Correlation of Vitamin D levels with feto-maternal outcome

Background: Vitamin D deficiency in adult females may increase risk of pre-eclampsia, gestational diabetes, bacterial vaginosis. Various malpresentation, cephalo-pelvic disproportion and difficult deliveries increases the risk of caesarean section. It may also increase the risk of fetal hypovitaminosis D, neonatal rickets and tetany, lower respiratory tract infections, low birth weight, the largest cause of infant mortality in India. This study was under taken to study the impact of vitamin D deficiency on feto-maternal outcome.Methods: The study was conducted in the Department of Obstetrics and Gynaecology, Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, over a period of 12 months. Sample size was 100 pregnant females attending antenatal clinic.Results: Out of 100 subjects, pre-eclampsia was seen in 15, among which 5 (23.80%) had deficient, 9 (13.04%) had insufficient and 1 (10%) had sufficient vitamin D levels. Eclampsia was seen in 3 subjects, out of which 1 (4.76%) had deficient, 2 (2.89%) had insufficient vitamin D status. IUGR was seen in 8 subjects, out of which 4 (19.04%) had deficient vitamin D levels, 4 (5.79%) had insufficient vitamin D status. Neither of the two had sufficient vitamin D status. Deficient vitamin D status with birth weight ≤2.5 kg was seen in 9 (42.85%) subjects and 12 (57.14%) subjects with >2.5 kg Insufficient Vitamin D status was seen in 22 (31.88%) subjects with birth weight ≤2.5 kg and 48 (69.56%) with birth weight >2.5 kg.Conclusions: Prevalence of vitamin D deficiency and insufficiency was noted in this region and its association with pre-eclampsia (23.80%, 13.04% and 10% in deficient, insufficient and sufficient group respectively) was seen. Higher incidence of LSCS was also present among the deficient and the insufficient group

A Comparitive Assessement of Cytokine Expression in Human-Derived Cell Lines Exposed to Alpha Particles and X-Rays

Alpha- (α-) particle radiation exposure has been linked to the development of lung cancer and has been identified as a radiation type likely to be employed in radiological dispersal devices. Currently, there exists a knowledge gap concerning cytokine modulations associated with exposure to α-particles. Bio-plex technology was employed to investigate changes in proinflammatory cytokines in two human-derived cell lines. Cells were irradiated at a dose of 1.5 Gy to either α-particles or X-rays at equivalent dose rates. The two cell lines exhibited a unique pattern of cytokine expression and the response varied with radiation type. Of the 27 cytokines assessed, only vascular endothelin growth factor (VEGF) was observed to be modulated in both cell lines solely after α-particle exposure, and the expression of VEGF was shown to be dose responsive. These results suggest that certain proinflammatory cytokines may be involved in the biological effects related to α- particle exposure and the responses are cell type and radiation type specific

Vitamin D levels in pregnant women in Uttarakhand, India

Background: A balanced, nutritious diet is an important aspect of a healthy pregnancy and its outcome. Vitamin D plays an important role in regular bone growth and in adequate function of innate immune system, including barrier function of mucous membrane. Vitamin D deficiency in adult females may increase risk of pre-eclampsia, gestational diabetes, bacterial vaginosis. The present study was undertaken to find the prevalence of Vitamin D deficiency in the women of Uttarakhand, India.Methods: The study was conducted in the Department of Obstetrics and Gynecology, Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, India over a period of 12 months. Sample size was 100 pregnant females attending antenatal clinic.Results: Out of 100 subjects, 21 (21%) had deficient, 69 (69%) had insufficient and 10 (10%) had sufficient vitamin D status. Out of 21 deficient subjects, 18 (85.71%) were Hindus, 2 (9.52%) were Muslims, 1 (4.76%) was Sikh and no deficiency was seen in Christian. In the present study, deficient vitamin D status was seen in 1 (4.76%) in lower, 16 (76.19%) in middle and 4 (19.04%) subjects in upper socioeconomic status.Conclusions: It is concluded from our study that there is serious vitamin D deficiency and insufficiency in the women of Uttarakhand, India

Differential Effects of Alpha-Particle Radiation and X-Irradiation on Genes Associated with Apoptosis

This study examined differential effects of alpha-(α-) particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to α-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of α-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X-rays were <5% apoptotic at ~1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-α were common to the α-irradiated cells. This data suggests that α-particle radiation initiates cell death by TNF-α and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells

A role for DNA-dependent activator of interferon regulatory factor in the recognition of herpes simplex virus type 1 by glial cells

