Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2)

The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa · s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement.KEY WORDS: amorphous solid dispersion, itraconazole, polyvinyl alcohol, PVAL, solubility enhancement     

Correlates of distribution and nesting success in a Welsh upland Eurasian Curlew Numenius arquata population

Capsule: Habitat structure and composition explained spatial variation in breeding distribution and nesting success in a declining upland Eurasian Curlew Numenius arquata population in North Wales.

Aims: To identify environmental correlates of Curlew breeding distribution, nesting success and change in distribution.

Methods: Thirty random 1?km squares stratified by historical population trend were surveyed for Curlew density and nesting success, and habitat- and predation-related variables in a landscape containing agriculturally improved farmland, and moorland that was partly protected and subject to grazing reductions for nature conservation. Analyses tested for associations between Curlew measures and environmental variables.

Results: Curlew breeding density declined by 29% between 1994 and 2008, and was highest in squares comprising a mixture of moorland and agriculturally improved farmland, and in squares with lower vegetation density and higher cover of Nardus stricta (characteristic of rough grazing). Nesting success was positively associated with cover of Trichophorum germanicum (characteristic of mire). Vegetation density was lower than average in squares with the highest Curlew densities, while in the protected area vegetation density was higher than average.

Conclusion: Habitat and vegetation variables influenced Curlew distribution and nesting success in North Wales, largely in line with previous results but with no evidence for predator-related influences. Habitat condition for Curlew in the protected area could probably be increased through targeted increases in grazing alongside the protection of priority habitats.     

Negative fire feedback in a transitional forest of southeastern Amazonia

Anthropogenic understory fires affect large areas of tropical forest, particularly during severe droughts. Yet, the mechanisms that control tropical forests' susceptibility to fire remain ambiguous. We tested the widely accepted hypothesis that Amazon forest fires increase susceptibility to further burning by conducting a 150 ha fire experiment in a closed-canopy forest near the southeastern Amazon forest–savanna boundary. Forest flammability and its possible determinants were measured in adjacent 50 ha forest plots that were burned annually for 3 consecutive years (B3), once (B1), and not at all (B0). Contrary to expectation, an annual burning regime led to a decline in forest flammability during the third burn. Microclimate conditions were more favorable compared with the first burn (i.e. vapor pressure deficit increased and litter moisture decreased), yet flame heights declined and burned area halved. A slight decline in fine fuels after the second burn appears to have limited fire spread and intensity. Supporting this conclusion, fire spread rates doubled and burned area increased fivefold in B3 subplots that received fine fuel additions. Slow replacement of surface fine fuels in this forest may be explained by (i) low leaf litter production (4.3 Mg ha⁻¹ yr⁻¹), half that of other Amazon forests; and (ii) low fire-induced tree and liana mortality (5.5±0.5% yr⁻¹, SE, in B3), the lowest measured in closed-canopy Amazonian forests. In this transitional forest, where severe seasonal drought removed moisture constraints on fire propagation, a lack of fine fuels inhibited the intensity and spread of recurrent fire in a negative feedback. This reduction in flammability, however, may be short-lived if delayed tree mortality or treefall increases surface fuels in future years. This study highlights that understanding fuel input rate and timing relative to fire frequency is fundamental to predicting transitional forest flammability – which has important implications for carbon emissions and potential replacement by scrub vegetation.     

How do Meat Scarcity and Bushmeat Commodification Influence Sharing and Giving among Forest Foragers? A View from the Central African Republic

Meat sharing is a societal norm among hunter-gatherer societies that provisions families and supports social networks. Meat is also a valued resource central to traditional barter exchange. Ethnographic research often cites prey scarcity and commodification as two factors reducing traditional meat transactions among indigenous Central African foragers. We present quantitative data based on ethnographic observations of foragers in the Central African Republic that show that neither scarcity nor commodification eliminates sharing. The bushmeat market is associated with changes in village demographic structure that limits the distribution of meat among extended kin. Although cash generated from the sale of forest products reduces the need for inter-ethnic barter, gift giving and exchange maintain these important relationships. Our data show the persistence of traditional meat transactions and identify potential changes in demographic structure as a less obvious outcome of the bushmeat trade that can have extended consequences for forager populations.     

Some Problems and Principles of Development

Certain supracellular aspects of embryonic differentiation,illustrated by studies of young chick blastoderms, are discussed.Specifically, the following principles and guidelines seem tobe involved in early development of the chick: egg organization,relative movement, differential growth, regulation, restrictionof regulative capacities, synonomy of regulation and growth,gradients and fields', developmental centers, dominance, integration,environmental control, and induction.     

Surface histidine mutations for the metal affinity purification of a β-carbonic anhydrase

Metal affinity chromatography using polyhistidine tags is a standard laboratory technique for the general purification of proteins from cellular systems, but there have been no attempts to explore whether the surface character of a protein may be engineered to similar affinity. We present the Arg160His mutation of Haemophilus influenzae carbonic anhydrase (HICA), which mimics the endogenous metal affinity of Escherichia coli carbonic anhydrase (ECCA). The purity and activity of the mutant are reported, and the purification is discussed. This is the first step toward developing a general method to engineer surface metal affinity for use in purification and metal labeling techniques.     

Reduced Motor Cortex Activity during Movement Preparation following a Period of Motor Skill Practice

Experts in a skill produce movement-related cortical potentials (MRCPs) of smaller amplitude and later onset than novices. This may indicate that, following long-term training, experts require less effort to plan motor skill performance. However, no longitudinal evidence exists to support this claim. To address this, EEG was used to study the effect of motor skill training on cortical activity related to motor planning. Ten non-musicians took part in a 5-week training study learning to play guitar. At week 1, the MRCP was recorded from motor areas whilst participants played the G Major scale. Following a period of practice of the scale, the MRCP was recorded again at week 5. Results showed that the amplitude of the later pre-movement components were smaller at week 5 compared to week 1. This may indicate that, following training, less activity at motor cortex sites is involved in motor skill preparation. This supports claims for a more efficient motor preparation following motor skill training.