Efficacy of N-Acetylcysteine, Glutathione, and Ascorbic Acid in Acute Toxicity of Paraoxon to Wistar Rats: Survival Study

There are a great number of reports with assertions that oxidative stress is produced by organophosphorus compound (OPC) poisoning and is a cofactor of mortality and morbidity in OPC toxicity. In addition, antioxidants have been suggested as adjuncts to standard therapy. However, there is no substantial evidence for the benefit of the use of antioxidants in survival after acute intoxication of OPCs. The present study was conducted to assess the effectiveness of three non-enzymatic antioxidants (NEAOs), N-acetylcysteine (NAC), glutathione (GSH), and ascorbic acid (AA), in acute intoxication of adult male Wister rats with paraoxon. The efficacy of the antioxidants was estimated as both a pretreatment and a concurrent application along with the standard oxime, pralidoxime (2-PAM). Relative risk of death after 48 hours of application was estimated by Cox regression analysis. The results revealed no benefit of either tested NEAO to the improvement in survival of experimental rats. The application of these antioxidants was found to be deleterious when administered along with pralidoxime compared to the treatment with pralidoxime alone. It has been concluded that the tested non-enzymatic antioxidants are not useful in acute toxicity for improving survival rates. However, the individual toxic dynamics of diversified OPCs should not be overlooked and further studies with different OPCs are suggested

Front-end electronics for cable reduction in Intracardiac Echocardiography (ICE) catheters

3-D imaging ICE catheters with large element counts present design challenges in achieving simultaneous data readout from all elements while significantly reducing cable count for a small catheter diameter. Current approaches such as microbeamformer techniques tend to rely on area and power hungry circuits, making them undesirable for ICE catheters. In this paper, a system which uses are an efficient real-time programmable on-chip transmit (TX) beamformer circuitry to reduce the cable count on the TX side and analog 8/1 Time Division Multiplexing (TDM) with Direct Digital Demodulation (DDD) to reduce the cable count on the receive (RX) side is presented

Single-Chip Reduced-Wire CMUT-on-CMOS System for Intracardiac Echocardiography

CMUT-on-CMOS integration is particularly suitable for catheter based ultrasound imaging applications, where electronics integration enables multiplexing capabilities to reduce the number of electrical connections leading to smaller catheter cable profiles. Here, a single-chip CMUT-on-CMOS system for intracardiac echocardiography (ICE) is presented. In this system, a 64 element 1-D CMUT array is fabricated over an application specific integrated circuit (ASIC) that features a programmable transmit beamformer with high voltage (HV) pulsers and receive circuits using 8:1 time division multiplexing (TDM). Integration of pitch matched 64 channel front-end circuits with CMUT arrays in a single-chip configuration allows for implementation of catheter probes with miniaturization, reduced number of cables, and better mechanical flexibility. The ASIC is implemented in 60 V 0.18 μm HV process. It occupies 2.6×11 mm 2 which can fit in the catheter size of 9F, and reduces the number of wires from more than 64 to 22. This system is used for B-mode imaging of imaging phantoms and its potential application for 2D CMUT-on-CMOS arrays is discussed

Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes

Foregoing researches made on the N/OFQ system brought up a possible role for this system in cardiovascular regulation. In this study we examined how N/OFQ levels of the blood plasma changed in acute cardiovascular diseases. Three cardiac patient groups were created: enzyme positive acute coronary syndrome (EPACS, n = 10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11). We compared the patients to healthy control subjects (n = 31). We found significantly lower N/OFQ levels in the EPACS [6.86 (6.21–7.38) pg/ml], ENACS [6.97 (6.87–7.01) pg/ml and IHD groups [7.58 (7.23–8.20) pg/ml] compared to the control group [8.86 (7.27–9.83) pg/ml]. A significant correlation was detected between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ depression is in association with the level of ischemic stress and the following inflammatory response. Further investigations are needed to clarify the relevance and elucidate the exact effects of the ischemic stress on the N/OFQ system

Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is an open access article available at http://www.eje-online.org/content/172/6/697.BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.The genetic testing was funded by the Wellcome Trust (Senior Investigator Award to Profs S Ellard and A T Hattersley), and by Diabetes UK (Project funding to Dr D J Mackay). H Demirbilek was funded by European Society for Paediatric Endocrinology (ESPE) and The Scientific and Technological Research Council of Turkey (TUBITAK) for his 1 year clinical fellowship at University College London (UCL), Institute of Child Health, Great Ormond Street Hospital for Children, NHS Trust, Department of Paediatric Endocrinology

Single-Chip Reduced-Wire Active Catheter System with Programmable Transmit Beamforming and Receive Time-Division Multiplexing for Intracardiac Echocardiography

Intracardiac echocardiography (ICE) provides real-time ultrasound imaging of the heart anatomy from inside, guiding interventions like valve repair, closure of atrial septal defects (ASD) and catheter-based ablation to treat atrial fibrillation. With its better image quality and ease of use, ICE is becoming the preferred imaging modality over transesophageal echography (TEE) for structural heart interventions. The existing commercial ICE catheters, however, offer a limited 2-D or 3-D field of view despite catheters utilizing large number of wires. In these catheters, each element in the ICE array is connected to the backend data-acquisition channel with a separate wire, which is a critical barrier for improving image quality and widening the field of view. In order to use ICE catheters under MRI instead of the ionizing X-ray radiation-based angiography, the number of interconnect wires in the catheter should be minimized to reduce RF-induced heating. Furthermore, reducing the number of wires improves the flexibility and lowers the cost of the single-use ICE catheters

