Réduction des dommages myocardiques par le célécoxib suite à une ischémie transitoire chez le rat

Cette étude a été conçue afin d’évaluer l’effet d’un pré-traitement à long terme au célécoxib sur la taille d’infarctus suite à un infarctus du myocarde. Sachant que le célécoxib est un anti-inflammatoire et que des dommages myocardiques peuvent découler des processus inflammatoires, l’inhibition de l’inflammation devrait hypothétiquement réduire la taille d’un éventuel infarctus. Pour ce faire, un traitement au célécoxib (3 mg/kg/jour i.p.) ou au véhicule (DMSO 50% ; EtOH 15% ; eau distillée) a été administré chroniquement pendant 28 jours à des rats mâles Sprague-Dawley (n=18 par groupe) par pompes osmotiques ALZET. Après avoir été anesthésiés, les animaux ont été sujets à l’occlusion de l’artère coronaire gauche descendante, suivie d’une période de reperfusion de 24 heures. Les résultats démontrent que la taille de l’infarctus des animaux traités au célécoxib est significativement réduite comparativement à celle du groupe témoin (37,5±2,5% versus 48,0±2,6% de la zone à risque, p < 0,05). Par la suite, l’accumulation de neutrophiles indique une hausse de ces leucocytes pour la zone ischémique, sans toutefois discriminer entre les groupes traité et non-traité, qui contenaient aussi les couches sub-endocardique et sous-épicardique. Cependant, aucune différence significative est notée entre les groupes traité et témoin au niveau de l’expression de la prostaglandine E2 plasmatique et du facteur de nécrose tumorale alpha. D’un autre côté, l’apoptose, déterminée par le ratio de Bax/Bcl2 et par un essai TUNEL est significativement réduite pour la couche sub-endocardique de la zone à risque des animaux traités au célécoxib. Enfin, l’agrégation plaquettaire, induite à l’adénosine diphosphate et analysée dans le sang complet, suggère que le célécoxib diminue l’agrégation plaquettaire. Cette étude indique alors qu’un pré-traitement au célécoxib peut réduire la taille d’infarctus par un mécanisme impliquant l’apoptose.This study was designed to evaluate the effect of long-term pre-treatment with celecoxib, a cyclooxygenase-2 inhibitor, on myocardial infarct size. Since celecoxib is an anti-inflammatory and that myocardial damages can be present in the occurrence of inflammatory processes, inhibition of inflammation should hypothetically reduce the size of an eventual infarct. Celecoxib (3 mg/kg/day i.p.) or vehicle (DMSO 50%; EtOH 15%; distilled water) was administered chronically to male Sprague-Dawley rats (n=18 per group) through ALZET osmotic pumps for 28 days. Under anaesthesia, the animals were then subjected to left anterior descending coronary artery occlusion for 40 minutes, followed by 24-hour reperfusion. The results show that myocardial infarct size in celecoxib-treated rats was significantly reduced compared to the control group (37.5±2.5% versus 48.0±2.6% of the area at risk, p < 0.05). Accumulation of neutrophils, estimated by myeloperoxidase levels, indicated an increase in the ischemic area without any significant difference between groups. No significant difference was observed between the treated and vehicle groups in terms of plasma prostaglandin E2 and tumour necrosis factor-alpha. Apoptosis, evaluated by Bax/Bcl-2 and terminal dUTP nick-end labelled-positive cells, was significantly decreased in the subendocardial layer of the ischemic area in celecoxib-treated rats. Adenosine diphosphate-induced platelet aggregation in whole blood suggested that celecoxib diminished platelet aggregation. This study indicates that pre-treatment with celecoxib can reduce infarct size by a mechanism which may involve apoptosis

