Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery

Purpose: The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods: Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers (L-arginine and L-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results: Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79±3.24), fine particle dose (FPD) (14.42±1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86±0.24 μm. However, L-leucine was significantly superior in enhancing the aerosolization performance ( L-arginine:%FPF 27.61±4.49-26.57±1.85; FPD 12.40±0.99-19.54±0.16 μg and MMAD 2.18±0.35-2. 98±0.25 μm, L-leucine:%FPF 36.90±3.6-43.38±5. 6; FPD 18.66±2.90-21.58±2.46 μg and MMAD 2.55±0.03-3. 68±0.12 μm). Incorporating L-leucine (1.5%w/w) reduced the burst release (24.04±3.87%) of SF compared to unmodified formulations (41.87±2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o-cell lines, resulted in cell viability of 85.57±5.44 and 60.66±6.75%, respectively, after 72 h treatment. Conclusion:The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery. © Springer Science+Business Media, LLC 2011.

Deregulation and the Marketing of Airline Carriers

No student of the hospitality industry can long be insensitive to the role of air transportation in creating much, though by no means all, of the "place demand" for his industry. This article confines itself to a discussion of the impact of deregulation on carriers in the industry and discusses implications for the hospitality field

Targeted Brain Derived Neurotropic Factors (BDNF) Delivery across the Blood-Brain Barrier for Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effectivein-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.

Avaliação da pressão inspiratória nasal sniff na população obesa

Introdução: a avaliação da pressão inspiratória nasal (SNIP) é considerada uma manobra complementar da Pressão Inspiratória Máxima estática (PImax) em várias condições clínicas, porém não há relatos na obesidade. Por outro lado, a obesidade tem um importante impacto nos músculos respiratórios especialmente com maiores gordura abdominal o que provavelmente pode ser detectado na avaliação da SNIP que mensura mais precisamente a pressão diafragmática. Objetivo: analisar em obesos a relação entre SNIP e variáveis respiratórias e marcadores de adiposidade. Material e Método: num estudo transversal um total de 92 obesos (38.3±10.2 anos) sem história de doença respiratória ou cardíaca diagnosticada. Foram avaliados na espirometria (capacidade vital forçada-CVF; volume expiratório forçado no primeiro segundo-VEF1; volume de reserva expiratório-VRE) e pressões respiratórias estática (PImax, PEmax e SNIP) e dinâmica (ventilação voluntária máxima-VVM). Sendo considerados os marcadores de adiposidade: índice de adiposidade corporal-IAC; índice de massa corporal-IMC e circunferências do quadril (CQ), cintura (CC) e pescoço (CP). Resultados: 65 obesos mórbidos (IMC=50.8±8.1Kg/m2) e 27 obesos não mórbidos (IMC=35.6±2.7Kg/m2) foram homogêneos (p>0.05) na SNIP (99.1±24.5cmH2O, 87% do predito) e PImax (107.3±26.4cmH2O, 109% do predito). Existe correlação (r=0.5) entre SNIP e PImax somente no grupo de obesos mórbidos. De acordo com as correlações houve associação entre variáveis respiratórias (CVF r=0.48; VEF1 r=0.54; e VVM r=0.54), valores antropométricos (idade r=-0.44) e SNIP somente para os obesos mórbidos. Esses achados foram certificados quando também comparados a quantidade de gordura ao redor do pescoço (CP≥43cm). O modelo de regressão linear stepwise mostrou que a VVM parece ser o melhor preditor para explicar a SNIP nos obesos mórbidos. Nestes obesos a SNIP foi levemente mais baixa (87%predito) que os valores esperados para indivíduos brasileiros saudáveis. Conclusão: em obesos mórbidos a SNIP é moderadamente relacionada a PImax. A SNIP parece ser mais relacionada a VVM que à marcadores de adiposidade.

Low cost carriers and the changing fortunes of airports in the UK

This paper investigates how low cost carrier (LCC) developments have affected the traffic and financial performance of UK airports from 2002 to 2014. Considerable growth in traffic was experienced from 2002 to 2007, especially at regional airports as a result of LCC expansion. This was replaced with a more volatile period from 2008 to 2014 where many of the regional airports that experienced the greatest increases in traffic during the early years, then experienced the largest reductions. This has clearly had an impact on their financial well-being, resulting in reduced profits for many airports. It has also meant that many regional airports that seemed like attractive investments as a result of LCC expansion are now less financially appealing, especially given that the LCC sector in the UK appears to be shifting capacity to larger regional airports, and in some cases, London airports.

Discerning the sub-phonemic identity of pre-nasal /æ/ in British Columbia English

There are two features of /æ/ in British Columbia (BC) English that are widely attested in the literature: it is undergoing retraction and lowering and it is sensitive to the influence of certain following consonants. The present study aims to utilize both features to evaluate the phonological status of /æ/ before nasal consonants in BC English by examining the progression of sound change and the phonemic organization of /æ/ in different environments. Specifically, production and perception results are taken together to evaluate the phonetic position of pre-nasal /æ/ relative to other environments. These results are interpreted within a modular feedforward architecture of phonology to establish the phonological (allophonic) and phonetic (shallowphonic) rules that govern the internal relationships between the subphonemic elements of /æ/ in BC English. Further, the findings of this study provide evidence for the allophone being the target of sound change, rather than the phoneme.

