Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals.

BACKGROUND/AIMS: Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. METHODS: We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. RESULTS: The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 +/- 1.41 (P = .009) and 2.34 +/- 1.47 (P = .15). Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. CONCLUSION: Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load.

A novel post-translational modification involving bromination of tryptophan. Identification of the residue, L-6-bromotryptophan, in peptides from Conus imperialis and Conus radiatus venom.

We report a novel post-translational modification involving halogenation of tryptophan in peptides recovered from the venom of carnivorous marine cone snails (Conus). The residue, L-6-bromotryptophan, was identified in the sequence of a heptapeptide, isolated from Conus imperialis, a worm-hunting cone. This peptide does not elicit gross behavioral symptoms when injected centrally or peripherally in mice. L-6-Bromotryptophan was also identified in a 33-amino acid peptide from Conus radiatus; this peptide has been shown to induce a sleep-like state in mice of all ages and is referred to as bromosleeper peptide. The sequences of the two peptides and were determined using a combination of mass spectrometry, amino acid, and chemical sequence analyses, where Pca = pyroglutamic acid, Hyp = hydroxyproline, Gla = gamma-carboxyglutamate, and Trp* = L-6-bromotryptophan. The precise structure and stereochemistry of the modified residue were determined as L-6-bromotryptophan by synthesis, co-elution, and enzymatic hydrolysis experiments. To our knowledge this is the first documentation of tryptophan residues in peptides/proteins being modified in a eukaryotic system and the first report of halogenation of tryptophan in vivo.

Electrostatic spraying: a novel technique for preparation of polymer coatings on electrodes.

A liquid flow emerging from a tip or a thin tube under the influence of a strong electric field will, due to charging of the dielectric liquid, break up into small droplets. Thus, if a polymer material is dissolved in the liquid, this electrodeposition technique can be utilized for producing polymer coatings on electrodes. The method was applied for in situ formation of ultrathin (∼3000 Å) cellulose acetate (CA) phase inversion membranes on glassy carbon electrodes. The purpose of the membrane was to protect the electrode surface from fouling by macromolecular species. The spraying liquid consisted of CA, acetone, and aqueous magnesium perchlorate as pore former, and the spraying voltage was 14 kV. Profilometric measurements showed that the thickness of the spray-cast membranes was much more uniform than that of similar membranes formed by solvent casting. By using cadmium and lead as test analytes and differential pulse anodic stripping voltammetry as detection method, it was found that the membranes prepared by spray casting offered better protection against interference from poly(ethylene glycol) (PEG) 6000 than those prepared by solvent casting. Also, the interference from PEG 2000 was significantly reduced. Experimental details of the electrostatic spraying technique are given.

Isolation of Lys-conopressin-G from the venom of the worm-hunting snail, Conus imperialis.

Vasopressin homologs have previously been isolated from the venom of fish-hunting cone snails. We investigated whether a vasopressin-like peptide is found in the worm-hunter, Conus imperialis. Using i.c. injections in mice, we isolated a peptide from the venom of C. imperialis which induces scratching and grooming behavior characteristic of the conopressins. Biochemical characterization showed that this peptide is identical to Lys-conopressin-G. The results led us to speculate that the vasopressin-like peptides in Conus venoms may be examples of an evolving conversion of endogenous peptides for specialized venom uses.

A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI.

We report the isolation, characterization, and total synthesis of a small peptide ligand for nicotinic acetylcholine receptors (nAChRs). It is highly active against the neuromuscular receptor in frog but not in mice. In contrast, it induces seizures when injected centrally in mice and rats, suggesting that it may target neuronal nAChRs in mammals. Although such receptors may be important in both normal cognition and the pathophysiology of several neuropsychiatric disorders, there are few ligands to discriminate between the multiple receptor subtypes. The new peptide is a highly divergent alpha-conotoxin from the snail Conus imperialis, which preys on polychaete worms. In this article, the purification, structural analysis, synthesis, and preliminary physiological characterization of alpha-conotoxin ImI (alpha-CTx-ImI) are reported. The sequence of the peptide is: Gly-Cys-Cys-Ser-Asp-Pro-Arg-Cys-Ala-Trp-Arg-Cys-NH2. The peptide shows striking sequence differences from all alpha-conotoxins of fish-hunting Conus, but its disulfide-bridging is similar: [2-8; 3-12]. We suggest that cone venoms may provide an array of ligands with selectivity for various neuronal nAChR subtypes.

