Preferential location of lidocaine and etidocaine in lecithin bilayers as determined by EPR, fluorescence and H-2 NMR

We have examined the effect of the uncharged species of lidocaine (LDC) and etidocaine (EDC) on the acyl chain moiety of egg phosphatidylcholine liposomes. Changes in membrane organization caused by both anesthetics were detected through the use of EPR spin labels (5, 7 and 12 doxyl stearic acid methyl ester) or fluorescence probes (4, 6, 10, 16 pyrene-fatty acids). The disturbance caused by the LA was greater when the probes were inserted in more external positions of the acyl chain and decreased towards the hydrophobic core of the membrane. The results indicate a preferential insertion of LDC at the polar interface of the bilayer and in the first half of the acyl chain, for EDC. Additionally, 2 H NMR spectra of multilamellar liposomes composed by acyl chain-perdeutero DMPC and EPC (1:4 mol%) allowed the determination of the segmental order (S-mol) and dynamics (T-1) of the acyl chain region. In accordance to the fluorescence and EPR results, changes in molecular orientation and dynamics are more prominent if the LA preferential location is more superficial, as for LDC while EDC seems to organize the acyl chain region between carbons 2-8, which is indicative of its positioning. We propose that the preferential location of LDC and EDC inside the bilayers creates a "transient site", which is related to the anesthetic potency since it could modulate the access of these molecules to their binding site(s) in the voltage-gated sodium channel. (C) 2007 Elsevier B.V. All rights reserved.

Pharmacokinetic Profile of Liposome-Encapsulated Ropivacaine after Maxillary Infiltration Anaesthesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O elo microbiano como alimento alternativo para o zooplâncton em reservatórios dominados por cianobactérias

Protozoa may be an important alternative food source for Calanoida copepods in these environments. Aiming to quantify the feeding preferences of N. cearensis by ciliates in the presence of cyanobacteria, in vitro experiments were conducted, using mixed cultures in different concentrations of total food for copepod. Two ciliates species (Paramecium sp. and Cyclidium sp.) and a cyanobacteria toxic strain (Microcystis aeruginosa) were offered as food. Previous experiments were done to identify the copepod s maximum ingestion rate through the use of a type II functional response model when each prey is offered separately. High maximum ingestion rate were found when those protists were offered as prey. N. cearensis showed significant preference for protozoal prey over the cyanobacterium tested both in low (corresponding 95.15% of the diet) and in high food concentration treatments (about 91.56% of the diet), preferring the bigger ciliate in lower concentrations (67.52% of the diet). The meaningful involvement of heterotrophic organisms in the zooplankton diet emphasis the microbial loop participation in the energy transition from copepods to higher trophic levels. This data contributes to understand the stability of existing trophic interactions in reservoirs subjected to eutrophication and assists trophic cascade studies in these environments

Degradabilidade ruminal da matéria seca, da fração fibrosa e da proteína bruta de forrageiras

O objetivo deste trabalho foi avaliar a degradabilidade ruminal da matéria seca, da fibra em detergente neutro, da fibra em detergente ácido e da proteína bruta da alfafa (Medicago sativa), aveia-preta (Avena strigosa), leucena (Leucaena leucocephala) e guandu (Cajanus cajan). Amostras de 3 g das forragens foram incubadas no rúmen de três novilhos por períodos de 0, 6, 12, 24, 36, 48 e 72 horas. As degradabilidades efetivas da matéria seca da alfafa e da aveia, para a taxa de passagem de 5% por hora, foram elevadas (acima de 60%). A leucena e o guandu apresentaram valores inferiores, 50,9 e 56,0%, respectivamente. A partir de 24 horas de incubação, a aveia se destacou com maior desaparecimento da fibra em detergente neutro e da fibra em detergente ácido, e ainda apresentou as mais elevadas taxas de degradação efetiva destas frações. A aveia foi a forragem que apresentou maior degradabilidade da matéria seca, da fibra em detergente neutro, da fibra em detergente ácido e da proteína bruta no rúmen. O guandu, entretanto, foi a forragem com as piores taxas de degradação.

