Polygala anatolica Boiss. et Heldr.: is a potential remedy for inflammation and pain? / Polygala anatolica Boiss. et Heldr.: ¿es un remedio potencial para la inflamación y el dolor?

Species of Polygala genus have been used for the treatment of inflamation and pain in Turkish traditional medicine. The aim of the present study is to assess the anti-inflammatory and analgesic activities of P. anatolica. n-Hexane, ethyl acetate and methanol extracts of the aerial parts and roots of P. anatolica were investigated for their anti-inflammatory and analgesic effects. The methanol extracts prepared from the aerial parts and roots of P. anatolica were found to be active in carrageenan- and PGE2-induced paw edema models and in Whittle method. Methanolic extract of the aerial part inhibited serotonin-induced hind paw edema, while the root extract did not exert inhibitory effect in the same model. In addition, Fr. B and C obtained from the methanol extract of P. anatolica aerial parts showed significant anti- inflammatory activity. Morover, the analgesic effect of the methanol extracts prepared from the roots and aerial parts and Fr.B and Fr.C were found to be statistically significant without inducing ulceration. The methanol extract obtained from the aerial parts of the plant and its saponoside and flavonoid fractions showed anti-inflammatory and analgesic activities in the trials.

Las especies del género Polygala se han utilizado para el tratamiento de la inflamación y el dolor en la medicina tradicional turca. El objetivo del presente estudio es evaluar las actividades antiinflamatorias y analgésicas de P. anatolica. Se investigaron los extractos de n-hexano, acetato de etilo y metanol de las partes aéreas y raíces de P. anatolica por sus efectos antiinflamatorios y analgésicos. Los extractos de metanol preparados a partir de las partes aéreas y raíces de P. anatolica se encontraron activos en modelos de edema de pata inducidos por carragenina y PGE2 por el método de Whittle. El extracto metanólico de la parte aérea inhibió el edema de la pata trasera inducido por serotonina, mientras que el extracto de raíz no ejerció un efecto inhibidor en el mismo modelo. En suma, la fracción B y C obtenidos a partir del extracto metanólico de partes aéreas de P. anatolica mostraron actividad antiinflamatoria significativa. Además, el efecto analgésico de los extractos de metanol preparados a partir de las raíces y las partes aéreas y la fracción B y C resultaron ser estadísticamente significativas sin inducir la ulceración. El extracto de metanol obtenido de las partes aéreas de la planta y sus fracciones de saponósidos y flavonoides mostraron actividades antiinflamatorias y analgésicas en los ensayos.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

Effect of rhubarb on extravascular lung water in patients with acute respiratory distress syndrome

Summary Objective: The aim of this study was to evaluate the effect of rhubarb on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). Method: A total of 80 patients with ARDS were randomly divided into a treatment group (40 cases) and control group (40 cases). Patients in the treatment group received rhubarb (30.0 g/d) and patients in the control group received conventional therapy for seven consecutive days. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were determined using pulse contour cardiac output (PiCCO) technology, and the oxygenation index was measured by blood gas analysis at baseline and on days 3, 5 and 7 after treatment. Results: The oxygenation index was higher and the levels of EVLWI and PVPI were lower after treatment in the two groups; however, these indexes showed significant differences on the 5th and 7th days after rhubarb treatment compared with the results in the control group (p<0.05). Conclusion: Rhubarb can decrease EVLWI and PVPI, and improve oxygenation in patients with ARDS.

