PURPOSE:To investigate the effects of locally applied simvastatin plus biphasic calcium phosphate (BoneCeramic ® ) or collagen sponge on bone formation in critical-sized bone defects. METHODS:Thirty defects of 5mm in diameter were created bilaterally with a trephine bur in the calvariae of fifteen Wistar rats. The defects were divided into five groups: group 1 -control, no treatment; group 2 (BoneCeramic ® ); group 3 (BoneCeramic ® + 0.1mg simvastatin); group 4 (collagen sponge); and group 5 (collagen sponge + 0.1mg simvastatin). After eight weeks the animals were euthanized and their calvariae were histologically processed. Hematoxylin and eosin-stained sections were subjected to histological and histomorphometrical analyses. The area of newly formed bone was calculated and compared between groups. RESULTS:The greater amount of a bone-like tissue was formed around the carrier in group 3 (BoneCeramic ® + 0.1mg simvastatin)followed by group 2 (BoneCeramic ® ), and almost no bone was formed in the other groups. Group 3 was significantly different compared to group 2, and both groups were significantly different compared to the other groups. CONCLUSION:Simvastatin combined with BoneCeramic ® induced significantly greater amounts of newly formed bone and has great potential for the healing of bone defects.Key words: Simvastatin. Osteogenesis. Calcium Phosphates. Rats. Simvastatin and biphasic calcium phosphate affects bone formation in critical-sized rat calvarial defects

There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the caecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, 1 hr after caffeine administration, the animals were submitted to open-field, elevated plus maze (EPM), forced swimming and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed.

PURPOSE:To analyze the effects of simvastatin (SVT) in the locomotion, anxiety and memory of rats, as a reflection of the administration of a minimum dose capable of stimulating bone regeneration in defects in the calvariae. METHODS:Surgical procedures were performed in 15 female Wistar rats, 2-month old, to insert the grafting material regenerator (Bone-ceramic ® ) and/or SVT, followed by behavioural and cognitive assessments in the 7 th , 30 th and 60 th days post surgery. RESULTS:The SVT locally applied with the goal of bone regeneration in defects created in rat calvariae does not interfere with locomotion, anxiety levels and/or memories of rats, except for the first week following surgery, when an anxiolytic effect was observed, as a result of a possible central action. CONCLUSION:Failure to provoke any response within 30 and 60 days post surgical procedures suggests that SVT may constitute a good choice in stimulating bone regeneration without affecting the long term neural functions.

To evaluate the local effect of simvastatin (SVT) combined with deproteinized bovine bone (DBB) with hydroxyapatite/β-tricalcium phosphate biphasic ceramics (HA/TCP) and with collagen sponge (CS) on bone repair in critical size defects (CSDs) in rat calvaria. Methods: Forty-two 5-mm diameter CSDs were made bilaterally in the calvaria of 18 rats. The animals were allocated according to the type of biomaterial and associations used to fill the CSD. After 8 weeks, the animals were euthanized, and their calvaria were evaluated for repaired tissue composition using histologic and histometric analyses. Results: In the histometric analysis, the use of SVT showed to increase bone formation in the CSDs when combined with all the bone substitutes tested in this study (p<0.05). Greater bone formation was observed in the groups with SVT compared to the groups without SVT. Conclusions: The use of SVT without the need for a vehicle and combined with a commercially available biomaterial may be a cheaper way to potentiate the formation of bone tissue without the need to produce new biomaterials. Therefore, SVT combined with DBB induced significantly greater new bone formation than did the other treatments.