Hypertension in obesity may reflect a homeostatic thermogenic response

Systemic hypertension of mild to moderate degree is often associated with obesity. The hypothesis is that over-eating leads to increased sympathetic activity targeted at the peripheral vasculature as well as other tissues in an attempt (that in many cases may be futile) to stimulate facultative thermogenesis and burn-off the excess energy. This hypothesis represents an important modification of one proposed by Landsberg and is supported by: 1) recent observations that carbohydrate feeding to humans specifically increases muscle sympathetic vasoconstrictor activity in the peroneal nerve, and 2) studies with animal models in which active vasoconstriction in the limbs and elsewhere is associated with marked increases in oxygen consumption (energy expenditure).     

mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species

Reconstructions of the human-African great ape phylogeny by using mitochondrial DNA (mtDNA) have been subject to considerable debate. One confounding factor may be the lack of data on intraspecific variation. To test this hypothesis, we examined the effect of intraspecific mtDNA diversity on the phylogenetic reconstruction of another Plio- Pleistocene radiation of higher primates, the fascicularis group of macaque (Macaca) monkey species. Fifteen endonucleases were used to identify 10 haplotypes of 40-47 restriction sites in M. mulatta, which were compared with similar data for the other members of this species group. Interpopulational, intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of divergence time and branching order incorporating this variation were substantially different from those based on single representatives of each species. We conclude that intraspecific mtDNA diversity is substantial in at least some primate species. Consequently, without prior information on the extent of genetic diversity within a particular species, intraspecific variation must be assessed and accounted for when reconstructing primate phylogenies. Further, we question the reliability of hominoid mtDNA phylogenies, based as they are on one or a few representatives of each species, in an already depauperate superfamily of primates.      

The modes of action of gallamine

The action of gallamine, a classical competitive neuromuscular blocking agent, has been examined on voltage-clamped endplates of frog skeletal muscle fibres. Gallamine produces a parallel shift of the equilibrium log (concentration)--response curves in concentrations of up to about 40 microM. At a membrane potential of -70 mV the Schild plot of the dose ratios so measured has a gradient of slightly less than the theoretical value, for a competitive antagonist, of unity. The apparent equilibrium constant for 'competitive' block is about 2 microM, and is approximately independent of the membrane potential. Fluctuation analysis of the endplate current shows two components in the presence of gallamine. The results can be fitted, over the range tested, by a mechanism that involves block of open ion channels by gallamine in a manner similar to that by procaine or quaternary local anaesthetic analogues. The rate constants for this action are strongly dependent on the membrane potential. At -100 mV the association rate constant is about 4 x 10(7) M-1S-1, the dissociation rate constant is about 600 s-1, and the equilibrium constant about 15 microM. Other kinetic measurements (voltage-jump relaxation, and nerve-evoked endplate currents) give results consistent with this conclusion, but apparently these results are valid over a range of conditions narrower than that for fluctuation analysis.     

Fine structure of an octopaminergic neuron and its terminals

The large octopaminergic dorsal unpaired median neuron of the locust that innervates the extensor tibiae muscle, DUMETi, was examined electronmicroscopically. Its soma contains many Golgi complexes apparently making dense-core vesicles similar to those found in peripheral branches and terminals. There are also larger stores of the dense material in the soma, especially near the exit of the principal neurite, that are not in vesicular form. Since the neurons can be penetrated and stimulated by microelectrodes, they form favorable subjects for direct studies of the control of neurosecretion. Preterminal fine branches of the neuron were located in proximal outer bundles of muscle fibers into which they had been traced electrophysiologically. They contain numerous large dense-core vesicles arrayed in rows near microtubules. These fine branches have a thick layer of collagenous connective tissue between the axon and the muscle fiber. Final terminals have varicosities containing many vesicles, lying inside the outer layers of the sarcolemmal complex of muscle fibers. They do not form synaptic structures. Terminals of another DUM neuron, one that innervates the dorsal longitudinal flight muscles (DUMDL), were similar in detail to those of DUMETi. DUMETi swelled about 20-fold in cross-sectional area above a ligature, in a 12-hr period, indicating that there is an extensive centrifugal flow of material in it, and sprouted a branch.     

Interglacial high sea levels—an absolute chronology derived from shoreline elevations

The heights of some stranded shores in Gippsland, Australia, greatly exceed the level to which the ocean would rise if all present-day ice were to melt, and uplift is thus implied. Differences in level shown by comparison of these interglacial shorelines with others in South Carolina may therefore be the result of movement of one area relative to the other. Contemporary shorelines in the two localities can nevertheless be recognized from certain physiographic similarities and from the meagre measured age data presently available. We believe, furthermore, that there is sufficient information to permit estimation of the average rate of relative movement, and we attempt to analyse the field observations by applying a simple model that relates shoreline elevation to implied rate of uplift. This model is based on the supposition that the earth movements actually experienced were continuous, or can be reasonably represented as small fluctuations about a regular long-term trend. use of the model permits estimation of absolute ages (calculated from differences in altitude of correlated levels) for each high sea level stage that is recognized. Although the calculated or “altimetric” ages derived in this way are quite speculative, they agree with radiometric ages of Alaskan transgressions, interglacial littoral faunas, and warm intervals identified in deep-sea cores, and seem therefore to be verified by these comparisons. Particular correlations between high sea levels and warm core stages are implied: if these pairings are accepted, the altimetric ages can be re-estimated using the ages of the core stages. Predictions which use the calculated ages also provide tests of their value.     

