Pre-Hypertension among Young Adults (20–30 Years) in Coastal Villages of Udupi District in Southern India: An Alarming Scenario

IntroductionAccording to Joint National Committee-7 (JNC-7) guidelines, a systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic blood pressure (DBP) of 80 to 89 mm Hg is considered as pre-hypertension. Existing evidence suggest that the cardiovascular morbidities are increasing among pre-hypertensive individuals compared to normal.ObjectiveTo assess the magnitude and factors associated with pre-hypertension among young adults (20–30 years) in coastal villages of Udupi Taluk (an area of land with a city or town that serves as its administrative centre and usually a number of villages), Udupi District, Karnataka state, India.DesignCommunity based cross sectional studySetting6 (out of total 14) coastal villages of Udupi Taluk, Karnataka state, India.Sample1,152 young adults (age group: 20–30 years) selected by stratified random sampling in 6 coastal villages of Udupi Taluk, Karnataka state, IndiaMethodA semi structured pre-tested questionnaire was used to elicit the details on socio-demographic variables, dietary habits, tobacco use, alcohol consumption, physical activity, family history of hypertension and stress levels. Anthropometric measurements and blood pressure were recorded according to standard protocols. Serum cholesterol was measured in a sub sample of the study population. Multivariate logistic regression was applied to identify the independent correlates of pre-hypertension among young adults (20–30 years).ResultsThe prevalence of pre-hypertension in the study population was 45.2% (95%CI: 42.4–48). Multivariate logistic regression analysis revealed that age group of 25–30 years (adj OR: 4.25, 95% CI: 2.99–6.05), white collared (adj OR: 2.29, 95% CI: 1.08–4.85) and skilled occupation (adj OR: 3.24, 95% CI: 1.64–6.42), students (adj OR: 2.46, 95% CI: 1.22–4.95), using refined cooking oil (adj OR: 0.53, 95% CI: 0.29–0.95), extra salt in meals (adj OR: 2.46, 95% CI: 1.52–3.99), salty food items (adj OR: 6.99, 95% CI: 3.63–13.48), pre-obese (adj OR: 1.66, 95% CI: 1.03–2.67) and obese (adj OR: 9.16, 95% CI: 2.54, 36.4) were the significant correlates of pre-hypertension.ConclusionIn the study population, prevalence of pre-hypertension among young adults (20–30 years) was high (45.2%). Biological (age 25–30 years, pre-obesity and obesity) and behavioral (sedentary occupation, intake of extra salt in meals/salty food and not using refined cooking oil) factors were associated with pre-hypertension. Study emphasizes the need of community based screening of pre-hypertension under National Rural Health Mission. It also provides apt information for the evidence based designing of interventions for lifestyle modifications among high risk young adults in the study area.     

Global DNA methylation patterns in placenta and its association with maternal hypertension in pre-eclampsia

Maternal nutrition is an important determinant of one-carbon metabolism that lies at the heart of intrauterine epigenetic programming. Exchange of nutrients and other vital molecules between the mother and fetus takes place across the placenta and hence may play direct role in fetal programming. Pre-eclampsia (PE) originates in the placenta and altered maternal nutrition may influence epigenetic patterns in the placenta, thereby affecting birth outcome. In the present study, we investigated the global DNA methylation levels in placentas of pre-eclampsia women (i.e., women delivering at term and those delivering preterm) and studied their associations with maternal blood pressure and birth outcome. Increased homocysteine and global DNA methylation levels were seen in the pre-eclampsia group (term and preterm PE) when compared with the normotensive group (p?相似文献   

Optimum DNA Curvature Using a Hybrid Approach Involving an Artificial Neural Network and Genetic Algorithm

Abstract

In the present paper, a hybrid technique involving artificial neural network (ANN) and genetic algorithm (GA) has been proposed for performing modeling and optimization of complex biological systems. In this approach, first an ANN approximates (models) the nonlinear relationship(s) existing between its input and output example data sets. Next, the GA, which is a stochastic optimization technique, searches the input space of the ANN with a view to optimize the ANN output. The efficacy of this formalism has been tested by conducting a case study involving optimization of DNA curvature characterized in terms of the R_L value. Using the ANN-GA methodology, a number of sequences possessing high R_L values have been obtained and analyzed to verify the existence of features known to be responsible for the occurrence of curvature. A couple of sequences have also been tested experimentally. The experimental results validate qualitatively and also near-quantitatively, the solutions obtained using the hybrid formalism. The ANN-GA technique is a useful tool to obtain, ahead of experimentation, sequences that yield high R_L values. The methodology is a general one and can be suitably employed for optimizing any other biological feature.     

