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This present study deals with the facile synthesis of Zinc (Zn), Strontium (Sr) Co‐substituted hydroxyapatite (M‐HAP)/lignin composite for biomedical applications. For composite formation, HAP was isolated from egg shell through wet precipitation method, biopolymer of lignin was extracted from neem wood through organosolve technique then HAP composites (HAP, HAP/lignin, Zn‐HAP/lignin, Sr‐HAP/lignin, Zn, Sr‐HAP/lignin) were obtained using freeze drying performance. The synthesized HAP composites were characterized using X‐ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Energy‐dispersive X‐ray analysis (EDAX). The antibacterial behavior of the HAP composites was investigated against E. Coli, B. Subtilies, P. Aeruginosa and S. Aureus pathogens. Then the mechanical property of the HAP composites was carried out using Vicker's microhardness test which reveals a better improvement in mechanical hardness. The antibacterial activity confirms that the HAP composite exhibits enhanced antibacterial activity. Further, the cell viability analysis shows that the co‐substitution of Zn and Sr in HAP lattice improved cell viability analysis, which indicates that the obtained Zn, Sr co‐substituted HAP/lignin biocomposite acts as a potential biomaterial for better biomedical application. [ABSTRACT FROM AUTHOR]

Heart disease, known interchangeably as "Cardio Vascular Disease," blocks the blood vessels in the heart and causes heart attack, chest pain, and stroke. Heart disease is one of the leading causes of morbidity and mortality worldwide and it is one of the major causes of morbidity and mortality globally and a trending topic in clinical data analysis. Assessing risk factors related to heart disease is considered as an important step in diagnosing the disease at an early stage. Clinical data present in the form of electronic health records (EHR) can be extracted with the aid of machine learning (ML) algorithms to provide valuable decisions and predictions. ML approaches also play a vital role in early diagnosis and therapeutic monitoring of heart disease. Several research works have been carried out recently to predict heart disease. To this end, we propose a novel hybrid recurrent neural network (RNN)‐logistic chaos‐based whale optimization (LCBWO) structured hybrid framework for predicting heart disease within 5 years using EHR data. Meanwhile, in the hybrid model established multilayer bidirectional LSTM is used for feature selection, LCBWO algorithm for structural improvement and fast convergence, and LSTM for disease prediction. This research used 10 cross‐validations to obtain generalized accuracy and error values. The findings and observations provided here are focused on the knowledge obtained from the EHR report. The results show that the proposed novel hybrid RNN‐LCBWO framework achieves a higher accuracy of 98%, a specificity of 99%, precision of 96%, Mathews correlation coefficient of 91%, F‐measure of 0.9892, an area under the curve value of 98%, and a prediction time of 9.23 seconds. The accurate predictions obtained from the comparative analysis shows the significant performance of our proposed framework. [ABSTRACT FROM AUTHOR]

An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (ΔλB) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c, a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in ΔλB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules. [ABSTRACT FROM AUTHOR]

The health of the human population has been continuously challenged by viral infections. Herpes simplex virus (HSV) is one of the common causes of illness and can lead to death in immunocompromised patients. Existing anti-HSV therapies are not completely successful in eliminating the infection due to anti-viral drug resistance, ineffectiveness against the latent virus and high toxicity over prolonged use. There is a need to update our knowledge of the current challenges faced in anti-HSV therapeutics and realize the necessity of developing alternative treatment approaches. Protein therapeutics are now being explored as a novel approach due to their high specificity and low toxicity. This review highlights the significance of HSV viral glycoproteins and host receptors in the pathogenesis of HSV infection. Proteins or peptides derived from HSV glycoproteins gC, gB, gD, gH and host cell receptors (HSPG, nectin and HVEM) that act as decoys to inhibit HSV attachment, entry, or fusion have been discussed. Few researchers have tried to improve the efficacy and stability of the identified peptides by modifying them using a peptidomimetic approach. With these efforts, we think developing an alternative treatment option for immunocompromised patients and drug-resistant organisms is not far off., (© 2023 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)

