Bordetella bronchiseptica flagellin is a proinflammatory determinant for airway epithelial cells

Motility is an important virulence phenotype for many bacteria, and flagellin, the monomeric component of flagella, is a potent proinflammatory factor. Of the three Bordetella species, Bordetella pertussis and Bordetella parapertussis are nonmotile human pathogens, while Bordetella bronchiseptica expresses flagellin and causes disease in animals and immunocompromised human hosts. The BvgAS two-component signal transduction system regulates phenotypic-phase transition (Bvg+, Bvg-, and Bvg(i)) in bordetellae. The Bvg- phase of B. bronchiseptica is characterized by the expression of flagellin and the repression of adhesins and toxins necessary for the colonization of the respiratory tract. B. bronchiseptica naturally infects a variety of animal hosts and constitutes an excellent model to study Bordetella pathogenesis. Using in vitro coculture models of bacteria and human lung epithelial cells, we studied the effects of B. bronchiseptica flagellin on host defense responses. Our results show that B. bronchiseptica flagellin is a potent proinflammatory factor that induces chemokine, cytokine, and host defense gene expression. Furthermore, we investigated receptor specificity in the response to B. bronchiseptica flagellin. Our results show that B. bronchiseptica flagellin is able to signal effectively through both human and mouse Toll-like receptor 5.     

Smoking Cessation in the Chicago Coronary Prevention Evaluation Program

Quit-rates for cigarette smokers in a lifestyle intervention program aimed at reducing coronary risk were 24 percent for all participants and 34 percent for non-dropouts. Recidivism remained very low during participation in the program. Half of the smokers who quit did so after being in the program more than two years. These data suggest that while engaging in an effort to make other changes in lifestyle, many smokers can be helped to quit. Sustained antismoking efforts in the clinical practice of medicine can be expected to share these same positive aspects. While mass public health programs to eliminate smoking and prevent young people from taking up the habit are being developed, health practitioners can make a significant contribution by including vigorous efforts at smoking cessation as part of routine practice.     

Seasonal dynamics of the fecal excretion of Elaphostrongylus cervi (Nematoda, Metastrongyloidea) first-stage larvae in Iberian red deer (Cervus elaphus hispanicus) from southern Spain

Elaphostrongylus cervi (Nematoda, Metastrongyloidea) is an extrapulmonary lungworm of red deer (Cervus elaphus) whose first-stage larvae (L1) require terrestrial gastropods as intermediate hosts. The seasonal pattern of fecal excretion of E. cervi L1 in Iberian red deer (Cervus elaphus hispanicus) was monitored during three annual periods (June 2000–May 2003) on a hunting estate from south-central Spain. The lowest rates of mean intensity of fecal L1 were found in summer, whereas no seasonal variation was found for prevalence. Monthly intensity of excretion was positively associated with early rainfall (the next month) rather than with rainfall of the same month. This seasonal rhythm of E. cervi L1 discharge may be the result of parasite adaptation to the seasonal Mediterranean climate and habitat constraints to improve the chance of parasite transmission. We have standardized the sampling period to compare E. cervi L1 infection rates of Iberian red deer populations in Mediterranean Spain, a natural limit of both the parasite and deer historical ranges, for potential use in the assessment of management strategies.     

Early-rectal Cancer Treatment: A Decision-tree Making Based on Systematic Review and Meta-analysis

Local excision (LE) has arisen as an alternative to total mesorectal excision for the treatment of early rectal cancer. Despite a decreased morbidity, there are still concerns about LE outcomes.This systematic-review and meta-analysis design is based on the “PICO” process, aiming to answer to three questions related to LE as primary treatment for early-rectal cancer, the optimal method for LE, and the potential role for completion treatment in high-risk histology tumors and outcomes of salvage surgery.The results revealed that reported overall survival (OS) and disease-specific survival (DSS) were 71%–91.7% and 80%–94% for LE, in contrast to 92.3%–94.3% and 94.4%–97% for radical surgery. Additional analysis of National Database studies revealed lower OS with LE (HR: 1.26; 95%CI, 1.09–1.45) and DSS (HR: 1.19; 95%CI, 1.01–1.41) after LE. Furthermore, patients receiving LE were significantly more prone develop local recurrence (RR: 3.44, 95%CI, 2.50–4.74). Analysis of available transanal surgical platforms was performed, finding no significant differences among them but reduced local recurrence compared to traditional transanal LE (OR:0.24;95%CI, 0.15–0.4). Finally, we found poor survival outcomes for patients undergoing salvage surgery, favoring completion treatment (chemoradiotherapy or surgery) when high-risk histology is present.In conclusion, LE could be considered adequate provided a full-thickness specimen can be achieved that the patient is informed about risk for potential requirement of completion treatment. Early-rectal cancer cases should be discussed in a multidisciplinary team, and patient's preferences must be considered in the decision-making process.     

¿Cómo medir el estatus migratorio de la población infantil y juvenil? Estudios sobre salud y desigualdades en salud en Europa

ObjectiveTo analyse how the migration status of the child and young population is measured in the scientific literature on health and social inequalities in health in Europe.MethodA systematic search of the literature published in Spanish, English and French between 2007 and 2017 in PubMed and Social Sciences Citation Index was carried out. The included studies analysed health and social inequalities in health of a population under 18 years old according to its migration origin in Europe. The variables used to measure the migration status were described.Results50 articles were included. Twenty studies analysed perinatal health, eleven mental health, nine dental health, and ten studies other variables. The main variables to define migration status were the country of birth (32 studies), either of the child, the mother, or one of the parents, and sometimes in a complementary way. Less frequent was the use of nationality (15 studies), of the child, or of the parents, especially the mother. Migration status is referred to in very different ways, not always comparable and sometimes the variable used is not clearly explained.ConclusionsThere is a great diversity of ways to measure migration status in the child and young population. A better definition and consensus is needed to improve the temporal and geographical comparability of knowledge in this area, which will help to design public policies aimed at reducing social inequalities in health from childhood.     

Effects of L-NG-nitro-arginine on noradrenaline induced contraction in the rat anococcygeus muscle

1. The influence of L-N^G-nitro-arginine (L-NOARG, 30 μM) on contractile responses to exogenous noradrenaline was studied in the rat anococcygeus muscle.
2. Noradrenaline (0.1–100 μM) contracted the muscle in a concentration-dependent manner. L-NOARG (30 μM) had no effect on noradrenaline responses.
3. Phenoxybenzamine (Pbz 0.1 μM) depressed by 46% (P<0.001) the maximum response and shifted to the right (P<0.001) the E/[A] curve to noradrenaline (pEC₅₀ control: 6.92±0.09; pEC₅₀ Pbz: 5.30±0.10; n=20).
4. The nested hyperbolic null method of analysing noradrenaline responses after phenoxybenzamine showed that only 0.61% of the receptors need to be occupied to elicit 50% of the maximum response, indicating a very high functional receptor reserve.
5. Contractile responses to noradrenaline after partial α₁-adrenoceptor alkylation with phenoxybenzamine (0.1 μM) were clearly enhanced by L-NOARG.
6. The potentiating effect of L-NOARG on noradrenaline responses after phenoxybenzamine was reversed by (100 μM) L-arginine but not by (100 μM) D-arginine.
7. These results indicate that spontaneous release of NO by nitrergic nerves can influence the α₁-adrenoceptor-mediated response to exogenous noradrenaline.

     

Glucocorticoids and androgens up-regulate the Zn-α2-glycoprotein messenger RNA in human breast cancer cells

Summary We have studied the hormonal regulation of the gene encoding Zn-₂-glycoprotein (Zn-₂-gp), a human protein with a high degree of amino acid sequence similarity to class I histocompatibility antigens that is produced by a specific subset of breast carcinomas. Northern blot analysis revealed that dexamethasone and 5-dihydrotestosterone strongly induced the accumulation of Zn-₂-gp mRNA in T-47D human breast cancer cells. Furthermore, the effect of these two hormones was shown to be additive, since the combination of both hormones produced a stimulation of Zn-₂-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5-dihydrotestosterone, 17-estradiol, or progesterone failed to induce the expression of Zn-₂-gp. The stimulatory effect of glucocorticoids and androgens on Zn-₂-gp expression was produced in a time and dose dependent manner, without significantly affecting the cell proliferation rate. A time-course study demonstrated that the induction of Zn-₂-gp mRNA by androgens and glucocorticoids reached a level of 4 or 3.2-fold over the untreated control after seven days of incubation in the presence of a 10^–7 M concentration of 5-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10^–11 M of 5-dihydrotestosterone or dexamethasone produced an accumulation of Zn-₂-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-₂-gp may be useful as a biochemical marker of breast carcinomas with a specific pattern of hormone responsiveness in whose development glucocorticoids and/or androgens may play a significant role.     

Genetic markers in primary open-angle glaucoma

Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP^*C allele (² = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes.     

Effect of an opiate antagonist (naloxone) on the gastric acid secretory response to sham feeding,pentagastrin, and histamine in man

We studied the effect of the opiate antagonist naloxone on the human gastric acid secretory response to three secretory stimulants: sham feeding, pentagastrin, and histamine. Intravenous naloxone (40 g/kg/hr) significantly inhibited the acid secretory response to sham feeding without affecting the serum gastrin response to sham feeding. Naloxone also significantly reduced pentagastrin- and histamine-stimulated acid secretion. These studies indicate that naloxone reduces acid secretion in response to all stimulants of acid secretion yet tested in humans.This study was supported by grants AM-16816 and AM-17328, from the National Institute of Arthritis, Metabolism and Digestive Diseases.Presented in part at the Plenary Session of the American Gastroenterological Association, Salt Lake City, Utah, May 19, 1980.