Plasma levels and biochemical characterisation of circulating met-enkephalin in canine endotoxin shock

Endogenous opioid peptides have been implicated in the pathophysiology of shock (1-5). In anaesthetised mongrel dogs, administration of E coli endotoxin caused a rise in plasma met-enkephalin-like immunoreactivity (MLI). Biochemical characterisation of MLI by gel filtration chromatography revealed various molecular forms: 31K, 8K, 3-5K and the native pentapeptide in approximately equal amounts. After enzymatic treatment of column fractions the 31K form predominated (90.7%). This is the first demonstration of elevated MLI in endotoxin shock.     

Noradrenaline: a circulating inhibitor of sodium transport.

Leucocytes were isolated from venous blood of 11 normotensive volunteers with no family history of hypertension and the sodium efflux rate constants determined both alone and in the presence of increasing physiological concentrations of noradrenaline. There was a significant dose dependent reduction of total sodium efflux rate constant due to a reduction in ouabain sensitive sodium pump activity, glycoside insensitive efflux rate constants being unaffected. The magnitude of this effect was similar to the reduction in leucocyte sodium efflux rate constants observed in hypertensive patients (and their normotensive relatives). The noradrenaline induced depression of sodium pump activity was prevented by propranolol in a further seven experiments, suggesting that the effect was mediated by beta adrenoceptors. Catecholamines possibly functioning as circulating inhibitors of sodium transport may contribute to some of the disturbances in membrane electrolyte handling both in essential hypertension in man and in some experimental models of hypertension.     

Beverage specific alcohol intake in a population-based study: Evidence for a positive association between pulmonary function and wine intake

Background  

Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA.     

Fibrinogen: a possible link between social class and coronary heart disease.

Mortality from coronary heart disease in civil servants in the lowest grade of employment has been found to be about three times that of men in the highest grade of employment. As part of an investigation of this finding several haemostatic variables were measured in a sample of 29 men in lower grades of employment and 45 men in higher grades. There was a significant difference in plasma fibrinogen concentrations between men in lower grades of employment and those in higher grades (mean 3.39 g/l v 2.95 g/l, respectively; p less than 0.01) but not in other haemostatic variables. Multiple regression analyses showed significant independent associations of fibrinogen concentration with smoking (p less than 0.05) and grade of employment (p less than 0.05). The size of the observed difference between the grades of employment was similar to that between those dying of coronary heart disease or surviving during longitudinal study; it may therefore be an important part of the mechanism underlying social class differences in coronary heart disease. The statistical relation between fibrinogen concentrations and other characteristics that may be concerned in the aetiology of coronary heart disease was examined. A summary measure of job stress was significantly related to fibrinogen concentration (p less than 0.01) and made a substantial contribution to explaining the differences between grades of employment. Behaviour type and a score of physical activity were not significantly related to fibrinogen concentration.     

Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation.

RNA granules are a macromolecular structure observed in neurons, where they serve as motile units that translocate mRNAs. Isolated RNA granules are highly enriched in Staufen protein and ultrastructurally contain densely packed clusters of ribosomes. With depolarization, many mRNAs, including those involved in plasticity, rapidly shift from the RNA granule fraction to polysomes. Depolarization reorganizes granules and induces a less compact organization of their ribosomes. RNA granules are not translationally competent, as indicated by the failure to incorporate radioactive amino acids and the absence of eIF4E, 4G, and tRNAs. We concluded that RNA granules are a local storage compartment for mRNAs under translational arrest but are poised for release to actively translated pools. Local release of mRNAs and ribosomes from granules may serve as a macromolecular mechanism linking RNA localization to translation and synaptic plasticity.     

Establishing a link between oncogenes and tumor angiogenesis.

We have tried to stress that mutant oncogenes or overexpressed, nonmutated proto-oncogenes, in addition to their direct affect on promoting aberrant tumor cell proliferation (and survival), may possess a crucial indirect means of stimulating tumor cell growth through regulation of angiogenesis. This effect would never be observed in tissue culture studies of oncogene function using pure cultures of tumor cells, which probably helps explain why the pro-angiogenic function of oncogenes has not been appreciated until only relatively recently. Indeed, the very first indication of a possible contributory role of oncogenes, such as ras and myc, to tumor angiogenesis was first reported by Thompson et al. in 1989, who used reconstituted organ cultures of the mouse prostate gland for their studies (69). This potentially important contribution of oncogenes to tumor growth and development may prove to have an impact on how various signal transduction inhibitors that are now in early phase clinical trials, e.g., monoclonal neutralizing antibodies to the human EGF receptor (70), function in vivo as anti-tumor agents.     

