Summary
Background TZP‐101 is a synthetic, selective ghrelin agonist in development for gastroparesis.
Aim To assess safety and effects of TZP‐101 in diabetes patients with symptomatic ...gastroparesis.
Methods Adults with type 1 or type 2 diabetes mellitus received placebo and TZP‐101 (80, 160, 320 or 600 μg/kg) infusions in a cross‐over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic‐euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses.
Results Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate‐to‐severe gastroparesis symptoms and ≥29% retention 4 h after a radiolabelled solid meal were enrolled. TZP‐101 produced significant reductions in solid meal half‐emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP‐101 infusion were not statistically significant. Most adverse events were mild and self‐limiting and there were no identifiable differences in numbers or types of adverse events between TZP‐101 and placebo.
Conclusions This proof‐of‐concept study demonstrates that the ghrelin agonist TZP‐101 is well‐tolerated in diabetes patients with moderate‐to‐severe chronic gastroparesis and shows statistically significant improvements in gastric emptying.
The Danish sperm donor number 7042 has fathered several offspring with neurofibromatosis type 1 (NF1) worldwide. NF1 is caused by loss‐of‐function mutations in the NF1 gene and more than 1000 NF1 ...mutations are identified. Analysis of the donor sperm demonstrated gonosomal mosaicism with an intragenic deletion involving exons 15–29 in the NF1 gene. At the two Danish reference centres for NF1 patients, we evaluated 23 half‐siblings from the donor. Nine were diagnosed with NF1. The severity grade of NF1 progressed from minimal to mild/moderate within 3 years of follow‐up. The NF1 phenotype shows great variability in intra‐ and inter‐family expressivity and to date only two NF1 genotype–phenotype correlations have been established. This rare possibility of a long‐term follow‐up of a cohort of half‐siblings with NF1 makes further studies including phenotypic variability and search for modifier genes possible. To achieve this goal, we have initiated The International Donor 7042 NF1 Offspring Registry. Research facilitated via this registry may reveal important new knowledge of clinical characteristics and prognostics for the specific NF1 genotype and thereby contribute to future individualised targeted clinical follow‐up and treatment.
A combination of high-resolution scanning tunneling microscopy and density functional theory is utilized to study the interaction of water with the reduced TiO2(110)-(1 x 1) surface. As the direct ...product of water dissociation in oxygen vacancies, paired hydroxyl groups are formed. These pairs are immobile and stable unless they interact with adsorbed water molecules. As a result of these interactions, protons are transferred to adjacent oxygen rows, thereby forming single hydroxyl groups. Additionally, we show that hydroxyl groups facilitate the diffusion of water molecules over the oxygen rows.
Context: We have previously shown that exercise-induced GH release is not mediated by ghrelin, but it remains to be studied whether the increase in GH may suppress postexercise ghrelin levels.
...Objective: The objective of this study was to characterize systemic ghrelin levels after exercise with and without concomitant GH administration.
Design, Participants, and Intervention: Group A: Twenty-nine elite athletes (age, 18–37 yr) were studied after a maximal exercise test. Group B: In a double blind, placebo-controlled, parallel study, 32 healthy subjects (age, 18–33 yr) were randomized to placebo, GH 0.1 IU/kg per day, or GH 0.2 IU/kg per day for 4 wk. These subjects performed a multistage fitness test to assess maximum oxygen uptake at baseline and after 4 wk. We measured total circulating ghrelin levels before and immediately after exercise and at 15, 30, 60, 90, and 120 min after exercise.
Results: Group A: Serum ghrelin levels after exercise decreased significantly (P < 0.01). Group B: Exercise at baseline was associated with a significant lowering of ghrelin levels after exercise (P < 0.0001). In addition, 4 wk of high-dose GH were followed by a further approximately 20% reduction in basal and after exercise serum ghrelin (micrograms per liter): 0.78 (range 0.52–1.17) vs. 0.63 (range 0.50–0.91), P < 0.05.
Conclusions: 1) Ghrelin levels decrease significantly after exercise in elite athletes and healthy subjects. 2) High-dose GH suppresses ghrelin levels. 3) These data support the hypothesis that GH feedback inhibits ghrelin secretion.
Oxidation of Pt(110) LI, W. X; ÖSTERLUND, L; VESTERGAARD, E. K ...
