2,654 research outputs found
Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis
Microporous, poly (ε-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis
Bumps and rings in a two-dimensional neural field: splitting and rotational instabilities
In this paper we consider instabilities of localised solutions in planar neural field firing rate models of Wilson-Cowan or Amari type. Importantly we show that angular perturbations can destabilise spatially localised solutions. For a scalar model with Heaviside firing rate function we calculate symmetric one-bump and ring solutions explicitly and use an Evans function approach to predict the point of instability and the shapes of the dominant growing modes. Our predictions are shown to be in excellent agreement with direct numerical simulations. Moreover, beyond the instability our simulations demonstrate the emergence of multi-bump and labyrinthine patterns.
With the addition of spike-frequency adaptation, numerical simulations of the resulting vector model show that it is possible for structures without rotational symmetry, and in particular multi-bumps, to undergo an instability to a rotating wave. We use a general argument, valid for smooth firing rate functions, to establish the conditions necessary to generate such a rotational instability. Numerical continuation of the rotating wave is used to quantify the emergent angular velocity as a bifurcation parameter is varied. Wave stability is found via the numerical evaluation of an associated eigenvalue problem
Design and synthesis of 5-hydroxytryptamine analogues: The photochemistry of certain steroids
Design and Synthesis of 5-Hydroxytryptamine Analogues. - The primary processes of drug absorption, distribution, and metabolism are outlined, and their possible influence upon attempted correlations between chemical structure and pharmacological action emphasised. Theories concerning the mode of action of drugs and in particular the role of the receptor theory are reviewed. The general pharmacological and physiological properties of 5-hydroxytryptamine and related compounds are also discussed. Current views concerning the role of endogenous 5-hydroxytryptamine and the nature of the 5-hydroxytryptamine receptor are included. Certain previously reported compounds which may be regarded as "less flexible" analogues of 5-hydroxytryptamine and tryptamine are noted and attempts to prepare other similarly "rigid" analogues are described. Such compounds should prove useful in investigations aimed at determining the structural requirements of the 5-hydroxytryptamine receptor. Routes to 4- and 5-amino-1,3,4,5-tetrahydrobenz [c,d]indole and the corresponding 6-hydroxy derivatives, 3-amino-6-hydroxy-1,2,3,4-tetrahydrocarbazole, and 3-amino-7-hydroxy-1,2,3,4-tetrahydrocyclopent[b]indole are investigated, and successful syntheses are recorded. The Photochemistry of Certain Steroids.- The transformations by which light-sensitive compounds are modified under the influence of ultraviolet light are briefly outlined according to the chromophore responsible for the initial excitation; examples of such transformations are drawn, wherever possible, from previously reported light-induced reactions of pharmacologically and physiologically active molecules. The photochemistry of cortisone acetate, 11-ketoprogesterone and progesterone in ethanol is reported; the major products isolated from these reactions were the corresponding 5 beta-dihydrosteroids resulting from photochemically-induced reduction of the C (4,5) double bond. The photochemistry of certain 3-substituted 6-nitrocholest-5-enes is also reported; 3beta-chloro-, 3beta-acetoxy- and 3beta-trifluoroacetoxy-6-nitrocholest-5-enes in ethanol gave, as the major product, cholest-4-ene-3,6-dione-3-oxime. The 3beta-hydroxy derivative (6-nitrocholesterol), however, gave no oxime but 3beta-hydroxycholest-4-en-6-one and 6beta-nitrocholest-4-en-3beta-ol as major products. The mechanism of formation of these photo-products is discussed; the nature of the product would appear to depend upon the solvent employed for the irradiation, the C(3) substituent, and the wavelength of the radiation employed
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Health-related quality-of-life outcome measures in paediatric palliative care: A systematic review of psychometric properties and feasibility of use
BACKGROUND: The number of children worldwide requiring palliative care services is increasing due to advances in medical care and technology. The use of outcome measures is important to improve the quality and effectiveness of care.
AIM: To systematically identify health-related quality-of-life outcome measures that could be used in paediatric palliative care and examine their feasibility of use and psychometric properties.
DESIGN: A systematic literature review and analysis of psychometric properties.
