Stability and in vitro penetration study of rutin incorporated in a cosmetic emulsion through an alternative model biomembrane

Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifice. The objectives of this research were the development and stability evaluation of a cosmetic emulsion containing rutin and propylene glycol (penetration enhancer) and the evaluation or rutin in vitro cutaneous penetration and retention from the emulsion, employing an alternative model biomembrane. Emulsion was developed with rutin and propylene glycol, both at 5.0% w/w. Active substance presented on the formulation was quantified by a validated spectrophotometric method at 361.0 nm. Rutin Rutin cutaneous penetration and retention was performed in vertical diffusion cells with shed snake skin of Crotalus durissus, as alternative model biomembrane, and distilled water and ethanol 99.5% (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 +/- 0.5 degrees C with constant stirring of 300 rpm. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after cutaneous penetration/ retention. Emulsion did not promote rutin cutaneous penetration through C. durissus skin, retaining 0.931 +/- 0.0391 mu g rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after stored at 25.0 +/- 2.0 degrees C, 5.0 +/- 0.5 degrees C and 45.0 +/- 0.5 degrees C. In conclusion, it has not been verified the active cutaneous penetration through the model biomembrane, but only its retention on the Crotalus durissus stratum corneum, condition considered stable for 30 days.

Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate

Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (similar to 82%), a mean diameter of 3.0 mu m and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); prenatal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.

A valuation of patients` willingness-to-pay for insulin delivery in diabetes

Objectives: The aim of this study was to determine the insulin-delivery system and the attributes of insulin therapy that best meet patients` preferences, and to estimate patients` willingness-to-pay (WTP) for them. Methods: This was a cross-sectional discrete choice experiment (DCE) study involving 378 Canadian patients with type 1 or type 2 diabetes. Patients were asked to choose between two hypothetical insulin treatment options made up of different combinations of the attribute levels. Regression coefficients derived using conditional logit models were used to calculate patients` WTP. Stratification of the sample was performed to evaluate WTP by predefined subgroups. Results: A total of 274 patients successfully completed the survey. Overall, patients were willing to pay the most for better blood glucose control followed by weight gain. Surprisingly, route of insulin administration was the least important attribute overall. Segmented models indicated that insulin naive diabetics were willing to pay significantly more for both oral and inhaled short-acting insulin compared with insulin users. Surprisingly, type 1 diabetics were willing to pay $C11.53 for subcutaneous short-acting insulin, while type 2 diabetics were willing to pay $C47.23 to avoid subcutaneous short-acting insulin (p < .05). These findings support the hypothesis of a psychological barrier to initiating insulin therapy, but once that this barrier has been overcome, they accommodate and accept injectable therapy as a treatment option. Conclusions: By understanding and addressing patients` preferences for insulin therapy, diabetes educators can use this information to find an optimal treatment approach for each individual patient, which may ultimately lead to improved control, through improved compliance, and better diabetes outcomes.

Excised Porcine Cornea Integrity Evaluation in an in vitro Model of Iontophoretic Ocular Research

Background/Aims: It is a challenge to adapt traditional in vitro diffusion experiments to ocular tissue. Thus, the aim of this work was to present experimental evidence on the integrity of the porcine cornea, barrier function and maintenance of electrical properties for 6 h of experiment when the tissue is mounted on an inexpensive and easy-to-use in vitro model for ocular iontophoresis. Methods: A modified Franz diffusion cell containing two ports for the insertion of the electrodes and a receiving compartment that does not need gassing with carbogen was used in the studies. Corneal electron transmission microscopy images were obtained, and diffusion experiments with fluorescent markers were performed to examine the integrity of the barrier function. The preservation of the negatively charged corneal epithelium was verified by the determination of the electro-osmotic flow of a hydrophilic and non-ionized molecule. Results: The diffusion cell was able to maintain the temperature, homogenization, porcine epithelial corneal structure integrity, barrier function and electrical characteristics throughout the 6 h of permeation experiment, without requiring CO(2) gassing when the receiving chamber was filled with 25 m M of HEPES buffer solution. Conclusion: The system described here is inexpensive, easy to handle and reliable as an in vitro model for iontophoretic ocular delivery studies. Copyright (C) 2010 S. Karger AG, Basel

