Smoking in the 21st century

Jean Nicot de Villemain (1530 - 1600) was a French diplomat who became famous for introducing tobacco to France. Little could he imagine the immense upheaval he would bring to future generations. Up until the early 1900's, smoking cigarettes was made to look glamorous and even had health benefits attributed to it. However, the link between smoking and respiratory diseases had been established back in the early 1900s in studies by European and American doctors but this remained a taboo up until the 1950s. As time went by, the evidence linking smoking as the cause of disease continued to accumulate and, what was a controversy in the 1960s and 1970s, turned into outright condemnation in the 1980s. Although the medical profession had more knowledge about the harm caused by smoking, the general public was less informed because cigarette manufacturers were doing their best to cast doubt on how true these "allegations" were. Mass legal action instituted in the 1990s led to the Master Settlement Agreement in 1998 with US courts condemning major US cigarette companies to pay huge sums of money to the US government over a period of 25 years to compensate for some of the damage and expenses incurred in caring for the millions of people suffering ill health directly caused by smoking over the years. [excerpt]peer-reviewe

Epithelial Cell-Specific MyD88 Signaling Mediates Ischemia/Reperfusion-induced Intestinal Injury Independent of Microbial Status

The Toll-like receptor/MyD88 signaling pathway has been shown to mediate protective functions during intestinal exposure to various noxious events. The goal of this study was to define the role of bacteria and MyD88 signaling in intestinal response to damage using an ischemia–reperfusion (I/R)-induced injury model. We showed that conventionalized mice displayed a better outcome to I/R-induced injury than germ-free mice (3.8 ± 1.98 vs. 11.8 ± 1.83, P < 0.05). However, mice with intestinal epithelial cell (IEC)-specific deletion of Myd88 (Myd88(IEC−/−)) were protected from I/R-induced injury compared with Myd88(f/f) control mice. Myd88(IEC−/−) mice also displayed a significantly reduced bacterial translocation (~85%) into lymph nodes compared with Myd88(f/f) mice. Expression of ccl2 and cxcl1 mRNA was significantly reduced (85% and 62%, respectively) in intestinal tissue of Myd88(IEC−/−) mice compared with Myd88(f/f) mice, which associated with a reduced number of myeloperoxidase-positive cells in intestinal tissues of I/R-exposed Myd88(IEC−/−) mice. Immunohistochemistry analysis showed a reduced IgA deposition and complement staining in ischemic tissue of Myd88(IEC−/−) mice compared with Myd88(f/f) mice. These findings suggest that I/R-induced intestinal injury involves IEC-derived MyD88 signaling leading to increased IgA deposition/degradation, and complement activation in conjunction with an influx of neutrophils mediated by chemokine production

Meta-analysis: The treatment of irritable bowel syndrome

To evaluate therapies available for the treatment of irritable bowel syndrome, and provide consensus recommendations for their use, a total of 51 double-blind clinical trials using bulking agents, prokinetics, antispasmodics, alosetron, tegaserod and antidepressants were selected. The quality of studies was assessed using 5-point scale. Meta-analyses were performed on all studies, and on 'high-quality studies'. The efficacy of fibre in the global irritable bowel syndrome symptoms relief (OR: 1.9; 95% CI:1.5-2.4) was lost after exclusion of low-quality trials (OR: 1.4; 95% CI: 1.0-2.0, P = 0.06). When excluding the low-quality trials, an improvement of global irritable bowel syndrome symptoms with all antispasmodics (OR: 2.1; 95% CI:1.8-2.9) was maintained only for octylonium bromide, but on the basis of only two studies. Antidepressants were effective (OR: 2.6, 95% CI: 1.9-3.5), even after exclusion of low-quality studies (OR: 1.9, 95% CI: 1.3-2.7). Alosetron (OR: 2.2; 95% CI: 1.9-2.6) and tegaserod (OR: 1.4; 95% CI: 1.2-1.5) showed a significant effect in women. We recommend the use of tegaserod for women with irritable bowel syndrome with constipation and alosetron for women with severe irritable bowel syndrome with diarrhoea. Antidepressants can be beneficial for irritable bowel syndrome with diarrhoea patients with severe symptoms. Loperamide can be recommended in painless diarrhoea. Evidence is weak to recommend the use of bulking agents in the treatment of irritable bowel syndrome with constipation