Validation of an HPLC Method for quantitative Determination of Benzocaine in PHBV-Microparticles and PLA-Nanoparticles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Screening of Formulation Variables for the Preparation of Poly(epsilon-caprolactone) Nanocapsules Containing the Local Anesthetic Benzocaine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bloqueio contínuo do plexo lombar via posterior bilateral com bomba de infusão descartável: relato de caso

JUSTIFICATIVA E OBJETIVOS: O número de artroplastia total de quadril (ATQ) bilateral tem aumentado a cada ano. Analgesia pós-operatória pela infusão contínua perineural com anestésico local tem se mostrado favorável quando comparada com analgesia sistêmica. O uso de bombas elastoméricas tem aumentado a satisfação do paciente quando em comparação com os modelos eletrônicos. O objetivo deste relato foi descrever um caso de analgesia contínua bilateral do plexo lombar via posterior, com infusão contínua através de bomba elastomérica, em paciente submetido à uma artroplastia bilateral de quadril. RELATO do CASO: Paciente feminina, 46 anos, 65 kg, 162 cm, com artrite reumatoide e hipertensão arterial, estado físico ASA II, escalada para ser submetida a ATQ bilateral em um único estágio. Uso de corticosteroide por 13 anos. Hemoglobina = 10,1 g.dL-1, hematócrito = 32,7%. Monitoração de rotina. Raquianestesia com 15 mg de bupivacaína 0,5% isobárica. Anestesia geral com propofol (PFS) e remifentanil e intubação sem bloqueadores neuromusculares. ATQ direita e no final, bloqueio plexo lombar com estimulador e conjunto agulha 150 mm e injeção de 20 mL bupivacaína 0,2% e passagem de cateter. ATQ esquerda e, no final, mesmo procedimento. Estudado dispersão do anestésico e contraste. Instalado bomba elastomérica com bupivacaína 0,1% (400 mL) em velocidade de 14 mL.h-1. Transferida para Unidade de Cuidados Intensivos (UCI). Vinte e quatro horas após, nova bomba com a mesma solução. Nenhum bolus durante 50 horas. Após remoção de cateter, dor controlada por via oral com cetoprofeno e dipirona. CONCLUSÕES: O bloqueio bilateral contínuo periférico com infusão de bupivacaína a 0,1% com bombas elastoméricas é um procedimento seguro e efetivo em adultos.

Protozoários de vida livre em ambientes aquáticos do RN: ocorrência, caracterização e importância para a educação básica