Glucose-stimulated translation regulation of insulin by the 5' UTR-binding proteins

Insulin is the key regulator of glucose homeostasis in mammals, and glucose-stimulated insulin biosynthesis is essential for maintaining glucose levels in a narrow range in mammals. Glucose specifically promotes the translation of insulin in pancreatic β-islet, and the untranslated regions of insulin mRNA play a role in such regulation. Specific factors in the β-islets bind to the insulin 5' UTR and regulate its translation. In the present study we identify protein-disulfide isomerase (PDI) as a key regulator of glucose-stimulated insulin biosynthesis. We show that both in vitro and in vivo PDI can specifically associate with the 5' UTR of insulin mRNA. Immunodepletion of PDI from the islet extract results in loss of glucose-stimulated translation indicating a critical role for PDI in insulin biosynthesis. Similarly, transient overexpression of PDI resulted in specific translation activation by glucose. We show that the RNA binding activity of PDI is mediated through PABP. PDI catalyzes the reduction of the PABP disulfide bond resulting in specific binding of PABP to the insulin 5' UTR. We also show that glucose stimulation of the islets results in activation of a specific kinase that can phosphorylate PDI. These findings identify PDI and PABP as important players in glucose homeostasis.     

The cytolytic activity of pulmonary CD8+ lymphocytes, induced by infection with a vaccinia virus recombinant expressing the M2 protein of respiratory syncytial virus (RSV), correlates with resistance to RSV infection in mice.

Previous studies demonstrated that the pulmonary resistance to respiratory syncytial virus (RSV) challenge induced by immunization with a recombinant vaccinia virus expressing the M2 protein of RSV (vac-M2) was significantly greater 9 days after immunization than at 28 days and was mediated predominantly by CD8+ T cells. In this study, we have extended these findings and sought to determine whether the level of CD8+ cytotoxic T-lymphocyte (CTL) activity measured in vitro correlates with the resistance to RSV challenge in vivo. Three lines of evidence documented an association between the presence of pulmonary CTL activity and resistance to RSV challenge. First, vac-M2 immunization induced pulmonary CD8+ CTL activity and pulmonary resistance to RSV infection in BALB/c (H-2d) mice, whereas significant levels of pulmonary CTL activity and resistance to RSV infection were not seen in BALB.K (H-2k) or BALB.B (H-2b) mice. Second, pulmonary CD8+ CTL activity was not induced by infection with other vaccinia virus-RSV recombinants that did not induce resistance to RSV challenge. Third, the peak of pulmonary CTL activity correlated with the peak of resistance to RSV replication (day 6), with little resistance being observed 45 days after immunization. An accelerated clearance of virus was not observed when mice were challenged with RSV 45 days after immunization with vac-M2. The results indicate that resistance to RSV induced by immunization with vac-M2 is mainly mediated by primary pulmonary CTLs and that this resistance decreases to very low levels within 2 months following immunization. The implications for inclusion of CTL epitopes into RSV vaccines are discussed in the context of these observations.     