Process understanding and characterization forms the foundation, ensuring consistent and robust biologics manufacturing process. Using appropriate modeling tools and machine learning approaches, the process data can be monitored in real time to avoid manufacturing risks. In this article, we have outlined an approach toward implementation of chemometrics and machine learning tools (neural network analysis) to model and predict the behavior of a mixed-mode chromatography step for a biosimilar (Teriparatide) as a case study. The process development data and process knowledge was assimilated into a prior process knowledge assessment using chemometrics tools to derive important parameters critical to performance indicators (i.e., potential quality and process attributes) and to establish the severity ranking for the FMEA analysis. The characterization data of the chromatographic operation are presented alongwith the determination of the critical, key and non- key process parameters, set points, operating, process acceptance and characterized ranges. The scale-down model establishment was assessed using traditional approaches and novel approaches like batch evolution model and neural network analysis. The batch evolution model was further used to demonstrate batch monitoring through direct chromatographic data, thus demonstrating its application for continuos process verification. Assimilation of process knowledge through a structured data acquisition approach, built-in from process development to continuous process verification was demonstrated to result in a data analytics driven model that can be coupled with machine learning tools for real time process monitoring. We recommend application of these approaches with the FDA guidance on stage wise process development and validation to reduce manufacturing risks., (© 2022 American Institute of Chemical Engineers.)

Background: Studies of World Trade Center (WTC)-exposed rescue/recovery workers report the increased occurrence of health conditions after work at the WTC disaster site. However, the extent to which these associations are due to WTC exposure is unclear, in part due to the lack of suitable comparison groups. Accordingly, we identified a previously assembled National Institute for Occupational Safety and Health (NIOSH) cohort of career firefighters from three US cities (n = 29,992). Here, we document the challenges in establishing this non-WTC-exposed firefighter cohort for the goal of tracking and comparing cancer and chronic health conditions in WTC-exposed and non-WTC-exposed firefighters., Methods: Follow-up process included institutional review board applications, data use agreements, state cancer registry linkages and vital status determination for the NIOSH firefighter cohort. After completion of these steps, we undertook outreach to the three original city fire departments and union officials, before contact tracing and direct recruitment of 14,566 living firefighters to complete a confidential health survey. We staggered recruitment efforts by the city, using letters, postcards, emails, videos, and telephone outreach. Participants who completed the survey received $10., Results: A total of 4962 of 14,566 alive firefighters responded to the baseline survey (34.1% response rate). Respondents were older and more likely to be non-Hispanic white than nonrespondents., Conclusions: We provide an overview of the process for the first survey to collect information on physical and mental health conditions among US firefighters. The data collected will have an important impact on studies of WTC rescue/recovery work, firefighting, and related health conditions., (© 2021 Wiley Periodicals LLC.)

Aims: The metabolic syndrome (MetS) is an inflammatory disorder associated with an increased risk for diabetes and atherosclerotic cardiovascular disease (ASCVD). Studies in patients and animal models of obesity and diabetes have shown increased NOD-like receptor family pyrin domain containing 3 (NLPR3) inflammasome activity. However, there is scanty data on the activity of the NLRP3 inflammasome in patients with nascent MetS. The aim of this study was to determine the status of the inflammasome in subcutaneous adipose tissue (SAT) of patients with nascent MetS without concomitant diabetes, ASCVD and smoking., Materials and Methods: Patients with nascent MetS and controls were recruited from Sacramento County. Fasting blood samples were collected for biomediators of inflammation and SAT was obtained by biopsy for immunohistochemical (IHC) staining for caspase 1, IL-1β and IL-18., Results: Caspase1, a marker of inflammasome activity and its downstream mediators IL-1β and IL-18 were significantly increased in SAT of patients with MetS compared to controls. Significant positive correlations of caspase 1 were obtained with certain cardio-metabolic features, biomediators of inflammation and markers of angiogenesis and fibrosis in SAT. Both mast cell and eosinophil abundance but not macrophage density correlated with caspase1., Conclusions: We make the novel observation that the SAT of patients with nascent MetS displays increased NLRP3 inflammasome activity manifest by increased caspase 1 in SAT and this may contribute to increased insulin resistance, inflammation and SAT fibrosis in these patients., (2020 John Wiley & Sons Ltd.)

