Monotoring adherence to prescribed medication in type 2 diabetic patients treated with sulfonylureas

Data on adherence to prescribed medication amongst diabetics are scarce. The purpose of this study was to collect information about the dynamics and patterns of compliance of elderly patients with type 2 diabetes mellitus on oral treatment by using different assessment techniques.

Evidence for the existence of a sulfonylurea-receptor-like protein in plants: Modulation of stomatal movements and guard cell potassium channels by sulfonylureas and potassium channel openers

Limitation of water loss and control of gas exchange is accomplished in plant leaves via stomatal guard cells. Stomata open in response to light when an increase in guard cell turgor is triggered by ions and water influx across the plasma membrane. Recent evidence demonstrating the existence of ATP-binding cassette proteins in plants led us to analyze the effect of compounds known for their ability to modulate ATP-sensitive potassium channels (K-ATP) in animal cells. By using epidermal strip bioassays and whole-cell patch-clamp experiments with Vicia faba guard cell protoplasts, we describe a pharmacological profile that is specific for the outward K+ channel and very similar to the one described for ATP-sensitive potassium channels in mammalian cells. Tolbutamide and glibenclamide induced stomatal opening in bioassays and in patch-clamp experiments, a specific inhibition of the outward K+ channel by these compounds was observed. Conversely, application of potassium channel openers such as cromakalim or RP49356 triggered stomatal closure. An apparent competition between sulfonylureas and potassium channel openers occurred in bioassays, and outward potassium currents, previously inhibited by glibenclamide, were partially recovered after application of cromakalim. By using an expressed sequence tag clone from an Arabidopsis thaliana homologue of the sulfonylurea receptor, a 7-kb transcript was detected by Northern blot analysis in guard cells and other tissues. Beside the molecular evidence recently obtained for the expression of ATP-binding cassette protein transcripts in plants, these results give pharmacological support to the presence of a sulfonylurea-receptor-like protein in the guard-cell plasma membrane tightly involved in the outward potassium channel regulation during stomatal movements.

Drugs for diabetes and obesity

14.1 Drugs for diabetes 14.1.1 Diabetes mellitus 14.1.2 Physiology of the pancreas 14.1.3 Insulin replacement therapy 14.1.4 Metformin 14.1.5 Acarbose 14.1.6 Sulfonylureas 14.1.7 Glitazones 14.1.8 Glucagon-like peptide-1, exenatide and sitagliptin 14.2 Drugs for obesity 14.2.1 Introduction 14.2.2 Amphetamine 14.2.3 Phentermine 14.2.5 Orlistat

Hydrolysis of triasulfuron, metsulfuron-methyl and chlorsulfuron in alkaline soil and aqueous solutions

The hydrolysis of triasulfuron, metsulfuron-methyl and chlorsulfuron in aqueous buffer solutions and in soil suspensions at pH values ranging from 5.2 to 11.2 was investigated. Hydrolysis of all three compounds in both aqueous buffer and soil suspensions was highly pH-sensitive. The rate of hydrolysis was much faster in the acidic pH range (5.2-6.2) than under neutral and moderately alkaline conditions (8.2-9.4), but it increased rapidly as the pH exceeded 10.2. All three compounds degraded faster at pH 5.2 than at pH 11.2. Hydrolysis rates of all three compounds could be described well with pseudo-first-order kinetics. There were no significant differences (P =0.05) in the rate constants (k, day-1) of the three compounds in soil suspensions from those in buffer solutions within the pH ranges studied. A functional relationship based on the propensity of nonionic and anionic species of the herbicides to hydrolyse was used to describe the dependence of the 'rate constant' on pH. The hydrolysis involving attack by neutral water was at least 100-fold faster when the sulfonylurea herbicides were undissociated (acidic conditions) than when they were present as the anion at near neutral pH. In aqueous buffer solution at pH > 11, a prominent degradation pathway involved O-demethylation of metsulfuron-methyl to yield a highly polar degradate, and hydrolytic opening of the triazine ring. It is concluded that these herbicides are not likely to degrade substantially through hydrolysis in most agricultural (C) 2000 Society of Chemical Industry.

Fate and transport of bensulfuron-methyl and imazosulfuron in paddy fields: Experiments and model simulation

Experiments were conducted to determine the fate of bensulfuron-methyl (BSM) and imazosulfuron (IMS) under paddy conditions. Initially, laboratory experiments were conducted and the photolysis half-lives of the two herbicides were found to be much shorter than their hydrolysis half-lives in aqueous solutions. In the aerobic water–soil system, dissipation followed first-order kinetics with water half-lives of 9.1 and 11.0 days and soil half-lives of 12.4 and 18.5 days (first phase) and 35.0 and 44.1 days (second phase) for bensulfuron-methyl and imazosulfuron, respectively. However, the anaerobic soil half-lives were only 12.7 and 9.8 days for BSM and IMS, respectively. The values of K d were determined to be 16.0 and 13.8 for BSM and IMS, respectively. Subsequent field measurements for the two herbicides revealed that dissipation of both herbicides in paddy water involved biphasic first-order kinetics, with the dissipation rates in the first phase being much faster than those in the second phase. The dissipation of bensulfuron-methyl and imazosulfuron in the paddy surface soil were also followed biphasic first-order kinetics. These results were then used as input parameters for the PCPF-1 model to simulate the fate and transport of BSM and IMS in the paddy environment (water and 1-cm surface soil layer). The measured and simulated values agreed well and the mass balance error during the simulation period was −1.2 and 2.8% of applied pesticide, respectively, for BSM and IMS.