Mechanisms of the beneficial effect of sevoflurane in liver ischemia/reperfusion injury

PURPOSE: To evaluate the underlying mechanisms by which sevoflurane protects the liver against ischemia/reperfusion injury evaluate the mechanism by which sevoflurane exerts this protective effect. METHODS: Twenty-six rats were subjected to partial ischemia/reperfusion injury for 1h: one group received no treatment, one group received sevoflurane, and sham group of animals received laparotomy only. Four hours after reperfusion, levels of alanine and aspartate aminotransferases, tumor necrosis factor-a, and interleukins 6 and 10 were measured. Analyses of mitochondrial oxidation and phosphorylation, malondialdehyde content, histology, and pulmonary vascular permeability were performed. RESULTS: Serum levels of alanine and aspartate aminotransferases were significantly lower in the sevoflurane group compared to untreated controls (p<0.05). The sevoflurane group also showed preservation of liver mitochondrial function compared to untreated controls (p<0.05). Sevoflurane administration did not alter increases in serum levels of tumor necrosis factor-a, and interleukins 6 and 10. Sevoflurane treatment significantly reduced the coagulative necrosis induced by ischemia/reperfusion (p<0.05). Pulmonary vascular permeability was preserved in the sevoflurane group compared to untreated controls. CONCLUSION: Sevoflurane administration protects the liver against ischemia/reperfusion injury, via preservation of mitochondrial function, and also preserves lung vascular permeability.

Effects of sevoflurane on tight junction protein expression and PKC-alpha translocation after pulmonary ischemia-reperfusion injury

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-alpha after ischemia-reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev-IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-alpha in the lung. Lung permeability was significantly increased after ischemia-reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-alpha. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-alpha, which also contributed to the lung-protective effect of sevoflurane.

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability.

Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

Cariniana rubra Miers (Lecythidaceae), popularly known as "jequitibá-vermelho'', is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EM Cr) using experimental animals. Anti-inflammatory activity of EM Cr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EM Cr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception.Phytochemical analysis with EM Cr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (β-sitosterol, stigmasterol), pentacyclic triterpenes (α- and β-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-β-D-glucopyranoside), and triterpenoid saponins (28-β-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-β-glucopyranosyl arjunolic acid and 28-O-[α-L-Rhamnopyranosyl-(1→2)-β-glucopyranosyl]-23- O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EM Cr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation.

Cariniana rubra Miers (Lecythidaceae), popularmente conhecido como "jequitibá-vermelho'', é uma árvore brasileira de grande porte, cuja casca é utilizada nas formas de infusão e decocção para o tratamento de condições inflamatórias. Os efeitos antiinflamatório, antinociceptivo e antipirético do extrato metanólico da casca do caule de Cariniana rubra (EM Cr) foram avaliados em animais experimentais. A atividade antiinflamatória do EM Cr foi testada nos modelos de edema depata induzido por carragenina e dextrana em ratos, pleurisia induzida por carragenina em ratos e permeabilidade vascular aumentada por ácido acético em ratos. As atividades antinociceptiva e antipirética foram avaliadas utilizando os modelos de nocicepções induzidos por ácido acético e formalina, placa quente em camundongos e de pirexia, pela injeção de levedura de cerveja em ratos. O extrato inibiu o edema induzido porcarragenina e dextrana, reduziu o volume de exsudato e a migração de leucócitos na pleurisia induzida por carragenina eo aumento da permeabilidade vascular induzida por ácidoacético. O EM Cr inibiu a nocicepção nas contorções induzidas por ácido acético e na segunda fase do teste de formalina e diminuiu a temperatura retal. No entanto, foi inefetivo no teste da placa quente. A análise química por via úmida deu resultados positivos para saponinas, triterpenos, esteroides e compostos fenólicos. Fitosteróis e triterpenóides pentacíclicos (β-sitosterol, estigmasterol, α and β-amirinas em mistura e ácido arjunólico) e as saponinas triterpenoidais: 3-O-β-D-glucopiranosideo de sitosterol; ácido arjunólico 28-β-glucopiranosila-23-O-acetila; ácido arjunólico 3-O-β-glucopiranosila e ácido arjunólico 28-O-[α-L-rhamnopiranosil-(1→2)-β-D-glucopiranosila]-23-O-acetila. Pode-se presumir que os efeitos do EM Cr foram causados pela inibição da liberação e/ou ação de diversos mediadores inflamatórios. Estes resultados validam o uso tradicional das preparações caseiras de Cariniana rubra para tratar a inflamação.

