High speed DSC (hyper-DSC) as a tool to measure the solubility of a drug within a solid or semi-solid matrix

Conventional differential scanning calorimetry (DSC) techniques are commonly used to quantify the solubility of drugs within polymeric-controlled delivery systems. However, the nature of the DSC experiment, and in particular the relatively slow heating rates employed, limit its use to the measurement of drug solubility at the drug's melting temperature. Here, we describe the application of hyper-DSC (HDSC), a variant of DSC involving extremely rapid heating rates, to the calculation of the solubility of a model drug, metronidazole, in silicone elastomer, and demonstrate that the faster heating rates permit the solubility to be calculated under non-equilibrium conditions such that the solubility better approximates that at the temperature of use. At a heating rate of 400 degrees C/min (HDSC), metronidazole solubility was calculated to be 2.16 mg/g compared with 6.16 mg/g at 20 degrees C/min. (C) 2005 Elsevier B.V. All rights reserved.

Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics

BACKGROUND: Sensory neuropeptides have been suggested to play a role in the pathogenesis of a number of respiratory diseases including asthma and chronic non-productive cough.

OBJECTIVES: To investigate the action of sensory neuropeptides on airway mast cells obtained by bronchoalveolar lavage (BAL).

METHODS: BAL was performed on 23 nonasthmatic patients with cough (NAC), 11 patients with cough variant asthma (CVA) and 10 nonatopic controls. Washed lavage cells were stimulated (20 min, 37 degrees C) with calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and substance P (25 and 50 micromol/L).

RESULTS: The neuropeptides tested induced histamine release in all groups studied. Only CGRP (50 micromol/L) induced significantly more histamine release from both NAC and CVA patients compared with control subjects (P = 0.038 and 0.045, respectively).

CONCLUSION: Regardless of aetiology, mast cells from patients with chronic cough appear to have an increased responsiveness to CGRP compared with controls. The results of the present study suggest that the role of CGRP in chronic cough should be further investigated.

Complex weathering in drylands: implications of 'stress' history for rock debris breakdown and sediment release

Weathering studies have often sought to explain features in terms of a prevailing set of environmental conditions. However, it is clear that in most present-day hot desert regions, the surface rock debris has been exposed to a range of weathering environments and processes. These different weathering conditions can arise in two ways, either from the effects of long-term climate change acting on debris that remains relatively static within the landscape or through the spatial relocation of debris from high to low altitude. Consequently, each fragment of rock may contain a unique weathering-related legacy of damage and alteration — a legacy that may greatly influence its response to present-day weathering activity. Experiments are described in which blocks of limestone, sandstone, granite and basalt are given ‘stress histories’ by subjecting them to varying numbers of heating and freezing cycles as a form of pre-treatment. These imposed stress histories act as proxies for a weathering history. Some blocks were used in a laboratory salt weathering simulation study while others underwent a 2 year field exposure trial at high, mid and low altitude sites in Death Valley, California. Weight loss and ultrasonic pulse velocity measurements suggest that blocks with stress histories deteriorate more rapidly than unstressed samples of the same rock type exposed to the same environmental conditions. Laboratory data also indicate that the result of imposing a known ‘weathering history’ on samples by pre-stressing them is an increase in the amount of fine sediment released during salt weathering over a given period of time in comparison to unstressed samples.

Reduced K-theory for Azumaya algebras

Abstract In the theory of central simple algebras, often we are dealing with abelian groups which arise from the kernel or co-kernel of functors which respect transfer maps (for example K-functors). Since a central simple algebra splits and the functors above are “trivial” in the split case, one can prove certain calculus on these functors. The common examples are kernel or co-kernel of the maps Ki(F)?Ki(D), where Ki are Quillen K-groups, D is a division algebra and F its center, or the homotopy fiber arising from the long exact sequence of above map, or the reduced Whitehead group SK1. In this note we introduce an abstract functor over the category of Azumaya algebras which covers all the functors mentioned above and prove the usual calculus for it. This, for example, immediately shows that K-theory of an Azumaya algebra over a local ring is “almost” the same as K-theory of the base ring. The main result is to prove that reduced K-theory of an Azumaya algebra over a Henselian ring coincides with reduced K-theory of its residue central simple algebra. The note ends with some calculation trying to determine the homotopy fibers mentioned above.

Eye movements and neurocognitive function in treatment resistant schizophrenia: a pilot study.

