Browsing by Author "Manko, Anna"

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    Anti-Inflammatory and Cytoprotective Actions of Hydrogen Sulfide: Translation to Therapeutics
    (Antioxidants & Redox Signaling, 2015-04-15) Wallace, John L.; Blackler, Rory W.; Chan, Melissa V.; Da Silva, Gabriela J.; Elsheikh, Wagdi; Flannigan, Kyle L.; Gamaniek, Iulia; Manko, Anna; Wang, Lu; Motta, Jean-Paul; Buret, Andre G.
    Significance: There is a rapidly expanding body of evidence for important roles of hydrogen sulfide in protecting against tissue injury, reducing inflammation, and promoting repair. There is also growing evidence that H2S can be successfully exploited in drug development. Recent Advances: H2S synthesis and degradation are regulated in circumstances of inflammation and injury so as to promote repair and re-establish homeostasis. Novel H2S-releasing drugs exhibit enhanced anti-inflammatory and pro-restorative effects, while having reduced adverse effects in many tissues. Critical Issues: H2S is a pleiotropic mediator, having effects on many elements in the inflammatory cascade and promoting the resolution of inflammation and injury. It also contributes significantly to mucosal defence in the gastrointestinal tract, and in host defence against infection. There is strong evidence that novel, H2S-based therapeutics are safe and effective in animal models, and several are progressing through human trials. Future Directions: A better understanding of the physiological and pathophysiological roles of H2S continues to be restrained by the lack of simple, reliable methods for measurement of H2S synthesis, and the paucity of highly selective inhibitors of enzymes that participate in endogenous H2S synthesis. On the other hand, H2S donors show promise as therapeutics for several important indications. Antioxid. Redox Signal. 22, 398–410.
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    Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors
    (Current Tropical Medicine Reports, 2015-07-11) Buret, Andre G.; Amat, Christina B.; Manko, Anna; Beatty, Jennifer K.; Halliez, Marie C. M.; Bhargava, Amol; Motta, Jean-Paul; Cotton, James A.
    Giardia duodenalis is a very common, ubiquitous, intestinal protozoan parasite infecting animals and humans. Of the eight distinct genetic assemblages known to date, assemblages A and B are infectious to humans. Giardia is the most commonly recognized cause of traveller’s diarrhea. Giardiasis impairs weight gain and is responsible for a variety of extra-intestinal and post-infectious complications, including post-infectious irritable bowel syndrome, chronic fatigue, failure to thrive, and cognitive impairment. Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. In endemic parts of the World where the infection is often concurrent with bacterial enteritis causing inflammation-driven diarrheal disease, giardiasis appears to be protective against diarrhea. Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. No known toxin has yet been directly implicated in the pathophysiology of giardiasis. Diarrhea in giardiasis is mostly malabsorptive in nature, rather than hypersecretory. Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection.