A new methodology for polyvalent intravenous immunoglobulin solution production with a two-stage process of viral inactivation

Highly purified intravenous immunoglobulin G concentrate (IV IgG) was produced with the use of polyethylene glycol associated to a single-stage precipitation by ethanol, instead of the classic Cohn-Oncley process, which employs cold alcohol as the precipitating agent, in a three-stage process. Precipitation of crude fraction containing more than 95% of immunoglobulin G was performed by liquid chromatography with a cation exchanger, CM-Sepharose, as a stationary phase. During the process, the product was subjected to two-stage viral inactivation. The first stage was performed by the action of sodium caprylate, 30 mM at pH 5.1+/- 0.1, and the second stage was performed by the action of a solvent-detergent mixture. The finished product was formulated at 5% with 10% sucralose as the stabilizing agent. The process yields 3.3g of IgG/liter of plasma. The finished product analysis showed an anti-complementary activity lower than 1CH50. Polymer and aggregate percent levels were lower than 3% in the five batches studied. The analysis of neutralizing capacity showed the presence of antibacterial and antiviral antibodies in at least three times higher concentrations than the levels found in source plasma. The finished product fulfilled all purity requirements stated in the 4th edition of the European pharmacopeia.Obteve-se concentrado de imunoglobulina G intravenosa IgGIV, altamente purificado, utilizando-se polietilenoglicol associado a uma única etapa de precipitação por etanol, em substituição ao tradicional método descrito por Cohn-Oncley, que emprega, em três etapas, o mesmo álcool resfriado, como agente precipitante. A purificação da fração bruta contendo mais de 95% de imunoglobulina G foi realizada utilizando-se cromatografia líquida com um trocador de cátion, a CM-Sepharose, como fase estacionária. Durante o processamento o produto foi submetido a dupla inativação viral sendo a primeira pela ação do caprilato de sódio, 30 mM a pH 5,1+/- 0,1 e a segunda por ação de mistura de solvente/detergente. O produto acabado foi formulado a 5% utilizando-se sucralose 10% como estabilizante. O rendimento da metodologia foi de 3,3g de IgG/litro de plasma. A análise do produto acabado demonstrou atividade anti-complementar inferior a 1CH50. O valor percentual de polímeros e agregados em cinco lotes realizados foi inferior a 3%. O estudo da capacidade de neutralização demonstrou a presença de anticorpos anti-bacterianos e anti-virais em concentração pelo menos três vezes maior que o plasma de origem. O produto acabado apresentou conformidade com todos os requisitos de pureza dispostos na farmacopéia européia IV edição

As gravuras rupestres do Alto Pantanal de Mato Grosso do Sul

Em dezembro de 2013 uma equipe de arqueólogos ligados à Universidade Federal da Grande Dourados empreendeu uma expedição científica com o objetivo de inventariar a arte rupestre das áreas mais remotas em torno do Rio Paraguai. Foram três os sítios registrados: um em Baía Vermelha e dois em Lagoa Gaíva, todos em território do município de Corumbá. Esta expedição integra um projeto maior de inventário de toda a arte rupestre do estado de Mato Grosso do Sul, que conta com o desembolso financeiro da Eletrosul Centrais Elétricas e com o apoio do Instituto do Patrimônio Histórico e Artístico Nacional (IPHAN). Os dados coletados pela expedição ao Alto Pantanal de Mato Grosso do Sul estão expostos neste artigo

Subversion of early innate antiviral responses during antibody-dependent enhancement of Dengue virus infection induces severe disease in immunocompetent mice

Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1–4). Epidemiologic and observational studies demonstrate that the majority of severe dengue cases, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), occurs predominantly in either individuals with cross-reactive immunity following a secondary heterologous infection or in infants with primary DENV infections born from dengue-immune mothers, suggesting that B-cell-mediated and antibody responses impact on disease evolution. We demonstrate here that B cells play a pivotal role in host responses against primary DENV infection in mice. After infection, μMT[superscript −/−] mice showed increased viral loads followed by severe disease manifestation characterized by intense thrombocytopenia, hemoconcentration, cytokine production and massive liver damage that culminated in death. In addition, we show that poly and monoclonal anti-DENV-specific antibodies can sufficiently increase viral replication through a suppression of early innate antiviral responses and enhance disease manifestation, so that a mostly non-lethal illness becomes a fatal disease resembling human DHF/DSS. Finally, treatment with intravenous immunoglobulin containing anti-DENV antibodies confirmed the potential enhancing capacity of subneutralizing antibodies to mediate virus infection and replication and induce severe disease manifestation of DENV-infected mice. Thus, our results show that humoral responses unleashed during DENV infections can exert protective or pathological outcomes and provide insight into the pathogenesis of this important human pathogen

Vasovagal reactions in whole blood donors at three REDS-II blood centers in Brazil

