Glucagon-like peptide 1 improved glycemic control in type 1 diabetes

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 ± 0.9, mean ± se, vs 5.4 ± 0.8 mmol/l, p < .05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 ± 3.1 vs 37 ± 9.6 pmol/l, p < .05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 ± 2.5 vs 3.1 ± 1.9 ng/l, p < .04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 ± 0.33 vs 0.34 ± 0.26 mmol/l, p < .05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs

Single-Layer WEBs: Intrasaccular Flow Disrupters for Aneurysm Treatment-Feasibility Results from a European Study

ABSTRACT BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use

A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs

BACKGROUND: A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. METHODS: Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P < 0.05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis. RESULTS: At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004) and the insulin response was significantly lower in the Paleolithic group (p = 0.001). The geometric mean of C-reactive protein was 82% lower (p = 0.0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group. CONCLUSION: This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure when compared to a cereal based diet

Latent autoimmune diabetes in adults (LADA) should be less latent

n/

Genome amplification and gene expression in the ciliate macronucleus

The focus of this review is on the micronucleus and macronucleus in the ciliated protozoa and the organization and function of the DNA molecules within them. We present (1) some of the structural and functional differences which are known, (2) the genetic evidence for macronuclear units, (3) two hypotheses for the organization of the DNA molecules in the macronucleus to explain these units, and (4) experiments designed to discriminate between these hypotheses. We conclude that the size of the genome is not reduced in the macronucleus and that there are 45 copies of the haploid genome present in the macronucleus of normal strains of Tetrahymena pyriformis and 800 copies in the macronucleus of Paramecium aurelia . The ciliate genome is relatively simple in terms of repeated sequences. However, not all copies of the genes present in the macronucleus may be identical since fractions of differing thermal stability appear after renaturation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44178/1/10528_2004_Article_BF00486122.pd

First-line lesional aspiration in acute stroke thrombectomy using a novel intermediate catheter: Initial experiences with the SOFIA

Introduction Five randomized controlled trials (RCTs) on endovascular therapy (EVT) of stroke have proven a clinical benefit over conservative treatment or IV-thrombolysis alone. Lesional clot aspiration with a dedicated system can achieve revascularization without an additional retriever (a direct-aspiration first-pass technique, ADAPT), and the SOFIA has been shown to be both safe and efficacious in a multicentric retrospective study. We have evaluated a subset of these data acquired in two major stroke centers with regard to using the SOFIA for first-line lesional aspiration. Methods Thirty patients with large-vessel occlusions treated with first-line lesional aspiration were identified. Procedural data, clot length, reperfusion success (mTICI), procedural timings, complications, and clinical status at admission, discharge and at 90 days were analyzed. Results The median baseline NIHSS was 16. IV thrombolysis was administered in 15/30 patients. Ninety-three percent of occlusions were in the anterior circulation. TICI2b was achieved in 90% of multimodality treatments; lesional aspiration was successful in 67% within a median time of 20 minutes. The highest first-attempt success rate was in MCA occlusions (median time to recanalization 10 minutes). There were no device-related events. Symptomatic intracerebral hemorrhage (sICH) occurred in 10%, but never with sole lesional aspiration. Embolization to new territories was recorded in 1/30 (3%). Median discharge NIHSS was 7; 30% were mRS2 at discharge and 43% at 90-day follow-up. Conclusions Lesional aspiration with SOFIA is in line with published data. The SOFIA may be used as a first-line device, aiming at fast recanalization by sole aspiration with good safety and efficacy. If unsuccessful, it converts into part of a stent retriever-based multimodality treatment

Nanoscale mapping of confinement potentials in single semiconductor quantum wires by near-field spectroscopy

The quasi-one-dimensional confinement potential and its influence on carrier transport in a GaAs quantum wire structure are directly mapped by low-temperature near-field scanning optical spectroscopy with subwavelength spatial resolution. Shallow asymmetric potential barriers in the vicinity of the quantum wire are detected, and their height and width are determined quantitatively. We demonstrate the strong influence of such local barriers on carrier transport and trapping into the quantum wire, suppressing carrier trapping at low temperature.FWN – Publicaties zonder aanstelling Universiteit Leide

Single-layer WEBs: intrasaccular flow disrupters for aneurysm treatment — feasibility results from a European study

BACKGROUND AND PURPOSE: The safety and efficiency of the dual-layer Woven EndoBridge (WEB) device has already been published. However, this international multicenter study sought to evaluate the safety of single-layer devices, which are the newest generation of the WEB intrasaccular flow-disrupter family. They have been designed to offer smaller-sized devices with a lower profile to optimize navigability and delivery, which may, in turn, broaden their range of use. MATERIALS AND METHODS: Data from all consecutive patients treated with a single-layer WEB device, in 10 European centers from June 2013 to May 2014 were included. Clinical presentations, technical details, intra- and perioperative complications, and outcomes at discharge were recorded. Clinical and angiographic data at last follow-up were also analyzed when available. RESULTS: Ninety patients with 98 WEB-treated aneurysms were included in this study. In 93 cases (95%), WEB placement was possible. Complete occlusion at the end of the procedure was obtained in 26 instances (26%). Additional treatment during the procedure (coiling and/or stent placement) was necessary in 12 cases (12.7%). Procedure-related complications occurred in 13 cases, leading to permanent neurologic deficits in 4 patients (4.4%). Early vascular imaging follow-up data were available for 44 patients (57%), with an average time interval of 3.3 months. Treatment-related morbidity and mortality rates at last follow-up were 2.2% and 1.1%, respectively. CONCLUSIONS: In this study, the feasibility and safety of the single-layer WEB device was comparable with that of the double-layer. However, further studies are needed to evaluate long-term efficacies