Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Abstract\ud \ud \ud \ud Background\ud \ud Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion.\ud \ud \ud \ud Results\ud \ud The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10.\ud \ud \ud \ud Conclusion\ud \ud Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion.This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 05/56855-8 to A.S.D. and studentship 2007/01874-3 to B.C.G.) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, studentship number 100.042/2008-2 to M.Z.). S.M.O is supported by grants from CNPq (grant numbers 302768/2010-6)

Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

BACKGROUND: \ud Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion.\ud RESULTS: \ud The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10.\ud CONCLUSION: \ud Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinalFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 05/56855-8)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2007/01874-3)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 100.042/2008-2)CNPq (302768/2010-6

The effects of a high-protein diet and resistance training on organ mass and metabolic profile in rats: Os efeitos de uma dieta rica em proteínas e treinamento de resistência sobre a massa dos órgãos e o perfil metabólico em ratos

A high-protein diet associated or not with strength exercise impacts satiety, fat accumulation, mass gain, changes biochemical and morphological. The study evaluated the association between adipose tissue mass and organs, in addition to the blood biochemical profile of rats fed a high-protein diet (HD) submitted to strength training (RT). Adult male Wistar rats were divided into groups (n=7/each): sedentary-normoprotein (SN-14%), sedentary-hyperprotein (SH-35%), trained-normoprotein (TN-14%), and trained-hyperprotein (TH-35%). RT consisted of 4 sets of 10 water jumps/8 weeks. HD and RT reduced the adiposity index (p<0.001). Regardless of HD, RT increased the mass of the gastrocnemius (p<0.001) and soleus (p=0.01). Heart mass was inversely correlated (p<0.01) with retroperitoneal fat. There was an inverse dependence between the mass of the gastrocnemius and retroperitoneal (p<0.01), omental (p<0.05), subcutaneous inguinal (p<0.01), and visceral adiposity (p<0.05). There was a positive dependence between kidney mass and serum creatinine levels (p<0.001). Liver mass showed a positive dependence (p<0.01) on total cholesterol, HDL-c (p<0.01), and triglycerides (p<0.05). The results showed that isolated HD and associated with RT reduced the visceral adiposity, but did not increase the gastrocnemius and soleus mass. The participation of DH and TR stands out as measures of behavior tendency among the studied variables

Dilodendron bipinnatum Radlk. extract alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration, TNF-α and IL-1β concentrations, IL-17 and COX-2 expressions, supporting mucus production and promotes an antioxidant effect.

Ethnopharmacological relevanceDilodendron bipinnatum (Sapindaceae) stem bark decoction and macerate were used to treat uterine inflammation, pain in general, dermatitis and bone fractures. These homemade preparations also have diuretic, stimulant, expectorants and sedative effects and are effective in treating worm infections in the Brazilian Pantanal population. Our previous research confirmed the anti-inflammatory activity of the hydroethanolic extract of inner stem bark of D. bipinnatum (HEDb).AimThis work aimed to investigate the efficacy of HEDb in ameliorating experimental colitis in rats and to elucidate the possible mechanisms involved in the anti-ulcerative colitis properties of HEDb in rats and Caco-2 cell line.Materials and methodsThe effects on cell viability, IL-8 and TNF-α in human colon adenocarcinoma (Caco-2) were determined by flow cytometer and ELISA. Wistar rats (n = 6-7) were orally gavaged with, vehicle (0.9% saline), HEDb at doses of 20, 100 or 500 mg/kg, or mesalazine at a dose of 500 mg/kg, at 48, 24 and 1 h prior to the administration of trinitrobenzene sulfonic acid via rectal administration to induce colitis. The anti-inflammatory effects of HEDb were assessed macroscopically, by myeloperoxidase (MPO) activity and for glutathione (GSH) concentration in the colon. Additionally, colonic histopathological analyses of UC severity were conducted by different staining methods (H&E, PAS and toluidine blue). Pro-inflammatory cytokines TNF-α and IL-1β were quantified in colonic tissue by ELISA and colonic expressions of COX-2 and IL-17 were analyzed by western blotting.ResultsHEDb was shown to be non-cytotoxic with mean viability of 80% in Caco-2 cells. HEDb pre-treatments of 1, 5 or 20 μg/mL significantly reduced TNF-α production in Caco-2 cells by 21.8% (p ConclusionsHEDb reduces colonic damage in the TNBS colitis model and relieves oxidative and inflammatory events, at least in part, by increasing mucus production, reducing leukocyte migration and reducing TNF-α (in vivo and in vitro), IL-1β, IL-17 and COX-2 expression. Therefore, HEDb requires further investigation as a candidate for treating IBD