Objectives: It is increasingly important to develop predictors of treatment response and outcome in schizophrenia. Neuropsychological impairments, particularly those reflecting frontal lobe function, appear to predict poor outcome. Eye movement abnormalities probably also reflect frontal lobe deficits. We wished to see if these two aspects of schizophrenia were correlated and whether they could distinguish a treatment resistant from a treatment responsive group. Methods: Ten treatment resistant schizophrenic patients were compared with ten treatment responsive patients on three eye movement paradigms (reflexive saccades, antisaccades and smooth pursuit), clinical psychopathology (BPRS, SANS and CGI) and a neuropsychological test battery designed to detect frontal lobe dysfunction. Ten aged-matched controls also carried out the eye movement tasks. Results: Both treatment responsive (p = 0.038) and treatment resistant (p = 0.007) patients differed significantly from controls on the antisaccade task. The treatment resistant group had a higher error rate than the treatment responsive group, but the difference was not statistically significant. Similar poor neuropsychological test performance was found in both groups. Conclusions: To demonstrate the biological differences characteristic of treatment resistance, larger sample sizes and wider differences in outcome between the two groups are necessary.

Anti-sized reed bed system for animal wastewater treatment: a comparative study

This paper presents a comparative study on the treatment of high-strength animal wastewater in two parallel lab-scale constructed reed bed systems, progressively-sized system and anti-sized system, which have same configuration but different arrangement of bed media. The reed bed systems were operated in a tidal flow pattern to treat diluted pig slurry. Detailed analyses were carried out for the removal of some key pollutants including COD, BOD5, NH4-N, P and suspended solids. The results showed that both systems have considerable capacity for the removal of solids, organic matter and inorganic nutrients. The formation of biofilms on the surfaces of gravel media in both reed bed systems was monitored by scanning selected gravel samples using scanning electron microscopy. In general, no significant difference was detected with regard to the percentage pollutant removal in the systems. However, the anti-sized system demonstrated a clear advantage in its ability to slow down the clogging of bed media and avoid the impairment of long-term functioning and sustainability of the beds. A conceptual model was developed to predict the occurrence of the clogging. The validity of the model was tested using data from this study and from the literatures.

Effect of the carburization of MoO3-based catalysts on the activity for butane hydroisomerization

Catalysts based on molybdena (MoO3) reduced at mild temperatures are highly active and selective for the hydroisomerization of alkanes: however, further catalyst development has been hampered by the structural complexity of the material and the controversy regarding the nature of the active phase. The present work is aimed at determining the relationship between the content of carbon present in an oxycarbide phase and the activity for n-butane hydroisomerization. A series of temperature-programmed oxidation (TPO) and temporal analysis of product (TAP) data showed that the oxycarbidic carbon content is not related to the activity of the sample for the isomerization of n-butane to isobutane. The formation of a carbon-containing phase is, therefore, not crucial to obtain an active catalyst. This study also highlights the capability of the multi-pulse TAP technique to investigate structure-activity relationships over materials with readily variable atomic composition. (C) 2008 Elsevier B.V. All rights reserved.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.

AIMS
To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the in?uence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or in?ammatory bowel disease (IBD).
METHODS
Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94?A and IVS2+21A?C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined.
RESULTS
Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients,P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A?C variants among ALL and IBD patients had signi?cantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients,P = 0.047 in IBD patients). The study con?rmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a signi?cant association between inosine triphosphatase IVS2+21A?C variants with thrombocytopenia (P = 0.012).
CONCLUSIONS
Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose
individualization.

Translating evidence into practice: A shared priority in public health?

Translational and transdisciplinary research is needed to tackle complex public health problems. This article has three aims. Firstly, to determine how academics and non-academics (practitioners, policy makers and community workers) identified with the goals of the UKCRC Centre of Excellence for Public Health in Northern Ireland and how their attitudes varied in terms of knowledge brokerage and translation. Secondly, to map and analyse the network structure of the public health sector and the placement of the Centre within this. Thirdly, to aggregate responses from members of the network by work setting to construct the trans-sectoral network and devise the Root Mean Sum of Squares to determine the quality and potential value of connections across this network.The analysis was based on data collected from 98 individuals who attended the launch of the Centre in June 2008. Analysis of participant expectations and personal goals suggests that the academic members of the network were more likely to expect the work of the Centre to produce new knowledge than non-academics, but less likely to expect the Centre to generate health interventions and influence health policy. Academics were also less strongly oriented than non-academics to knowledge transfer as a personal goal, though more confident that research findings would be diffused beyond the immediate network. A central core of five nodes is crucial to the overall configuration of the regional public health network in Northern Ireland, with the Centre being well placed to exert influence within this. Though the overall network structure is fairly robust, the connections between some component parts of the network - such as academics and the third sector - are unidirectional.Identifying these differences and core network structure is key to translational and transdisciplinary research. Though exemplified in a regional study, these techniques are generalisable and applicable to many networks of interest: public health, interdisciplinary research or organisational involvement and stakeholder linkage.

