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.

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.

Molecular cloning and biochemical characterization of a myotoxin inhibitor from Bothrops alternatus snake plasma

Phospholipases A(2) (PLA(2)s) are important components of Bothrops snake venoms, that can induce several effects on envenomations such as myotoxicity, inhibition or induction of platelet aggregation and edema. It is known that venomous and non-venomous snakes present PLA(2) inhibitory proteins (PLIs) in their blood plasma. An inhibitory protein that neutralizes the enzymatic and toxic activities of several PLA2s from Bothrops venoms was isolated from Bothrops alternatus snake plasma by affinity chromatography using the immobilized myotoxin BthTX-I on CNBr-activated Sepharose. Biochemical characterization of this inhibitory protein, denominated alpha BaltMIP, showed it to be a glycoprotein with Mr of similar to 24,000 for the monomeric subunit. CD spectra of the PLA(2)/inhibitor complexes are considerably different from those corresponding to the individual proteins and data deconvolution suggests that the complexes had a relative gain of helical structure elements in comparison to the individual protomers, which may indicate a more compact structure upon complexation. Theoretical and experimental structural studies performed in order to obtain insights into the structural features of aBaltMIP indicated that this molecule may potentially trimerize in solution, thus strengthening the hypothesis previously raised by other authors about snake PLIs oligomerization. (C) 2010 Elsevier Masson SAS. All rights reserved.

Chronic Treatment with Quercetin does not Inhibit Angiotensin-Converting Enzyme In Vivo or In Vitro

The precise mechanisms explaining the anti-hypertensive effects produced by quercetin are not fully known. Here, we tested the hypothesis that chronic quercetin treatment inhibits the angiotensin-converting enzyme (ACE). We examined whether quercetin treatment for 14 days reduces in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetised rats. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03-10 mu g/kg, by angiotensin II in doses of 0.01-3 mu g/kg, and to bradykinin in doses of 0.03-10 mu g/kg in anaesthetised rats pre-treated with vehicle (controls), or daily quercetin 10 mg/kg intraperitoneally for 14 days, or a single i.v. dose of captopril 2 mg/kg. Plasma ACE activity was determined by a fluorometric method. Plasma quercetin concentrations were assessed by high performance liquid chromatography. Quercetin treatment induced no significant changes in the hypertensive responses to angiotensin I and angiotensin II, as well in the hypotensive responses to bradykinin (all p > 0.05). Conversely, as expected, a single dose of captopril inhibited the hypertensive responses to angiotensin I and potentiated the bradykinin responses (all p < 0.01), while no change was found in the vascular responses to angiotensin II (all p > 0.05). In addition, although we found significant amounts of quercetin in plasma samples (mean = 206 ng/mL), no significant differences were found in plasma ACE activity in rats treated with quercetin compared with those found in the control group (50 +/- 6 his-leu nmol/min/mL and 40 +/- 7 his-leu nmol/min/mL, respectively; p > 0.05). These findings provide strong evidence indicating that quercetin does not inhibit ACE in vivo or in vitro and indicate that other mechanisms are probably involved in the antihypertensive and protective cardiovascular effects associated with quercetin.

Prosody of tone Sandhi in Vietnamese reduplications

In this paper we take advantage of the segmental control afforded by full and partial Vietnamese reduplication on a constant carrier phrase to obtain acoustic evidence of assymetrical prominence relations (van der Hulst 2005), in support of a hypothesis that Vietnamese reduplications are phonetically right headed and that tone sandhi is a reduction phenomenon occurring on prosodically weak positions (Shih 2005). Acoustic parameters of syllable duration (onset, nucleus and coda), F0 range, F0 contour, vowel intensity, spectral tilt and vowel formant structure are analyzed to determine: (1) which syllable of the two (base or reduplicant) is more prominent and (2) how the tone sandhi forms differ from their full reduplicated counterparts. Comparison of full and partial reduplicant syllables in tone sandhi forms provide additional support for this analysis.