Schizophrenia: Early Recognition and Prevention

Schizophrenia is a heterogenous disorder presenting as episodes of psychosis against a background of cognitive, social, and functional impairments. Schizophrenia, a multifaceted neuropsychiatric disorder, is affecting approximately 1% of the population worldwide. Its onset is the result of a complex interplay of genetic predisposition and environmental factors. The clinical staging model of psychotic disorders implies that early successful treatment may improve prognosis and prevent progression to more severe stages of disorder. So, prevention and early intervention of schizophrenia are correlated with the prodromal phase, especially with “at risk mental state” (ARMS) and the prediction of their transition to a full-blown psychotic disorder. The psychosis prodrome includes nonspecific signs and symptoms (such as depressed mood, anxiety, sleep disturbance, and deterioration in role functioning), “basic symptoms” (thought interference, disturbance of receptive language, and visual perception disturbance), attenuated or subthreshold psychotic symptoms, neurocognitive deficits, and neurobiological changes measured via magnetic resonance imaging (MRI). Increasing improvements in the identification of those truly at “high risk” for psychotic disorder have paved the way of early intervention strategies in this population and increased the possibility of minimizing distress and disability and delaying or even preventing the onset of an evident psychotic disorder. The treatment (antipsychotic medication, psychological and social interventions) for young people who meet ARMS criteria should not only focus on the symptoms that constitute the ARMS criteria but also address the broader range of difficulties with which the young person might present. There are some ethical issues to consider when selecting specific treatment options, and the potential risks of treatment have to be balanced against the potential benefits

A method for accurate detection of genomic microdeletions using real-time quantitative PCR

BACKGROUND: Quantitative Polymerase Chain Reaction (qPCR) is a well-established method for quantifying levels of gene expression, but has not been routinely applied to the detection of constitutional copy number alterations of human genomic DNA. Microdeletions or microduplications of the human genome are associated with a variety of genetic disorders. Although, clinical laboratories routinely use fluorescence in situ hybridization (FISH) to identify such cryptic genomic alterations, there remains a significant number of individuals in which constitutional genomic imbalance is suspected, based on clinical parameters, but cannot be readily detected using current cytogenetic techniques. RESULTS: In this study, a novel application for real-time qPCR is presented that can be used to reproducibly detect chromosomal microdeletions and microduplications. This approach was applied to DNA from a series of patient samples and controls to validate genomic copy number alteration at cytoband 22q11. The study group comprised 12 patients with clinical symptoms of chromosome 22q11 deletion syndrome (22q11DS), 1 patient trisomic for 22q11 and 4 normal controls. 6 of the patients (group 1) had known hemizygous deletions, as detected by standard diagnostic FISH, whilst the remaining 6 patients (group 2) were classified as 22q11DS negative using the clinical FISH assay. Screening of the patients and controls with a set of 10 real time qPCR primers, spanning the 22q11.2-deleted region and flanking sequence, confirmed the FISH assay results for all patients with 100% concordance. Moreover, this qPCR enabled a refinement of the region of deletion at 22q11. Analysis of DNA from chromosome 22 trisomic sample demonstrated genomic duplication within 22q11. CONCLUSION: In this paper we present a qPCR approach for the detection of chromosomal microdeletions and microduplications. The strategic use of in silico modelling for qPCR primer design to avoid regions of repetitive DNA, whilst providing a level of genomic resolution greater than standard cytogenetic assays. The implementation of qPCR detection in clinical laboratories will address the need to replace complex, expensive and time consuming FISH screening to detect genomic microdeletions or duplications of clinical importance

Perinatal asphyxia: we can anticipate and ameliorate the effects?