DATA SOURCES: PsychInfo, Medline and EMBASE were searched from 1 January 1990 to 10 December 2014. Hand searches of the reference list of included studies and relevant reviews were also performed.
RESULTS: From 3460 articles, 125 papers were selected for full-text assessment. A total of 41 articles met the eligibility criteria and examined the psychometric properties of 22 health-related quality-of-life measures. Evidence was limited as at least half of the information on psychometric properties per instrument was missing. Measurement error was not analysed in any of the included articles and responsiveness was only analysed in one study. The methodological quality of included studies varied greatly.
CONCLUSION: There is currently no 'ideal' outcome assessment measure for use in paediatric palliative care. The domains of generic health-related quality-of-life measures are not relevant to all children receiving palliative care and some domains within disease-specific measures are only relevant for that specific population. Potential solutions include adapting an existing measure or developing more individualized patient-centred outcome and experience measures. Either way, it is important to continue work on outcome measurement in this field
Derivation of the Statistical Distribution of the Mass Peak Centroids of Mass Spectrometers Employing Analog-to-Digital Converters and Electron Multipliers
The statistical distribution of mass peak centroids recorded on mass spectrometers employing analog-to-digital converters (ADCs) and electron multipliers is derived from the first principles of the data generation process. The resulting Gaussian model is discussed and is validated with experimental data and with Monte Carlo simulations
Limits and dynamics of stochastic neuronal networks with random heterogeneous delays
Realistic networks display heterogeneous transmission delays. We analyze here
the limits of large stochastic multi-populations networks with stochastic
coupling and random interconnection delays. We show that depending on the
nature of the delays distributions, a quenched or averaged propagation of chaos
takes place in these networks, and that the network equations converge towards
a delayed McKean-Vlasov equation with distributed delays. Our approach is
mostly fitted to neuroscience applications. We instantiate in particular a
classical neuronal model, the Wilson and Cowan system, and show that the
obtained limit equations have Gaussian solutions whose mean and standard
deviation satisfy a closed set of coupled delay differential equations in which
the distribution of delays and the noise levels appear as parameters. This
allows to uncover precisely the effects of noise, delays and coupling on the
dynamics of such heterogeneous networks, in particular their role in the
emergence of synchronized oscillations. We show in several examples that not
only the averaged delay, but also the dispersion, govern the dynamics of such
networks.Comment: Corrected misprint (useless stopping time) in proof of Lemma 1 and
clarified a regularity hypothesis (remark 1
Evaluation of polycaprolactone matrices for sustained intravaginal delivery of a natural macromolecular microbicide, lactoferrin
Polycaprolactone (PCL) matrices incorporating lactoferrin as a natural macromolecular microbicide, were prepared by rapidly cooling a suspension of lactoferrin particulates in PCL solution to induce crystallisation and hardening of the polymer. Thermal analysis revealed a 7% decrease in crystallinity of the PCL phase for 10% lactoferrin-loaded matrices compared with lactoferrin-free matrices and a 41% decrease in hardness of lactoferrin -loaded matrices, indicating a major influence of lactoferrin through inhibition of PCL crystal nucleation and growth. Exposure of the matrices to simulated vaginal fluid (SVF) at 37 °C resulted in rapid release of 13–14% of the lactoferrin content on day 1 and sustained delivery of the glycoprotein with high efficiency (90–95% of the content) over 14 days. SDS-PAGE analysis confirmed molecular weight preservation of the lactoferrin released from PCL matrices into SVF, indicating that it was not degraded during formulation and release. These findings recommend further investigations of PCL matrices as vaginal delivery systems for controlled release of macromolecular microbicides in the treatment and prevention of sexually transmitted infections
Ironbark: Developing a healthy community program for older Aboriginal people
