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https://www.readbyqxmd.com/read/28728153/genetic-variants-of-cytochrome-cyp2d6-in-two-mixed-chilean-populations
#1
Mónica Acuña, Eric Pinto, Paulina Olivares, Carolina Ríos
OBJECTIVES: It is known that the interindividual and interethnic variability of the genetic polymorphisms of CYP2D6 plays an important role in the presentation of adverse drug reactions and concerning lack of therapeutic effects in humans. However, there are few data available from mixed populations of Latin America, including the Chilean. The aim of this study was therefore to estimate the frequencies of CYP2D6 variants in two samples of hospitals from the northern (Hospital San José, HSJ) and eastern (Clínica Las Condes, CLC) parts of Santiago, Chile, with different degrees of Amerindian admixture (HSJ: 34...
July 21, 2017: Human Heredity
https://www.readbyqxmd.com/read/28728094/modelling-a-budgetary-impact-analysis-for-funding-drug-based-smoking-cessation-therapies-for-patients-with-major-depressive-disorder-in-spain
#2
J Rejas-Gutiérrez, E Bruguera, S Cedillo
BACKGROUND: Smoking is associated with high healthcare resource utilisation and cost to society. Patients with major depressive disorder (MDD) exhibit high susceptibility to nicotine dependence. Varenicline, bupropion and nicotine replacement therapy are all indicated for smoking cessation; however funding by the Spanish national health system (SNHS) is limited. We modelled a budgetary impact analysis (BIA) to estimate the impact of the SNHS funding drug-based therapies for smoking cessation in smokers with MDD...
June 3, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28727920/ballistic-penetration-of-highly-charged-nanoaerosol-particles-through-a-lipid-monolayer
#3
Victor N Morozov, Yuri M Shlyapnikov, Igor L Kanev, Elena Andreevna Shlyapnikova
To be used as a drug, inhaled nanoaerosol particles (NAPs) must first penetrate the lipid layer on top of the lung fluid before they will be able to reach the lung epithelium. We investigated how the penetration of NAPs through a model lipid monolayer (LM) depends upon their charging level and size. It was shown that deposition of NAPs 20-200 nm in diameter and charged to the Rayleigh limit gradually increased the surface tension of a dipalmitoylphosphatidylcholine monolayer (DPPC), indicating a loss of lipid molecules from the monolayer...
July 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#4
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28727804/effects-of-pre-surgical-administration-of-prostaglandin-analogs-on-the-outcome-of-trabeculectomy
#5
Takako Miki, Tomoko Naito, Miyuki Fujiwara, Ryoichi Araki, Rieko Kiyoi, Yusuke Shiode, Atsushi Fujiwara, Yuki Morizane, Fumio Shiraga
For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28727740/genetically-engineered-suicide-gene-in-mesenchymal-stem-cells-using-a-tet-on-system-for-anaplastic-thyroid-cancer
#6
Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Liya Zhu, Ho Won Lee, Yong Hyun Jeon, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28727662/paraphilic-thoughts-behaviors-and-sex-addiction-in-a-sample-of-persons-who-use-drugs-a-cross-sectional-study
#7
Jales Clemente, Sandra Cristina Pillon, Jair de Jesus Mari, Claudio Jeronimo da Silva, Paulo Roberto Henrique Santana, Alessandra Diehl
OBJECTIVE: The aim of this study was to evaluate the prevalence of paraphilic thoughts/behaviors (including paraphilic disorders) with and without sexual addiction and sexual-related conditions in a sample of substance disorder patients. METHODS: This was a cross-sectional study of substance-dependent individuals who sought outpatient treatment in São Paulo, Brazil. Data included sociodemographic information, drug of choice, responses to questions about sexual behavior, and to the following standardized questionnaires: (a) Sexual Addiction Screening Test, and (b) Childhood Trauma Questionnaire...
July 19, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28727190/tuning-the-effects-of-bacterial-membrane-permeability-through-photo-isomerization-of-antimicrobial-cationic-amphiphiles
#8
Micha Fridman, Joana Salta, Raphael I Benhamou, Ido M Herzog
Several last resort classes of antimicrobial drugs act by permeabilizing cell membranes. Here we demonstrate that insertion of a photo-isomerizable lipid into antimicrobial cationic amphiphiles can modify the intensity of their membrane-permeabilizing activity not only by their concentration but also through light-irradiation. We characterized the photo-isomerization effects of two types of cationic amphiphiles on their bacterial membrane permeabilizing activity and showed that while one photo-isomer inhibited cell growth and division, the other photo-isomer led to a rapid and lethal bacterial membrane-disrupting effect...
