A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS

In an aging western population, a significant number of patients continue to suffer from angina once all revascularization and optimal medical treatment options are exhausted. Under experimental conditions, oral supplementation with inorganic nitrate was shown to exhibit a blood pressure-lowering effect, and has also been shown to promote angiogenesis, improve endothelial dysfunction and mitochondrial efficiency in skeletal muscle. It is unknown whether similar changes occur in cardiac muscle. In the current study, we investigate whether oral sodium nitrate treatment will improve myocardial ischemia in patients with stable angina.

TRPV4 activation triggers the release of melatonin from human non-pigmented ciliary epithelial cells

Melatonin is a neurohormone mainly produced in the pineal gland; nevertheless, various ocular structures such as the ciliary body, lens and the retina produce it. One of the roles of melatonin in the eye is the modulation of intraocular pressure, although little is known about the mechanisms that causes its presence in the aqueous humour. TRPV4 is a membrane channel which is activated by both physical and chemical stimuli. Therefore, this channel is sensitive to osmotic and hydrostatic pressure. As a consequence, TRPV4 results as an interesting candidate to study the relation between the activation of the TRPV4 channel and the production of melatonin. In this sense we have studied the role of the TRPV4 agonist GSK1016790A to modulate the production of melatonin in a cell line derived from human non-pigmented ciliary epithelial cells. The stimulation of the TRPV4 produced an increase in the extracellular melatonin levels changing from 8.5 ± 0.6 nM/well/30 min (control) to 23.3 ± 2.1 nM/well/30 min after 10 nM GSK1016790A application, this action being blocked by the selective antagonist RN 1734. The activation of the TRPV4 by GSK1016790A permitted to observe a melatonin increase which was concentration-dependent, and provided a pD2 value of −8.5 ± 0.1 (EC50 of 3.0 nM). In conclusion, the activation of the TRPV4 present in human non-pigmented ciliary epithelial cells can modulate the presence of extracellular melatonin, this being of relevance since this substance controls the dynamics of the aqueous humour.

Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy

Because GABA (gamma-aminobutyric acid) receptor-mediated inhibition controls the excitability of principal neurons in the brain, deficits in GABAergic inhibition have long been favored to explain seizures. In an experimental model of temporal lobe epilepsy, we have identified a deficit of inhibition in presynaptic GABAergic terminals characterized by decreased GABA quantal activity associated with reduced synaptic vesicle density. This decrease in vesicle number primarily seems to affect the reserve pool, rather than the docked or the readily releasable pool.

Green nanocomposites as carriers for slow-release of tebuconazole.

2016

Dexamethasone-loaded poly(epsilon-caprolactone) intravitreal implants: a pilot study.

PURPOSE: Poly(epsilon-caprolactone) (PCL) is a biodegradable and biocompatible polymer that presents a very low degradation rate, making it suitable for the development of long-term drug delivery systems. The objective of this pilot study is to evaluate the feasibility and characteristics of PCL devices in the prolonged and controlled intravitreous release of dexamethasone. METHODS: The in vitro release of dexamethasone was investigated and the implant degradation was monitored by the percent of mass loss and by changes in the surface morphology. Differential scanning calorimetry was used to evaluate stability and interaction of the implant and the drug. The short-term tolerance of the implants was studied after intravitreous implantation in rabbit eye. Results: PCL implant allows for a controlled and prolonged delivery of dexamethasone since it releases 25% of the drug in 21 weeks. Its low degradation rate was confirmed by the mass loss and scanning electron microscopy studies. Preliminary observations show that PCL intravitreous implants are very well tolerated in the rabbit eye. CONCLUSION: This study demonstrates the PCL drug delivery systems allowed to a prolonged release of dexamethasone in vitro. The implants demonstrated a strikingly good intraocular short-term tolerance in rabbits eyes. The in vitro and preliminary in vivo studies tend to show that PCL implants could be of interest when long-term sustained intraocular delivery of corticosteroids is required.

Obtenção e caracterização de matriz apropriada para sistemas de liberação prolongada: estudos de liberação dos herbicidas atrazina e diuron

This study aimed to produce and characterize a novel material from fish scales and chitosan for use as a medium for the extended release of herbicides. The mechanism of release for the herbicides atrazine and diuron was influenced by diffusion and swelling according to the power law kinetic model. The atrazine release time was seven days, while that of diuron was four days. The results of this study will contribute to the development of environmental matrices for herbicide release systems.

Oxoisoaporphine nanocapsules for treating depression

Oxoisoaporphine nanocapsules for treating depression. Nanocapsule systems are described that incorporate compounds of formula I or II that allow controlled, timed release of said compounds. Also described are the production method, the pharmaceutical compositions and the use for preparing a drug.

Descripción de resultados de la reconstrucción de placa plantar en inestabilidad de la segunda articulación metatarsofalángica

Objetivo: Describir los desenlaces funcionales, complicaciones postoperatorias, dolor y satisfacción de un grupo de pacientes con diagnóstico de inestabilidad de segunda articulación metatarsofalángica y lesión de la placa plantar, que fueron intervenidos quirúrgicamente para su reconstrucción en el Hospital Universitario de cuarto nivel Fundación Santa Fé de Bogotá, en el periodo comprendido entre Enero de 2010 hasta Diciembre de 2015. Métodos: Estudio descriptivo de corte transversal que evalúa desenlaces funcionales, dolor y satisfacción para un grupo consecutivo de pacientes con diagnóstico de inestabilidad de la segunda articulación metatarsofalángica que fueron intervenidos quirúrgicamente mediante reconstrucción de la placa plantar entre Enero de 2010 a Diciembre de 2015 en el Hospital Universitario Fundación Santa fe de Bogotá. Resultados: El procedimiento se realizó a 39 pacientes (40 MTF), encontrando mejoría en dolor, función y satisfacción. El dolor postoperatorio paso de severo a leve en el 80% de los pacientes, 67.5% de los pacientes presentaron prueba de aprehensión positiva, 85% alineamiento adecuado, el reporte de escala de AOFAS postoperatoria fue de 87, y los resultados fueron satisfactorios en un 94.5%. La principal complicación con la cirugía fue la extensión residual del dedo operado (22.5%). Conclusiones: La reconstrucción de la placa plantar en casos de inestabilidad metatarsofalángica ha demostrado tener resultados satisfactorios, en el presente estudio encontramos mejoría respecto a dolor, función y satisfacción posterior a la realización del procedimiento. Sin embargo puede presentar complicaciones como extensión residual del dedo o elevación, rigidez y recidiva.

Apatite-Polymer Composite Particles for Controlled Delivery of BMP-2: In Vitro Release and Cellular Response

Bone morphogenetic protein-2 (BMP-2) has the ability to induce osteoblast differentiation of undifferentiated cells, resulting in the healing of skeletal defects when delivered with a suitable carrier. We have applied a versatile delivery platform comprising a novel composite of two biomaterials with proven track records – apatite and poly(lactic-co-glycolic acid) (PLGA) – to the delivery of BMP-2. Sustained release of this growth factor was tuned with variables that affect polymer degradation and/or apatite dissolution, such as polymer molecular weight, polymer composition, apatite loading, and apatite particle size. The effect of released BMP-2 on C3H10T1/2 murine pluripotent mesenchymal cells was assessed by tracking the expression of osteoblastic makers, alkaline phosphatase (ALP) and osteocalcin. Release media collected over 100 days induced elevated ALP activity in C3H10T1/2 cells. The expression of osteocalcin was also upregulated significantly. These results demonstrated the potential of apatite-PLGA composite particles for releasing protein in bioactive form over extended periods of time.

Development and In Vitro Evaluation of Propranolol Hydrochloride Controlled Release Tablets Using HPMC as Matrix Former

The purpose of this paper was to produce controlled-release matrices with 120 mg of propranolol hydrochloride (PHCl) employing hydroxypropyl methylcellulose (HPMC, Methocel (R) K100) as the gel forming barrier. Although this class of polymers has been commonly used for direct compression, with the intent of use reduced polymer concentrations to achieve controlled drug release, in this study tablets were produced by the wet granulation process. HPMC percentages ranged from 15-34 % and both soluble and non soluble diluents were tested in the 10 proposed tablet compositions. Dissolution testing of matrices was performed over a 12 h period in 1.2 pH medium (the first 2 h) and in pH 6.8 (10 h). Dissolution kinetic analysis was performed by applying Zero-order, First-order and Higuchi models with the aim of elucidating the drug release mechanism. All physical-chemical characteristics such as average weight, friability, hardness, diameter, height, and drug content were in accordance to the pharmacopeial specifications. Taking into account that PHCl is a very soluble drug, low concentrations (15 %) of HPMC were sufficient to reduce the drug release and to promote controlled release of PHCl, presenting good dissolution efficiencies, between 50 % and 63 %. The Higuchi model has presented the best fit to the 15 % HPMC formulations, indicating that the main release mechanism was diffusion. It could be concluded that the application of the wet granulation method reduced matrices erosion and promoted controlled release of the drug at low HPMC percentages.

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Endothelialization of sirolimus-eluting stents with slow and extended drug release in the porcine overstretch model

BACKGROUND: Vascular healing of intracoronary stents has been shown to be delayed in drug-eluting stents (DES) due to the cytotoxic compounds on the stent surface that prevent stent ingrowth and endothelialization. The lack of endothelialization explains the occurrence of late and very late stent thrombosis in DES. MATERIALS AND METHODS: In 11 house swines (body weight 38-45 kg), 3 stents were implanted randomly into the 3 large epicardial coronary arteries, namely a bare-metal stent (BMS), a sirolimus-eluting stent with slow-release (SES) and a SES with extended-release (SESXR). Stent length was 18 mm, and stent diameter 3 mm. All stents were of identical design. Animals were followed for 3 (n = 3), 7 (n = 4) and 14 (n = 4) days, respectively. One animal died before implantation due to hyperthermia. On the day of explantation, the animals were euthanized and endothelialization was tested by scanning electron microscopy after drying and sputtering the samples. Endothelial coverage was determined semiquantitatively by 2 observers. RESULTS: Endothelialization was more rapid with BMS and SESXR than SES at 3 and 14 days. At 7 days there were no significant differences between the 2 SES. CONCLUSIONS: Endothelialization of intracoronary stents is faster with BMS and SESXR at 3 days than with SES. These differences persist at 14 days, suggesting delayed vascular healing with the slow-release SES.

Characterization and greenhouse evaluation of Brazilian calcined nonapatite phosphate rocks for rice

Little information is available on the agronomic effectiveness of calcined nonapatite phosphate rock (PR) sources containing crandallite minerals in the form of Ca-Fe-Al-P for flooded and upland rice (Oryza sativa L.). We conducted laboratory and greenhouse studies to (i) characterize the mineralogical composition, (ii) investigate the solubility and dissolution behavior, and (iii) evaluate the agronomic effectiveness of two nonapatite PR sources (Juquia and Sapucaia) from Brazil and compared them with (i) a highly reactive Gafsa PR (Tunisia) containing apatite in the form of Ca-P and (ii) a reference water-soluble triple superphosphate (TSP) for flooded and upland rice. After calcination at 500 degrees C for 4 h, the solubility of Juquia PR and Sapucaia PR in neutral ammonium citrate (NAC) significantly increased from almost nil to a maximum of 39.3 and 114 g P kg(-1), respectively. X-ray diffraction showed that crystalline crandallite mineral was transformed to an amophorus form after calcination. The solubility behavior of the two calcined PR sources followed the same trend as Gafsa PR, that is, P release decreased with increasing equilibrium pH in the 0.01 M KCl solution (PH 3.0-8.0). At PH 3, the solubility followed: Gafsa PR > calcined Sapucaia PR > calcined Juquia PR. No P release was detected from any of the PR sources at pH >= 5.0 in the solution, indicating the Ca-P characteristic of the Ca-Fe-Al-P mineral controlled P dissolution of the calcined PR. Without calcination, both Juquia PR and Sapucaia PR were totally ineffective for upland rice grown on a Hiwassee clay loam (fine, kaolinitic, thermic Rhodic Kanhapludult) with pH 5.4 whereas a significant P response was observed with the calcined PR samples. For flooded rice grown on Hiwassee soil, the calcined Juquia PR and Sapucaia PR were 66 and 72%, respectively, as effective as TSP in increasing rice grain yield whereas Gafsa PR was ineffective. For upland rice grown on the unlimed soil, Gafsa PR was as effective as TSP in increasing rice grain yield whereas calcined Juquia PR and Sapucaia PR were 89 and 83% of TSP. The effectiveness of Gafsa PR was reduced to 0% after the soil was limed to pH 7.0 whereas the two calcined PR sources were reduced to 49% of TSP. Soil available P extracted by iron oxide impregnated filter paper (Pi test) or anion-exchange resin after rice harvest correlated well with P uptake by rice grain for flooded and upland rice.

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder

Objective: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filters ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). Results: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. Conclusions: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.