165 research outputs found
Author's personal copy Postconditioning with curaglutide, a novel GLP-1 analog, protects against heart ischemia-reperfusion injury in an isolated rat heart
Aim: GLP-1(7-36)amide (GLP-1) is an intestinal hormone with effects on glucose metabolism and feeding behavior, including insulinotropic, insulinomimetic, glucagonostatic and anorectic actions. In experimental settings, GLP-1 has also been shown to diminish infarct size following heart ischemia-reperfusion. GLP-1 analogs with extended half-lives are continuously being developed against type 2 diabetes mellitus. Of these, only exendin-4 (exenatide, registered as Byetta) has been shown to mimic the infarct size-limiting effect of GLP-1 in a clinically relevant application as a postconditioning agent. The aim of this work was to test, in a postconditioning mode, a novel, proteolysis-resistant GLP-1 analog N-Ac-GLP-1(7-34)amide, herein termed curaglutide, for its cardioprotective ability. Method: Global ischemia (35 min)-reperfusion (120 min) was applied in isolated, retrogradely perfused rat hearts. Peptides were present for 15 min at the onset of reperfusion. Cardiac function parameters (beats per minute, left ventricle developed and diastolic pressures, rate-pressure product) were measured. Infarct size was determined by 2,3,5-tripehyltetrazolium chloride staining and planimetry. Results: Curaglutide did not affect any of the functional heart parameters when administered without preceding ischemia. Curaglutide 0.3 nM diminished significantly the postischemic hypercontracture, with no significant effect on the left ventricle developed pressure or rate-pressure product. Infarct size was reduced by curaglutide postconditioning from 24.8% (SEM 2.8, N = 14) to 11.4% (SEM 3.2, N = 8; P b 0.05). These effects of curaglutide on postischemic hypercontracture and infarct size were similar in magnitude to corresponding effects of GLP-1 receptor agonist exendin-4. The cardioprotective effects of both agents were abolished in the presence of a GLP-1 receptor antagonist exendin(9-39). Conclusion: Curaglutide is a new, proteolysis-resistant GLP-1 analog with a beneficial effect on reperfusion-injury in an isolated rat heart. Curaglutide was here shown to act through GLP-1 receptors. Based on the present results, more extensive experimental studies in vivo, comparing dose-response characteristics and efficacy of curaglutide and exendin-4 appear warranted
Intersubband gain in a Bloch oscillator and Quantum cascade laser
The link between the inversion gain of quantum cascade structures and the
Bloch gain in periodic superlattices is presented. The proposed theoretical
model based on the density matrix formalism is able to treat the gain mechanism
of the Bloch oscillator and Quantum cascade laser on the same footing by taking
into account in-plane momentum relaxation. The model predicts a dispersive
contribution in addition to the (usual) population-inversion-dependent
intersubband gain in quantum cascade structures and - in the absence of
inversion - provides the quantum mechanical description for the dispersive gain
in superlattices. It corroborates the predictions of the semi-classical
miniband picture, according to which gain is predicted for photon energies
lower than the Bloch oscillation frequency, whereas net absorption is expected
at higher photon energies, as a description which is valid in the
high-temperature limit. A red-shift of the amplified emission with respect to
the resonant transition energy results from the dispersive gain contribution in
any intersubband transition, for which the population inversion is small.Comment: 10 pages, 6 figure
Maternal effects on anogenital distance in a wild marmot population
Peer reviewedPublisher PD
Inelastic quantum transport in superlattices: success and failure of the Boltzmann equation
Electrical transport in semiconductor superlattices is studied within a fully
self-consistent quantum transport model based on nonequilibrium Green
functions, including phonon and impurity scattering. We compute both the drift
velocity-field relation and the momentum distribution function covering the
whole field range from linear response to negative differential conductivity.
The quantum results are compared with the respective results obtained from a
Monte Carlo solution of the Boltzmann equation. Our analysis thus sets the
limits of validity for the semiclassical theory in a nonlinear transport
situation in the presence of inelastic scattering.Comment: final version with minor changes, to appear in Physical Review
Letters, sceduled tentatively for July, 26 (1999
Organ-Specific and Age-Dependent Expression of Insulin-like Growth Factor-I (IGF-I) mRNA Variants: IGF-IA and IB mRNAs in the Mouse
Insulin-like growth factor-I (IGF-I) gene generates several IGF-I mRNA variants by alternative splicing. Two promoters are present in mouse IGF-I gene. Each promoter encodes two IGF-I mRNA variants (IGF-IA and IGF-IB mRNAs). Variants differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain-coding region. Functional differences among IGF-I mRNAs, and regulatory mechanisms for alternative splicing of IGF-I mRNA are not yet known. We analyzed the expression of mouse IGF-IA and IGF-IB mRNAs using SYBR Green real-time RT-PCR. In the liver, IGF-I mRNA expression increased from 10 days of age to 45 days. In the uterus and ovary, IGF-I mRNA expression increased from 21 days of age, and then decreased at 45 days. In the kidney, IGF-I mRNA expression decreased from 10 days of age. IGF-IA mRNA levels were higher than IGF-IB mRNA levels in all organs examined. Estradiol-17 beta (E2) treatment in ovariectomized mice increased uterine IGF-IA and IGF-IB mRNA levels from 3 hr after injection, and highest levels for both mRNAs were detected at 6 hr, and relative increase was greater for IGF-IB mRNA than for IGF-IA mRNA. These results suggest that expression of IGF-I mRNA variants is regulated in organ-specific and age-dependent manners, and estrogen is involved in the change of IGF-I mRNA variant expression
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