ATIA: a link between inflammation and hypoxia

In this issue of Molecular Cell,Choksi et al. (2011) report the identification of an NF-κB-independent ATIA (anti-TNFα-induced apoptosis)-Thioredoxin 2 axis that inhibits TNFα- and hypoxia-induced apoptosis through elimination of excessive reactive oxygen species directly.     

Release of beta endorphin and met-enkephalin during exercise in normal women: response to training.

Plasma beta endorphin and met-enkephalin concentrations were measured in response to treadmill exercises in 15 normal women before, during, and after an intensive programme of exercise training. Significant release of beta endorphin occurred in all three test runs, and the pattern and amount of release were not altered by training. Before training dramatic release of met-enkephalin was observed in seven subjects and smaller rises observed in a further four, and this response was almost abolished by training. This represents the first observed "physiological" stimulus to met-enkephalin release. Endogenous opioid peptides play a part in adaptive changes to exercise training and probably contribute to the menstrual disturbances of women athletes.     

Estradiol influences the LH response to met-enkephalin. An immunocytochemical and morphometric study.

In order to test the possible role of estradiol in the response of the LH-adenohypophyseal cells to the administration of met-enkephalin in the albino male rat, an immunocytochemical (peroxidase-antiperoxidase), morphometric (cellular and nuclear areas and numerical density) and radioimmunoassay (LH serum levels at the moment of sacrifice) study was carried out. The intraventricular administration of met-enkephalin (150 micrograms in 25 microliters of distilled water) does not produce any changes in the parameters considered. However, when the animals were pretreated with estradiol (chronically, 15 days), met-enkephalin produced a significant decrease in all the parameters considered.     

Gonadal steroids deficiency and prolactin response to a met-enkephalin analog in man

The aim of this study was to ascertain whether there is a correlation between gonadal steroids and opioid control of prolactin (PRL) secretion. Four castrated men, aged 18 to 24 years were submitted to intravenous injection of 250 ug of a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-Enkephalin, FK 33824) (DAMME). In normal men DAMME injection was also performed on the 6th day after treatment with clomiphene citrate (CC) (200 mg/day for 5 days), a specific nonsteroidal estrogen receptor blocker. In castrated men and in normal men after CC treatment, there was a lower PRL response to DAMME than in controls (P less than 0.0005). These results suggest that gonadal steroid deficiency seems to cause a change in the opioid system and/or dopaminergic control of prolactin secretion.     

Life's unity and flexibility: the ecological link.

The small size, ubiquity, metabolic versatility and flexibility, and genetic plasticity (horizontal transfer) of microbes allow them to tolerate and quickly adapt to unfavorable and/or changing environmental conditions. Prokaryotes are endowed with sophisticated cellular envelopes that contain molecules not found elsewhere in the biological world. Although prokaryotic cells lack the organelles that characterize their eukaryotic counterparts, their interiors are surprisingly complex. Prokaryotes sense their environment and respond as individual cells to specific environmental challenges; but prokaryotes also act cooperatively, displaying communal activities. In many microbial ecosystems, the functionally active unit is not a single species or population (clonal descendence of the same bacterium) but a consortium of two or more types of cells living in close symbiotic association. Only recently have we become aware that microbes are the basis for the functioning of the biosphere. Thus, we are at a unique time in the history of science, in which the interaction of technological advances and the exponential growth in our knowledge of the present microbial diversity will lead to significant advances not only in microbiology but also in biology and other sciences in general.     

Genetic recombination: Helicases and topoisomerases link up.

RecQ helicases and topoisomerase III are both required for genome stability, particularly to prevent 'promiscuous' genetic recombination. A recent study demonstrates that, together, these enzymes can catalyse the interlinking of plasmid DNA, and suggests a novel mechanism for the control of recombination.     

Molecular conformations of met-enkephalin: Comparison of the zwitterionic and cationic forms

Apparent discrepancies in published assignments of the pmr spectrum of Met-enkephalin are due to the existence of two forms, cationic and zwitterionic. The pmr parameters of these two forms indicate different secondary conformations. The pmr parameters of the zwitterionic form are indicative of a 2–5 β-I turn but no secondary conformation can be suggested for the cationic form with the present data.     

Phosphatidylinositol phosphate kinase: a link between protein kinase and glutathione synthase folds.

Comparisons of serine/threonine protein kinase (PK) and type IIbeta phosphatidylinositol phosphate kinase (PIPK) structures with each other and also with other proteins reveal structural and functional similarity between the two kinases and proteins of the glutathione synthase fold (ATP-grasp). This suggests that these enzymes are evolutionarily related. The structure of PIPK, which clearly resembles both PK and ATP-grasp, provides a link between the two proteins and establishes that the C-terminal domains of PK, PIPK and ATP-grasp share the same fold. The functional implications of the proposed homology are discussed.