Assessment of the percutaneous penetration of cisplatin: The effect of monoolein and the drug skin penetration pathway

It was intended to examine the in vitro penetration of cisplatin (CIS) through porcine skin in the presence of different concentrations of monoolein (MO) as well as to verify the main barrier for CIS skin penetration. In vitro skin penetration of CIS was studied from propylene glycol (PG) solutions containing 0%, 5%, 10%, and 20% of MO using Franz-type diffusion cell and porcine ear skin. Pretreatment experiments with MO and experiments with skin without stratum corneum (SC) were also carried out. Skin penetration studies of CIS showed that the presence of MO doubled the drug permeation through the intact skin. However, permeation studies through the skin without SC caused only a small enhancement of CIS permeation compared to intact skin. Moreover, pretreatment of skin with MO formulations did not show any significant increase in the flux of the drug. In conclusion, MO did not act as a real penetration enhancer for CIS, but it increased the drug partition to the receptor solution improving CIS transdermal permeation. The absence of improvement in drug permeation by MO pretreatment and by the removal of SC indicates that the SC is not the main barrier for the permeation of the metal coordination compound. (c) 2009 Elsevier B.V. All rights reserved.

Titanium phosphate for Fuel Cell Proton Conduction Membranes

Environmental issues due to increases in emissions of air pollutants and greenhouse gases are driving the development of clean energy delivery technologies such as fuel cells. Low temperature Proton Exchange Membrane Fuel Cells (PEMFC) use hydrogen as a fuel and their only emission is water. While significant advances have been made in recent years, a major limitation of the current technology is the cost and materials limitations of the proton conduction membrane. The proton exchange membrane performs three critical functions in the PEMFC membrane electrode assembly (MEA): (i) conduction of protons with minimal resistance from the anode (where they are generated from hydrogen) to the cathode (where they combine with oxygen and electrons, from the external circuit or load), (ii) providing electrical insulation between the anode and cathode to prevent shorting, and (iii) providing a gas impermeable barrier to prevent mixing of the fuel (hydrogen) and oxidant. The PFSA (perfluorosulphonic acid) family of membranes is currently the best developed proton conduction membrane commercially available, but these materials are limited to operation below 100oC (typically 80oC, or lower) due to the thermochemical limitations of this polymer. For both mobile and stationary applications, fuel cell companies require more durable, cost effective membrane technologies capable of delivering enhanced performance at higher temperatures (typically 120oC, or higher. This is driving research into a wide range of novel organic and inorganic materials with the potential to be good proton conductors and form coherent membranes. There are several research efforts recently reported in the literature employing inorganic nanomaterials. These include functionalised silica phosphates [1,2], fullerene [3] titania phosphates [4], zirconium pyrophosphate [5]. This work addresses the functionalisation of titania particles with phosphoric acid. Proton conductivity measurements are given together with structural properties.

