Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects against different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors are present in the retina. In this study, we summarize the current knowledge on retinal PACAP with focus on the retinoprotective effects. Results of histological, immunohistochemical, and molecular biological analysis are reviewed. In vitro, PACAP shows protection against glutamate, thapsigargin, anisomycin, and anoxia. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models of retinal degeneration in rats: excitotoxic injury induced by glutamate and kainate, ischemic injury, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy. Studying the molecular mechanism has revealed that PACAP acts by activating antiapoptotic and inhibiting proapoptotic signaling pathways in the retina in vivo. These studies strongly suggest that PACAP is an excellent candidate retinoprotective agent that could be a potential therapeutic substance in various retinal diseases.

Introduction In addition to nitric oxide (NO), it is thought that an endothelium-derived hyperpolarizing factor (EDHF) plays an important role in the relaxation of penile arteries. Recently, it has been shown that C-type natriuretic peptide (CNP) shows the characteristics of EDHF in systemic small arteries. Aim To investigate the mechanism involved in CNP-evoked vasodilatation and to address whether CNP is an EDHF in human penile resistance arteries. Methods Erectile tissue was obtained in connection with transsexual operations. Intracavernous penile resistance arteries were isolated and mounted in microvascular myographs for recording of isometric tension. Membrane potential was recorded by the use of a small glass electrode inserted in the smooth muscle layer. Main Outcome Measure In vitro evidence for hyperpolarization and vasorelaxation induced by CNP. Results Acetylcholine (ACh) and CNP hyperpolarized smooth muscle membrane potential in resting penile resistance arteries. In penile small arteries incubated with inhibitors of NO synthase and cyclooxygenase and contracted with phenylephrine, ACh and CNP evoked concentration-dependent relaxations with maximum of 56±6% and 71±6%, respectively. Addition of a combination of blockers of small- and intermediate-conductance calcium-activated K+ channels, apamin plus charybdotoxin, respectively, and a combination thought to block the smooth muscle response of EDHF-type relaxation, barium plus ouabain, markedly reduced ACh- and CNP-evoked relaxation. Iberiotoxin, a blocker of big-conductance calcium-activated K+ channels inhibited the vasorelaxant responses evoked by ACh and CNP. A selective natriuretic peptide receptor type C (NPR-C) agonist, C-atrial natriuretic factor4−23 (cANF4−23), induced relaxations with less maximum response compared to CNP. Conclusion The present findings suggest that CNP possesses the characteristics of an EDHF in human penile resistance arteries. By activation of natriuretic peptide receptor type B and NPR-C receptors, CNP causes relaxation by activation, respectively, of large-conductance calcium-activated K+ channels and Na+/K+-adenosine triphosphatase (ATPase), and barium-sensitive inward rectifier K+ channels. Modulation of the CNP pathway opens for new treatment modalities of erectile dysfunction.

A hybrid-type terahertz pulse source is proposed for high energy terahertz pulse generation. It is the combination of the conventional tilted-pulse-front setup and a transmission stair-step echelon-faced nonlinear crystal with a period falling in the hundred-micrometer range. The most important advantage of the setup is the possibility of using plane parallel nonlinear optical crystal for producing good-quality, symmetric terahertz beam. Another advantage of the proposed setup is the significant reduction of imaging errors, which is important in the case of wide pump beams that are used in high energy experiments. A one dimensional model was developed for determining the terahertz generation efficiency, and it was used for quantitative comparison between the proposed new hybrid setup and previously introduced terahertz sources. With lithium niobate nonlinear material, calculations predict an approximately ten-fold increase in the efficiency of the presently described hybrid terahertz pulse source with respect to that of the earlier proposed setup, which utilizes a reflective stair-step echelon and a prism shaped nonlinear optical crystal. By using pump pulses of 50 mJ pulse energy, 500 fs pulse length and 8 mm beam spot radius, approximately 1% conversion efficiency and 0.5 mJ terahertz pulse energy can be reached with the newly proposed setup.

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