July 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28727127/the-assessment-of-overall-survival-os-after-adjuvant-chemotherapy-for-patients-with-malignant-endometrial-cancer-in-poland
#9
Zbigniew Teter, Andrzej Śliwczyński, Melania Brzozowska, Marcin Świerkowski, Andrzej Jacyna, Jarosław Pinkas, Aleksandra Sierocka, Michał Marczak, Anna Dańska-Bidzińska, Mariusz Bidziński, Waldemar Wierzba
OBJECTIVES: In 2013 malignant endometrial cancers have amounted to 7.3% of all cancers diagnosed among women in the report by the Polish National Cancer Registry Raw prevalence rate amounted to 28.7, whereas standardised prevalence rate 15.6 per 100 000 population. Among the causes of death, these cancers amounted to 3% and were ranked ninth on the list of the most common causes of oncologic mortality of women. In the year 2013 a total of 1243 women died of malignant endometrial cancers...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28726961/functional-single-walled-carbon-nanotubes-car-for-targeting-dopamine-delivery-into-the-brain-of-parkinsonian-mice
#10
Qing Guo, Huihui You, Xu Yang, Bencheng Lin, Zhihong Zhu, Zhisong Lu, Xiaoxiao Li, Yun Zhao, Lin Mao, Shiping Shen, Haoyan Cheng, Jiting Zhang, Lingfu Deng, Jianhua Fan, Zhuge Xi, Rui Li, Chang Ming Li
Current treatments for Parkinson's disease (PD) are limited, partly due to the difficulties posed by the blood brain barrier (BBB) when delivering drugs to the brain. Herein, we explore the feasibility and efficacy of functional single-walled carbon nanotubes 'CAR' (SWCNT-PEGs-Lf) which carry and target-deliver dopamine (DA) to the brain in PD mice for treatment. SWCNTs can penetrate the cell-membrane remarkably, with the characteristics including high drug-loading and pH-dependent therapeutic unloading capacities...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28726848/patch-clamp-technique-to-characterize-ion-channels-in-enlarged-individual-endolysosomes
#11
Cheng-Chang Chen, Chunlei Cang, Stefanie Fenske, Elisabeth Butz, Yu-Kai Chao, Martin Biel, Dejian Ren, Christian Wahl-Schott, Christian Grimm
According to proteomics analyses, more than 70 different ion channels and transporters are harbored in membranes of intracellular compartments such as endosomes and lysosomes. Malfunctioning of these channels has been implicated in human diseases such as lysosomal storage disorders, neurodegenerative diseases and metabolic pathologies, as well as in the progression of certain infectious diseases. As a consequence, these channels have engendered very high interest as future drug targets. Detailed electrophysiological characterization of intracellular ion channels is lacking, mainly because standard methods to analyze plasma membrane ion channels, such as the patch-clamp technique, are not readily applicable to intracellular organelles...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28726801/accumbens-mechanisms-for-cued-sucrose-seeking
#12
Ana-Clara Bobadilla, Constanza Garcia-Keller, Jasper A Heinsbroek, Michael Scofield, Victoria Chareunsouk, Cara Monforton, Peter W Kalivas
Many studies support a perspective that addictive drugs usurp brain circuits used by natural rewards, especially for the dopamine-dependent reinforcing qualities of both drugs and natural rewards. Reinstated drug seeking in animal models of relapse relies on glutamate spillover from cortical terminals synapsing in the nucleus accumbens core (NAcore) to stimulate metabotropic glutamate receptor5 (mGluR5) on neuronal nitric oxide synthase (nNOS) interneurons. Contrasting the release of dopamine that is shared by sucrose and drugs of abuse, reinstated sucrose seeking does not induce glutamate spillover...
July 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28726800/role-of-nicotinamide-n-methyltransferase-in-dorsal-striatum-in-cocaine-place-preference
#13
Li Luo, Fei-Fei Shang, Hailei Long, Linhong Jiang, Ruiming Zhu, Qian Zhao, Hui Gu, Jueying Kong, Wei Xu, Yinglan Zhao, Xiaobo Cen
Nicotinamide N-methyltransferase (NNMT) transfers the methyl from S-adenosyl-L-methionine (SAM) to nicotinamide (NA) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide (MeN). NNMT has been implicated in a variety of diseases; however, the role of NNMT in drug addiction is largely unknown. Here, we found that the expression of Nnmt was significantly upregulated in the dorsal striatum (DS) of cocaine-conditioned mice. Cocaine significantly decreased SAM/SAH ratio levels in the DS, which was accompanied with the decreased activities of Rac1 and RhoA...
July 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28726797/multiple-myeloma
#14
REVIEW
Shaji K Kumar, Vincent Rajkumar, Robert A Kyle, Mark van Duin, Pieter Sonneveld, María-Victoria Mateos, Francesca Gay, Kenneth C Anderson
Multiple myeloma is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. The diagnosis of multiple myeloma is made when clear end-organ damage attributable to the plasma cell proliferative disorder or when findings that suggest a high likelihood of their development are present. Distinguishing symptomatic multiple myeloma that requires treatment from the precursor stages of monoclonal gammopathy of undetermined significance and smouldering multiple myeloma is important, as observation is the standard for those conditions...