The prospects for immunotherapy in smoking cessation

Context Smoking is a major preventable cause of death and disability that is maintained by dependence on nicotine. Smoking cessation reduces mortality and morbidity. Although existing pharmacological aids to smoking cessation and relapse prevention (nicotine replacement therapy and bupropion) improve on unassisted quitting and behavioural methods, they are only modestly effective. More effective pharmacological methods are required that improve compliance, reduce side-effects, and can be used in combination with existing cessation methods. Starting point A nicotine vaccine is a promising immunotherapeutic approach to smoking cessation and relapse prevention. Such a vaccine would induce the immune system to form specific antibodies to nicotine to prevent it from crossing the blood-brain barrier to act on receptor sites in the central nervous system. Recent studies in rats provide proof of principle by showing that nicotine-specific antibodies can prevent the reinstatement of nicotine self-administration (N Lindblom et al, Respiration 2002; 69: 254–60) and block dopamine release in the shell of the nucleus accumbens (Sde Villiers et al, Respiration 2002; 69: 247–53). A phase 1 trial of a human cocaine vaccine has also recently been successfully completed (T Kosten et al, Vaccine 2002; 20: 1196–204). A safe and effective human nicotine vaccine would potentially have fewer side-effects and better compliance than existing smoking-cessation pharmacotherapies. It could also be used in combination with some of them (eg, bupropion). Where next? The most promising clinical application of a human nicotine vaccine is likely to be in relapse prevention in abstinent smokers. A vaccine may also have a role in preparing smokers to quit. Clinical trials of safety and efficacy in human smokers and ex-smokers are warranted. If a nicotine vaccine proves to be safe and effective, the health-care system will need to ensure that it is registered for clinical use and that the poorer members of the community (among whom smoking prevalence is now highest in developed countries) have access to the vaccine. The community will need to be appropriately informed about the role of a nicotine vaccine to ensure that it is not prematurely used for preventive purposes in children and adolescents.

Cryptic vicariance in Gulf of California fishes parallels vicariant patterns found in Baja, California mammals and reptiles

Comparisons across multiple taxa can often clarify the histories of biogeographic regions. In particular, historic barriers to movement should affect multiple species and, thus, result in a pattern of concordant intraspecific genetic divisions among species. A striking example of such comparative phylogeography is the recent observation that populations of many small mammals and reptiles living on the Baja, California peninsula have a large genetic break between northern and southern peninsular populations. In the present study, I demonstrate that five species of near-shore fishes living on the Baja coastline of the Gulf of California share this genetic pattern. The simplest explanation for this concordant genetic division within both terrestrial and marine vertebrates is that the Baja peninsula was fragmented by a Plio-Pleistocene marine seaway and that this seaway posed a substantial barrier to movement for near-shore fishes. The genetic divisions within Gulf of California fishes also coincide with recognized biogeographic regions based on fish community composition and several environmental factors. It is likely that adaptation to regional environments and present-day oceanographic circulation limits gene exchange between biogeographic regions and helps maintain evidence of past vicariance.

Differential patterns of Male and Female mtDNA exchange across the Atlantic Ocean in the blue mussel, Mytilus edulis

Comparisons among loci with differing modes of inheritance can reveal unexpected aspects of population history. We employ a multilocus approach to ask whether two types of independently assorting mitochondrial DNAs (maternally and paternally inherited: F- and M-mtDNA) and a nuclear locus (ITS) yield concordant estimates of gene flow and population divergence. The blue mussel, Mytilus edulis, is distributed on both North American and European coastlines and these populations are separated by the waters of the Atlantic Ocean. Gene flow across the Atlantic Ocean differs among loci, with F-mtDNA and ITS showing an imprint of some genetic interchange and M-mtDNA showing no evidence for gene flow. Gene flow of F-mtDNA and ITS causes trans-Atlantic population divergence times to be greatly underestimated for these loci, although a single trans-Atlantic population divergence time (1.2 MYA) can be accommodated by considering all three loci in combination in a coalescent framework. The apparent lack of gene flow for M-mtDNA is not readily explained by different dispersal capacities of male and female mussels. A genetic barrier to M-mtDNA exchange between North American and European mussel populations is likely to explain the observed pattern, perhaps associated with the double uniparental system of mitochondrial DNA inheritance.