Issue addressed: Programs by, with and for Aboriginal older people must be culturally safe and relevant. Successful elements include being Aboriginal specific and group based. Co-design with Aboriginal people and stakeholders is essential. We describe the co-design process of developing the Ironbark: Healthy Community program. Methods: Aboriginal ways of knowing, being and doing and yarning conversational methods guided the development process, during 2018. A desktop review provided details of current group characteristics and key community stakeholders. Stakeholder engagement regarding views about group operations, participants and benefits also occurred. Aboriginal Elders views of their groups were gathered through yarning circles in New South Wales (NSW). Grounded theory approach was used to ascertain key themes. Results: Initial engagement occurred with 13 different community stakeholders and organisations in three Australian states (NSW, South Australia (SA), Western Australia (WA)). Three yarning circles occurred with Elders from urban (N = 10), regional coastal (N = 10) and regional country (N = 4) groups. Six key themes were organised in three groups according to an Aboriginal ontology. 1. Knowing: groups provide opportunities to share knowledge and connect socially. Adequate program resourcing and sustainability are valued. 2. Being: groups strengthen culture, providing important social, emotional and other forms of support to age well. 3. Doing: previous program experiences inform perceptions for new program operations. Group venues and operational aspects should be culturally safe, acknowledging diversity among Elders, their preferences and community control. Themes were used to develop the program and its resource manual that were finalised with stakeholders, including steering committee approval. Conclusions: Stakeholder feedback at multiple stages and Aboriginal Elders’ perspectives resulted in a new co-designed community program involving weekly yarning circles and social activities. So what?: Co-design, guided by Aboriginal ways of knowing, being and doing, can develop programs relevant for Aboriginal people
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Kernel reconstruction for delayed neural field equations
Understanding the neural field activity for realistic living systems is a challenging task in contemporary neuroscience. Neural fields have been studied and developed theoretically and numerically with considerable success over the past four decades. However, to make effective use of such models, we need to identify their constituents in practical systems. This includes the determination of model parameters and in particular the reconstruction of the underlying effective connectivity in biological tissues. In this work, we provide an integral equation approach to the reconstruction of the neural connectivity in the case where the neural activity is governed by a delay neural field equation. As preparation, we study the solution of the direct problem based on the Banach fixed point theorem. Then we reformulate the inverse problem into a family of integral equations of the first kind. This equation will be vector valued when several neural activity trajectories are taken as input for the inverse problem. We employ spectral regularization techniques for its stable solution. A sensitivity analysis of the regularized kernel reconstruction with respect to the input signal u is carried out, investigating the Frechet differentiability of the kernel with respect to the signal. Finally, we use numerical examples to show the feasibility of the approach for kernel reconstruction, including numerical sensitivity tests, which show that the integral equation approach is a very stable and promising approach for practical computational neuroscience
a-Tocopherol and a-Lipoic Acid Enhance the Erythrocyte Antioxidant Defence in Cyclosporine A-Treated Rats
Abstract: The aim of this study was to determine the effects of dietary antioxidant supplementation with a-tocopherol and a-lipoic acid on cyclosporine A (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats were randomly assigned to either control, antioxidant (a-tocopherol 1000 IU/kg diet and a-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or cyclosporine π antioxidant treatments. Cyclosporine was administered for 7 days after an 8 week feeding period. Plasma was analysed for a-tocopherol, total antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, a-tocopherol and malondialdehye. Cyclosporine administration caused a significant decrease in superoxide dismutase activity (PϽ0.05 control versus cyclosporine) and this was improved by antioxidant supplementation (PϽ0.05 cyclosporine versus cyclosporine π antioxidant; PϽ0.05 control versus cyclosporine π antioxidant). Animals receiving cyclosporine and antioxidants showed significantly increased (PϽ0.05) catalase activity compared to both groups not receiving cyclosporine. Cyclosporine administration induced significant increases in plasma malondialdehyde and creatinine concentration (PϽ0.05 control versus cyclosporine). Antioxidant supplementation prevented the cyclosporine induced increase in plasma creatinine (PϽ0.05 cyclosporine versus cyclosporine π antioxidant; PϾ0.05 control versus cyclosporine π antioxidant), however, supplementation did not alter the cyclosporine induced increase in plasma malondialdehyde concentration (PϾ0.05 cyclosporine versus cyclosporine π antioxidant). Antioxidant supplementation resulted in significant increases (PϽ0.05) in plasma and erythrocyte a-tocopherol in both of the supplemented groups compared to non-supplemented groups. In conclusion, dietary supplementation with a-tocopherol and a-lipoic acid enhanced the erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine treated animals
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