Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques

The solubility of penciclovir (C10N5O3H17) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15–0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoretically determined differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) data. Intra- and inter-batch data precision values were determined; intra values were more precise. Microscopy was additionally useful for examining crystal shape, size distribution and homogeneity of drug distribution within the film. Whereas DSC also determined melting point, XRPD identified polymorphs and release data provided relevant kinetics.

Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses

Synaptic vesicle glycoprotein (SV)2A is a transmembrane protein found in secretory vesicles and is critical for Ca2+-dependent exocytosis in central neurons, although its mechanism of action remains uncertain. Previous studies have proposed, variously, a role of SV2 in the maintenance and formation of the readily releasable pool (RRP) or in the regulation of Ca2+ responsiveness of primed vesicles. Such previous studies have typically used genetic approaches to ablate SV2 levels; here, we used a strategy involving small interference RNA (siRNA) injection to knockdown solely presynaptic SV2A levels in rat superior cervical ganglion (SCG) neuron synapses. Moreover, we investigated the effects of SV2A knockdown on voltage-dependent Ca2+ channel (VDCC) function in SCG neurons. Thus, we extended the studies of SV2A mechanisms by investigating the effects on vesicular transmitter release and VDCC function in peripheral sympathetic neurons. We first demonstrated an siRNA-mediated SV2A knockdown. We showed that this SV2A knockdown markedly affected presynaptic function, causing an attenuated RRP size, increased paired-pulse depression and delayed RRP recovery after stimulus-dependent depletion. We further demonstrated that the SV2A–siRNA-mediated effects on vesicular release were accompanied by a reduction in VDCC current density in isolated SCG neurons. Together, our data showed that SV2A is required for correct transmitter release at sympathetic neurons. Mechanistically, we demonstrated that presynaptic SV2A: (i) acted to direct normal synaptic transmission by maintaining RRP size, (ii) had a facilitatory role in recovery from synaptic depression, and that (iii) SV2A deficits were associated with aberrant Ca2+ current density, which may contribute to the secretory phenotype in sympathetic peripheral neurons.

Melatonin and IP(3)-induced Ca(2+) Release from Intracellular Stores in the Malaria Parasite Plasmodium falciparum within Infected Red Blood Cells

IP(3)-dependent Ca(2+) signaling controls a myriad of cellular processes in higher eukaryotes and similar signaling pathways are evolutionarily conserved in Plasmodium, the intracellular parasite that causes malaria. We have reported that isolated, permeabilized Plasmodium chabaudi, releases Ca(2+) upon addition of exogenous IP(3). In the present study, we investigated whether the IP(3) signaling pathway operates in intact Plasmodium falciparum, the major disease-causing human malaria parasite. P. falciparum-infected red blood cells (RBCs) in the trophozoite stage were simultaneously loaded with the Ca(2+) indicator Fluo-4/AM and caged-IP(3). Photolytic release of IP(3) elicited a transient Ca(2+) increase in the cytosol of the intact parasite within the RBC. The intracellular Ca(2+) pools of the parasite were selectively discharged, using thapsigargin to deplete endoplasmic reticulum (ER) Ca(2+) and the antimalarial chloroquine to deplete Ca(2+) from acidocalcisomes. These data show that the ER is the major IP(3)-sensitive Ca(2+) store. Previous work has shown that the human host hormone melatonin regulates P. falciparum cell cycle via a Ca(2+)-dependent pathway. In the present study, we demonstrate that melatonin increases inositol-polyphosphate production in intact intraerythrocytic parasite. Moreover, the Ca(2+) responses to melatonin and uncaging of IP(3) were mutually exclusive in infected RBCs. Taken together these data provide evidence that melatonin activates PLC to generate IP(3) and open ER-localized IP(3)-sensitive Ca(2+) channels in P. falciparum. This receptor signaling pathway is likely to be involved in the regulation and synchronization of parasite cell cycle progression.