Physical review letters,
10/2004, Letnik:
93, Številka:
14
Journal Article
Recenzirano
Using scanning tunneling microscopy and temperature programmed desorption we investigate the Pt(110) surface under strongly oxidizing conditions involving either high-pressure O2 or atomic oxygen ...exposure. At low temperatures, only disordered Pt oxide structures are observed. After annealing ordered surface oxide islands are observed to coexist with a highly stable reconstructed (12x2)-O chemisorption structure. From density functional theory calculations a model for the surface oxide phase is revealed. The phase is found to be metastable, and its presence is explained in terms of stabilizing defects in the chemisorption layer and reduced Pt mobility.
Aim: Adrenaline has widespread metabolic actions, including stimulation of lipolysis and induction of insulin resistance and hyperlactatemia. Systemic adrenaline administration, however, generates a ...very complex hormonal and metabolic scenario. No studies employing regional, placebo controlled and adrenaline infusion exist. Our study was designed to test the hypothesis that local placebo controlled leg perfusion with adrenaline directly increases local lactate release, stimulates lipolysis, induces insulin resistance and leaves protein metabolism unaffected.
Methods: We studied seven healthy volunteers with bilateral femoral vein and artery catheters during 3‐h basal and 3‐h hyperinsulinemic (0.6 mU kg−1 min−1) euglycemic clamp conditions. One femoral artery was perfused with saline and the other with adrenaline (0.4 μg min m−2). Lipid metabolism was quantified with 9,10‐3H palmitate and amino acid metabolism with 15N‐phenylalanine and lactate and glucose by raw arterio‐venous differences.
Results: Femoral vein plasma adrenaline increased ≈eightfold in the perfused leg with unaltered blood flows. Adrenaline perfusion significantly increased local leg lactate release from 0.01 to 0.25 mmol min−1 per leg, palmitate release in the basal state 11.5–16.9 μmol min−1 per leg and during the clamp 2.62–8.44 μmol min−1 per leg. Glucose uptake decreased during the clamp from ≈180 to 30 μmol min−1 per leg. Phenylalanine kinetics was not affected by adrenaline.
Conclusion: Adrenaline directly increases lactate release and lipolysis and inhibits insulin‐stimulated glucose uptake in the perfused human leg. Adrenaline has no direct effects on peripheral amino acid metabolism. Adrenaline‐induced lactate release from striated muscle may be an important mechanism underlying hyperlactatemia in the critically ill.
Introduction
We present a case of an infertile male with 46,XX/46,XYchimerism fathering a child after ICSI procedure.
Methods
Conventional cytogenetic analysis on chromosomes, derived from ...lymphocytes, using standard Q-banding procedures with a 450–550-band resolution and short-tandem-repeat analysis of 14 loci.
Results
Analysis of 20 metaphases from lymphocytes indicated that the proband was a karyotypic mosaic with an almost equal distribution between male and female cell lines. In total, 12 of 20 (60%) metaphases exhibited a normal female karyotype 46,XX, while 8 of 20 (40%) metaphases demonstrated a normal male karyotype 46,XY. No structural chromosomal abnormalities were present. Out of 14 STR loci, two loci (D18S51 and D21S11) showed four different alleles in peripheral blood, buccal mucosal cells, conjunctival mucosal cells, and seminal fluid. In three loci (D2S1338, D7S820, and vWA), three alleles were detected with quantitative differences that indicated presence of four alleles. In DNA extracted from washed semen, four alleles were detected in one locus, and three alleles were detected in three loci. This pattern is consistent with tetragametic chimerism. There were no quantitative significant differences in peak heights between maternal and paternal alleles. STR-analysis on DNA from the son confirmed paternity.
Conclusion
We report a unique case with 46,XX/46,XY chimerism confirmed to be tetragametic, demonstrated in several tissues, with male phenotype and no genital ambiguity with oligospermia fathering a healthy child after IVF with ICSI procedure.
Diffusion of oxygen molecules on transition metal oxide surfaces plays a vital role for the understanding of catalysis and photocatalysis on these materials. By means of time-resolved scanning ...tunneling microscopy, we provide evidence for a charge transfer-induced diffusion mechanism for O2 molecules adsorbed on a rutile TiO2(110) surface. The O2 hopping rate depended on the number of surface donors (oxygen vacancies), which determines the density of conduction band electrons. These results may have implications for the understanding of oxidation processes on metal oxides in general.
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