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Annelies Cannaert, Jolien Storme, Florian Franz, Volker Auwärter, Christophe P Stove
Synthetic cannabinoids (SCs) are the largest group of compounds currently monitored in Europe by the EU Early Warning System on new psychoactive substances. Emerging recreational use of these products has led to multiple cases of adverse health effects and even death. In contrast to marijuana, where Δ9-tetrahydrocannabinol (Δ9THC) is metabolized to only one major active metabolite, it has been reported that several major phase I metabolites of SCs remain biologically active, exerting cannabinoid (CB) receptor affinity, potency and efficacy greater than Δ9THC...
October 25, 2016: Analytical Chemistry
Vagner Bezerra Dos Santos, Daniela Daniel, Melina Singh, Claudimir Lucio do Lago
A capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for amphetamine (AM), phentermine (PTM), methamphetamine (MAM), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA) in commercial samples of homeopathic and phytotherapic medicines and dietary supplements is presented. The samples were submitted to a modified QuEChERS extraction procedure (at apparent pH 13) followed by electrophoretic separation in 0.1molL(-1) formic acid electrolyte (pH 2...
October 17, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Bradley C Carthon, Emmanuel S Antonarakis
Despite the numerous regulatory approvals for prostate cancer, metastatic prostate cancer remains a huge burden for men worldwide. In an exciting development, James et al. recently published data from the Systemic Therapy in Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: a multi-stage multi-arm randomised control trial (STAMPEDE). This is an innovative multi-arm multi-stage (MAMS) trial that has utilized one control arm and several comparator arms in order to provide evidence for the inclusion of therapies beyond standard androgen deprivation alone...
September 2016: Translational Cancer Research
Tamas Yelland, Snezana Djordjevic
Neuropilins (NRPs) are single-pass transmembrane receptors involved in several signaling pathways that regulate key physiological processes such as vascular morphogenesis and axon guidance. The MAM domain of NRP, which has previously been implicated in receptor multimerization, was the only portion of the ectopic domain of the NRPs for which the structure, until now, has been elusive. Using site-directed mutagenesis in the linker region preceding the MAM domain we generated a protein construct amenable to crystallization...
October 3, 2016: Structure
Juliana Tournebize, Valérie Gibaja, Jean-Pierre Kahn
BACKGROUND: Cannabis is the most widely used illicit drug in the United States and Europe. In recent years, a range of new substances with cannabis-like effects - known as synthetic cannabinoids (SCs) - have suddenly burst on the drug scene. However, there is limited information about the clinical hazards linked to the use of these emerging substances. This review summarizes the literature to date relating the health effects of SCs. METHOD: A systematic literature review of original case studies was performed using 'Pubmed' and the 'Web of Science' (January, 1980 - July, 2015)...
August 11, 2016: Substance Abuse
M Rodríguez-Arribas, S M S Yakhine-Diop, J M Bravo-San Pedro, P Gómez-Suaga, R Gómez-Sánchez, G Martínez-Chacón, J M Fuentes, R A González-Polo, M Niso-Santano
Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i...
October 6, 2016: Molecular Neurobiology
Manoj Prasad, Anna N Walker, Jasmeet Kaur, James L Thomas, Shirley A Powell, Amit V Pandey, Randy M Whittal, William E Burak, Guy Petruzzelli, Himangshu S Bose
The acute response to stress consists of a series of physiological programs to promote survival by generating glucocorticoids and activating stress-response genes that increase the synthesis of many chaperone proteins specific to individual organelles. In the endoplasmic reticulum (ER), short-term stress triggers activation of the unfolded protein response (UPR) module that either leads to neutralization of the initial stress or adaption to it; chronic stress favors cell death. UPR induces expression of the transcription factor, C/EBP homology protein (CHOP), and its deletion protects against the lethal consequences of prolonged UPR...
October 3, 2016: Molecular and Cellular Biology
Mam Kamel, Msa Elsedeek, Kaa Mohamed
No abstract text is available yet for this article.
