95 research outputs found
Long-Term Safety and Effectiveness of Lubiprostone, a Chloride Channel (ClC-2) Activator, in Patients with Chronic Idiopathic Constipation
Development of a polymer endovascular prosthesis and its implantation in porcine arteries
A polyethylene-terephthalate braided mesh stent has been developed for application in the (coronary) arterial tree. In vitro measurements showed that the radial pressure delivered by this device was in the same range as that of a stainless steel stent. Hysteresis-like behavior, however, occurred after constraining the polyester stent for a period of only 15 minutes on a delivery system for percutaneous implantation. This implies that the polymer stent must be mounted on this delivery system immediately before the placement procedure, and that either a diameter in the unconstrained condition must be selected, which is considerably larger than the diameter of the target vessel, or stent expansion has to be enhanced by balloon expansion. Taking into account the results obtained during the in vitro studies, we investigated the angiographic patency and histologic features after implantation of this polyester stent in peripheral arteries of pigs. In four animals eight stents were placed. Except for heparin during the implantation procedure only, antithrombotic or antiplatelet drugs were not administered. After 4 weeks repeat angiography was performed. Angiography revealed that five of the six correctly placed stents were patent. At autopsy, two additional patent stents proved to be located in the aortic bifurcation, probably due to failure of the delivery system. Quantitative assessment showed that the mean luminal diameters of the site of stent placement were 3.3 +/- 0.2 mm before, 3.2 +/- 0.2 mm immediately after, and 3.1 +/- 0.3 mm at 4 weeks after implantation. Histology demonstrated an inflammatory reaction of variable severity around the stent fibers. Quantitative histologic measurements showed that the thickness of the neointima was 114 +/- 38 mum after 4 weeks. In conclusion, polyester stents can be constructed with mechanical properties similar to stainless steel stents. Hysteresis-like behavior of polyester stents, however, influences the selection of the nominal stent diameter as well as the forces exerted to the vessel wall. After implantation in porcine peripheral arteries, five of six correctly placed stents were patent at 4 weeks. The extent of neointimal proliferation was similar to that observed after placement of metal stents in swine, despite the presence of a more pronounced inflammatory reaction
Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century
The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis
Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial
Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms
include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and
loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years
as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit
and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D.
Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with
embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from
outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily)
or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool
frequency, and stool consistency on a daily basis.
The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA)
recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and
quality of life will also be assessed.
Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline
and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the
barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact
of ondansetron.
Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining
ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond
Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23
Extrinsic primary afferent signalling in the gut
Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.Australian National Health and Medical Research Counci
Honey, a Gift from Nature to Health and Beauty: A Review
Benefits of honey are contributed by the composition of its elements such as glucose, fructose, glucose oxidase, vitamins and phenolic compounds. For health, honey can be used to treat wounds due to the antibacterial activity conferred by the hydrogen peroxide produced by glucose oxidase in honey. Anti-inflammatory, anti-oxidant, deodorizing and tissue regeneration activities in honey also help in the wound healing process. It can also be an alternative sweetener for diabetic patients to ensure compliance to a healthy diet. Moreover, honey exerts several effects such as lowering low density lipids and increasing high density lipids, thus reducing risk of atherosclerosis. In terms of beauty, honey can be used on skin and hair. It moisturizes skin through its natural humectant properties contributed by high contents of fructose and glucose. Honey treats acne on the skin due to its antibacterial activity, anti-inflammatory action and tissue repair. The hair can benefit from honey in such a way that the hair has abundance, and becomes easier to comb. However, there have not been as many studies regarding the use of honey in skin in comparison to its use for health. Therefore, future studies on honey could research its use, action and benefits in both cosmetics and dermatology
Detection of selected bacterial species in intraoral sites of patients with chronic periodontitis using multiplex polymerase chain reaction
Scoping review of indicators and methods of measurement used to evaluate the impact of dog population management interventions
Background:
Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change.
Methods:
This scoping review collates 26 studies that have assessed the impacts of dog population management interventions.
Results:
It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators.
Conclusion:
The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment
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