A search for activation of C nociceptors by sympathetic fibers in complex regional pain syndrome

Although the term 'reflex sympathetic dystrophy' has been replaced by 'complex regional pain syndrome' (CRPS) type I, there remains a widespread presumption that the sympathetic nervous system is actively involved in mediating chronic neuropathic pain ["sympathetically maintained pain" (SMP)], even in the absence of detectable neuropathophysiology.

Abolishing myofibroblast arrhythmogeneicity by pharmacological ablation of α-smooth muscle actin containing stress fibers

Rationale: Myofibroblasts typically appear in the myocardium after insults to the heart like mechanical overload and infarction. Apart from contributing to fibrotic remodeling, myofibroblasts induce arrhythmogenic slow conduction and ectopic activity in cardiomyocytes after establishment of heterocellular electrotonic coupling in vitro. So far, it is not known whether α-smooth muscle actin (α-SMA) containing stress fibers, the cytoskeletal components that set myofibroblasts apart from resident fibroblasts, are essential for myofibroblasts to develop arrhythmogenic interactions with cardiomyocytes. Objective: We investigated whether pharmacological ablation of α-SMA containing stress fibers by actin-targeting drugs affects arrhythmogenic myofibroblast–cardiomyocyte cross-talk. Methods and Results: Experiments were performed with patterned growth cell cultures of neonatal rat ventricular cardiomyocytes coated with cardiac myofibroblasts. The preparations exhibited slow conduction and ectopic activity under control conditions. Exposure to actin-targeting drugs (Cytochalasin D, Latrunculin B, Jasplakinolide) for 24 hours led to disruption of α-SMA containing stress fibers. In parallel, conduction velocities increased dose-dependently to values indistinguishable from cardiomyocyte-only preparations and ectopic activity measured continuously over 24 hours was completely suppressed. Mechanistically, antiarrhythmic effects were due to myofibroblast hyperpolarization (Cytochalasin D, Latrunculin B) and disruption of heterocellular gap junctional coupling (Jasplakinolide), which caused normalization of membrane polarization of adjacent cardiomyocytes. Conclusions: The results suggest that α-SMA containing stress fibers importantly contribute to myofibroblast arrhythmogeneicity. After ablation of this cytoskeletal component, cells lose their arrhythmic effects on cardiomyocytes, even if heterocellular electrotonic coupling is sustained. The findings identify α-SMA containing stress fibers as a potential future target of antiarrhythmic therapy in hearts undergoing structural remodeling.

Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations

To assess the relationship between endometriotic lesions with associated nerve fibers with both pain and peritoneal fluid (PF) cytokine concentrations based on lesion location.

Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers

We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

Analysis of nonlinear gain-induced effects on short-pulse amplification in doped fibers by use of an extended power equation

Optical pulse amplification in doped fibers is studied using an extended power transport equation for the coupled pulse spectral components. This equation includes the effects of gain saturation, gain dispersion, fiber dispersion, fiber nonlinearity, and amplified spontaneous emission. The new model is employed to study nonlinear gain-induced effects on the spectrotemporal characteristics of amplified subpicosecond pulses, in both the anomalous and the normal dispersion regimes.

Electrospun Quaternized Chitosan Fibers for Virus Removal from Drinking Water

Membrane filtration has become an accepted technology for the removal of pathogens from drinking water. Viruses, known to contaminate water supplies, are too small to be removed by a size-exclusion mechanism without a large energy penalty. Thus, functionalized electrospun membranes that can adsorb viruses have drawn our interest. We chose a quaternized chitosan derivative (HTCC) which carries a positively-charged quaternary amine, known to bind negatively-charged virus particles, as a functionalized membrane material. The technique of electrospinning was utilized to produce nanofiber mats with large pore diameters to increase water flux and decrease membrane fouling. In this study, stable, functionalized, electrospun HTCC-PVA nanofibers that can remove 3.6 logs (99.97%) of a model virus, porcine parvovirus (PPV), from water by adsorption and filtration have been successfully produced. This technology has the potential to purify drinking water in undeveloped countries and reduce the number of deaths due to lack of sanitation.