November 2015: Journal of Minimally Invasive Gynecology
Alice Oppetit, Julie Bourgin, Gilles Martinez, Mathilde Kazes, Célia Mam-Lam-Fook, Raphael Gaillard, Jean-Pierre Olié, Marie-Odile Krebs
AIM: The aim is to describe a centre operating in Paris that pioneers the early intervention for young people at the onset and at high risk of psychosis in France. METHODS: Comprehensive descriptive analysis of different clinical and service measures is used in describing the implementation of the C'JAAD (Evaluation Centre for Young Adults and Adolescents) using data from an ongoing prospective non-interventional research programme. RESULTS: Over a 2-year period, 151 patients were referred to the C'JAAD and included in the ICAAR research programme...
September 28, 2016: Early Intervention in Psychiatry
Pierre Theurey, Jennifer Rieusset
Metabolic diseases are associated with nutrient excess and metabolic inflexibility. Mitochondria and endoplasmic reticulum are important organelles and nutrient sensors, and their dysfunction has been extensively and independently implicated in metabolic diseases. Both organelles interact at sites known as mitochondria-associated membranes (MAMs), in order to exchange metabolites and calcium. Recent evidence indicates that MAM could be a hub of hepatic insulin signaling and nutrient sensing. In this review, we discuss the roles organelle function and communication play in the cell's adaptation to nutrient availability, in both physiology and metabolic diseases...
September 23, 2016: Trends in Endocrinology and Metabolism: TEM
André Gottås, Marianne Arnestad, Per Steinar Halvorsen, Liliana C Bachs, Gudrun Høiseth
Vitreous humor (VH) is an alternative matrix for drug analysis in forensic toxicology. However, little is known about the distribution of xenobiotics, such as opioids, into VH in living organisms. The aim of this study was to simultaneously measure heroin and metabolite concentrations in blood and VH after injection of heroin in a living pig model. Six pigs were under non-opioid anesthesia during the surgical operation and experiment. Ocular microdialysis was used to acquire dialysate from VH, and a venous catheter was used for blood sampling...
2016: Forensic Toxicology
Mam Siddique, O Linhart, R Kujawa, S Krejszeff, Iae Butts
Seminal plasma (SP) and ovarian fluid (OF) plays an important role as storage media to prevent the activation of gametes both in vivo and under artificial conditions. The objectives of this study were to quantify gamete biochemistry and explore correlations among quantitative characteristics of SP, OF and sperm performance traits of Ide Leuciscus idus and Northern pike Esox lucius. Generally, Na(+) , K(+) and Cl(-) were found to be the most dominating ions, although concentrations of K(+) were higher in SP, while Na(+) and Cl(-) concentrations were higher in OF for both species...
September 21, 2016: Reproduction in Domestic Animals, Zuchthygiene
Misako Sato-Matsubara, Norifumi Kawada
Nielsen SR, Quaranta V, Linford A, et al.(1) (Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol. 2016;18:549-60) recently described a new mechanism for the tumor-stromal interaction in the metastatic progression of pancreatic ductal adenocarcinoma (PDAC) in the liver via granulin that is secreted by metastasis-associated macrophages (MAMs).(1) MAM-derived granulin transactivates hepatic stellate cells (hStCs), which leads to the production of periostin and extracellular matrix (ECM) at the metastatic site...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Steven A Connor, Ina Ammendrup-Johnsen, Allen W Chan, Yasushi Kishimoto, Chiaki Murayama, Naokazu Kurihara, Atsushi Tada, Yuan Ge, Hong Lu, Ryan Yan, Jeffrey M LeDue, Hirotaka Matsumoto, Hiroshi Kiyonari, Yutaka Kirino, Fumio Matsuzaki, Toshiharu Suzuki, Timothy H Murphy, Yu Tian Wang, Tohru Yamamoto, Ann Marie Craig
Mutations in a synaptic organizing pathway contribute to autism. Autism-associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) are thought to reduce excitatory/inhibitory transmission. However, we show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2 blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse development. Mdga2(+/-) mice, modeling autism mutations, demonstrated increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with no change in measures of inhibitory synapses...
