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Inflammatory diseases are a major source of morbidity and mortality world-wide, the pathogenesis of which are characterised by the interplay of key pro-inflammatory and oxidative enzymes. Here, we report the development of a small molecule dual inhibitor targeting vascular adhesion protein-1 (VAP-1) and myeloperoxidase (MPO), two clinically relevant pro-inflammatory/oxidative enzymes that play complementary pathogenic roles in various inflammatory diseases. This agent, SNT-8370 [(E)-3-(3-((2-(aminomethyl)-3-fluoroallyl)oxy)benzyl)-2-thioxo-1,2,3,7-tetrahydro-6H-purin-6-one)], irreversibly inhibits VAP-1 and MPO activity with equivalent and enhanced nanomolar potency, respectively, when compared to benchmark clinical VAP-1 and MPO inhibitors. SNT-8370 is selective, exhibiting >100-1000-fold more potency for VAP-1 and MPO versus other mammalian (per)oxidases and shows no significant off-target activity in established preclinical screening panels. In vivo, SNT-8370 is metabolically stable, exhibits a favourable pharmacokinetic/pharmacodynamic profile without CNS penetration, and effectively inhibits VAP-1 and MPO activities. Moreover, compared to monotherapy, SNT-8370 more effectively inhibits leukocyte infiltration in mouse peritonitis, carrageenan air pouch, and lipopolysaccharide-induced lung injury models of acute inflammation. SNT-8370 is also protective in preclinical models of myocardial ischemia-reperfusion injury and unilateral-ureteral-obstruction-induced nephropathy. Collectively, our results support SNT-8370 as a first-in-class, mechanism-based dual inhibitor of VAP-1 and MPO, and as a promising therapeutic for the clinical treatment of inflammatory disorders. Targeting proinflammatory/oxidative enzymes is a promising approach to treat inflammatory diseases. Here the authors present a dual-specificity inhibitor for the simultaneous targeting of Vascular Adhesion Protein-1 and Myeloperoxidase, two cooperative but functionally independent enzymes, and report potent anti-inflammatory effects of the dual inhibitor in multiple animal models of inflammatory disease.

ObjectivesTrichomonas vaginalis (TV) has a low profile in urban sexually transmitted infection (STI) clinics in many developed countries. The objective of this study was to determine the true prevalence of TV in an Australian urban sexual health setting using sensitive molecular diagnostic techniques.MethodsA cross-sectional study investigating the aetiology of cervicitis in women attending two urban sexual health clinics in Sydney, Australia, enrolled 356 consecutive eligible women from 2006 to 2008. The diagnostic yield from the standard clinical practice of discretionary high vaginal wet preparation microscopy in women with suspicious vaginal discharge was compared with universal use of nested PCR for TV of cervical samples.ResultsTV was detected by PCR in 17/356 women (4.8%, 95% CI 2.8 to 7.5%), whereas only four cases (1.1%, 95% CI 0.3 to 2.8%) were detected by discretionary wet preparation microscopy. Eleven of the 17 women (p=0.003) were of culturally and linguistically diverse background. Additionally, cervicitis was found to be significantly associated with TV, RR 1.66 (1.14 to 2.42), p=0.034.ConclusionsTraditional TV-detection methods underestimate TV prevalence in urban Australia. The TV prevalence of 4.8% by PCR testing in this study exceeds previously reported urban Australian TV rates of <1%. An increase in trichomoniasis-associated adverse reproductive outcomes and enhanced HIV transmission poses a salient public health threat. Accordingly, TV warrants a higher profile in urban STI clinic settings in developed countries, and we suggest that priority be given to development of standardised molecular TV detection techniques and that these become part of routine STI testing.

One is the return of artists from the post-punk era to claim some credit for the influence they've had and to show the kids how it's done. Thus, for every young pretender like She Wants Revenge or the Organ aping the fey drama and chugging rhythms of the skinny-tie era, there's a resurgent Gang of Four - who destroyed a downtown rooftop yesterday evening at a party hosted by Urb magazine - or Echo and the Bunnymen to demonstrate to us where all this stuff came from. Performances by the remarkably well-preserved Morrissey and the Charlatans served as reminders that we were going mad for Brits long before the Arctic Monkeys came along. A Friday-night showcase by the Kid 606's Tigerbeat 6 label at the Velvet Spade featuring Genders, Drop the Lime, Quintron and Miss Pussycat and the Kid himself pulled 'em in. A rollicking tag-team DJ set by Ghostly International labelmates Matt Dear and Ryan Elliott at Karma Lounge the same night was as crammed and sweaty as any rock 'n' roll gig.

