Evidence-based clinical practice guidelines for the management of sedoanalgesia and delirium in critically ill adult patients. / Guías de práctica clínica basadas en la evidencia para el manejo de la sedoanalgesia y delirium en el paciente adulto críticamente enfermo.

Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.

Estudo preliminar toxicológico, antibacteriano e fitoquímico do extrato etanólico das folhas de Jatropha mollissima (Pohl) Baill. (pinhão-bravo, Euphorbiaceae), coletada no Município de Tauá, Ceará, Nordeste Brasileiro / Toxicological, antibacterial, and phytochemical preliminary study of the ethanolic extract of Jatropha mollissima (Pohl) Baill (pinhão-bravo, Euphorbiaceae) leaves, collected in Tauá, Ceará, Northeastern Brazil

RESUMO A cada dia, cepas bacterianas estão tornando-se resistentes a diversos antibióticos, o que faz necessária a busca de novas substâncias eficazes para o tratamento de doenças. Desta forma, este trabalho reporta o estudo preliminar toxicológico, antibacteriano e fitoquímico do extrato etanólico das folhas de Jatropha mollissima (pinhão-bravo, Euphorbiaceae), coletada no Município de Tauá, Ceará, Nordeste Brasileiro. Inicialmente, realizou-se o teste de toxicidade do extrato contra Artemia salina. Na sequencia, foi realizado o ensaio antibacteriano contra quatro cepas bacterianas Gram-negativas (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Hafnia alvei ATCC 51873, Klebsiella pneumoniae ATCC 13883) e uma cepa Gram-positiva (Enterococcus faecalis ATCC 29212). Finalmente, fez-se a análise fitoquímica preliminar do extrato ativo para detecção das principais classes de metabólitos especiais. Como resultado, o extrato etanólico das folhas de J. mollissima se mostrou tóxico para Artemia salina, pois apresentou CL50 igual a 406,02 μg/mL. Quanto à ação antibacteriana, o extrato se mostrou ativo contra a bactéria Gram-positiva Enterococcus faecalis ATCC 29212, apresentando moderada atividade antibacteriana (halo de inibição igual a 7,03 mm). Evidenciou-se no extrato bioativo a presença de cumarinas, fenóis, taninos, flavonoides (flavonóis e flavanonas), alcaloides e esteroides, ambas as classes reportadas como antimicrobianos. Portanto, esse extrato tem potencial para ser usado na produção de fármacos contra infecções causadas por bactérias Gram-positivas. No entanto, as informações direcionam estudos futuros para o isolamento e identificação dos compostos bioativos, monitorados sob a ação antibacteriana mais expressiva.

ABSTRACT Each day, bacterial strains are becoming more resistant to various antibiotics, which requires the search for new effective substances for the treatment of diseases. Thus, this study reports the toxicological, antibacterial, and phytochemical preliminary study of the ethanolic extracts of Jatropha mollissima (pinhão-bravo, Euphorbiaceae) leaves, collected in Tauá, Ceará, Northeast of Brazil. Initially, we performed the toxicity testing of the extract against Artemia salina. Then, we conducted the antibacterial assay against four Gram-negative bacterial strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Hafnia alvei ATCC 51873, Klebsiella pneumoniae ATCC 13883), and one Gram-positive strain (Enterococcus faecalis ATCC 29212). Finally, we carried out the preliminary phytochemical analysis of the active extract to detect the main classes of special metabolites. As a result, the ethanolic extract of J. mollissima leaves was toxic to Artemia salina, because it presented LC50 equal to 406.02 µg/mL. Regarding antibacterial action, the extract was active against the Gram-positive bacteria Enterococcus faecalis ATCC 29212, with moderate antibacterial activity (inhibition zone equal to 7.03 mm). The bioactive extract had the presence of coumarins, phenols, tannins, flavonoids (flavanols and flavonones), alkaloids and steroids, both classes reported as antimicrobials. Therefore, this extract has the potential to be used in the production of drugs against infections caused by Gram-positive bacteria. However, these information require further studies for the isolation and identification of bioactive compounds, monitored under the more expressive antibacterial action.

Use of submerged anaerobic membrane bioreactor (SAMBR) containing powdered activated carbon (PAC) for the treatment of textile effluents.

This work investigated the use of submerged anaerobic membrane bioreactors (SAMBRs) in the presence and absence of powdered activated carbon (PAC) for the treatment of genuine textile wastewater. The reactors were operated at 35 °C with an HRT of 24 h and the textile effluent was diluted (1:10) with nutrient solution containing yeast extract as the source of the redox mediation riboflavin. The results showed that although both SAMBRs exhibited an excellent performance, the presence of PAC inside SAMBR-1 enhanced reactor stability and removal efficiency of chemical oxygen demand (COD), volatile fatty acids (VFA), turbidity and color. The median removal efficiencies of COD and color in SAMBR-1 were, 90 and 94% respectively; whereas for SAMBR-2 (without PAC) these values were 79 and 86%, In addition, the median values of turbidity and VFA were 8 NTU and 8 mg/L for SAMBR-1 and 14 NTU and 26 mg/L for SAMBR-2, indicating that the presence of PAC inside SAMBR-1 led to the production of an anaerobic effluent of high quality regarding such parameters.

Effect of orally administered misoprostol and cimetidine on the steady state pharmacokinetics of diazepam and nordiazepam in human volunteers.

