Biopharmaceuticals from microorganisms: from production to purification

ABSTRACT The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN α, β, and γ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.

Biopharmaceuticals from microorganisms: from production to purification

ABSTRACT The use of biopharmaceuticals dates from the 19th century and within 5-10 years, up to 50% of all drugs in development will be biopharmaceuticals. In the 1980s, the biopharmaceutical industry experienced a significant growth in the production and approval of recombinant proteins such as interferons (IFN , , and ) and growth hormones. The production of biopharmaceuticals, known as bioprocess, involves a wide range of techniques. In this review, we discuss the technology involved in the bioprocess and describe the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals.

Análise contínua de medidas de cateter de artéria pulmonar volumétrico, ecotransesofágico, variações da pressão arterial sistêmica e marcadores de hipoperfusão tissular no choque hemorrágico em suínos / Continuous analyses of pulmonary, volumetric artery catheter parameters, transesophageal echocardiography, pressure pulse variation, and biomarkers of tissue hypoperfusion during hemorrhagic shock in swine: experimental study in swines

INTRODUÇÃO: Diferentes parâmetros hemodinâmicos, incluindo os indicadores estáticos de pré-carga cardíaca como o índice de volume diastólico final ventrículo direito (IVDFVD) e parâmetros dinâmicos como a variação de pressão de pulso (VPP) têm sido usados na tomada de decisão para considerar o processo da expansão volêmica em pacientes em estado grave. O objetivo deste estudo foi comparar a reanimação por fluidos guiados tanto por VPP ou IVDFVD após choque hemorrágico induzido experimentalmente. MÉTODO: vinte e seis suínos anestesiados e ventilados mecanicamente foram alocados em três grupos: controle (Grupo I), VPP (Grupo II) e IVDFVD (Grupo III). Foi induzido choque hemorrágico por retirada de sangue até atingir a pressão arterial média de 40mmhg, que foi mantida por 60 minutos. Parâmetros foram medidos no tempo basal (B), no tempo do choque (Choque 0), sessenta minutos depois do choque (Choque 60), imediatamente depois da ressuscitação com hidroxietilamido 6% (130/0. 4) (R0), uma hora (R60) e duas horas (R120) depois ressuscitação. Os pontos de avaliação da reanimação por fluidos foram determinados pelo retorno aos valores basais iniciais de VPP e IVDFVD. A análise estatística dos dados foi baseada em ANOVA para medidas repetidas seguidos pelo teste de Bonferroni (P<0.05%). RESULTADOS: O volume e tempo para ressuscitação foram maiores no grupo III do que no grupo II (Grupo III = 1305±331ml e Grupo II = 965±245ml; p<0.05 e Grupo III = 24.8± 4.7min e Grupo II = 8.8 ± 1.3 min, p<0.01, respectivamente). Todos os parâmetros estáticos e dinâmicos, bem como os biomarcadores de oxigenação tecidual foram afetados pelo choque hemorrágico e quase todos os parâmetros foram totalmente restaurados após a reanimação em ambos os grupos. CONCLUSÃO: Neste estudo em modelo de choque hemorrágico, a reanimação guiada pelo VPP utilizou menor quantidade de fluido e menor quantidade de tempo do que quando guiado por IVDFVD derivado de cateter de artéria pulmonar.

INTRODUCTION: Different hemodynamic parameters, including static indicators of cardiac preload as right ventricular end-diastolic volume index (RVEDVI) and dynamic parameters as pulse pressure variation (PPV) have been used in the decision-making process regarding volume expansion in critically ill patients. The objective of this study was to compare fluid resuscitation guided by either PPV or RVEDVI after experimentally-induced hemorrhagic shock. METHODS: 26 anesthetized and mechanically ventilated pigs were allocated into control (Group-I), PPV (Group-II) and RVEDVI (Group- III). Hemorrhagic shock was induced by blood withdrawal to target mean arterial pressure of 40mmHg, maintained for 60 minutes. Parameters were measured at baseline, time of shock, sixty minutes after shock, immediately after resuscitation with hydroxyethyl starch 6% (130/0.4), one hour and two hours thereafter. The endpoint of fluid resuscitation was determined as the baseline values of PPV and RVEDVI. Statistical analysis of data was based on ANOVA for repeated measures followed by the Bonferroni test (P<0.05). RESULTS: Volume and time to resuscitation were higher in Group-III than in Group-II (Group-III = 1305±331ml and Group-II = 965±245ml; p<0.05 and Group-IIII = 24.8±4.7min and Group-II = 8.8±1.3 min, p<0.05, respectively). All static and dynamic parameters and biomarkers of tissue oxygenation were affected by hemorrhagic shock and nearly all parameters were restored after resuscitation in both groups. CONCLUSION: In the proposed model of hemorrhagic shock, resuscitation to the established endpoints was achieved within a smaller amount of time and with less volume when guided by PPV than when guided by pulmonary artery catheter-derived RVEDVI.