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Exposing adrenal chromaffin cells to 5 ns electric pulses (nsPEF) causes a rapid rise in intracellular Ca 2+ ([Ca 2+ ] i ) that is solely the result of Ca 2+ influx through voltage-gated Ca 2+ channels (VGCCs). This study explored the effect of longer duration nsPEF on [Ca 2+ ] i . Single 150, 200, or 400 ns pulses at 3.1 kV/cm evoked rapid increases in [Ca 2+ ] i , the magnitude of which increased linearly with pulse width and electric field amplitude. Recovery of [Ca 2+ ] i to prestimulus levels was faster for 150 ns exposures. Regardless of pulse width, no rise in [Ca 2+ ] i occurred in the absence of extracellular Ca 2+ , indicating that the source of Ca 2+ was from outside the cell. Ca 2+ responses evoked by a 150 ns pulse were inhibited to varying degrees by ω -agatoxin IVA, ω -conotoxin GVIA, nitrendipine or nimodipine, antagonists of P/Q-, N-, and L-type VGCCs, respectively, and by 67% when all four types of VGCCs were blocked simultaneously. The remaining Ca 2+ influx insensitive to VGCC inhibitors was attributed to plasma membrane nanoporation, which comprised the E -field sensitive component of the response. Both pathways of Ca 2+ entry were inhibited by 200  μ M Cd 2+ . These results demonstrate that, in excitable chromaffin cells, single 150-400 ns pulses increased the permeability of the plasma membrane to Ca 2+ in addition to causing Ca 2+ influx via VGCCs.

This study was designed to determine whether marine-derived proteins other than cod could have beneficial effects on inflammation following muscle injury. Macrophage and neutrophil densities were measured from bupivacaine-injured tibialis anterior muscle of rats fed isoenergetic diets containing either shrimp hydrolysate (Shr), casein hydrolysate (CaH), or whole casein (Ca). In this study, Shr reduced ED 1+ -macrophages at day 2 ( p = 0.013), day 5 ( p = 0.006), and day 14 after injury ( p = 0.038) compared with Ca, indicating faster resolution of inflammation in Shr. Except for day 2 after injury where Shr led to lower ED 1+ -macrophages compared with CaH ( p = 0.006), both Shr and CaH responded similarly at days 5, 14, and 28 after injury. This findings suggest that beneficial effects of Shr on ED 1+ -cells might be related to generation of anti-inflammatory peptides through the hydrolysis process, in addition to its high content of anti-inflammatory amino acids. However, while increasing myofiber cross-sectional area in noninjured muscles compared with both Ca and CaH, Shr failed to have a positive effect in corresponding injured muscles. These data indicate that shrimp hydrolysate can facilitate resolution of inflammation after muscle injury mainly through modulating proinflammatory macrophage accumulation but have less effect on optimal recovery in terms of muscle mass and fiber size.

Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca(2+) levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K(+) channels (e.g., Kv1.5) and increased expression and activity of voltage-dependent (Cav1.2) and voltage-independent (e.g., canonical and vanilloid transient receptor potential [TRPC and TRPV]) Ca(2+) channels play an important role in the functional remodeling of pulmonary arteries in PH. This review focuses on an anion-permeable channel that is now considered a novel excitatory mechanism in the systemic and pulmonary circulations. It is permeable to Cl(-) and is activated by a rise in intracellular Ca(2+) concentration (Ca(2+)-activated Cl(-) channel, or CaCC). The first section outlines the biophysical and pharmacological properties of the channel and ends with a description of the molecular candidate genes postulated to encode for CaCCs, with particular emphasis on the bestrophin and the newly discovered TMEM16 and anoctamin families of genes. The second section provides a review of the various sources of Ca(2+) activating CaCCs, which include stimulation by mobilization from intracellular Ca(2+) stores and Ca(2+) entry through voltage-dependent and voltage-independent Ca(2+) channels. The third and final section summarizes recent findings that suggest a potentially important role for CaCCs and the gene TMEM16A in PH.

Background: Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD., Methods: Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively., Results: Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (β = -0.140, P = 0.023) and greater impairment (β = 0.141, P = 0.035) among individuals with AD., Conclusions: Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted., (© 2013 Wiley Periodicals, Inc.)

Background and Purpose: T16A(inh) -A01 is a recently identified inhibitor of the calcium-activated chloride channel TMEM16A. The aim of this study was to test the efficacy of T16A(inh) -A01 for inhibition of calcium-activated chloride channels in vascular smooth muscle and consequent effects on vascular tone., Experimental Approach: Single channel and whole cell patch clamp was performed on single smooth muscle cells from rabbit pulmonary artery and mouse thoracic aorta. Isometric tension studies were performed on mouse thoracic aorta and mesenteric artery as well as human abdominal visceral adipose artery., Key Results: In rabbit pulmonary artery myocytes T16A(inh) -A01 (1-30 μM) inhibited single calcium (Ca(2+) )-activated chloride (Cl(-) ) channels and whole cell currents activated by 500 nM free Ca(2+) . Similar effects were observed for single Ca(2+) -activated Cl(-) channels in mouse thoracic aorta, and in both cell types, channel activity was abolished by two antisera raised against TMEM16A but not by a bestrophin antibody. The TMEM16A potentiator, F(act) (10 μM), increased single channel and whole cell Ca(2+) -activated Cl(-) currents in rabbit pulmonary arteries. In isometric tension studies, T16A(inh) -A01 relaxed mouse thoracic aorta pre-contracted with methoxamine with an IC(50) of 1.6 μM and suppressed the methoxamine concentration-effect curve. T16A(inh) -A01 did not affect the maximal contraction produced by 60 mM KCl and the relaxant effect of 10 μM T16A(inh) -A01 was not altered by incubation of mouse thoracic aorta in a cocktail of potassium (K(+) ) channel blockers. T16A(inh) -A01 (10 μM) also relaxed human visceral adipose arteries by 88 ± 3%., Conclusions and Implications: T16A(inh) -A01 blocks calcium-activated chloride channels in vascular smooth muscle cells and relaxes murine and human blood vessels., (© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.)

