Vaginal Progesterone to Prevent Spontaneous Preterm Birth in Women With a Sonographic Short Cervix: The Story of the PREGNANT Trial.

The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.

Can we improve the outcome of pregnancies with low serum PAPP-A in the first trimester?

OBJECTIVE: This study aimed to assess the impact of micronized progesterone (VMP4) supplementation on pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) values during first-trimester screening. METHODS: Out of 8933 patients evaluated, 116 pregnant women with low PAPP-A concentrations in their blood and no fetal chromosomal anomalies (CAs) were included. Three groups were formed: group 1 received VMP4 from 11 to 16 weeks (29 women, 25%), group 2 received VMP4 from 11 to 36 weeks (25 women, 21.5%), and group 3 (62 women, 53.5%) served as controls without receiving progesterone. RESULTS: Results indicated that group 3 had higher rates of complications, including miscarriages (16.37%), preterm delivery (17.8%), and fetal developmental abnormalities (19.4%). Birthweight variations were elevated in pregnancies without progesterone, contrasting with lower variations in VMP4 groups. Group 2, receiving VMP4 until 36 weeks, reported the lowest incidence of abortion and preterm birth (PB), along with the highest mean birth weight. CONCLUSIONS: The conclusion suggests that 200 mg per day of VMP4 up to 36 weeks of supplementation led to fewer placental-related complications in women with very low PAPP-A at first-trimester screening (0.399 MoM). By reporting lower rates of miscarriages, PBs, and fetal developmental abnormalities in the micronized progesterone-treated groups, the study suggests a potential reduction in complications.

Phytofabricated bimetallic synthesis of silver-copper nanoparticles using Aerva lanata extract to evaluate their potential cytotoxic and antimicrobial activities.

In this study, we demonstrate the green synthesis of bimetallic silver-copper nanoparticles (Ag-Cu NPs) using Aerva lanata plant extract. These NPs possess diverse biological properties, including in vitro antioxidant, antibiofilm, and cytotoxic activities. The synthesis involves the reduction of silver nitrate and copper oxide salts mediated by the plant extract, resulting in the formation of crystalline Ag-Cu NPs with a face-centered cubic structure. Characterization techniques confirm the presence of functional groups from the plant extract, acting as stabilizing and reducing agents. The synthesized NPs exhibit uniform-sized spherical morphology ranging from 7 to 12 nm. They demonstrate significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, inhibiting extracellular polysaccharide secretion in a dose-dependent manner. The Ag-Cu NPs also exhibit potent cytotoxic activity against cancerous HeLa cell lines, with an inhibitory concentration (IC50) of 17.63 µg mL-1. Additionally, they demonstrate strong antioxidant potential, including reducing capability and H2O2 radical scavenging activity, particularly at high concentrations (240 µg mL-1). Overall, these results emphasize the potential of A. lanata plant metabolite-driven NPs as effective agents against infectious diseases and cancer.

SPP1, a potential therapeutic target and biomarker for lung cancer: functional insights through computational studies.

NIH reported 128 different types of cancer of which lung cancer is the leading cause of mortality. Globally, it is estimated that on average one in every seventeen hospitalized patients was deceased. There are plenty of studies that have been reported on lung cancer draggability and therapeutics, but yet a protein that plays a central specific to cure the disease remains unclear. So, this study is designed to identify the possible therapeutic targets and biomarkers that can be used for the potential treatment of lung cancers. In order to identify differentially expressed genes, 39 microarray datasets of lung cancer patients were obtained from various demographic regions of the GEO database available at NCBI. After annotating statistically, 6229 up-regulated genes and 10324 down-regulated genes were found. Out of 17 up-regulated genes and significant genes, we selected SPP1 (osteopontin) through virtual screening studies. We found functional interactions with the other cancer-associated genes such as VEGF, FGA, JUN, EGFR, and TGFB1. For the virtual screening studies,198 biological compounds were retrieved from the ACNPD database and docked with SPP1 protein (PDBID: 3DSF). In the results, two highly potential compounds secoisolariciresinol diglucoside (-12.9 kcal/mol), and Hesperidin (-12.0 kcal/mol) showed the highest binding affinity. The stability of the complex was accessed by 100 ns simulation in an SPC water model. From the functional insights obtained through these computational studies, we report that SPP1 could be a potential biomarker and successive therapeutic protein target for lung cancer treatment.

