Synthesis and Evaluation of Biotinylated Small Molecular Drugs with Long Chain / 中国药学杂志

OBJECTIVE: To set up an easy and effective method for biotinylation of small molecule drugs with long chain. METHODS: Biotinylated 6-aminocaproic acid was synthesized as intermediate by one step method, doxorubicin(DOX) with auto-fluorescence was used as the first drug, and by DCC and DMAP catalysis, biotinylated DOX was synthesized. Using the double fluorescence system of DOX, the binding ability of biotinylated DOX to avidin and its biological activity were determined. When verified to be reasonable and effective, the method was applied to catalyze biotinylated paclitexal (PTX) which didn′t have auto-fluorescence itself, and the physical and chemical characteristics, and biological activities as well as the visualization were tested. RESULTS: The binding rate of synthesized DOX to avidin was 93.7%; the cells inhibition rate and localization were the same as DOX; the purity of biotinylated PTX was 84.42%, and the structure shown by NMR was correct; the cell inhibition rate was the same as PTX; the combination of PTX with microtubules was observed by visual modification. CONCLUSION: The method supplies a temperate way for biotinylation, and can be used for the synthesis and visualization of small molecules as probes and research of drug mechanism.

Implantação de protocolo institucional para o uso racional de hemoderivados e seu impacto no pós-operatório de cirurgias de revascularização miocárdica / Implementation of an institutional protocol for rational use of blood products and its impact on postoperative of coronary artery bypass graft surgery

OBJETIVO: Cirurgias cardíacas são, por vezes, acompanhadas de perdas sanguíneas significativas, e transfusões de sangue podem ser necessárias. No entanto, o uso indiscriminado de hemoderivados pode resultar em efeitos danosos para o paciente. Neste estudo, avaliamos os efeitos imediatos da implantação de um protocolo para o uso racional de hemoderivados no perioperatório de cirurgias de revascularização miocárdica. MÉTODOS: Entre os meses de abril e junho de 2011, foi implementado um protocolo institucional em um hospital privado especializado em cardiologia com a anuência e a colaboração de sete equipes de cirurgia cardíaca, visando ao uso racional de hemoderivados. Foram verificados dados clínicos e demográficos dos pacientes, e avaliados o uso de hemoderivados e os desfechos clínicos no período intra-hospitalar, antes e após a implantação do protocolo. O protocolo consistiu em uma campanha institucional junto às equipes cirúrgicas, de anestesiologia e intensivistas, para difundir a prática do uso de hemoderivados com base em critérios clínicos objetivos (anemia com repercussões hemodinâmicas e disfunção ventricular significativa), bem como tornar rotineira a prescrição de ácido epsilon-aminocaproico no intraoperatório, que é prática recomendada por diretrizes internacionais baseadas em evidência científica. RESULTADOS: Após os 3 meses de implantação do protocolo, houve aumento do uso de ácido epsilon-aminocaproico de 31% para 100%. Antes da implantação do protocolo, 67% das cirurgias utilizaram alguma transfusão sanguínea; após a implantação, 40% das cirurgias necessitaram de alguma transfusão sanguínea nos meses subsequentes do mesmo ano (p<0,001). Não houve diferença significativa nos desfechos clínicos avaliados antes e após implantação do protocolo. CONCLUSÃO: O uso racional de hemoderivados, associado à infusão do ácido epsilon-aminocaproico, tem o potencial de reduzir o número de hemotransfusões no perioperatório de cirurgias cardíacas...

OBJECTIVE: Cardiac surgeries are sometimes followed by significant blood loss, and blood transfusions may be necessary. However, indiscriminant use of blood components can result in detrimental effects for the patient. We evaluated the short-term effects of implementation of a protocol for the rational use of blood products in the perioperative period of cardiac surgery. METHODS: Between April and June 2011, an institutional protocol was implemented in a private hospital specializing in cardiology to encourage rational use of blood products, with the consent and collaboration of seven cardiac surgery teams. We collected clinical and demographic data on the patients. The use of blood products and clinical outcomes were analyzed during hospital stay before and after protocol implementation. The protocol consisted of an institutional campaign with an educational intervention to surgical and anesthesiology teams; the goal was to tailor blood transfusion practice according to clinical goals (anemia with hemodynamic changes and significant ventricular dysfunction) and to make routine the prescription of å-aminocaproic acid intraoperatively, which is recommended by international guidelines based on scientific evidence. RESULTS: After three months of protocol implementation, the use of å-aminocaproic acid increased from 31% to 100%. A total of 67% of surgeries before protocol implementation required any blood transfusion, compared with 40% that required any blood transfusion after protocol implementation in subsequent months of the same year (p<0.001). There was no significant difference in clinical outcomes assessed before and after implementation of the protocol. CONCLUSION: The rational use of blood products associated with infusion of å-aminocaproic acid has the potential to reduce the number of blood transfusions in perioperative of cardiac surgeries, but it can affect the risk of complications.

