Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin

To promote transungual permeation of nystatin (NYST), molecule with high molecular weight, no water-soluble, amphoteric by iontophoresis. The synergic effect of the combination of cetylpyridinium chloride, CPC, or polyoxyethylene (20) sorbitan monooleate, TW80, and iontophoresis was investigated. In vitro permeation experiments were carried out through bovine hoof slices using vertical diffusion cells. A low current density (0.2 mA/cm2) was applied by introducing Ag/AgCl electrodes in the donor (anode) and receptor (cathode) chambers. The donor phase consisted of a solution, a suspension, or gel-type vehicles containing NYST and surfactants in pH 5.6 HEPES buffer. The addition of CPC to NYST suspension (SOSP) produced a fivefold increase on the permeability of the bovine hoof membrane to the drug. The application of anodal iontophoresis further improved NYST flux. Conversely, NYST transungual permeation was not influenced by TW80 either in the passive diffusion or iontophoretic flux. Furthermore, the iontophoretic treatment does not appear to induce irreversible alterations to the hoof bovine membranes. The present work demonstrated the efficacy of iontophoresis as a treatment for different nail pathologies with large molecules very slightly soluble in water without irreversibly affecting the nail structure. A synergistic effect between CPC and iontophoresis was observed

Antiphospholipid Antibody Testing in a General Population Sample from the USA: An Administrative Database Study

We sought to characterized patterns of aPL testing in a large general population sample from the United States. Using Truven Health MarketScan laboratory data from 2010-2015 we identified individuals tested for lupus anticoagulant(LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein1(aGP1). Our research was approved by the McGill institutional review board (A04-M47-12B). We identified 33,456 individuals with at least one aPL test. Among these, only 6,391 (19%) had all three tests (LA, aCL, aGP1) performed. Confirmatory aPL testing was performed at least 12 weeks later in 77%, 45%, and 41% of initially positive LA, aCL, and aGP1, respectively. Of those re-tested after ≥12 weeks, only 255 (10.6%) were found to have a confirmatory positive aPL test. These findings highlight that aPL testing may often be incompletely performed. Further investigations will be required to better understand the low rate of a confirmatory positive aPL test ≥12 weeks after the initial test

Altered Arterial Stiffness and Subendocardial Viability Ratio in Young Healthy Light Smokers after Acute Exercise

Studies showed that long-standing smokers have stiffer arteries at rest. However, the effect of smoking on the ability of the vascular system to respond to increased demands (physical stress) has not been studied. The purpose of this study was to estimate the effect of smoking on arterial stiffness and subendocardial viability ratio, at rest and after acute exercise in young healthy individuals.Healthy light smokers (n = 24, pack-years = 2.9) and non-smokers (n = 53) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest, and 2, 5, 10, and 15 minutes following an exercise test to exhaustion. Smokers were tested, 1) after 12h abstinence from smoking (chronic condition) and 2) immediately after smoking one cigarette (acute condition). At rest, chronic smokers had higher augmentation index and lower aortic pulse pressure than non-smokers, while subendocardial viability ratio was not significantly different. Acute smoking increased resting augmentation index and decreased subendocardial viability ratio compared with non-smokers, and decreased subendocardial viability ratio compared with the chronic condition. After exercise, subendocardial viability ratio was lower, and augmentation index and aortic pulse pressure were higher in non-smokers than smokers in the chronic and acute conditions. cfPWV rate of recovery of was greater in non-smokers than chronic smokers after exercise. Non-smokers were also able to achieve higher workloads than smokers in both conditions.Chronic and acute smoking appears to diminish the vascular response to physical stress. This can be seen as an impaired 'vascular reserve' or a blunted ability of the blood vessels to accommodate the changes required to achieve higher workloads. These changes were noted before changes in arterial stiffness or subendocardial viability ratio occurred at rest. Even light smoking in young healthy individuals appears to have harmful effects on vascular function, affecting the ability of the vascular bed to respond to increased demands

Interaction between neuroanatomical and psychological changes after mindfulness-based training

Several cross-sectional studies have documented neuroanatomical changes in individuals with a long history of meditation, while a few evidences are available about the interaction between neuroanatomical and psychological changes even during brief exposure to meditation. Here we analyzed several morphometric indexes at both cortical and subcortical brain level, as well as multiple psychological dimensions, before and after a brief -8 weeks- Mindfulness Based Stress Reduction (MBSR) training program, in a group of 23 meditation naı¨ve-subjects compared to age-gender matched subjects. We found a significant cortical thickness increase in the right insula and the somatosensory cortex of MBSR trainees, coupled with a significant reduction of several psychological indices related to worry, state anxiety, depression and alexithymia. Most importantly, an interesting correlation between the increase in right insula thickness and the decrease in alexithymia levels during the MBSR training were observed. Moreover, a multivariate pattern classification approach allowed to identify a cluster of regions more responsive to MBSR training across subjects. Taken together, these findings documented the significant impact of a brief MBSR training on brain structures, as well as stressing the idea of MBSR as a valuable tool for alexithymia modulation, also originally providing a plausible neurobiological evidence of a major role of right insula into mediating the observed psychological changes

Iontophoresis and Surfactants Combination on in Vitro Transungual Permeation of Nystatin

The present investigation was aimed to evaluate in vitro permeation of Nystatin through bovine hoof membranes from topical liquid formulations containing surfactants (Tween 80 and cetylpyridinium chloride) after iontophoretic treatment

Characterization and in vitro evaluation of an (ipn)-hydrogel for transdermal delivery of diltiazem.

Aim The aim of this work was the preparation and the evaluation of an interpenetrating polymer network (IPN)-hydrogel composed of a polyvinyl alcohol (PVA)/chitosan (CS) mixture for transdermal drug delivery. Materials and Methods The IPN-hydrogel was prepared by dissolving the CS in 10% (w/w) solution of PVA acidified with lactic acid, and adding Glyoxal at 50°C as crosslinking agent and was characterized by Fourier-transform infrared spectroscopy (FTIR) and by Differential Scanning Calorimetry (DSC). The dynamic swelling behavior of the PVA/chitosan IPN-hydrogel was studied at 32°C by immersion of the hydrogel both in pH 5.2 phosphate buffer solution (PBS) and in deionised water. It was used to prepare matrices containing diltiazem hydrochloride as a model drug, alone (M1) or added of penetration enhancers: PEG-8 caprylic/capric glycerides (Labrasol®, M2) and C1-C9-Br-morpholinium (a room temperature ionic liquid, M3). Each matrix was submitted to in vitro release test using the paddle-over-disk method (Apparatus 5, USP 29) and 500 ml of PBS pH 5.2 as dissolution medium; the drug concentration in dissolution medium, withdrawn at predetermined time intervals, was quantified by HPLC method. Moreover, in vitro permeation through hairless rat skin of drug from the formulations was determined using Gummer-type vertical cells. Results and Discussion The FTIR spectra of crosslinked IPN-hydrogel showed a reduction of the peak intensity at 1580 cm-1 with respect to uncrosslinked hydrogel, probably due to the reduction of free-NH2 groups of chitosan. DCS analysis highlighted an increase of tg value when compared to uncrosslinked matrix. The formation of a crosslinked polymeric structure leads to a considerable reduction in mobility and to an increase rigidity of the polymer. The swelling index (SI) of the IPN-hydrogel was higher in deionised water, arising up to 1400 % of the initial weight, while the SI was 30 % in PBS solution. The drug release from M1, M2 and M3 formulations was characterized by a diffusive mechanisms and the amount of drug permeated through the skin was related to the physico – chemical characteristics of the matrices. The preliminary results confirm that INP-hydrogel could be useful to diffusion-controlled system for hydrophilic drug solubilised in the matrix