Atividade antiinflamatória, antiúlcera gástrica e toxicidade subcrônica do extrato etanólico de própolis

Avaliou-se a atividade antiinflamatória do extrato etanólico de própolis - EEP, . sobre o edema desencadeado por carragenina, dextrana e histamina. O EEP apresentou dose eficaz (DE50) de 650 mg/kg (v.o), inibindo significativamente o processo inflamatório desencadeado pela carragenina, mas não inibiu o produzido por dextrana. O EEP antagonizou ainda o efeito edematogênico produzido por histamina. Nas úlceras produzidas por estresse, o EPP inibiu de forma significativa a geração dos diversos tipos classificados. em todos os parâmetros analisados no estudo da toxicidade em fase de tratamento subcrônico , (hematológicos, bioquímicos e histopatológicos), o grupo tratado com o EEP não apresentou diferença significativa em relação ao grupo controle. Desta forma, sugere-se que na dose de 650 mg/kg (dose eficaz) não existe a presença de efeitos tóxicos que possam comprometer a utilização deste extrato.

In vivo CYP2E1 phenotyping as a new potential biomarker of occupational and experimental exposure to benzene

Assessing CYP2E1 phenotype in vivo may be important to predict individual susceptibility to those chemicals, including benzene, which are metabolically activated by this isoenzyme. Chlorzoxazone (CHZ), a specific CYP2E1 substrate, is readily hydroxylated to 6-OH-chlorzoxazone (6-OH-CHZ) by liver CYP2E1 and the metabolic ratio 6-OH-CHZ/CHZ in serum (MR) is a specific and sensitive biomarker of CYP2E1 activity in vivo in humans. We used this MR as a potential biomarker of effect in benzene-treated rats and, also, in humans occupationally exposed to low levels of benzene. Male Sprague-Dawley rats (375-400 g b.w.) were treated i.p. for 3 days with either a 0.5 ml solution of benzene (5 mmol/kg b.w.) in corn oil, or 0.5 ml corn oil alone. Twenty-four hours after the last injection, a polyethylene glycol (PEG) solution of CHZ (20 mg/kg b.w.) was injected i.p. in both treated and control animals. After 2, 5.10,15, 20,30,45, 60, 90, 120, 180, and 240 min from injection, 0.2 ml blood was taken from the tip tail and stored at -20 degrees C until analysis. A modified reverse phase HPLC method using a 5 mu m Ultrasphere C18 column equipped with a direct-connection ODS guard column, was used to measure CHZ and its metabolite 6-OH-CHZ in serum. No statistically significant difference in the MR was observed, at any sampling time, between benzene-treated and control rats. The concentration-versus-time area under the curve (AUC), however, was lower (p < 0.05, Mann-Whitney test), whereas the systemic clearance was higher (p < 0.05) in treated than in control rats. Eleven petrochemical workers occupationally exposed to low levels of airborne benzene (mean +/- SD, 25.0 +/- 24.4 mu g/m(3)) and 13 non-exposed controls from the same factory (mean +/- SD, 6.7 +/- 4.0 mu g/m(3)) signed an informed consent form and were administered 500 mg CHZ p.o. Two hours later a venous blood sample was taken for CHZ and 6-OH-CHZ measurements. Despite exposed subjects showed significantly higher levels of t,t-MA and S-PMA, two biomarkers of exposure to benzene, than non-exposed workers, no difference in the MR mean values +/- SD was found between exposed (0.59 +/- 0.29) and non-exposed (0.57 +/- 0.23) subjects. So, benzene was found to modify CHZ disposition, but not CYP2E1 phenotype in benzene-treated rats, nor in workers exposed to benzene, probably due to the levels of exposure being too low. (C) 2009 Elsevier B.V. All rights reserved.

Efeitos do ultrassom terapêutico sobre parâmetros morfométricos e clínicos e método de extração de metaloproteinases em sujeitos com úlceras venosas

Venous wounds cause physical, psychological and financial problems that impact the quality of life of patients. Treatment alternatives are investigated in order to reduce healthcare costs and improve quality of life of people affected by this problem. Physical resources, such as therapeutic ultrasound (US), are being considered in the treatment of ulcers as a potential healing agent. This study aimed to investigate the application of US as a treatment for venous ulcers. Subjects were divided into two groups: US group, where treatment consisted of 5 sessions of pulsed US (3 MHz, 1W/cm²) associated with compression and kinesiotherapy; and sham group, where individuals went through the same procedures, but with sham US therapy. Subjects were evaluated for wound size by planimetry and digital photography, visual analogue scale for pain, quality of life by the questionnaires SF- 36 and VEINES-QoL/Sym and enzymatic activity of metalloproteinases 2 and 9 by zymography. It was observed mean reduction in wound area of 41.58±53.8% for the US group and 63.47±37.2% for the placebo group, maintenance of quality of life scores in the US group and significant improvement (p<0.05) in the placebo group by VEINES questionnaire. It was observed decreased perception of pain in the placebo group. Sample feasibility for analysis of the protein activity of metalloproteinases 2 and 9 by zymography collected by swab method was also confirmed. Our data did not give us evidence to support the theory that the US accelerates healing of venous ulcers in a short-term analysis. However, we observed that standard care associated with compression therapy and kinesiotherapy were able to significantly shorten the progression of chronic venous ulcers

