Characterization of Viral Entry Inhibitors

Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) are pathogenic viruses known to cause liver disorder, acquired immunodeficiency and skin lesions, respectively. Although current therapies have played substantial roles in the fight against these pathogens, their use is limited and for the most part does not result in viral eradication. Moreover, most antivirals target viral encoded structures which overtime foster the development of resistant strains. Hence, antivirals aimed at preventing initial infection represent a promising strategy for viral combat. This dissertation focuses on the characterization of viral entry inhibitors and their potential use. The first compounds evaluated come from the phenothiazines family, widely used as antipsychotic drugs. Phenothiazines were shown to suppress HCV entry by intercalating into cholesterol-rich membrane domains of target cells thus reducing viral-host fusion. The second candidates studied are two members of the H1-anthistamines currently used for allergy treatment. Both compounds strongly reduce HCV entry, likely at the fusion step, and its inhibition was associated with cholesterol content in the virion and host cells, pointing to the use of an NPC1L1-receptor dependent mechanism. Lastly, we evaluated the antiviral activity of PD 404,182 (PD) as an alternate treatment for HCV-HIV coinfected patients as well as its potential use as an anti-HIV microbicide. PD is able to reduce viral entry of the three pathogens through physical disruption of virions releasing the nucleic acids into the surrounding medium. Moreover, PD possesses several qualities pointing to its use as a potential microbicide

Value Chain Analysis of Bamboo Production: The Case of Bule Woreda, Gedeo Zone, Snnprs

Bamboo plays very important role socially, economically and ecologically. Despite the fact that bamboo play important role in improving the livelihood of the local community it has an insignificant contribution due to the products are at a very rudimentary level and inexistence of well established bamboo industry. These situations hampered the opportunity of the potential of bamboo that will improve the poor living standards and hence sustainable utilization of the resources. This study was initiated to analyze the existing bamboo market chain in Bule Woreda Gedeo Zone, Southern Nations Nationalities and Regional State. The focus of the study was to  analyze the determinants of marketable supply of Bamboo, identify actors involved in the processes and what do they actually do, investigate the costs incurred by each participants and the benefits driven by each. The data were collected by using a semi-structured questionnaires together with secondary data gathered from agricultural bureau offices and other unpublished sources. Robust Ordinary least square regression econometric model was used to analyze the determinants of market supply of bamboo. The results from this analysis indicates that price of bamboo culm, educational level of producers, distance to the nearest market, and access to market information were found to be  significant variables influencing bamboo supply to the market. A significant amount (70.16%) of bamboo produced is channeled through producers- traders- processors- consumers chain. The concentration ratio of two firms measures of market structure indicated there exist  super tight oligopolistic nature of bamboo market. Moreover, marketing margins also indicate that the producers get much lower benefit than any other market chain actors. The major problems of the production identified by bamboo producers in the study area arised from road infrastructure and market information. Therefore improving road infrastructure, provision of formal education and market information,  and improving the existing chain through creating appropriate market linkage are recommended. Keywords: Value chain, value chain analysis, structure- conduct- performance, concentration ratio, marketing channel and marketing margin

Composição proximal em filés, rendimento de carcaça e de cortes de jundiá (rhamdia quelen) alimentados com rações contendo diferentes óleos vegetais.

Este trabalho teve por objetivos avaliar a influência de óleos vegetais no desenvolvimento corporal de jundiá (Rhamdia quelen, Heptapteridae) e sua relação com o rendimento de carcaça, partes comestíveis e composição química do filé. Testaram-se seis rações com 32% de proteína bruta, sendo avaliados óleos de arroz, canola ou soja com 5 e 10% de inclusão durante 90 dias. Foram utilizados 180 peixes (peso inicial=71±0,81g) distribuídos ao acaso em 18 caixas de 280L (10 peixes/caixa) em um sistema de recirculação de água, com temperatura controlada (25,9±0,9ºC). Não houve diferenças para os parâmetros produtivos entre os tratamentos testados ao final do experimento (P<0,05). Os peixes alimentados com maiores níveis de óleo nas dietas depositaram maior porcentagem de gordura no filé. Conclui-se que os óleos de canola, arroz e soja utilizados como alternativas em dietas na recria de jundiá proporcionam bom rendimento de carcaça e de partes comestíveis. E, as rações contendo óleo de canola possibilitam menor deposição de gordura no filé de juvenis de jundiá em nível de 5%

The antitumor drug, 1,3-bis(2-chloroethyl)-1-nitroso-urea, inactivates human nicotinamide mononucleotide adenylyltransferase.