<p>Abstract</p> <p>Background</p> <p>The rapid onset of potentially lethal neuroinflammation is a defining feature of viral encephalitis. Microglia and astrocytes are likely to play a significant role in viral encephalitis pathophysiology as they are ideally positioned to respond to invading central nervous system (CNS) pathogens by producing key inflammatory mediators. Recently, DNA-dependent activator of IFN regulatory factor (DAI) has been reported to function as an intracellular sensor for DNA viruses. To date, the expression and functional role of DAI in the inflammatory responses of resident CNS cells to neurotropic DNA viruses has not been reported.</p> <p>Methods</p> <p>Expression of DAI and its downstream effector molecules was determined in C57BL/6-derived microglia and astrocytes, either at rest or following exposure to herpes simplex virus type 1 (HSV-1) and/or murine gammaherpesvirus-68 (MHV-68), by immunoblot analysis. In addition, such expression was studied in ex vivo microglia/macrophages and astrocytes from uninfected animals or mice infected with HSV-1. Inflammatory cytokine production by glial cultures following transfection with a DAI specific ligand (B-DNA), or following HSV-1 challenge in the absence or presence of siRNA directed against DAI, was assessed by specific capture ELISA. The production of soluble neurotoxic mediators by HSV-1 infected glia following DAI knockdown was assessed by analysis of the susceptibility of neuron-like cells to conditioned glial media.</p> <p>Results</p> <p>We show that isolated microglia and astrocytes constitutively express DAI and its effector molecules, and show that such expression is upregulated following DNA virus challenge. We demonstrate that these resident CNS cells express DAI <it>in situ</it>, and show that its expression is similarly elevated in a murine model of HSV-1 encephalitis. Importantly, we show B-DNA transfection can elicit inflammatory cytokine production by isolated glial cells and DAI knockdown can significantly reduce microglial and astrocyte responses to HSV-1. Finally, we demonstrate that HSV-1 challenged microglia and astrocytes release neurotoxic mediators and show that such production is significantly attenuated following DAI knockdown.</p> <p>Conclusions</p> <p>The functional expression of DAI by microglia and astrocytes may represent an important innate immune mechanism underlying the rapid and potentially lethal inflammation associated with neurotropic DNA virus infection.</p

Binding characteristics of a panel of monoclonal antibodies against the ligand binding domain of the human LDLr

To obtain a panel of monoclonal antibodies (MAbs) to study the folding and conformation of the low density lipoprotein receptor (LDLr), we have generated hybridomas from LDLr-deficient mice that had been immunized with the extracellular domain of the human LDLr. The 12 MAbs were specific for the ligand binding domain of the LDLr, with individual MAbs recognizing epitopes in ligand binding repeats 1, 2, 3, 5, and 7. A subset of the MAbs failed to react with the LDLr when disulfide bonds were reduced, and one MAb, specific for an epitope that spans ligand binding repeats 1 and 2, recognized two conformational forms of the LDLr with different affinities. Antibodies specific for ligand binding repeats 3, 5, and 7 completely blocked the binding of LDL particles to the LDLr on cultured human fibroblasts, whereas MAbs with epitopes in ligand binding repeats 1 and 2 partially blocked the binding of LDL to the LDLr. These anti-LDLr MAbs will serve as useful probes for further analysis of LDLr conformation and LDLr-mediated lipoprotein binding

Exacerbated metastatic disease in a mouse mammary tumor model following latent gammaherpesvirus infection

BACKGROUND: Controversy exists as to the ability of human gammaherpesviruses to cause or exacerbate breast cancer disease in patients. The difficulty in conducting definitive human studies can be overcome by investigating developing breast cancer in a mouse model. In this study, we utilized mice latently infected with murine gammaherpesvirus 68 (HV-68) to question whether such a viral burden could exacerbate metastatic breast cancer disease using a mouse mammary tumor model. RESULTS: Mice latently infected with HV-68 had a similar primary tumor burden, but much greater metastatic disease, when compared to mock treated mice given the transplantable tumor, 4 T1. This was true for lung lesions, as well as secondary tumor masses. Increased expression of pan-cytokeratin and VEGF-A in tumors from HV-68 infected mice was consistent with increased metastatic disease in these animals. Surprisingly, no viral particles could be cultured from tumor tissues, and the presence of viral DNA or RNA transcripts could not be detected in primary or secondary tumor tissues. CONCLUSIONS: Latent HV-68 infection had no significant effect on the size of primary 4 T1 mammary tumors, but exacerbated the number of metastatic lung lesions and secondary tumors when compared to mock treated mice. Increased expression of the tumor marker, pan-cytokeratin, and VEGF-A in tumors of mice harboring latent virus was consistent with an exacerbated metastatic disease. Mechanisms responsible for this exacerbation are indirect, since no virus could be detected in cancerous tissues

Adverse Outcome Pathway: A Path towards better Data Consolidation and Global Co-ordination of Radiation Research

The AOP framework has undergone substantial maturation in the field of hazard characterization of chemicals over the last decade, and has also recently gained attention from the radiological protection and research communities as a means to advance the mechanistic understanding of human and ecological health effects from exposure to ionizing radiation at low dose and low dose-rates. To fully exploit the value of such approaches for facilitating risk assessment and management in the field of radiation protection, solicitation of experiences and active cooperation between chemical and radiation communities are needed. As a result, the Radiation and Chemical (Rad/Chem) AOP joint topical group was formed on June 1, 2021 as part of the initiative from the High Level Group on Low Dose Research (HLG-LDR). HLG-LDR is overseen by the OECD Nuclear Energy Agency (NEA) Committee on Radiological Protection and Public Health (CRPPH). The main aims of the joint AOP topical group are to advance the use of AOPs in radiation research and foster broader implementation of AOPs into hazard and risk assessment. With global representation, it serves as a forum to discuss, identify and develop joint initiatives that support research and take on regulatory challenges. The Rad/Chem AOP joint topical group aims to actively liaise with the OECD EAGMST AOP developmental program to collectively advance areas of common interest and, specifically, provide recommendations for harmonization of the AOP framework to accommodate non-chemical stressors, such as radiation. The current presentation will provide an overview of the mission and work of the Topical Group.The 1st Adverse Outcome Pathways Community of Practice Symposium 202

Considerations for application of benchmark dose modeling in radiation research: workshop highlights

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Report of the 1st and 2nd Mystery of Reactive Oxygen Species Conferences

Non peer reviewe