Relation between blood pressure,weight, and plasma sugar and serum insulin levels in schoolchildren aged 9-12 years in Westland,Holland.

In 2388 schoolchildren aged 9-12 years who took part in a study of cardiovascular risk factors in Westland, Holland, plasma sugar concentrations were found to be positively correlated with systolic and diastolic blood pressure, independently of weight. Serum cholesterol levels were also related to systolic blood pressure in boys, but much less strongly than plasma sugar levels. The relation between serum insulin and blood pressure, independent of plasma sugar, was weak. The relation between plasma sugar and systolic pressure existed for both sexes and regardless of whether measurements were made in the morning or afternoon; its association with diastolic pressure was weaker, and was not so consistent over all groups. These findings suggest that the relations between risk factors for coronary heart disease that exist in adults are already evident in childhood.     

Comparative field cage tests of the population suppressing efficiency of three genetic control systems for Aedes Aegypti.

Cycling populations of Aedes aegypti were set up in cages and managed in such a way that the populations had a maximum of threefold recovery potential in response to control measures. Into three such populations daily releases were made of males which had been chemosterilised, or were double translocation heterozygotes (T1T3) or T1T3 with sex ration distortion (DT1T3). Eradication of the populations was achieved with all cases, but the rate of suppression was markedly slower with T1T3 than the other two systems, with which the rates were similar. T1T3 and DT1T3 releases introduced considerable inherited genetic loads into the target populations. The results were in general agreement with computer predictions.     

Evolution of specialized microbial cooperation in dynamic fluids

Here, we study the evolution of specialization using realistic computer simulations of bacteria that secrete two public goods in a dynamic fluid. Through this first‐principles approach, we find physical factors such as diffusion, flow patterns and decay rates are as influential as fitness economics in governing the evolution of community structure, to the extent that when mechanical factors are taken into account, (a) generalist communities can resist becoming specialists despite the invasion fitness of specialization; (b) generalist and specialists can both resist cheaters despite the invasion fitness of free‐riding; and (c) multiple community structures can coexist despite the opposing force of competitive exclusion. Our results emphasize the role of spatial assortment and physical forces on niche partitioning and the evolution of diverse community structures.     

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared.Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction.All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity.This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.     

Acid-base effects on intestinal Na(+) absorption and vesicular trafficking

We examined for vesicular traffickingof the Na⁺/H⁺ exchanger (NHE) in pH-stimulatedileal and CO₂-stimulated colonic Na⁺absorption. Subapical vesicles in rat distal ileum were quantified bytransmission electron microscopy at ×27,500 magnification. Internalization of ileal apical membranes labeled withFITC-phytohemagglutinin was assessed using confocal microscopy, andpH-stimulated ileal Na⁺ absorption was measured afterexposure to wortmannin. Apical membrane protein biotinylation of ilealand colonic segments and Western blots of recovered proteins wereperformed. In ileal epithelial cells incubated inHCO/Ringer or HEPES/Ringer solution, the number ofsubapical vesicles, the relative quantity of apical membrane NHEisoforms 2 and 3 (NHE2 and NHE3, respectively), and apical membranefluorescence under the confocal microscope were not affected by pHvalues between 7.1 and 7.6. Wortmannin did not inhibit pH-stimulatedileal Na⁺ absorption. In colonic epithelial apicalmembranes, NHE3 protein content was greater at aPCO₂ value of 70 than 21 mmHg, was internalized when PCO₂ was reduced, and was exocytosed whenPCO₂ was increased. We conclude that vesicletrafficking plays no part in pH-stimulated ileal Na⁺absorption but is important in CO₂-stimulated colonicNa⁺ absorption.

     

A solid-phase approach towards the synthesis of PDE5 inhibitors

PDE5 inhibitors based upon the xanthine scaffold 8 have been expediently synthesized using a solid-phase route. Attachment of the xanthine scaffold 8 using the Rink chloride linker 4 and N-1 functionalization using Mitsunobu chemistry is described. A library of compounds was produced in multi-milligram quantities with excellent purities and acceptable yields. The compounds were tested for their PDE5 inhibitory activity.     

Cdk5 is essential for synaptic vesicle endocytosis

Synaptic vesicle endocytosis (SVE) is triggered by calcineurin-mediated dephosphorylation of the dephosphin proteins. SVE is maintained by the subsequent rephosphorylation of the dephosphins by unidentified protein kinases. Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE. Thus Cdk5 has an essential role in SVE and is the first dephosphin kinase identified in nerve terminals.