Sexually Dimorphic Tegumental Gland Openings in Laniatores (Arachnida, Opiliones), With New Data on 23 Species

Sexually dimorphic glands often release sexual pheromones both in vertebrates and invertebrates. Species of Laniatores (Arachnida, Opiliones) seem to depend on chemical communication but few studies have addressed this topic. In this study, we review the literature for the Phalangida and present new data for 23 species of Laniatores. In 16 taxa, we found previously undescribed sexually dimorphic glandular openings on the femur, patella, metatarsus, and tarsus of legs I and metatarsus of legs III and IV For the other species, we provide scanning electron micrographs of previously undescribed sexually dimorphic setae and pegs located on swollen regions of the legs. We also list additional species in which males have swollen regions on the legs, including the tibia, metatarsus, and tarsus of legs I, trochanter and tibia of legs II, femur, metatarsus, and tarsus of legs III, and metatarsus and tarsus of legs IV. The function and biological role of the secretions released by these glands are discussed. J. Morphol. 271:641-653, 2010. (C) 2009 Wiley-Liss, Inc.

Effect of plant neutrophil elastase inhibitor on leucocyte migration, adhesion and cytokine release in inflammatory conditions

BACKGROUND AND PURPOSE The serine and cysteine peptidase inhibitor, BbCI, isolated from Bauhinia bauhinioides seeds, is similar to the classical plant Kunitz inhibitor, STI, but lacks disulphide bridges and methionine residues. BbCI blocks activity of the serine peptidases, elastase (K(iapp) 5.3 nM) and cathepsin G (K(iapp) 160.0 nM), and the cysteine peptidase cathepsin L (K(iapp) 0.2 nM). These three peptidases play important roles in the inflammatory process. EXPERIMENTAL APPROACH We measured the effects of BbCI on paw oedema and on leucocyte accumulation in pleurisy, both induced by carrageenan. Leucocyte-endothelial cell interactions in scrotal microvasculature in Wistar rats were investigated using intravital microscopy. Cytokine levels in pleural exudate and serum were measured by ELISA. KEY RESULTS Pretreatment of the animals with BbCI (2.5 mg.kg(-1)), 30 min before carrageenan-induced inflammation, effectively reduced paw oedema and bradykinin release, neutrophil migration into the pleural cavity. The number of rolling, adhered and migrated leucocytes at the spermatic fascia microcirculation following carrageenan injection into the scrotum were reduced by BbCI pretreatment. Furthermore, levels of the rat chemokine cytokine-induced neutrophil chemo-attractant-1 were significantly reduced in both pleural exudates and serum from animals pretreated with BbCI. Levels of interleukin-1 beta or tumour necrosis factor-alpha, however, did not change. CONCLUSIONS AND IMPLICATIONS Taken together, our data suggest that the anti-inflammatory properties of BbCI may be useful in investigations of other pathological processes in which human neutrophil elastase, cathepsin G and cathepsin L play important roles.

On the release of metronidazole from natural rubber latex membranes

The controlled release of drugs can be efficient if a suitable encapsulation procedure is developed, which requires biocompatible materials to hold and release the drug. In this study, a natural rubber latex (NRL) membrane is used to deliver metronidazole (MET), a powerful antiprotozoal agent. MET was found to be adsorbed on the NRL membrane, with little or no incorporation into the membrane bulk, according to energy dispersive X-ray spectroscopy. X-ray diffraction and FTIR spectroscopy data indicated that MET retained its structural and spectroscopic properties upon encapsulation in the NRL membrane, with no molecular-level interaction that could alter the antibacterial activity of MET. More importantly, the release time of MET in a NRL membrane in vitro was increased from the typical 6-8 h for oral tablets or injections to ca. 100 h. The kinetics of the drug release could be fitted with a double exponential function, with two characteristic times of 3.6 and 29.9 h. This is a demonstration that the induced angiogenesis known to be provided by NRL membranes can be combined with a controlled release of drugs, whose kinetics can be tailored by modifying experimental conditions of membrane fabrication for specific applications. (C) 2010 Elsevier B.V. All rights reserved.

End-Permian catastrophe by a bolide impact: evidence of a gigantic release of sulfur from the mantle

Our studies in southern China have revealed a remarkable sulfur and strontium isotope excursion at the end of the Permian, along with a coincident concentration of impact- metamorphosed grains and kaolinite and a significant decrease in manganese, phosphorous, calcium, and microfossils (foraminifera). These data suggest that an asteroid or a comet hit the ocean at the end of Permian time and caused a rapid and massive release of sulfur from the mantle to the ocean-atmosphere system, leading to significant oxygen consumption, acid rain, and the most severe biotic crisis in the history of life on Earth.