One-Pot Synthesis of Silver Nanoparticles from Garcinia gummi-gutta: Characterisation, Antimicrobial, Antioxidant, Anti-Cancerous and Photocatalytic Applications.

BACKGROUND: Methods like the bio-synthesis of silver nanoparticles (Ag NPs) using plant extracts have become promising due to their eco-friendly approach. The study aimed to examine the utilization of Garcinia gummi-gutta fruit phytochemicals as agents in the biosynthesis of Ag NPs, evaluation of the antimicrobial, antioxidant, and anti-cancerous properties, as well as the photocatalytic ability of bio-synthesized Ag NPs against Crystal Violet (CV), a triphenylmethane dye. METHODS: The characterization of the physical properties of the Ag NPs synthesized via the green route was done using UV-Vis spectrophotometry (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared Spectrophotometry (FTIR), Scanning Electron Microscopy (SEM), Zeta potential analysis, and Transmission Electron Microscopy (TEM). The dye degradation efficiency of CV was determined using synthesized Ag NPs under UV light by analyzing the absorption maximum at 579 nm. The antimicrobial efficacy of Ag NPs against E. coli, S. aureus, Candida tropicalis, and Candida albicans was examined using the broth dilution method. The antioxidant and anti-cancer properties of the synthesized Ag NPs were assessed using the DPPH and MTT assays. RESULTS: The UV analysis revealed that the peak of synthesized Ag NPs was 442 nm. Data from FTIR, XRD, Zeta potential, SEM, and TEM analysis confirmed the formation of nanoparticles. The SEM and TEM analysis identified the presence of spherical nanoparticles with an average size of 29.12 nm and 24.18 nm, respectively. Maximum dye degradation efficiency of CV was observed at 90.08% after 320 min without any silver leaching, confirming the photocatalytic activity of Ag NPs. The bio-efficiency of the treatment was assessed using the Allium cepa root growth inhibition test, toxicity analysis on Vigna radiata, and Brine shrimp lethality assay. CONCLUSIONS: The findings revealed the environmentally friendly nature of green Ag NPs over physical/chemically synthesized Ag NPs. The synthesized Ag NPs can effectively be used in biomedical and photocatalytic applications.

Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection.

OBJECTIVE: Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. METHODS: This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. RESULTS: (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p < 0.001) or term delivery (p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p < 0.001); (5) among women with PTL and IAI, the amniotic fluid concentration of CHCHD2/MNRR1 correlated with that of interleukin-6 (Spearman's Rho = 0.7; p < 0.001); and (6) no correlation was observed between amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations among women with PTL. CONCLUSION: CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.

DNA Damage on Buccal Epithelial Cells, Personal Working in the Rubber Industry Occupationally Exposed to Carbon Disulfide (CS2).

INTRODUCTION: The most significant industrial utilization of carbon disulfide (CS2) has been in the manufacture of cellulose rayon, cellophane, and rubber industry. CS2 prompts expanded recurrence of chromosomal variations in laborers occupationally exposed to CS2. MATERIALS AND METHODS: In the current study, the DNA analysis was carried out from exfoliated buccal epithelial cells from rubber industry workers exposed to CS2 and an equal number of healthy control subjects. Both the control and experimental subjects were categorized by their smoking habits such as smokers (S) and non-smokers (NS). Furthermore, experimental subjects were further separated based on their exposure period. Students t-test statistical tools were used to analyze the final results. RESULTS: The present analysis identified a high frequency of DNA damage in rubber industry workers (16.55±0.43) than control subjects (9.8±0.21). Also, maximum number of DNA damage detected in smoking experimental group (18.27±0.02) than non-smoking experimental (15.02±0.01) and smoking control groups (10.25±0.04 ). CONCLUSION: Smoking habits synergistically increased the DNA damage in the rubber industry workers exposed to CS2.

Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death.

OBJECTIVES: Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma. METHODS: This retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages. RESULTS: Nineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log2-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p < .001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients. CONCLUSION: Pregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics.

