Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

A laboratory evaluation of cell viability, radiopacity and tooth discoloration induced by regenerative endodontic materials.

AIM: To analyse the cytotoxicity, colour change and radiopacity of MTA Flow (MTA), UltraCal XS (UC) and Bio-C Temp (BT). METHODOLOGY: Human dental pulp cells (hDPCs) stimulated with lipopolysaccharide (LPS) were placed in contact with several dilutions of culture media previously exposed to the experimental materials and tested for cell viability using MTT. Bovine teeth were prepared to simulate an open apex and to mimic extensive crown fracture. The roots were filled with a mixture of agar and blood, and the materials placed over this mixture. The control group consisted of teeth filled only with agar and blood. Colour assessment analyses were performed before and immediately after material insertion and repeated at 30, 45 and 60 days using a spectrophotometer. The total colour change (ΔEab , ΔE00 and whiteness index (WI)) was calculated based on the CIELAB colour space. Digital radiographs were acquired for radiopacity analysis. Cell viability was analysed by one-way anova, whilst differences in colour parameters (ΔEab , ΔE00 and WI) were assessed by two-way repeated measures anova (α = 0.05). Tukey's test was used to compare the experimental groups, and Dunnett's test was used to compare the experimental groups with the control group. RESULTS: MTA, UC and BT had similar cell viability to that of the control group (DMEM) (P > 0.05), except for the BT group at the 1 : 1 and 1 : 2 dilutions, which had significantly lower viability (P < 0.001). All materials were associated with discoloration values greater than what is considered to be the acceptable threshold, and BT resulted in less or similar tooth colour change than MTA and UC, respectively. Decreasing radiopacity over time was observed only in the MTA group (P = 0.007). Lower values of radiopacity were found in the BT group compared with the UC and MTA groups (P < 0.001). CONCLUSIONS: The new bioceramic material (BT) had acceptable cell viability, similar to that of MTA and UC at the highest dilutions, and BT resulted in less tooth colour change than MTA and UC. Despite its lower radiopacity, BT was identified radiographically.

Intra-articular leflunomide-loaded poly(ε-caprolactone) implants to treat synovitis in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune pathology that manifests as chronic inflammatory arthropathy and synovitis. Treatment of rheumatoid arthritis is based on the administration of different types of drugs, including leflunomide, an antirheumatic drug. However, the long-term systemic use of leflunomide may be associated with adverse effects. Local therapy could be an efficient strategy to treat synovitis triggered by rheumatoid arthritis without inducing adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) implants (leflunomide PCL implants) were evaluated as local drug delivery systems capable of attenuating inflammation and angiogenesis, which represent events of synovitis. Leflunomide PCL implants were designed by hot molding technique; and they were characterized by FTIR and DSC. These analytical techniques demonstrated the chemical integrity and dispersion of drug into the polymeric chains. Then, a spectrophometric method was developed and validated to quantify the leflunomide incorporated into the PCL implants and released from them. Linearity was obtained by ordinary least squares regression method to estimate the linear regression equation. Residues were evaluated considering normality, independence and homoscedasticity. Precision was lower than 5 %, and accuracy ranged from 98 to 104.5 %. Quantitation limit was 2.0 µg mL-1. PCL implants provided controlled and sustained release of leflunomide for 30 consecutive days after inserting these systems in the subcutaneous tissue of mice. The main mechanisms of drug delivery were solubilization and diffusion from polymer. Then, a non-biocompatible sponge was inserted into the subcutaneous tissue of mice to function as a frame to develop the inflammatory and angiogenic processes. Leflunomide PCL implants were inserted in direct contact with the sponge. At 4, 7 and 10 days after-sponge implantation, the key components of inflammatory angiogenesis were measured to verify the regression of these events induced by drug. Leflunomide controlled released from polymeric implants downregulated the neutrophil and monocyte/macrophage infiltration due to the reduced expression of myeloperoxidase (MPO) and N-acetyl-ß-d-glucosaminidase (NAG), respectively. As the influx of these pro-inflammatory cells was modulated by leflunomide, the production of nitric oxide (NO), a pro-inflammatory substance, reached low concentrations in the sponge. As a consequence of the modulation of inflammation at the pathological site, the angiogenic process was downregulated, since the hemoglobin levels in the sponge were drastically reduced. The accumulation of leflunomide in the pathological site did not induce nephrotoxicity or hepatototoxicity, as confirmed by histological analyses. Finally, intra-articular leflunomide PCL implants represent a potential therapeutic alternative to treat locally the synovitis triggered by rheumatoid arthritis without inducing systemic adverse effects.