Rationale, Aims and Objectives: To assess the outcomes of a clinical decision support (CDS) intervention designed for home care patients with high medication regimen complexity (MRC) and to examine correlates of CDS use., Method: The CDS consisted of a computerized algorithm that identified high MRC patients, electronic alerts and a care management module. Nurses were randomized upon identification of an eligible patient. Full intention to treat and intervention group-only analyses were completed. Regression-adjusted outcomes were hospitalization, emergency department use and reduction in MRC., Results: Five hundred nurses were randomized with 7919 of their patients. Approximately 20% of the intervention group was hospitalized versus 21% in the control group; 16.5% versus 16.7% had an emergency department visit; and 6% in each group dropped below the high MRC threshold. No statistically significant differences were found in the intention to treat analysis. Eighty-two percent of intervention nurses used the CDS but for only 42% of their patients. Among intervention patients, CDS use (vs. non-use) was associated with reduced MRC and hospitalization. CDS use was associated with various clinician and patient characteristics., Conclusion: CDS use was limited, negating the impact of the intervention overall. Findings on correlates of CDS use and the relationship between CDS use and positive outcomes suggest that CDS use and outcomes could be enhanced by avoiding short patient lengths of stay, improving continuity of care, increasing reliance on salaried nurses and/or increasing per diem nurses' incentives to use CDS., (© 2015 John Wiley & Sons, Ltd.)

The asymmetric unit of the title mol-ecular salt, C3H10N(+)·C12H9N4O7 (-) [alternative name: tri-methyl-ammonium 5-(2,4-di-nitro-phen-yl)-1,3-dimethyl barbiturate], contains one anion and two half-occupancy cations. The cations are disordered about inversion centres. The tetra-hydro-pyrimidine ring is essentially planar [maximum deviation = 0.007 (2) Å] and forms a dihedral angle of 41.12 (6)° with the plane of the benzene ring. In the crystal, N-H⋯O hydrogen bonds link the cations to the anions.

Background: Plasma or circulating miRNAs (cir miRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol (EtOH) altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate., Methods: Pregnant sheep were exposed to a binge model of EtOH consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a third-trimester-equivalent period from gestational day 4 (GD4) to GD132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte, and leukocytes obtained from nonpregnant ewes, and plasma from pregnant ewes 24 hours following the last binge EtOH episode, and from newborn lambs, at birth on ~GD147., Results: Pregnant ewe and newborn lamb cir miRNA profiles were similar to each other and different from nonpregnant female plasma, erythrocyte, or leukocyte miRNAs. Significant changes in cir miRNA profiles were observed in the EtOH-exposed ewe and, at birth, in the in utero, EtOH-exposed lamb. Cir miRNAs including miR-9, -15b, -19b, and -20a were sensitive and specific measures of EtOH exposure in both pregnant ewe and newborn lamb. Additionally, EtOH exposure altered guide-to-passenger strand cir miRNA ratios in the pregnant ewe, but not in the lamb., Conclusions: Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. Cir miRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment., (Copyright © 2014 by the Research Society on Alcoholism.)

Background: Fetal alcohol exposure produces multiorgan defects, making it difficult to identify underlying etiological mechanisms. However, recent evidence for ethanol (EtOH) sensitivity of the miRNA miR-9 suggests one mechanism, whereby EtOH broadly influences development. We hypothesized that loss of miR-9 function recapitulates aspects of EtOH teratology., Methods: Zebrafish embryos were exposed to EtOH during gastrulation, or injected with anti-miR-9 or nonsense control morpholinos during the 2-cell stage of development and collected between 24 and 72 hours postfertilization (hpf). We also assessed the expression of developmentally important, and known miR-9 targets, FGFR-1, FOXP2, and the nontargeted transcript, MECP2. Methylation at CpG islands of mammalian miR-9 genes was assessed in fetal murine neural stem cells (mNSCs) by methylation-specific PCR, and miRNA processing assessed by qRT-PCR for pre-miR-9 transcripts., Results: EtOH treatment and miR-9 knockdown resulted in similar cranial defects including microcephaly. Additionally, EtOH transiently suppressed miR-9, as well as FGFR-1 and FOXP2, and alterations in miR-9 expression were correlated with severity of EtOH-induced teratology. In mNSCs, EtOH increased CpG dinucleotide methylation at the miR-9-2 locus and accumulation of pre-miR-9-3., Conclusions: EtOH exerts regulatory control at multiple levels of miR-9 biogenesis. Moreover, early embryonic loss of miR-9 function recapitulated the severe range of teratology associated with developmental EtOH exposure. EtOH also disrupts the relationship between miR-9 and target gene expression, suggesting a nuanced relationship between EtOH and miRNA regulatory networks in the developing embryo. The implications of these data for the expression and function of mature miR-9 warrant further investigation., (Copyright © 2013 by the Research Society on Alcoholism.)