Water is considered an essential right to life, besides being a determinant of economic development and social welfare, represented by both the quantity available, and the quality. In semi-arid Northeast, droughts occurring on a regular basis combined with human activities, aggravate the situation regarding the conservation of water resources in this area. To alleviate this condition is common to construction of artificial reservoirs, such as reservoirs and dams. As in natural aquatic environments, these reservoirs are potential sites for the proliferation, growth and development of diverse biological communities, whether of animals, plants and microorganisms. Research on the composition and ecology of these communities, especially microbial, are still restricted. One of the least studied groups in these environments are free-living protozoa, which over time have been neglected and after discoveries about its various functions in the aquatic ecosystem are beginning to receive more attention from scholars. They are, in quantitative terms, the most important consumers of microorganisms (mainly bacteria and algae) in aquatic environments, and therefore control the abundance of these. They may therefore influence the structure of the aquatic food chain in terms of species composition, abundance, biomass and biodiversity. Despite the recognition of the importance of protozoa in the final of the trophic transfer in aquatic environments, there are few data and, in general, are still precarious knowledge of them. Given the importance of protozoa in aquatic environments and the paucity of research on this group, especially in the state of Rio Grande do Norte, the present study aimed at identifying the genus and species of free-living protozoa that are present in the Armando Ribeiro Gonçalves Dam as well as to relate the occurrence and dynamics of the trophic conditions in the environment in which they are inserted, in order to support the hypothesis that species that are in these environments can serve to indicate the water quality. We observed the presence of 65 taxa of free-living protozoa, of which 29 were identified at the species level. There was a similarity space in taxonomic composition of protozoa, suggesting a possible regulation of this type of community for limnological variables other than those studied in this work (chlorophyll a, pH, temperature). Although it was aimed to analyze the conceptions of teachers and students from nearby towns Dam Armando Ribeiro Gonçalves, on issues relating to water quality and the role of protozoa. For this, we applied questionnaires with teachers and pupils of public schools of San Rafael and Itajá. It was concluded that teachers and students recognize the multi-dam Armando Ribeiro Gonçalves, although unaware of important aspects of the dynamics and ecology of this environment. Conceptions of teachers and students are matched at various times, especially with regard to waterborne diseases. In an attempt to identify possible misconceptions about the knowledge of the protozoa, assuming that these organisms have neglected their ecological role, and are seen as only, disease, a study was done with teachers and students, following a particular methodology that allowed look so clear and precise results. It was clear that knowledge about the free-living protozoa is still quite limited. The alternative conceptions that were found show a direct relation of protozoans and diseases. From the data obtained by these studies, we planned a series of science communication activities, environmental education and health education in schools close to study environments in order to promote a didactic transposition of accumulated knowledge about these organisms, favoring continuing education of teachers and the increase of information to the local community through the knowledge of biodiversity and ecology of these organisms. Moreover, the results found in this study and reflections on it that led to propose the elaboration of a book Readers with an emphasis on the group of freeliving protozoa in the populations for use in public schools in the region where it was developed the semiarid work

Hiperoxalúria primária com insuficiência renal crônica terminal em lactente

Objetivo: descrever caso clínico de um lactente com insuficiência renal crônica terminal, causada por hiperoxalúria primária.Método: após revisão da literatura, verifica-se a raridade da doença; na França, a prevalência é de 1,05/milhão, com taxa de incidência de 0,12/milhão/ano. Pesquisa abordando centros especializados mundiais detectou, em 1999, 78 casos em lactentes; destes, em 14% o quadro inicial foi de uremia. A gravidade e a raridade da doença sugerem o relato deste caso.Resultados: criança de sexo feminino, com quadro de vômitos e baixo ganho de peso desde os primeiros meses de vida, desenvolveu insuficiência renal terminal aos 6 meses de idade, sendo mantida em tratamento dialítico desde então. Aos 8 meses, foi encaminhada para esclarecimento diagnóstico, apresentando déficit pôndero-estatural grave e os seguintes exames laboratoriais: uréia= 69 mg/dl, creatinina=2,2 mg/dl e clearance de creatinina= 12,5 ml/min/1.73m²SC. O exame de urina foi normal, a ultra-sonografia renal revelou tamanho normal e hiperecogenicidade de ambos os rins. A dosagem de oxalato urinário foi de 9,2mg/kg/dia ou 0,55 mmol/1.73m²SC, e a relação oxalato:creatinina, de 0,42. A biópsia renal diagnosticou presença de grande quantidade de depósitos de cristais de oxalato de cálcio no parênquima renal. A radiografia de ossos longos evidenciou sinais sugestivos de osteopatia oxalótica, e a fundoscopia indireta, sinais de retinopatia por oxalato. A criança foi mantida em diálise peritoneal ambulatorial contínua, tendo sido iniciado tratamento com piridoxina.Conclusões: a hiperoxalúria primária deve ser considerada como um dos diagnósticos diferenciais de insuficiência renal crônica em lactentes, especialmente na ausência de história sugestiva de outras patologias.

Preparação e caracterização físico-química de complexos de inclusão entre anestésicos locais e hidroxipropil-beta-ciclodextrina

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização do complexo de inclusão ropivacaína: β-ciclodextrina

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Anestésicos locais: interação com membranas biológicas e com o canal de sódio voltagem-dependente

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)