BACKGROUND: In Brazil little is known about adverse reactions during donation and the donor characteristics that may be associated with such events. Donors are offered snacks and fluids before donating and are required to consume a light meal after donation. For these reasons the frequency of reactions may be different than those observed in other countries. STUDY DESIGN AND METHODS: A cross-sectional study was conducted of eligible whole blood donors at three large blood centers located in Brazil between July 2007 and December 2009. Vasovagal reactions (VVRs) along with donor demographic and biometric data were collected. Reactions were defined as any presyncopal or syncopal event during the donation process. Multivariable logistic regression was performed to identify predictors of VVRs. RESULTS: Of 724,861 donor presentations, 16,129 (2.2%) VVRs were recorded. Rates varied substantially between the three centers: 53, 290, and 381 per 10,000 donations in Recife, Sao Paulo, and Belo Horizonte, respectively. Although the reaction rates varied, the donor characteristics associated with VVRs were similar (younger age [18-29 years], replacement donors, first-time donors, low estimated blood volume [EBV]). In multivariable analysis controlling for differences between the donor populations in each city younger age, first-time donor status, and lower EBV were the factors most associated with reactions. CONCLUSION: Factors associated with VVRs in other locations are also evident in Brazil. The difference in VVR rates between the three centers might be due to different procedures for identifying and reporting the reactions. Potential interventions to reduce the risk of reactions in Brazil should be considered

Custo médio do Módulo de Coleta de sangue total pelo método ABC

Os procedimentos em hemoterapia são complexos e caros. Exigem processos controlados e validados, equipamentos calibrados e monitorados e insumos qualificados, validados e inspecionados antes e durante o uso. Isto acarreta, além dos gastos diretos, gastos indiretos especificamente relacionados à garantia da qualidade e da segurança transfusionais, além dos gastos indiretos usuais de qualquer produto ou serviço. Procurando avaliar com maior aproximação estes custos e buscando evitar as distorções das apropriações de custos por rateios, o presente estudo utilizou o sistema de Custeio Baseado em Atividades - ABC, para apurar o custo médio do Módulo de Coleta de sangue total no Hemocentro de Ribeirão Preto - SP, unidade sede, no primeiro semestre de 2006. O maior impacto no custo médio apurado se deveu aos custos monetários diretos, entretanto os custos indiretos não foram desprezíveis. O custo médio obtido para desempenho das atividades que compõem o Módulo de Coleta foi de R$35,20, que é 68,75$ 35.20, which is 68.75% higher than the value paid by the Brazilian government for this unit. The developed methodology can be applied to other procedures of services in hemotherapy allowing the evaluation of process costs, avoiding waste, improving performance and generating objective evidence to demonstrate the real cost of quality hemotherapy activities for public and private fund source

Logistic model for determining factors associated with HIV infection among blood donor candidates at the Fundação HEMOPE

OBJECTIVE: To determine factors associated with HIV infection in blood donor candidates in Recife, Brazil. METHODS:A transversal study was performed of 106,203 blood donor candidates found eligible by the routine clinical screening process in the blood bank in Recife of the Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE) in the period from January 1998 to November 2003. Additional indirect immune and western blot confirmation tests for HIV infection were performed and the candidates were classified as HIV positive or negative. The Chi-squared test and stepwise multiple logistic regression were conducted to examine any association between HIV infection and age, gender, place of residence, schooling, number of donations and serological tests for core hepatitis B antigen virus (anti-HBc), the hepatitis C antivirus (anti-HCV), human T-type antivirus lymph cells (anti-HTLV 1 and 2), serological tests for syphilis (VDRL) and the hepatitis B virus surface antigen (HBsAg). RESULTS: In the observed sample, 0.204% of blood donor candidates were found to be HIV positive. Among the studied variables, the age, education level, residency, donation type, and serologic status for anti-HBc and VDRL tests were found to be associated with HIV infection. CONCLUSION: The younger, spontaneous donor candidates living in the Recife metropolitan area with a low level of education and positive for anti-HBc and VDRL have an higher risk of HIV infection than the other candidates. Data such as these are useful to understand the dynamics of infection and to guide healthcare policies.OBJETIVO: Determinar fatores associados à infecção por HIV em doadores de sangue no Recife, Brasil. MÉTODOS: Desenvolveu-se um estudo transversal com 106.203 doadores de sangue de 1ª doação, aptos na Triagem Clínica (TC) no Hemocentro Recife da Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE), considerando-se os critérios rotineiros empregados pelo Hemocentro para seleção de candidatos no período de janeiro de 1998 a novembro de 2003. Os testes Imunofluorescência Indireta e Western Blot foram utilizados para confirmação da infecção HIV, e doadores foram classificados como HIV positivo ou negativo. O teste do qui-quadrado e método stepwise de regressão logística múltipla foram realizados para examinar associação entre a infecção pelo HIV e as variáveis: idade, sexo, área de residência, escolaridade, tipo de doação e testes sorológicos de triagem para Anti-HBc, HBsAg, Anti-HCV, Anti-HTLV 1/2 e VDRL. RESULTADOS: Na amostra observada, foram encontrados 0,204% doadores de sangue HIV positivo. Entre as variáveis estudadas, idade, escolaridade, residência, tipo de doação e status sorológico para Anti-HBc e VDRL foram associados com a infecção pelo HIV. CONCLUSÃO: Doadores com doação espontânea, da área metropolitana de Recife, de menor idade e nível de ensino, positivo para o Anti-HBc e VDRL, apresentam risco aumentado de infecção pelo HIV. Tais dados são necessários para compreender a dinâmica da infecção e para guiar políticas sanitárias