Aim: To study the effect of Kangaroo mother care in the Kangaroo ward in comparison with conventional care at neonatal unit on growth and breastfeeding in very low birth weight infants at 40 weeks' corrected gestational age., Methods: One hundred and forty neonates with birth weight <1500 g were randomized. The primary outcome was the average weight gain (g/kg/day) from the time of randomization to term gestational age., Results: Mean birth weight, age in days and weight at randomization were similar in both the groups. At term gestational age, average weight gain (g/kg/day) post randomization (23.3 ± 8.7 g vs. 22.64 ± 9.1 g, p = 0.67) and breastfeeding rate (85.9% vs. 87.0%) were comparable. There was no difference in weight gain (g/kg/day) from randomization to hospital discharge between the Kangaroo care group and conventional care group (18.01 g vs. 15.64 g, p = 0.12). Mortality, morbidities like sepsis, hypothermia, apnoea, hypoglycaemia and duration of hospitalization were equally distributed. On average, 11.5 days of intermediate care were saved in the kangaroo group., Conclusion: Kangaroo mother care in the Kangaroo ward is as effective as conventional care in the neonatal unit without any increase in morbidity or mortality in stable VLBW infants., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Undesired cell migration after targeted cell transplantation potentially limits beneficial effects for cardiac regeneration. MicroRNAs are known to be involved in several cellular processes, including cell migration. Here, we attempt to reduce human cardiomyocyte progenitor cell (hCMPC) migration via increasing microRNA-155 (miR-155) levels, and investigate the underlying mechanism. Human cardiomyocyte progenitor cells (hCMPCs) were transfected with pre-miR-155, anti-miR-155 or control-miR (ctrl-miR), followed by scratch- and transwell-assays. These functional assays displayed that miR-155 over-expression efficiently inhibited cell migration by 38 ± 3.6% and 59 ± 3.7% respectively. Conditioned medium from miR-155 transfected cells was collected and zymography analysis showed a significant decrease in MMP-2 and MMP-9 activities. The predicted 3'-UTR of MMP-16, an activator of MMP-2 and -9, was cloned into the pMIR-REPORT vector and luciferase assays were performed. Introduction of miR-155 significantly reduced luciferase activity which could be abolished by cotransfection with anti-miR-155 or target site mutagenesis. By using MMP-16 siRNA to reduce MMP-16 levels or by using an MMP-16 blocking antibody, hCMPC migration could be blocked as well. By directly targeting MMP-16, miR-155 efficiently inhibits cell migration via a reduction in MMP-2 and -9 activities. Our study shows that miR-155 might be used to improve local retention of hCMPCs after intramyocardial delivery., (© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Background: Ethanol (EtOH) and nicotine are often co-abused. However, their combined effects on fetal neural development, particularly on fetal neural stem cells (NSCs), which generate most neurons of the adult brain during the second trimester of pregnancy, are poorly understood. We previously showed that EtOH influenced NSC maturation in part, by suppressing the expression of specific microRNAs (miRNAs). Here, we tested in fetal NSCs the extent to which EtOH and nicotine coregulated known EtOH-sensitive (miR-9, miR-21, miR-153, and miR-335), a nicotine-sensitive miRNA (miR-140-3p), and mRNAs for nicotinic acetylcholine receptor (nAChR) subunits. Additionally, we tested the extent to which these effects were nAChR dependent., Methods: Gestational day 12.5 mouse fetal murine cerebral cortical-derived neurosphere cultures were exposed to EtOH, nicotine, and mecamylamine, a noncompetitive nAChR antagonist, individually or in combination, for short (24 hour) and long (5 day) periods, to mimic exposure during the in vivo period of neurogenesis. Levels of miRNAs, miRNA-regulated transcripts, and nAChR subunit mRNAs were assessed by quantitative reverse transcription polymerase chain reaction., Results: EtOH suppressed the expression of known EtOH-sensitive miRNAs and miR-140-3p, while nicotine at concentrations attained by cigarette smokers induced a dose-related increase in these miRNAs. Nicotine's effect was blocked by EtOH and by mecamylamine. Finally, EtOH decreased the expression of nAChR subunit mRNAs and, like mecamylamine, prevented the nicotine-associated increase in α4 and β2 nAChR transcripts., Conclusions: EtOH and nicotine exert mutually antagonistic, nAChR-mediated effects on teratogen-sensitive miRNAs in fetal NSCs. These data suggest that concurrent exposure to EtOH and nicotine disrupts miRNA regulatory networks that are important for NSC maturation., (Copyright © 2012 by the Research Society on Alcoholism.)