Molecular modeling of protein tyrosine phosphatase 1B (PTP 1B) inhibitors

Binding modes of a series of aryloxymethylphosphonates and monoanionic biosteres of phosphate group from a series of benzylic alpha,alpha-diflluoro phosphate and its biosteres as protein tyrosine phosphatase 1B (PTP 1B) inhibitors have been identified by molecular modeling techniques. We have performed docking and molecular dynamics simulations of these inhibitors with PTP 1B enzyme. The initial conformation of the inhibitors for docking was obtained from simulated annealing technique. Solvent accessible surface area calculations suggested that active site of PTP 1B is highly hydrophobic. The results indicate that for aryloxymethylphosphonates, in addition to hydrogen bonding interactions, Tyr46, Arg47, Asp48, Val49, Glu115, Lys116, Lys120 amino acid residues of PTP 1B are responsible for governing inhibitor potency of the compounds. The sulfonate and tetrazole functional groups have been identified as effective monoanionic biosteres of phosphate group and biphenyl ring system due to its favorable interactions with Glu115, Lys116, Lys120 residues of PTP 1B found to be more suitable aromatic functionality than naphthalene ring system for benzylic alpha,alpha-diflluoro phosphate and its biosteres. The information generated from the present study should be useful in the design of more potent PTP 1B inhibitors as anti diabetic agents.     

Low plasma albumin levels are associated with increased plasma protein glycation and HbA1c in diabetes

Albumin is one of the most abundant plasma proteins and is heavily glycated in diabetes. In this study, we have addressed whether variation in the albumin levels influence glycation of plasma proteins and HbA1c. The study was performed in three systems: (1) streptozotocin (STZ)-induced diabetic mice plasma, (2) diabetic clinical plasma, and (3) in vitro glycated plasma. Diabetic mice and clinical plasma samples were categorized as diabetic high albumin plasma (DHAP) and diabetic low albumin plasma (DLAP) on the basis of their albumin levels. For the in vitro experiment, two albumin levels, high albumin plasma (HAP) and low albumin plasma (LAP), were created by differential depletion of plasma albumin. Protein glycation was studied by using a combination of two-dimensional electrophoresis (2DE), Western blotting, and LC-MS(E). In both mice and clinical experiments, an increased plasma protein glycation was observed in DLAP than in DHAP. Additionally, plasma albumin levels were negatively correlated with HbA1c. The in vitro experiment with differential depletion of albumin mechanistically showed that the low albumin levels are associated with increased plasma protein glycation and that albumin competes for glycation with other plasma proteins.     

Spatial and temporal activity of the dentin sialophosphoprotein gene promoter: differential regulation in odontoblasts and ameloblasts

Dentin sialoprotein and dentin phosphoprotein are non-collagenous proteins that are cleavage products of dentin sialophosphoprotein (DSPP). Although these two protein products are believed to have a crucial role in the process of tooth mineralization, their precise biological functions and the molecular mechanisms of gene regulation are not clearly understood. To understand such functions, we have developed a transgenic mouse model expressing a reporter gene (lacZ) under the control of approximately 6 kb upstream sequences of Dspp. The transgenic fusion protein was designed to reside within the cells to facilitate the precise identification of cell type and developmental stages at which the Dspp-lacZ gene is expressed. The results presented in this report demonstrate: (a) the 6 kb upstream sequences of Dspp have the necessary regulatory elements to direct the tissue specific expression of the transgene similar to endogenous Dspp, (b) both odontoblasts and ameloblasts exhibit transgene expression in a differentiation dependent manner, and (c) a differential regulation of the transgene in odontoblasts and ameloblasts occurs during tooth development and mineralization.     

Antinociceptive action of FK506 in mice

Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-binding agents like FK506 are known to inactivate neuronal nitric oxide synthase (nNOS) by inhibiting calcineurin and decrease the production of nitric oxide. Nitric oxide is involved in the mediation of nociception at the spinal level. In the present study, the effect of FK506 on the tail flick response in mice and the possible involvement of NO-L-arginine pathway in this paradigm was evaluated. FK506 (0.5, 1 and 3 mg/kg, ip) produced a significant antinociception in the tail flick test. Nitric oxide synthase (NOS) inhibitor L-NAME significantly and dose dependently (10-40 mg/kg, ip) potentiated the FK506 (0.5 mg/kg)-induced antinociception. On the other hand, NOS substrate L-arginine (100, 200 and 400 mg/kg) inhibited the FK506-induced antinociception in a dose-dependent manner. Concomitant administration of L-NAME (20 and 40 mg/kg) with L-arginine (200 mg/kg) blocked the inhibition exerted by L-arginine on the FK506-induced antinociception. Thus, it was concluded that NO- L-arginine pathway may be involved in the FK506-induced antinociception in tail flick test.