INJECTABLE HYBRID SYSTEM FOR STRONTIUM LOCAL DELIVERY TO PROMOTE BONE REGENERATION

In bone tissue regeneration strategies, injectable bone substitutes are very attractive since they can be applied with minimally invasive surgical procedures and can perfectly fill irregular defects created in cases of trauma, infection or tumor resection. These materials must combine adequate mechanical properties with the ability to induce new bone formation. Incorporating strontium (Sr) in bone substitute biomaterials may be a strategy to achieve high Sr concentrations, not in a systemic but in a local environment, taking advantage of the osteoanabolic and anti-osteoclastic activity of Sr, for the enhancement of new bone formation. In this context, the aim of the present work was to evaluate the response of a Sr-hybrid injectable system for bone regeneration, designed by our group, consisting of hydroxyapatite microspheres doped with Sr and an alginate vehicle crosslinked in situ with Sr, in an in vivo scenario. Two different animal models were used, rat (Wistar) and sheep (Merino Branco) critical sized bone defect. Non Sr-doped similar materials (Ca-hybrid) or empty defects were used as control. Sr-hybrid system led to an increased bone formation in both center and periphery of a rat critical sized defect compared to a non Sr–doped similar system, where new bone formation was restricted to the periphery. Moreover newly formed bone was identified as early as one week after its implantation in a sheep model. After eight weeks, the bone surrounded the microspheres, both in the periphery and in the center of the defect. Most importantly, the hybrid system provided a scaffold for cell migration and tissue ingrowth and offered structural support, as observed in both models. The effective improvement of local bone formation suggests that this might be a promising approach for bone regeneration, especially in osteoporotic conditions

Effects of diazoxide in experimental acute necrotizing pancreatitis

OBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt’s scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h

IN VIVO STUDY OF THE EFFECT OF A STRONTIUM-­‐RICH INJECTABLE SYSTEM ON BONE REGENERATION, USING A SHEEP MODEL

Bone has the capacity to regenerate as part of the repair process,being newly formed boné indistinguishable from the adjacente uninjured bone. However,there are cases in which boné regeneration is required in large quantity, beyond the normal potential for self-­‐healing, such as for lesions caused by trauma, infection, tumour resection or cases in which the regenerative process is compromised such as avascular necrosis and osteoporosis. Biomaterials such as alginate are very promising due to its ability to form hydrogels in situ under mild conditions in the presence of divalente cations. The combination with ceramic microspheres results in a mechanically improved injectable system, adequate for minimally invasive procedures. Moreover, the combination with chemical elements such as strontium, described as promoter of boné formation, inhibiting boné resorption provides ion Exchange between the implanted biomaterial and surrounding tissue, enhancing boné regeneration. Our goal is to study in na invivo sheep model, the effect of na injectable system composed of strontium doped hydroxyapatite microspheres, delivered in na alginate vehicle, crosslinked with strontium

Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

AbstractObjective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy

Evidence towards the involvement of nitric oxide in drought tolerance of sugarcane

© 2017 Elsevier Masson SAS Exogenous supply of nitric oxide (NO) increases drought tolerance in sugarcane plants. However, little is known about the role of NO produced by plants under water deficit. The aim of this study was to test the hypothesis that drought-tolerance in sugarcane is associated with NO production and metabolism, with the more drought-tolerant genotype presenting higher NO accumulation in plant tissues. The sugarcane genotypes IACSP95-5000 (drought-tolerant) and IACSP97-7065 (drought-sensitive) were submitted to water deficit by adding polyethylene glycol (PEG-8000) in nutrient solution to reduce the osmotic potential to−0.4MPa. To evaluate short-time responses to water deficit, leaf and root samples were taken after 24h under water deficit. The drought-tolerant genotype presented higher root extracellular NO content, which was accompanied by higher root nitrate reductase (NR) activity as compared to the drought-sensitive genotype under water deficit. In addition, the drought-tolerant genotype had higher leaf intracellular NO content than the drought-sensitive one. IACSP95-5000 exhibited decreases in root S-nitrosoglutathione reductase (GSNOR) activity under water deficit, suggesting that S-nitrosoglutathione (GSNO) is less degraded and that the drought-tolerant genotype has a higher natural reservoir of NO than the drought-sensitive one. Those differences in intracellular and extracellular NO contents and enzymatic activities were associated with higher leaf hydration in the drought-tolerant genotype as compared to the sensitive one under water deficit

Optimal Cutoff Scores for Dementia and Mild Cognitive Impairment in the Brazilian Version of the Montreal Cognitive Assessment among the Elderly

Objective: To propose cutoff scores for the Brazilian version of the Montreal Cognitive Assessment (MoCA-BR) stratified by education in order to detect mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD) in the elderly. Method: A transversal study in health centers was performed on 159 elderly people with 4–12 years of education and 70 of their peers with over 12 years of schooling. The MoCA-BR cutoff scores for screening cognitive impairment were determined based on an ROC curve analysis. Results: The ROC curve analysis indicated that cutoff scores under 20 were good for screening elderly people with cognitive impairment with more than 12 years of education, and scores under 21 were good for screening those with 4–12 years of education. Conclusions: MoCA-BR scores under 21 points (after adding 1 point to the elderly with ≤12 years of education) indicate a need to continue the diagnostic investigation with regular follow-ups