WASP-24 b: A New Transiting Close-in Hot Jupiter Orbiting a Late F-star

We report the discovery of a new transiting close-in giant planet, WASP-24 b, in a 2.341 day orbit, 0.037 AU from its F8-9 type host star. By matching the star's spectrum with theoretical models, we infer an effective temperature T eff = 6075 ± 100 K and a surface gravity of log g = 4.15 ± 0.10. A comparison of these parameters with theoretical isochrones and evolutionary mass tracks places only weak constraints on the age of the host star, which we estimate to be 3.8+1.3 –1.2 Gyr. The planetary nature of the companion was confirmed by radial velocity measurements and additional photometric observations. These data were fit simultaneously in order to determine the most probable parameter set for the system, from which we infer a planetary mass of 1.071+0.036 –0.038 M Jup and radius 1.3+0.039 –0.037 R Jup.

Effectiveness of different footbath solutions in the treatment of digital dermatitis in dairy cows

Three experiments were conducted to test the effectiveness of different footbath solutions and regimens in the treatment of digital dermatitis (DD) in dairy cows. During the study, groups of cows walked through allocated footbath solutions after milking on 4 consecutive occasions. All cows were scored weekly for DD lesion stage on the hind feet during milking. A “transition grade” was assigned on the basis of whether the DD lesions improved (1) or deteriorated or did not improve (0) from week to week. This grade per cow was averaged for all cows in the group. In experiment 1, 118 cows were allocated to 1 of 3 footbath treatments for 5 wk: (1) 5% CuSO4 each week, (2) 2% ClO- each week, or (3) no footbath (control). The mean transition grade, and proportion of cows without DD lesions at the end of the trial were significantly higher for treatment 1 above (0.36, 0.13, and 0.11, respectively; standard error of the difference, SED=0.057). In experiment 2, 117 cows were allocated to 1 of 4 footbath treatment regimens for 8 wk: (1) 5% CuSO4 each week, (2) 2% CuSO4 each week, (3) 5% CuSO4 each fortnight, or (4) 2% CuSO4 each fortnight. For welfare reasons, cows allocated to the weekly and fortnightly footbath regimens had an average prevalence of >60% and =25% active DD at the start of the trial, respectively. Significantly more cows had no DD lesions (0.53 vs. 0.36, respectively; SED=0.049), and the mean transition grade of DD lesions was higher in the 5% compared with the 2% weekly CuSO4 treatment (0.52 vs. 0.38, respectively; SED=0.066). Similarly, significantly more cows had no DD lesions in the 5% compared with the 2% fortnightly CuSO4 treatments (0.64 vs. 0.47, respectively; SED=0.049). In experiment 3, 95 cows were allocated to 1 of 3 footbath treatments: (1) each week alternating 5% CuSO4 with 10% salt water, (2) each week alternating 5% CuSO4 with water, or (3) 5% CuSO4 each fortnight (control). After 10 wk, more cows had no DD in the salt water treatment than in the control treatment (0.35 vs. 0.26, respectively; SED=0.038), but levels of active lesions were higher for this treatment than in the other 2 treatments (0.17, 0.00, and 0.13, respectively; SED=0.029). Treatment did not affect mean transition grade of DD lesions. In conclusion, CuSO4 was the only footbath solution that was consistently effective for treatment of DD. In cases when DD prevalence was high, a footbath each week using 5% CuSO4 was the most effective treatment.

The Economic Costs of Health Service Treatments for Asbestos-Related Mesothelioma Deaths

This article explores the complex and neglected picture of occupational and environmental disease healthcare costs specifically relating to asbestos. Diagnosed mesothelioma cases in Scotland in one calendar year were used to investigate the subject in greater depth. Data from UK sources on asbestos disease types recorded in 2000 and their disease treatment costs were obtained. Acute care economic costs of these diseases are estimated. One hundred and twenty diagnosed, recorded, and treated cases of asbestos-related diseases occurred in 2000 in Scotland. Mesothelioma accounted for 100 cases and directly cost Scottish National Health Service hospitals an estimated 942,038 pounds. The estimated UK figure in 2000 was at least 16,014,646 pounds because official figures for diagnosed and recorded deaths from mesothelioma are running at over 1700 a year with rises predicted for 2010 of 2000 deaths. By 2003, 50,000 people in the UK had died from diagnosed and recorded mesothelioma since records began. Earlier disease treatment costs would have been significantly lower than those in 2000 but, at 2000 prices, cost to the UK was roughly 471,019,000 pounds in acute hospital expenditure. Figures for primary care costs, including caregiver costs, are incomplete or unknown. These disease costs are substantial and have some international generalizability. Treatment patterns and costs vary greatly. Many lung cancer cases due to asbestos exposure occur globally for each mesothelioma case. Hence figures provided in this article are certain to be gross underestimates of the total health service and personal economic costs of asbestos illness and treatment in Scotland.