Association between biomechanical alterations and migratory ability of semaphorin-3A-treated thymocytes.

BACKGROUND: Class 3 semaphorins are soluble proteins involved in cell adhesion and migration. Semaphorin-3A (Sema3A) was initially shown to be involved in neuronal guidance, and it has also been reported to be associated with immune disorders. Both Sema3A and its receptors are expressed by most immune cells, including monocytes, macrophages, and lymphocytes, and these proteins regulate cell function. Here, we studied the correlation between Sema3A-induced changes in biophysical parameters of thymocytes, and the subsequent repercussions on cell function. METHODS: Thymocytes from mice were treated in vitro with Sema3A for 30min. Scanning electron microscopy was performed to assess cell morphology. Atomic force microscopy was performed to further evaluate cell morphology, membrane roughness, and elasticity. Flow cytometry and/or fluorescence microscopy were performed to assess the F-actin cytoskeleton and ROCK2. Cell adhesion to a bovine serum albumin substrate and transwell migration assays were used to assess cell migration. RESULTS: Sema3A induced filopodia formation in thymocytes, increased membrane stiffness and roughness, and caused a cortical distribution of the cytoskeleton without changes in F-actin levels. Sema3A-treated thymocytes showed reduced substrate adhesion and migratory ability, without changes in cell viability. In addition, Sema3A was able to down-regulate ROCK2. CONCLUSIONS: Sema3A promotes cytoskeletal rearrangement, leading to membrane modifications, including increased stiffness and roughness. This effect in turn affects the adhesion and migration of thymocytes, possibly due to a reduction in ROCK2 expression. GENERAL SIGNIFICANCE: Sema3A treatment impairs thymocyte migration due to biomechanical alterations in cell membranes.

Genetic diversity and relatedness between Canindé and British Alpine goat breeds in Northeastern Brazil accessed by microsatellite markers.

The aim of this study was to access the genetic diversity and relatedness between Canindé and British Alpine goat breeds in the States of Piauí and Ceará using microsatellite markers. Genomic DNA was isolated from hair samples of 99 goats belonging to six different flocks. A panel of polymorphic heterologous microsatellite loci was used to genotype individuals. The microsatellite markers resulted in a total number of 145 alleles, with an average of 8.5 alleles per locus. The observed and expected heterozygosities were ≥0.687 and ≥0.627, respectively, for all loci. The polymorphic information content showed that all loci were highly informative with an overall mean of 0.757. Overall FST across all populations and loci was 18%, which was consistent with the coefficient of gene differentiation (GST = 0.104). AMOVA revealed that 12.8% of the variation was captured between breeds. The Bayesian STRUCTURE clustering detected the maximum likelihood for a model of two genetically distinct groups, in agreement with the number of predefined studied breeds and the two-dimensional plot from the PCoA analysis. The exotic British Alpine breed and the naturalized Brazilian Canindé breed were clearly differentiated by the microsatellite markers, indicating that these two breeds have distant genetic identities, despite the phenotypic similarity.

Implants composed of digoxin and poly(ε-caprolactone): development, characterization, anti-proliferative and anti-angiogenic activities.

Drug delivery systems could be applied to locally treat cervical cancer, thus preventing the drawbacks of conventional therapy. In this study, anti-proliferative and anti-angiogenic effects of digoxin incorporated into poly(ε-caprolactone) implants were evaluated, aiming at the local treatment of cervical cancer. Implants were characterized, and the in vitro release profile of digoxin was demonstrated. Anti-proliferative and anti-angiogenic activities of digoxin were investigated by using chorioallantoic membrane and human cervix carcinoma (HeLa) cells, respectively. The chemical structure of digoxin and the semi-crystalline nature of poly(ε-caprolactone) were preserved after designing implants. The hydrophobicity of drug and polymer as well as the semi-crystalline structure provided a controlled diffusion of digoxin from implants. Digoxin released from implantable devices exhibited anti-proliferative activity against HeLa cells. The anti-angiogenic effect was also shown. Finally, implants composed of digoxin and poly(ε-caprolactone) could be applied as a therapeutic alternative to treat the early stage of cervical cancer, once they were able to locally control the release of this anti-angiogenic and anti-proliferative drug, minimizing its systemic side effects and toxicity.

