Investigations on the new free radical scavenger polynitroxyl-albumin to prevent ischemia and reperfusion injury after orthotopic heart transplantation in the pig model

Objective: Nitroxides have strong antioxidant capacity but their effectiveness is limited by their rapid intracellular inactivation. Poly nitroxyl-Albumin (PNA) is capable of regenerating inactivated nitroxide. We tested the effect of PNA against reperfusion injury in heart transplantation. Methods: Pig hearts were transplanted orthotopically. In the control group (n = 9) reperfusion was performed without reperfusion modifications. In the experimental group (n = 10) 1 ml/kg PNA was given before cross-clamp release. Results: Hemodynamic performance was impaired after transplantation in both groups without significant intergroup differences. Plasma malonedialdehyde levels were significantly diminished in the PNA group as compared to the controls. CK-MB levels in both groups were increased within the first 2 h of reperfusion without significant intergroup differences. In contrast, there were found significant higher values of myocardial specific lactate dehydrogenase (LD1) in the controls versus PNA group. Conclusions: PNA was able to reduce lipid peroxidation and attenuate free radical activity. Contractile dysfunction could no be improved, indicating that (a) the radical scavenging effect was to weak or (b) other mechanisms than free oxygen radicals are responsible for myocardial damage in this experimental model. (C) 2001 Elsevier B.V. B.V. All rights reserved.

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

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

Force patterns of hypoxic myocardium applied to oxygenated muscle preparations: Comparison with effects of regional ischemia on the contraction of non-ischemic myocardium

Objective: To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. Methods: Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. Results: Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. Conclusion: The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.

Effect of α-tocopherol, taurine and selenium on the attenuation of ischemia/reperfusion injury of splanchnic organs

Background: Splanchnic artery occlusion shock is caused by increased capillary permeability and cellular injury precipitated by oxygen derived free radicals following ischemia and reperfusion of splanchnic organs. The purpose of this study was to assess the role of several well-known oxygen- derived free radical scavengers in ameliorating or preventing this syndrome. Study design: Anesthetized rats were subjected to periods of occlusion of the visceral arteries and reperfusion. Tocopherol, taurine, selenium or a 'cocktail' of these three agents was injected subcutaneously for 4 consecutive days prior to operation. Mean arterial blood pressure was measured throughout the experimental period. Fluorometry and technetium-99m pyrophosphate counting of the visceral organs were performed as well as a histologic grading system for intestinal viability. Results: Final mean arterial blood pressure associated with the 'cocktail' and selenium groups was 79.1 ± 27.4 mmHg and 83.6 ± 17.8 mmHg, respectively. These values were significantly higher than the control group, 40.8 ± 11.4 mmHg (P < 0.05). Similar patterns of the benefit of selenium in contrast with the other groups were obtained with fluorescein perfusion, radioisotopic activity and histologic analysis. Conclusion: Pretreatment with selenium of splanchnic ischemia and reperfusion in the rat improves mean arterial blood pressure and microcirculatory visceral perfusion. Further analysis of the precise protective mechanism of selenium for reperfusion injury will enable visceral organs to withstand the consequences of increased capillary leakage and oxidant injury.

Pathophysiology of mesenteric ischemia/reperfusion: a review.

During ischemia, the cell structures are progressively damaged, but restoration of the blood flow, paradoxically, intensifies the lesions caused by the ischemia. The mechanisms of ischemia injury and reperfusion (I/R) have not been completely defined and many studies have been realized in an attempt to find an ideal therapy for mesenteric I/R. The occlusion and reperfusion of the splanchnic arteries provokes local and systemic alterations principally derived from the release of cytotoxic substances and the interaction between neutrophils and endothelial cells. Substances involved in the process are discussed in the present review, like oxygen-derived free radicals, nitric oxide, transcription factors, complement system, serotonin and pancreatic proteases. The mechanisms of apoptosis, alterations in other organs, therapeutic and evaluation methods are also discussed.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (- log EC50) nor maximal responses (Emax) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23 ± 0.06) compared to SD/IR group (7.85 ± 0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75 ± 0.06 and TR/IR: 6.62 ± 0.04) compared to SD/SHAM (7.33 ± 0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place. © 2006 Elsevier Inc. All rights reserved.

