Bi- and trimetallic complexes with macrocyclic xanthene-4,5-diNHC ligands.

Three different types of bimetallic NHC-metal complexes were synthesized, whose NHC units are attached at the 4,5-positions of xanthene. The NHC units are in close proximity and are designed such that each carbene coordinates one ML unit, while the chelation of one metal by two NHC is not possible. Several xanthene-((NHC)ML)2 complexes with ML = RhCl(cod), IrCl(cod), RhCl(CO)2, IrCl(CO)2, AuCl, AgCl, CuCl and Pd(allyl)Cl were synthesized and investigated.

Discovery of Irbesartan Derivatives as BLT2 Agonists by Virtual Screening.

Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and in vitro assay of the most promising compounds. Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resulting in the discovery of a new potent BLT2 agonist (8f, EC50 = 67.6 nM). Irbesartan and 8f were shown to promote proliferation of epithelial colon cells, an effect which was reversible by a BLT2 antagonist.

First Structure-Activity Relationship Study of Potent BLT2 Agonists as Potential Wound-Healing Promoters.

The first potent leukotriene B4 (LTB4) receptor type 2 (BLT2) agonists, endogenous 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), and synthetic CAY10583 (CAY) have been recently described to accelerate wound healing by enhanced keratinocyte migration and indirect stimulation of fibroblast activity in diabetic rats. CAY represents a very valuable starting point for the development of novel wound-healing promoters. In this work, the first structure-activity relationship study for CAY scaffold-based BLT2 agonists is presented. The newly prepared derivatives showed promising in vitro wound-healing activity.

Predictors and determinants for weight reduction in overweight and obese children and adolescents.

INTRODUCTION: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods for weight reduction have remained elusive. This multicenter non-randomised trial aimed to identify parameters and determinants of long-term weight reduction. PATIENTS AND METHODS: A total of 143/159 overweight and obese children and adolescents (90 %) completed the prospective multicenter trial (age 13.9±2.4 years, BMI 31.2±5.4kg/m2, BMI-SDS 2.51±0.57). During a 6-week rehabilitation period the patients participated in a structured treatment and teaching program (STTP). Following in-patient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, standardized questionnaires to assess socio-demographic and socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress management, social support, actual body shape). RESULTS: 66% of the children and adolescents had abnormal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. The mean carotid intima-media thickness was 0.53±0.09mm (range 0.40 to 0.80); 15% of the patients showed normal range values (< 0.45mm), 40% a slightly elevated (≥ 0.45 to ≤ 0.50mm) and 45% an elevated (> 0.50mm) thickness. After the inpatient treatment lasting 40.4±4.1 (range 28 to 49) days, children and adolescents reached a mean weight reduction of 5.52±3.94 (0.4 to 13.3) kg (p<0.01) that was accompanied by a reduction in body fat mass. Using multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square=0.53): well-being (ß=-0.543), resilience (ß=0.434), and sense of coherence (ß=0.315). CONCLUSION: The different parameters (i. e., well-being, resilience, sense of coherence) have demonstrated their utility, and strategies should be developed allowing an adaption of these into the STTPs.

Identification of Predictors for Weight Reduction in Children and Adolescents with Overweight and Obesity (IDA-Insel Survey).

INTRODUCTION: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods of prevention and therapy for overweight and obesity have remained elusive. It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction. PATIENTS AND METHODS: In total 143/159 children and adolescents (90%) with overweight and obesity completed the prospective, multicenter trial (age 13.9 ± 2.4 years, BMI 31.2 ± 5.4 kg/m², BMI-SDS 2.51 ± 0.57). During a six-week rehabilitation patients participated in a structured treatment and teaching program (STTP). Following the inpatient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, and standardized questionnaires to assess socio-demographic, socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress-management, social support, and actual body shape). RESULTS: 66% of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. Mean thickness of carotid intima-media was 0.53 ± 0.09 mm (range, 0.40-0.80); 15% of the patients showed a normal range (<0.45 mm), 40% slightly elevated (0.45-0.50 mm) and 45% an elevated (>0.50 mm) thickness. After an inpatient treatment lasting 40.4 ± 4.1 (range, 28-49) days, children and adolescents reached a mean weight reduction of 5.52 ± 3.94 (0.4-13.3) kg (p < 0.01) accompanied by a reduction of body fat mass. Performing multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square = 0.53): Well-being (ß = -0.543), resilience (ß = 0.434) and intrafamilial conflicts (ß = 0.315). CONCLUSION: The different parameters (i.e., resilience, intrafamilial conflicts, structured daily schedule) have demonstrated their utility and strategies should be developed allowing an adaption of these into the STTPs and the integration of intervention into the therapeutic setting.