Effects of 5 IU oxytocin bolus and 20 IU oxytocin infusion compared to 5 IU oxytocin bolus and normal saline infusion in the control of blood loss during and after ante-partum lower segment caesarean section: a randomized controlled trial

Introduction: Obstetric haemorrhage is the leading cause of maternal mortality worldwide and in most cases it relates to uterine atony. Even though an oxytocin bolus is used routinely, additional infusion of oxytocin may be required if haemorrhage occurs. Objectives: To compare the effects of 20 IU oxytocin infusion and 5 IU bolus with 5 IU bolus and 500ml normal saline on the control of blood loss in antepartum lower segment caesarean section. Methods: A double-blind randomized controlled trial was conducted in the Teaching Hospital, Peradeniya, Sri Lanka. Ninety two pregnant women, forty six from each group were randomized to receive either intravenous slow 5 IU oxytocin bolus over 1 minute and additional 20 IU oxytocin infusion in 500 ml of 0.9% saline solution over 4 hours (Group-A) or 5 IU oxytocin bolus over 1 minute and 500 ml of 0.9% Saline over 4 hours (Group B). Visual assessment of mean blood loss was done by the surgeon and anaesthetist. Blood loss was calculated based on the body weight and haematocrit before and 48 hours after delivery. Results: Calculated mean blood loss (456.0ml vs 569.8ml) was significantly less in group A (p=0.046). Visual estimation of blood loss by surgeon (476.9 vs 552.1) (p=0.01) and anaesthetist (492.7 vs 557.2) (p= 0.03) were also significantly less in group A. Conclusions: Additional oxytocin infusion at antepartum caesarean section reduces blood loss during and after caesarean section significantly.

PLGA Implants containing vancomycin and dexamethasone: development, characterization and bactericidal effects.

Post-operative endophthalmitis is an infection and an inflammation of the eye following a surgical procedure. Its treatment is based on drug injections into the eye. However, this treatment can lead to ocular complications. Intraocular implants could substitute the conventional therapy. Poly(lactic-co-glycolic acid) (PLGA) implants comprising on vancomycin and dexamethasone were evaluated as drug delivery system to treat endophthalmitis after cataract surgery. Implants were characterized by drug content uniformity, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Wide Angle X-ray Scattering (WAXS), Scanning Electron Microscopy (SEM) and in vitro drug release. The bactericidal effect of vancomycin, eluted from the implants, was demonstrated against Staphylococcus aureus and Staphylococcus epidermidis. The drugs were uniformly distributed in the polymer. The analytical techniques revealed the chemical integrity of the drugs incorporated into the polymer and the modification of dexamethasone semi-crystalline nature. Drugs were controlled released from implants; and the eluted vancomycin showed bactericidal effects. In conclusion, PLGA implants containing vancomycin and dexamethasone may represent a therapeutic alternative to treat post-operative endophthalmitis.

Antioxidant and haematological biomarkers in different groups of horses supplemented with polyunsaturated oil and vitamin E.

Oxidative stress has been correlated with pathologies that impair the performance of athlete horses. The aim of this study was to assess the effects of supplementation with a mixture of polyunsaturated oil and vitamin E on the antioxidant and haematological biomarkers of horses. Horses under maintenance care (n = 6) and horses in training (n = 10) received 100 and 300 ml of the oil mixture respectively. Supplementation was provided for a period of 8 weeks, together with isocaloric inclusion. Blood samples were collected at three time periods (pretest, after 4 weeks and after 8 weeks) to analyse the following: the red blood cell count (RBCc); haemoglobin (Hb); haematocrit (HT); leucocytes; lymphocytes; platelets; the mean corpuscular volume (MCV); the mean corpuscular haemoglobin concentration (MCHC); the standard deviation of the red blood cell distribution width (RDW-SD); the coefficient of variation of the red blood cell distribution width (RDW-CV); glutathione peroxidase (GPx); superoxide dismutase (SOD); uric acid (UrAc); total plasma proteins (TPP); and creatine kinase (CK). After the 8 weeks of supplementation, animals under maintenance care exhibited significant increases in SOD, UrAc, the white blood cell count (WBCc), the RDW-SD and the RDW-CV (p < 0.05). The animals in training exhibited increases in GPx, SOD and UrAc (p < 0.05). In conclusion, supplementation with polyunsaturated oil and vitamin E increases blood antioxidants among animals under maintenance and in training, with different trends, while contributing to the fight against oxidative stress in each group analysed.

