The cancer drug tamoxifen: a potential therapeutic treatment for spinal cord injury.

Tamoxifen (TMX) is a selective estrogen receptor modulator that can mimic the neuroprotective effects of estrogen but lacks its systemic adverse effects. We found that TMX (1 mg/day) significantly improved the motor recovery of partially paralyzed hind limbs of male adult rats with thoracic spinal cord injury (SCI), thus indicating a translational potential for this cancer medication given its clinical safety and applicability and the lack of currently available treatments for SCI. To shed light on the mechanisms underlying the beneficial effects of TMX for SCI, we used proteomic analyses, Western blots and histological assays, which showed that TMX treatment spared mature oligodendrocytes/increased myelin levels and altered reactive astrocytes, including the upregulation of the water channels aquaporin 4 (AQP4), a novel finding.

Inhibition of IL-6 signaling: A novel therapeutic approach to treating spinal cord injury pain.

To characterize the contribution of interleukin-6 (IL-6) to spinal cord injury pain (SCIP), we employed a clinically relevant rat contusion model of SCIP. Using Western blots, we measured IL-6 levels in lumbar segments (L1-L5), at the lesion site (T10), and in the corresponding lumbar and thoracic dorsal root ganglia (DRG) in 2 groups of similarly injured rats: (a) SCI rats that developed hind-limb mechanical allodynia (SCIP), and (b) SCI rats that did not develop SCIP. Only in SCIP rats did we find significantly increased IL-6 levels.

Some components of hibernation rhythms.

At low ambient temperatures some small mammals drastically reduce their body temperature and enter a state of dormancy known as hibernation. They exhibit endogenous rhythms of heterothermy/homeothermy and body mass fluctuations with the period close to one year. At high ambient temperature only body mass cycling is expressed for almost one year as well.

Mechanisms of immediate temperature compensation: experiments with brain synaptosomes from rat and ground squirrel.

Glucose conversion by brain synaptosomes can be regarded as a special case of intrinsic kinetic properties of the enzyme substrate system. Temperature modulation of apparent K(m) for this process can be described with our kinetic model. Using experimental data and the kinetic model, the minimal K(m) value for glucose conversion in ground squirrel synaptosomes was found at the lower temperature (6.

Radoslav K. Andjus (1926-2003): a brief summary of his life and work.

Radoslav K. Andjus was a professor of physiology and biophysics at the University of Belgrade, Serbia, from 1953 to 1992. He was an elected member of the Serbian Academy of Sciences and Arts, the International Academy of Astronautics, and the Montenegrin Academy of Sciences and Arts.

Endothelin-induced, long lasting, and Ca2+ influx-independent blockade of intrinsic secretion in pituitary cells by Gz subunits.

The G protein-coupled receptors in excitable cells have prominent roles in controlling Ca2+-triggered secretion by modulating voltage-gated Ca2+ influx. In pituitary lactotrophs, spontaneous voltage-gated Ca2+ influx is sufficient to maintain prolactin release high. Here we show that endothelin in picomolar concentrations can interrupt such release for several hours downstream of spontaneous and high K+-stimulated voltage-gated Ca2+ influx.

Membrane estrogen receptor-alpha levels predict estrogen-induced ERK1/2 activation in MCF-7 cells.

Introduction: We examined the participation of a membrane form of estrogen receptor (mER)-alpha in the activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK]1 and ERK2) related to cell growth responses in MCF-7 cells.

Methods: We immunopanned and subsequently separated MCF-7 cells (using fluorescence-activated cell sorting) into mER-alpha-enriched (mERhigh) and mER-alpha-depleted (mERlow) populations. We then measured the expression levels of mER-alpha on the surface of these separated cell populations by immunocytochemical analysis and by a quantitative 96-well plate immunoassay that distinguished between mER-alpha and intracellular ER-alpha.

Membrane estrogen receptor-alpha levels in MCF-7 breast cancer cells predict cAMP and proliferation responses.

Introduction: 17beta-estradiol (E2) can rapidly induce cAMP production, but the conditions under which these cAMP levels are best measured and the signaling pathways responsible for the consequent proliferative effects on breast cancer cells are not fully understood. To help resolve these issues, we compared cAMP mechanistic responses in MCF-7 cell lines selected for low (mERlow) and high (mERhigh) expression of the membrane form of estrogen receptor (mER)-alpha, and thus addressed the receptor subform involved in cAMP signaling.

Methods: MCF-7 cells were immunopanned and subsequently separated by fluorescence activated cell sorting into mERhigh (mER-alpha-enriched) and mERlow (mER-alpha-depleted) populations.

Kinetic properties of the enzyme-substrate system: a basis for immediate temperature compensation.

One-minimum U-shaped temperature profiles of the dissociation constant (K(m)) have been observed experimentally with a variety of enzyme-substrate (E-S) systems. The increase of E-S affinity with falling temperature ("positive thermal modulation of affinity"), which opposes the cold-induced reduction in catalytic velocity, has been often interpreted as significant for both immediate and evolutionary temperature compensations and of major importance in setting thermal limits in ectothermic organisms. This role was denied to enzymes from endotherms, on the ground that their minimal K(m) values were situated well below their normal body temperature.

Ca(2+)-mobilizing endothelin-A receptors inhibit voltage-gated Ca(2+) influx through G(i/o) signaling pathway in pituitary lactotrophs.

In excitable cells, receptor-induced Ca(2+) release from intracellular stores is usually accompanied by sustained depolarization of cells and facilitated voltage-gated Ca(2+) influx (VGCI). In quiescent pituitary lactotrophs, however, endothelin-1 (ET-1) induced rapid Ca(2+) release without triggering Ca(2+) influx. Furthermore, in spontaneously firing and depolarized lactotrophs, the Ca(2+)-mobilizing action of ET-1 was followed by inhibition of spontaneous VGCI caused by prolonged cell hyperpolarization and abolition of action potential-driven Ca(2+) influx.

Cell-type specific messenger functions of extracellular calcium in the anterior pituitary.

Calcium can serve not only as an intracellular messenger, but also as an extracellular messenger controlling the gating properties of plasma membrane channels and acting as an agonist for G protein-coupled Ca(2+)-sensing receptors. Here we studied the potential extracellular messenger functions of this ion in anterior pituitary cells. Depletion and repletion of the extracellular Ca(2+) concentration ([Ca(2+)]e) induced transient elevations in the intracellular Ca(2+) concentration ([Ca(2+)]i), and elevations in [Ca(2+)]e above physiological levels decreased [Ca(2+)]i in somatotrophs and lactotrophs, but not in gonadotrophs.