Evaluation of the genotoxic and antigenotoxic potential of Brassica oleracea L. var. acephala D.C. in different cells of mice

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

Antiulcerogenic Activity of the Essential Oil of Baccharis dracunculifolia on Different Experimental Models in Rats

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

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study: In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis.Material and methods: The anti-ulcer assays were performed using the following protocols: nonsteroidal-antinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated.Results: It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastricjuice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg.Conclusions: In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity. (c) 2008 Elsevier B.V. All rights reserved.

The early systemic and gastrointestinal oxygenation effects of hemorrhagic shock resuscitation with hypertonic saline and hypertonic saline 6% dextran-70: A comparative study in dogs

The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed. in the stomach for intramucosal gastric CO2 (Pgco(2)) determination and for the calculation of intramucosal. pH (pHi):[pHi = pHa - log(Pgco(2)/Paco(2))].The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL / kg; HSD (n = 12), 6 mL / kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po-2 and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.

Efeitos da efedrina sobre as funções cardiovascular e renal de cães sob anestesia com pentobarbital sódico

JUSTIFICATIVA E OBJETIVOS: Com a perspectiva criada por algumas pesquisas de ações diferenciadas da efedrina sobre a função renal, dependendo da dose utilizada, e considerando-se as controvérsias ainda existentes a respeito dos seus efeitos sobre a função renal, esta pesquisa experimental tem como objetivo verificar se doses diferentes de efedrina determinam efeitos hemodinâmicos e renais diferenciados. MÉTODO: em 32 cães anestesiados com pentobarbital sódico (PS), submetidos a preparação cirúrgica, cateterismo, monitorização, expansão do volume do fluido extracelular e respiração controlada, foi estudada a hemodinâmica cardiovascular e renal e a função renal. Os cães foram distribuídos aleatoriamente em quatro grupos: G controle (n = 8), com os cães permanecendo apenas sob o efeito do PS, G ef. 2 µg (n = 8), G ef. 10 µg (n = 8) e G ef. 100 µg (n = 8), com os cães recebendo efedrina nas doses respectivas de 2, 10 e 100 µg.kg-1.min-1. Os atributos cardiovasculares e renais foram estudados em 5 momentos: controle (M1 e M2), durante a infusão de efedrina (M3 e M4) e após a suspensão da infusão de efedrina (M5). RESULTADOS: Não houve diferença significante entre os grupos em relação aos atributos estudados. em G ef. 2 µg houve aumento significante de freqüência cardíaca, fluxo sangüíneo aórtico, débito urinário e excreção fracionária de sódio. em G ef. 10 µg houve aumento apenas da freqüência cardíaca e fração de filtração, enquanto em G ef. 100 µg ocorreu aumento de freqüência cardíaca, pressão arterial média, pressão venosa central, fluxo sangüíneo aórtico e hematócrito; por outro lado, ocorreu diminuição dos fluxos plasmático e sangüíneo renais e aumento da resistência vascular renal. CONCLUSÕES: A efedrina, dependendo da dose utilizada, apresenta ações hemodinâmicas e renais diferenciadas.

DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia

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

The Effects of 6% Hydroxyethyl Starch-Hypertonic Saline in Resuscitation of Dogs with Hemorrhagic Shock

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dexmedetomidine Alters the Cardiovascular Response During Infra-Renal Aortic Cross-Clamping in Sevoflurane-Anesthetized Dogs

Some properties of the volatile anesthetics, such as vasodilatation and myocardial depression, combined with the sympathetic inhibition that alpha 2-agonists can produce may determine hemodynamic alterations during aortic, surgery. The interaction between dexmedetomidine (DEX), an alpha 2-agonist, and sevoflurane during aortic surgery is unknown. We studied the effects of DEX on hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and unclamping (UAox) in sevoflurane-anesthetized dogs Twenty dogs were. anesthetized with sevoflurane and were randomly assigned to two groups prior to Aox and UAox: control, n = 10, received saline infusion only, and DEX (1 mu g.kg(-1) load followed by 1 mu g.kg(-1).h(-1) infusion), n = 10. Hemodynamic and oxygenation variables were measured at baseline, after saline or DEX loading dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX administration, heart rate, cardiac index l and systemic oxygen transport index (131021) were lower than in control group. Aox increased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but the effects were greater with DEX. Cl, heart rate, and DO(2)I were lower, while central venous pressure (CVP) and pulmonary artery occlusion pressure were higher in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs DEX alters the cardiovascular response during aortic surgery.