Mechanical and Optical Characterization of Single-shade Resin Composites Used in Posterior Teeth.

OBJECTIVES: This study aimed to evaluate the optical and mechanical performance of two single-shade resin-based composites (RBCs) compared to those of a conventional RBC for restoring posterior teeth. METHODS: Two single-shade RBCs, Omnichroma (Tukoyama) and Vittra Unique APS (FGM), and a conventional RBC, Filtek Z350XT shade A2 (3M Oral Care), were evaluated in this study. The optical shade-matching performance was measured using a spectrophotometer. The light emitted by VALO Grand (Ultradent) and transmitted through the 2.0-mm RBC specimens was evaluated using beam profiling. Knoop hardness (KH, N/mm2), degree of conversion (DC, %) at the top and bottom, flexural strength (FS, MPa), elastic modulus (E, GPa), postgel shrinkage (Shr, %), and shrinkage stress (MPa) were evaluated. Scanning electron microscopy (SEM) was used to characterize the filler. Data for FS, E, and Shr were analyzed by one-way analysis of variance (ANOVA) and KH and DC by repeated one-way ANOVA measurement followed by Tukey test (α=0.05). The modified von Mises stress values, light transmission, and SEM images were analyzed qualitatively. RESULTS: All single-shade RBCs exhibited higher chromatic adaptation than the Filtek Z350XT (p<0.001). Omnichroma exhibited less color difference than Vittra Unique APS, irrespective of the shade. The light transmitted through Omnichroma and Vittra Unique APS increased during polymerization. KH and DC values were significantly reduced from the top to the bottom of the specimens for all RBCs (p<0.001); however, the ratio values were always higher than 80%. In general, all RBCs demonstrated similar mechanical properties. All RBCs exhibited a similar FS (p=0.083) and Shr value (p=0.144). Filtek Z350XT exhibited significantly higher E (p<0.001) than both single-shade RBCs. All RBCs exhibited similar shrinkage stress during restoration and similar residual stress during occlusal loading. CONCLUSIONS: Single-shade Omnichroma and Vittra Unique APS increased light transmission during light-activation, demonstrating better chromatic adaptation than conventional Filtek Z350XT. In general, Omnichroma and Vittra Unique APS exhibited similar mechanical properties and shrinkage stress distributions as Filtek Z350XT during light-activation and occlusal loading.

Analysis of Calcium and Phosphate Ion Extraction From Dental Enamel by Bleaching Gels Using Ion Chromatography, Micro-CT, and SEM.

OBJECTIVES: To evaluate the volume and depth of enamel loss promoted by 37.5% and 7.5% hydrogen peroxide (HP) gels, and quantify the loss of calcium (Ca) and phosphate (P) ions by using ion chromatography (IC) analysis after bleaching. METHODS: Sixty bovine enamel specimens were randomly divided into three groups: Control - no bleaching gel; HP37.5%, application of HP 37.5% for 45 minutes for 14 days; and HP7.5%, application of HP 7.5% for 3 applications of 8 minutes. The surface analysis (n=5) was performed using a scanning electron microscope (SEM) and dispersive energy system (EDS) to calcium and phosphorus dosage. The micro-CT was used for the enamel loss analysis (n=5). IC was used to analyze extracted Ca and P (n=10). Data were analyzed by one-way ANOVA and two-way repeated measures ANOVA, followed by Tukey and Dunnett's tests (α=0.05). RESULTS: Significantly higher volume and depth of enamel loss were found for bleached groups compared with the control group. HP7.5% had significantly higher enamel change than HP37.5%. SEM showed higher enamel porosity for HP37.5% and HP7.5% compared to control. The IC demonstrated a significant increase of Ca incorporated into the gel, however, only HP7.5% had a higher P presence than the control group. The HP7.5% showed higher Ca and P ion exchange than HP37.5% (p<0.001). CONCLUSION: HP37.5% and HP7.5%, caused enamel mineral changes compared with the control group. The IC method was demonstrated to be an effective methodology for detecting enamel mineral loss by the bleaching gel.

Analysis of acyclovir in vitreous humor by a validated HPLC method.

