A new nanoemulsion formulation improves antileishmanial activity and reduces toxicity of amphotericin B

This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL). When the NE was submitted to gradual increases in pressure, the PI values and droplet size decreased. The droplet size (～145?nm) was lower than that obtained in previous studies. The zeta potential was negative and the EE was almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB-loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at 2?mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same dose, did not result in any sign of acute toxicity, promoting a significant reduction in parasite burden as compared to the C-AmB. These findings suggest that this new AmB-loaded NE constitutes an attractive alternative for the treatment of VL due to improved efficacy and lower toxicity.     

Comparative analysis of preemptive analgesic effect of tramadol chlorhydrate and nimesulide following third molar surgery

The aim of this prospective, randomized, controlled, paired trial was to perform a comparative analysis of the preemptive analgesic effect of nimesulide and tramadol chlorhydrate during third molar surgery. The study was carried out between March and November 2009, involving 94 operations in 47 male and female patients with bilateral impacted lower third molars in comparable positions. The sample was divided into two groups. Group A received an oral dose of 100 mg of nimesulide 1 h prior to surgery. Group B received an oral dose of 100 mg of tramadol chlorhydrate 1 h prior to surgery. The following aspects were evaluated in the postoperative period: adverse effects of the drugs; amount of rescue medication used (acetaminophen 750 mg); and pain 5, 6, 24, 36, 48, 60, 72 and 84 h after surgery using a visual analog pain scale. Peak pain occurred 5 h after surgery in both groups, with a mean pain score of 2.3 in Group A and 3.0 in Group B; this difference did not achieve statistical significance (p > 0.141). Based on the sample studied, nimesulide and tramadol chlorhydrate demonstrate similar preemptive analgesic effects when used in lower third molar surgeries.     

Molecular characterization,serotyping, and antibiotic susceptibility profile of Leptospira interrogans serovar Copenhageni isolates from Brazil

Leptospira interrogans serogroup Icterohaemorrhagiae is the major serogroup infecting humans worldwide, and rodents and dogs are the most significant transmission sources in urban environments. Knowledge of the prevalent serovars and their maintenance hosts is essential to understand the epidemiology of leptospirosis. In this study, 20 Leptospira isolates were evaluated by pulsed-field gel electrophoresis (PFGE), variable number tandem-repeat analysis (VNTR), serotyping, and determination of antimicrobial resistance profile. Isolates, originated from bovine, canine, human, and rodent sources, were characterized by microscopic agglutination test with polyclonal and monoclonal antibodies and were identified as L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni. MICs of antimicrobials often used in veterinary medicine were determined by broth microdilution test. Most of tested antibiotics were effective against isolates, including penicillin, ampicillin, and ceftiofur. Higher MIC variability was observed for fluoroquinolones and neomycin; all isolates were resistant to trimethoprim/sulfamethoxazole and sulphadimethoxine. Isolates were genotyped by PFGE and VNTR; both techniques were unable to discriminate between serovars Copenhageni and Icterohaemorrhagiae, as expected. PFGE clustered all isolates in 1 pulsotype, indicating that these serovars can be transmitted between species and that bovine, rodent, and dogs can maintain them in the environment endangering the human population.     

Intrasphincteric botulinum toxin injection in the treatment of chagasic achalasia.

According to the WHO, 16-18 million people in Central and South America are infected by Trypanosoma cruzi. Chagasic achalasia affects between 7.1% and 10.6% of the population. The aim of this study was to evaluate the effects of Botox injections in the clinical response and esophageal function of patients with dysphagia due to chagasic achalasia. In total, 24 symptomatic patients with chagasic achalasia were randomly chosen to receive Botulinum Toxin (BT) or saline injected by endoscopy in the lower esophageal sphincter (LES). Patients were monitored with a clinical score of dysphagia and an objective assessment (esophagograms, scintillography, manometry, and nutritional assessment) for a period of 6 months. Clinical improvement of dysphagia was statistically significant (P < 0.001) in patients receiving BT when compared with the placebo. There was no significant difference in the placebo group regarding clinical score, LES basal pressure and esophageal emptying time. Esophageal emptying time in the toxin group was significantly lower than in the placebo (P=0.04) after 90 days. There were non-significant increases in esophageal emptying of 25.36% and 17.39%, respectively, at 90 and 180 days, in the BT group (P=0.266). Gender, age, and baseline LES pressure did not influence the response to BT. Our data strongly suggests that intrasphincteric injection of BT in LES is clinically effective in the treatment of chagasic achalasia.