Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.     

Identifying technology horizons for strategic investment decisions

Technology investment models usually assume that a known number of technologies will appear in the future, though their appearance, cost, and revenue parameters may be uncertain. In practice, however, it is not always clear how many future technologies or periods need to be considered. We introduce the concept of a technology horizon, which we define as the minimum number of future technologies and future periods that need to be considered to guarantee that the optimal decision would not change even if additional technologies or periods worth of data were to be considered. We also allow the costs and revenue of existing technologies in our model to vary depending on the latest technology introduced. Further, we allow for implementation costs, which enables us to model situations where it may cost more to leapfrog technologies than if one were to buy intervening technologies. We then provide a fast algorithm to identify such technology horizons     

Novel A-sandwich radome design for airborne applications

A novel A-sandwich hybrid variable thickness radome design, based on optimised power reflection, is presented. The radome performance parameters are evaluated accurately by a 3D ray-tracing procedure in conjunction with the aperture integration method. This design is demonstrated to be a better choice when multiple performance parameters need to be satisfied simultaneously.     

Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing

We have previously observed that bovine papillomavirus type 1 (BPV-1) induces the appearance of five cellular proteins in C127 mouse fibroblasts, four of which appear to arise by altered processing of resident endoplasmic reticulum proteins. Studies of various cell lines revealed that expression of the 3' end of the BPV early region was sufficient for induction of these changes. To identify the BPV gene responsible, we have utilized the simian virus 40 (SV40)/BPV-1 recombinant virus Pava-1, which expresses the 3' end of the BPV early region behind an SV40 early promoter. C127 cells infected with Pava-1 for 48 h show the expected BPV-associated alterations, as do cells infected with Pava constructs mutated in the E5 or E2 genes. However, a mutation in the start codon of a previously ignored open reading frame extending from nucleotides 4013 to 4170 (E5B) eliminated the BPV-associated changes. Similar results were obtained with COS cells infected with the Pava mutants and C127 cells transformed by full-length mutated BPV. Despite its influence on the processing of cellular endoplasmic reticulum proteins, this mutation in E5B did not alter BPV-transforming efficiency or the ability of transformants to form colonies in soft agar. The E5B open reading frame encodes a hydrophobic 52-amino-acid polypeptide that shares structural similarities with HPV6 E5A and HPV16 E5. Speculations on a role for E5B in the viral life cycle are discussed.     

Dual frequency miniature microstrip antenna

A single-feed dual frequency compact microstrip antenna with a shorting pin is described. This new antenna configuration gives a large variation in frequency ratio of the two operating frequencies, without increasing the overall size of the antenna     

A reliability test-plan for series systems with components havingstochastic failure rates

This paper proposes a reliability test plan for a series system, by considering the parameter λ_j of the exponential distribution to be a random variable having uniform distribution over [0, &thetas;_j], j = 1, 2,..., n. Explicit expressions are obtained for the optimal values of the t_j, when the number of components in the system is 2. The general solution, albeit implicit, has also been obtained when the number of components in a given system is ⩾3. Mathematical programming is used to find the optimal solution and to illustrate it with numerical results     

Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients

We present the first case of esophagogastric devascularization and esophagogastric transection using a stapler through laparoscopic surgery. The procedure was performed in a 71-year-old diabetic woman with alcoholic liver cirrhosis (Child-Pugh B class), portal hypertension, bleeding grade III esophageal varices, and a previous bleeding episode. The surgical technique was carried out without problems, and the patient had an excellent postoperative condition. Esophagogastric devascularization with esophageal transection using a stapler through laparoscopic surgery is a feasible technique that accomplishes the same and all objectives of the open procedure. Operative time in both methods is the same, whereas surgical trauma, inmunologic depletion, amount of transfused blood, pain, use of analgesics, and hospital stay are reduced in the laparoscopic technique.     

Dynamic analysis of three point bend specimens under impact

A simple one dimensional inertial model is presented for transient response analysis of notched beams under impact, and extracting dynamic initiation toughness values. The model includes the effects of striker mass interactions, and contact deformations of the beam. Displacement time history of the striker mass is applied to the model as forcing function, The model is validated by comparison with the experimental investigation on ductile aluminium 6061 alloy and brittle polymer, PMMA.