Maintaining Tissue Perfusion in High-Risk Surgical Patients: A Systematic Review of Randomized Clinical Trials

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Aspectos clínicos e laboratoriais em ovinos submetidos a dietas com níveis elevados de enxofre com objetivo de indução de polioencefalomalácia

A polioencefalomalacia (PEM) é uma doença neurológica que acomete ruminantes e pode ser desencadeada por diversos fatores, dentre eles o consumo excessivo de enxofre. Este trabalho teve como objetivo verificar a relação entre dietas ricas em enxofre, altos níveis de gás sulfídrico ruminal e a ocorrência de polioencefalomalácia em ovinos. Foram utilizados 18 ovinos, divididos em três grupos (G1, G2 e G3) que receberam diferentes níveis de enxofre na dieta; 0,2%, 0,9% e 1,2%, respectivamente. Exames físicos (frequência cardíaca, frequência respiratória, temperatura retal e motricidade ruminal) e complementares (concentração de sulfeto de hidrogênio ruminal, hemogasometria venosa, pH do fluído ruminal, concentração de cobre sérico e hepático, tomografia computadorizada, necropsia e histopatologia) foram realizados. A temperatura retal, a hemogasometria venosa e o pH do fluido ruminal permaneceram dentro dos valores de referência para a espécie. A motricidade ruminal estava diminuída nos grupos G2 e G3 em comparação com o G1 (controle). Quanto maior a ingestão de enxofre, menores foram os níveis de cobre sérico e hepático. Valores elevados de sulfeto de hidrogênio ruminal foram detectados nos grupos G2 e G3. Nenhum animal apresentou sinais clínicos de PEM. Nos exames de tomografia computadorizada, necropsia e exame histopatológico do sistema nervoso central (SNC), não foram observadas alterações compatíveis com PEM. É provável que algum outro fator esteja associado ao excesso de enxofre na dieta para o desenvolvimento de PEM em ovinos.

Comportamento hemodinâmico e metabólico do choque hemorrágico: estudo experimental no cão

JUSTIFICATIVA E OBJETIVOS: Diversos modelos experimentais têm sido utilizados para ilustrar as alterações hemodinâmicas e metabólicas que ocorrem durante o choque hemorrágico. O objetivo da pesquisa é o de observar os comportamentos hemodinâmicos e metabólicos que acontecem em um modelo seqüencial e progressivo de choque hemorrágico no cão, verificando quais índices alteram-se mais precocemente. MÉTODO: O estudo foi realizado em 13 cães sob anestesia venosa total com pentobarbital sódico, em normoventilação e previamente esplenectomizados. Os animais não foram hidratados e a velocidade do sangramento foi ditada pela pressão arterial em que o animal se encontrava. Os atributos estudados foram divididos em hemodinâmicos (freqüência cardíaca - FC, pressão arterial média - PAM, índice de resistência vascular sistêmica - IRVS, índice sistólico - IS, índice cardíaco - IC, índice de choque - I.choque, índice de trabalho sistólico do ventrículo esquerdo - ITSVE, pressão capilar pulmonar - PCP, pressão venosa central - PVC) e metabólicos (saturação venosa mista - SvO2, pressão venosa de oxigênio - PvO2, transporte de oxigênio - DO2, consumo de oxigênio - VO2, extração de oxigênio - TEO2, lactato sérico). A coleta de dados e os atributos foram estudados em 6 momentos distintos, sendo M1, o momento controle e os outros momentos correspondentes a decréscimos gradativos de 10% da volemia calculada para cada animal. RESULTADOS: A hemorragia determinou diminuição significativa da FC somente em M6; queda da PAM, IC, IS e ITSVE a cada momento estudado; discreta alteração da PVC e PCP em cada momento; diminuição da PvO2 e da SvO2 nos momentos estudados; redução do DO2, estabilização do VO2 e elevação da TEO2 nos momentos; o índice de choque apresentou elevação até M3, diminuição em M4 e nova elevação até M6; o IRVS elevou-se até M6, ficou inalterado em M5 e apresentou diminuição significativa em M6; o lactato apresentou elevações a partir de M5 e M6. CONCLUSÕES: Considerou-se que a pressão arterial média, freqüência cardíaca, pressão venosa central e pressão capilar pulmonar não refletem o real estado volêmico dos cães no nosso modelo experimental e que o transporte, consumo e a taxa de extração de oxigênio são parâmetros úteis na determinação da reversibilidade e prognóstico do choque hemorrágico.