Changes in plasma inbulin related to the type of dietary carbohydrate in overweight hyperlipidemic male patients

Five patients with mild diabetes mellitus or angina pectoris were studied, each of whom consumed two sequential diets containing 40 to 50% carbohydrate. When 75% of the dietary carbohydrate was derived from food containing polysaccharides, the mean plasma insulin response to oral glucose was decreased relative to that seen following complementary diets providing carbohydrate mainly as simple sugars. Under both dietary conditions, glucose tolerance was improved compared to that seen prior to the study. These results suggest that with sugar restriction an improvement in the efficiency of the pancreatic beta-cell mechanism occurs. This effect may have been mediated by changes in the rate of secretion of pancreatic glucagon, or by an enteric secretogogue of insulin.     

Counterintuitive migration patterns by Atlantic salmon Salmo salar smolts in a large lake

What little is known about the seaward migration of Salmo salar smolt migration through standing waters indicates that it is both slow and results in high mortality rates, compared with riverine migration. This may be partly because smolts in lakes need to swim more actively and require more complex directional cues than they do in rivers. In this telemetry study of smolt migration through Loch Lomond, S. salar smolts made repeated movements in directions away from the outflowing river, which considerably increased migration time.     

DNA binding studies of a new dicationic porphyrin. Insights into interligand interactions

Cationic porphyrins have an affinity for DNA and potential for applications in the fields of photodynamic therapy and cellular imaging. This report describes a new dicationic porphyrin, 5,15-dimethyl-10,20-di(N-methylpyridinium-4-yl)porphyrin, abbreviated H2tMe2D4. Although tetrasubstituted, H2tMe2D4 presents modest steric requirements and forms in reasonable yield by a "2+2" synthetic method. Accordingly, studies of the zinc(II)- and copper(II)-containing derivatives, Zn(tMe2D4) and Cu(tMe2D4), have also been possible. Methods used to characterize DNA-binding motifs include absorption, emission, linear, and circular dichroism spectroscopies, as well as viscometry. An unusually detailed picture of porphyrin uptake emerges. As the ratio of DNA to porphyrin increases during a typical titration, H2tMe2D4 or Cu(tMe2D4) initially aggregates on the host and then shifts to intercalative binding at close quarters before finally dispersing into non-interacting intercalation sites of the host. Emission studies of the copper(II) porphyrin have been very valuable. The existence of a measurable signal is diagnostic of intercalative binding, and the saturation behavior establishes that internalization typically monopolizes approximately three base pairs. In the moderate loading regime, emission data are most telling because dipole-dipole interactions between near-neighbor porphyrins tend to confuse other spectroscopic assays. The third ligand, Zn(tMe2D4), behaves differently in that the uptake is a strictly cooperative process. The mode of binding also varies with the base content of the DNA host. When the DNA is rich in A=T base pairs, the porphyrin remains five-coordinate and binds externally; however, Zn(tMe2D4) loses its axial ligand and binds by intercalation if the host contains only G[triple bond]C base pairs.     

The discovery of rofecoxib, [MK 966, Vioxx, 4-(4'-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2-inhibitor.

The development of a COX-2 inhibitor rofecoxib (MK 966, Vioxx) is described. It is essentially equipotent to indomethacin both in vitro and in vivo but without the ulcerogenic side effect due to COX-1 inhibition.     

Spectroscopic studies of 9-hydroxyellipticine binding to DNA

The binding of 9-hydroxyellipticine to calf thymus DNA, poly[d(A-T)]₂, and poly-[d(G-C)]₂ has been studied in detail by means of CD, linear dichroism, resonance light scattering, and molecular dynamics. The transition moment polarizations of 9-hydroxyelliptiycine were determined in polyvinyl alcohol stretched film. Spectroscopic solution studies of the DNA/drug complex are combined with theoretical CD calculations using the final 50 ps of a series of molecular dynamics simulations as input. The spectroscopic data shows 9-hydroxyellipticine to adopt two main binding modes, one intercalative and the other a stacked binding mode involving the formation of drug oligomers in the DNA major groove. Analysis of the intercalated binding mode in poly[d(A-T)]₂ suggests the 9-hydroxyellipticine hydroxyl group lies in the minor groove and hydrogen bonds to water with the pyridine ring protruding into the major groove. The stacked binding mode was examined using resonance light scattering and it was concluded that the drug was forming small oligomer stacks rather than extended aggregates. Reduced linear dichroism measurements suggested a binding geometry that precluded a minor groove binding mode where the plane of the drug makes a 45° angle with the plane of the bases. Thus it was concluded that the drug stacks in the major groove. No obvious differences in the mode of binding of 9-hydroxyellipticine were observed between different DNA sequences; however, the stacked binding mode appeared to be more favorable for calf thymus DNA and poly[d(G-C)]₂ than for poly[d(A-T)]₂, an observation that could be explained by the slightly greater steric hindrance of the poly[d(A-T)]₂ major groove. A strong concentration dependence was observed for the two binding modes where intercalation is favored at very low drug load, with stacking interactions becoming more prominent as the drug concentration is increased. Even at DNA : drug mixing ratios of 70:1 the stacked binding mode was still important for GC-rich DNAs. © 1998 John Wiley & Sons, Inc. Biopoly 46: 127–143, 1998     

Honey bee‐collected pollen in agro‐ecosystems reveals diet diversity,diet quality,and pesticide exposure

European honey bees Apis mellifera are important commercial pollinators that have suffered greater than normal overwintering losses since 2007 in North America and Europe. Contributing factors likely include a combination of parasites, pesticides, and poor nutrition. We examined diet diversity, diet nutritional quality, and pesticides in honey bee‐collected pollen from commercial colonies in the Canadian Maritime Provinces in spring and summer 2011. We sampled pollen collected by honey bees at colonies in four site types: apple orchards, blueberry fields, cranberry bogs, and fallow fields. Proportion of honey bee‐collected pollen from crop versus noncrop flowers was high in apple, very low in blueberry, and low in cranberry sites. Pollen nutritional value tended to be relatively good from apple and cranberry sites and poor from blueberry and fallow sites. Floral surveys ranked, from highest to lowest in diversity, fallow, cranberry, apple, and blueberry sites. Pesticide diversity in honey bee‐collected pollen was high from apple and blueberry sites and low from cranberry and fallow sites. Four different neonicotinoid pesticides were detected, but neither these nor any other pesticides were at or above LD₅₀ levels. Pollen hazard quotients were highest in apple and blueberry sites and lowest in fallow sites. Pollen hazard quotients were also negatively correlated with the number of flower taxa detected in surveys. Results reveal differences among site types in diet diversity, diet quality, and pesticide exposure that are informative for improving honey bee and land agro‐ecosystem management.