Movement of ions (Ca(2+) , K(+) , Na(+) , and Cl(-) ) and second messenger molecules like inositol 1, 4, 5-trisphosphate inside and in between different cells is the basis of many signaling mechanisms in the microcirculation. In spite of the vast experimental efforts directed toward evaluation of these fluxes, it has been a challenge to establish their roles in many essential microcirculatory phenomena. Recently, detailed theoretical models of calcium dynamics and plasma membrane electrophysiology have emerged to assist in the quantification of these intra and intercellular fluxes and enhance understanding of their physiological importance. This perspective reviews selected models relevant to estimation of such intra and intercellular ionic and second messenger fluxes and prediction of their relative significance to a variety of vascular phenomena, such as myoendothelial feedback, conducted responses, and vasomotion., (© 2012 John Wiley & Sons Ltd.)

1. Curcumin is the active ingredient of the dietary spice turmeric and has been consumed for medicinal purposes for thousands of years. Modern science has shown that curcumin modulates various signalling molecules, including inflammatory molecules, transcription factors, enzymes, protein kinases, protein reductases, carrier proteins, cell survival proteins, drug resistance proteins, adhesion molecules, growth factors, receptors, cell cycle regulatory proteins, chemokines, DNA, RNA and metal ions. 2. Because of this polyphenol's potential to modulate multiple signalling molecules, it has been reported to possess pleiotropic activities. First demonstrated to have antibacterial activity in 1949, curcumin has since been shown to have anti-inflammatory, anti-oxidant, pro-apoptotic, chemopreventive, chemotherapeutic, antiproliferative, wound healing, antinociceptive, antiparasitic and antimalarial properties as well. Animal studies have suggested that curcumin may be active against a wide range of human diseases, including diabetes, obesity, neurological and psychiatric disorders and cancer, as well as chronic illnesses affecting the eyes, lungs, liver, kidneys and gastrointestinal and cardiovascular systems. 3. Although many clinical trials evaluating the safety and efficacy of curcumin against human ailments have already been completed, others are still ongoing. Moreover, curcumin is used as a supplement in several countries, including India, Japan, the US, Thailand, China, Korea, Turkey, South Africa, Nepal and Pakistan. Although inexpensive, apparently well tolerated and potentially active, curcumin has not been approved for the treatment of any human disease. 4. In the present article, we discuss the discovery and key biological activities of curcumin, with a particular emphasis on its activities at the molecular and cellular levels, as well as in animals and humans., (© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.)

Background: S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione, the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALDs). The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoints were changes in serum levels of methionine metabolites., Methods: We randomized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects, and a posttreatment liver biopsy was performed in 14 subjects., Results: Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment, but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies., Conclusions: Whereas abstinence improved liver function, 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD., (Copyright © 2011 by the Research Society on Alcoholism.)

Cardiovascular disease is the leading cause of death in postmenopausal women. While diet and lifestyle remain the cornerstones of prevention, a low-fat/high-carbohydrate diet is associated with hyperglycemia and hyperlipemia-atherosclerotic risk factors affected by postprandial conditions. The objective of this study was to examine the acute response of lipids and insulin to a low-fat/high-carbohydrate meal with either a high-glycemic or a low-glycemic index in healthy postmenopausal women. Fifteen healthy postmenopausal women were enrolled in a randomized crossover dietary intervention study. Levels of glucose, triglyceride, free fatty acids (FFAs), and insulin were measured preprandially and for 240 minutes after consumption of the test meals. In response to the high-glycemic compared with the low-glycemic index meal, postprandial insulin levels had a higher peak (65.4 vs 48.1 microU/mL, respectively), the homeostasis model assessment-insulin resistance (HOMA-IR) was significantly higher (P=.014), serum triglyceride levels declined significantly (P<.001), and there was a small reduction in FFA levels, although the difference did not reach statistical significance. The results suggest a postprandial impact of glycemic index on cardiovascular metabolic biomarkers in postmenopausal women and may have implications for dietary glycemic modification of cardiovascular risk in women., (2009 Wiley Periodicals, Inc.)

1. Many studies have evaluated the effectiveness of alpha-tocopherol (vitamin E) in the development and progression of cardiovascular diseases, with conflicting results reported on the protective effect of this anti-oxidant. 2. The present study examined the effectiveness of a novel tocopheryl phosphate mixture (TPm) compared with that of alpha-tocopherol (TA) on key pro-inflammatory markers involved in atherogenesis, including interleukin (IL)-1beta, IL-6, IL-8, plasminogen activator inhibitor-1, tumour necrosis factor-alpha and C-reactive protein (CRP), as well as vascular function and lesion development in rabbits fed a 2% cholesterol diet. 3. Treatment with TPm, incorporated into the rabbit food at four doses ranging from 60 to 360 mg/kg chow, resulted in a significant reduction in plasma levels of all pro-inflammatory cytokines and biomarkers that appeared to be somewhat dose dependent. Conversely, treatment with TA, at a dose equivalent to the highest dose of TPm used, only decreased plasma levels of CRP, IL-6 and IL-8. Both TPm and TA treatment significantly improved vascular function to a similar extent, although TPm was more effective in reducing lesion development. 4. The reduction in these key pro-inflammatory markers appears to follow the improvement in the atherogenic state of the animals, indicating that the anti-inflammatory properties of TPm may be potentially beneficial in inflammatory disease states.

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small. A separate study, the Maudsley Bipolar Family Study, reported diminished P50 gating in unaffected relatives of psychotic bipolar patients. However, genetic and environmental influences are confounded in family studies due to lack of monozygotic (MZ) twin pairs. The current study combines the twin sample and the family sample in order to improve statistical power and study design, with the aims of: (1) substantiating the association between psychotic bipolar disorder and diminished P50 suppression and (2) verifying the genetic overlap between the two traits reported in the twin sample. We also assessed the relationship between bipolar disorder and an alternative suppression index, the P50 Condition-Testing (C-T) amplitude difference. A total of 309 subjects was included in this study, comprising 91 twin pairs, 31 bipolar families, and 45 unrelated healthy controls. Statistical analyses were based on structural equation modeling. Bipolar disorder was significantly associated with a diminished P50 suppression ratio and decreased C-T amplitude difference. Shared genetic factors were the main source of these associations. Suppression impairment was due to larger, poorly gated, T amplitude responses. The results provide further evidence that impaired P50 suppressions are promising endophenotypes for psychotic bipolar disorder. The non-specificity of impaired P50 suppression may reflect the impact of shared psychosis susceptibility genes., (Copyright 2008 Wiley-Liss, Inc.)

Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation. Some MZ female twin pairs are discordant for monogenic X linked disorders because of differential X inactivation. We postulated that similar mechanisms may also occur in disorders with more complex inheritance including BD and SZ. Examination of X-chromosome inactivation patterns in DNA samples from blood and/or buccal swabs in a series of 63 female MZ twin pairs concordant or discordant for BD or SZ and healthy MZ controls suggests a potential contribution from X-linked loci to discordance within twin pairs for BD but is inconclusive for SZ. Discordant female bipolar twins showed greater differences in the methylation of the maternal and paternal X alleles than concordant twin pairs and suggest that differential skewing of X-chromosome inactivation may contribute to the discordance observed for bipolar disorder in female MZ twin pairs and the potential involvement of X-linked loci in the disorder., ((c) 2007 Wiley-Liss, Inc.)

Background: To demonstrate a causative role for abnormal methionine metabolism in the pathogenesis of alcoholic steatohepatitis (ASH), we measured the preventive effects of supplementing folate deficient and ethanol containing diets in the micropig with S-adenosylmethionine (SAM), a metabolite that regulates methionine metabolism., Methods: Yucatan micropigs were fed folate-deficient diets as control, with ethanol at 40% of kcal, or with ethanol supplemented with SAM at 0.4 g/1000 kcal for 14 weeks. Histopathology, markers of liver injury, and regulatory enzymes were measured in terminal liver samples., Results: Among the ethanol group, livers showed hepatocellular necrosis together with increased levels of S-adenosylhomocysteine (SAH) and reduced levels of SAM and its ratio to SAH and glutathione (GSH), together with increased malondialdehyde plus hydroxynonenol (MDA + HNE) and nitrotyrosine (NT), transcripts and protein levels of cytochrome P4502E1 (CYP2E1), activity of NADPH oxidase, and activity and protein levels of inducible nitric oxide (iNOS). These findings were attenuated partially or completely to control levels by SAM supplementation of the ethanol diet., Conclusions: The present results indicate that SAM supplementation attenuates ethanol induced liver injury through its effects on the expressions and activities of oxidative stress pathways, and are consistent with the concept that the pathogenesis of oxidative liver injury is regulated in part through altered hepatic methionine metabolism.

We report 17 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency with drug-induced haemolytic anaemia. In most cases the drug involved was an antimalarial. However, we also found two cases in which other drugs could have been responsible for the haemolysis. The degree of severity of haemolysis differed in the individuals and most required multiple transfusions.