September 7, 2016: Neuron
Chueh-Lin Hsu, Feng-Hsiang Chung, Chih-Hao Chen, Tzu-Ting Hsu, Szu-Mam Liu, Dao-Sheng Chung, Ya-Fen Hsu, Chien-Lung Chen, Nianhan Ma, Hoong-Chien Lee
Cancer stem cells (CSCs), or cancer cells with stem cell-like properties, generally exhibit drug resistance and have highly potent cancer inducing capabilities. Genome-wide expression data collected at public repositories over the last few years provide excellent material for studies that can lead to insights concerning the molecular and functional characteristics of CSCs. Here, we conducted functional genomic studies of CSC based on fourteen PCA-screened high quality public CSC whole genome gene expression datasets and, as control, four high quality non-stem-like cancer cell and non-cancerous stem cell datasets from the Gene Expression Omnibus database...
2016: Scientific Reports
Mabrouka Doghman-Bouguerra, Enzo Lalli
Steroidogenesis is a multistep process where interorganelle communications between the endoplasmic reticulum and mitochondria are critical. These intimate interactions physically occur through the Mitochondria-Associated ER membranes called MAMs. MAMs play important roles in mitochondrial morphology and in many cellular functions ranging from lipid metabolism, to calcium signaling and apoptosis together with a critical effect on steroidogenesis. Moreover, our recent characterization of new MAM resident proteins in adrenocortical cells extends the function of MAM in the mechanism of resistance of cancer cells to apoptotic stimuli and offers new perspectives in targeted therapeutic approaches for adrenocortical tumorigenesis...
September 1, 2016: Molecular and Cellular Endocrinology
Alexandra Maas, Michael Krämer, Konrad Sydow, Pai-Shan Chen, Torsten Dame, Frank Musshoff, Bernd W K Diehl, Burkhard Madea, Cornelius Hess
Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of detection. A novel opportunity to overcome these hindrances is represented by the new potential street heroin marker acetylated-thebaine-4-metabolite glucuronide (ATM4G), originating from thebaine during street heroin synthesis followed by metabolic reactions after administration...
August 26, 2016: Drug Testing and Analysis
Chen Li, Noel W Solomons, Marilyn E Scott, Kristine G Koski
BACKGROUND: Breast milk is the recommended source of nutrients for infant growth, but its adequacy to meet infants' mineral and trace element needs is unknown. OBJECTIVES: We used breast-milk mineral and trace element concentrations of Guatemalan mothers at 3 lactation stages to estimate total daily intakes and to determine whether intakes were associated with early infant growth. METHODS: In this cross-sectional study, breast-milk samples were collected from Mam-Mayan mothers during transitional (5-17 d, n = 56), early (18-46 d, n = 75), and established (4-6 mo, n = 103) lactation; z scores for weight (WAZ), length (LAZ), and head circumference (HCAZ) were measured...
October 2016: Journal of Nutrition
Sonia Missiroli, Massimo Bonora, Simone Patergnani, Federica Poletti, Mariasole Perrone, Roberta Gafà, Eros Magri, Andrea Raimondi, Giovanni Lanza, Carlo Tacchetti, Guido Kroemer, Pier Paolo Pandolfi, Paolo Pinton, Carlotta Giorgi
The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence that the tumor suppressor promyelocytic leukemia protein (PML) controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, autophagy induction. Our in vitro and in vivo results demonstrate how PML functions as a repressor of autophagy. PML loss promotes tumor development, providing a growth advantage to tumor cells that use autophagy as a cell survival strategy during stress conditions...
August 30, 2016: Cell Reports
Kyly C Whitfield, Crystal D Karakochuk, Hou Kroeun, Daniela Hampel, Ly Sokhoing, Benny B Chan, Mam Borath, Prak Sophonneary, Judy McLean, Aminuzzaman Talukder, Larry D Lynd, Eunice C Y Li-Chan, David D Kitts, Lindsay H Allen, Timothy J Green
Importance: Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, remains a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine concentrations, placing breastfed infants at risk of beriberi. Objective: To determine if consumption of thiamine-fortified fish sauce yields higher erythrocyte thiamine diphosphate concentrations (eTDP) among lactating women and newborn infants and higher breast milk thiamine concentrations compared with a control sauce...
October 3, 2016: JAMA Pediatrics
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