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.     

Jitter reduction through feedback for picosecond pulsed InGaAsPlasers

Following a comparison of picosecond-pulse generation techniques, feedback schemes are reported for the generation of picosecond pulse trains with improved jitter for both multicontact and conventional single-contact InGaAsP-InP lasers. Subpicosecond jitter is achieved for Q-switched laser sources using a novel optoelectronic feedback scheme. The use of resonant electrical feedback is shown to improve the timing jitter of gain-switched pulses by up to six times. Pulse-to-pulse timing jitter as low as 250 fs is demonstrated for a hybrid of optical and electrical feedback schemes. Limits for timing jitter in diode lasers are established for optoelectronic, electrical, and optical feedback schemes, and the key picosecond pulse generation schemes are compared in terms of timing jitter for the first time     

Interaction of an arbitrary force with a flexible punch or with an external circular crack

Two mathematically equivalent problems are solved exactly and in terms of elementary functions. An. external circular crack in a transversely isotropic elastic space is interacting with arbitrarily located point forces, applied in such a way, that the tangential displacements in the crack neck vanish. The problem of finding the tangential stress produced by such loading is solved exactly and in closed form. The second problem is that of interaction of an arbitrary point force inside the transversely isotropic elastic half-space and a flexible punch. The method of solution is based on the previously published results of the author. The results are of fundamental value, since they effectively give the Green's functions for solving any relevant problem of interaction.     

Silicon-substrate microelectrode arrays for parallel recording ofneural activity in peripheral and cranial nerves

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve settings, from several microelectrodes in parallel     

Oculomotor paralysis. The perspective of a neuro-ophthalmology consultation

Ocular paresis is a usual diagnosis in neuro-ophthalmologic consultation, and its aetiology is indeed a challenge. The authors studied 3400 records concerning this consultation, between 1982 and the third quarter of 1993. During this period 221 cases with ocular paresis were selected. During this retrospective study we point out the following items: the cranial nerve affected; the neuro-ophthalmologic semiology; the aetiology and clinical evolution, according to the age groups. From 221 cases selected, 111 were paresis from the VIth pair (50.2%), 88 from the IIIrd pair (39.8%), 14 multiple paresis (6.4%) and 8 paresis from the IVth pair (3.6%). The most frequent complaint was diplopia (> 90%). As far as the aetiological diagnosis is concerned, this was easier to establish in patients > 50 years of age. In this age group the most usual aetiology was vascular and traumatic pathologies. In younger patients the most frequent pathologies were traumatic and tumoral. The prognostic was better in the vascular group, the paresis recovery being > 50% in all other pathologies, except the tumoral one.     

A general interaction analysis for large deformations

A method is presented for the finite element analysis of the interaction of geometrically and materially non-linear bodies. Interaction is considered at predefined interfaces. Equations for interaction forces are assembled via static condensation, and the solution for these forces is utilized for the full analysis of the problem. An interface function using the interpolating functions is defined to maintain the equilibrium of interaction forces and the displacement compatibility at the interface nodes. The method permits large rotations and slipping as well as the occurrence of new contacts at the interfaces. Additionally, solutions can be found using high- or low-order elements and when nodes at either side of the interface are not aligned.     

Comparison of three different methods for measurement of plaque-pH in humans after consumption of soft bread and potato chips

Three different techniques for measurement of plaque-pH--the sampling, the microtouch, and the telemetric methods--were compared after subjects had consumed different starch products. Ten volunteers, equipped with partial lower prostheses, incorporating a miniature glass pH electrode, refrained from toothbrushing for 3 days. Four products were tested: (1) soft bread, (2) potato chips, (3) 5% starch, and (4) 5% sucrose. The pH of plaque was measured for 45 min by means of all three of the methods. The results showed that the mean pH at 10 min was 1.5 units lower with the telemetric than with the sampling method and 1.0 unit lower with the telemetric than with the microtouch method. Relatively small differences were found among the effects of the four test products for all three methods, with the clearest distinctions among the pH curves being with the microtouch and telemetric methods. The main conclusions from the present investigation are: (1) that there were large differences in pH levels measured with the sampling, the microtouch, and the telemetric methods, even though they ranked the test products in about the same order, and (2) that the two starchy foods, bread and potato chips, were both easily fermented by dental plaque.