Nicotinamide mononucleotide (NMN) adenylyltransferase (EC 2.7.7.1) from human placenta is rapidly inactivated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A similar inactivation is observed with other C- and N-nitroso compounds. The inactivation by BCNU is dependent on incubation time, temperature and BCNU concentration. Protective reagents for -SH groups, dithiothreitol and beta-mercaptoethanol, and the substrate NMN are very effective in protecting NMN adenylyltransferase from BCNU inactivation and in preserving its catalytic properties, while ATP is less efficient. Incubation of BCNU-inactivated and dialysed NMN adenylyltransferase with dithiothreitol results in a partial recovery of the enzymatic activity

Physicochemical Characterization And Antioxidant Capacity Of Pitanga Fruits (eugenia Uniflora L.) [caracterização Fisico-química E Capacidade Antioxidante De Pitangas (eugenia Uniflora L.)]

This study was carried out to obtain more information about the physicochemical properties, composition, and antioxidant activity of pitanga fruits (Eugenia uniflora L.), particularly fruits from the State of Rio Grande do Sul, Brazil. Pitanga with different flesh colors (purple, red, and orange) from tree selections cultivated at Embrapa Clima Temperado (RS-Brazil) were analyzed. Only slight differences were observed in the quality parameters and in the proximate and fatty acid compositions among the fruits studied. The extracts from purple-fleshed pitanga had the highest total phenolic and anthocyanin contents along with the highest antioxidant capacity. The antioxidant capacity (DPPH and FRAP assays) of methanolic pitanga extracts was highly correlated with the total phenolic content, but in ethanolic extracts, the anthocyanin content was correlated only with the FRAP antioxidant capacity. Orange fleshed pitanga had higher β-cryptoxanthin and β-carotene levels than those of the red fruit, which had higher lycopene content. The results indicate that the purple-fleshed pitanga, cultivated in Rio Grande do Sul, is a rich source of phenolic compounds and has high antioxidant capacity. The red and orange-fleshed pitanga, on the other hand, are rich sources of carotenoids.311147154Abidille, M.D.H., Antioxidant activity of the extracts from Dillenia indica fruits (2005) Food Chemistry, 90 (4), pp. 891-896Adebajo, A.C., Oloki, K.J., Aladesanmi, A., Antimicrobial activity of the leaf extract of Eugenia uniflora (1989) Journal of Phytotherapy Resource, 3 (6), pp. 258-259Aherne, S.A., O'Brien, N.M., Dietary flavonols: Chemistry, food content, and metabolism (2002) Nutrition, 18 (1), pp. 75-81(1995) Official methods of analysis of the Association of the Official Analytical Chemists, , ASSOCIATION OF OFFICIAL ANALYTICAL CHEMISTS-AOAC, 16th ed. Arlington, Virginia: AOACAzevedo-Meleiro, C.H., Rodriguez-Amaya, D.B., Confirmation of the identity of the carotenoids of tropical fruits by HPLC-DAD and HPLC-MS (2004) Journal of Food Composition and Analysis, 17 (3-4), pp. 385-396Bagetti, M., Antioxidant capacity and composition of pitanga seeds (2009) Ciência Rural, 39 (8), pp. 204-2510Beekwilder, J., Antioxidant in raspberry: On-line analysis links antioxidant activity to a diversity of individual metabolites (2005) Journal of Agricultural and Food Chemistry, 53 (9), pp. 3313-3320Benzie, F.F.I., Strain, J.J., The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": The FRAP assay (1996) Analytical Biochemistry, 239 (1), pp. 70-76Bligh, E.G., Dyer, W.J., A rapid method of total lipid extraction and purification (1959) Journal of Biochemistry and Physiology, 37 (8), pp. 911-917Block, G., Patterson, B., Subar, A., Fruits, vegetables and cancer prevention: A review of the epidemiological evidence (1992) Nutrition and Cancer, 18 (1), pp. 1-29Bors, W., Flavonoids as antioxidants: Determination of radical scavenging efficiencies (1990) Methods in Enzymology, 186, pp. 343-355Brand-Williams, W., Cuvelier, M.E., Berset, C., Use of a free radical method to evaluated antioxidant activity (1995) Lebensmittel-Wissenschaft und-Technologie, 28 (1), pp. 25-30Regulamento técnico geral para fixação dos padrões de identidade e qualidade para polpa de fruta (2000) Diário Oficial da República Federativa do Brasil, p. 54. , http://extranet.agricultura.gov.br/sislegisconsulta/consultarLegislacao. do?operacao=visualizar&id=7777, BRASIL. Instrução Normativa, no 1, de 7 de janeiro de 2000, Brasília, DF, 10 jan, Seção 1, Disponível em:, Acesso em: 18 dez. 2008Cavalcante, M.L., Rodriguez-Amaya, D.B., Carotenoid composition of the tropical fruits Eugenia uniflora and Malpighia glabra (1992) Food Science and Human Nutrition, pp. 643-650. , In: CHARALAMBOUS, G. (Ed.), Amsterdam: Elsevier Science PublishersClinton, S.K., Lycopene: Chemistry, biology, and implications for human health and disease (1998) Nutrition Reviews, 56 (2), pp. 35-51Consolini, A.E., Sarubbio, M., Pharmacological effects of Eugenia uniflora L. (Myrtaceae) aqueous extract on rat's heart (2002) Journal of Ethnopharmacology, 81 (1), pp. 57-63di Mascio, P., Kaiser, S., Sies, H., Lycopene as the most efficient biological carotenoid singlet oxygen quencher (1989) Archives of Biochemistry and Biophysics, 274 (2), pp. 532-538Dillard, C.J., German, J.B., Phytochemicals: Neutraceuticals and human health (2000) Journal of the Science of Food and Agriculture, 80 (12), pp. 1744-1756Diplock, A.T., Functional food sciences and defense against reactive oxidative species (1998) British Journal of Nutrition, 80 (1), pp. 77-112Escarpa, A., Gonzalez, M.C., Approach to the content of total extractable phenolic compounds from different food samples by comparison of chromatographic and spectrophotometric methods (2001) Analytica Chimica Acta, 427 (1), pp. 119-127Gemtchüjnicov, I.D., (1976) Manual de taxonomia vegetal: Plantas de interesse econômico, agrícola, ornamentais e medicinais, p. 368. , São Paulo: CeresGenovese, M.I., Bioactive compounds and antioxidant capacity of exotic fruits commercial frozen pulps from Brazil (2008) Food Science and Technology International, 4 (3), pp. 207-214Hartman, L., Lago, B.C., A rapid preparation of fatty methyl esters from lipids (1973) Laboratory Practice, 22 (6), pp. 475-477Hassimotto, N.M.A., Genovese, M.I., Lajolo, F.M., Antioxidant activity of dietary fruits, vegetables, and commercial frozen fruit pulps (2005) Journal of Agricultural and Food Chemistry, 53 (8), pp. 2928-2935Kaur, C., Kapoor, H., Antioxidants in fruits and vegetables-the millennium's health (2001) International Journal of Food Science and Technology, 36 (7), pp. 703-725Kimura, M., Rodriguez-Amaya, D.B., Yokoyama, S.M., Cultivar differences and geographic effects on the carotenoid composition and vitamin A value of papaya (1991) Lebensmittel-Wissenschaft und-Technologie, 24 (5), pp. 415-418Krinsky, N.I., Johnson, E.J., Carotenoid actions and their relation to health and disease (2005) Molecular Aspects of Medicine, 26 (6), pp. 459-516Kris-Etherton, P.M., Bioactive compounds in foods: Their role in the prevention of cardiovascular disease and cancer (2002) American Journal of Medicine, 113 (9), pp. 71-88Kuskoski, M.E., Frutas tropicais silvestres e polpas de frutas congeladas: Atividade antioxidante, polifenóis e antocianinas (2006) Ciência Rural, 36 (4), pp. 1283-1287Lees, D.H., Francis, F.J., Standardization of pigment analyses in cranberries (1972) Hortscience, 7 (1), pp. 83-84Lima, V.L.A.G., Mélo, E.A., Lima, D.E.S., Fenólicos e carotenóides totais em pitanga (2002) Scientia Agricola, 59 (3), pp. 447-450Niizu, P.Y., Rodriguez-Amaya, D.B., A melancia como fonte de licopeno (2003) Revista do Instituto Adolfo Lutz, 62 (3), pp. 195-199Oliveira, A.L., Volatile compounds from pitanga fruit (Eugenia uniflora L.) (2006) Food Chemistry, 99 (1), pp. 1-5Padula, M., Rodriguez-Amaya, D.B., Characterization of the carotenoids and assessment of the vitamin A value of Brazilian guavas (Psidium guajava L.) (1986) Food Chemistry, 20 (1), pp. 11-19Pellegrini, N., Evaluation of antioxidant capacity of some fruit and vegetable foods: Efficiency of extraction of a sequence of solvents (2007) Journal of the Science of Food and Agriculture, 87 (1), pp. 103-111Pietta, P.G., Flavonoids as antioxidants (2000) Journal of Natural Products, 63 (7), pp. 1035-1042Pinto, M.S., Lajolo, F.M., Genovese, M.I., Bioactive compounds and quantification of total ellagic acid in strawberries (Fragaria × ananassa Duch.) (2007) Food Chemistry, 107 (4), pp. 1629-1635Porcu, O.M., Rodriguez-Amaya, D.B., Variation in the carotenoid composition of the lycopene-rich Brazilian fruit Eugenia uniflora L (2008) Plant Foods for Human Nutrition, 63 (4), pp. 195-199Prior, R.L., Cao, G., Antioxidant phytochemicals in fruits and vegetables: Diet and health implications (2000) Horticulture Science, 35 (4), pp. 588-592Rahman, I., Adcock, I.M., Oxidative stress and redox regulation of lung inflammation in COPD (2006) European Respiratory Journal, 28 (1), pp. 219-242Reynerston, K.A., Quantitative analysis of antiradical phenolic constituents from fourteen edible Myrtaceae fruits (2008) Food Chemistry, 109 (4), pp. 883-890Robards, K., Antolovich, M., Analytical chemistry of fruit bioflavonoids (1997) Analyst, 122, pp. 11R-34RRodriguez-Amaya, D.B., (1999) A guide to carotenoid analysis in foods, , Washington, D.C.: ILSI PressSalgado, S.M., Guerra, N.B., Melo Filho, A.B., Frozen fruit pulps: Effects of the processing on dietary fiber contents (1999) Brazilian Journal of Nutrition, 12 (3), pp. 303-308Scalzo, J., Plant genotype affects total antioxidant capacity and phenolic contents in fruit (2005) Nutrition, 21 (2), pp. 207-213Singleton, V.L., Rossi Jr., J.A., Colorimetry of total phenolic with phosphomolybdic-phosphotungstic acid reagents (1965) American Journal of Enology and Viticulture, 16 (3), pp. 144-158Stahl, W., Sies, H., Bioactivity and protective effects of natural carotenoids (2005) Biochimica et Biophysica Acta, 1740 (2), pp. 101-107Tapiero, H., Townsend, D.M., Tew, K.D., The role of carotenoids in the prevention of human pathologies (2004) Biomedicine and Pharmacotherapy, 58 (2), pp. 100-110(2006) Tabela brasileira de composição de alimentos-TACO, p. 113. , UNIVERSIDADE DE CAMPINAS-UNICAMP, 2. ed. Version II. Campinas: NEPA/UNICAMPVison, J.A., Phenol antioxidant quantity and quality in foods: Vegetables (1998) Journal of Agricultural and Food Chemistry, 46 (9), pp. 4113-4117Weyerstahl, P., Volatile constituents of Eugenia uniflora leaf oil (1988) Planta Médica, 54 (6), pp. 546-54

