Maria Fernanda Torres

Preparation, characterization and in vitro evaluation of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microspheres.

BACKGROUND AND OBJECTIVES: Microspheres can be used as a controlled delivery system to prolong the duration of action of local anesthetics. The objective of this study was the preparation, characterization and analysis of the in vitro release of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microspheres. METHODS: Microspheres were prepared using the copolymer of polylactide-co-glycolic acid by the spray-dryed method. RESULTS: Characterization of microspheres regarding their size and content were similar to the theoretical values. The in vitro release demonstrated a biphasic pattern. CONCLUSIONS: Manufacturing of 50% enantiomeric excess bupivacaine-loaded microspheres by the spray-dryed method with results similar to bupivacaine-loaded microspheres can be done.

Effect of fractionated radiotherapy on the parotid gland: an experimental study in Brazilian minipigs

Summary Introduction: Radiotherapy (RT) of head and neck neoplasms often damages the salivary glands. Aim: To examine the pattern of morphologic changes resulting from RT of the head and neck region in minipig parotid glands in a clinical and experimental research setting. Methods: Twelve 18-month-old male Brazilian minipigs weighing 30–40 kg were selected. Eight minipigs were assigned to the experimental group (group 1) and 4 to the control group (group 2). The RT was performed under general anesthesia at Erasto Gaertner Hospital, Curitiba, Brazil, using an á/â ratio of 2.5. The minipigs from group 1 underwent 3 sessions of irradiation with Cobalt 60 of the head and neck, bilaterally, with 3 exposures of 8 Gy each at 7-day intervals for a total dose of 24 Gy. The animals were sacrificed 12 weeks post-RT. Results: The irradiated parotid glands displayed reductions in the size and number of acini as well as loss of secretory granules. The presence of fibrosis and loss of parenchyma relative to non-irradiated glands were observed, with an average reduction in volume of 54%. Conclusions: Our results demonstrate that this model for parotid gland damage resulting from an RT regimen appears to be useful for preclinical large animal studies of RT-induced damage and testing novel potential treatment options. Although recent advances in radiation therapy, such as intensity-modulated radiation therapy, have reduced the dose and limited the field of radiation, considerable salivary gland injury still occurs and can greatly impact the patients quality of life after cancer treatment.

Hypolipidemic and Antiatherosclerotic Potential of Pleurotus ostreatus, Cultived by Submerged Fermentation in the High-fat Diet Fed Rats

The ability of Pleurotus ostreatus biomass, cultived by submerged fermentation, to produce beneficial effect on lipid profile and macrophages activity during a high-fat diet (HFD) for a long-term intake was investigated. Blood samples were collected through cardiac puncture to measure the plasma cholesterol, triglycerides, low-density protein (LDL), high-density protein (HDL), aspartate aminotransferase (AST) activity, urea-blood urea nitrogen (BUN)/creatinine ratio of rats fed on an HFD for 4 months. Dosage of lipid hydroperoxides was carried out on methanolic extract of liver tissue. Peritoneal macrophages activity was evaluated in relation to the superoxide anion, hydrogen peroxide and nitric oxide production, phagocytosis and lysosomal volume. The administration of P. ostreatus significantly altered the lipid profile and oxidative stress as related to the LDL and triglycerides decrease and inhibitory effects on superoxide anion and hydrogen peroxide production. All findings of this study lead us to suggest that the P. ostreatus maybe a beneficial agent in the hyperlipidemia and atherosclerosis treatments.

Effect of radiotherapy on osseointegration of dental implants immediately placed in postextraction sites of minipigs mandibles.

Introduction: The aim of this study was to compare the osseointegration and the survival of dental implants (DIs) immediately placed in postextraction sites, in mandibles of minipigs that underwent radiotherapy (RT). Materials and Methods: Twelve Brazilian minipigs were divided into the following groups: A, control; B, implants placement 15 days before RT; C, implants placement 3 months after RT. Implant loss rate (ILR), fibrointegration rate (FIR), bone-implant contact (BIC), and bone density inside the threads (BDIT) were determined in each group 90 days after implantation. Results: ILR was higher in group C (68.7%) than in groups B (28.1%) and A (21.9%), (P = 0.001). FIR was more frequent in group C (30%) than in groups B (21.7%) and A (4%), although not statistically significant. The averages of BIC and BDIT were, respectively, 33.1 and 41.5 in group C; 18.5 and 26.6 in group B; and 11.5 and 16.3 in group A (P = 0.003 for both variables). Conclusions: RT showed a negative effect in periimplant bone regeneration. The implants placement before RT showed better results compared with the implants performed after RT, suggesting that DIs in head and neck cancer patients must be placed before RT or simultaneously during ablative tumor surgery.

Analysis of the Acute Cytotoxic Potential of Bupivacaine and 50% Enantiomeric Excess Bupivacaine (S75-R25) Incorporated into Microspheres in Rat Sciatic Nerves

BACKGROUND AND OBJECTIVES The duration of Local Anesthetic (LA) effects can be expanded by its incorporation into systems of sustained release microspheres. However, the possibility that LA sustained release systems are neurotoxic has not received due attention in literature. The objective of this study was to investigate the effects of pure microspheres of poly(lactic-co-glycolic acid), filled with 50% enantiomeric excess bupivacaine or bupivacaine (BP), as well as the effects of 50% enantiomeric excess bupivacaine in the sciatic nerve of Wistar rats. METHODS The rats were allocated into four groups according to the evaluation time (two, four, six, and eight days) and nominated according to the injected solution on the sciatic nerve: Microspheres with 50% Enantiomeric excess Bupivacaine (MEB), Microspheres with Bupivacaine (MB), Pure Microspheres (PM), and 50% Enantiomeric excess Bupivacaine (EB). RESULTS In semi-fine histologic sections, no regular homogeneous distribution of collagen fibers in the endoneurium or degenerative changes of axons and myelin sheaths were observed. In ultrathin sections, we found myelinated axons and normal Remak fibers with axoplasm showing homogeneous distribution of neurofilaments and microtubules. Histomorphometric analysis of axons revealed no significant difference between the axon diameters of the studied groups.

Association between decrease in salivary iron levels and caries experience in children

OBJECTIVE: Human saliva has numerous components that are important for maintaining oral health. We investigated the association between iron levels in saliva in children and their caries experience. METHODS: We conducted a case-control study that included 186 healthy children, aged 11-14 years. The decayed-filled teeth/decayed-missing-filled teeth (DMFT) score was estimated according to the Brazilian Oral Health Project. The children were divided into two groups: caries-free group (DMFT=0, n=55) and caries experience group (DMFT≥1, n=131). Saliva was collected from each child using the spitting method and analyzed for stimulated saliva flow (SSF), pH, and iron levels. The SSF, pH, and salivary iron levels were analyzed for statistical assumptions of normality and homoscedasticity and compared between groups. All of the statistical tests were performed using R and SPSS software, with a level of significance of 0.05. RESULTS: No statistically significant differences in mean pH were found between groups (t=-0.0488, p=0.51). Children with caries experience had significantly lower salivary iron levels than caries-free children (w=5088, p<0.0001). The SSF values were significantly different between children with caries experience and children without caries (w=4198, p=0.03). CONCLUSION: Salivary iron levels were significantly lower in children with dental caries experience, suggesting that salivary iron plays a role in maintaining oral health.

Immediate postoperative evaluation of enteric anastomosis after the use of meloxicam in rats

PURPOSE To compare ileal anastomoses in the immediate postoperative healing period after meloxicam use. METHODS Forty two male Wistar rats were randomly divided into two groups of 21, COX and control group. To COX meloxicam in combination with morphine was given in 3 days period. Control group received only morphine during the same period. Each group was divided into three sub-groups of 7, which were euthanized at 5, 10, and 21 days postoperatively. Comparison was based in histological evaluation of collagen type I and III using sirius red, immunohistochemical through vascular endothelial growth factor and matrix metalloproteinase-9. RESULTS Healing process in scheduled periods did not show significant differences (p>0.05) between the COX and control groups during any of the periods. CONCLUSION The use of meloxicam in the postoperative period following ileal anastomosis did not affect healing.

Cordyceps sinensis biomass produced by submerged fermentation in high-fat diet feed rats normalizes the blood lipid and the low testosterone induced by diet

This study investigated the effect of Cordyceps sinensis biomass supplementation obtained from submerged fermentation on blood lipid and low testosterone induced by high-fat diet (HFD). The experiments were carried out using a long-term intake of HFD and HFD plus Simvastatin or C. sinensis (4 months). Our results show that plasma cholesterol, triglycerides and LDL were decreased by Cordyceps sinensis biomass supplementation (CSBS). A long-term intake of HFD caused a significant liver damage which has been reverted by CSBS. CSBS normalized decreasing testosterone levels observed in high-fat diet feed rats. All these findings lead us to suggest that C. sinensis was able to decrease blood lipid concentration, increase hepatoprotective activity and normalize testosterone levels.

Análise do potencial citotóxico agudo da bupivacaína e bupivacaína em excesso enantiomerico de 50% (S75-R25) incorporadas a microesferas sobre o nervo ciático de ratos

JUSTIFICATIVA Y OBJETIVOS: La duracion del efecto de los anestesicos locales (AL), puede ser ampliada por su incorporacion a los sistemas de liberacion prolongada como microesferas. Sin embargo, la posibilidad de que los sistemas de liberacion prolongada de AL sean neurotoxicos, no ha recibido la debida atencion en la literatura. Este estudio tuvo el objetivo de investigar los efectos de microesferas de acido polilactico-co-glicolico puras, rellenados con bupivacaina en exceso enantiomerico de 50% o con bupivacaina (BP), como tambien los efectos de la bupivacaina en exceso enantiomerico de 50% en nervio ciatico de ratones Wistar. METODO: Los ratones se dividieron en cuatro grupos de acuerdo con el tiempo de evaluacion (dos, cuatro, seis y ocho dias), y fueron denominados conforme a la solucion inyectada sobre el nervio ciatico: microesferas con bupivacaina en exceso enantiomerico de 50% (MBE), microesferas con bupivacaina (MB); microesferas puras (MP) y bupivacaina en exceso enantiomerico de 50% (BE). RESULTADOS: En los cortes semifinos se observo la distribucion regular homogenea en las fibras de colageno en el endoneuro y no se comprobo ninguna alteracion degenerativa de los axones o de las vainas de mielina. En los cortes ultrafinos fueron observados axones mielinizados y fibras de Remak de aspecto normal con axoplasma presentando una distribucion homogenea de neurofilamentos y microtubulos. El analisis histomorfometrico de los axones no revelo diferencias significativas entre los diametros de los axones de los grupos estudiados.