Side effects of cyclosporine-A treatment in rats: gingival overgrowth and early hyperglycemia

Gingival overgrowth is an adverse side effect of cyclosporine A (CsA) in the treatment of transplanted patients. The purpose of this study was to evaluate the effects of CsA on new-onset diabetes mellitus and gingival overgrowth in rats, by measuring collagen, nitric oxide and microvascular permeability. Blood glucose level, collagen, nitric oxide level and vascular permeability were determined. Blood glucose level increased significantly from 6.5 +/- 0.9 for the control group to 15+/- 1.2, 17 +/- 1.2 and 21.6+/- 1.6 mM/L at 1, 4 or 8 weeks of CsA treatment, respectively. Collagen (ug HO Proline/mg p) increased significantly from 2.5+/- 0.5 for the control group to 4.2+/- 0.8, 5.9+/- 0.6 and 7.3 +/- 0.8 at 1, 4 or 8 weeks of CsA treatment, respectively. Vascular permeability was 10.3+/- 1.2 for the control group and 15+/-1; 17.2 +/- 1.3, and 22.1+/- 2.1 ug EB/g T; at 1, 4 or 8 weeks of CsA treatment, respectively. Nitric oxide level was 3.5 +/- .9 umol/mg P for the control group and 4+/- 0.2, 8.2+/- 0.9 and 11+/-1 for 1, 2 or 8 weeks of CsA treatment, respectively. These findings appear to indicate that the development of significant gingival changes induced by CsA is related to new-onset of diabetes mellitus during the immunosuppressive treatment.

La hiperplasia gingival es un efecto colateral adverso del tratamiento con ciclosporina A (CsA) en pacientes transplantados. El proposito de este estudio fue evaluar el efecto de CsA en el inicio de diabetes mellitus, la concentracion de colageno, y de oxido nitrico y la permeabilidad capilar gingival. El nivel de glucosa en sangre de los animales controles fue: 6.5+/- 0.9, en tanto que los tratados con CsA fue: 15+/-1.2; 17+/- 1.1 y 21.6+/- 1.6 mM/L a las 1, 4 y 8 semanas respectivamente. El colageno (ug OH prolina/mg p) mostro un aumento significativo en los animales tratados con CsA respecto de los controles: 2.5+/- 0.5; 4.2+/- 0.8; 5.9+/- 0.6; 7.3+/- 0.8 respectivamente a las 1,4 y 8 semanas de tratamiento. Los valores de permeabilidad capilar (ug AE/ g T) fueron: en los animales control 10.3+./- 1.2; en los animales tratados con CsA, a las 1, 4 y 8 semanas 15+/- 1.0; 17.2 +/- 1.3 y 22.1+/- 2.1 respectivamente. Los valores de oxido nitrico (umol/mg p) en los animales control: 3.5+/-0.9; y en los animales tratados con CsA 4+/- 0.2; 8.2+/- 0.9 y 11.2 +/- 1.0 respectivamente. Estos resultados parecen indicar que el desarrollo de los significativos cambios gingivales inducidos por la administracion de CsA esta relacionado con la hiperglucemia temprana que se asocia al tratamiento con inmunosupresores.

The Effect of Intravitreal Bevacizumab in Patients with Acute Central Serous Chorioretinopathy

PURPOSE: To evaluate the effect of intravitreal bevacizumab injection (IVBI) in acute central serous chorioretinopathy (CSC) patients. METHODS: Patients with acute CSC received IVBI (1.25 mg/0.05 mL) or observation by randomization. Twelve eyes in each group completed 6 months of regular follow-up and were ultimately included in this study. Each patient was assessed using best corrected visual acuity measurements, fluorescein angiography, and optical coherence tomography at baseline and had regular follow-ups after treatment. RESULTS: All patients showed improvements in visual acuity and fluorescein angiographic leakage and had resolution of their neurosensory detachment following treatment. There were no significant differences in visual acuity, central retinal thickness, or remission duration between the IVBI group and the control group at baseline or after treatment (p>0.05). CONCLUSIONS: Intravitreal bevacizumab showed no positive effect in acute CSC patients compared to the observation group, and there were no adverse effects of treatment. Further investigation will be helpful to understand this therapy in patients with CSC.

