Oxygen/Glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors

Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A3 receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca2+ also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3 receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotectio

Evaluation de l’antibioprophylaxie en chirurgie urologique au sein de l’Hôpital Militaire Moulay Ismail de Meknès L’antibioprophylaxie en urologie

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Adénome de prostate révélé par des hypoglycémies profondes: A propos d'un cas

RésuméIntroductionEnviron 90% des patients diabétiques présentent un diabète de type 2. L'hypoglycémie constitue le principal effet indésirable des antidiabétiques oraux. Elle est d'autant plus grave qu'elle s'accompagne d'une insuffisance rénale.Cas cliniqueNous rapportons le cas d'un homme âgé de 85ans suivi pour un diabète de type 2 et une hypertension artérielle. Il a été admis via les urgences dans un tableau de trouble de conscience associé à une fièvre. Le bilan réalisé a objectivé une hypoglycémie profonde, une insuffisance rénale obstructive et un taux de PSA élevé (antigène spécifique de la prostate). Les antidiabétiques oraux ont été arrêtés et un sondage vésical a été effectué avec comme résultats une correction des hypoglycémies et de la fonction rénale. Le patient a eu une résection trans-urétrale de la prostate (RTUP) et l'examen anatomopathologique était en faveur d'un adéno-myo-fibrome. Les troubles neurologiques en rapport avec l'hypoglycémie étaient sous forme d'agitations, délire, trouble des fonctions supérieures et troubles du sommeil. Cependant notre patient n'a pas présenté de déficit neurologique. L’évolution clinique était favorable.ConclusionL'insuffisance rénale obstructive peut constituer une complication de l'adénome de la prostate à un stade ultime. Elle est responsable d'accumulation dans le sang de médicaments y compris les antidiabétiques oraux. L'hypoglycémie qui en résulte est délétère pour la qualité de vie du patient et peut être responsable d'accidents neurologiques.AbstractIntroductionApproximately 90% of patients with diabetes have type 2 diabetes. Hypoglycemia is the main side effect of oral antidiabetics, and it can be more serious when it is accompanied by renal failure.Clinical caseWe report the case of a man aged 85 years followed for type 2 diabetes and hypertension. He was admitted via the emergency with a disturbed level of consciousness associated with fever. The medical evaluation revealed profound hypoglycemia, obstructive renal failure and an elevated PSA (prostate specific antigen). Oral hypoglycemic agents were discontinued and catheterization was performed resulting in correction of hypoglycemia and renal function. The patient underwent a transurethral resection of prostate (TURP) and pathologic examination was in favor of benign hyperplasia. Neurological disorders related to hypoglycemia were agitation, delirium, impaired higher functions and sleep disorders. However our patient did not present any neurological deficit. The clinical course was favorable.ConclusionThe obstructive renal failure can be a complication of benign prostatic hyperplasia in a final stage. It is responsible for accumulation in the blood of drugs including oral anti-diabetic agents. The resulting hypoglycemia is deleterious to the quality of life of the patient and may be responsible for neurological disorders

Pneumothorax spontané et emphysème pulmonaire chez les consommateurs de cannabis

INTRODUCTION: If pulmonary complications of tobacco smoking are well documented, those associated with cannabis use are less known. OBJECTIVES: Systematic literature review of data on pneumothorax and lung emphysema in cannabis users. DOCUMENTARY SOURCES: Medline, on the period 1980-2018 with the following keywords cannabis or marijuana and pneumothorax or emphysema, limits "title/abstract". Among 97 articles, 42 abstracts have given use to a dual reading to select 20 studies. RESULTS: Eighteen case reports (8 with SP) showed bullae in the upper lobes in combined cannabis and tobacco smokers (CS) and in the 2 cannabis only smokers (COS). The risk of SP was increased in CS, but not in COS. In patients less than 35-years old presenting with SP, the incidence of bullae on thoracic computed tomography (CT) was higher in CS than in tobacco only smokers (TOS). CT in patients with SP showed no significant difference as regards of the prevalence, location and type of emphysema between CS and TOS. Proportion of low lung density areas was higher in CS than in non-smokers (NS), but was similar in TOS and NS. CONCLUSION: These results suggest a cumulative toxic effect of tobacco and cannabis on the risk of SP and lung emphysema

The Role of Liposomal CpG ODN on the Course of L. major Infection in BALB/C Mice

"nBackground: Historically, leishmanization is the most effective protective measure against Cutaneous Leishmaniasis (CL), CL lesion induced by leishmanization sometimes takes a long time to heal. Ma­nipulation of leishmanization inoculums needed to induce a mild and acceptable CL lesion. The aim of this study was to explore if liposomal form of CpG ODN (Cytosin phosphate Guanin Oligodeoxynu­cleotides) mixed with Leishmania major   would induce a milder lesion size in Balb/c mice."nMethods: This study was performed in Biotechnology Research Center, Mashhad, and Center for Re­search and Training in Skin Diseases and Leprosy, Tehran, Iran during 2008-2009.  mice were subcutaneously (SC) inoculated with L. major mixed with liposomal form of CpG ODN, or L. major plus free CpG ODN, or L. major mixed with empty liposomes or L. major in PBS. The lesion onset and the size of lesion were recorded; the death rate was also monitored. "nResult: Footpad thickness was significantly (P<0.01) smaller, death rate was also significantly (P<0.05) lower in the mice received L. major mixed with liposomal CpG ODN or free CpG ODN than control groups received L. major in PBS or L. major plus liposomes, also mice which received L. ma­jor mixed with CpG ODN in soluble form showed a significantly (P < 0.001) smaller lesion size than control groups."nConclusion: CpG ODN seems to be an appropriate immunopotentiator mixed with Leishmania stabi­late in leishmanization

Enhanced SUMOylation and SENP-1 protein levels following oxygen and glucose deprivation in neurones

Here, we show that oxygen and glucose deprivation (OGD) causes increased small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 conjugation to substrate proteins in cultured hippocampal neurones. Surprisingly, the SUMO protease SENP-1, which removes SUMO from conjugated proteins, was also increased by OGD, suggesting that the neuronal response to OGD involves a complex interplay between SUMOylation and deSUMOylation. Importantly, decreasing global SUMOylation in cultured hippocampal neurones by overexpression of the catalytic domain of SENP-1 increased neuronal vulnerability to OGD-induced cell death. Taken together, these results suggest a neuroprotective role for neuronal SUMOylation after OGD