Effects of pentoxifylline and n-acetylcysteine on injuries caused by ischemia and reperfusion of splanchnic organs in rats

Aim. Occlusion and reperfusion of splanchnic arteries cause local and systemic changes due to the release of cytotoxic substances and the interaction between neutrophils and endothelial cells. This study evaluated the role of pentoxifylline (PTX) and n-acetylcysteine (NAC) in the reduction of ischemia, reperfusion shock and associated intestinal injury. Methods. Sixty rats were divided into 6 groups of 10 animals. Rats in three groups underwent mesenteric ischemia for 30 minutes followed by 120 minutes of reperfusion, and were treated with saline (SAL-5 mL/kg/ h), pentoxifylline (PTX-50 mg/kg) or n-acetylcysteine (NAC-430 mg/kg/h). The other 3 groups underwent sham ischemia and reperfusion (I/R) and received the same treatments. Hemodynamic, biochemical and histological parameters were evaluated. Results. No significant hemodynamic or intestinal histological changes were seen in any sham group. No histological changes were found in the lung or liver of animals in the different groups. There was a progressive decrease in mean arterial blood pressure, from mean of 111.53 mmHg (30 minutes of ischemia) to 44.30±19.91 mmHg in SAL-I/R. 34.52±17.22 mmHg in PTX-I/R and 33.81±8.39 mmHg in NAC-I/R (P<0.05). In all I/R groups, there was a progressive decrease in: aortic blood flow, from median baseline of 19.00 mL/min to 2.50±5.25 mL/min in SAL-I/ R; 2.95±6.40 mL/min in PTX-I/R and 3.35±3.40 mL/min in NAC-I/R (P<0.05); in the heart rate, from mean baseline of 311.74 bpm to 233.33±83.88 bpm in SAL-I/R, 243.20±73.25 bpm in PTX-I/R and 244.92±76.05 bpm in NAC-I/R (P<0.05); and esophageal temperature, from mean baseline of 33.68°C to 30.53±2.05°C in SAL-I/R, 30.69±2.21°C in PTX-I/R and 31.43±1.03°C in NAC-I/R (P<0.05). In the other hand, there was an attenuation of mucosal damage in the small intestine of the animals receiving PTX, and only in the ileum of the animals receiving NAC. No changes were found in ileum or plasma malondialdehyde levels in any group. Conclusion. PTX was more efficient in reducing histological lesions than NAC, but neither treatment prevented hemodynamic changes during splanchnic organs I/R.

Técnica do grupo focal como método de avaliação do conhecimento de adolescentes sobre saúde bucal

This study aims to the understanding of adolescents regarding oral health, using the Focus Group technique. The study was conducted at three public schools in the city of Araçatuba, São Paulo State, Brazil, with ten students in each. In order to conduct the focus groups, the following words, which featured high error levels, were addressed in survey questions on oral health: oral health; plaque, permanent teeth; fluoride; gum bleeds?; dental floss; transmission of cavities. During the discussions in the focus groups, it was observed that many teenagers were surprised at the situation to which they were submitted and at the topic they were discussing. The word 'oral health' was associated with the condition of cleanliness of the oral cavity, not identifying oral health as part of general health. The term 'transmission of cavities' did not have a sufficient understanding. The term 'permanent tooth' was well understood and was associated with a type of tooth that would not be replaced. The word 'fluoride' had more association with the task of cleaning than protection of the teeth. It is concluded that the use of the focus group technique is of great importance in the interpretation of the knowledge of adolescents on oral health and the appropriateness of the terminology of questionnaires on the same subject.

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

Background: 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. Results: 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. Conclusion: 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. © 2013 Guido et al.; licensee BioMed Central Ltd.