The carrier’s exemption from liability in the Hague, Hamburg and Rotterdam Rules : an examination from the perspectives of fairness and clarity

Le commerce international est souvent relié au transport maritime. La poursuite des règles uniformes se rapportant à ce dernier avait débuté à la fin du XIXe siècle et a abouti à l’émergence des Règles de La Haye, des Règles de Hambourg et des Règles de Rotterdam. L’exonération du transporteur maritime, qui suscitait des controverses favorisant le développement des règles maritimes internationales, a été réglementée de trois façons différentes dans les trois Règles précitées. La question principale abordée dans la thèse présente est si elles sont suffisamment satisfaisantes. Une autre question, qui se pose s’il est prouvé qu’aucune d’entre elles ne l’est, est quelle serait une meilleure façon. Pour y répondre, deux critères, soit la justice et la clarté, ont été choisis. Les recherches effectuées dans le cadre de la thèse présente visent à donner une évaluation profonde des régimes existants en matière de réglementation de l’exonération du transporteur maritime ainsi que des suggestions d’amélioration à cet égard.

Slow Oscillations in the Mouse Hippocampus Entrained by Nasal Respiration

Different types of network oscillations occur in different behavioral, cognitive, or vigilance states. The rodent hippocampus expresses prominentoscillations atfrequencies between 4 and 12Hz,which are superimposed by phase-coupledoscillations (30 –100Hz).These patterns entrain multineuronal activity over large distances and have been implicated in sensory information processing and memory formation. Here we report a new type of oscillation at near- frequencies (2– 4 Hz) in the hippocampus of urethane-anesthetized mice. The rhythm is highly coherent with nasal respiration and with rhythmic field potentials in the olfactory bulb: hence, we called it hippocampal respiration-induced oscillations. Despite the similarity in frequency range, several features distinguish this pattern from locally generatedoscillations: hippocampal respiration-induced oscillations have a unique laminar amplitude profile, are resistant to atropine, couple differentlytooscillations, and are abolished when nasal airflow is bypassed bytracheotomy. Hippocampal neurons are entrained by both the respiration-induced rhythm and concurrent oscillations, suggesting a direct interaction between endogenous activity in the hippocampus and nasal respiratory inputs. Our results demonstrate that nasal respiration strongly modulates hippocampal network activity in mice, providing a long-range synchronizing signal between olfactory and hippocampal networks.

Sistemas semissólidos à base de nanopartículas lipídicas

As nanopartículas lipídicas foram desenvolvidas no início dos anos 90 e, atendendo às vantagens que apresentam comparativamente a outros sistemas coloidais, têm-se demonstrado muito promissoras, tanto para uso cosmético como farmacêutico. No entanto, atualmente apenas existem comercializados produtos cosméticos à base de nanopartículas lipídicas, o que pode ser justificado pelas restrições regulamentares relacionadas com a introdução de medicamentos no mercado. Existem dois tipos de nanopartículas lipídicas, as nanopartículas de lípidos sólidos (Solid Lipid Nanoparticles, SLN) e os vetores lipídicos nanoestruturados (Nanostructured Lipid Carriers, NLC), consistindo ambos em dispersões aquosas de nanopartículas sólidas. A baixa viscosidade destes sistemas dificulta a sua aplicação tópica. Neste contexto, têm sido desenvolvidas várias formulações semissólidas à base de nanopartículas lipídicas para aplicação tópica, nomeadamente cutânea, ocular, nasal e vaginal. A primeira parte desta dissertação consiste na revisão bibliográfica relativa ao estado da arte dos sistemas semissólidos à base de nanopartículas lipídicas, para uso farmacêutico e cosmético, baseada nos estudos realizados por diversos autores, entre 2012 e 2016. Na segunda parte, são apresentados resultados do trabalho experimental relativo ao desenvolvimento e caraterização de uma formulação semissólida à base de nanopartículas lipídicas.

Nanostructured lipid carriers as vehicles for the delivery of poorly water-soluble drugs

186 p.

Dacriocistorrinostomia endoscópica nasal: resultados do Hospital Professor Doutor Fernando Fonseca

Objectivo: analisar os resultados da experiência de um hospital distrital na realização de dacriocistorrinostomias (DCR) endoscópicas e determinar o papel actual desta técnica para tratamento de obstruções da via nasolacrimal. Materiais e Métodos: Reviram-se os processos clínicos de 67 dacriocistorrinostomias endoscópicas consecutivas realizadas no Hospital Fernando Fonseca entre Janeiro de 1997 e Dezembro de 2012. Analisou-se a clínica apresentada pelos doentes, o nível da estenose detectado na dacriocistografia, as complicações intra e pós-operatórias e os resultados funcionais e anatómicos pós-operatórios. Resultados: Dos 51 doentes, 12 eram do sexo masculino e 34 do sexo feminino, com média de idades de 57 anos. A epífora foi a queixa predominante. Com a excepção de dois casos, todas as cirurgias foram executadas com instrumentos de dissecção motorizados. O sucesso da DCR endoscópica foi de 78,1%. Conclusões: A DCR endoscópica é uma técnica simples, segura e eficaz para o tratamento das obstruções distais da via nasolacrimal.

New approach to study the real exposure to fungi in cork industry: nasal swabs mycobiota investigation coupled with screening on fungal resistance to azoles

The permanent contact with cork may lead to constant exposure to fungi, raising awareness as a potential occupational hazard in the cork industry.The presence of fungi belonging to the Penicillium glabrum complex has been associated with the development of respiratory diseases such as suberosis, one of the most prevalent diseases among workers from cork industries, besides occupational asthma. Azoles are used as pesticides but also the first line therapy in the treatment of Aspergillus infections; azole-resistance as been described as to have also an environmental source and is considered an emerging public health problem.The aim of this work was to characterize fungal distribution and to evaluate the presence of azole-resistant Aspergillus isolates in nose swab samples from the cork industry workers.

Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase Behavior and Antimicrobial Effect

International audience