Liquid distribution as a means to describing the granule growth mechanism

Copper concentrate (chalcopyrite) was granulated in a rotating drum with a diameter of 0.3 m and a length of 0.2 m. Water was used as the binder and it was sprayed onto the powder bed with a nozzle. This material exhibited induction type behaviour, which was defined by Iveson and Litster [AIChE J. 44 (1998) 1510]. Induction type behaviour is characterized by the occurrence of an induction stage, during which the granules are gradually being compacted and little or no growth occurs. At the end of this induction stage, binder liquid is squeezed from the interior of the granules onto the granule surface and the granules are then surface-wet. This results in a rapid growth rate of the granules. Different types of experiments were conducted. The influence of the nozzle pressure and the distance from the nozzle to the powder bed on the growth behaviour of the granules as well as on the binder distribution was examined. The results of these experiments led to the postulation of a modified mechanism for induction type behaviour: it was found that after the binder was delivered, there were large granules containing a high amount of binder and small granules containing less binder. During the induction stage, the granules are compacted and binder liquid continuously appears at the surface of the large granules. These wet spots that are continuously being formed pick up the dry and small granules. When all the small granules have been picked up, further expulsion of binder liquid onto the granules' surface results in granules that remain surface-wet. This phenomenon marks the end of the induction stage and it coincides with the disappearance of the small granules. The hypothesis was tested by selectively removing the smaller granules during an experiment. As expected, this resulted in a shorter induction time.

[beta]-Hydroxy-F128b-Methylbutyrate (HMB) Supplementation and the Promotion of Muscle Growth and Strength

[beta]-Hydroxy [beta]-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, is one of the latest dietary supplements promoted to enhance gains in strength and lean body mass associated with resistance training. Unlike anabolic hormones that induce muscle hypertrophy by increasing muscle protein synthesis, HMB is claimed to influence strength and lean body mass by acting as an anticatabolic agent, minimising protein breakdown and damage to cells that may occur with intense exercise. Research on HMB has recently tested this hypothesis, under the assumption that it may be the active compound associated with the anticatabolic effects of leucine and its metabolites. While much of the available literature is preliminary in nature and not without methodological concern, there is support for the claims made regarding HMB supplementation, at least in young, previously untrained individuals. A mechanism by which this may occur is unknown, but research undertaken to date suggests there may be a reduction in skeletal muscle damage, although this has not been assessed directly. The response of resistance trained and older individuals to HMB administration is less clear. While the results of research conducted to date appear encouraging, caution must be taken when interpreting outcomes as most manuscripts are presented in abstract form only, not having to withstand the rigors of peer review. Of the literature reviewed relating to HMB administration during resistance training, only 2 papers are full manuscripts appearing in peer reviewed journals. The remaining 8 papers are published as abstracts only, making it difficult to critically review the research. There is clearly a need for more tightly controlled, longer duration studies to verify if HMB enhances strength and muscular hypertrophy development associated with resistance training across a range of groups, including resistance trained individuals.

Geographic variation and positive selection on M7 lysin, an acrosomal sperm protein in mussels (Mytilus spp.)

Successful fertilization in free-spawning marine organisms depends on the interactions between genes expressed on the surfaces of eggs and sperm. Positive selection frequently characterizes the molecular evolution of such genes, raising the possibility that some common deterministic process drives the evolution of gamete recognition genes and may even be important for understanding the evolution of prezygotic isolation and speciation in the marine realm. One hypothesis is that gamete recognition genes are subject to selection for prezygotic isolation, namely reinforcement. In a previous study, positive selection on the gene coding for the acrosomal sperm protein M7 lysin was demonstrated among allopatric populations of mussels in the Mytilus edulis species group (M. edulis, M. galloprovincialis, and M. trossulus). Here, we expand sampling to include M7 lysin haplotypes from populations where mussel species are sympatric and hybridize to determine whether there is a pattern of reproductive character displacement, which would be consistent with reinforcement driving selection on this gene. We do not detect a strong pattern of reproductive character displacement; there are no unique haplotypes in sympatry nor is there consistently greater population structure in comparisons involving sympatric populations. One distinct group of haplotypes, however, is strongly affected by natural selection and this group of haplotypes is found within M. galloprovincialis populations throughout the Northern Hemisphere concurrent with haplotypes common to M. galloprovincialis and M. edulis. We suggest that balancing selection, perhaps resulting from sexual conflicts between sperm and eggs, maintains old allelic diversity within M. galloprovincialis.

Radiative Relaxation Quantum Yields for Synthetic Eumelanin

We report absolute values for the radiative relaxation quantum yield of synthetic eumelanin as a function of excitation energy. These values were determined by correcting for pump beam attenuation and emission reabsorption in both eumelanin samples and fluorescein standards over a large range of concentrations. Our results confirm that eumelanins are capable of dissipating >99.9% of absorbed UV and visible radiation through nonradiative means. Furthermore, we have found that the radiative quantum yield of synthetic eumelanin is excitation energy dependent. This observation is supported by corrected emission spectra, which also show a clear dependence of both peak position and peak width on excitation energy. Our findings indicate that photoluminescence emission in eumelanins is derived from ensembles of small chemically distinct oligomeric units that can be selectively pumped. This hypothesis lends support to the theory that the basic structural unit of eumelanin is oligomeric rather than heteropolymeric.

The effects of Australian tall poppy attitudes on American value based leadership theory

A survey study of twenty-two Australian CEOs and their subordinates assessed relationships between Australian leader motives, Australian value based leader behaviour, subordinate tall poppy attitudes and subordinate commitment, effectiveness, motivation and satisfaction (CEMS). On the whole, the results showed general support for value based leadership processes. Subsequent regression analyses of the second main component of Value Based Leadership Theory, value based leader behaviour, revealed that the collectivistic, inspirational, integrity and visionary behaviour sub-scales of the construct were positively related with subordinate CEMS. Although the hypothesis that subordinate tall poppy attitudes would moderate value based leadership processes was not clearly supported, subsequent regression analyses found that subordinate tall poppy attitudes were negatively related with perceptions of value based leader behaviour and CEMS. These findings suggest complex relationships between the three constructs, and the proposed model for the Australian context is accordingly amended. Overall, the research supports the need to consider cultural-specific attitudes in management development.

What is the Problem of Ad Hoc Hypotheses?

The received view of an ad hoc hypothesis is that it accounts for only the observation(s) it was designed to account for, and so non-adhocness is generally held to be necessary or important for an introduced hypothesis or modification to a theory. Attempts by Popper and several others to convincingly explicate this view, however, prove to be unsuccessful or of doubtful value, and familiar and firmer criteria for evaluating the hypotheses or modified theories so classified are characteristically available. These points are obscured largely because the received view fails to adequately separate psychology from methodology or to recognise ambiguities in the use of 'ad hoc'.

Popper's Explications of Ad hocness: Circularity, Empirical Content, and Scientific Practice

Popper's explications of 'ad hoc' in relation to hypotheses and explanations turn out to be either trivial, confused or mistaken. One such explication I discuss at length is circularity; another is reduction in empirical content. I argue that non-circularity is preferable to non-ad hocness for an acceptable explanation or explanans, and I isolate some persistent errors in his analysis. Second, Popper is barking up the wrong tree in proscribing reductions in empirical content in novel hypotheses. Such reductions may constitute scientific progress. He fails to show that ad hoc hypothesis are the threat to science he claims.

Popper and his Commentators on the Discovery of Neptune: a close shave for the Law of Gravitation?

Knowledge of residual perturbations in the orbit of Uranus in the early 1840s did not lead to the refutation of Newton's law of gravitation but instead to the discovery of Neptune in 1846. Karl Popper asserts that this case is atypical of science and that the law of gravitation was at least prima facie falsified by these perturbations. I argue that these assertions are the product of a false, a priori methodological position I call, 'Weak Popperian Falsificationism' (WPF). Further, on the evidence the law was not prima facie false and was not generally considered so by astronomers at the time. Many of Popper's commentators (Kuhn, Lakatos, Feyerabend and others) presuppose WPF and their views on this case and its implications for scientific rationality and method suffer from this same defect.

Task Complexity and Variation in L2 Learner’s Oral Discourse

There are many factors which affect the L2 learner’s performance at the levels of phonology, morphology and syntax. Consequently when L2 learners attempt to communicate in the target language, their language production will show systematic variability across the above mentioned linguistic domains. This variation can be attributed to some factors such as interlocutors, topic familiarity, prior knowledge, task condition, planning time and tasks types. This paper reports the results of an on going research investigating the issue of variability attributed to the task type. It is hypothesized that the particular type of task learners are required to perform will result in variation in their performance. Results of the statistical analyses of this study investigating the issue of variation in the performance of twenty L2 learners at the English department of Tabriz University provided evidence in support of the hypothesis that performance of L2 learners show systematic variability attributed to task.

Dependence of public support for survival of wildlife species on their likeability

We surveyed a sample of 204 individuals selected from the public in Brisbane, Australia, to ascertain the extent to which they like or dislike 24 species of wildlife present in tropical Australia. The species belong to three classes: mammals, birds and reptiles. We calculated likeability indices for each of these species. We also asked respondents if they favoured the survival of each of these species and so the percentage of respondents favouring survival of each of these species could be calculated. Thus, using linear regression analysis, the percentage of respondents favouring survival of each of the species was related to their indices of likeability. In addition, the data enables the average likeability of species in the three classes (mammals, birds and reptiles) to be compared with the average support for survival of species in each of these three classes. As a result, we are able to assess how important stated likeability seems to be for preferences for survival of species, and to reconsider the hypothesis in the literature that there is likely to be more public support for the survival of mammals than for birds than for reptiles.