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

Electrochemical methods in pesticides control

The state of the art of voltammetric and amperometric methods used in the study and determination of pesticides in crops, food, phytopharmaceutical products, and environmental samples is reviewed. The main structural groups of pesticides, i.e., triazines, organophosphates, organochlorides, nitrocompounds, carbamates, thiocarbamates, sulfonylureas, and bipyridinium compounds are considered with some degradation products. The advantages, drawbacks, and trends in the development of voltammetric and amperometric methods for study and determination of pesticides in these samples are discussed.

Antidiabetic drugs and kidney disease - Recommendations of the Swiss Society for Endocrinology and Diabetology.

Patients with diabetes are at risk of early renal function decline. Therefore, kidney function needs monitoring at least once per year. Once the glomerular filtration rate (GFR) is less than 60 ml/min, the pharmacokinetics of antidiabetic drugs may be altered. Sulfonylurea and glinide therapies are associated with a risk of hypoglycaemia which is increased in the presence of renal impairment. Most sulfonylureas must be discontinued once GFR is <60 ml/min. Some glinides may be continued beyond this threshold, in particular repaglinide, which may be used in dialysis patients. In the absence of comorbidities, metformin can be continued at lower doses until a GFR of 45 ml/min, but must be withdrawn in case of dehydration or during the administration of a nephrotoxic drug including dye for radiological investigations. Glitazones may worsen water and sodium retention in patients with renal impairment. The pharmacokinetics of all DPP-IV inhibitors except linagliptin are altered with impaired renal function. Only sitagliptin, saxagliptin and linagliptin may be used in advanced kidney disease, but experience is as yet very limited. GLP-1 agonists are contraindicated in moderate to advanced kidney disease.

Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients.

Participation of the liver gluconeogenesis in the glibenclamide-induced hypoglycaemia in rats

We previously demonstrated an increased liver gluconeogenesis (LG) during insulin-induced hypoglycaemia. Thus, an expected effect of sulphonylureas induced hypoglycaemia (SIH) could be the activation of LG. However, sulphonylureas infused directly in to the liver inhibits LG. Considering these opposite effects we investigated herein LG in rats submitted to SIH. For this purpose, 24 h fasted rats that received glibenclamide (10 mg kg(-1)) were used (SIH group). Control group received oral saline. Glycaemia at 30, 60, 90, 120 and 150 min after oral administration of glibenclamide were evaluated. Since the lowest glycaemia was obtained 120 min after glibenclamide administration, this time was chosen to investigate LG in situ perfused livers. The gluconeogenesis from precursors that enters in this metabolic pathway before the mitochondrial step, i.e. L-alanine (5 mM), L-lactate (2 mM), pyruvate (5 mM) and L-glutamine were decreased (p < 0.05). However, the gluconeogenic activity using glycerol (2 mM), which enters in the gluconeogenesis after the mitochondrial step was maintained. Taken together, the results suggest that the inhibition of LG promoted by SIH overcome the activation of this metabolic pathway promoted by IIH and could be attributed, at least in part, to its effect on mitochondrial function. Copyright (C) 2011 John Wiley & Sons, Ltd.

Efeito do estresse hídrico sobre a eficiência do halosulfuron no controle de tiririca

Foi conduzido um trabalho em casa de vegetação com o objetivo de estudar o efeito de 10 dias de estresse hídrico (Yw de ³2,6; -2,2; -0,35 e -0,2 MPa) sobre a eficiência do halosulfuron (150g p.c./ha+Aterbane-0,25% v/v) no controle de tiririca em pós-emergência . A aplicação do halosulfuron em plantas de tiririca sob estresse de até -2,6 MPa controlou satisfatoriamente a tiririca desde que irrigadas até 24 horas após a aplicação, mas quando a irrigação ocorreu 48 horas após, houve comprometimento na translocação do herbicida nas plantas. Quando o estresse foi menor que -2,0 MPa, o herbicida manteve-se eficaz no controle de tiririca, principalmente para aquelas com Yw de -0,35 MPa.

Seletividade do nicosulfuron em três estádios fenológicos de milho-pipoca

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about I month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Tolerância de híbridos de milho ao herbicida nicosulfuron

Objetivou-se com este trabalho avaliar a tolerância de híbridos de milho ao nicosulfuron e relacionar estudos de seletividade desse herbicida conduzidos em casa de vegetação com estudos desenvolvidos em campo. em casa de vegetação, o experimento foi conduzido no delineamento de blocos ao acaso, em arranjo fatorial 33 x 3, sendo o primeiro fator constituído por híbridos de milho e o segundo por doses do herbicida (0, 30 e 60 g ha-1). Após aplicação do herbicida, avaliou-se a massa seca de parte aérea das plantas. em campo, o experimento foi conduzido no delineamento de blocos ao acaso, em arranjo fatorial 5 x 3, em que os fatores eram constituídos por cinco híbridos de milho, selecionados a partir dos resultados em casa de vegetação, e três doses herbicidas (0, 30 e 60 g ha-1). Após aplicação do herbicida, foram avaliados o crescimento e a produtividade dos híbridos. Por meio dos resultados obtidos em casa de vegetação, foi possível agrupar os híbridos em diferentes níveis de tolerância ao herbicida. Com relação à produtividade em campo, o híbrido B 761 apresentou redução significativa (17,4%) na dose de 60 g ha-1 do nicosulfuron. Ao avaliar a seletividade do nicosulfuron para híbridos de milho, é necessária a etapa de campo para verificar se os tratamentos herbicidas têm influência sobre a produtividade de grãos.