The Anti-angiogenic Effect of Chlorogenic Acid on Choroidal Neovascularization

PURPOSE: To evaluate the inhibitory effect of chlorogenic acid on laser-induced choroidal neovascularization (CNV) in a rat model. METHODS: Intraperitoneal injection of chlorogenic acid (10 mg/kg) was inititated one day prior to laser photocoagulation and continued for eight days. Eyes were removed 14 days after laser photocoagulation. Fluorescein angiography was employed at seven and 14 days to assess the CNV lesions, and histological examination was performed. Quantification of CNV size and leakage were performed both in histological sections and fluorescein angiography in order to compare the inhibitory effects of chlorogenic acid on CNV with the results of the control. RESULTS: Histological analysis showed no significant difference in CNV size between the treated and control groups. However, CNV leakage on fluorescein angiography had significantly decreased in the chlorogenic acid-treated group at 14 days after laser photocoagulation compared with that of the control group. In addition, CNV size on fluorescein angiography had significantly decreased in the treated group at seven and 14 days. CONCLUSIONS: These results suggest that chlorogenic acid has anti-angiogenic effects on CNV and may be useful as an inhibitor in the treatment or prevention of neovascular age-related macular degeneration.

Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1 beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1 alpha) and NF-kappa B in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kappa B and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.

The Steroid Effect on the Blood-Ocular Barrier Change Induced by Triolein Emulsion as seen on Contrast-Enhanced MR Images

OBJECTIVE: The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. MATERIALS AND METHODS: An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. RESULTS: Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). CONCLUSION: Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.

Efeito protetor de antagonista das gliproteínas IIb/IIa nas alterações hepáticas e pulmonares secundárias à isquemia e reperfusão do fígado em ratos / Protective effects of an inhibitor of glycoprotein IIb/IIIa in the hepatic and pulmonary disturbances secondary to ischemia and reperfusion injury of rat’s liver

RACIONAL: A lesão de isquemia e reperfusão hepática é um evento comum e responsável por considerável morbidade e mortalidade. OBJETIVO: Avaliar efeitos de inibidor da glicoproteína IIb/IIIa, cloridrato de tirofiban, nas alterações hepáticas e pulmonares da lesão de isquemia e reperfusão de fígado de ratos. MÉTODO: Vinte e três ratos Wistar divididos em três grupos: laparotomia (n = 6), isquemia e reperfusão que receberam solução fisiológica (n = 8), e submetidos a isquemia e reperfusão e tratados com o cloridrato de tirofiban (n = 9). Foram realizadas dosagens das aminotransferases e análise histológica hepática. Avaliação pulmonar foi realizada pelo teste do azul de Evans e pela dosagem tecidual da mieloperoxidase no parênquima pulmonar. A oxidação e fosforilação mitocondrial das células hepáticas também foram avaliadas. RESULTADOS: O grupo tratado com cloridrato de tirofiban apresentou menores níveis de aminotransferases, assim como alterações histológicas menos intensas. Avaliação pulmonar demonstrou diminuição no teste de azul de Evans no grupo tratado com cloridrato de tirofiban. Grupo tratado com cloridrato de tirofiban apresentou aumento significativo do estado 3 da respiração mitocondrial e das relações adenosina difosfato utilizado para fosforilação sobre o oxigênio consumido na reação e de coeficiente respiratório. CONCLUSÕES: O uso do cloridrato de tirofiban exerceu papel protetor da lesão hepática de isquemia e reperfusão e impediu o aumento da permeabilidade vascular secundária à lesão de reperfusão hepática.