An HPLC-UV method was developed and validated for the determination of acyclovir in vitreous humor. The method was carried out in isocratic mode using 0.02 mol/L acetic acid/methanol (95:5) as mobile phase, a C18 column at 25 degrees C and UV detection at 254 nm. The method was linear (r2> 0.99) over the range of 35-700 microg/mL, precise (RSD <5%), accurate (recovery ranged from 98.18 to 99.64%), robust, selective regarding of the vitreous humor, and robust remaining unaffected by deliberate variations in relevant parameters. The validated HPLC-UV method can be successfully applied to determine acyclovir directly injected into the vitreous cavity of rabbits' eye.

Research Note: Antimicrobial resistance profile of Enterococcus spp. isolated from the eggshell of laying hens submitted to pharmacological treatment.

The occurrence of antimicrobial resistance in microorganisms isolated from eggshells, especially Enterococcus, might serve as a parameter to assess the selection of bacteria due to the use of drugs in the diet of laying hens. In order to evaluate the frequency and the antimicrobial resistance profile of Enterococcus spp. isolated from the eggshells, 225 Hy-line laying hens were submitted to a 25-d long trial. The treatments were the following: hens fed ration without antimicrobials (control) and groups that received oxytetracycline (10 mg kg-1), doxycycline (20 mg kg-1), lincomycin (50 mg kg-1), and enrofloxacin (10 mg kg-1) in the ration for 5 d. Six replications were analyzed per treatment, composed of a pool of 5 eggs each. They were collected before treatment and on days 3, 6, 15, and 25, totaling 150 samples. Eggshells were submitted to counts of Enterococcus spp., which were identified by proteomic analyses. Antimicrobial resistance was determined by the disk-diffusion test. It was observed that 97.3% (n = 146) of the samples were contaminated with Enterococcus spp. There were no differences (P > 0.05) in the bacterial counts between treatments on the same day of evaluation. E. faecalis and E. faecium were the most frequent on the eggshells of all treatments. Multiresistance to the four classes of antimicrobials was also verified in the isolated bacteria. A total of 83% of the Enterococcus isolates showed resistance to neomycin, which was not administered to the hens, demonstrating an environmental problem. Thus, feeding laying hens with diets added with antimicrobials induces drug resistance in Enterococcus spp., isolated form the eggshells.

Effect of anti-rotation devices on biomechanical behaviour of teeth restored with cast post-and-cores.

AIM: To test the hypothesis that the presence of an anti-rotation device (ARD) and its location can influence the biomechanical behaviour of root filled teeth restored with cast post-and-cores and metallic crowns. METHODOLOGY: Fifth two bovine incisor roots were selected and divided into four groups (n = 13): Nd- without ARD; Bd- buccal ARD; Ld- lingual ARD; BLd- buccal and lingual ARD. The specimens were restored with cast post-and-cores and metallic crowns. After a fatigue process (3 x 10(5) 50 N), three strain gauges were attached on the buccal, lingual and proximal surfaces and the samples of each group (n = 3) were submitted to a 0-100 N load. Fracture resistance was assessed in a mechanical testing machine (n = 10). Strain values and fracture resistance data were analysed by one-way anova and Tukey Honestly Significant Difference (HSD) test (alpha = 0.05). The failure mode was then evaluated under an optical stereomicroscope. Bidimensional models of each group were generated for finite element analysis (FEA) and analysed using the von Mises criteria. RESULTS: No significant difference in fracture resistance values and fracture modes occurred between the four groups. The BLd group had higher stress concentrations in the buccal dentine and higher strain values on the proximal surfaces. CONCLUSIONS: The anti-rotation devices did not influence significantly the fracture resistance and fracture mode. However, the stress-strain values were increased when the anti-rotation device was prepared on the buccal and lingual faces concomitantly.

Effect of Simulated Pulpal Microcirculation on Temperature When Light Curing Bulk Fill Composites.

