Altitude diuresis: endocrine and renal responses to acute hypoxia of acclimatized and non-acclimatized subjects

As a result of our recently published studies we have thought that altitude diuresis resulting from hypoxic stimulation of the arterial chemoreceptors reduces the cardiac volume overload. To test this hypothesis, cardiovascular, endocrine and renal responses to stepwise acute exposure to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers a mean of 24 days, SD 11, after descending from Himalayan altitudes of at least 4,000 m, with those found in ten non-acclimatized recumbent volunteers. The results showed that natriuresis and diuresis typified the renal responses to altitude exposure of both the acclimatized as well as non-acclimatized subjects, as long as altitude was well tolerated. It was concluded that the renal effects were mediated by atrial natriuretic peptide release and slight suppression of arginine-vasopressin (AVP) secretion, that the increased urine flow at altitude offset the cardiac (volume) overload resulting from hypoxic stimulation of the arterial chemoreceptors, and that enhanced AVP secretion, as found in the non-acclimatized subjects at and above 4,000 m, coincided with subjective and objective distress, i.e. with inadequate altitude adjustment owing to insufficient chemoreflex effects and central hypoxia.     

myo-Inositol oxygenase from rat kidneys. I: Purification by affinity chromatography; physical and catalytic properties.

Using the technique of affinity chromatography on a myo-inositol-substituted Sepharose, the myo-inositol oxygenase from rat kidneys was purified to homogeneity. The active enzyme contains iron, most probably in its divalent form. Electrophoresis on polyacrylamide gel containing sodium dodecylsulphate causes the cleavage of the enzyme protein into apparently identical subunits with a molecular weight of approximately 17,000. The smallest active unit consists of 4 subunits, and is in a pH-dependent equilibium with species consisting of 8, 12, and 16 subunits, respectively, which all show the same specific enzyme activity. In the presence of oxygen the enzyme is highly unstable; at the early stages of inactivation it can be reactivated by reducing agents like NaBH4. Under anaerobic conditions or under the influence of Fe2-chelating agents, the enzyme is also inactivated; this inactivation is caused by the loss of iron and concomitant cleavage into the subunits. It can be reversed by incubation with FeSO4 in the presence of air. If myo-inositol and FeSO4 are present, the reactivation involves an oligomerization to the species with 16 subunits with the uptake of 8 gram-atoms of iron per mole of this species. The enzyme reaction follows Michaelis-Menten kinetics; the Michaelis constants are 4.5 x 10(-2)M for myo-inositol and 9.5 x 10(-6)M for oxygen.     

Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20–30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health.     

Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal-lysosomal system in the ARPE-19 retinal pigment epithelial cell line

The endosomal-lysosomal system is central for cell homeostasis and comprises the functions and dynamics of particular organelles including endosomes, lysosomes and autophagosomes. In previous studies, we found that the cysteinyl leukotriene receptor 1 (CysLTR1) regulates autophagy in the retinal pigment epithelial cell line ARPE-19 under basal cellular conditions. However, the underlying mechanism by which CysLTR1 regulates autophagy is unknown. Thus, in the present study, the effects of CysLTR1 inhibition on the endosomal-lysosomal system are analyzed in detail to identify the role of CysLTR1 in cell homeostasis and autophagy regulation. CysLTR1 inhibition in ARPE-19 cells by Zafirlukast, a CysLTR1 antagonist, depleted the lysosomal pool. Furthermore, CysLTR1 antagonization reduced endocytic capacity and internalization of epidermal growth factor and decreased levels of the transferrin receptor, CD71. Serum starvation abolished the effect of Zafirlukast on the autophagic flux, which identifies the endocytic regulation of serum components by CysLTR1 as an important autophagy-modulating mechanism. The role of CysLTR1 in inflammation and cell stress has been exceedingly studied, but its involvement in the endosomal-lysosomal pathway is largely unknown. This current study provides new insights into basal activity of CysLTR1 on cellular endocytosis and the subsequent impact on downstream processes like autophagy.     

Über Chromatophorensystem,Farbensinn und Farbwechsel bei Crangon vulgaris

Ohne Zusammenfassung     

Biotechnological production of poly(3-hydroxybutyrate) with Wautersia eutropha by application of green grass juice and silage juice as additional complex substrates

Alternative inexpensive complex nitrogen- and phosphate sources from agriculture, green grass juice (GGJ) and silage juice (SJ), were added to cultivation medium in order to investigate their impact on growth of the well-known polyhydroxyalkanoate (PHA) accumulating strain Wautersia eutropha. The influence of these additives was directly compared with cultivations on defined minimal mineral medium (M) as well as on the same medium supplemented with more expensive complex additives: corn steep liquor (CSL) and casamino acids (CA). It turned out that the supplementation with most complex additives results in shortening of lag-phases of bacterial growth and in higher end-concentrations of residual biomass compared with M-medium. Finally, higher volumetric productivities for poly(3-hydroxybutyrate) (3-PHB) were achieved. The effect of the inexpensive additive SJ on volumetric productivity was similar to the result for the expensive CA (0.653 vs. 0.619 g L^-1 h^-1). The same was found for the biomass concentration (7.00 vs. 7.44 g L^-1 respectively). Together with an economic appraisal presented in this study, the results suggest it is possible to make the sustainable process of microbial PHA-production more economically feasible. A survey of the thermal characteristics and molecular mass properties of the isolated polymers completes this work.