BACKGROUND Hepatic ischemia-reperfusion injury is responsible for a considerable morbidity and mortality. Aim - To evaluate the effect of a platelet glycoprotein IIb/IIIa receptor inhibitor (tirofiban) on hepatic and pulmonary disturbances associated with hepatic ischemia-reperfusion injury. METHODS: Twenty-three Wistar rats divided in three groups: rats sham-operated (n = 6), rats submitted to ischemia-reperfusion that received saline solution (n = 8), and rats submitted to ischemia-reperfusion treated with 0.7 mg/kg of tirofiban (n = 9). Serum aminotransferases (AST and ALT) were also determined, and the study of hepatic tissue histology was carried out. The evaluation of the pulmonary disturbances was done using the Evans blue test and the tissular determination of myeloperoxidase. Hepatic mitochondrial oxidation and phosphorylation were also measured. RESULTS: There was an increase in the state 3 respiration, ADP/O ratio and respiration control rate in the group treated with tirofiban. This group had also lower levels of aminotransferases and the histological findings were significantly less intense. Pulmonary evaluation demonstrated decrease of the Evans blue test in the tirofiban group and an increase of its tissular determination of myeloperoxidase. CONCLUSION: The inhibition of glycoprotein IIb/IIIa receptor with tirofiban protected the hepatic disturbances and prevented the increase of pulmonary vascular permeability secondary to the ischemia-reperfusion injury of the liver.

An antioxidant modulates expression of receptor activator of NF-kappaB in asthma

Oxidative stress plays critical roles in airway inflammation that is usually accompanied by increased vascular permeability and plasma exudation. VEGF increases vascular permeability and leads to airway inflammation. In addition, VEGF has been shown to enhance receptor activator of NF-kappaB (RANK) expression in endothelial cells. An aim of the study was to determine the potential role of antioxidant in the regulation of RANK expression in murine model of asthma. We have used a C57BL/6 mouse model of allergic asthma to evaluate the effect of L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, which acts as an antioxidant, and VEGF receptor inhibitor on RANK mRNA expression. The mice develop the following pathophysiological features of asthma in the lungs: increased expression of RANK mRNA, increased number of inflammatory cells of the airways, increased vascular permeability, and increased levels of VEGF. Administration of OTC and VEGF receptor inhibitor markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that the increased RANK mRNA expression at 72 h after ovalbumin inhalation were reduced by the administration of OTC or VEGF receptor inhibitor. The results indicate that OTC and VEGF receptor inhibitor which inhibit up-regulation of VEGF expression modulate RANK expression that may be in association with the regulation of vascular permeability, and suggest that VEGF may regulate the RANK expression. These findings provide a crucial molecular mechanism for the potential use of antioxidants to prevent and/or treat asthma and other airway inflammatory disorders.

Effect of anticholinesterase compound phosalone on blood-brain barrier (BBB) permeability.

To elucidate the role of acetylcholinesterase (AChE) enzyme in BBB function, phosalone, an organophosphorous compound, was studied using rat brain micro vessels in vitro. Phosalone at 100 mg/kg b. wt. induced convulsions and caused a significant inhibition of AChE resulting in increased permeability as assessed by volume distribution. The anaesthetized phosalone treated group also increased permeability as compared to the control but the values were significantly (P<0.05) lower than phosalone alone treated group. The inhibition of AChE enzyme has altered the barrier function at the dose level at which it caused convulsion and had an added effect on permeability of BBB.

Biocompatibility of EDTA, EGTA and citric acid

Este estudo in vivo avaliou o potencial irritativo do EDTA, EGTA, ácido cítrico e soro fisiológico (controle) durante a fase exsudativa do processo inflamatório. Aplicou-se, intravenosamente na veia caudal lateral de 32 ratos machos da linhagem "Wistar", variação albina, 20 mg/kg de azul de Evans 2%. Em seguida, no tecido subcutâneo da região dorsal dos animais injetou-se 0,01 mL das soluções testes. Após os intervalos de ½, 1, 3 e 6 horas, os animais foram sacrificados, suas peles dorsais foram excisadas e submetidas à análise do corante extravasado pela espectrofotometria de absorção de luz. Os dados obtidos foram avaliados pela análise de variância a 2 critérios e teste de Tukey. Em todos os períodos de tempo estudados, os maiores valores de corante extravasado foram observados no grupo do EDTA seguido pelos grupos do EGTA e ácido cítrico, em comparação ao grupo controle. Houve diferença estatisticamente significante entre todas as soluções testadas (p<0.01). Quando considerado o fator tempo, notou-se diferença significante entre os grupos de 3 e 6 horas (p<0.05). Entretanto, não houve diferença entre os grupos de tempo de ½ e 1 hora. Dentre os ácidos orgânicos avaliados, os resultados demonstraram que o ácido cítrico apresentou o menor potencial irritativo.

Polylactic acid nanoparticles targeted to brain microvascular endothelial cells / 华中科技大学学报（医学）（英德文版）

In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.

Ascorbic acid improves vascular permeability in experimental-induced diabetic rats

The most devastating manifestations of diabetes mellitus are vascular complications. Although there are many factors involved in the pathogenesis of diabetic vasculopathy, many studies suggest a role for glucose-induced oxidative stress. Studies in animal models, have demonstrated that the administration of antioxidants restores normal endothelial functions. The study was designed to examine the possible beneficial effects of ascorbic acid, which have antioxidant properties, on vascular permeability in the duodenum of rats with streptozotocin-induced diabetes. Female adult rats were divided into two control and three diabetic groups. Diabetes was induced by a single injection of streptozotocin [55 mg/kg, ip]. One control and two diabetic groups received ascorbic acid in drinking water [800 mg/kg]. Diabetic groups received ascorbic acid either as therapeutic for 4 weeks, starting after the induction of diabetes or as combination therapy for 8 weeks starting 3-4 weeks before the induction of diabetes. Vascular permeability was estimated by measuring the extravasations of Evans blue dye and water content of duodenal tissue. As compared to the control group, diabetic animals significantly increased both Evans blue extravasations and water content by 202%. Ascorbic acid, used as treatment or in combination therapy, similarly restored these two variables to normal level. The findings of this study suggest that ascorbic acid might have a role in restoring some dysfunctions of experimental diabetes

Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil.

To examine the association of intestinal barrier function with vitamin A deficiency and whether supplementation of micronutrients improves intestinal function and/or linear growth, height-for-age z-score (HAZ), concentrations of serum retinol and zinc, and intestinal permeability were determined in a cross-sectional sample of 75 children in northeastern Brazil. Effects of vitamin A and supplementation of zinc on intestinal permeability and growth were also determined comparing results before and after treatment in 20 children and age-matched controls. Lactulose:mannitol (L/M) permeability ratios inversely correlated with serum retinol concentrations (r = -0.55, p < 0.0005). Increased L/M permeability ratios with reduced concentrations of serum retinol were predominantly attributable to lower absorption of mannitol (r = 0.28, p = 0.02). L/M permeability ratios (p = 0.001) and HAZ scores (p = 0.007) improved with supplementation. It is concluded that impaired intestinal barrier function and linear growth shortfalls improve following supplementation of vitamin A and zinc in this setting.

Effect of dental adhesives on the exudative phase of the inflammatory process in subcutaneous tissue of rats

The vascular changes in the subcutaneous connective tissue of rats induced by dentin bonding systems (one step) was studied and compared to those induced by saline solution (negative control) and Furacin (positive control), during the exudative phase of the inflammatory process. Twenty mg/kg of Evan's blue were injected intravenously in the vein of the rats' penises; 0.1 ml of each substance tested was inoculated in the subcutaneous tissue. After a 3 hour period the animals were sacrificed and their skins were excised and punched out with a standard steel 2.5 cm in diameter. The specimens were immediately immersed in 8 ml of formamide and taken to a double boiler for 72 hours at 37ºC, to remove the dye. The liquid containing the overflowed dye was filtered, analyzed in the spectrophotometer (620 nm) and classified according to the criteria established by Nagem-Filho, Pereira (1976). After statistical analysis, the irritative potential of the substances was ranked as follows: Furacin (severe) > Single Bond and Bond 1 (moderate - no significant differences between the dentin bonding systems tested) > saline solution (not significant as regards the irritation degree)