The novel ruthenium—γ‐linolenic complex [Ru2(aGLA)4Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential,increased reactive oxygen species generation and apoptosis in vitro

The present study reports the synthesis of a novel compound with the formula [Ru₂(aGLA)4Cl] according to elemental analyses data, referred to as Ru₂GLA. The electronic spectra of Ru₂GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru₂GLA was synthesized with the aim of combining and possibly improving the anti‐tumour properties of the two active components ruthenium and γ‐linolenic acid (GLA). The properties of Ru₂GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru₂GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru₂GLA enters the cells and ICP‐AES elemental analysis found an increase in ruthenium from <0.02 to 425 mg/Kg in treated cells. The sub‐G1 apoptotic cell population was increased by Ru₂GLA (22 ± 5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru₂GLA (44 ± 2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18 ± 1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru₂GLA exposed cells. The EC₅₀ for Ru₂GLA decreased with increasing time of exposure from 285 µM at 24 h, 211 µM at 48 h to 81 µM at 72 h. In conclusion, Ru₂GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright © 2009 John Wiley & Sons, Ltd.     

Structure and conformation of a novel genetically engineered polysaccharide P2

A new exocellular polysaccharide (P2) has been produced by the manipulation of a glycosyl transferase gene (aceP) involved in the biosynthesis of the polysaccharide acetan by the bacterium Acetobacter xylinum strain CKE5. The P2 polysaccharide has been studied by methylation analysis, reductive cleavage, and 1H and 13C NMR spectroscopy. The data are consistent with the structure predicted when the aceP gene is deactivated: [Molecular structure: see text]. The effect of cooling on proton NMR line width indicates a coil-helix transition in P2 at about 70 degrees C.     

Eicosapentaenoic acid and docosahexaenoic acid effects on tumour mitochondrial metabolism, acyl CoA metabolism and cell proliferation

In order to investigate the effects of high-fat diets rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), Wistar rats bearing subcutaneous implants of the Walker 256 tumour were fed pelleted chow containing low DHA/EPA or high DHA/EPA. The presence of n-3 polyunsaturated fatty acids (PUFAs) led to a marked suppression (35-46%) of tumour growth over a 12 day period. Both the whole tumour homogenate and the Percoll-purified mitochondrial fraction presented significant changes in fatty acid composition. The levels of EPA increased in both n-3 dietary groups while the levels of DHA increased only in the high DHA/EPA group, in comparison with the control chow-fed group. The presence of n-3 PUFAs led to an increase in mitochondrial acyl CoA synthetase activity, but neither the cytoplasmic acyl CoA content nor the n-3 fatty acid composition of the cytoplasmic acyl CoAs was altered by the diet. The content of thiobarbituric acid-reactive substances (TBARS) was increased in the low DHA/EPA group but was unchanged in the high DHA/EPA group. In vitro studies with the Walker 256 cell line showed a 46% decrease in cell growth in the presence of either EPA or DHA which was accompanied by a large decrease in the measured mitochondrial membrane potential. The TBARS content was increased only in the EPA-exposed cells. Cell cycle analysis identified a decrease in G0-G1 phase cells and an increase in G2-M phase cells and apoptotic cells, for both EPA and DHA-exposed cells. The data show that the presence of n-3 PUFAs in the diet is able to significantly after the growth rate of the Walker 256 tumour. The involvement of changes in mitochondrial membrane composition and membrane potential have been indicated for both EPA and DHA, while changes in lipid peroxidation have been identified in the presence of EPA but not of DHA.     

Bipedicle paraspinous muscle flaps for spinal wound closure: an anatomic and clinical study

The purpose of this study was to evaluate the vascular anatomy of the paraspinous muscles and review their clinical use as bipedicled flaps in spinal wound closure. Anatomically, through cadaver dissections, lead oxide injections, and radiographic imaging, the blood supply to the paraspinous muscles was determined. Clinically, 29 consecutive patients treated with spinal wounds and exposed bone or hardware were reviewed retrospectively. Of these patients, 19 underwent closure in delayed primary fashion, whereas 10 were referred to plastic surgery for reconstruction because of the complex nature of their wounds. The cadaver study demonstrated the paraspinous muscles to possess a segmental arterial supply through medial and lateral perforators. Division of the medial perforators allowed for medial advancement of the muscles. Lead oxide injection of the lateral perforators demonstrated adequate medial muscle perfusion with ligation of the medial perforators. Ten of the 29 patients (six women, four men, 32 to 62 years of age) were reconstructed with paraspinous (eight), latissimus (one), and trapezius (one) muscle flaps. A higher complication rate was found in wounds closed in delayed primary fashion (13 of 19 patients, 68 percent) than those reconstructed with muscle flaps (2 of 10 patients, 20 percent) (p = 0.021). Follow-up of the muscle flap reconstructed patients averaged 12 months (range, 3 to 27 months). Cadaver muscle injections predicted and clinical cases confirmed that the paraspinous muscles can be raised on lateral perforators and advanced medially to close lumbar spine wounds reliably with fewer complications.