Universitatea de Medicină şi Farmacie, Tîrgu-Mureş, Institutul de Boli Cardiovasculare şi Transplantm, Tîrgu-MureşIntroduction: Despite the progress in monitoring the fetus in utero and broadening knowledge of pathophysiology, asphyxia at birth remains a very topical issue due to the impact on the immediate and late outcome prognosis. Posthypoxic impairment of the brain is the most serious consequence of perinatal asphyxia, causing the clinical outline of hypoxic-ischemic encephalopathy, resulting in cerebral palsy. Case presentation: authors expose the cases of two-term newborns who presented birth asphyxia, who have received a similar treatment, but had a different short-term outcome. The first case was a newborn of the diabetic and hypertensive mother which subsequently developed multicystic encephalomalacia. The second case, which suffered acute asphyxia due to maternal intrapartum hypotension had a favorable outcome, with a normal neurological examination at discharge. Conclusion: anticipating the effects of perinatal asphyxia is difficult, but the presence of seizures, early and persistent pathological changes on electroencephalogram, cerebral edema detected by ultrasounds, and abnormal neurological examination at discharge can be considered poor prognostic factors.Introducere: În ciuda progreselor făcute în monitorizarea fătului in utero şi a lărgirii orizontului cunoaşterii fiziopatologiei, asfixia la naştere continuă să rămână o problemă de mare actualitate datorită răsunetului asupra prognosticului imediat şi îndepărtat. Afectarea posthipoxică a creierului este consecinţa cea mai gravă a asfixiei perinatale, determinând conturarea tabloului clinic de encefalopatie hipoxic-ischemică, având ca urmare paralizia cerebrală. Prezentări de caz: autorii expun cazurile a doi nou-născuţi la termen care au prezentat asfixie la naştere, care au beneficiat de o atitudine terapeutică similară, dar care au avut o evoluţie precoce diferită. Primul caz este al unui nounăscut din mamă diabetică şi hipertensivă care a dezvoltat ulterior encefalomalacie multichistică. Al doilea caz, care a suferit o asfixie acută pe fondul hipotensiunii materne postanestezie a avut o evoluţie favorabilă, examenul neurologic fiind normal la externare. Concluzii: anticiparea efectelor asfixiei perinatale este dificilă, dar prezenţa convulsiilor, a modificărilor EEG precoce şi persistente, a edemului cerebral detectat prin ETF, precum şi examenul neurologic anormal la externare pot fi consideraţi factori de prognostic nefavorabil

Influence of Fusarium spp. Inoculation Dose Simulating Pathogen Pressure on Grain Production Parameters of Zea mays L.

Several fungi species from genus Fusarium can infect maize crop and cause seedling blight, root rot, stalk rot, cob and ear rot. Maize yield and grain quality are negatively affected by the disease, while mycotoxins accumulating in grains represent a serious threat to human and animal health. In this research two maize hybrids were subject to artificial infection in field with Fusarium spp. suspension at three incremental dose levels simulating increasing pathogen pressure. Results indicated that earlier maturing hybrid (lsquo%253BTurda 248 ndash%253B FAO 300 maturity group) following artificial infection displayed lower infection index of ears (up to 15.33%25) while the later-maturing hybrid (lsquo%253BTurda 332 ndash%253B FAO 380 maturity group) displayed higher infection levels of up to 30.87%25. Uninoculated controls presented infection index of ears below 2%25 for both hybrids. For the hybrid lsquo%253BTurda 248 the highest pathogen pressure (inoculation dose 12 mL%252Fear) caused 23.10%25 yield decrease relative to control, while same dose for the hybrid lsquo%253BTurda 332 caused 21.20%25 yield decrease relative to control. Once with increased inoculation dose the grain quality parameters displayed changes. The observed trend was an increasing protein content and decreasing starch content once with increased pathogen pressure. Identification of resistant genotypes and study of the climatic factors that undergo disease development remain important research approaches for efficient control of the pathogen populations in agroecosystems

Identification of dorsal cutaneous perforator vessels using angio CT technique

The pig is used very often as an experimental model in plastic surgery. Identification of the correct skin flap require also identification of the cutaneous perforate vessel that irrigate the flap. The contrast medium used in radiology and CT have the capability to highlight the small vessel of the skin

Hunter disease eClinic: interactive, computer-assisted, problem-based approach to independent learning about a rare genetic disease

<p>Abstract</p> <p>Background</p> <p>Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).</p> <p>Aim</p> <p>To develop interactive teaching software functioning as a virtual clinic for the management of MPS II.</p> <p>Implementation and Results</p> <p>The <it>Hunter disease eClinic</it>, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (<url>http://www.lysosomalstorageresearch.ca</url>), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The <it>Hunter disease eClinic </it>consists of an <it>eBook </it>and an <it>eClinic</it>. The <it>eClinic </it>is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The <it>eBook </it>provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the <it>eClinic</it>, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available.</p> <p>Conclusions</p> <p>The Hunter disease <it>eClinic </it>employs a CBT model providing the trainee with realistic clinical problems, coupled with comprehensive basic and clinical reference information by instantaneous access to an electronic textbook, the <it>eBook</it>. The program was rated highly by attendees at national and international presentations. It provides a potential model for use as an educational approach to other rare genetic diseases.</p