Consistency of laboratory animal food following incubation prior to autoclaving

In this study the conventional autoclaving technique was modified by incubating the food overnight prior to autoclaving. This treatment resulted in a markedly improved consistency of the food pellets, comparable with that of untreated food. The modified autoclaved food did not adhere to the walls of feeders or clog the transport passage. Furthermore, the losses in thermolabile vitamins resulting from this treatment were the same as those resulting from conventional autoclaving.     

Cell-specific expression of human HGF by alveolar type II cells induces remodeling of septal wall tissue in the lung: a morphometric study

Hepatocyte growth factor (HGF) is involved in development and regeneration of the lungs. Human HGF, which was expressed specifically by alveolar epithelial type II cells after gene transfer, attenuated the bleomycin-induced pulmonary fibrosis in an animal model. As there are also regions that appear morphologically unaffected in fibrosis, the effects of this gene transfer to normal lungs is of interest. In vitro studies showed that HGF inhibits the formation of the basal lamina by cultured alveolar epithelial cells. Thus we hypothesized that, in the healthy lung, cell-specific expression of HGF induces a remodeling within septal walls. Electroporation of a plasmid of human HGF gene controlled by the surfactant protein C promoter was applied for targeted gene transfer. Using design-based stereology at light and electron microscopic level, structural alterations were analyzed and compared with a control group. HGF gene transfer increased the volume of distal air spaces, as well as the surface area of the alveolar epithelium. The volume of septal walls, as well as the number of alveoli, was unchanged. Volumes per lung of collagen and elastic fibers were unaltered, but a marked reduction of the volume of residual extracellular matrix (all components other than collagen and elastic fibers) and interstitial cells was found. A correlation between the volumes of residual extracellular matrix and distal air spaces, as well as total surface area of alveolar epithelium, could be established. Cell-specific expression of HGF leads to a remodeling of the connective tissue within the septal walls in the healthy lung, which is associated with more pronounced stretching of distal air spaces at a given hydrostatic pressure during instillation fixation.     

Evolutionary melting pots: a biodiversity hotspot shaped by ring diversifications around the Black Sea in the Eastern tree frog (Hyla orientalis)

Hotspots of intraspecific genetic diversity, which are of primary importance for the conservation of species, have been associated with glacial refugia, that is areas where species survived the Quaternary climatic oscillations. However, the proximate mechanisms generating these hotspots remain an open issue. Hotspots may reflect the long‐term persistence of large refugial populations; alternatively, they may result from allopatric differentiation between small and isolated populations, that later admixed. Here, we test these two scenarios in a widely distributed species of tree frog, Hyla orientalis, which inhabits Asia Minor and southeastern Europe. We apply a fine‐scale phylogeographic survey, combining fast‐evolving mitochondrial and nuclear markers, with a dense sampling throughout the range, as well as ecological niche modelling, to understand what shaped the genetic variation of this species. We documented an important diversity centre around the Black Sea, composed of multiple allopatric and/or parapatric diversifications, likely driven by a combination of Pleistocene climatic fluctuations and complex regional topography. Remarkably, this diversification forms a ring around the Black Sea, from the Caucasus through Anatolia and eastern Europe, with terminal forms coming into contact and partially admixing in Crimea. Our results support the view that glacial refugia generate rather than host genetic diversity and can also function as evolutionary melting pots of biodiversity. Moreover, we report a new case of ring diversification, triggered by a large, yet cohesive dispersal barrier, a very rare situation in nature. Finally, we emphasize the Black Sea region as an important centre of intraspecific diversity in the Palearctic with implications for conservation.     

Potent and selective xanthine-based inhibitors of phosphodiesterase 5

Inhibitors of PDE5 are useful therapeutic agents for treatment of erectile dysfunction. A series of novel xanthine derivatives has been identified as potent inhibitors of PDE5, with good levels of selectivity against other PDE isoforms, including PDE6. Studies in the dog indicate excellent oral bioavailability for compound 21.     

Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans.

Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15-18 degrees C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling. Cardiac output (heart rate x stroke volume) and indexes of vascular conductance (flux or blood velocity/MAP) were calculated. Skin-surface cooling increased MAP (n = 26; 78 +/- 5 to 88 +/- 5 mmHg; mean +/- SD) and decreased mean skin temperature (n = 26; 33.7 +/- 0.7 to 27.5 +/- 1.2 degrees C) and cutaneous (n = 12; 0.93 +/- 0.68 to 0.36 +/- 0.20 flux/mmHg), brachial (n = 10; 32 +/- 15 to 20 +/- 12), celiac (n = 8; 85 +/- 22 to 73 +/- 22 cm.s(-1).mmHg(-1)), superior mesenteric (n = 8; 55 +/- 16 to 48 +/- 10 cm.s(-1).mmHg(-1)), and renal (n = 8; 74 +/- 26 to 64 +/- 20 cm.s(-1).mmHg(-1); all P < 0.05) vascular conductance, without altering oral temperature, cardiac output, heart rate, or stroke volume. These data identify decreases in vascular conductance of skin and of brachial, celiac, superior mesenteric, and renal arteries. Thus it appears that vasoconstriction in both peripheral and visceral arteries contributes importantly to the pressor response produced during skin-surface cooling in humans.     

A supramolecular enzyme model catalyzing the central cleavage of carotenoids

Several bis-beta-cyclodextrin porphyrins have been prepared as supramolecular receptors of carotenoids. The binding constants of carotenoids to receptors were determined by quenching the fluorescence of the porphyrins on hydrophobic binding of carotenoids within the cavities of cyclodextrins. K(a)=8.3 x 10(6) M(-1) was calculated for binding of beta,beta-carotene to bis-beta-cyclodextrin Zn porphyrin. The corresponding Ru complex catalyzes the central cleavage of carotenoids in the presence of tert-butyl hydroperoxide in a biphasic system.     

Child mortality and malaria transmission intensity in Africa

The desirability of controlling malaria transmission in the areas of highest endemicity of Plasmodium falciparum has long been debated. Most recently, it has been claimed that rates of malaria morbidity are no higher in areas of very high transmission in Africa than they are in places with lower inoculation rates. We now review the literature on the relationship of morbidity and mortality to malaria transmission intensity, and have linked published child mortality and malaria transmission rates to examine how age-specific mortality actually varies with the inoculation rate of P. falciparum.     

Asymmetric microbial reduction of ethyl and isoprophyl α,1,3-trioxo-2-isoindolinebutyrate

Summary Microorganisms are capable of the asymmetric reduction of various types of ketones. From a limited screening with 103 selected microbial strains two have been chosen which reduce ethyl and isopropyl ,1,3-trioxo-2-isoindolinebutyrate (1a and 1b) stereoselectively. The optically active products ethyl and isopropyl -hydroxy-1,3-dioxo-2-isoindoline butyrate (2a and 2b) are useful precursors of the cerebral insufficiency improver hydroxy-aniracetam. Up to 3% of substrates 1a or 1b can be added in the reaction medium and converted by Candida parapsilosis. The isolated (R)-enantiomers of the product alcohols 2a and 2b show an enantiomeric excess (ee) of 98%–99%. The process was successfully tested on a 200-1 scale, the transformation rate being 0.83 g/1 per day and the yield of isolated product 72%. With Torulopsis magnoliae (S)-enantiomers of the products 2a and 2b were formed with an ee of 97%–99%.Offprint requests to: Hans G. W. Leuenberger     

Sympathetic discharge and vascular resistance after bed rest

Shoemaker, J. Kevin, Cynthia S. Hogeman, Urs A. Leuenberger,Michael D. Herr, Kristen Gray, David H. Silber, and Lawrence I. Sinoway. Sympathetic discharge and vascular resistance after bedrest. J. Appl. Physiol. 84(2):612-617, 1998.The effect of 6° head-down-tilt bedrest (HDBR) for 14 days on supine sympathetic discharge andcardiovascular hemodynamics at rest was assessed. Mean arterialpressure, heart rate (n = 25), musclesympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow(n = 14) were measured, and forearmvascular resistance (FVR) was calculated. Stroke distance,our index of stroke volume, was derived from measurements of aorticmean blood velocity (Doppler) and R-R interval(n = 7). With these data, an index oftotal peripheral resistance was determined. Heart rate at rest wasgreater in the post (71 ± 2 beats/min)- compared with the pre-HDBRtest (66 ± 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic strokedistance during post-HDBR (15.5 ± 1.1 cm/beat) was reduced frompre-HDBR levels (20.0 ± 1.5 cm/beat)(P < 0.03). Also, MSNA burstfrequency was reduced in the post (16.7 ± 2.8 beats/min)- comparedwith the pre (25.2 ± 2.6 beats/min)-HDBR condition(P < 0.01). Bed rest did not alterforearm blood flow, FVR, or total peripheral resistance. Thusreductions in MSNA with HDBR were not associated with a decrease inFVR.