Aplicação da técnica de grupo focal em pesquisa da Rede-SANS sobre as ações de alimentação e nutrição na atenção básica em saúde

Focus groups are seen as important tools in qualitative research for evaluating projects aimed at articulating social networks and movements. Six focus groups were held as one of the stages in research as part of the Food Safety and Sustainable Nutrition Project (SANS). This social network articulates the academic world with social movements and government in defense of the human right to suitable nutrition. This report is aimed at discussing the experience of applying focus groups to the investigation of perceptions by health professionals of activities related to food and nutrition in basic health care. These groups made it possible to bring together 52 professionals from 13 municipalities in the State of São Paulo, Brazil, and they exchanged experiences and debated issues related to food safety in the area of health care. The group discussions identified eating, nutrition vigilance and intersectoriality as emerging topics. The focus group technique proved to be a suitable tool for investigating the topic quickly and in depth, with a large number of professionals working in different contexts. In fact, the discussions went beyond the objectives of the research, since the group work made it possible to strengthen the process of articulation carried out by a network that promoting local measures in food safety and sustainable nutrition.

Evaluation of Renal Protection From High Doses of Melatonin in an Experimental Model of Renal Ischemia and Reperfusion in Hyperglycemic Rats

Background. Melatonin is a free radical scavenger with important actions in the study of renal ischemia and reperfusion (I/R). This study evaluated possible renal protection of high doses of melatonin in an experimental model of I/R in which rats were submitted to acute hyperglycemia under anesthesia with isoflurane.Method. Forty-four male Wistar rats, weighing more than 300 g, were randomly divided into 5 groups: G1, sham (n = 10); G2, melatonin (n = 10; 50 mg.kg(-1)); G3, hyperglycemia (n = 9; glucose 2.5 g.kg(-1)); G4, hyperglycemia/melatonin (n = 10; 2.5 g.kg(-1) glucose + melatonin 50 mg.kg(-1)); and G5, I/R (n = 5). In all groups, anesthesia was induced with 4% isoflurane and maintained with 1.5% to 2.0% isoflurane. Intraperitoneal injection of melatonin (G1, G4), glucose (G3, G4), or saline (G1, G5) was performed 40 minutes before left renal ischemia. Serum plasma values for creatinine and glucose were determined at baseline (M1), immediately following reperfusion (M2), and 24 hours after completion of the experiment (M3). Histological analysis was performed to evaluate tubular necrosis (0-5).Results. Serum glucose was higher at M2 in the groups supplemented with glucose, hyperglycemia (356.00 +/- 107.83), and hyperglycemia/melatonin (445.3 +/- 148.32). Creatinine values were higher at T3 (P = .0001) for I/R (3.6 +/- 0.37), hyperglycemia/melatonin (3.9 +/- 0.46), and hyperglycemia (3.71 +/- 0.69) and lower in the sham (0.79 +/- 0.16) and melatonin (2.01 +/- 1.01) groups, P < .05. Histology showed no necrosis injury in the G1, lesion grade 2 in the G2, and severe acute tubular necrosis in the G3: (grade 4), G4: (grade 5) and G5: (grade 4) groups (P < .0001).Discussion. Melatonin protected the kidneys submitted to I/R in rats without hyperglycemia; however, this did not occur when the I/R lesion was associated with hyperglycemia.Conclusions. Due to its antioxidant and antiapoptotic action, melatonin was able to mitigate, but not prevent acute tubular necrosis in rats with hyperglycemia under anesthesia by isoflurane.

Cord blood cytokine levels in focal early-onset neonatal infection after preterm premature rupture of membranes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Microbial invasion: focal infection and relationship with atherosclerosis

Os extraordinários avanços no desempenho de técnicas laboratoriais corroboram na evolução do entendimento dos mecanismos das doen- ças de modo geral, facilitando o tratamento e/ou a prevenção. De fato, informações equilibradas, acuradas e atuais estão colaborando de forma estimulante no estudo da relação entre doença periodontal e periapical crônica com o desenvolvimento ou estabelecimento de algumas doen- ças cardiovasculares. Dessa forma, o objetivo da presente trabalho foi descrever de forma sucinta e objetiva a relação entre doença periodontal crônica e doença periapical como fatores de risco para o desenvolvimento ou estabeleciomento da aterosclerose. Estudos epidemiológicos têm procurado demonstrar que indivíduos com doença periodontal ou periapical poderiam apresentar um aumento significativo do risco de desenvolver algumas doenças sistêmicas incluindo a aterosclerose.