Deepika Sharma

Role of the renin angiotensin system in diabetic nephropathy.

Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.

Role of Endothelin and Inflammatory Cytokines in Pre‐eclampsia – A Pilot North Indian Study

Citation Sharma D, Singh A, Trivedi SS, Bhattacharjee J. Role of endothelin and inflammatory cytokines in pre‐eclampsia – a pilot north Indian study. Am J Reprod Immunol 2011; 65: 428–432

Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of pre-eclampsia.

Citation Singh A, Sharma D, Raghunandan C, Bhattacharjee J. Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of pre‐eclampsia. Am J Reprod Immunol 2010; 63: 244–251

Intergenotypic variation of nitric oxide and inflammatory markers in preeclampsia: A pilot study in a North Indian population

Cytokines appeared to contribute to the development of pathologic condition and eNOS gene polymorphism may affect cytokine production. The aim of this study was to evaluate cytokines pattern in preeclampsia and whether there is any relationship between gene and cytokines production and cytokine with disease severity. This cross-sectional study included 100 women with preeclampsia and 100 healthy pregnant women. Their blood samples were analyzed for nitric oxide (NO), inflammatory cytokines, and eNOS gene polymorphism. Decreased NO and increased cytokine (tumor necrosis factor-α, interleukin-2, and interferon-γ) levels were found in preeclampsia (p < 0.001). Significant differences were found in genotype/allele distribution between the two groups. A significant negative correlation was observed between NO and cytokine levels (tumor necrosis factor-α and interferon-γ) in the preeclamptic group (p = 0.001). We conclude that preeclampsia is associated with decreased levels of NO and increased levels of circulating inflammatory cytokines due to single nucleotide polymorphisms, pointing toward the role of endothelial and inflammatory components.

Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study

Objective: To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM). Methods: Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24–34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umblical cord was studied. The data were analyzed using t test and χ2 test. Results: IL-6 levels ≥ 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM. Conclusion: Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity.

ORIGINAL ARTICLE: Role of Inflammatory Cytokines and eNOS Gene Polymorphism in Pathophysiology of Pre-Eclampsia

Citation Singh A, Sharma D, Raghunandan C, Bhattacharjee J. Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of pre‐eclampsia. Am J Reprod Immunol 2010; 63: 244–251

Intergenotypic Variation of Endothelial Dysfunction and Inflammatory Markers in Eclampsia

Background. Cytokine imbalance and endothelial dysfunction are suggested to have a pivotal role in eclampsia. Pathophysiological processes are influenced by genetic factors and nitric oxide (NO) synthases seem to play important roles, although their role is still unclear. Endothelial NO synthase (eNOS) gene polymorphism may affect cytokine production. The aim of this study was to test the hypothesis that inflammatory cytokines impairs endothelium-dependent relaxation and NO production gets vitiated due to eNOs Glu298Asp gene polymorphism causing endothelial dysfunction in eclampsia. Methods. This cross-sectional study included 100 women with eclampsia and 100 healthy pregnant women. Their blood samples were analyzed for NO (indirectly), and inflammatory cytokines and eNOS (Glu298Asp) gene polymorphism were determined by DNA extraction, followed by restriction fragment length polymorphism. Results. Decreased NO metabolites and increased cytokines (tumor necrosis factor-α; interleukin-2, -6; and interferon-γ) levels were found in eclampsia (p < 0.001). Significant differences were found in genotype/allele distribution between the two groups. Occurrence of “T” allele frequency was found to be 0.27 among patients and 0.05 among controls (CI = 95%, OR = 0.7–0.9, p < 0.001). Significant negative correlation was seen between NO and cytokines levels (tumor necrosis factor-α and interferon-γ) in eclamptic women (p = 0.001). Conclusion. This study concluded that eclampsia is associated with decreased levels of NO and increased levels of circulating inflammatory cytokines, which might be contributed due to single-nucleotide polymorphism, pointing toward the role of endothelial and inflammatory components.

ORIGINAL ARTICLE: Role of Inflammatory Cytokines and eNOS Gene Polymorphism in Pathophysiology of Pre-Eclampsia: PRE-ECLAMPSIA, NO, ENOS GENE POLYMORPHISM AND IMMUNOLOGICAL MARKERS

Citation Singh A, Sharma D, Raghunandan C, Bhattacharjee J. Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of pre‐eclampsia. Am J Reprod Immunol 2010; 63: 244–251