Attack vector analysis and privacy-preserving social network data publishing

This paper addresses the problem of privacy-preserving data publishing for social network. Research on protecting the privacy of individuals and the confidentiality of data in social network has recently been receiving increasing attention. Privacy is an important issue when one wants to make use of data that involves individuals' sensitive information, especially in a time when data collection is becoming easier and sophisticated data mining techniques are becoming more efficient. In this paper, we discuss various privacy attack vectors on social networks. We present algorithms that sanitize data to make it safe for release while preserving useful information, and discuss ways of analyzing the sanitized data. This study provides a summary of the current state-of-the-art, based on which we expect to see advances in social networks data publishing for years to come.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians : a model process

Background
The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients.

Methods
The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug.

Results
Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug.

Conclusions
Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.

Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process

BACKGROUND: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. METHODS: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. RESULTS: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. CONCLUSIONS: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Capture, hold, release: an ontology of motion capture

In proposing an ontology of motion capture, this paper identifies three modalities — capture, hold, release — to conceptualise the peculiar affordances of motion capture technology in its relationship to a performer's movement. Motion capture is unique among contemporary moving image media in its capacity to re-perform a performer'srecorded movement a potentially limitless number of times, e.g. as applied to innumerable different CG characters. Unlike live-action film or even rotoscoping (motion capture's closest equivalent), the movement extracted from the captured performance lives on, but only by way of the inimagable (non-visible) domain of motion data.Motion data 'holds' movement itself in inimagable form, and 'releases' it in the domain of the digital moving image. This tri-fold conception relates an important dimension of (Heideggerian) Being to the idea of movement as fundamental to an ontology or 'being' of motion capture. At the same time, the proposed ontology challenges the 'illusion of life' metaphor as the accepted definition of (motion capture) animation.The Oscar's Special Rules for the Animated Feature Film Award asserts that 'by itself' motion capture does not qualify as an animation method. The notion that a technology could do or be anything 'by itself' affords a conceptual leap toward Heideggerian thinking on the nature of Being as embodied in temporality, in which past, present and future are unified.In its capacity to operate outside the domain of the digital moving image, the concept of 'movement itself' not only articulates an ontology of motion capture: motion capture itself can be understood to be brought into being by movement, thus also challenging the notion that capture technology has a parasitic relationship to a performer's originary performance.

A field study to describe diel, tidal and semilunar rhythms of larval release in an assemblage of tropical rocky shore crabs

Available information on the larval release rhythms of brachyurans is biased to temperate estuarine species and outcomes resulting from some sort of artificial manipulation of ovigerous females. In this study we applied field methods to describe the larval release rhythms of an assemblage of tropical rocky shore crabs. Sampling the broods of ovigerous females of Pachygrapsus transversus at two different shores indicated a spatially consistent semilunar pattern, with larval release maxima around the full and new moon. Yet, synchronism between populations varied considerably, with the pattern obtained at the site exposed to a lower wave action far more apparent. Breeding cohorts at one of the sampled shores apparently belonged to actual age groups composing the ovigerous population. The data suggest that these breeding groups release their larvae in alternate syzygy periods, responding to a lunar cycle instead of the semilunar pattern observed for the whole population. For the description of shorter-term rhythms, temporal series at hour intervals were obtained by sampling the plankton and confinement boxes where ovigerous females were held. Unexpectedly, diurnal release activity prevailed over nocturnal hatching. Yet, only grapsids living higher on the shore exhibited strong preferences over the diel cycle, with P. transversus releasing their larvae during the day and Geograpsus lividus during the night. The pea crab Dissodactylus crinitichelis, the spider crab Epialtus brasiliensis and a suite of xanthoids undertook considerable releasing activity in both periods. Apart from the commensal pea crab D. crinitichelis, all other taxa revealed tide-related rhythms of larval release, with average estimates of the time of maximum hatching always around the time of high tides; usually during the flooding and slack, rather than the ebbing tide. Data obtained for P. transversus females held in confinement boxes indicated that early larval release is mostly due to nocturnal hatching, while zoeal release in diurnal groups took place at the time of high tide. Since nocturnal high tides at the study area occurred late, sometimes close to dusk, early release would allow more time for offshore transport of larvae when the action of potential predators is reduced.

On the release of metronidazole from natural rubber latex membranes

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

Nitric oxide release using natural rubber latex as matrix

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

Semisolid systems containing propolis for the treatment of periodontal disease: In vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G ''), and dynamic viscosity (n') at 5 degrees C, G '' exceeded G'. At 25 and 37 degrees C, n' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation. (c) 2007 Wiley-Liss, Inc.