Impact of information technology on the therapy of type-1 diabetes: a case study of children and adolescents in Germany.

Being able to manage and adjust insulin doses is a key part of managing type-1 diabetes. Children and adolescents with type-1 diabetes mellitus often have serious difficulties with this dosage adjustment. Therefore, this paper aims to investigate the impact of using novel mobile, web and communication technologies in assisting their therapy and treatment. A trial was conducted in the north-eastern part of Germany to evaluate the impact of the "Mobil Diab", a mobile diabetes management system, on the clinical outcome. 68 subjects aged between 8 and 18 years, divided randomly into control and intervention groups, were included into the study. Metrics such as changes in the quality of metabolic control, changes in psychological parameters, usability and acceptance of the technology were used for evaluation purpose. Metabolic control was mainly assessed by the mean HbAlc. Analysis showed a good acceptance of the proposed system. An overall improvement in mean levels of HbA1c was observed, however further studies will be conducted to prove evidence of the weight and BMI improvements. Moreover, initial indications of positive impact on the improvement in psychological parameters were presumed based on the result of the conducted study. The system appeared to be an efficient and time saving tool in diabetes management.

Electronic health technology for the assessment of physical activity and eating habits in children and adolescents with overweight and obesity IDA.

OBJECTIVE: It was the goal of the trial to study the impact of electronic healthcare technology into treatment. METHODS: One hundred and twenty-four children/adolescents (females 56%, age 13.5±2.8 years, height 1.64±0.13 m, weight 85.4±23.0 kg, body-mass index (BMI) 31.3±5.2 kg/m(2), BMI-standard deviation score (SDS) 2.50±0.5) were included. To assess physical activity and eating habits, a mobile motion sensor integrated into a mobile phone with digital camera was used. RESULTS: The children/adolescents had a significant weight reduction of 7.1±3.0 kg. BMI/BMI-SDS decreased (p<0.01). Intensity (14.1±6.4 activity units) and duration of physical activity (290.4±92.6 min/day) were assessed with sensors. Time walking: median 45.5 (range, 2.5-206.5), running 8.0 (range, 0-39.5), cycling 27.7 (range, 0-72.5), car driving 23.7 (range, 0-83.0) min/day. Comparing self-reported physical activity (walking 292.9 (range, 9.6-496.1), running 84.8 (range, 8.4-130.2) min/day) with assessment with sensors there were significant differences (p<0.01). Duration of physical activity documented by children/adolescents was higher than the assessment with motion sensors (walking 292.9 vs 45.5 min, p<0.01, running 84.8 vs 8.0 min, p<0.01). Sensor derived energy intake was higher than recommended (469.14±88.75 kcal vs 489.03±108.25 kcal, p=0.09). Performing multivariate analysis the following parameters showed associations with weight reduction (R-square=0.75): body weight (ß=-0.95, p<0.01), C-reactive protein (CRP, ß=0.15, p=0.07), physical activity, time spent in activities measured with sensors (ß=-0.18, p=0.04), stress management (ß=0.16, p=0.06), body fat mass at onset of the trial (ß=0.45, p<0.01) and body shape (ß=-0.25, p=0.01). CONCLUSION: The innovative mobile movement detection system is highly accepted by children and adolescents. The system is able to augment existing weight reduction and stabilization strategies.

Identification of determinants for weight reduction in overweight and obese children and adolescents.

We conducted a pilot trial of electronic technology integrated into the treatment of children and adolescents who are overweight or obese. A total of 30 patients (mean age 14 years, mean BMI 32.7 kg/m(2)) were admitted to our hospital to participate in a structured treatment and teaching programme (STTP). To assess physical activity and eating habits, a mobile motion sensor board (MoSeBo) or a sensor for physical activity, integrated into a mobile phone with digital camera (DiaTrace) was used. Over an average period of four days of monitoring, the mean intensity (15.4 activity units) and duration of physical activity (267 min/d) were recorded with the mobile sensors. The mean time spent walking was 64 min/d, running 11 min/d, cycling 24 min/d and car driving 21 min/d. There were significant differences (P < 0.001) between self-reported physical activity and objective assessment: in general the duration of physical activity documented by children and adolescents was much higher than the objective assessment. Similarly, the real caloric intake was higher than the self-estimates (P = 0.085). A multivariate analysis showed that the following variables were significantly associated with weight reduction in the hospital STTP (R-squared = 0.59): high motivation, intrafamilial conflicts, duration of physical activity assessed with the MoSeBo/DiaTrace system, and the body fat mass at onset of therapy. All children and adolescents included in the trial completed it. Although the MoSeBo/DiaTrace system was used for a relatively short period in each patient, the high acceptance demonstrated that it could be integrated into therapy easily.