Alcohol exposure during late gestation: Multiple developmental outcomes in sheep

Alcohol consumption during pregnancy remains common in many countries. Exposure to even low amounts of alcohol (i.e. ethanol) in pregnancy can lead to the heterogeneous fetal alcohol spectrum disorders (FASD), while heavy alcohol consumption can result in the fetal alcohol syndrome (FAS). FAS is characterized by cerebral dysfunction, growth restriction and craniofacial malformations. However, the effects of lower doses of alcohol during pregnancy, such as those that lead to FASD, are less well understood. In this article, we discuss the findings of recent studies performed in our laboratories on the effects of fetal alcohol exposure using sheep, in which we investigated the effects of late gestational alcohol exposure on the developing brain, arteries, kidneys, heart and lungs. Our studies indicate that alcohol exposure in late gestation can (1) affect cerebral white matter development and increase the risk of hemorrhage in the fetal brain, (2) cause left ventricular hypertrophy with evidence of altered cardiomyocyte maturation, (3) lead to a decrease in nephron number in the kidney, (4) cause altered arterial wall stiffness and endothelial and smooth muscle function and (5) result in altered surfactant protein mRNA expression, surfactant phospholipid composition and pro-inflammatory cytokine mRNA expression in the lung. These findings suggest that fetal alcohol exposure in late gestation can affect multiple organs, potentially increasing the risk of disease and organ dysfunction in later life

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)

BACKGROUND: I'm-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I'm-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I'm-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I'm-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I'm-Yunity™ (PSP) elicits these effects. METHODS: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I'm-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins. RESULTS: Aqueous extracts of I'm-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G(1)/S and G(2)/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I'm-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-κB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I'm-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase). CONCLUSION: Aqueous extracts of I'm-Yunity™ (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I'm-Yunity™ (PSP)

Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors

Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Le fluor : utilisations thérapeutiques et toxicité

Isolé en 1886 à Paris par Henri Moissan, le fluor est devenu un élément indispensable en médecine, en pharmacie, mais aussi dans de nombreuses applications industrielles. Plus qu'être présent dans nos dentifrices pour prévenir l'apparition de la carie dentaire, le fluor, par ses propriétés physico-chimiques particulières, est devenu un élément indispensable en chimie pharmaceutique et en biologie : modulant les propriétés pharmacodynamiques de certaines molécules, permettant la synthèse de substituts sanguins ou étant utile en tomographie par émission de positons. Depuis les années 1950 et les premiers travaux de H. T. Dean, le fluor est largement utilisé à travers le monde dans la prévention bucco-dentaire. De la fluoration artificielle de l'eau de boisson et du sel de table jusqu'à l'utilisation de dentifrices fluorés ou la prescription de compléments chez le nourrisson, les sources d'apport en fluor se sont multipliées ces dernières années. Cependant, la prise régulière de fluor à forte dose peut être responsable de l'apparition d'une fluorose dentaire ou osseuse. Cette pathologie modifiant la structure de l'émail ou du squelette est endémique dans certaines régions du monde, comme la Chine ou l'Inde, et est aussi en recrudescence aux États-Unis et en Europe. Le pharmacien d'officine, acteur de santé au quotidien, est en première ligne pour informer les patients lors de la dispensation de tout produit fluoré, et doit participer à la prévention de cette maladie

Identification of degraded driving conditions through image analysis of pavement.

Les situations dégradées d'éclairage et certaines conditions météorologiques sont deux problèmes impactant la sécurité routière. La détection et la caractérisation éventuelle de celles-ci, à l'aide d'une caméra embarquée à bord des véhicules, constitueraient un élément clé permettant d'assister le conducteur. En effet, la visibilité de ce dernier peut être largement réduite, d'une part à cause des conditions météorologiques et, d'autre part, à cause des situations d'éclairages qui, dans certains cas, peuvent éblouir le conducteur.Cependant, la visibilité n'est pas le seul risque pour l'automobiliste, l'état de la route joue également un rôle important dans la sécurité du conducteur. En effet, une chaussée mouillée peut perturber les conditions de circulation des automobilistes. Elle peut engendrer des pertes d'adhérence et, ainsi, elle peut nuire directement à la sécurité des personnes présentes sur la scène routière. Associée à des conditions d'éclairage défavorables, la chaussée mouillée peut occasionner des risques d'éblouissement du conducteur. C'est pourquoi la détection de chaussées mouillées présente un intérêt certains permettant de favoriser les conditions de circulations des automobilistes. La chaussée mouillée réémet plus de lumière qu'une chaussée sèche de part ses propriétés optiques qui sont modifiées par la pellicule d'eau à sa surface. Afin d'identifier l'état réel de la chaussée (sèche, mouillée), nous étudions la quantité de lumière reçue par une caméra embarquée dans un véhicule. Cette étude se fait par le biais d'un modèle physique de réflexion de la lumière ou modèle de la BRDF. Ce modèle est alimenté par un modèle d'illumination du ciel et nous donne la valeur de luminance de la route pour une direction d'observation donnée. La différenciation chaussée sèche/ chaussée mouillée se fera en analysant les valeurs de luminance obtenues.Dans un premier temps, nous avons généré des images de synthèses de routes sècheset mouillées en s'appuyant sur un modèle de BRDF différent. Dans un second temps, les modèles présentés précédemment sont utilisés sur des images réelles afin de répondre à notre problématique à savoir l'identification de l'état réel de la chaussée.Les résultats obtenus pourront être utilisé, d'une part, par d'autres systèmes d'aide à la conduite, pour proposer une vitesse et une trajectoire adéquate au véhicule améliorant ainsi la sécurité du conducteur. Et d'autre part, ces résultats permettront de fiabiliser les aides à la conduite qui s'appuient sur les images issues de caméras.Adverse lighting conditions and meteorological conditions are two critical issues for the road safety as they are subjected to jeopardize the driver perception of the environment. Thus, their detection and characterization with a vehicle embedded camera will be a key element to assist the driver. However, visibility is not the only risk for the driver, the road's state plays also a major role in driver's safety. Indeed, a wet road may cause on the one hand losses of grip and thus harming user's safety on road scene. On the other hand, it increases the risk of glaring in case of adverse lighting conditions. It's why wet road detection is very useful to improve motorist driving conditions. A wet road reflects more light than the dry one due to its optical properties which are modified by the presence of water film on its surface. In order to identify the actual road's state (dry or wet), we study the light quantity observed by a vehicle embedded camera. This study is based on bidirectional reflectance distribution function (BRDF) model. The BRDF model is combined with a sky model to give the road's luminance value for a given direction. The wet/dry road differentiation is based on the analyze of luminance values.The first step consists in implementing each model in order to generate synthetic images of dry and wet roads.In the second step these models are carried out on real road scene images acquired by an embedded camera in order to identify the actual road's state. The results can be used by others driver assistance systems, on the one hand, in order to suggest an appropriate speed limit and trajectory for the vehicle, thus improving driver's safety, on the other hand, in order to improve ADAS's reliability based on camera

Le Management de la qualité appliqué à l'officine selon la norme ISO 9001 : 2000 (une illustration)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

De l'ordonnance au suivi en officine (enquêtes sur les stupéfiants réalisées en région Centre)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF