Hemophagocytic lymphohistiocytosis associated with HBV‐HCV coinfection in adult: Case report

The case reported is the first case in Morocco to our knowledge. The reason for sharing this case is to facilitate knowledge transfer between physicians, caring for adult patients with HLH, with the aim to improve the outcome of these patients.     

Ryanodine Receptor Blockade Reduces Amyloid-β Load and Memory Impairments in Tg2576 Mouse Model of Alzheimer Disease

In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca(2+)) homeostasis has been linked to presenilins, the catalytic core in γ-secretase complexes cleaving the amyloid precursor protein (APP), thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes to ER Ca(2+) homeostasis and whether ER Ca(2+) could in turn influence Aβ production. We show that overexpression of wild-type human APP (APP(695)), or APP harboring the Swedish double mutation (APP(swe)) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER Ca(2+) release in SH-SY5Y neuroblastoma cells and in APP(swe)-expressing (Tg2576) mice. Interestingly, dantrolene-induced lowering of RyR-mediated Ca(2+) release leads to the reduction of both intracellular and extracellular Aβ load in neuroblastoma cells as well as in primary cultured neurons derived from Tg2576 mice. This Aβ reduction can be accounted for by decreased Thr-668-dependent APP phosphorylation and β- and γ-secretases activities. Importantly, dantrolene diminishes Aβ load, reduces Aβ-related histological lesions, and slows down learning and memory deficits in Tg2576 mice. Overall, our data document a key role of RyR in Aβ production and learning and memory performances, and delineate RyR-mediated control of Ca(2+) homeostasis as a physiological paradigm that could be targeted for innovative therapeutic approaches.     

Chemically modified carbon-based electrodes for the determination of paracetamol in drugs and biological samples

Paracetamol is a non-steroidal, anti-inflammatory drug widely used in pharmaceutical applications for its sturdy, antipyretic and analgesic action. However, an overdose of paracetamol can cause fulminant hepatic necrosis and other toxic effects. Thus, the development of advantageous analytical tools to detect and determine paracetamol is required. Due to simplicity, higher sensitivity and selectivity as well as costefficiency, electrochemical sensors were fully investigated in last decades. This review describes the advancements made in the development of electrochemical sensors for the paracetamol detection and quantification in pharmaceutical and biological samples. The progress made in electrochemical sensors for the selective detection of paracetamol in the last 10 years was examined, with a special focus on highly innovative features introduced by nanotechnology. As the literature is rather extensive, we tried to simplify this work by summarizing and grouping electrochemical sensors according to the by which manner their substrates were chemically modified and the analytical performances obtained.     

HLA-B*27 allele associated to Behçet's disease and to anterior uveitis in Moroccan patients

Human leukocyte antigen HLA-B51 is the most strongly associated gene with Beh?et disease (BD) in different ethnic populations. We analyze the influence of HLA-B alleles in BD predisposition in Moroccan population and its association with clinical manifestations. The HLA-B phenotype frequencies were analyzed by serologic HLA class I typing and by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) reverse dot blot hybridization in 120 unrelated Moroccan patients: all of whom fulfilled the international study group criteria for Beh?et's disease, and in 112 ethnically matched healthy controls. Besides HLA-B*51 allele (20%), a significant increased frequency of the HLA-B*27 allele was found in Moroccans patients with Beh?et's disease when compared to controls (13.3% of patients versus 2.7% of controls, chi square =?8.75, OR =?5.59, 95% IC [1.58-19.75] and particularly in the patients who presented an anterior uveitis (25% vs. 5.5%, p 相似文献   

Is contralateral inguinal exploration necessary in preterm girls undergoing inguinal hernia repair during the first months of life?

Background

To assess the need for contralateral surgical exploration in preterm girls with symptomatic unilateral inguinal hernia.

Methods

The medical data of girls operated for inguinal hernia between 2004 and 2016 in a single pediatric surgery center were retrospectively collected. Preterm girls operated for unilateral hernia before 6 months of life were selected (55/517 cases) to assess the incidence and risk factors for contralateral metachronous inguinal hernia (CMIH).

Results

CMIH was observed in 7% of cases (4 girls with a right inguinal hernia in 3 cases) at a mean age of 4.2 years. Only one case occurred early (3 months). Birth weight and term were comparable (1674?±?620 g and 32?±?5 WA without CMIH vs. 1694?±?582 g and 33?±?3 WA with CMIH).

Conclusion

Contralateral inguinal hernia is very rare and generally occurs several years after inguinal repair surgery in preterm girls, which should encourage practitioners to follow these children throughout childhood for the subsequent development of inguinal hernia. This study did not find any arguments in favor of systematic contralateral exploration in preterm girls.

     

Monitoring vaccine safety using case series cumulative sum charts

We adapt the self-controlled case series method for routine surveillance of vaccine safety using cumulative sum (CUSUM) charts. The CUSUM surveillance method we propose is applicable for detecting associations that arise in a short pre-determined risk period following vaccination. The performance of the case series CUSUM is investigated through simulations. We illustrate the method using retrospective analyses of influenza vaccine and Bell's palsy, and MMR vaccine and febrile convulsions.     

The potential utility of acetyltanshinone IIA in the treatment of HER2-overexpressed breast cancer: Induction of cancer cell death by targeting apoptotic and metabolic signaling pathways

Increased lipogenesis and protein synthesis is a hallmark of cancer cell proliferation, survival, and metastatic progression and is under intense investigation as a potential antineoplastic target. Acetyltanshinone IIA (ATA) is a compound that was obtained from chemical modifications of tanshinone IIA (TIIA), a potent anticancer agent extracted from the dried roots of the Chinese herbal medicine Salvia miltiorrhiza Bunge. A previous investigation indicated that ATA is more effective in inhibiting the growth of breast cancer especially cells with HER2 overexpression. However, the molecular mechanism(s) mediating this cytotoxic effect on HER2-positive breast cancer remained undefined. Studies described here report that ATA induced G1/S phase arrest and apoptosis in the HER2-positive MDA-MB-453, SK-BR-3, and BT-474 breast cancer cell lines. Mechanistic investigations revealed that the ATA-induced apoptosis effect is associated with remarkably down-regulation of receptor tyrosine kinases (RTKs) EGFR/HER2 and inhibition of their downstream pro-survival signaling pathways. Interestingly, ATA was found to trigger oxidative and endoplasmic reticulum (ER) stresses and to activate AMP activated protein kinase (AMPK) leading to inactivation of key enzymes involved in lipid and protein biogenesis. Intraperitoneal administration of ATA significantly inhibited the growth of MDA-MB-453 xenografts in athymic mice without causing weight loss and any other side effects. Additionally, transwell migration, invasion, and wound healing assays revealed that ATA could suppress tumor angiogenesis in vitro. Taken together, our data suggest that ATA may have broad utility in the treatment of HER2-overexpressed breast cancers.