the transport of metabolites within a cell or between cells. The development of knowledge in basic sciences together with technology development in medical field has helped to better understand the molecular and biochemical basis of IEM. Environmental factors, ethnicity, race, consanguinity and genetic factors contribute to the increased prevalence of genetic disorders. The analytical methods have evolved over the years from thin layer chromatography (TLC), high performance liquid chromatography (HPLC) to tandem mass spectrometry (TMS) including gas chromatography mass spectrometry (GC/MS). Their applications for È¡7_Ø‹5_g of IEM has opened the door for screening of conditions that previously required molecular testing or another methodology that was not practical for population-based screening. Future technologies such as Matrix-assisted laser desorption/ ionization timeof- flight mass spectrometry (MALDI-TOF MS), has the potential for rapid and reliable identification of small metabolites and disease biomarkers in daily clinical laboratories, whereas DNA based screening by DNA microarrays or gene chips will allow much more improved diagnosis.These can be the boon to screening programs which will require excellent detection and follow-up servicesInternational Journal of Human and Health Sciences Vol. 03 No. 02 April’19. Page: 58-63

Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P 0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.

Homocysteine (Hcys) has been implicated to be associated with diabetes and its complications. To study the association of plasma Hcys with diabetes complications (cardiovascular disease [CVD], cerebrovascular disease [CBVD], peripheral vascular disease [PVD], nephropathy, retinopathy and neuropathy). 316 type 2 diabetic patients were enrolled for the study. Plasma Hcys was done by Chemiluminescence Micropart assay. Elevated plasma Hcys correlated significantly with duration of the disease, CVD, CBVD, PVD, Nephropathy, Retinopathy and Neuropathy showed significant association with abnormal plasma Hcys level. Total cholesterol and triglyceride was significantly associated with abnormal plasma Hcys level. However Hb1Ac, LDL and HDL did not show significant correlation. Plasma Hcys level can be considered as an early marker of progression of diabetes and its complications.

Psoriasis is a T cell mediated inflammatory skin disease. Complex network of cytokine induces and maintain the psoriatic lesion. Study was performed to evaluate the correlation between the level of TNF- α and IL-6, in the psoriasis patients with HLA-Cw6. Cytokine levels were assayed by sandwich ELISA and HLA-Cw6 typing was done by microcytoxicity method. Serum TNF-α and IL-6 were significantly (p=

Seronegative spondyloarthropathies (SSA) are a group of inflammatory disorders, which clinically involve the axial skeleton and the sacroiliiac and shoulder joints. The aim of the present study was to study the association of HLA B27, B7, Bw4 and Bw6 with some inflammatory diseases, in SSA patients in our area. A total of 220 SSA patients were studied and HLA typing for these antigens were done by the complement-mediated microcytotoxicity method. The total positivity of B27 was found to be 68.64% in SSA patients. Tubercular infection (chi(2) = 8.06) and acute anterior uveitis (chi(2) = 6.19) were found to be statistically significant (P < 0.05) in B27-positive SSA patients. Tuberculosis was also found to be significantly (chi(2) = 6.40) associated with Bw4. In SSA urinary tract infection, gastrointestinal infection and streptococcal infection were not significantly associated with B27, B7, Bw4 or Bw6 antigens. Our study concludes that microbial infections do have some pathogenic role in causing SSA.

INTRODUCTION Renal transplant rejection involves both immunological and non-immunological factors. The objective of the present study was to investigate the association between immunological factors, such as serum interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α), and non-immunological parameters, such as age, serum creatinine (SCr), creatinine clearance (CrCl) and dyslipidaemia, in renal transplant recipients (RTRs). METHODS This study included 90 RTRs and 90 healthy controls. Biochemical parameters, including serum IL-6 and TNF-α, were estimated using standard protocols. CrCl was calculated using the Cockroft-Gault equation, and the type of rejection was confirmed on biopsy. Student's t-test and univariate and multivariate analyses were performed using the Statistical Package for the Social Sciences for Windows version 15. RESULTS The mean levels of serum IL-6 and TNF-αwere significantly higher in RTRs than in the control group (p < 0.001). These parameters were also found to be significantly different between the transplant rejection (TR) and transplant stable (TS) groups (p < 0.001). CrCl was significantly decreased in the TR group when compared to the TS group (p < 0.001). The two cytokines, IL-6 and TNF-α, correlated significantly with all metabolic parameters, such as SCr, CrCl and dyslipidaemia. Multiple regression analysis showed that TNF-α and CrCl were the strongest predictors of IL-6. CONCLUSION We conclude that immunological factors, as well as non-immunological factors such as CrCl, SCr and dyslipidaemia, play important roles in the pathogenesis of graft rejection and renal graft dysfunction.

Human Immunodeficiency Virus (HIV) infection is a global pandemic. According to the data released by UNAIDS in 2007, India had 2.5 million people living with HIV infection.[1] Next to sub-Saharan Africa, it has the second largest burden of HIV-related illness. Though the main targets of HIV infection are the cells of the immune system, the nervous system is often damaged during the course of infection, not only by disease processes that are secondary to immune dysfunction but also by more fundamental effects of the retrovirus.

Tumor necrosis factor alpha (TNF alpha) is a cytokine secreted by macrophages, helper T cells, natural killer cells, B lymphocytes and non lymphoid cells e.g. endothelial cells, fibroblast and tumor cell lines. Aim of the study was to find the utility of TNF alpha in diagnosing renal transplant rejection among the renal transplant cases (n=29), and comparison with the levels in patients on maintenance hemodialysis (n=21) and healthy controls (n=20). TNF alpha in healthy controls varied from 2 to 15 pg/mL. In chronic renal failure and renal transplant rejection cases TNF alpha was above 45 pg/mL. In stable renal transplant patients it was higher than normal (16 to 30 pg/mL). In both acute and chronic transplant rejection TNF alpha increase correlated well with histology. Thus our study suggests that TNF alpha level more than 45 pg/mL can be taken as an immunological marker of renal transplant rejection.

Seronegative Spondyloarthropathies (SSA) is a very common problem in our area. The main aim of present study was (1) to find the HLA B27 positivity in patients presenting with sacroileitis (2) to see the correlation of B27 positivity on haematological, radiological and extra articular manifestations. Total 110 patients of SSA were studied between July 2004 to June 2005. Routine haematological and immunological test were done by standard method. Total positivity of B27 in SSA was 43.63%, HLA B27 positivity was higher in children (68.75%). Sex wise analysis of B27 positive cases showed that 81.81% B27 positive patients were males. In HLA B27 positive cases lower spine, hip, sacroiliac, shoulder and knee joints were more involved (77.08%, 79.16%, 79.16%, 37.50% and 50.00% respectively). Urinary tract infection (UTI), diarrhoea and constipation were more common in B27 positive cases. Leukocytosis of neutrophilic type (33.33%), raised ESR (77.55%)., CRP positivity (63.63%) and anaemia (65.00%) were seen more frequently in B27 positive cases. In bilateral sacroiliitis diagnosed by X-ray, only 69.23% patient were B27 positive. Our study concludes that HLA B 27 positivity is higher in SSA seen in childhood and in young adult males. B27 positive patients have more severe disease and systemic manifestation Hence, male patients specially young adolescent or young adults with sacroileitis must be subjected for B27 typing.

We present three cases of unusual and complicated malaria caused by Plasmodium vivax. Parenteral artemisinin derivatives or quinine should be used, irrespective of chloroquine sensitivity, for treatment of severe malaria.

Coexistence of ankylosing spondylitis with connective tissue diseases is uncommon. We describe here the coexistence of ankylosing spondylitis and systemic lupus erythematosus in a 35-year-old man. He presented with a 4-year history of pain in the hip joint and lower spine, and he later developed a malar rash and discoid rash. Immunological tests revealed that antinuclear antibody and double stranded DNA antibody were positive. The human leukocyte antigen B27 antigen was also found to be positive. We propose that development of systemic lupus erythematosus in this case may have been due to low grade chronic inflammation.

Heat stroke is a life-threatening condition which is characterised by nausea, vomiting, confusion, disorientation and coma. Aggressive treatment in the form of intravenous fluids along with other symptomatic management can be life saving. Here we present an unusual case of heat stroke followed by disseminated intravascular coagulation, multiple organ dysfunction with bilateral intracerebral bleed who survived with judicious management and recovered without any neurological sequeale.