To top off the weirdness, the entire event- dubbed Ignition 2003 and featuring a who's-who of Detroit techno luminaries, including Stacey Pullen, Eddie Fowlkes, Blake Baxter and K.Hand- is being thrown by the Detroit Historical Society. Seems odd, perhaps, but techno- the futuristic, steely-but-soulful electronic music nurtured (and named) in the ravaged Motor City during the early 1980s is one of the most important developments in Detroit's recent history. The world's, too: Hometown boy Derrick May's 1987 single \"Strings Of Life,\" for many the consummate Detroit-techno moment, was one of the key tracks fuelling the rise of U.K. rave during Britain's storied \"Second Summer of Love\" and turned a localized club music made by and for urban, middle-class blacks into the blueprint for a worldwide dance-music movement and the standard soundtrack for today's movies, TV shows, commercials and hipper-than-thou shops. Credit for the turnaround probably goes to the DEMF, a free, three-day electronic-music festival launched over the 2000 Memorial Day weekend that championed hometown talent and belatedly paid homage to techno's three, Detroit-born \"innovators\"- high-school chums May, Kevin Saunderson and \"techno godfather\" Juan Atkins, who put his first record out as Cybotron in 1981- on their own soil. The inaugural festival, funded by the city, stunned its organizers by drawing an estimated one million people through Hart Plaza that first weekend. Two more have drawn similar numbers, although financial losses and a nasty rift between the Detroit techno community and the DEMF's producers over the 2001 firing of Detroit DJ/producer Carl Craig as artistic director almost killed the festival this year. JASON KRYK FOR THE TORONTO STARJASON KRYK FOR THE TORONTO STAR A Prince gold album hangs on the wall at the First Techno Music exhibit which recently opened at the Detroit Historical Museum. Detroit-area students, right, tour the exhibit.PAUL WARNER/ap Julie Glassco, 24, of Auburn Hills, Mich. lets loose at Roostertail in Detroit during \"Ignition 2003,\" a party celebrating the new exhibit, \"Techno: Detroit's Gift to the World,\" which opened at the Detroit Historical Museum last Saturday. The exhibit, which chronicles the rise of Detroit Techno music around the world, will tour the world after it closes in Detroit in June of next year.

Electronic music is under-represented, for sure, although every indie-rock act from TV on the Radio to the Unicorns is incorporating electro-doodads of one sort or another into their music these days. As an uncharacteristically awkward Saturday-night showcase staged by Detroit label Ghostly Recordings at the Zero Degrees club demonstrated, too, it's hard for a laptop-techno genius like Matthew Dear or a heads-down, instrumental electro combo like Midwest Product to compete in an environment overwhelmed by beer, meat and guitars, guitars, guitars. We love the Hiss. Probably not wise to let your sister date one of them, mind you, but these sleaze-charged Atlanta rockers were so thrillingly loud and dirty Friday night that they qualify as my favourite SXSW moment. Imagine Kyuss blasting through the more Zep- ish entries in the Stone Roses catalogue with maximum locked-riff precision and heaviness, then keep your fingers crossed the band hits Toronto soon. The razor wire lining the walls above the open- air stage at Red Eyed Fly only heightened the effect. David Cross is bigger than Jesus. He's more popular than George W. Bush in the liberal enclave of Austin, anyway. Couldn't get near a Friday-night stand-up routine at Emo's by the Mr. Show alumnus and current Arrested Development star as part of a \"Rock Against Bush\" showcase with Cali-punk oldsters NOFX, unfortunately. Cross nevertheless cemented his reputation as a consummate rock 'n' roll comic by enthusiastically making the party rounds and, more importantly, demonstrating his ardent fanhood for Toronto's Constantines at the Blender Bar on Friday night. Bashfully running into him around town for a few days was almost as good as seeing him perform, I guess.

Easily meeting and exceeding high expectations set by their seething debut, Chat And Business, these prickly young Brits justified the entire trip to Texas in a single, electrifying performance. The frenetic record promised a certain, blinding level of intensity, but Ikara Colt- three stylish indie boys and a fiendishly noisy girl guitarist- proved a real joy to watch, too, dispensing practiced poses and post-punk pummelling in equal measure and turning several hundred heat stricken SXSW refugees into giddy teenagers. Soft-spoken singer Paul Resende is a rock showman who has nicked the best moves from Mick Jagger and Iggy Pop. When Ikara Colt opens for Sahara Hotnights at the Horseshoe on April 3, you are strongly encouraged to be there. A boozy busman's holiday for Young Fresh Fellow Scott McCaughey, R.E.M.'s Peter Buck, Model Rocket John Ramberg and sometime Ministry (!!!) drummer Bill Rieflin, this late-afternoon set at Austin's pre- eminent indie record shop was a total gas. The sight of four immensely talented players having a laugh with McCaughey's punchy, four-chord power-pop songbook was enough, but the shaggy frontman's droll, half-cut between-song banter was as entertaining as his tunes. Looking for all the world like a pack of 12-year-olds who'd slipped into the bar with fake IDs, youthful, 905-spawned space- country ensemble Cuff the Duke played an all-Canadian showcase hosted by Toronto's North by Northeast festival to a slightly diminished crowd after packed and powerful showcases by Broken Social Scene and Montreal's the Stills. The Three Gut Records underdogs rose to the occasion, however, nimbly switching gears from country jangle to prog-rock majesty to shoegazer guitar grind in an evening-capping set that showed off Cuff the Duke's remarkable musicianship and old-beyond-their-years songwriting abilities.

Merkules is one of Canada's best-kept hip-hop secrets-- and also highly in demand as a shoulder to cry on.