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[PMID]: 28542252 [Au] Autor: Boyle NR; Sengupta N; Morgan JA [Ad] Endereço: School of Chemical Engineering, Purdue University, West Lafayette, Indiana, United States of America. [Ti] Título: Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii. [So] Source: PLoS One;12(5):e0177292, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA) was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid) included in the model. Two citrate synthases were found to potentially be involved in acetyl-coA metabolism; one localized in the mitochondria and the other acting outside the mitochondria. Labeling patterns demonstrate that Acetyl-coA synthesized in the plastid is directly incorporated in synthesis of fatty acids. Despite having a complete TCA cycle in the mitochondria, it was also found that a majority of the malate flux is shuttled to the cytosol and plastid where it is converted to oxaloacetate providing reducing equivalents to these compartments. When compared to predictions by flux balance analysis, fluxes measured with 13C-MFA were found to be suboptimal with respect to biomass yield; C. reinhardtii sacrifices biomass yield to produce ATP and reducing equivalents. [Mh] Termos MeSH primário: Chlamydomonas reinhardtii/crescimento & desenvolvimento Chlamydomonas reinhardtii/metabolismo Processos Heterotróficos/fisiologia [Mh] Termos MeSH secundário: Acetilcoenzima A/metabolismo Trifosfato de Adenosina/metabolismo Carbono/metabolismo Isótopos de Carbono Citrato (si)-Sintase/metabolismo Coenzima A/metabolismo Citosol/metabolismo Ácidos Graxos/metabolismo Malatos/metabolismo Análise do Fluxo Metabólico Mitocôndrias/metabolismo Modelos Biológicos Ácido Oxaloacético/metabolismo Proteínas de Plantas/metabolismo Plastídeos/metabolismo Acetato de Zinco/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Carbon Isotopes); 0 (Fatty Acids); 0 (Malates); 0 (Plant Proteins); 2F399MM81J (Oxaloacetic Acid); 72-89-9 (Acetyl Coenzyme A); 7440-44-0 (Carbon); 817L1N4CKP (malic acid); 8L70Q75FXE (Adenosine Triphosphate); EC 2.3.3.1 (Citrate (si)-Synthase); FM5526K07A (Zinc Acetate); SAA04E81UX (Coenzyme A) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170919 [Lr] Data última revisão: 170919 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170526 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0177292

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[PMID]: 28171869 [Au] Autor: Ruppersberg HS; Goebel MR; Kleinert SI; Wünsch D; Trautwein K; Rabus R [Ad] Endereço: General and Molecular Microbiology, Institute for Chemistry and Biology of the Marine Environment (ICBM), Carl von Ossietzky University Oldenburg, Oldenburg, Germany. [Ti] Título: Photometric Determination of Ammonium and Phosphate in Seawater Medium Using a Microplate Reader. [So] Source: J Mol Microbiol Biotechnol;27(2):73-80, 2017. [Is] ISSN: 1660-2412 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: To more efficiently process the large sample numbers for quantitative determination of ammonium (NH4+) and phosphate (orthophosphate, PO43-) generated during comprehensive growth experiments with the marine Roseobacter group member Phaeobacter inhibens DSM 17395, specific colorimetric assays employing a microplate reader (MPR) were established. The NH4+ assay is based on the reaction of NH4+ with hypochlorite and salicylate, yielding a limit of detection of 14 µM, a limit of quantitation of 36 µM, and a linear range for quantitative determination up to 200 µM. The PO43-assay is based on the complex formation of PO43- with ammonium molybdate in the presence of ascorbate and zinc acetate, yielding a limit of detection of 13 µM, a limit of quantitation of 50 µM, and a linear range for quantitative determination up to 1 mM. Both MPR-based assays allowed for fast (significantly lower than 1 h) analysis of 21 samples plus standards for calibration (all measured in triplicates) and showed only low variation across a large collection of biological samples. [Mh] Termos MeSH primário: Compostos de Amônio/análise Meios de Cultura/química Fosfatos/análise Fotometria/métodos Água do Mar/química [Mh] Termos MeSH secundário: Compostos de Amônio/química Ácido Ascórbico/química Ácido Hipocloroso/química Molibdênio/química Fosfatos/química Fotometria/instrumentação Roseobacter/crescimento & desenvolvimento Roseobacter/metabolismo Salicilatos/química Sensibilidade e Especificidade Estatística como Assunto Acetato de Zinco/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Ammonium Compounds); 0 (Culture Media); 0 (Phosphates); 0 (Salicylates); 712K4CDC10 (Hypochlorous Acid); 81AH48963U (Molybdenum); FM5526K07A (Zinc Acetate); OGI154X474 (ammonium molybdate); PQ6CK8PD0R (Ascorbic Acid) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170208 [St] Status: MEDLINE [do] DOI: 10.1159/000454814