Patterns of species diversity in the gastrointestinal helminths of a coral reef fish, Epinephelus merra (Serranidae), from French Polynesia and the south Pacific Ocean

Large-scale patterns of species diversity in the gastrointestinal helminth faunas of the coral reef fish Epinephelus merra (Serranidae) were investigated in French Polynesia and the South Pacific Ocean. The richer barrier reef community in French Polynesia supported richer parasite communities in E. merra than that on the fringing reef. While parasite communities among fish from the same archipelago were similar, differences in potential host species and the distance between archipelagos may have contributed to a qualitative difference in parasite communities between archipelagos. Digenean community diversity in coral reef fishes was greater in the western South Pacific, following similar patterns in free-living species. However, overall species diversity of camallanid nematodes of coral reef fishes does not appear to have been similarly affected.

When oceans meet: a teleost shows secondary intergradation at an Indian-Pacific interface

The Indo-West Pacific is characterized by extraordinary marine species diversity. The evolutionary mechanisms responsible for generating this diversity remain puzzling, but are often linked to Pleistocene sea level fluctuations. The impact of these sea level changes on the population genetic architecture of the estuarine fish Lates calcarifer are investigated via a natural experiment in a region of the Indo-West Pacific known to have undergone considerable change during the Pleistocene. L. calcarifer, a coastline-restricted catadromous teleost, provides an excellent model for studying the effects of sea level change as its habitat requirements potentially make it sensitive to the region's physical history. Evidence was found for a large phylogenetic break (4% mtDNA control region; 0.47% ATPase 6 and 8) either side of the Torres Strait, which separates the Western Pacific and Indian Oceans, although some mixing of the clades was evident. This suggests clinal secondary introgression of the clades via contemporary gene flow. Further, populations on Australia's east coast appear to have passed through a bottleneck. This was linked to the historical drying of the Great Barrier Reef coastal lagoon, which resulted in a significant loss of habitat and forced retreat into isolated refugia. These results suggest that historical eustatic changes have left a significant imprint on the molecular diversity within marine species as well as among them in the Indo-West Pacific.

Vascular leakage stimulates phenotype alteration in ocular cells, contributing to the pathology of proliferative vitreoretinopathy

Plasma leaking from damaged retinal blood vessels can have a significant impact on the pathologies of the posterior segment of the eye. Inflammation in the eye and metabolic change resulting from diabetes mellitus causes vascular leakage with alteration of the phenotype of retinal pigment epithelial (RPE) cells and fibrocytes, resulting in changes in cell function. Phenotypically altered cells then significantly contribute to the pathogenesis of retinopathies by being incorporated into tractional membranes in the vitreous, where they secrete matrix molecules, such as fibronectin, and express altered cell surface antigens. We hypothesize that there is a direct relationship between the leaking of plasma and the proliferation and phenotypic change of RPE cells and fibroblasts, thus exacerbating the pathology of retinal disease. If the hypothesis is correct, control of vascular leakage becomes an important target of therapy in proliferative vitreoretinopathy.

Classical and quantum noise in electronic systems

We review the description of noise in electronic circuits in terms of electron transport. The Poisson process is used as a unifying principle. In recent years, much attention has been given to current noise in light-emitting diodes and laser diodes. In these devices, random events associated with electron transport are correlated with photon emission times, thus modifying both the current statistics and the statistics of the emitted light. We give a review of experiments in this area with special emphasis on the ability of such devices to produce subshot-noise currents and light beams. Finally we consider the noise properties of a class of mesoscopic devices based on the quantum tunnelling of an electron into and out of a bound state. We present a simple quantum model of this process which confirms that the current noise in such a device should be subshot-noise.

Managing the Yongala Historic Shipwreck

The Yongala Historic Shipwreck lies within the Great Barrier Reef Marine Park in northeastern Australia. A draft management plan, produced by the Queensland Museum in 1992, provided primarily for the management of the historical and archaeological values of the wreck. The plan did not outline comprehensive strategies for management of either the special ecological values of the site or an increasing demand by recreational divers to dive the wreck This article will outline the processes involved in integrating management of the social, ecological, and historical values of the wreck into a format that is acceptable to all stakeholders associated with the site.