Genotoxic repercussion of high-intensity radiation (x-rays) on hospital radiographers.

Recent technological advances in the medical field have increased the plausibility of exposing humans to high-intensity wavelength radiations like x-rays and gamma rays while diagnosing or treating specific medical maladies. These radiations induce nucleotide changes and chromosomal alterations in the exposed population, intentionally or accidentally. A radiological investigation is regularly used in identifying the disease, especially by the technicians working in intensive care units. The current study observes the genetic damages like chromosomal abnormalities (CA) in clinicians who are occupationally exposed to high-intensity radiations (x-rays) at their workplaces using universal cytogenetic tools like micronucleus assay (MN), sister chromatid exchange and comet assay. The study was conducted between 100 exposed practitioners from the abdominal scanning, chest scanning, cranial and orthopedic or bone scanning department and age-matched healthy controls. We observed a slightly higher rate of MN and CA (p < .05) in orthopedic and chest department practitioners than in other departments concerning increasing age and duration of exposure at work. Our results emphasize taking extra precautionary measures in clinical and hospital radiation laboratories to protect the practitioners.

Ochratoxin A as an alarming health threat for livestock and human: A review on molecular interactions, mechanism of toxicity, detection, detoxification, and dietary prophylaxis.

Ochratoxin A (OTA) is a toxic metabolite produced by Aspergillus and Penicillium fungi commonly found in raw plant sources and other feeds. This review comprises an extensive evaluation of the origin and proprieties of OTA, toxicokinetics, biotransformation, and toxicodynamics of ochratoxins. In in vitro and in vivo studies, the compatibility of OTA with oxidative stress is observed through the production of free radicals, resulting in genotoxicity and carcinogenicity. The OTA leads to nephrotoxicity as the chief target organ is the kidney. Other OTA excretion and absorption rates are observed, and the routes of elimination include faeces, urine, and breast milk. The alternations in the Phe moiety of OTA are the precursor for the amino acid alternation, bringing about Phe-hydroxylase and Phe-tRNA synthase, resulting in the complete dysfunction of cellular metabolism. Biodetoxification using specific microorganisms decreased the DNA damage, lipid peroxidation, and cytotoxicity. This review addressed the ability of antioxidants and the dietary components as prophylactic measures to encounter toxicity and demonstrated their capability to counteract the chronic exposure through supplementation as feed additives.

Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer.

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects (n = 65) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking (P < 0.05) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

Carcinogens in Food: Evaluating the Presence of Cadmium, Lead, in Poultry Meat in South India.

OBJECTIVE: Local chickens were spontaneously sampled and slaughtered in the central markets of Coimbatore, Erode, and Namakkal districts, South India. MATERIALS AND METHODS: Wet digestion was used to extract lead (Pb), cadmium (Cd), and zinc (Zn) in their blood and selected different organs (intestine, breast, liver, and gizzard), and their concentrations were measured using an atomic absorption spectrophotometer. RESULTS: Apart from the blood of chickens from Coimbatore and Namakkal, where Pb was not found, the concentrations of Pb in the blood and organs of chickens from the three towns ranged from 1.8 to 8.33 mg/kg, exceeding the maximum tolerance thresholds (0.1 mg/kg) in internal organs of poultry birds. Except for the intestine of chickens from the three areas, Cd was only found in the heart, blood, and gizzard of Erode chickens, as well as the liver and gizzard of Namakkal chickens, in concentrations ranging from 0.13 to 0.58. According to threshold level, the upper limit met the maximum limits (0.5 mg/kg). Zn was found in all sections of chickens from the three selected districts, with concentrations ranging from 4.96 to 174.17 mg/kg. CONCLUSION: Its concentrations were within the permissible limits (10-50 mg/kg) in some areas of certain chickens, but it surpassed the permissible limit in the liver of chicken from Coimbatore. Any organs and blood from local chickens sold in Coimbatore, Erode, and Namakkal areas can be hazardous to one's health.

Cytogenetic Consequences of Food Industry Workers Occupationally Exposed to Cooking Oil Fumes (COFs).

