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Current Pharmaceutical Design

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https://www.readbyqxmd.com/read/28641547/recent-advances-on-the-role-of-micrornas-in-both-insulin-resistance-and-cancer
#1
Adele Vivacqua, Paola De Marco, Antonino Belfiore, Marcello Maggiolini
BACKGROUND: Insulin resistance is a pathological condition characterized by the failure of target cells to uptake and metabolizes glucose in response to insulin. In particular, the elevated concentrations of glucose, insulin and free insulin growth factor-1, which result from insulin resistance, may generate a pro-inflammatory and pro-tumorigenic state. These alterations may underlie the increased risk to develop various types of cancer as well as the worse cancer prognosis observed in obese and diabetic patients...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641546/targeting-astrocytes-for-treating-neurological-disorders-carbon-monoxide-and-noradrenaline-induced-increase-in-lactate
#2
Anemari Horvat, Nina Vardjan, Robert Zorec
There are at least three reasons why brain astrocytes represent a new target for treating neurological disorders. First, although the human neocortex represents over 80% of brain mass, neurons are outnumbered by non-neuronal cells, including astrocytes, a neuroglial cell type. Second, as in neurons, vesicle-based release of transmitters is present in astrocytes, however with much slower kinetics than in neurons. Third, astrocytes contain glycogen, which can be transformed to L-lactate in glycolysis. L-lactate is considered to be a fuel and a signalling molecule involved in cognition and neuroprotection...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641545/role-of-bradykinin-in-the-regulation-of-endothelial-nitric-oxide-synthase-expression-by-cardiovascular-drugs
#3
Jin Bo Su
NO produced by eNOS plays important roles in the cardiovascular system. Alterations in eNOS activity and expression occur in various cardiovascular disorders and eNOS constitutes a therapeutic target. In addition to posttranslational modifications of eNOS that affect eNOS activity, transcriptional and post-transcriptional regulation of eNOS expression also controlls eNOS-derived NO production. Bradykinin is an important determinant of vascular function and participates in the regulation of eNOS activity and expression...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641544/post-mortem-redistribution-of-drugs-current-state-of-knowledge
#4
Caroline Sastre, Christophe Bartoli, Valerie Baillif-Couniou, Georges Leonetti, Anne-Laure Pelissier-Alicot
BACKGROUND: Drug concentrations obtained from post mortem samples do not necessarily reflect the concentrations at the time of death, and variations of concentration may be observed between different sites and/or different sampling times. These phenomena, collectively termed post mortem redistribution, concern numerous molecules (medications, drugs of abuse, gases, etc.) and can complicate the interpretation of toxicological analyses. METHODS: Literature review...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641543/zein-based-nanocarriers-as-potential-natural-alternatives-for-drug-and-gene-delivery-focus-on-cancer-therapy
#5
Ahmed Elzoghby, May Freag, Hadeer Mamdouh, Kadria Elkhodairy
Protein nanocarriers possess unique merits including minimal cytotoxicity, numerous renewable sources, and high drug-binding capability. In opposition to delivery carriers utilizing hydrophilic animal proteins, hydrophobic plant proteins (e.g, zein) have great tendency in fabricating controlled-release particulate carriers without additional chemical modification to stiffen them, which in turn evades the use of toxic chemical crosslinkers. Moreover, zein is related to a class of alcohol-soluble prolamins and generally recognized as safe (GRAS) carrier for drug delivery...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641542/functional-nanoparticles-and-their-interactions-with-mesenchymal-stem-cells
#6
Weiwei Wang, Zijun Deng, Xun Xu, Zhengdong Li, Friedrich Jung, Nan Ma, Andreas Lendlein
Mesenchymal stem cells (MSCs) have become one of the most important cell sources for regenerative medicine. However, some mechanisms of MSC-based therapy are still not fully understood. The clinical outcome may be restricted by some MSC-related obstacles such as the low survival rate, differentiation into undesired lineages and malignant transformation. In recent years, with the emergence of nanotechnology, various types of multifunctional nanoparticles (NPs) have been designed, prepared and explored for bio-related applications...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641541/-stress-is-80-years-old-from-hans-selye-original-paper-in-1936-to-recent-advances-in-gi-ulceration
#7
Sandor Szabo, Masashi Yoshida, Janos Filakovszky, Gyorgy Juhasz
The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical students and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad")...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641540/metallothionein-is-a-potential-therapeutic-strategy-for-amyotrophic-lateral-sclerosis
#8
Shin-Ichi Ono
Lou Gehrig's disease, a synonym of amyotrophic lateral sclerosis, is an adult-onset lethal neurodegenerative disorder. Irrespective of extensive efforts to elucidate the pathogenesis of the disease and searches for therapies, no favorable pharmacotherapeutic strategies have yet to be proposed. In a popular rodent model of ALS, G93A SOD1 mice, intracellular copper conditions were geared toward copper accumulation inside cells, resulting in an acceleration of oxidative stress and apoptotic process. Disruption of intracellular copper homeostasis was common to transgenic mice expressing human mutant SOD1s...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#9
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641538/glt-1-upregulation-as-a-potential-therapeutic-target-for-ischemic-brain-injury
#10
Yu-Yan Hu, Li Li, Xiao-Hui Xian, Min Zhang, Xiao-Cai Sun, Shu-Qin Li, Xin Cui, Jie Qi, Wen-Bin Li
Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which plays an important role in many aspects of normal brain function such as neural development, motor functions, learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous system is mainly regulated by the uptake activity of excitatory amino acid transporters...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641537/lsd-detection-and-interpretation-in-hair
