The Influence and Compatibility of Vegetable Oils and other Additives on Release of Ketoprofen from Transdermal Films

The vegetable oils used as skin permeation enhancers were selected on the basis of compatibility studies data. A total of eight monolithic systems were prepared by using different concentrations of drug-polymers-permeation enhancers. The permeation parameters, flux, permeability coefficient, enhancement ratio and diffusion rate constants were determined. The maximum flux of 9.08 x 10-2 mg/cm2.h was observed with hydroxy propyl methyl cellulose monolithic system containing 30% w/w olive oil. Further improvement of flux was observed, when 30% w/w olive oil was applied directly onto the skin prior to the studies. The release was sustained up to 24 hours with zero-order kinetics and diffusion controlled mechanism. The 30% w/w olive oil formulation showed promising results with in vivo results showing significant analgesic and anti-inflammatory activities (P < 0.01) with no hypersensitivity reactions. Stability studies and scanning electron microscopy studies were also conducted. Keywords: Vegetable oils, flux, ketoprofen, polymersEast and Central African Journal of Pharmaceutical Sciences Vol. 13 (2010) 19-2

Xenon in Mercury-Manganese Stars

Previous studies of elemental abundances in Mercury-Manganese (HgMn) stars have occasionally reported the presence of lines of the ionized rare noble gas Xe II, especially in a few of the hottest stars with Teff ~ 13000--15000 K. A new study of this element has been undertaken using observations from Lick Observatory's Hamilton Echelle Spectrograph. In this work, the spectrum synthesis program UCLSYN has been used to undertake abundance analysis assuming LTE. We find that in the Smith & Dworetsky sample of HgMn stars, Xe is vastly over-abundant in 21 of 22 HgMn stars studied, by factors of 3.1--4.8 dex. There does not appear to be a significant correlation of Xe abundance with Teff. A comparison sample of normal late B stars shows no sign of Xe II lines that could be detected, consistent with the expected weakness of lines at normal abundance. The main reason for the previous lack of widespread detection in HgMn stars is probably due to the strongest lines being at longer wavelengths than the photographic blue. The lines used in this work were 4603.03A, 4844.33A and 5292.22A

Preparation and characterization of 5-fu loaded microspheres of eudragit and ethylcellulose

En la presente investigación, se han preparado microesferas de Eudragit (RS 100, RL 100 y RSPO) y etilcelulosa cargadas con 5-fluorouracilo. Se ha utilizado la técnica de “evaporación del disolvente o/o” para preparar las microesferas utilizando el sistema de (metanol + acetona)/ parafina líquida. Se ha utilizado estearato de magnesio como estabilizador de gotículas y se ha añadido n-hexano para endurecer las microesferas. Las microesferas preparadas se caracterizan por sus propiedades micromeríticas y su eficaz compresión, así como a través de la espectroscopia infrarroja transformada de Fourier (FTIR, por sus siglas en inglés) y la cromatografía en capa fina. Se han tomado microfotografías para estudiar la forma de las microesferas. La mejor cinética de liberación se ha alcanzado con el modelo de Higuchi. El tamaño de la partícula principal, la eficacia de compresión y los rendimientos de producción han sido fuertemente influenciados por el tipo de polímero y su concentración. Tras la presente investigación, se ha determinado que el Eudragit y la Etilcelulosa tienen carreras muy prometedoras en la liberación controlada para el 5-FUIn the present investigation, 5-fluorouracil loaded microspheres of Eudragit (RS 100, RL 100 and RSPO) and ethylcellulose were prepared. “O/O solvent evaporation” technique was used for preparation of microspheres using (methanol + acetone)/liquid paraffin system. Magnesium stearate was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeretic properties and entrapment efficiency; as well by Fourier transform infrared spectroscopy (FTIR) and thin layer chromatography (TLC). Photomicrographs were taken to study the shape of microspheres. The best fit release kinetics was achieved with Higuchi plot. Mean particle size, entrapment efficiency and production yields were highly influenced by the type of polymer and polymer concentration. It is concluded from the present investigation that various Eudragit and Ethylcellulose are promising controlled release carriers for 5-FU

Direct and indirect effects of rotavirus vaccination: Comparing predictions from transmission dynamic models

Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research

Conservative and disruptive modes of adolescent change in human brain functional connectivity

Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: “conservative” and “disruptive.” Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman’s correlation between edgewise baseline FC (at 14 y, FC14) and adolescent change in FC (ΔFC14−26), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas

TLR2 ligation induces corticosteroid insensitivity in A549 lung epithelial cells: Anti-inflammatory impact of PP2A activators

© 2016 Elsevier Ltd Corticosteroids are effective anti-inflammatory therapies widely utilized in chronic respiratory diseases. But these medicines can lose their efficacy during respiratory infection resulting in disease exacerbation. Further in vitro research is required to understand how infection worsens lung function control in order to advance therapeutic options to treat infectious exacerbation in the future. In this study, we utilize a cellular model of bacterial exacerbation where we pretreat A549 lung epithelial cells with the synthetic bacterial lipoprotein Pam3CSK4 (a TLR2 ligand) to mimic bacterial infection and tumor necrosis factor α (TNFα) to simulate inflammation. Under these conditions, Pam3CSK4 induces corticosteroid insensitivity; demonstrated by substantially reduced ability of the corticosteroid dexamethasone to repress TNFα-induced interleukin 6 secretion. We then explored the molecular mechanism responsible and found that corticosteroid insensitivity induced by bacterial mimics was not due to altered translocation of the glucocorticoid receptor into the nucleus, nor an impact on the NF-κB pathway. Moreover, Pam3CSK4 did not affect corticosteroid-induced upregulation of anti-inflammatory MAPK deactivating phosphatase—MKP-1. However, Pam3CSK4 can induce oxidative stress and we show that a proportion of the MKP-1 produced in response to corticosteroid in the context of TLR2 ligation was rendered inactive by oxidation. Thus to combat inflammation in the context of bacterial exacerbation we sought to discover effective strategies that bypassed this road-block. We show for the first time that known (FTY720) and novel (theophylline) activators of the phosphatase PP2A can serve as non-steroidal anti-inflammatory alternatives and/or corticosteroid-sparing approaches in respiratory inflammation where corticosteroid insensitivity exists

Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania.

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse. This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors. This population-based survey of mothers of children aged 0-36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was "yes" to 8 or more items on the scale were defined as "at risk of CMD." Of the 1,922 mothers (15-48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective. Taken together, our results indicate the significance of the quality of relations with one's partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings

Long-Acting β<inf>2</inf>-Agonists Increase Fluticasone Propionate-Induced Mitogen-Activated Protein Kinase Phosphatase 1 (MKP-1) in Airway Smooth Muscle Cells

Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type. © 2013 Manetsch et al

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

BACKGROUND: Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. METHODS: This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. FINDINGS: Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. INTERPRETATION: These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. FUNDING: National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat