Oxidative stress-A key determinant of complications and negative outcome in hepatitis E virus infected pregnancies: A comprehensive account involving cases from northeast India.

Regulated oxidative stress (OS) is important during pregnancy. Sporadic studies suggest the significance of deregulated OS in hepatitis E virus (HEV) infected pregnancy, but with limited reactive oxygen species (ROS) or antioxidant markers. The present novel study, therefore, aimed to evaluate the significance of ROS-antioxidant imbalance and resulting altered OS in HEV infected pregnancy complications like preterm delivery (PTD) and outcome. Difference in serum levels of ROS and antioxidant panel of markers were evaluated by ELISA for HEV immunoglobulin M RNA positive genotype 1 cases (including acute [acute viral hepatitis, AVH] and fulminant [fulminant hepatic failure, FHF] cases) and healthy term delivery subjects, and analyzed statistically. Direct ROS marker H2 O2 levels and indirect OS marker for DNA damage 8-hydroxy-2'-deoxyguanosine was significantly increased in HEV-cases compared to controls, and was associated and prognostic factor for PTD and fetal death in HEV cases. A comparatively lower total serum antioxidant capacity was observed in the FHF cases compared to the control subjects and the AVH cases. Glutathione (GSH) levels and superoxide dismutase (SOD) activity were significantly associated with PTD in the FHF sub-cohorts (p = 0.017) and AVH sub-cohorts (p < 0.001), respectively, and was associated with poor prognosis in HEV cases. The serum H2 O2 levels were found to be negatively correlated with SOD activity (p = 0.016) and GSH levels (p = 0.001) in the HEV-AVH cases; and positively correlated with the viral load in HEV cases (p = 0.023). The ROS-antioxidant imbalance resulting OS plays a detrimental associative role in HEV infected pregnancy complications like PTD and adverse pregnancy outcomes; and holds therapeutic significance.

Increased homocysteine mediated oxidative stress as key determinant of hepatitis E virus (HEV) infected pregnancy complication and outcome: A study from Northeast India.

With the background of association of oxidative stress and Hepatitis E virus (HEV) infection in pregnancy complications the present novel study aimed to evaluate the significance of changes in maternal homocysteine levels and the related mechanism(s) in the pathophysiology of HEV related pregnancy complications and negative outcomes. Term delivery (TD, N = 194) and HEV-IgM positive pregnancy cases [N = 109] were enrolled. Serum and placental homocysteine levels were evaluated by ELISA and immunofluorescence and in turn correlated with serum Vitamin B12 levels. Distribution of variant MTHFR C➔T and TYMS1494del6bp genotyping were studied by PCR-RFLP. Differential folate receptor alpha (FR-α) expression in placenta was evaluated by real-time PCR and immunofluorescence respectively. The HEV viral load was significantly higher in both FHF and AVH cases. Higher serum homocysteine levels was associated with preterm delivery (PTD) and fetal death in HEV infected cases and was significantly inversely correlated with serum VitaminB12 levels in HEV cases. Placental homocysteine expression was upregulated in HEV cases, and in cases with negative pregnancy outcome. A Homocysteine level was associated with MTHFR C677T status. Genetic alterations in folate pathway was associated with increased risk of PTD in HEV infected pregnancy cases, disease severity, and negative pregnancy outcome in AVH and FHF groups. FR-α expression was downregulated in placental tissues of HEV infected pregnancy.Placental stress caused by HEV inflicted increased homocysteine due to alterations in maternal vitamin B12 levels and folate pathway components is detrimental mechanism in PTD and negative pregnancy outcome in HEV infected pregnancy cases and holds prognostic and therapeutic significance.

Significance of RANTES-CCR5 axis and linked downstream immunomodulation in Dengue pathogenesis: A study from Guwahati, India.

We aimed to evaluate the significance of the RANTES-CCR5 axis and resulting immunomodulatory status in Dengue pathogenesis involving a Guwahati, India based population where Dengue cases have increased alarmingly. An increased CC-chemokine receptor type 5 (CCR5) messenger RNA expression and CCR5 positive cell count profile was observed in Dengue cases, the highest being in severe cases. CCR5 ligand RANTES expression was significantly decreased in Dengue cases and inversely correlated with Dengue viremia fold change in severe cases. Monocytes are involved in Dengue virus homing and replication. Its levels and activation profile were higher in Dengue cases. A hyper Th1-biased immunomodulatory profile with upregulated tumor necrosis factor-α levels, and downregulated expression of antiviral cytokine interferon-γ and key regulatory Th2 anti-inflammatory cytokine interleukin 10 was observed in severe Dengue cases compared with mild Dengue cases and controls. The results, therefore, suggest the significance of RANTES-CCR5 axis deregulation and resulting altered immunomodulation in Dengue pathogenesis, and holds prognostic and therapeutic significance.