#11
Camille Richeval, Delphine Allorge, X Vanhoye, Jean-Michel Gaulier
Lysergic acid diethylamide (LSD) is a powerful hallucinogen, active at very low dosages, with, as a direct consequence, potential difficulties to be detected and quantified in a clinical or forensic context, in body fluids and even more in hair. The aim of this work is to review literature data related to hair analysis of LSD with a particular focus on the main issues encountered in LSD detection in hair. Results of LSD investigation in hair remain difficult to interpret regarding the very sparse data available on LSD concentrations in hair (n=10)...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641536/overview-of-forensic-toxicology-yesterday-today-and-in-the-future
#12
Heesun Chung, Sanggil Choe
BACKGROUND: The scope of forensic toxicology has been tremendously expanded over the past 50 years. From two general sections forensic toxicology can be further classified into 8-9 sections. METHODS: The most outstanding improvement in forensic toxicology is the changes brought by instrumental development. The field of forensic toxicology was revolutionized by the development of immunoassay and bench-top GC-MS in the 1980's and LC-MS-MS in 2000's. Detection of trace amounts of analytes has allowed the use of new specimens such as hair and oral fluids, along with blood and urine...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641535/hiv-1-transcription-inhibitors-increase-the-synthesis-of-viral-non-coding-rna-that-contribute-to-latency
#13
Yao A Akpamagbo, Catherine DeMarino, Michelle L Pleet, Angela Schwab, Myosotys Rodriguez, Robert A Barclay, Gavin Sampey, Sergey Iordanskiy, Nazira El-Hage, Fatah Kashanchi
BACKGROUND: HIV-1 can be preserved in long-lived resting CD4+ T- and myeloid cells, forming a viral reservoir in tissues of the infected individuals. Infected patients primarily receive cART, which, to date, is the most efficient treatment against HIV/AIDS. However, the major problem in the eradication of HIV-1 from patients is the lack of therapeutic approaches to recognize the latent HIV-1 provirus and to eliminate latently infected cells. RESULTS: In the current review, we describe the effect of HIV-1 transcriptional inhibitors CR8#13 and F07#13 using a series of in vitro and in vivo assays...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641534/interest-of-single-hair-analysis-to-document-drug-exposure-literature-review-and-a-case-report-involving-zuclopenthixol
#14
Nathalie Allibe, Pascal Kintz, Amandine Faure, François Paysant, Anne-Pascale Michard-Lenoir, Françoise Stanke-Labesque, Virginie Scolan, Hélène Eysseric-Guerin
The analysis of hair to detect drugs and drugs of abuse is performed in various contexts, including child protection cases, abstinence control programs, and workplace drug testing. This alternative matrix offers several advantages, such as a large detection window (months) and non-invasive collection. Segmental analysis of multiple hair strands for drugs and metabolites has been widely reported in the literature over the past three decades, whereas a review of the literature showed that there are only 26 articles that report the analysis of a single hair...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641530/method-development-in-forensic-toxicology
#15
Frank T Peters, Dirk K Wissenbach, Francesco Paolo Busardò, Emilia Marchei, Simona Pichini
BACKGROUND: In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. METHODS: The presented article will provide an overview on the process of developing methods for forensic applications. RESULTS: This includes the definition of the method's purpose (e...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641533/role-and-therapeutic-potential-of-astrocytes-in-amyotrophic-lateral-sclerosis
#16
Mariana Pehar, Benjamin A Harlan, Kelby M Killoy, Marcelo R Vargas
Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641532/trimethylamine-n-oxide-tmao-as-a-new-potential-therapeutic-target-for-insulin-resistance-and-cancer
#17
Jens Oellgaard, Signe Abitz Winther, Tobias Schmidt Hansen, Peter Rossing, Bernt Johan von Scholten
BACKGROUND: The intake of animal products in food has been associated with both the development of insulin resistance and gastrointestinal cancers (GIC). Through the digestion of animal protein and other constituents of animal products, the commensal bacteria in the gut (the gut microbiota) forms metabolites that can contribute to the development of both insulin resistance and cancer. Trimethylamine-N-Oxide (TMAO) is such a molecule and has recently drawn a lot of attention as it may be a risk factor for - and a link between - the gut microbiota and cardiovascular and renal disease...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641531/application-of-alphaviral-vectors-for-immunomodulation-in-cancer-therapy
#18
Anna Zajakina, Karina Spunde, Kenneth Lundstrom
BACKGROUND: The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. METHODS: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28625138/membrane-bound-atp-dependent-energy-systems-as-extra-and-intracellular-key-signals-for-gastrointestinal-functions-and-their-regulations-in-the-gastrointestinal-mucosa
#19
Gyula Mózsik, Imre László Szabó, József Czimmer
AIMS: Our research group has carried out various biochemical examinations in rat gastric ulcer models and in human gastrointestinal resecates obtained from patient who underwent gastric intervention due to peptic ulcer disease. Biochemical methods gave excellent possibility to approach the biochemical events taking place in tissues, cellular and subcellular regulatory levels during of ulcer development and of its prevetions. This paper gives a briefsummary of these biochemical examinations conducted during this study period started from the 1960's up till now...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28625137/chemokine-like-receptor-1-cmklr-1-receptor-a-potential-therapeutic-target-in-management-of-chemerin-induced-type-2-diabetes-mellitus-and-cancer
#20
Sangeetha Perumalsamy, Nurul Ain Aqilah Mohd Zin, Riyanto Teguh Widodo, Wan Azman Wan Ahmad, Shireene Ratna Db Vethakkan, Hasniza Zaman Huri
BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality. AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer...
June 15, 2017: Current Pharmaceutical Design
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