Microalbuminuria in type 2 diabetic patients: a cross-sectional study of frequency, sex distribution and relation to hypertension.

We studied 112 type 2 diabetic patients. Fourteen patients had frank proteinuria, and 37 of the remaining 98 had microalbuminuria which was more frequent in men than in women (P < 0.02). Hypertension was found in 47 of the patients, equally distributed between sexes. Male diabetics with microalbuminuria had higher systolic blood pressure than diabetics without microalbuminuria (P < 0.02). Body mass index was higher in both sexes with hypertension compared to patients without hypertension. In the hypertensive men plasma C-peptide values were higher compared to patients without hypertension (P < 0.01) irrespective of the presence of microalbuminuria. A positive correlation between blood pressure and C-peptide was found (P < 0.01) in the men. We suggest that gender should be taken into account in the analysis and interpretation of microalbuminuria in type 2 diabetes.

The effect of natural toxins on reproduction in livestock.

Reproductive efficiency is the most important economic factor in livestock production. Thus, the hypothalamo-pituitary-gonadal regulatory axis, accessory sexual organ functionality, and the complex events involved in fertilization, implantation, and embryonic and fetal development may be sensitive to therapeutic agents, environmental pollutants, and natural toxicants. There are many factors that adversely affect reproduction, one of which is toxic substances in the diets of animals. Toxic materials can affect reproductive success by causing abortions, interfering with libido, estrus, oogenesis, or spermatogenesis, causing emaciation and subsequent abnormal mating behavior, birth defects, and increasing the time between parturition and rebreeding. Examples of natural toxicants in poisonous plants interfering with reproduction are numerous. Abortion in livestock from locoweeds, ponderosa pine needles, broom snakeweeds, fescue, and others are reported in studies. Selenium and seleniferous forage inhibit estrus in cattle and swine. Emaciation and temporary illness from sneezeweeds, bitterweed, locoweed, larkspur, lupines, and others may interfere with mating. Embryonic loss and birth defects from Veratrum, lupines, locoweeds, poison hemlock, and so on, may occur. As suggested, toxins have many diverse and economically adverse effects on reproductive performance in livestock.

Cattle grazing Wahweap milkvetch in southeastern Utah.

Cattle's grazing of the locoweed Wahweap milkvetch (Astragalus lentiginosus var. wahweapensis) was evaluated on desert and foothill winter range during the winter of 1986 to 1987. Dry, dead stalks of Wahweap milkvetch that had grown in 1985 and 1986 made up 15% of cattle diets overall, and 24% of diets when cattle grazed gravelly benches where it was abundant. Nutritional quality of Wahweap milkvetch was higher than of most associated forage, but its alkaloid concentration varied among the senescent stages. One cow aborted and two cows developed clinical signs of locoweed poisoning, including water belly (hydrops amnii). Microscopic lesions consisting of cytoplasmic foamy vacuolation were evident in both the dam and fetus. Because senescent stalks of Wahweap milkvetch are palatable and readily grazed by cattle, ranchers should not permit cattle to graze infested sites until other green forage is available in the spring.

Economic impact of poisonous plants on the rangeland livestock industry.

Poisonous plants on rangelands cost producers and consumers upwards of $250 million annually in the U.S. These costs are attributable not only to livestock deaths and diminshed productivity related to plant poisoning, but also to the management costs associated with usage of forage in areas infested with poisonous plants. At present, even relatively small losses from plant poisoning can cause financial and economic impacts that threaten range enterprises, particularly those using public lands.