Analytical Parametric Model Used to Study the Influence of Electrostatic Force on Surface Coverage During Electrospinning of Polymer Fibers

Electrospinning (ES) can readily produce polymer fibers with cross-sectional dimensions ranging from tens of nanometers to tens of microns. Qualitative estimates of surface area coverage are rather intuitive. However, quantitative analytical and numerical methods for predicting surface coverage during ES have not been covered in sufficient depth to be applied in the design of novel materials, surfaces, and devices from ES fibers. This article presents a modeling approach to ES surface coverage where an analytical model is derived for use in quantitative prediction of surface coverage of ES fibers. The analytical model is used to predict the diameter of circular deposition areas of constant field strength and constant electrostatic force. Experimental results of polyvinyl alcohol fibers are reported and compared to numerical models to supplement the analytical model derived. The analytical model provides scientists and engineers a method for estimating surface area coverage. Both applied voltage and capillary-to-collection-plate separation are treated as independent variables for the analysis. The electric field produced by the ES process was modeled using COMSOL Multiphysics software to determine a correlation between the applied field strength and the size of the deposition area of the ES fibers. MATLAB scripts were utilized to combine the numerical COMSOL results with derived analytical equations. Experimental results reinforce the parametric trends produced via modeling and lend credibility to the use of modeling techniques for the qualitative prediction of surface area coverage from ES. (Copyright: 2014 American Vacuum Society.)

Modification of Actin Fibers Changes the Electrical Phenotype of Cardiac Myofibroblasts

Background: Slow conduction and ectopic activity are major determinants of cardiac arrhythmogenesis. Both of these conditions can be elicited by myofibroblasts (MFBs) following establishment of heterocellular gap junctional coupling with cardiomyocytes. MFBs appear during structural remodeling of the heart and are characterized by the expression of α-smooth muscle actin (α-SMA) containing stress fibers. In this study, we investigated whether pharmacological interference with the actin cytoskeleton affects myofibroblast arrhythmogeneicity. Methods: Experiments were performed with patterned growth strands of neonatal rat ventricular cardiomyocytes coated with cardiac MFBs. Impulse conduction velocity (θ) and maximal upstroke velocities of propagated action potentials (dV/dtmax), expressed as % action potential amplitude change (%APA) per ms, were measured optically using voltage sensitive dyes. Actin was destabilized by latrunculin B (LtB) and cytochalasin D and stabilized with jasplakinolide. Data are given as mean ± S.D. (n = 5-22). Single cell electrophysiology was assessed using standard patch-clamp techniques. Results: As revealed by immunocytochemistry, exposure of MFBs to LtB (0.01-10 μmol/L) profoundly disrupted stress fibers which led to drastic changes in cell morphology with MFBs assuming an astrocyte-like shape. In control cardiomyocyte strands (no MFB coat), LtB had negligible effects on θ and dV/dtmax. In contrast, LtB applied to MFB-coated strands increased θ dose-dependently from 197 ± 35 mm/s to 344 ± 26 mm/s and dV/dtmax from 38 ± 5 to 78 ± 3% APA/ms, i.e., to values virtually identical to those of cardiomyocyte control strands (339 ± 24 mm/s; 77 ± 3% APA/ms). Highly similar results were obtained when exposing the preparations to cytochalasin D. In contrast, stabilization of actin with increasing concentrations of jasplakinolide exerted no significant effects on impulse conduction characteristics in MFB-coated strands. Whole-cell patch-clamp experiments showed that LtB hyperpolarized MFBs from -25 mV to -50 mV, thus limiting their depolarizing effect on cardiomyocytes which was shown before to cause arrhythmogenic slow conduction and ectopic activity. Conclusion: Pharmacological interference with the actin cytoskeleton of cardiac MFBs affects their electrophysiological phenotype to such an extent that they loose their detrimental effects on cardiomyocyte electrophysiology. This result might form a basis for the development of therapeutic strategies aimed at limiting the arrhythmogenic potential of MFBs.