Operação Bororos: vivências de saúde, educação e cultura na Chapada dos Guimarães

Trabalho apresentado no II Congresso Nacional do PROJETO RONDON, realizado em Florianópolis, SC, no período de 23 a 25 de setembro de 2015 - Universidade Federal de Santa Catarina.Introdução: O Projeto Rondon é um programa interministerial, coordenado pelo Ministério da Defesa, que visa integrar e desenvolver ações comunitárias em regiões com maiores índices de pobreza e exclusão social, bem como áreas isoladas do território nacional necessitadas de maior aporte de bens e serviços. Em parceira com as universidades, o projeto pretende contribuir com a formação do universitário como cidadão, integrá-lo ao processo de desenvolvimento nacional por meio de ações participativas sobre a realidade do país. Além disso, visa consolidar no universitário o sentido de responsabilidade social coletiva, em prol da cidadania estimulando a produção de projetos coletivos locais, em parceria com as comunidades, com foco na capacitação de agentes multiplicadores, estimulando ações que valorizem o cidadão, a cultura local e promovam o intercâmbio de informações. Com esse espírito, a Instituição de Ensino Superior (IES) desenvolveu um plano de trabalho, aprovado para execução no município de Chapada dos Guimarães, estado do Mato Grosso, durante a Operação Bororos, no período de 10 a 26 de julho de 2015. Objetivo: Descrever as atividades realizadas no município, direcionadas aos profissionais de saúde, educação, assistência social e à comunidade em geral. Metodologia: A descrição se dará a partir do registro documental e fotográfico das atividades desenvolvidas e das avaliações feitas pelos participantes. Resultados: Foram realizadas 22 atividades de cultura, comunicação, saúde e educação, por meio de oficinas teórico-práticas, simpósios, mutirão de saúde e rodas de conversa, com participação de 293 pessoas. A maior parte das atividades foi concentrada na área urbana do município, em escolas, creches, centros culturais, praças e feiras ao ar livre. Observaram-se benefícios à comunidade com a troca de saberes e informações ofertadas pelos universitários, uma vez que agregaram novos subsídios para o trabalho cotidiano, seja dos multiplicadores ou dos cidadãos em geral que tiveram acesso às atividades desenvolvidas. Conclusão: O Projeto Rondon consolida-se como oportunidade única para os universitários colocarem em prática os conhecimentos adquiridos ao longo de suas vivências acadêmicas em prol da sociedade. Observou-se a necessidade de adequação das atividades priorizando-se as populações rurais caracterizadas como mais vulneráveis

The biological basis and clinical significance of hormonal imprinting, an epigenetic process

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to epigenetic imprinting or metabolic imprinting. In the case of hormonal imprinting, the first encounter between a hormone and its developing target cell receptor—usually at the perinatal period—determines the normal receptor-hormone connection for life. However, in this period, molecules similar to the target hormone (members of the same hormone family, synthetic drugs, environmental pollutants, etc), which are also able to bind to the receptor, provoke faulty imprinting also with lifelong—receptorial, behavioral, etc.,—consequences. Faulty hormonal imprinting could also be provoked later in life in continuously dividing cells and in the brain. Faulty hormonal imprinting is a disturbance of gene methylation pattern, which is epigenenetically inherited to the further generations (transgenerational imprinting). The absence of the normal or the presence of false hormonal imprinting predispose to or manifested in different diseases (e.g., malignant tumors, metabolic syndrome) long after the time of imprinting or in the progenies

Screening of Hungarian cattle herds for Mycoplasma mycoides subspecies mycoides small colony infection with negative results

At abattoirs and farms, 1248 sera were collected from animals representing 121 farms, and examined by complement fixation test using Mycoplasma mycoides subspecies mycoides small colony type (MmmSC) antigen. All sera were negative except seven from four farms, giving ++ reactions in the serum dilution of 1:10. On retesting, these sera and additional 30 sera collected repeatedly in both farms gave negative results. In isolation attempts, 953 lung samples collected from slaughtered cattle at the same abattoirs, and 326 nasal swabs collected from 11 herds proved to be negative for the presence of MmmSC, but M. bovis was isolated frequently. In the small farms 23.95% of the animals had pleurisy and/or pneumonia while in the large herds 34.69% had lesions. DNA extracted from 50 nasal swabs and 430 lung samples was examined by polymerase chain reaction (PCR) using M. mycoides cluster-specific primers. DNA from further 325 lung samples was tested by the more specific M. mycoides subspecies mycoides small colony/large colony/capri specific primers and 196 samples by nested PCR specific for MmmSC. All gave negative results. The detection level of cluster-specific primers and the more specific primers was 33.4 pg of DNA, whereas that of nested PCR was 0.33 pg

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy