Large mechanical properties enhancement in ceramics through vacancy-mediated unit cell disturbance.

Tailoring vacancies is a feasible way to improve the mechanical properties of ceramics. However, high concentrations of vacancies usually compromise the strength (or hardness). We show that a high elasticity and flexural strength could be achieved simultaneously using a nitride superlattice architecture with disordered anion vacancies up to 50%.

Design of Laves phase-reinforced compositionally complex alloy.

Topologically close-packed (TCP) phases such as Laves phases are usually considered to harm the mechanical properties of classical superalloys for high-temperature applications. However, if an optimal fraction and size are designed, this situation can completely change for some compositionally complex alloys (CCA). Based on existing studies on austenitic or ferritic steels, we propose in this paper a design strategy aimed at exploiting the role of the Laves phase in defining the mechanical properties of wrought CCAs at elevated temperatures.

Sinus Node Dysfunction, Atrial Arrhythmias, and the Sinus Node Microcirculation.

A patient with sinus node dysfunction (SND) developed atrial arrhythmias that were abolished after avoidance of nonsteroidal anti-inflammatory medication and by the institution of a deliberate, modest increase in blood pressure, suggesting that there was a vascular component to the rhythm disturbance. Published anatomical evidence for a unique sinus node microcirculation substantiates the premise that SND may be sensitive to arterial flow. Because physicians have been unaware of the presence of a unique sinus node microcirculation, recognition of its presence may alter the approach to treatment of patients with SND and atrial arrhythmias, particularly in the elderly and those with diabetes.

Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study.

Background: Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines.

Methods: We calculated defined daily doses for statistical purposes (S-DDD) per million inhabitants per day of opioid analgesics worldwide and for regions and countries from 2001 to 2013, and we used generalised estimating equation analysis to assess longitudinal change in use.

Complex interactions of NO/cGMP/PKG systems on Ca2+ signaling in afferent arteriolar vascular smooth muscle.

Little is known about the effects of nitric oxide (NO) and the cyclic GMP (cGMP)/protein kinase G (PKG) system on Ca(2+) signaling in vascular smooth muscle cells (VSMC) of resistance vessels in general and afferent arterioles in particular. We tested the hypotheses that cGMP-, Ca(2+)-dependent big potassium channels (BK(Ca(2+))) buffer the Ca(2+) response to depolarization by high extracellular KCl and that NO inhibits adenosine diphosphoribose (ADPR) cyclase, thereby reducing the Ca(2+)-induced Ca(2+) release. We isolated rat afferent arterioles, utilizing the magnetized microsphere method, and measured cytosolic Ca(2+) concentration ([Ca(2+)](i)) with fura-2, a preparation in which endothelial cells do not participate in [Ca(2+)](i) responses.

Differential role of circulating endothelial progenitor cells in cirrhotic patients with or without hepatocellular carcinoma.

Background And Aims: Circulating endothelial progenitor cells have a negative prognostic impact in patients with hepatocellular carcinoma, but may play a different role in portal hypertension according to preclinical data. Here, we address this issue for the first time in cirrhotic patients+/-hepatocellular carcinoma.

Methods: Portal hypertension in cirrhotic and hepatocellular carcinoma patients was determined by hepatic venous pressure gradient.

Angiotensin II-stimulated Ca2+ entry mechanisms in afferent arterioles: role of transient receptor potential canonical channels and reverse Na+/Ca2+ exchange.

In afferent arterioles, the signaling events that lead to an increase in cytosolic Ca(2+) concentration ([Ca(2+)](i)) and initiation of vascular contraction are increasingly being delineated. We have recently studied angiotensin II (ANG II)-mediated effects on sarcoplasmic reticulum (SR) mobilization of Ca(2+) and the role of superoxide and cyclic adenosine diphosphoribose in these processes. In the current study we investigated the participation of transient receptor potential canonical channels (TRPC) and a Na(+)/Ca(2+) exchanger (NCX) in Ca(2+) entry mechanisms.

Effect of the ABCB1 modulators elacridar and tariquidar on the distribution of paclitaxel in nude mice.

Purpose: Previously, we studied the effect of co-administration of paclitaxel with the second generation ABCB1 (p-gp) modulator valspodar on the intracerebral growth of human U118-MG glioblastoma in nude mice. Valspodar significantly increased the brain levels of paclitaxel by inhibition of p-gp expressed at the blood brain barrier. Thus, the tumour burden was reduced by 90%, which was considered as a proof of concept.

ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo.

An important role for the enzyme ADP-ribosyl cyclase (ADPR cyclase) and its downstream targets, the ryanodine receptors (RyR), is emerging for a variety of vascular systems. We hypothesized that the ADPR cyclase/RyR pathway contributes to regulation of renal vasomotor tone in vivo. To test this, we continuously measured renal blood flow (RBF) in anesthetized Sprague-Dawley rats.

Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in preglomerular arterioles.

We have previously shown that in afferent arterioles, angiotensin II (ANG II) involves activation of the inositol trisphosphate receptor (IP(3)R), activation of adenine diphosphoribose (ADPR) cyclase, and amplification of the initial IP(3)R-stimulated release of cytosolic Ca(2+) ([Ca(2+)](i)) from the sarcoplasmic reticulum (SR) (Fellner SK, Arendshorst WJ. Am J Physiol Renal Physiol 288: F785-F791, 2004). The response of the ryanodine receptor (RyR) to local increases in [Ca(2+)](i) is defined as calcium-induced calcium release (CICR).

Endothelin-A and -B receptors, superoxide, and Ca2+ signaling in afferent arterioles.

It is unknown if endothelin-A and -B receptors (ET(A)R and ET(B)R) activate the production of superoxide via NAD(P)H oxidase and subsequently stimulate the formation of cyclic adenine diphosphate ribose (cADPR) in afferent arterioles. Vessels were isolated from rat kidney and loaded with fura 2. Endothelin-1 (ET-1) rapidly increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) by 303 nM.

Angiotensin II, reactive oxygen species, and Ca2+ signaling in afferent arterioles.

In afferent arteriolar vascular smooth muscle cells, ANG II induces a rise in cytosolic Ca(2+) ([Ca(2+)](i)) via inositol trisphosphate receptor (IP(3)R) stimulation and by activation of the adenine diphosphate ribose (ADPR) cyclase to form cyclic ADPR, which sensitizes the ryanodine receptor (RyR) to Ca(2+). We hypothesize that ANG II stimulation of NAD(P)H oxidases leads to the formation of superoxide anion (O(2)-*, which, in turn, activates ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca(2+)](i).

Endothelin-1, superoxide and adeninediphosphate ribose cyclase in shark vascular smooth muscle.

In vascular smooth muscle (VSM) of Squalus acanthias, endothelin-1 (ET-1) signals via the ET(B) receptor. In both shark and mammalian VSM, ET-1 induces a rise in cytosolic Ca(2+) concentration ([Ca(2+)](i)) via activation of the inositol trisphosphate (IP(3)) receptor (IP(3)R) and subsequent release of Ca(2+) from the sarcoplasmic reticulum (SR). IP(3)R-mediated release of SR Ca(2+) causes calcium-induced calcium release (CICR) via the ryanodine receptor (RyR), which can be sensitized by cyclic adeninediphosphate ribose (cADPR).

Ca2+ signaling in prothoracicotropic hormone-stimulated prothoracic gland cells of Manduca sexta: evidence for mobilization and entry mechanisms.

Prothoracicotropic hormone (PTTH) stimulates ecdysteroidogenesis in lepidopteran prothoracic glands (PGs), thus indirectly controlling molting and metamorphosis. PTTH triggers a signal transduction cascade in PGs that involves an early influx of Ca2+. Although the importance of Ca2+ has been long known, the mechanism(s) of PTTH-stimulated changes in cytoplasmic Ca2+ [Ca2+]i are not yet well understood.

Angiotensin II Ca2+ signaling in rat afferent arterioles: stimulation of cyclic ADP ribose and IP3 pathways.

ANG II induces a rise in cytosolic Ca(2+) ([Ca(2+)](i)) in vascular smooth muscle (VSM) cells via inositol trisphosphate receptor (IP(3)R) activation and release of Ca(2+) from the sarcoplasmic reticulum (SR). The Ca(2+) signal is augmented by calcium-induced calcium release (CICR) and by cyclic adeninediphosphate ribose (cADPR), which sensitizes the ryanodine-sensitive receptor (RyR) to Ca(2+) to further amplify CICR. cADPR is synthesized from beta-nicotinamide adenine dinucleotide (NAD(+)) by a membrane-bound bifunctional enzyme, ADPR cyclase.

BDNF regulates NMDA receptor activity in developing retinal ganglion cells.

Brain-derived neurotrophic factor (BDNF) modulates glutamate receptors of the NMDA type in many areas of the brain. We assessed whether BDNF exerts an effect on NMDA receptor properties in retinal ganglion cells during early postnatal development. Electrophysiological responses to the glutamate agonist NMDA (500 microM-2 mM) in retinal slices of wildtype and BDNF deficient mice (bdnf-/-) were recorded using the whole-cell patch-clamp technique.

Endothelin B receptor Ca2+ signaling in shark vascular smooth muscle: participation of inositol trisphosphate and ryanodine receptors.

In mammals, endothelin receptors are sub-classified into ET(A) receptors (ET(A)R), which are purely constrictive in vascular smooth muscle (VSM), and ET(B)R, which may produce constriction in VSM or dilatation by stimulating the production of nitric oxide (NO) from endothelial cells. In contrast, previous studies suggested that shark VSM is stimulated exclusively by ET(B)R. The Ca(2+) signaling pathways utilized by shark VSM in response to stimulation by endothelin-1 (ET-1) have not previously been investigated.

Endothelin A and B receptors of preglomerular vascular smooth muscle cells.

Background: The endothelin (ET) receptors are subclassified into ET(A,) which are purely vasoconstrictive, and ET(B). The ET(B) receptors may cause either vasodilation by stimulating the release of nitric oxide from endothelial cells, or vasoconstriction of vascular smooth muscle cells (VSMC). The relative contribution of ET(A) and ET(B) receptors to calcium signaling and vasoconstriction in the renal microcirculation is not clear.

Ionic strength and the polyvalent cation receptor of shark rectal gland and artery.

The dogfish shark Squalus acanthias regulates plasma osmolality and extracellular volume by secreting a fluid from its rectal gland which has a higher NaCl and lower urea concentration than plasma. We have previously identified the presence of a calcium-sensing receptor or polyvalent cation sensing receptor (CaSR) on vascular smooth muscle of the rectal gland artery (RGA) and rectal gland tubules (RGT). Activity of the CaSR is influenced by changes in ionic strength.

Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo.

Paclitaxel concentrations in the brain are very low after intravenous injection. Since paclitaxel is excluded from some tumors by p-glycoprotein (p-gp), the same mechanism may prevent entry into the brain. In vitro, paclitaxel transport was examined in capillaries from rat brains by confocal microscopy using BODIPY Fl-paclitaxel.

Gordon Murray: heparin, hemodialysis and hubris.

Gordon Murray (1894-1976), a brilliant and innovative surgeon who spent the majority of his professional career at the University of Toronto, Ont., Canada, is properly credited with having performed the first successful hemodialyses in humans in North America. Neither he nor Kolff, working in the Netherlands, were aware of each other's work during the middle 1940s when wartime hampered communication.

A Ca(2+)-sensing receptor modulates shark rectal gland function.

The elasmobranch Squalus acanthias controls plasma osmolality and extracellular fluid volume by secreting a hypertonic fluid from its rectal gland. Because we found a correlation between extracellular Ca(2+) concentration and changes in cytosolic Ca(2+) ([Ca(2+)](i)), we sought the possible presence of a calcium-sensing receptor in rectal gland artery and tubules. Cytosolic Ca(2+) of both tissues responded to the addition of external Ca(2+) (0.