OBJECTIVES: To evaluate the effect of light curing bulk fill resin composite restorations on the increase in the temperature of the pulp chamber both with and without a simulated pulpal fluid flow. METHODS AND MATERIALS: Forty extracted human molars received a flat occlusal cavity, leaving approximately 2 mm of dentin over the pulp. The teeth were restored using a self-etch adhesive system (Clearfil SE Bond, Kuraray) and two different bulk fill resin composites: a flowable (SDR, Dentsply) and a regular paste (AURA, SDI) bulk fill. The adhesive was light cured for 20 seconds, SDR was light cured for 20 seconds, and AURA was light cured for 40 seconds using the Bluephase G2 (Ivoclar Vivadent) or the VALO Cordless (Ultradent) in the standard output power mode. The degree of conversion (DC) at the top and bottom of the bulk fill resin composite was assessed using Fourier-Transform Infra Red spectroscopy. The temperature in the pulp chamber when light curing the adhesive system and resin composite was measured using a J-type thermocouple both with and without the presence of a simulated microcirculation of 1.0-1.4 mL/min. Data were analyzed using Student t-tests and two-way and three-way analyses of variance (α=0.05 significance level). RESULTS: The irradiance delivered by the light-curing units (LCUs) was greatest close to the top sensor of the MARC resin calibrator (BlueLight Analytics) and lowest after passing through the 4.0 mm of resin composite plus 2.0 mm of dentin. In general, the Bluephase G2 delivered a higher irradiance than did the VALO Cordless. The resin composite, LCU, and region all influenced the degree of cure. The simulated pulpal microcirculation significantly reduced the temperature increase. The greatest temperature rise occurred when the adhesive system was light cured. The Bluephase G2 produced a rise of 6°C, and the VALO Cordless produced a lower temperature change (4°C) when light curing the adhesive system for 20 seconds without pulpal microcirculation. Light curing SDR produced the greatest exothermic reaction. CONCLUSIONS: Using simulated pulpal microcirculation resulted in lower temperature increases. The flowable composite (SDR) allowed more light transmission and had a higher degree of conversion than did the regular paste (AURA). The greatest temperature rise occurred when light curing the adhesive system alone.

Effects of post system and length on the strain and fracture resistance of root filled bovine teeth.

AIM: To investigate ex vivo the effects of different post systems and lengths on the strain and fracture resistance of root-filled teeth. METHODOLOGY: One hundred and thirty-five bovine incisors were sectioned 15 mm from their apices, root-filled and divided into three groups (n = 45): fibreglass post; prefabricated steel post; cast post and core. Each group was divided into three subgroups (n = 15) according to the post length: 5.0 mm; 7.5 mm; 10.0 mm. All teeth were restored with metal crowns. For strain-gauge measurement, two strain gauges per sample were used. The fracture resistance (N) was measured and the data were analysed with two-way analyses of variance, followed by the Tukey's HSD test (alpha = 05). RESULTS: For all posts, decreased lengths resulted in increased microstrain values. However, the fibreglass posts were associated with lower increases when compared with cast post and cores and prefabricated steel posts, which showed microstrain values two times higher when the post length was 5.0 mm. The two-way analyses of fracture resistance values revealed that post length was statistically significant for the metal posts and not significant for the fibreglass post. The fracture mode analysis indicated that all groups tended to demonstrate root fractures in groups restored with metal posts and resin core fractures in groups restored with fibreglass posts. CONCLUSIONS: The cast post and core when the length was 10.0 mm had the highest fracture resistance; however, the fibreglass post was effective with the three post lengths, with higher fracture resistance than metal posts when the length was 5.0 mm.

Involvement of kinins, mast cells and sensory neurons in the plasma exudation and paw oedema induced by staphylococcal enterotoxin B in the mouse.