Shot peening of a sintered Ni-Cu-Mo steel produced by diffusion bonded powders

The influence of the mechanical properties of a diffusion bonded Ni-Cu-Mo sintered steel on the residual stressesand the plastic deformation promoted by both steel and ceramic shot peening was investigated. While steel shotsdeform the surface more extensively than ceramic ones, leading to a thicker surface densification, ceramic shotsare more effective in terms of maximum compressive residual stresses. The increase in the yield strength of thebase material enhances residual stresses and reduces plastic deformation. The strain induced transformation ofNi-rich austenite in martensite causes a slight decrease of tensile elongation and of impact energy in specimenssintered at low temperature

Dietary Leucine - An Environmental Modifier of Insulin Resistance Acting on Multiple Levels of Metabolism

Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor—leucine—can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance

The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas

Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load

The role of the osteoplastic flap in the endoscopic era : a retrospective multicentre experience on revision surgery

Objective. To retrospectively review the experience of five tertiary-care university hospitals on frontal sinus revision surgery with osteoplastic flap (OPF). Methods. Descriptive analysis of patients who underwent frontal sinus surgery with OPF after one or more endoscopic procedures for benign and inflammatory pathologies from 2000 to 2022. Clinical charts were reviewed for demographics, indications, clinical presen-tation, previous frontal procedures, OPF technique and outcomes. Results. Of the 124 patients who underwent an OPF procedure, 33 met inclusion criteria. With a mean of 2.1 previous endoscopic surgeries, Draf III was the most common former procedure. In 30 (91%) cases OPF was part of a combined procedure. The most common indications were inverted papilloma (61%), mucocele (9%) and chronic rhinosinusitis (6%). Frontal outflow stenosis (36%) and mucocele (9%) were the most frequent complications observed. Improvement of overall symptoms and patient satisfaction after the OPF procedure were recorded. Conclusions. Even in the endoscopic era, OPF still represents a paramount procedure that should be included in the rhino-surgeon’s armamentarium, in particular in patients with challenging pathologies and anatomy when previous endoscopic endonasal attempts have failed