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.     

Influence of age on reactivity to diverse emotional challenges in low- and high-anxiety rats

Studies have revealed that the extent of reactivity of high-anxiety rats to diverse challenges is different than low-anxiety rats and have provided important insights into the psychopathology of anxiety. Various factors intervene to allow defensive mechanisms to react to diverse threatening challenges, including ontogeny and the nature of the emotional challenge (e.g., conditioned vs. unconditioned). The present study investigated the extent to which a particular type of fear extrapolates to other emotional responses to diverse threatening challenges. Groups of 30- and 60-day-old rats were assigned to low freezing behavior (LFB) and high freezing behavior (HFB) groups using the contextual fear conditioning paradigm and subjected to either the fear-potentiated startle (FPS) test, novelty-induced ultrasound vocalizations (USVs) or elevated plus-maze (EPM) tests. At 30 days of age, HFB rats exhibited greater FPS than LFB rats. In contrast, prior selection of HFB and LFB did not affect the performance of 30-day-old animals in the EPM and novelty-induced USVs. Sixty-day-old animals exhibited a performance deficit in all three tests. These data suggest that the performance of young rats in animal models of anxiety parallels their selection as LFB and HFB in the contextual fear conditioning paradigm. However, the increased fear-like behavior exhibited by the 60-day-old HFB rats may elicit performance deficits in conditioned and unconditioned fear tests. These results suggest that the interaction between hyperanxiety and age may cause a performance deficit despite the animals’ increased fear-like behavior when facing emotional challenges, thus resembling psychiatric patients in many respects.     

Endoluminal Nd:YAG laser application in ex vivo biliary porcine tissue

Adequate biliary drainage with endoscopic or percutaneous placement of self-expandable metal stents represents the goal of palliation in patients with inoperable malignant obstruction of the biliary tree. As an adjunct to stenting, various tissue ablation treatments have been proposed with conflicting results. The aim of this study was to test the effect on biliary tissue of a new ablation technique based on Nd:YAG laser light delivery. The study was conducted on ex vivo specimens of 18 healthy farm pigs, using cystic ducts that are the simplest biliary structures to isolate and cannulate ex vivo. A 22G cannula was positioned into the cystic duct and a quartz optical fibre, with a prototypal cooling system, was inserted into the cannula. Nd:YAG laser output powers of 10, 12, and 15 W were tested, with a total delivered energy of 1000 J in continuous mode in each case. After laser treatment, histological analysis was performed. At macroscopical examination, no lesions of the external wall of the cystic ducts were detected. At histopathological examination, a coagulative necrosis involving the entire mucosa up to the muscolaris propria without significant changes of periductal tissues was observed in all specimens. This study shows the possibility of using Nd:YAG laser on ex vivo porcine biliary ducts with the effect of obtaining a coagulative necrosis involving the whole mucosa.     

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.     

Bone mineral density: Methods of measurement and its influence on primary stability of miniscrews

Objective:To verify whether bone mineral density (BMD) of cortical bone, trabecular bone, and total bone influence the primary stability of orthodontic miniscrews and to verify whether there is a correlation between the measurement of BMD by cone-beam computed tomography (CBCT) and central dual-energy x-ray absorptiometry (DEXA).Materials and Methods:Twenty bovine bone sections were extracted from the pubic and iliac bones from regions with cortical thicknesses of approximately 1 mm. The BMD of the total bone block was evaluated using two methods: CBCT and DEXA. The BMD of cortical, trabecular, and total bone in the region of interest (ROI) were also evaluated by CBCT. After scanning the bone blocks, 20 self-drilling miniscrews (INP®) 1.4 mm in diameter and 6 mm long were inserted into them. The peak implant insertion torque (IT) was registered. After this, the pull-out test (PS) was performed and the maximum force registered. The Pearson correlation test was applied to verify the correlations between variables.Results:The BMD of the total bone block verified by CBCT and DEXA showed a positive and strong correlation (r  =  0.866, P  =  .000). The BMD of the ROI for cortical bone influenced the IT (r  =  0.518, P  =  .40) and the PS of miniscrews (r  =  0.713, P  =  .001, Table 2). However, the total bone BMD (verified by CBCT and DEXA) and trabecular bone BMD presented weak and not statistically significant correlations with primary stability.Conclusions:There was a positive correlation between total bone block BMD measured by DEXA and CBCT. The cortical BMD influenced the IT and PS.     

Factors associated to persistence with hormonal therapy in women with breast cancer

OBJECTIVE

To analyze factors associated with persistence to breast cancer hormone therapy in order to contribute to the quality of care improvement.

METHODS

Retrospective longitudinal study, based on secondary data. A cohort of 5,861 women with breast cancer registered in different datasets of the Brazilian National Cancer Institute and the Brazilian Unified Health System were analyzed. All women were treated at this hospital, which provides free medication, and the follow-up period was from January 2004 to October 2010. Sociodemographic, behavioral, and clinical variables, as well as aspects of lifestyle and health care, were considered in the explanation of variations in the persistence to hormone therapy, applying the Kaplan-Meier method and the Cox proportional hazard model.

RESULTS

Overall persistence to hormone therapy was 79.0% at the end of the first year, and 31.0% in five years of treatment. The risk of discontinuing hormone therapy was higher among women under 35 years old, with more advanced disease (stages III and IV), alcohol drinkers, those undergoing chemotherapy, and for each additional hospitalization, exam performed, and month between diagnosis and beginning of treatment. In the opposite direction, the risk of discontinuity was lower among women who had at least finished high school, those with partner, with a family history of cancer, those who had undergone breast surgery, and who had outpatient visits to a Mastologist, and a Clinical Oncologist.

CONCLUSIONS

The majority of the women with breast cancer (69.0%) do not persist with hormone treatment for the five years recommended, increasing the risk of inadequate clinical results. The results show aspects of care that can provide better results.