The putative role of ovary removal and progesterone when considering the effect of formaldehyde exposure on lung inflammation induced by ovalbumin

OBJECTIVE: \ud \ud Formaldehyde exposure during the menstrual cycle is known to affect the course of allergic lung inflammation. Because our previous data demonstrated that formaldehyde combined with an ovariectomy reduced allergic lung inflammation, we investigated the putative role of ovary removal and progesterone treatment when considering the effect of formaldehyde on allergic lung inflammation.\ud \ud METHOD: \ud \ud Ovariectomized rats and their matched controls were exposed to formaldehyde (1%, 3 days, 90 min/day) or vehicle, and immediately after exposure, the rats were sensitized to ovalbumin by a subcutaneous route. After 1 week, the rats received a booster by the same route, and after an additional week, the rats were challenged with ovalbumin (1%) by an aerosol route. The leukocyte numbers, interleukin-10 (IL-10) release, myeloperoxidase activity, vascular permeability, ex vivo tracheal reactivity to methacholine and mast cell degranulation were determined 24 h later.\ud \ud RESULTS: \ud \ud Our results showed that previous exposure to formaldehyde in allergic rats decreased lung cell recruitment, tracheal reactivity, myeloperoxidase activity, vascular permeability and mast cell degranulation while increasing IL-10 levels. Ovariectomy only caused an additional reduction in tracheal reactivity without changing the other parameters studied. Progesterone treatment reversed the effects of formaldehyde exposure on ex vivo tracheal reactivity, cell influx into the lungs and mast cell degranulation.\ud \ud CONCLUSION: \ud \ud In conclusion, our study revealed that formaldehyde and ovariectomy downregulated allergic lung inflammation by IL-10 release and mast cell degranulation. Progesterone treatment increased eosinophil recruitment and mast cell degranulation, which in turn may be responsible for tracheal hyperreactivity and allergic lung inflammationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no.09/51886-3)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no. 2011/51711-9)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP no. 2008/5108-3

Analysis of the lymphocyte cell population during malaria caused by Plasmodium vivax and its correlation with parasitaemia and thrombocytopaenia

Abstract Background The mechanisms of activation and regulation of T lymphocytes and their cytokines in malaria caused by Plasmodium vivax are complex and poorly understood. Previous data suggest that T cells balance protective immune responses with immune mediated pathology in malaria. This study investigates the lymphocytic profile of patients infected with P. vivax by identifying and quantifying the specific sub-populations of Th1, Th2, Th17 and Treg cells and observing the correlation between parasitaemia and the number of platelets. Methods A cross-sectional study was carried out in an endemic area of the state of Acre, Brazil. In order to obtain identification and quantification of lymphocyte sub-populations through flow cytometry, blood samples were collected from 50 individuals infected with P. vivax and 20 non-infected controls. To differentiate Th1 from Th2, the presence of cytokines IL-4 and TNF was examined by enzyme-linked immunosorbent assay. Utilizing the Mann–Whitney and Spearman coefficient tests, comparison and correlation analysis were rendered to test the parasitaemia and the number of platelets relationship. Results The data indicate that individuals infected with P. vivax present a significant reduction in Th1, Th2 and Th17 cell sub-populations when compared to the non-infected control group. A negative correlation exists between parasitaemia and platelet counts in individuals infected with P. vivax. There is no correlation of parasitaemia or thrombocytopaenia with any sub-population of T lymphocytes analysed. Interestingly, patients with serum Th1 cytokine profile present inversely proportional parasitaemia to the increase in the number of Th1, Th2, Th17 and Treg cells while patients with serum Th2 cytokine profile present directly proportional parasitaemia to the increase in number of Th1 and Th2 cells. Regarding the number of platelets, patients with serum Th1 cytokine profile show a correlation directly proportional to the Th17 sub-population. In contrast, platelet counts are directly proportional only to Treg and activated Treg cells in patients with serum Th2 cytokine profile. Conclusions During the P. vivax infection patients with serum Th1 versus Th2 cytokine profile present different biological mechanisms for activating the immune system against parasite load

Frequency and diversity of phlebotomine sand flies (Diptera: Psychodidae) in Sinop, State of Mato Grosso, Brazil

Abstract INTRODUCTION: Understanding the diversity of sand flies is important for the epidemiology and control of leishmaniasis. This study aimed to understand the frequency, diversity, and seasonality of medically important sand flies in the municipality of Sinop, State of Mato Grosso, Brazil. METHODS: The study was conducted in an urban area, including four ecotypes with different levels of urbanization. The sand flies were collected using light traps for three nights per month, from May 2014 to April 2015. RESULTS: A total of 62,745 sand flies was collected, 52.34% of which were female. The frequency and diversity of sand flies was the highest in areas of permanent preservation (APPs) (96.85%), and was lower in more urbanized areas. Lutzomyia dasypodogeton was the most frequent species in the APPs. Lutzomyia antunesi was the most frequent in neighborhoods with forest fragments and neighborhoods around APPs, and L. aragaoi was the most frequent in completely urbanized neighborhoods. A higher frequency and diversity of sand flies was observed in the rainy season (87.92%) than in the dry season (12.08%). Eight medically important species were captured, and Lutzomyia antunesi, which is associated with American cutaneous leishmaniasis and visceral leishmaniasis, was observed in all ecotypes throughout the year. CONCLUSIONS: We observed a high frequency and diversity of sand flies in all urban areas, and some species collected were major vectors of leishmaniasis. These results support the need for further studies of the natural rates of infection of these insects and the circulation of the disease in hosts and vectors

Frequency and diversity of phlebotomine sand flies (Diptera: Psychodidae) in Sinop, State of Mato Grosso, Brazil

Abstract INTRODUCTION: Understanding the diversity of sand flies is important for the epidemiology and control of leishmaniasis. This study aimed to understand the frequency, diversity, and seasonality of medically important sand flies in the municipality of Sinop, State of Mato Grosso, Brazil. METHODS: The study was conducted in an urban area, including four ecotypes with different levels of urbanization. The sand flies were collected using light traps for three nights per month, from May 2014 to April 2015. RESULTS: A total of 62,745 sand flies was collected, 52.34% of which were female. The frequency and diversity of sand flies was the highest in areas of permanent preservation (APPs) (96.85%), and was lower in more urbanized areas. Lutzomyia dasypodogeton was the most frequent species in the APPs. Lutzomyia antunesi was the most frequent in neighborhoods with forest fragments and neighborhoods around APPs, and L. aragaoi was the most frequent in completely urbanized neighborhoods. A higher frequency and diversity of sand flies was observed in the rainy season (87.92%) than in the dry season (12.08%). Eight medically important species were captured, and Lutzomyia antunesi, which is associated with American cutaneous leishmaniasis and visceral leishmaniasis, was observed in all ecotypes throughout the year. CONCLUSIONS: We observed a high frequency and diversity of sand flies in all urban areas, and some species collected were major vectors of leishmaniasis. These results support the need for further studies of the natural rates of infection of these insects and the circulation of the disease in hosts and vectors