The effects of misoprostol and cimetidine on diazepam pharmacokinetics were evaluated in order to determine whether the kinetic variables for diazepam and nordiazepam alone differ with the repeated oral administration of misoprostol and cimetidine to healthy adult volunteers. The trial was conducted as an open crossover study in 12 normal subjects, divided into two groups with all subjects receiving both regimens. Total study duration was 5 weeks. An initial clinical assessment, including blood biochemistry and assessment of subject oxidation status was carried out on study day 1. On this day, subjects began taking diazepam (10 mg) orally for one week, with pharmacokinetic studies performed at day 8, when steady state levels of diazepam were reached. This was followed by one week with active drug, misoprostol to Group I and cimetidine to Group II, with pharmacokinetic studies performed at the end of a 1-week treatment. After a 2-week wash-out period, both groups took for one week, the alternate drug, i.e. cimetidine plus diazepam to Group I and misoprostol plus diazepam to Group II. On days 8, 15 and 36, subjects were admitted to the hospital for 12 h, during which time a clinical examination was carried out and blood samples were taken at time zero and at 4, 8, 12, 24, and 36 h post-dosing for the measurement of serum diazepam and nordiazepam. The main parameters measured and evaluated were diazepam and nordiazepam pharmacokinetics at steady state (days 8, 15 and 36). These were areas under the curve in the dose intervals (AUC0-24h), maximum plasma concentrations (Cmax), time to peak concentrations (Tmax), elimination half-life (t1/2), elimination constant (Kel), distribution volume (Vd), total body clearance (ClB) and clearance after oral administration (Cloral). The results demonstrated that plasma diazepam and nordiazepam concentrations had a significant increase after steady states have been reached with the simultaneous administration of 800 mg of cimetidine daily for one week. The simultaneous administration of 800 micrograms of misoprostol did not cause any significant change in diazepam and nordiazepam plasma levels after steady states had been reached. Comparing the pharmacokinetic parameters of Groups A and B as well as within groups on days 8, 15 and 36, a significant increase in plasma diazepam and nordiazepam levels was detected. This was due to a cimetidine-induced impairment in microsomal oxidation of diazepam and nordiazepam, which caused a decrease in total metabolic clearance and increased mean steady state plasma concentrations. A more prolonged half-life was observed for both groups taking cimetidine as well as an increase of mean maximum plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Grandes nosmes da medicina grega (Helenica). / Great names of the greek medicine (Hellenic)

As realizacoes dos antigos gregos foram as mais notaveis na historia da humanidade.Sem grandes riquezas naturais desenvolveram a mais importante civilizacao de sua epoca, fundamentada em ideias de liberdade de democracia, de otimismo, de racionalismo e de grande respeito pela dignidade e merito de cada individuo. Nesta civilizacao, a medicina atingiu seu apogeu, particularmente em Atenas, lider intelectual das cidades-estados da Grecia Antiga. Mas grandes nomes existiram desde o inicio da civilizacao grega, como Esculapio, Homero, Pitagoras, Hipocrates, Teofrastos, Praxagoras e Chrysipos, os quais deixaram contribuicoes eternas para o conhecimento humano. Neste trabalho o autor aborda aspectos referentes da civilizacao grega e grandes nomes da sua medicina, como meritos praticantes e estudiosos da mais bela das ciencias humanas

Comparison of four different beta-adrenoceptor blocking drugs on lymphocyte isoprenaline-stimulated cyclic AMP production.

1 The influence of acebutolol, atenolol, pindolol and timolol on human lymphocyte cyclic AMP (cAMP) and its stimulation by isoprenaline in vitro has been studied. 2 Acebutolol and atenolol (10(-8)-10(-6)M) had no significant influence on lymphocyte cAMP levels or on isoprenaline-stimulated increase in cAMP. 3 Pindolol and timolol significantly antagonised the effect of isoprenaline, and pA2 values were calculated to be 8.12 and 8.04 respectively. This suggests that beta 2-adrenoceptors are involved in this phenomenon. 4 Only pindolol produced a significant increase in lymphocyte cAMP, which is consistent with its partial agonist activity.

Farmacologia clinica do endotelio vascular. / Clinical pharmacology of the vascular endothelium

O desenvolvimento de tecnicas para o isolamento das celulas endoteliais tem permitido um estudo mais detalhado desta outrora simples estrutura morfologica. A descoberta de que o endotelio vascular exerce funcoes metabolicas e de sintese, salientando-se a elaboracao da prostaciclina, tem fornecido evidencias que permitem denominar o endotelio cardiovascular de um "orgao" com funcoes altamente especializadas. Seu papel na coagulacao sanguinea, controle de tono vascular, aterogenese, resposta inflamatoria e imunologica e morfogenese vascular sao apresentados. A pesquisa ao nivel basico e clinico, particularmente apos o aparecimento de Departamentos de Farmacologia Clinica nas principais universidades e centros de pesquisa em todo o mundo, permitira num futuro proximo um entendimento mais adequado deste fascinante mas ilusorio "orgao"

Prostacyclin increases cyclic-nucleotide responsiveness of lymphocytes from patients with systemic sclerosis.

Low cyclic-AMP levels within lymphocytes from five patients with systemic sclerosis showed a striking increase in response to isoprenaline after intravenous infusion of prostacyclin.