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[PMID]: 28091924 [Au] Autor: Yakimoskii AF; Shantyr II; Vlasenko MA; Yakovleva MV [Ad] Endereço: Laboratory of Physiology and Pathology of Motor Behavior, I. P. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia. jakin2010@gmail.com. [Ti] Título: Effects of Acyzol on Zinc Content in Rat Brain and Blood Plasma. [So] Source: Bull Exp Biol Med;162(3):293-294, 2017 Jan. [Is] ISSN: 1573-8221 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Zinc level in the blood plasma and brain of rats was studied by inductively coupled plasma mass spectrometry. Maximum amount of zinc was observed in the cerebellum (15.0±5.5 µg/mg wet tissue). Single intraperitoneal administration of a zinc donor acyzol (24 mg/kg) did not change the content of this element in the tissues. Repeated injections of acyzol (7 injections over 14 days) significantly increased zinc level in rat plasma and brain. This elevation was most pronounced in the forebrain (cortex and subcortical structures). The rise in zinc concentration in blood plasma correlated with its level in the brain. [Mh] Termos MeSH primário: Cerebelo/metabolismo Prosencéfalo/metabolismo Acetato de Zinco/administração & dosagem Zinco/administração & dosagem [Mh] Termos MeSH secundário: Animais Cerebelo/química Complexos de Coordenação/administração & dosagem Complexos de Coordenação/química Complexos de Coordenação/metabolismo Esquema de Medicação Imidazóis/química Injeções Intraperitoneais Masculino Prosencéfalo/química Ratos Ratos Wistar Zinco/metabolismo Acetato de Zinco/química Acetato de Zinco/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Coordination Complexes); 0 (Imidazoles); FM5526K07A (Zinc Acetate); J41CSQ7QDS (Zinc); ODY9ION63A (N-vinylimidazole) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170117 [St] Status: MEDLINE [do] DOI: 10.1007/s10517-017-3597-1

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[PMID]: 27475433 [Au] Autor: Luévano-Hipólito E; Martínez-de la Cruz A; López Cuéllar E [Ad] Endereço: CIIDIT, Facultad de Ingeniería Mecánica y Eléctrica, Universidad Autónoma de Nuevo León, Ciudad Universitaria, C.P. 66451, San Nicolás de los Garza, N.L, Mexico. [Ti] Título: Performance of ZnO synthesized by sol-gel as photocatalyst in the photooxidation reaction of NO. [So] Source: Environ Sci Pollut Res Int;24(7):6361-6371, 2017 Mar. [Is] ISSN: 1614-7499 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: ZnO samples were prepared by sol-gel method applying a factorial design in order to improve the photocatalytic properties of the semiconductor oxide in the NO photooxidation reaction. The concentrations of zinc acetate and ammonium hydroxide were selected as critical variables in the synthesis of ZnO. Nine samples of ZnO were obtained as product of the factorial design and were characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, diffuse reflectance spectroscopy, and N adsorption-desorption isotherms. The photocatalytic activity of ZnO samples was associated with the physical properties developed by each sample according to its respective conditions of synthesis. Some photocatalytic reaction parameters, such as mass of photocatalyst, irradiance, and relative humidity, were modified in order to evaluate its effect in the photocatalytic conversion of NO. As a relevant point, the relative humidity played an important role in the increase of the selectivity of the NO photooxidation reaction to innocuous nitrate ions when ZnO was used as photocatalyst. [Mh] Termos MeSH primário: Poluentes Ambientais/química Óxido Nítrico/química Processos Fotoquímicos Óxido de Zinco/química Óxido de Zinco/síntese química [Mh] Termos MeSH secundário: Adsorção Hidróxido de Amônia/química Catálise Poluentes Ambientais/isolamento & purificação Óxido Nítrico/isolamento & purificação Oxirredução Acetato de Zinco/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Environmental Pollutants); 31C4KY9ESH (Nitric Oxide); 5138Q19F1X (Ammonium Hydroxide); FM5526K07A (Zinc Acetate); SOI2LOH54Z (Zinc Oxide) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171104 [Lr] Data última revisão: 171104 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160801 [St] Status: MEDLINE [do] DOI: 10.1007/s11356-016-7310-0

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[PMID]: 28661325 [Au] Autor: Soboh YM; Sorensen DL; Sims RC [Ad] Endereço: Department of Biological Engineering, Utah State University, Logan, Utah 84322, USA. [Ti] Título: Upflow Anaerobic Sludge Blanket Reactor Codigestion of Algae and Acetate to Produce Methane. [So] Source: Water Environ Res;88(11):2094-2103, 2016 Nov 01. [Is] ISSN: 1061-4303 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Algae grown in wastewater treatment lagoons are a potentially important substrate for biofuel production. The feasibility of using upflow anaerobic sludge blanket (UASB) reactors in anaerobic digestion of algae to produce methane was investigated. A favorable carbon to nitrogen (C/N) weight ratio of 21/1 was determined in batch reactor experiments in which the ratio was adjusted by blending algal biomass with sodium acetate as a carbon source. This blend of algae and acetate was used in the feedstock applied to the UASB reactors. Duplicate, 34-L, UASB reactors initially received an organic loading rate (OLR) of 0.9 g chemical oxygen demand (COD)/L.d at a 7.2-day hydraulic retention time (HRT). The OLR was gradually increased to 5.4 g/L.d and the HRT was decreased to 5.5 days resulting in a methane production increase from 247 to 298 mL/g COD biodegraded. The COD removal efficiency was 80% with a biogas methane composition of 90%. [Mh] Termos MeSH primário: Reatores Biológicos Cianobactérias/química Metano/química Acetato de Zinco/química [Mh] Termos MeSH secundário: Anaerobiose [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: FM5526K07A (Zinc Acetate); OP0UW79H66 (Methane) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170803 [Lr] Data última revisão: 170803 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170630 [St] Status: MEDLINE [do] DOI: 10.2175/106143016X14733681695645

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[PMID]: 27915460 [Au] Autor: Lassi ZS; Moin A; Bhutta ZA [Ad] Endereço: The Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia, 5005. [Ti] Título: Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. [So] Source: Cochrane Database Syst Rev;12:CD005978, 2016 12 04. [Is] ISSN: 1469-493X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily zinc supplements have been reported to prevent acute lower respiratory tract infection (LRTI) and reduce child mortality. This is an update of a review first published in 2010. OBJECTIVES: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months. SEARCH METHODS: We searched CENTRAL (Issue 21 October 2016), MEDLINE (1966 to October 2016), Embase (1974 to October 2016), LILACS (1982 to October 2016), CINAHL (1981 to October 2016), Web of Science (1985 to October 2016) and IMSEAR (1980 to October 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating zinc supplementation for the prevention of pneumonia in children aged from 2 months to 59 months. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants.Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932). AUTHORS' CONCLUSIONS: Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia. [Mh] Termos MeSH primário: Pneumonia/prevenção & controle Compostos de Zinco/administração & dosagem [Mh] Termos MeSH secundário: Pré-Escolar Gluconatos/administração & dosagem Seres Humanos Lactente Pneumonia/epidemiologia Ensaios Clínicos Controlados Aleatórios como Assunto Acetato de Zinco/administração & dosagem Sulfato de Zinco/administração & dosagem [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW [Nm] Nome de substância: 0 (Gluconates); 0 (Zinc Compounds); 7733-02-0 (Zinc Sulfate); FM5526K07A (Zinc Acetate) [Em] Mês de entrada: 1701 [Cu] Atualização por classe: 170131 [Lr] Data última revisão: 170131 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161205 [St] Status: MEDLINE [do] DOI: 10.1002/14651858.CD005978.pub3

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[PMID]: 27537870 [Au] Autor: Sun C; Wang H; Wang Y; Xiao S [Ad] Endereço: Institute of Special Wild Animals and Plants, Chinese Academy of Agricultural Science, Changchun 130122, China. 18611297241@126.com. [Ti] Título: Rapid Isolation and Determination of Flavones in Biological Samples Using Zinc Complexation Coupled with High-Performance Liquid Chromatography. [So] Source: Molecules;21(8), 2016 Aug 16. [Is] ISSN: 1420-3049 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: Chlorophyll-type contaminants are commonly encountered in the isolation and determination of flavones of plant aerial plant parts. Heme is also a difficult background substance in whole blood analysis. Both chlorophyll and heme are porphyrin type compounds. In this study, a rapid method for isolating flavones with 5-hydroxyl or ortho-hydroxyl groups from biological samples was developed based on the different solubilities of porphyrin-metal and flavone-metal complexes. It is important that other background substances, e.g., proteins and lipids, are also removed from flavones without an additional processing. The recoveries of scutellarin, baicalin, baicalein, wogonoside and wogonin, which are the primary constituents of Scutellaria baicalensis (skullcaps) were 99.65% ± 1.02%, 98.98% ± 0.73%, 99.65% ± 0.03%, 97.59% ± 0.09% and 95.19% ± 0.47%, respectively. As a sample pretreatment procedure, this method was coupled to high-performance liquid chromatography (HPLC) with good separation, sensitivity and linearity and was applied to determine the flavone content in different aerial parts of S. baicalensis and in dried blood spot samples. [Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos Teste em Amostras de Sangue Seco/métodos Flavonas/isolamento & purificação Scutellaria baicalensis/química Acetato de Zinco/química [Mh] Termos MeSH secundário: Apigenina/isolamento & purificação Flavanonas/isolamento & purificação Flavonas/química Flavonoides/isolamento & purificação Glucosídeos/isolamento & purificação Glucuronatos/isolamento & purificação Seres Humanos Componentes Aéreos da Planta/química Extratos Vegetais/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Flavanones); 0 (Flavones); 0 (Flavonoids); 0 (Glucosides); 0 (Glucuronates); 0 (Plant Extracts); 0 (wogonoside); 16IGP0ML9A (scutellarin); 347Q89U4M5 (baicalin); 49QAH60606 (baicalein); 7V515PI7F6 (Apigenin); FM5526K07A (Zinc Acetate); POK93PO28W (wogonin) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170417 [Lr] Data última revisão: 170417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160819 [St] Status: MEDLINE

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[PMID]: 27502587 [Au] Autor: Oe S; Miyagawa K; Honma Y; Harada M [Ad] Endereço: Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: ooes@med.uoeh-u.ac.jp. [Ti] Título: Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease. [So] Source: Exp Cell Res;347(1):192-200, 2016 Sep 10. [Is] ISSN: 1090-2422 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease. [Mh] Termos MeSH primário: Cobre/toxicidade Estresse do Retículo Endoplasmático/efeitos dos fármacos Hepatócitos/patologia Degeneração Hepatolenticular/patologia [Mh] Termos MeSH secundário: Adulto Apoptose/efeitos dos fármacos Caspase 3/metabolismo Linhagem Celular Tumoral Proliferação Celular/efeitos dos fármacos Dano ao DNA Feminino Imunofluorescência Células HEK293 Hepatócitos/efeitos dos fármacos Seres Humanos Peróxido de Hidrogênio/metabolismo Immunoblotting Antígeno Ki-67/metabolismo Masculino Meia-Idade Estresse Oxidativo/efeitos dos fármacos Inibidores de Proteassoma/farmacologia Acetato de Zinco/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Ki-67 Antigen); 0 (Proteasome Inhibitors); 789U1901C5 (Copper); BBX060AN9V (Hydrogen Peroxide); EC 3.4.22.- (Caspase 3); FM5526K07A (Zinc Acetate) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170515 [Lr] Data última revisão: 170515 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160810 [St] Status: MEDLINE

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[PMID]: 27437826 [Au] Autor: Friedland BA; Hoesley CJ; Plagianos M; Hoskin E; Zhang S; Teleshova N; Alami M; Novak L; Kleinbeck KR; Katzen LL; Zydowsky TM; Fernández-Romero JA; Creasy GW [Ad] Endereço: *The Population Council, New York, NY; and †University of Alabama at Birmingham; Birmingham, AL. [Ti] Título: First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics. [So] Source: J Acquir Immune Defic Syndr;73(5):489-496, 2016 Dec 15. [Is] ISSN: 1944-7884 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored. DESIGN: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days. METHODS: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis. RESULTS: Participants (n = 20) ranged from 19-44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti-herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity. CONCLUSIONS: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti-human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention. [Mh] Termos MeSH primário: Antivirais/administração & dosagem Carragenina/administração & dosagem Géis/administração & dosagem Profilaxia Pré-Exposição/métodos Piridinas/administração & dosagem Doenças Virais Sexualmente Transmissíveis/prevenção & controle Ureia/análogos & derivados Acetato de Zinco/administração & dosagem [Mh] Termos MeSH secundário: Administração Intravaginal Adulto Antivirais/efeitos adversos Antivirais/farmacocinética Carragenina/efeitos adversos Carragenina/farmacocinética Cromatografia Líquida Método Duplo-Cego Feminino Géis/efeitos adversos Seres Humanos Adesão à Medicação Aceitação pelo Paciente de Cuidados de Saúde Placebos/administração & dosagem Piridinas/efeitos adversos Piridinas/farmacocinética Espectrometria de Massas em Tandem Ureia/administração & dosagem Ureia/efeitos adversos Ureia/farmacocinética Adulto Jovem Acetato de Zinco/efeitos adversos Acetato de Zinco/farmacocinética [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Antiviral Agents); 0 (Gels); 0 (MIV 150); 0 (Placebos); 0 (Pyridines); 8W8T17847W (Urea); 9000-07-1 (Carrageenan); FM5526K07A (Zinc Acetate) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170606 [Lr] Data última revisão: 170606 [Sb] Subgrupo de revista: IM; X [Da] Data de entrada para processamento: 160721 [St] Status: MEDLINE

