Utilización de un modelo animal para entrenamiento, en oxigenación por membrana extracorporea (ECMO) / The use of an animal model for extracorporeal membrane oxygenation (ECMO) training

ECMO es un procedimiento de rescate de recién nacidos (RN) con fallo respiratorio hipoxémico severo que no responde al tratamiento convencional. Previo a la instrumentación de esta técnica en pacientes, se realizó el entrenamiento experimental en animales. Existe escasa bibliografía sobre la utilización de porcinos como modelo animal en ECMO. Se reportan, en cambio, la implementación de otros animales, tales como el cordero. Objetivo: determinar la utilidad y el comportamiento modelo animal eligido, su respuesta al procedimiento de ECMO, describir la técnica utilizada y sus resultados. Método: se utilizaron dos porcinos de la raza Landrace, de 30 y 45 días de vida. Se canularon la vena yugular interna y la arteria carótida interna derechas; se realizó el ensamblado y purgado del circuito. El bypass se inició con un flujo de bomba de 20 mL/K/min, aumentandose hasta 100-120 mL/K/min; logrado un flujo de 80 mL/K/min se disminuyeron los parámetros de Asistencia Respiratoria Mecánica (ARM) a nivel de reposo. Durante el curso de ECMO se practicaron diferentes acciones relacionadas con el manejo del sistema de perfusión y evaluación del comportamiento clínico del modelo. Finalmente se suspendió electivamente el procedimiento; luego el animal fue dacanulado y recuperado. Resultados: tiempo promedio de ECMO: 24.5 horas. Signos vitales del animal estables. No hubo complicaciones relacionadas con el circito, ni presencia de sangrado sistémico. Se lograron tasas deseadas de hemofiltración. Ambos animales sobrevivieron. Como complicación se registró hematuria en un caso. Conclusión: El modelo animal elegido, para el entrenamiento en el manejo de ECMO, fue satisfactorio.

Síntese e modelagem molecular do novo derivado indolinônico como candidato a antiinflamatório COX-2 seletivo / Synthesis and molecular modeling of a novel indolinone derivative as a candidate anti-inflammatory selectively inhibiting COX-2

Os fármacos antiinflamatórios são sabidamente os mais comercializados em todo o mundo, e apesar disto apresentam sérios efeitos colaterais, sobretudo no que se refere ao trato gastrintestinal. A descoberta de novos protótipos com atividade e segurança terapêutica melhoradas continua sendo uma busca constante. Com o adventoda química computacional torna-se mais fácil o estudo teórico do comportamento fisiológico de uma nova substância bem como a compreensão do possível mecanismo de ação destas novas moléculas. Assim, através de modelos matemáticos de moléculas e receptores estudou-se neste trabalho o composto I (1-(2,6- diclorofenil)indolin-2-ona) quanto à sua possibilidade deinibir seletivamente a isoforma COX-2 da enzima prostaglandina endoperóxido sintase (PGHS), e também as melhores posições para a introdução de grupamentos químicos e modificações moleculares.

Efeito do tratamento com algumas vitaminas B na potencialização do efeito antiinflamatório e antinociceptivo do diclofenaco e da talidomida / Potentiating effect of treatment with some B vitamins on the anti-inflammatory and antinociceptive properties of diclofenac and thalidomide

Mostrou-se que o pré-tratamento com as vitaminas tiamina[B1], piridoxina[B6] e cianocobalamina [B12], isoladas ou administradas conjuntamente, não inibiu o edema de pata produzido pela carragenina em ratos, nem as contorções abdominais produzidas pelo ácido acético em camundongos.Por outro lado, o diclofenaco [25 ou 50mg/kg] ou talidomida [45mg/kg] inibiram o edema de pata em ratos, e a associação das três vitaminas à estas drogas, mas não as vitaminas administradas isoladamente, potencializou os efeitos do diclofenaco [25 ou 50mg/kg] no tempo de quatro horas e a talidomida [45mg/kg], nos tempos de duas, três e quatro horas após a carragenina.As contorções abdominais em camundongos foram inibidas pelas doses de 25 ou 50mg/ kg de diclofenaco.A associação das três vitaminas ou apenas da cianocobalamina, potencializou as duas doses do diclofenaco utilizadas.As contorções abdominais foram inibidas também pela talidomida [45mg/kg] e a associação das três vitaminas, ou cada uma das vitaminas administradas isoladamente, foram capazes de potencializar os efeitos da talidomida.É provável que a diferença no mecanismo de ação destas drogas seja responsável por esta diferença dos efeitos das vitaminas.O presente estudo preconiza o uso de antiinflamatórios, combinados com as vitaminas tiamina[B1], piridoxina[B6] e cianocobalamina [B12], em doenças crônicas, diminuindo assim a dose destas drogas e seus efeitos colaterais

The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability: part i: the prevalence of drug use in drive the drug-positive group.

Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinnoids, benzodiazepines and stimulants. Overall, three-quarters of drivers tested negative for drugs. Alcohol was the most frequently detected drug. Cannabinoids were also detected at high rates, but the majority of drivers tested positive for THC-acid, the inactive metabolite of THC. Benzodiazepines and stimulants were detected at low rates, and detection rates for combinations of drugs were also low. Males were more likely to test positive for drugs, especially alcohol and THC, whereas females were more likely to test positive for benzodiazepines. A similar proportion of car drivers and motorcycle riders tested positive for drugs, although riders were more likely to test positive for THC. Single-vehicle crashes were particularly associated with alcohol for both car driver and riders, and for riders, multiple-vehicle crashes were particularly associated with THC.

The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst injured drivers and their role in driver culpability: part ii: the relationship between drug prevalence and drug concentration, and driver culpability.

Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinoids (measured by the presence of THC), benzodiazepines and stimulants. The relationship between the prevalence and concentration of drugs and the culpability of the driver was examined using an objective method for assessing culpability. There were no significant differences between males and females with respect to culpability. However, there was a relationship between age and culpability: drivers under 26 years and over 60 years were more likely to be culpable. Drivers who tested positive for alcohol only, benzodiazepines only and the combinations of alcohol and THC and alcohol and benzodiazepines were significantly more likely to be culpable for the crash compared with the drug-free group. Conversely, a lower percentage of drivers who only tested positive for THC were culpable for the crash compared with drug-free drivers. This difference was not statistically significant. For car drivers in single-vehicle crashes, the majority of drivers were judged culpable irrespective of drug use. In multiple-vehicle crashes, car drivers testing positive for alcohol only or benzodiazepines only were more likely to be culpable for the crash compared with drug-free drivers. For motorcycle riders in both single- and multiple-vehicle crashes, there were no significant differences between the drug-positive and drug-free groups. A higher percentage of drug-free riders in multiple-vehicle crashes were culpable compared with riders who only tested positive for THC, but this difference was not statistically significant. There was a significant concentration-dependent relationship between alcohol and culpability: as blood alcohol concentration increased, so did the percentage of culpable drivers. When THC was used alone, there was no significant increase in culpability. For those drivers with benzodiazepines at therapeutic concentrations and above, there was a significant increase in culpability. The relationship between stimulants and culpability was not significant, although a higher proportion of stimulant-positive drivers were culpable compared with drug-free drivers. The combinations of alcohol and THC, and alcohol and benzodiazepines also produced a significant increase in culpability, but this increase was not significantly greater than that produced by alcohol alone.

Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions.

Polymerase chain reactions (PCRs) synthesize abundant amplification products. Contamination of new PCRs with trace amounts of these products, called carry-over contamination, yields false positive results. Carry-over contamination from some previous PCR can be a significant problem, due both to the abundance of PCR products, and to the ideal structure of the contaminant material for re-amplification. We report that carry-over contamination can be controlled by the following two steps: (i) incorporating dUTP in all PCR products (by substituting dUPT for dTTP, or by incorporating uracil during synthesis of the oligodeoxyribonucleotide primers; and (ii) treating all subsequent fully preassembled starting reactions with uracil DNA glycosylase (UDG), followed by thermal inactivation of UDG. UDG cleaves the uracil base from the phosphodiester backbone of uracil-containing DNA, but has no effect on natural (i.e., thymine-containing) DNA. The resulting apyrimidinic sites block replication by DNA polymerases, and are very labile to acid/base hydrolysis. Because UDG does not react with dUTP, and is also inactivated by heat denaturation prior to the actual PCR, carry-over contamination of PCRs can be controlled effectively if the contaminants contain uracils in place of thymines.