Prostaglandin- and theophylline-induced Cl secretion in rat distal colon is inhibited by microtubule inhibitors

The aim of the present study was to examine the possible role of microtubules in chloride secretion by distal rat colon stimulated by prostaglandin (PGE 2 ) and theophylline. Distal colonic tissue from male rats was mounted in Ussing chambers, and short-circuit current (I sc ) was measured to assess chloride secretion. Three microtubule inhibitors, colchicine, nocodazole, and taxol, all inhibited the stimulated I sc and reduced the 60-min integrated secretory response to PGE 2 and theophylline (▪I sc dt) by 39–52%, whereas the inactive colchicine analog lumicolchicine did not. Atropine and tetrodotoxin had no effect on stimulated chloride secretion. To confirm the source of I sc , unidirectional 22 Na + and 36 Cl − fluxes were measured in tissues exposed to lumicolchicine (control) or colchicine. Control tissues absorbed both chloride [5.0 (1.1–8.6) (median and 95% confidence interval) μeq/cm 2 /hr] and sodium [2.8 (0.9–7.2) μeq/cm 2 /hr], and this net absorption was reduced by 96% and 79%, respectively, by treatment with PGE 2 and theophylline due to an increase in serosal-to-mucosal chloride and sodium movement. Colchicine-treated tissues exhibited similar net basal chloride and sodium absorption that was reduced by 71% and 75%, respectively, by treatment with PGE 2 and theophylline. Thus the PGE 2 - and theophylline-induced increase in chloride secretion was significantly reduced by colchicine ( P <0.05 by Wilcoxon rank-sum test), whereas colchicine had no effect on PGE 2 - and theophylline-induced changes in sodium fluxes. Furthermore, the colchinine-related changes in stimulated chloride secretion were numerically similar to colchicine-related changes in stimulated I sc . These findings indicate that microtubules are required for normal PGE 2 - and theophylline-induced chloride secretion in distal rat colon and suggest that induced chloride secretion may involve vesicular insertion of ion transporters into the plasma membrane or other microtubule-dependent regulatory processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44414/1/10620_2005_Article_BF01299864.pd

Discourse studies of scientific popularisation: questioning the boundaries.

This article critiques the `dominant view' of the popularization of science that takes it as a one-way process of simplification, one in which scientific articles are the originals of knowledge that is then debased by translation for a public that is ignorant of such matters, a blank slate. Recent work is surveyed in several disciplines that questions the boundaries of scientific discourse and genres of popularization: who the actors are, how the discourses interact, what modes are involved, and what is communicated. Implications are drawn from these studies for discourse analysis

Quantification of naive and memory T-cell turnover during HIV-1 infection

Background: In HIV infection, the homeostasis of CD4+ and CD8+ T cells is dramatically disturbed, and several studies have pointed out that T-cell turnover rates are increased. To understand how the CD4+ and CD8+ T-cell pools are affected, it is important to have quantitative insights into the lifespans of the cells constituting the different T-lymphocyte populations. Methods: We used long-term in-vivo 2H2O labeling and mathematical modeling to estimate the average lifespans of naive and memory CD4+ and CD8+ T cells in untreated (n = 4) and combination antiretroviral therapy-treated (n = 3) HIV-1-infected individuals. Results: During untreated chronic HIV-1 infection, naive CD4+ and CD8+ T cells lived on average 618 and 271 days, whereas memory CD4+ and CD8+ T cells had average lifespans of 53 and 43 days, respectively. These lifespans were at least three-fold shorter than those in healthy controls (n = 5). In patients on effective combination antiretroviral therapy with total CD4+ T-cell counts in the normal range, we found that naive CD4+ and CD8+ T-cell lifespans had not completely normalized and were still two-fold shortened. Conclusion: The average lifespan of both naive and memory CD4+ and CD8+ T cells decreased during untreated chronic HIV-1 infection. Although the turnover of the memory T-cell populations nearly normalized during effective treatment, the turnover of naive CD4+ and CD8+ T cells did not seem to normalize completely