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[PMID]: 27428377 [Au] Autor: Villegas G; Calenda G; Ugaonkar S; Zhang S; Kizima L; Mizenina O; Gettie A; Blanchard J; Cooney ML; Robbiani M; Fernández-Romero JA; Zydowsky TM; Teleshova N [Ad] Endereço: Population Council, New York, New York, United States of America. [Ti] Título: A Novel Microbicide/Contraceptive Intravaginal Ring Protects Macaque Genital Mucosa against SHIV-RT Infection Ex Vivo. [So] Source: PLoS One;11(7):e0159332, 2016. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Women need multipurpose prevention products (MPTs) that protect against sexually transmitted infections (STIs) and provide contraception. The Population Council has developed a prototype intravaginal ring (IVR) releasing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (M), zinc acetate (ZA), carrageenan (CG) and levonorgestrel (LNG) (MZCL IVR) to protect against HIV, HSV-2, HPV and unintended pregnancy. Our objective was to evaluate the anti-SHIV-RT activity of MZCL IVR in genital mucosa. First, macaque vaginal tissues were challenged with SHIV-RT in the presence of (i) MIV-150 ± LNG or (ii) vaginal fluids (VF); available from studies completed earlier) collected at various time points post insertion of MZCL and MZC IVRs. Then, (iii) MZCL IVRs (vs. LNG IVRs) were inserted in non-Depo Provera-treated macaques for 24h and VF, genital biopsies, and blood were collected and tissues were challenged with SHIV-RT. Infection was monitored with one step SIV gag qRT-PCR or p27 ELISA. MIV-150 (LCMS/MS, RIA), LNG (RIA) and CG (ELISA) were measured in different compartments. Log-normal generalized mixed linear models were used for analysis. LNG did not affect the anti-SHIV-RT activity of MIV-150 in vitro. MIV-150 in VF from MZC/MZCL IVR-treated macaques inhibited SHIV-RT in vaginal mucosa in a dose-dependent manner (p<0.05). MIV-150 in vaginal tissue from MZCL IVR-treated animals inhibited ex vivo infection relative to baseline (96%; p<0.0001) and post LNG IVR group (90%, p<0.001). No MIV-150 dose-dependent protection was observed, likely because of high MIV-150 concentrations in all vaginal tissue samples. In cervical tissue, MIV-150 inhibited infection vs. baseline (99%; p<0.05). No cervical tissue was available for MIV-150 measurement. Exposure to LNG IVR did not change tissue infection level. These observations support further development of MZCL IVR as a multipurpose prevention technology to improve women's sexual and reproductive health. [Mh] Termos MeSH primário: Anti-Infecciosos/farmacologia Anticoncepcionais Femininos/farmacologia Levanogestrel/farmacologia Piridinas/farmacologia Vírus Reordenados/efeitos dos fármacos Inibidores da Transcriptase Reversa/farmacologia Ureia/análogos & derivados Vagina/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Carragenina/farmacologia Dispositivos Anticoncepcionais Femininos Combinação de Medicamentos Feminino HIV/efeitos dos fármacos HIV/genética HIV/crescimento & desenvolvimento Macaca mulatta Membrana Mucosa/efeitos dos fármacos Membrana Mucosa/virologia Vírus Reordenados/genética Vírus Reordenados/crescimento & desenvolvimento Vírus da Imunodeficiência Símia/efeitos dos fármacos Vírus da Imunodeficiência Símia/genética Vírus da Imunodeficiência Símia/crescimento & desenvolvimento Resultado do Tratamento Ureia/farmacologia Vagina/virologia Acetato de Zinco/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Infective Agents); 0 (Contraceptive Agents, Female); 0 (Drug Combinations); 0 (MIV 150); 0 (Pyridines); 0 (Reverse Transcriptase Inhibitors); 5W7SIA7YZW (Levonorgestrel); 8W8T17847W (Urea); 9000-07-1 (Carrageenan); FM5526K07A (Zinc Acetate) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170719 [Lr] Data última revisão: 170719 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160719 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0159332

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