Antifibrinolítico em cirurgia cardíaca: como e quando usar? / Anfibrinolytic in cardiac surgery: how and when to use?

O sangramento pós-operatório continua sendo uma das principais complicações em cirurgia cardíaca. A etiologia desse sangramento é multifatorial, com hiperfibrinólise e disfunção plaquetária desempenhando papel fundamental Tendo em vista essas causas, as drogas antifibrinolíticas têm sido preconizadas. Desde a retirada da aprotinina do mercado, o ácido epsilon-aminocaproico e o ácido tranexâmico passaram a ser os únicos representantes disponíveis dessa classe de drogas. Essas medicações diminuem a perda de sangue e agem na resposta inflamatória associada ao procedimento cirúrgico. A eficácia variável dessas drogas ocorre devido aos vários esquemas terapêuticos e níveis séricos existentes. Recentemente têm surgido alguns questionamentos na literatura a respeito das complicações, doses, vias de administração e melhor momento para administração desses agentes...

The postoperative bleeding remains a major complication in cardiac surgery. The etiology of this bleeding is multifactorial, with hyperfibrinolysis and platelet dysfunction playing a key role. Given these causes antifibrinolytic drugs have been recommended Since the with drawal of aprotinin in the market, epsilon-aminocaproic acid and tranexamic acid became the sole representatives of this class of drugs available. These medications reduce blood loss and act on the inflammatory response associated with surgery. The variable efficacy of these drugs is due to multiple drug regimens and serum available. Recently some questions have arisen in the literature regarding the comptications, doses, routes of administration and timing for administration of these agents...

Uso del ácido épsilon aminocaproico en cirugía torácica electiva / I use of the sour épsilon aminocaproico in elective thoracic surgery

Se realizó un estudio no observacional, de tipo ensayo clínico terapéutico, comparativo, prospectivo y aleatorizado a 60 pacientes a quienes se les realizó cirugía torácica electiva, con el objetivo de evaluar la eficacia del ácido épsilon aminocaproico (AEAC) en cuanto a la disminución del sangramiento posoperatorio y las transfusiones homólogas en este período, así como describir sus posibles reacciones indeseables. Se encontró que la cantidad de sangre colectada en el posoperatorio fue significativamente menor en el grupo tratado con AEAC que en el control tanto a las 6 como a las 24 horas de finalizada la intervención. Las unidades de glóbulos transfundidas en el transoperatorio fueron semejantes en los 2 grupos, pero la cantidad de glóbulos administrados en el posoperatorio resultó significativamente menor en el grupo estudio, al igual que la proporción de pacientes que necesitó transfusión homóloga en este grupo. No se hallaron diferencias entre ambos grupos en cuanto a las reacciones indeseables(AU)

A randomized, prospective and comparative clinicotherapeutic trial was conducted as part of a non-observational study that included 60 patients who underwent elective thoracic surgery in order to evaluate the effectiveness of epsilon aminocaproic acid (EACA) in connection with the decrease of postoperative bleeding and homologous transfusions in this period, as well as to describe its potential undesirable reactions. It was found that the quantity of blood collected in the postoperaive period was much lower in the group treated with EACA than in the control group, both at 6.00 and at 24.00 hrs postintervention. The units of red blood cells transfunded in the transoperative period were similar in both groups, but the quantity of red blood cells administered in the postoperative was significantly lower in the study group, as well as the proportion of patients requiring homologous transfusions in this group. There were no differences between both groups as for undesirable reactions(AU)