Glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), secreted by enteroendocrine L‐cells located most densely in the colon and rectum, are of fundamental importance in blood glucose and appetite ...regulation. In animal models, colonic administration of bile acids can stimulate GLP‐1 and PYY by TGR5 receptor activation. We evaluated the effects of taurocholic acid (TCA), administered as an enema, on plasma GLP‐1 and PYY, as well as gastrointestinal sensations in 10 healthy male subjects, and observed that rectal administration of TCA promptly stimulated secretion of both GLP‐1 and PYY, and increased fullness, in a dose‐dependent manner. These observations confirm that topical application of bile acids to the distal gut may have potential for the management of type 2 diabetes and obesity.
Aims
To evaluate the effects of the dipeptidyl peptidase‐4 inhibitor sitagliptin on blood pressure and heart rate, measured during a previously reported study, in which the effects of sitagliptin ...during intraduodenal glucose infusion at the rate of 2 kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes.
Methods
A total of 10 people with Type 2 diabetes were studied on two different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo. Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), and blood pressure, heart rate, plasma glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide (total and intact), glucose, insulin and glucagon responses were evaluated.
Results
In response to intraduodenal glucose infusion, heart rate (treatment effect: P = 0.001) and serum insulin concentration (treatment × time interaction: P = 0.041) were higher after sitagliptin treatment than placebo, without a significant difference in blood pressure, plasma glucagon or glucose. During intraduodenal glucose infusion, there was a substantial increase in plasma total glucose‐dependent insulinotropic polypeptide on both days (time effect: P < 0.001), but not in total glucagon‐like peptide‐1. After sitagliptin, plasma intact glucagon‐like peptide‐1 concentration increased slightly (treatment × time interaction: P = 0.044) and glucose‐dependent insulinotropic polypeptide concentration increased substantially (treatment × time interaction: P = 0.003).The heart rate response to intraduodenal glucose was related directly to plasma intact glucose‐dependent insulinotropic polypeptide concentrations (r = 0.75, P = 0.008).
Conclusions
Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2 kcal/min in people with Type 2 diabetes, which was associated with augmentation of plasma intact glucose‐dependent insulinotropic polypeptide concentrations. These observations warrant further clarification of a potential role for glucose‐dependent insulinotropic polypeptide in the control of the ‘gut–heart’ axis.
What's new?
The release of glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide after meal ingestion may play a role in the regulation of postprandial cardiovascular function (i.e. the ‘gut–heart’ axis), and earlier studies have shown that postprandial variations in blood pressure, heart rate and splanchnic blood pooling paralleled variations in glucose‐dependent insulinotropic polypeptide, but not glucagon‐like peptide‐1, in healthy people.
In the present study, we showed that the dipeptidyl peptidase‐4 inhibitor, sitagliptin, increased heart rate in people with Type 2 diabetes, under conditions where glucose‐dependent insulinotropic polypeptide was the predominant incretin hormone, warranting further clarification of a potential role of glucose‐dependent insulinotropic polypeptide in the control of the gut–heart axis.
The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like ...peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut-incretin axis.
Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for ...their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification.
To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification.
Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England.
Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded.
Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio OR = 1.69; 95% confidence interval CI = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point.
There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison.
The aim of this questionnaire-based retrospective study was to ascertain veterinary practitioners in the British Isles' approaches to osteoarthritis in dogs. The Mann-Whitney U test, Kruskal-Wallis ...test and multiple ordinal logistic regression were used to compare demographic data with treatment options. Questionnaires were returned by 228 practitioners (a response rate of 22.8 per cent). The majority of responses were from males (70 per cent). Eighty-six per cent (188 of 220) of the respondents had graduated from veterinary schools in the UK and Ireland. Veterinarians who had graduated less recently used exercise modulation less frequently (P<0.004, odds ratio OR=1.06) and ranked exercise modulation as less important (P=0.008, OR=1.04). Veterinarians who had graduated outside the UK or Ireland were less likely (P=0.033, OR=0.46) to use exercise modulation than those who had graduated in the UK or Ireland. Veterinarians who had graduated more recently were less likely (P=0.008, OR=0.95) to use medications. Female veterinary surgeons were less likely to rank medications as important (P<0.0001, OR=0.29) and less likely to rank corticosteroids as important (P=0.046, OR=0.42) than male veterinary surgeons. Practitioners who had graduated outside the UK or Ireland were less likely (P=0.01, OR=0.30) to rank corticosteroids as important. There was a significant mild negative correlation between the frequency of use of structure-modifying osteoarthritis drugs (SMOADs) and practitioners' opinions on rank importance (-0.32, P<0.0001). Medications such as SMOADs and nutraceuticals were ranked as not important but were used frequently. Overall, age, sex, the university of graduation and the number of canine consultations per day had an impact on the practitioners' treatment protocols.
In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when ...attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons.
This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification.
Current Controlled Trials ISRCTN58823759.
Spray application technology JONES, K. M; BOUND, S. A; OAKFORD, M. J
Plant growth regulation,
07/2000, Letnik:
31, Številka:
3
Journal Article
Recenzirano
Spray application technology on perennial tree crops has been a poorly researched subject. Many of the nozzles and sprayers were originally developed for use on row crops which have an even, flat ...profile and spraying is downward. Some of the short-comings of these systems were exposed when tree crops were sprayed, particularly the large and dense trees of 30 years ago.Much of the variation experienced in experimental results where fruit trees had been thinned with bioregulators is likely to have been due to application methods. Air-blast sprayers using hydraulic nozzles resulted in inconsistent results causing many research workers to revert to the use of hand lances and small pumps for their trials. Translation of these results to commercial practices then became a problem, as growers were reluctant to revert to the use of hand lances for thinning, particularly as orchards increased in size.The increased emphasis on reducing the use of chemicals, including bioregulators, on food and the need to use ecologically less wasteful methods of applying them has recently promoted more research into spraying techniques.Early work with spray technology identified factors causing variation. Such factors as the range and size of spray droplets, effect of climate, use of wetters, spreaders and stickers, the carrier medium (oil, water or combination), the use of propelled air, the crop species and it's configuration all impacted on the results.PUBLICATION ABSTRACT
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