BACKGROUND: Cooking oil fumes (COFs) with smoking habits is a substantial risk that aggravates genetic modifications. The current study was to estimate the biological markers of genetic toxicity counting Micronucleus changes (MN), Chromosome Aberrations (CA) and DNA modifications among COFs exposures and control subjects inherent from South India. MATERIALS AND METHODS: Present analysis comprised 212 COFs with tobacco users and equivalent number of control subjects. RESULTS: High frequency of CA (Chromatid type: and chromosome type) were identified in group II experimental subjects also high amount of MN and DNA damage frequency were significantly (p < 0.05) in both subjects (experimental smokers and non-smokers). Present analysis was observed absence of consciousness among the COFs exposures about the destructive level of health effects of tobacco habits in working environment. CONCLUSION: COFs exposed workers with tobacco induce the significant alteration in chromosomal level. Furthermore, a high level of rate of genetic diseases (spontaneous abortion) were identified in the experimental subjects. This finding will be helpful for preventive measures of COFs exposed workers and supportive for further molecular analysis.

GalNAc-siRNA conjugates: Prospective tools on the frontier of anti-viral therapeutics.

The growing use of short-interfering RNA (siRNA)-based therapeutics for viral diseases reflects the most recent innovations in anti-viral vaccines and drugs. These drugs play crucial roles in the fight against many hitherto incurable diseases, the causes, pathophysiologies, and molecular processes of which remain unknown. Targeted liver drug delivery systems are in clinical trials. The receptor-mediated endocytosis approach involving the abundant asialoglycoprotein receptors (ASGPRs) on the surfaces of liver cells show great promise. We here review N-acetylgalactosamine (GalNAc)-siRNA conjugates that treat viral diseases such as hepatitis B infection, but we also mention that novel, native conjugate-based, targeted siRNA anti-viral drugs may also cure several life-threatening diseases such as hemorrhagic cystitis, multifocal leukoencephalopathy, and severe acute respiratory syndrome caused by coronaviruses and human herpes virus.

Dietary nutrients and their control of the redox bioenergetic networks as therapeutics in redox dysfunctions sustained pathologies.

Electrons exchange amongst the chemical species in an organism is a pivotal concomitant activity carried out by individual cells for basic cellular processes and continuously contribute towards the maintenance of bioenergetic networks plus physiological attributes like cell growth, phenotypic differences and nutritional adaptations. Humans exchange matter and energy via complex connections of metabolic pathways (redox reactions) amongst cells being a thermodynamically open system. Usually, these reactions are the real lifeline and driving forces of health and disease in the living entity. Many shreds of evidence support the secondary role of reactive species in the cellular process of control apoptosis and proliferation. Disrupted redox mechanisms are seen in malaises, like degenerative and metabolic disorders, cancerous cells. This review targets the importance of redox reactions in the body's normal functioning and the effects of its alterations in cells to obtain a better understanding. Understanding the redox dynamics in a pathological state can provide an opportunity for cure or diagnosis at the earlier stage and serve as an essential biomarker to predict in advance to give personalized therapy. Understanding redox metabolism can also highlight the use of naturally available antioxidant in the form of diet.

Extricating the Association Between the Prognostic Factors of Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is one of the recurring and lethal gastrointestinal tract disease rankings as the primary cause of worldwide morbidity and mortality. In general, the tumour node metastasis (TNM) and Dukes classification assist in diagnosis, prognosis and treatments of CRC along with haematological examinations and tumour demographic characterisations in patients. METHODS: The present investigation is carried out on clinically acknowledged sixty-five CRC patients based on haematological findings and are sorted into stages using TNM and Dukes. The present study is to find the association between haematological findings, demographic characters, differentiation position, lymph node invasion and tumour node metastasis in CRC patients in accordance with their age. RESULTS: We observed significant (p < 0.05) nexus between lymph node metastasis and tumour node metastasis on the basis of tumour's differentiation demographic positioning and age of the individuals. CONCLUSION: Earlier location tracing and medicinal treatment or surgery lessen the chance of CRC morbidity and mortality along with prolonging survival rate via prognostic factors and disease position determination.

Structure-based virtual screening, pharmacokinetic prediction, molecular dynamics studies for the identification of novel EGFR inhibitors in breast cancer.

Breast cancer is one of the most prevalent malignancy cancer types especially affecting women globally. EGFR is a proto onco gene as well as the first identified tyrosine kinase receptor. It plays a dynamic role in many biological tasks such as apoptosis, cell cycle progression, differentiation, development and transcription. Somatic mutation in the EGFR kinase domain derails the normal kinase activity and over expression leads to the progression of cancer especially breast cancer. EGFR is one of the well-known therapeutic targets for breast cancer. In this scenario, we attempt to identify novel potent inhibitors of EGFR. Initially, we performed structure-based virtual screening and identified four potential compounds effective against EGFR. Further, the compounds were subjected to ADME prediction as part of evaluation of the druggability and all the four compounds found to fall under satisfactory range with predicted pharmacokinetic properties. Eventually, the conformational stability of protein-ligand complex was analyzed at different time scale by using Gromacs software. Molecular dynamics simulation run of 20 ns is carried out and results were analyzed using root mean square deviation (RMSD), root mean square fluctuation (RMSF) to signify the stability of protein-igand complex. The stability of the protein-ligand complex is more stable throughout entire simulation. From the results obtained from in silico studies, we propose that these compounds are exceptionally useful for further lead optimization and drug development.Communicated by Ramaswamy H. Sarma.

Occupational health hazards on workers exposure to lead (Pb): A genotoxicity analysis.

BACKGROUND: The present investigation of genotoxicity of lead (Pb) among workers exposed to inorganic Pb environment, which appears to be first of its kind in South India, was undertaken to assess the seriousness, the ill effects of health contributed by this serious environmental pollutant. METHODS: A total of 144 samples comprising of exposed (n=72), and control (n=72) subjects were screened. Demographic data and their associated health levels were undertaken by means of a questionnaire. The blood samples collected were subjected to chromosomal analysis, micronuclei assessment and comet assay. RESULTS: A higher level of Pb was quantified in the blood samples of all exposed subjects. An overview of the genotoxic assessment helped us understand parameters such as age do not affect or bring about any difference in the genotoxic potential of the exposed and control subjects. The only signification feature that resulted in an enhanced genotoxic potential was the years of exposure to the Pb environment that accumulated the dosage of Pb over the years. CONCLUSION: The high positivity of genotoxic potential of Pb in a country like India highlights the need for labelling hazardous metals in paint containers as a means to assure strict regulations.

Pharmacogenetics of Vascular Risk Factors in Alzheimer's Disease.

Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic (APOE-APOB-APOC3-CETP-LPL) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE, NOS3, ACE, AGT, and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders.

Cytogenetic endpoints and Xenobiotic gene polymorphism in lymphocytes of hospital workers chronically exposed to ionizing radiation in Cardiology, Radiology and Orthopedic Laboratories.

Ionizing radiation (IR) is known as a classical mutagen capable of inducing various kinds of stable and unstable chromosomal aberrations (CA) including the possibility of increasing the incidence of DNA damage. This study aims to assess occupationally induced CA in workers chronically exposed to low doses of IR in Radiology (RL), Cardiology (CL) and Orthopedic (OL) Laboratories in hospitals of Tamil Nadu. We performed the analysis of CA by trypsin G-banding, micronucleus (MN) assay, Comet assay and Xenobiotic-metabolizing gene polymorphisms (GSTM1, GSTT1 and GSTP1) in 56 exposed and 56 control subjects who were matched for gender and age (± 2 years). Higher degree of CA and MN frequencies were observed in exposed groups, especially in CL subjects compared to other exposed groups and controls (p<0.05). Higher frequency of DNA tail length and tail moment was observed in the CL exposed subjects compared to the RL and OL subjects. The frequencies of GSTM1 and GSTT1 null genotypes were 39.3 percent and 14.3 percent, respectively. No significant difference in allele frequencies between exposed subjects and controls were observed (p=0.0128). Using multiple linear regression analysis, statistical significance was determined for work duration and age for the CL, RL and OL workers and the examination of the possible impact by confounding factors showed few significant influences on the radiation exposure, as a specific biomarker. However, the findings from the present study suggest that, awareness should be created among the personnel exposed to radiations in hospital laboratories, highlighting the necessity of applying radiation protection principles against medical radiation exposure.