Resveratrol stimulates hydrogen sulfide (H2S) formation to relax murine corpus cavernosum

Introduction: Resveratrol (RVT) found in red wine protects against erectile dysfunction and relaxes penile tissue (corpus cavernosum) via a nitric oxide (NO) independent pathway. However, the mechanism remains to be elucidated. Hydrogen sulfide (H2S) is a potent vasodilator and neuromodulator generated in corpus cavernosum. Aims: We investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2S. Methods: H2S formation is measured by methylene blue assay and vascular reactivity experiments have been performed by DMT strip myograph in CD1 MCC strips. Main Outcome Measures: Endothelial NO synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 0.1mM) or H2S inhibitor aminooxyacetic acid (AOAA, 2mM) which inhibits both cystathionine-β-synthase (CBS) and cystathionine-gamma-lyase (CSE) enzyme or combination of AOAA with PAG (CSE inhibitor) has been used in the presence/absence of RVT (0.1mM, 30min) to elucidate the role of NO or H2S pathways on the effects of RVT in MCC. Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide (NaHS) and acetylcholine (ACh) were studied. Results: Exposure of murine corpus cavernosum to RVT increased both basal and L-cysteine-stimulated H2S formation. Both of these effects were reversed by AOAA but not by L-NNA. RVT caused concentration-dependent relaxation of MCC and that RVT-induced relaxation was significantly inhibited by AOAA or AOAA+PAG but not by L-NNA. L-cysteine caused concentration-dependent relaxations, which are inhibited by AOAA or AOAA+PAG significantly. Incubation of MCC with RVT significantly increased L-cysteine-induced relaxation, and this effect was inhibited by AOAA+PAG. However, RVT did not alter the effect of exogenous H2S (NaHS) or ACh-induced relaxations. Conclusions: These results demonstrate that RVT-induced relaxation is at least partly dependent on H2S formation and acts independent of eNOS pathway. In phosphodiesterase 5 inhibitor (PDE-5i) nonresponder population, combination therapy with RVT may reverse erectile dysfunction via stimulating endogenous H2S formation. Yetik-Anacak G, Dereli MV, Sevin G, Ozzayim O, Erac Y, and Ahmed A. Resveratrol stimulates hydrogen sulfide (H2S) formation to relax murine corpus cavernosum.

Looking back or looking forward in corpus linguistics:what can the last 20 years suggest about the next?

Starting with a description of the software and hardware used for corpus linguistics in the late 1980s to early 1990s, this contribution discusses difficulties faced by the software designer when attempting to allow users to study text. Future human-machine interfaces may develop to be much more sophisticated, and certainly the aspects of text which can be studied will progress beyond plain text without images. Another area which will develop further is the study of patternings involving not just single words but word-relations across large stretches of text.

Candidate knowledge? Exploring epistemic claims in scientific writing:a corpus-driven approach

In this article I argue that the study of the linguistic aspects of epistemology has become unhelpfully focused on the corpus-based study of hedging and that a corpus-driven approach can help to improve upon this. Through focusing on a corpus of texts from one discourse community (that of genetics) and identifying frequent tri-lexical clusters containing highly frequent lexical items identified as keywords, I undertake an inductive analysis identifying patterns of epistemic significance. Several of these patterns are shown to be hedging devices and the whole corpus frequencies of the most salient of these, candidate and putative, are then compared to the whole corpus frequencies for comparable wordforms and clusters of epistemic significance. Finally I interviewed a ‘friendly geneticist’ in order to check my interpretation of some of the terms used and to get an expert interpretation of the overall findings. In summary I argue that the highly unexpected patterns of hedging found in genetics demonstrate the value of adopting a corpus-driven approach and constitute an advance in our current understanding of how to approach the relationship between language and epistemology.