Functional hybrid nanoemulsions for sumatriptan intranasal delivery

In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ −25 mV), and nanoparticle concentration (~ 2.1014 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41–69%, extending the in vitro release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its in vivo nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.Fil: Ribeiro, Lígia N. M.. Universidade Estadual de Campinas; BrasilFil: Rodrigues da Silva, Gustavo H.. Universidade Estadual de Campinas; BrasilFil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Breitkreitz, Márcia C.. Universidade Estadual de Campinas; BrasilFil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Processing of Apeiba tibourbou Aubl. extract via spray drying

The effects of drying air inlet temperature (IT) and concentration of Aerosil® 200 (CA) on several properties of spray-dried Apeiba tibourbou extracts were investigated following a 32 full factorial design. Powder recovery varied from 9.83 to 46.95% and dried products showed moisture contents below 7%. Although the spray-dried products lost some of their polyphenols, they still present excellent antioxidant activity, opening perspectives for its use to medicinal purpose. CA exerted a key role on the properties of spray-dried extracts, while IT did not present a significative influence. Aerosil® 200 proved to be an interesting alternative as an excipient for the drying of the herbal extract, even at intermediate concentrations such as 15%. The best combination of conditions to use for obtaining dry A. tibourbou extracts with adequate physicochemical and functional properties involves an IT of 100 ºC and a CA of 15%.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Decrease in APP and CP mRNA expression in Alzheimer’s disease patients suggests impairment of cellular iron export in this dementia

Recentemente tem-se assistido a um acumular de evidência sugerindo a implicação de uma desregulação do metabolismo do ferro (Fe) na fisiopatologia da doença de Alzheimer (DA). Neste trabalho, pretendemos esclarecer melhor os mecanismos moleculares subjacentes à homeostasia deste metal na DA, particularmente ao nível do efluxo celular. Assim, mediu-se em células mononucleares do sangue periférico de 73 doentes com DA e 74 controlos a expressão de genes diretamente envolvidos na regulação e exportação celular de Fe, utilizando a técnica de PCR quantitativo. Os resultados mostraram uma diminuição significativa na expressão dos genes aconitase (ACO1; P=0,007); ceruloplasmina (CP; P<0,001) e proteína precursora de beta amilóide (APP; P=0,006) em doentes com DA comparativamente com os voluntários saudáveis. Estas observações apontam para uma diminuição significativa da expressão dos genes associados com a exportação de Fe celular mediada pela ferroportina na DA. Assim, o presente estudo reforça resultados anteriores que mostram alterações no metabolismo do Fe e podem estar na origem da retenção intracelular deste metal e aumento de stress oxidativo caraterísticos desta patologia.A dysregulation of iron (Fe) metabolism in Alzheimer’s disease (AD) has been suggested previously. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD particularly at the level of cellular iron efflux. Thus, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 73 AD patients and 74 controls. A significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P<0.001) and amyloid peptide precursor (APP; P=0.006) genes was fund in AD patients compared with healthy volunteers. These observations point out to a significant downregulation of the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients. The present findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease

Validated HPLC-PDA method for rosmarinic acid quantification in Rosemary

A fast and simple HPLC-PDA method for rosmarinic acid quantification in Rosemary leaves powder was validated. The analyses were performed using a C18 column in isocratic conditions and detection at 254 nm. Performing the system suitability tests, the method showed to be capable of providing data of acceptable quality. Results showed that the method was selective, linear for concentration ranges between 2.5-50 μg.mL–1 , sensitive, precise, accurate and robust. The main advantages of the method were the simplicity and promptness of sample analysis, as well as equipment convenience. These results allowed us to conclude that it can be successfully applied on the routinely quality control of Rosemary phytopharmaceuticals inputs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pediatric tuberculosis in the metropolitan area of Rio de Janeiro

Aim: To evaluate the clinical characteristics, diagnostic approach, and treatment outcomes of tuberculosis (TB) in children living in a high-burden metropolitan area. Methods: This was a retrospective study, based on a medical chart review, involving children under 15 years old treated for TB between 2007 and 2016, in four primary health units (PHU) and three reference centers (RC) in five cities of Rio de Janeiro metropolitan area. Factors associated with TB treatment setting, microbiological diagnosis, and treatment outcomes were evaluated. Results: A total of 544 children were enrolled; 71% were treated in PHU, 36% were under 5 years old, and 72% had pulmonary TB (PTB). The HIV prevalence was 10% (31/322). Fifty-three percent had at least one microbiological test for TB, 68% of them (196/287) had TB confirmed. Among 222 children with previous TB contact, information on LTBI was available for 78 (35%), and only 17% (13/78) were treated. Extrapulmonary TB (56% vs 32%), microbiologically confirmed TB (77% vs 60%), and HIV positivity (18.5% vs 4.0%) were significantly more frequent in RC. Treatment in RC (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.74–5.44) and PTB (OR 2.47, 95% CI 1.34–4.56) were independently associated with a microbiological diagnosis of TB. The treatment success rate was 85%. In the logistic regression analysis, HIV-infected children had a 2.5-fold higher risk of an unfavorable outcome (OR 2.53, 95% CI 1.0–6.38; p = 0.05). Conclusions: Opportunities for TB prevention and early TB treatment are missed due to suboptimal close contact screening. Microbiological diagnosis of TB and drug susceptibility testing in children should be made available through more sensitive and accessible tests

Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis

The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB

Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.O diagnóstico precoce e adequado da tuberculose é um dos pilares mais importantes no controle da doença. A proposta deste consenso brasileiro é apresentar aos profissionais da área de saúde um documento com as evidências mais atuais e úteis para o diagnóstico da tuberculose. Para tanto, a Comissão de Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 membros da Sociedade com reconhecida experiência em tuberculose no Brasil. Foi realizada uma revisão não sistemática dos seguintes tópicos: diagnóstico clínico, diagnóstico bacteriológico, diagnóstico radiológico, diagnóstico histopatológico, diagnóstico da tuberculose na criança e diagnóstico da tuberculose latente