July 20, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28726723/mertensene-a-halogenated-monoterpene-induces-g2-m-cell-cycle-arrest-and-caspase-dependent-apoptosis-of-human-colon-adenocarcinoma-ht29-cell-line-through-the-modulation-of-erk-1-2-akt-and-nf-%C3%AE%C2%BAb-signaling
#15
Safa Tarhouni-Jabberi, Ons Zakraoui, Efstathia Ioannou, Ichrak Riahi-Chebbi, Meriam Haoues, Vassilios Roussis, Riadh Kharrat, Khadija Essafi-Benkhadir
Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S...
July 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28726640/c1q-tnf-related-protein-6-ctrp6-links-obesity-to-adipose-tissue-inflammation-and-insulin-resistance
#16
Xia Lei, Marcus M Seldin, Hannah C Little, Nicholas Choy, Thomas Klonisch, G William Wong
Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug, rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28726349/aspherical-nanostructured-microparticles-for-targeted-gene-delivery-to-alveolar-macrophages
#17
Michael Möhwald, Shashank Reddy Pinnapireddy, Bodo Wonnenberg, Marcel Pourasghar, Marijas Jurisic, Andrea Jung, Claudia Fink-Straube, Thomas Tschernig, Udo Bakowsky, Marc Schneider
Introducing novel shapes to particulate carrier systems adds unique features to modern drug and gene delivery. Depending on the route of administration, particle geometry can influence deposition and fate within biological environments. In this work, a template-assisted engineering technique is applied, providing full control of size and shape in the preparation of aspherical, nanostructured microparticles. Based on the interconnection of nanoparticles, stabilized by a functional layer-by-layer (LbL) coating, the resulting cylindrical micrometer architecture is especially qualified for pulmonary delivery...
July 20, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28726253/%C3%AE-9-and-%C3%AE-7-containing-receptors-mediate-the-pro-proliferative-effects-of-nicotine-in-the-a549-adenocarcinoma-cell-line
#18
Vanessa Mucchietto, Francesca Fasoli, Susanna Pucci, Milena Moretti, Roberta Benfante, Annalisa Maroli, Simona Di Lascio, Cristiano Bolchi, Marco Pallavicini, Cheryl Dowell, Michael McIntosh, Francesco Clementi, Cecilia Gotti
BACKGROUND AND PURPOSE: Tobacco smoke contains many classes of carcinogens and although nicotine is unable to initiate tumorigenesis in humans and rodents, it promotes tumour growth and metastasis in lung tumours by acting on neuronal nicotinic acetylcholine receptors (nAChRs). The aim of this study was to identify molecularly, biochemically and pharmacologically which nAChR subtypes are expressed and functionally activated by nicotine in lung cancer cell lines. EXPERIMENTAL APPROACH: We used A549 and H1975 adenocarcinoma cell lines derived from lung tumour to test the in vitro effects of nicotine, and nAChR subtype-specific peptides and compounds...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28726195/effects-of-secondary-metabolites-of-permafrost-bacillus-sp-on-cytokine-synthesis-by-human-peripheral-blood-mononuclear-cells
#19
L F Kalenova, S S Kolyvanova, A S Bazhin, I M Besedin, V P Mel'nikov
We studied the effects of secondary metabolites of Bacillus sp. isolated from late Neogene permafrost on secretion of proinflammatory (TNF-α, IL-1β, IL-8, IL-2, and IFNγ) and antiinflammatory (IL-4 and IL-10) cytokines by human peripheral blood mononuclear cells. It was found that metabolites of Bacillus sp. produced more potent effect on cytokine secretion than mitogen phytohemagglutinin and metabolites of Bacillus cereus, medicinal strain IP5832. Activity of metabolites depended on the temperature of bacteria incubation...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28726150/inhibition-mechanism-of-cdk-2-and-gsk-3%C3%AE-by-a-sulfamoylphenyl-derivative-of-indoline-a-molecular-dynamics-study
#20
Przemysław Czeleń
A good understanding of the inhibition mechanism of enzymes exhibiting high levels of similarity is the first step to the discovery of new drugs with selective potential. Examples of such proteins include glycogen synthase kinase-3 (GSK-3β) and cyclin-dependent kinase 2 (CDK-2). This article reports the mechanism of such enzyme inhibition as analyzed by an indoline sulfamylophenyl derivative (CHEMBL410072). Previous work has shown that such compounds exhibit selective properties towards their biological targets...
August 2017: Journal of Molecular Modeling
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