Intraplantar injection of staphylococcal enterotoxin B induces long-lasting oedema mediated by both cyclooxygenase and lipoxygenase products as well as by neuropeptides from sensory nerves. This study was undertaken to further clarify the role of peripheral primary afferent sensory nerves in staphylococcal enterotoxin B (25 microg/paw)-induced plasma extravasation and oedema formation. The tachykinin NK(1) receptor antagonist (S)-1-[2-[3-(3, 4-dichlorophenyl)-1 (3-isopropoxyphenylacetyl)piperidin-3-yl] ethyl]-4-phenyl-1 azoniabicyclo [2.2.2]octane cloride (SR140333; 120 nmol/kg, s.c.+120 nmol/kg, i.v.) significantly inhibited plasma exudation and paw oedema evoked by staphylococcal enterotoxin B. The tachykinin NK(2) receptor antagonist (S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3, 4-dichlorophenyl)butyl]-benzamide (SR48968) had no effect on the staphylococcal enterotoxin B-induced responses. The bradykinin B(2) receptor antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (Hoe 140; 400 nmol/kg, i.v.) significantly reduced staphylococcal enterotoxin B-induced responses. The magnitude of the inhibition observed with Hoe 140 alone was similar to that caused by concomitant treatment of animals with SR140333 and Hoe 140, suggesting that there is a final common pathway. Additionally, SR140333 given alone reduced bradykinin (3 nmol/paw)-induced paw oedema. The vanilloid receptor antagonist N-[2-(4-chlorophenyl) ethyl]-1,3,4,5-tetrahydro-7, 8-dihydroxy-2H-2-benzazepine-2-carbothioamide (capsazepine; 100 micromol/kg) significantly reduced staphylococcal enterotoxin B-induced responses. The 5-HT receptor antagonist methysergide (10 mg/kg, i.v.) and the histamine H(1) receptor antagonist mepyramine (10 mg/kg, i.v.) produced a significant reduction in paw oedema whereas plasma exudation was reduced only by methysergide. In diabetic mice, exudation and oedema evoked by staphylococcal enterotoxin B were markedly reduced. Acute administration of insulin (20 UI/kg, s.c., 30 min before) did not restore the increased permeability induced by staphylococcal enterotoxin B. We conclude that plasma exudation and paw oedema in response to staphylococcal enterotoxin B are a consequence of a complex neurogenic response involving direct activation of vanilloid receptors on sensory nerves, release of kinins and subsequent activation of bradykinin B(2) receptors at a prejunctional level, and direct or indirect degranulation of mast cells.

In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats.

The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10%) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27%) in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.

[Determinants of the process of domiciliary infestation by Panstrongylus megistus: the role of housing and deforesting]. / Determinantes do processo de infestação domiciliar por Panstrongylus megistus: o papel da habitação e do desmatamento.

This study investigates the housing conditions and deforesting in Caconde and São José do Rio Pardo, neighbouring towns located in the northeastern region of the State of São Paulo, Brazil. These localities have had different dwelling infestation rates by Panstrongylus megistus and they also show distinct socioeconomic development. The housing conditions were studied by the analysis of data collected during the 1970's by the Superintendência de Controle de Endemias (SUCEN), a government agency. Aerial photographs taken during flights performed by the Agricultural Department of the State were used to analyse the deforesting. The socioeconomic analysis was based on Agricultural Census and interview with agronomic officials. The study showed more precarious housing conditions in Caconde than in São José do Rio Pardo. It was related to lower socioeconomic development in Caconde, confirming a trend showed by previous studies. The deforesting was more intense in São José, where socioeconomic development has been higher and the infestation rates were lower, what demonstrates opposite behaviour between the two determinants in these towns. The links between deforesting and higher socioeconomic development can also be showed by the relation between productive activity and destruction of the natural agricultural covering. It is emphasized that the tendency of opposite effect of the deforesting did not change the final result, that is, the confrontation of these determinant forces resulted in higher infestation rates in Caconde than in São José do Rio Pardo. The existence of these opposite trends between the determinants disclosed therefore more complexity in the infestation process of P. megistus, although the final result was not reverted changed.

[Secular trends of height in adulthood of children born in the city of São Paulo, Brazil from 1950-1976]. / Tendência secular da altura na idade adulta de crianças nascidas na cidade de São Paulo entre 1950 e 1976.

OBJECTIVE: The purpose of this study was to estimate the secular trend/change in the height of young males born in the city of S. Paulo between 1950 and 1976 and measured in the year they turn 18 years. METHODS: A random and representative sample (6,942 individuals) was evaluated in military draft. Statistical analyses included Shapiro-Wilk test for normality of height distribution in each birth cohort, and linear regression analysis for trend on heights. RESULTS/CONCLUSIONS: Stature has increased 3.42 centimeters during the 27 years covered by the study (1.26 cm/decade). The trend was not linear: in the 50s, there was a statistically significant increase (0.84 cm/decade); in the 60s, a smaller but non-significant increase (0.5 cm/decade) was seen; in the period of 1970-76, a greater increase in heights (2.9 cm/decade) was observed. The secular change rate observed was comparable to the rate seen in other countries. The most recent birth cohorts (1975 and 1976) achieved the higher statures in the study (approximately 175 cm). Despite these height increments, deficits of 1.8 e 6.2 cm were seen when the taller cohorts of the study were compared to American young males born in 1961 (NCHS) and Dutch men born in 1972. If there won't be any changes in the accelerated rates of the 70s, young people of São Paulo may overcome these deficits in about one or three decades.