Several drugs are used in the treatment of irritable bowel syndrome （IBS） but all have side effects and variable efficacy. Considering the role of the gut-brain axis, immune, neural, and endocrine pathways in the pa...Several drugs are used in the treatment of irritable bowel syndrome （IBS） but all have side effects and variable efficacy. Considering the role of the gut-brain axis, immune, neural, and endocrine pathways in the patho- genesis of IBS and possible beneficial effects of benzodiazepines （BZD） in this axis, the present systematic review focuses on the efficacy of BZD receptor modulators in human IBS. For the years 1966 to February 2011, all literature was searched for any articles on the use of BZD receptor modulators and IBS. After thorough evaluation and omission of duplicate data, 10 out of 69 articles were included. BZD receptor modulators can be helpful, especially in the diarrhea-dominant form of IBS, by affecting the inflammatory, neural, and psychologic pathways, however, controversies still exist. Recently, a new BZD receptor modulator, dextofisoparn was synthesized and studied in human subjects, but the studies are limited to phase 11 b clinical trials. None of the existing trials considered the neuroimmunomodulatory effect of BZDs in IBS, but bearing in mind the concentration- dependent effect of BZDs on cytokines and cell proliferation, future studies using pharmacodynamic and pharmacokinetic approaches are highly recommended.展开更多
Transanal excision （TE）, endoscopic transanal resection （ETAR） and transanal endoscopic microsurgery （TEN） can be used to remove adenomatous polyps. However, their use is limited by the size or location of the t...Transanal excision （TE）, endoscopic transanal resection （ETAR） and transanal endoscopic microsurgery （TEN） can be used to remove adenomatous polyps. However, their use is limited by the size or location of the tumor. TE is limited to the lower rectum, TEN offers better access to lesions in the middle and upper rectum, and ETAR is used less frequently than it deserves for resection of rectal lesions.展开更多
The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and...The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.展开更多
文摘Several drugs are used in the treatment of irritable bowel syndrome （IBS） but all have side effects and variable efficacy. Considering the role of the gut-brain axis, immune, neural, and endocrine pathways in the patho- genesis of IBS and possible beneficial effects of benzodiazepines （BZD） in this axis, the present systematic review focuses on the efficacy of BZD receptor modulators in human IBS. For the years 1966 to February 2011, all literature was searched for any articles on the use of BZD receptor modulators and IBS. After thorough evaluation and omission of duplicate data, 10 out of 69 articles were included. BZD receptor modulators can be helpful, especially in the diarrhea-dominant form of IBS, by affecting the inflammatory, neural, and psychologic pathways, however, controversies still exist. Recently, a new BZD receptor modulator, dextofisoparn was synthesized and studied in human subjects, but the studies are limited to phase 11 b clinical trials. None of the existing trials considered the neuroimmunomodulatory effect of BZDs in IBS, but bearing in mind the concentration- dependent effect of BZDs on cytokines and cell proliferation, future studies using pharmacodynamic and pharmacokinetic approaches are highly recommended.
文摘Transanal excision （TE）, endoscopic transanal resection （ETAR） and transanal endoscopic microsurgery （TEN） can be used to remove adenomatous polyps. However, their use is limited by the size or location of the tumor. TE is limited to the lower rectum, TEN offers better access to lesions in the middle and upper rectum, and ETAR is used less frequently than it deserves for resection of rectal lesions.
基金supported in part by NIH grant AI054715 to C.C.B.
文摘The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.