The average funding of long-term care in Quebec, Canada, currently covers < 70% of the care hours required, which means that 30% of needs are unmet. The aims of this study were to understand how nurses, when they are in a position to do so, assign care hours, which needs are unmet by care dimensions and whether dimensions with unmet needs vary with client profiles. One-hundred-and-four nurses working in long-term care facilities participated in the study. They filled out individual questionnaires containing three case studies in the form of vignettes. When obliged to cut 30% of the care hours, the nurses ensured that treatment and diagnostic methods were done as prescribed and that vital feeding and elimination functions were preserved. However, they made the choice to cut some mobility and personal-care activities and, especially, communication with patients, families and other professionals. In this, they partly follow the theoretical care prioritization approach of Lefebvre and Dupuis, who take into account the degree of discomfort caused by the situation, the problem's place in Maslow's hierarchy of needs and the availability of a solution. Thus, although the choices made by the nurses follow a logical pattern, they could result in medium-term deterioration in the functional autonomy of their older patients. The overall consequences of these decisions are discussed.

Problem: To compare depressive symptoms in children with attention deficit hyperactivity disorder (ADHD) to those in healthy children, and to explore the influence of individual and family factors on level of depression., Methods: Individual interviews with 68 children, ages 7 to 12 years, in order to complete the Children's Depression Inventory., Findings: Children with ADHD reported significantly more depressive symptoms than did children without ADHD; 14.7% of children with ADHD reached the threshold of a 19 point score, which suggests clinical depression. No significant effects of individual and family factors on level of depression were found., Conclusions: Children with ADHD are more inclined to experience depressive symptoms than are healthy children. To plan appropriate interventions, nurses evaluating and working with children with ADHD should always consider a possible coexistence of depressive symptoms.

Increased peripheral resistance is a hallmark of chronic heart failure and has been primarily attributed to neurohumoral pathways involving both the renin-angiotensin and sympathetic nervous systems. The increased resistance is thought to serve as a compensatory mechanism to help maintain perfusion to the vital organs by sustaining blood pressure in the fate of a failing heart. Local mechanisms, and in particular endothelial dysfunction, have also been shown to be important contributors in regulating arterial resistance and vascular remodeling in this disease. In this issue of the British Journal of Pharmacology, Gschwend et al. (2003) present new data suggesting that in the absence of a functional endothelium, myogenic constriction of small pressurized mesenteric arteries, an intrinsic property of vascular smooth muscle cells, is enhanced in a coronary artery ligation-induced myocardial infarction model of congestive heart failure (CHF) in the rat. The increased myogenic tone appears to be tightly linked to angiotensin II type 1 receptors (AT(1)). The possibility that CHF-induced stimulation of myogenic constriction is due to the local release of preformed angiotensin II or constitutive upregulation of the AT(1) receptor signaling pathways are discussed along with other potential cellular and molecular mechanisms previously suggested to play a role in myogenic reactivity.

1. In order to assess the role of different ionic currents in hypoxia-induced action potential shortening, we investigated the effects of blockers of voltage-dependent and ATP-sensitive K(+)-channel on the membrane potential of hypoxic rabbit hearts and papillary muscles. The response to blocking of the inward rectifier was studied at three external K+ concentration: 2.5, 5, and 7.5 mM. 2. Hypoxia produced a progressive decline in action potential duration (APD) that levelled off after 15 to 20 min. Steady state APD values at 25% and 95% repolarization (APD25 and APD95) were 26.0 +/- 1.9% and 42.2 +/- 2.4% of controls respectively. 3. Tetraethylammonium (TEA, 10 mM) delayed but did not reduce APD shortening at the steady state. 4. Blocking of IK1 with a mixture of 0.2 mM Ba2+ and 4 mM Cs+ lengthened APD in normoxia and prevented APD95 shortening in hypoxia. The APD25 shortening was significantly attenuated at all [K]o. 5. Glibenclamide (Glib, 30 microM) did not prevent APD shortening, but produced a progressive action potential (AP) lengthening after 15 min of hypoxia. Steady levels of 48 +/- 3.5% and 62 +/- 5.0% of controls for APD25 and APD95 respectively were reached after 45 min. 6. The relation between APD25 and pacing rate was determined in normoxic and hypoxic papillary muscles and the effects of 2 mM 4-aminopyridine (4-AP) were examined. Hypoxia attenuated the APD25 shortening currently observed when the stimulation rate was lowered from 1 to 0.1 Hz without altering the plateau reduction occurring at frequencies above 2 Hz. These effects were potentiated by 4-AP.7. Our data suggest that the accelerated AP repolarization in hypoxic rabbit myocardium represents a delicate balance of several outward currents: IKI, IK-ATP. and at least one yet unidentified current component rather insensitive to changes in [K]o and to K+ channel blockers.