Radiochemical pharmacokinetic profile of P10 peptide with antifungal properties.

Paracoccidioidomycosis (PCM) is a chronic granulomatous disease that is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. It is endemic in some countries of Latin America and can cause a high-burden fungal infection with significant morbidity and mortality. The peptide P10, which demonstrates immune protection against experimental PCM, was radiolabeled with a radioisotope and evaluated in vivo. The radiolabeling was conducted to trace the pharmacokinetics of the molecule in principal organs and tissues. This was achieved with high radiochemical purity. Biodistribution and scintigraphic imaging showed fast blood clearance that was mainly renal; however, hepatobiliar excretion was also, with marked uptake in cervical lymph nodes. This profile may be useful for the development of a prophylactic drug or vaccine for patients exposed to PCM.

Radiotracers for different angiogenesis receptors in a melanoma model.

Early and reliable diagnosis of melanoma, a skin tumor with a poor prognosis, is extremely important. Phage display peptide libraries are a convenient screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was to evaluate two technetium-99m tracers for angiogenesis detection in a melanoma model, using cyclic pegylated pentapeptide with RGD and NGR motifs conjugated with the bifunctional chelator mercaptoacetyltriglycine (MAG(3)). The conjugated peptides (10 µl of a µg/µl solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was carried out by instant thin-layer chromatography and confirmed by high-performance liquid chromatography. The partition coefficient was determined and internalization assays were performed in two melanoma cell lines (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was carried out in healthy animals at different time points and also in tumor-bearing mice, 120 min post injection. Blocking studies were also conducted by coinjection of cold peptides. The conjugates displayed a rather similar pharmacokinetic profile. They were radiolabeled with high radiochemical purity (>97%) and both were hydrophilic with preferential renal excretion. Yet, tumor uptake was higher for human than for murine melanoma cells, especially for [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) (7.85±2.34%injected dose/g 120 min post injection). The performance of [(99m)Tc]-MAG(3)-PEG(8)-c(RGDyk) was better than the NGR tracer with regard to human melanoma uptake. In this sense, it should be considered for future radiotracer studies of tumor diagnosis.

Possibilities of high-nitrogen parenteral nutrition in malnourished surgical patients

A nutricao parenteral representa uma modalidade amplamente utilizada em pacientes submetidos a cirurgia gastrointestinal, porem casos como hipermetabolismo poderao responder de forma insatisfatoria frente a este regime. Um programa hiperproteico abrangendo ate 2,5-3,0 gramas de aminoacidos/kg/dia foi recomendado nestas circunstancias, mas a tolerancia e a eficacia desta alternativa nao estao bem demonstradas. Num estudo "cross over" realizado com casos refratarios a nutricao convencional durante, pelo menos, uma semana, os resultados clinicos foram averiguados. As duas prescricoes eram isocaloricas, mas os ingressos de aminoacidos foram, respectivamente 1,6 ñ 0,4 g/kg/d e s,5 g/kg/d. Houve ganho de peso na segunda fase do estudo (2,5 ñ 0,8 kg), mas sem alteracao das proteinas plasmaticas, e com elevacao moderada da ureia. A tolerancia clinica e hemodinamica a esta terapeutica foi boa. Concluiu-se que a nutricao parenteral hiperproteica pode representar um procedimento interessante para pacientes catabolicos, todavia estudos ulteriores sao necessarios nesta area.

Contaminaçäo da dieta enteral em ambiente nosocomial / Contamination of enteral diets in nosocomial environment

O trato gastrointestinal é comparativamente resistente aos germes veiculados pela dieta, mas estudos recentes sugerem que infecçöes hospitalares podem ter início nesta rota. Uma investigaçäo efetuada com dietas industrializadas, preparadas com cuidados satisfatórios de assepsia, e armazenadas por até 24 horas, pesquisou contaminantes aeróbios e anaeróbios porventura presentes nestas preparaçöes. A sistemática de cultivo abrangeu amostras de 0h, 8h, e 24h, sendo que estas últimas foram alternativamente conservadas em temperaturas ambiente ou em geladeira. A cultura inicial já revelou 50% de positividade microbiana, porém parte desta contaminaçäo era devida as espécies de bacilos näo patogênicos. Após 8h e 24h os índices observados revelaram-se de ordem de 90%, ainda com presença expressiva de bacilos Gram negativos, ao lado de ratas bactérias Gram positivas. Durante o período da realizaçäo desta pesquisa näo se observaram episódios significativos de diarréia ou febre, que pudessem ser atribuídos à contaminaçäo relatada, nem se registraram situaçöes de bacteremia ou choque séptico em qualquer paciente sob nutriçäo enteral. Esta ausência de repercussöes clínicas para os achados laboratoriais em questäo näo é inesperada, e sugere baixas contagens para os microorganismos em tela, as quais näo atingiram concentraçöes críticas. Näo obstante, um grau de atençäo maior deverá ser dedicado ao controle de qualidade das dietas enterais, especialmente quando as bactérias Gram negativas multi-resistentes forem identificadas, ou quando a populaçäo tratada constitui-se de pacientes muito debilitados ou imunologicamente comprometidos