Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

[Transition in diabetology]. / Transition en diabétologie.

For patients with type I diabetes, transition from pediatric to adult care is a challenge due to complex treatment requirements and the physical, psychological and social changes of adolescence. Members of the care team must recognize that while these emerging adults need to develop self-management skills, this may conflict at times with the developmentally appropriate desire for increasing autonomy. The role of nursing in coordinating a successful transition is critical for maintaining continuity of patient-centered care that responds to the specific needs of these young adults.

[Diabetes in elderly: a tailored management]. / Diabète de la personne âgée: une prise en charge sur mesure.

In developed countries, 12-25 % of the aged population (>65 years old) have diabetes. Treatment of the old diabetic patients is less well studied compared to younger patients although diabetic and geriatric medical associations have issued specific treatment and priority guidelines for these patients. Treatment and targets of glycemic control must be adapted to the functional condition of the patients, prevent symptoms and complications of the geriatric syndrome. Prevention and screening of chronic complication of diabetes have to be integrated in the overall care of aged diabetic patients to optimize their quality of life and health state.

[How to prevent severe hypoglycemia in older patients with type 2 diabetes]. / Hypoglycémie sévère chez le patient diabétique de type 2 âgé: quelle prévention?

Severe hypoglycemia is a feared complication of treatment in older diabetic patients (> 75 years) and a limiting factor for good glycemic control. Its real incidence is not well studied and probably underestimated. Cognitive impairment, malnutrition and/or cachexia, polypharmacy and a recent hospitalization are risk factors for severe hypoglycemia specific for older patients. Cognitive impairment screening can identify patients unable to manage their treatment. Simplification of treatment and/or transferring its execution to relatives must then be considered. Prevention also involves the detection of malnutrition and comorbidities, Age-adjusted therapeutic targets (HbA1c 7-8%) are important to avoid an exceedingly strict glycemic control. However, giving up on good glycemic control is not an adequate prevention strategy in itself.

The prevalence, characteristics and metabolic consequences of renal insufficiency in very old hospitalized diabetic patients.

AIMS: We aimed to characterize the determinants and characteristics of renal disease in very old diabetic patients in geriatric care. METHODS: Consecutive diabetic patients (96 women, 38 men) admitted to a geriatric service were studied. Glomerular filtration rate (GFR), albuminuria, vascular and general comorbidities, glycaemic control, malnutrition (using the Mini-Nutritional Assessment [MNA], serum albumin and cholesterol levels), haemoglobin and inflammation (CRP levels) were assessed. RESULTS: (a) 51.2 and 12.4% patients had moderate or severe renal insufficiency. The prevalence of normo-, micro- and macroalbuminuria was 45.0, 38.9 and 16.0% in the whole population, and was similar in patients with or without moderate renal insufficiency. Renal insufficiency was associated with previous stroke (P=0.024), heart failure (P=0.024), and atrial fibrillation (P=0.008), and possibly myocardial infarction (P=0.059, Mann-Whitney test). (b) Albuminaemia was associated with albuminuria, MNA scores, haemoglobin, total and HDL-cholesterol and CRP. However, in multiple linear regression analysis CRP was the only robust determinant of albuminaemia (P<0.0001). (c) Renal insufficiency was not associated with the MNA, serum albumin, haemoglobin and cholesterol levels. CONCLUSION: Renal insufficiency often occurs without albuminuria, suggesting aetiologies distinct from classical diabetic nephropathy, and is strongly associated with vascular comorbidities. Hypoalbuminaemia is more strongly associated with inflammation than with albuminuria and malnutrition. Malnutrition, hypoalbuminaemia, low cholesterol levels and anaemia are not associated with renal insufficiency, likely due to the very high prevalence of these abnormalities in the whole population. These features must be taken into account when organizing the global care of elderly diabetic patients.

The high prevalence of malnutrition in elderly diabetic patients: implications for anti-diabetic drug treatments.

BACKGROUND: Type 2 diabetes usually occurs in the context of obesity and associated insulin resistance. Current treatment recommendations are based on lifestyle modifications and incremental drug therapy. However, this approach could lead to inappropriate priorities upon ageing, when diabetes may be compounded by malnutrition and reduced insulin resistance. METHODS: We prospectively evaluated glycaemic and nutritional parameters in 146 consecutive diabetic patients (age 82.5 +/- 7.3 years, mean +/- sd) admitted to our geriatric service. We also implemented nutritional support therapy and a drug therapy adjustment protocol. Oral hypoglycaemic agent withdrawal was attempted in cases of good glycaemic control (HbA(1c) < 7.5% (<47 mmol/mol) or fasting blood glucose < 7.5 mmol/l). RESULTS: Mean BMI and HbA(1c) were 29.6 +/- 7.1 kg/m(2) and 6.9 +/- 1.2% (52 +/- 9 mmol/mol), respectively. Of the patients, 51.4% were taking 1-3 oral hypoglycaemic agents, 30.8% were on insulin and 9.6% on were on insulin and oral hypoglycaemic therapy. Low Mini Nutritional Assessment scores and serum marker levels indicated a high prevalence of malnutrition and/or chronic disease, even in obese patients. Mini Nutritional Assessment scores were positively associated with HbA(1c) values. Among patients treated by oral hypoglycaemic agents, complete drug withdrawal was achieved in 65.8%, much more often than new treatments were added (P = 0.002). Glycaemic control did not worsen after approximately 30 days, despite in-hospital nutritional therapy. Successful oral hypoglycaemic therapy withdrawal was associated with lower Mini Nutritional Assessment scores. CONCLUSIONS: Malnutrition is highly prevalent in elderly diabetic inpatients and, paradoxically, contributes to 'good' glycaemic control. Malnutrition should be screened for in these patients and, when present, should prompt a revision in diet and drug therapy. In particular, the possibility of reducing unnecessary drug therapy should be considered.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

[The diabetic child and the specifics of insulin therapy]. / L'enfant diabétique et les spécificités de son traitement insulinique.

The incidence of diabetes type I has increased considerably in young children with an annual increase in Switzerland of 23,8% over the last ten years. The development of rapid acting and long acting analogues allowed a significant progress in treatment. Multiple daily insulin injections together with carbohydrate counting as well as continuous subcutaneous insulin infusion (CSII) improved the quality of life and led to an increased daily flexibility. The incidence of severe hypoglycaemic events has decreased at the same time metabolic control improved. The development of interstitial glucose measurement (online) coupled to the insulin pump represents a step further towards the artificial pancreas. The new therapeutic strategies of immunomodulation will hopefully lead to secondary and tertiary prevention of diabetes.