Post-coital administration of levonorgestrel and post-fertilization events in the new-world monkey Cebus apella

Sir, The paper by Ortiz et al. (2004), which concludes that ‘Post-coitaladministration of levonorgestrel does not interfere with post-fertilizationevents in     

Sublingual misoprostol is as effective as intravenous oxytocin to reduce intra-operative blood loss during cesarean delivery in women living at high altitude

Objective: To assess the effect of sublingual misoprostol compared to intravenous oxytocin for blood loss during cesarean delivery in women living at high altitude.

Study design: In a randomized trial, conducted in Quito, Ecuador (2800?m above sea level), 100 women received either sublingual misoprostol (400?µg) or intravenous oxytocin (10?IU).

Results: Bleeding in the misoprostol was no different than in the oxytocin group. Shivering was reported in 66% of women in the misoprostol group.

Conclusion: Sublingual misoprostol might be a valid alternative to oxytocin reduce intra-operative blood loss during cesarean section in women living at high altitude.     

Vaccination of mice with a Yop translocon complex elicits antibodies that are protective against infection with F1- Yersinia pestis

Yersinia pestis, the bacterial agent of plague, secretes several proteins important for pathogenesis or host protection. The F1 protein forms a capsule on the bacterial cell surface and is a well-characterized protective antigen but is not essential for virulence. A type III secretion system that is essential for virulence exports Yop proteins, which function as antiphagocytic or anti-inflammatory factors. Yop effectors (e.g., YopE) are delivered across the host cell plasma membrane by a translocon, composed of YopB and YopD. Complexes of YopB, YopD, and YopE (BDE) secreted by Yersinia pseudotuberculosis were purified by affinity chromatography and used as immunogens to determine if antibodies to the translocon could provide protection against Y. pestis in mice. Mice vaccinated with BDE generated high-titer immunoglobulin G antibodies specific for BDE, as shown by enzyme-linked immunosorbent assay and immunoblotting, and were protected against lethal intravenous challenge with F1⁻ but not F1⁺ Y. pestis. Mice passively immunized with anti-BDE serum were protected from lethal challenge with F1⁻ Y. pestis. The YopB protein or a complex of YopB and YopD (BD) was purified and determined by vaccination to be immunogenic in mice. Mice actively vaccinated with BD or passively vaccinated with anti-BD serum were protected against lethal challenge with F1⁻ Y. pestis. These results indicate that anti-translocon antibodies can be used as immunotherapy to treat infections by F1⁻ Y. pestis.     

Interleukin-10 induction is an important virulence function of the Yersinia pseudotuberculosis type III effector YopM

Pathogenic Yersinia species modulate host immune responses through the activity of a plasmid-encoded type III secretion system and its associated effector proteins. One effector, YopM, is a leucine-rich-repeat-containing protein that is important for virulence in murine models of Yersinia infection. Although the mechanism by which YopM promotes virulence is unknown, we previously demonstrated that YopM was required for the induction of high levels of the immunosuppressive cytokine interleukin-10 (IL-10) in sera of C57BL/6J mice infected with Yersinia pseudotuberculosis. To determine if IL-10 production is important for the virulence function of YopM, C57BL/6J or congenic IL-10^−/− mice were infected intravenously with wild-type or yopM mutant Y. pseudotuberculosis strains. Analysis of cytokine levels in serum and bacterial colonization in the spleen and liver showed that YopM is required for IL-10 induction in C57BL/6J mice infected with either the IP32953 or the 32777 strain of Y. pseudotuberculosis, demonstrating that the phenotype is conserved in the species. In single-strain infections, the ability of the 32777ΔyopM mutant to colonize the liver was significantly increased by the delivery of exogenous IL-10 to C57BL/6J mice. In mixed infections, the competitive advantage of a yopM⁺ 32777 strain over an isogenic yopM mutant to colonize spleen and liver, as observed for C57BL/6J mice, was significantly reduced in IL-10^−/− animals. Thus, by experimentally controlling IL-10 levels in a mouse infection model, we obtained evidence that the induction of this cytokine is an important mechanism by which YopM contributes to Y. pseudotuberculosis virulence.     

Immunosensory signalling by carotid body chemoreceptors

Injections of lipopolysaccharide (LPS) have been used to produce the signs of sepsis and study their underlying mechanisms. Intravenous (IV) injections of LPS in anesthetized cats induce tachypnea, tachycardia and hypotension, but ventilatory changes are suppressed after sectioning carotid and aortic nerves. Otherwise, LPS increases the basal frequency of carotid chemosensory discharges, but reduces ventilatory and chemosensory responses to hypoxia and nicotine injections. Increases in cytokines (IL-1β, IL-6 and TNF-α) are observed in plasma and tissues after injecting LPS. In carotid bodies perfused in vitro, TNF-α reduces chemosensory discharges induced by hypoxia. The rat carotid body and its sensory ganglion constitutively express LPS canonical receptor, TLR4, as well as TNF-α and its receptors (TNF-R1 and TNF-R2). Increases of TNF-α and TNF-R2 expression occur after LPS administration. The activation of peripheral and central autonomic pathways induced by LPS or IL's is partly dependent on intact vagus nerves. Thus, the carotid and vagus nerves provide routes between the immune system and CNS structures involved in systemic inflammatory responses.     

Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation and intracellular calcium concentrations of human sperm

BACKGROUND: Previously we showed that the human sperm proteasome plays significant roles during mammalian fertilization. Here we studied the effect of fibronectin (Fn), an extracellular matrix protein present in the cumulus oophorus of the oocyte, on proteasome activity, acrosome reaction, intracellular calcium concentration ([Ca(2+)](i)) and protein tyrosine phosphorylation of human sperm. METHODS: Aliquots of motile sperm were incubated for 15 min (T0), 5 h (T5) and 18 h (T18), at 37 degrees C, 5% CO(2) and 95% air with Fn (0-100 microg/ml). The chymotrypsin- and trypsin-like activity of the proteasome was measured using the fluorogenic substrates, Suc-Leu-Leu-Val-Tyr-AMC and Boc-Gln-Ala-Arg-AMC, respectively. At T18, sperm aliquots were incubated for 15 min with Fn and/or progesterone in the presence or absence of epoxomicin (a proteasome inhibitor). The percentage of viable acrosome reacted sperm was evaluated using the Fluorescein isothiocyanate (FITC)-labeled Pisum sativum agglutinin. Tyrosine phosphorylation was evaluated by western blot and [Ca(2+)](i) using fura 2. RESULTS: Fn stimulated both enzymatic activities of the proteasome and the acrosome reaction of human sperm. Progesterone enhanced and epoxomicin drastically inhibited the effect of Fn. Fn treatment also increased the [Ca(2+)](i). Western blot analysis revealed that Fn increased tyrosine protein phosphorylation and that some proteasome subunits became tyrosine phosphorylated upon Fn treatment. CONCLUSIONS: These results suggest that Fn activates the proteasome and induces the acrosome reaction in human sperm. This effect may involve binding with specific receptors (integrins) on the sperm surface and the activation of tyrosine kinases.     

Early and late results of the acid suppression and duodenal diversion operation in patients with barrett's esophagus: analysis of 210 cases

The usual surgical treatment for patients with Barrett's esophagus (BE) is a classic Nissen fundoplication or posterior gastropexy with cardial calibration. However, some surgical reports as well as our experience suggest that the rate of failure of the Nissen fundoplication or Hill's posterior gastropexy in patients with BE is significantly higher than in those with reflux esophagitis without BE, probably due in part to the persistence of duodenal reflux into the esophagus. Our aim was to determine the late subjective and objective results of an operation consisting in "acid suppression" (vagotomy-partial gastrectomy) and "duodenal diversion" (Roux-en-Y anastomosis) as a primary surgical procedure for patients with BE. Altogether, 210 patients were subjected to this technique. It consisted in a primary operation in 142 patients and revision surgery in 68. They underwent complete clinical, radiologic, endoscopic, histologic, and manometric studies. In some cases 24-hour pH studies, Bilitec studies, gastric emptying, and gastric acid secretion evaluations were performed. There were two deaths (0.95%), and postoperative morbidity was low (5.3%). The late mean follow-up (58 months) for 146 patients who completed a follow-up longer than 24 months showed Visick I and II grades in 91.1% of the cases. In 14.9% of the cases 24-hour pH monitoring showed excessive acid reflux 1 year after surgery. No dysplasia or adenocarcinoma has appeared up to now. Functional studies showed significant alleviation of lower esophageal sphincter (LES) incompetence, with abolition of duodenal reflux into the esophagus. Gastric emptying of solids was normal, and basal and peak gastric acid output remained at a low level 8 to 10 years after surgery. In patients with BE, with severe damage of the LES and esophageal peristalsis, the "suppression diversion" operation completely abolishes the reflux of injurious components of the refluxate and improves sphincter competence. This effect is permanent and avoids the appearance of dysplasia or adenocarcinoma.     

Barrett’s Esophagus Complicated with Stricture: Correlation between Classification and the Results of the Different Therapeutic Options

Benign esophageal stricture is a serious complication of persistent gastroesophageal reflux in patients with esophagitis and Barrett's esophagus. A classification of the severity of the stricture is proposed, based on its internal diameter, its length, and the ease or difficulty in dilating it. Among 185 patients with esophageal strictures secondary to reflux esophagitis, 77 (41.6%) corresponded to type I or mild stricture, 73 (39.4%) to type II or moderate, and 35 (19.6%) to type III. Medical treatment was performed in only 15 cases, with 73% recurrence. Three types of surgical procedures were employed, always after dilatation, improvement of nutritional status, and a complete preoperative work-up: (1) conservative antireflux surgery, which had a high incidence of recurrence (41.1%); (2) acid suppression and duodenal diversion, in which 68 patients had a mortality rate of 2.9% and a recurrence rate of 4.4% (p <0.002); and (3) esophageal resection, which in 7 patients resulted in 1 death and no late recurrence. It is concluded that classification of the severity of the stricture is important to indicate the most appropriate treatment. Conservative antireflux surgery is followed by a high recurrence rate at late follow-up, whereas acid suppression and duodenal diversion seem to be an adequate procedure that is followed by a very low recurrence rate. Esophageal resection is indicated only for patients with severe or critical esophageal strictures.     

Heterotopic ossification after total hip arthroplasty: a critical analysis of the Brooker classification and proposal of a simplified rating system

We evaluated the reproducibility of the Brooker classification for heterotopic ossification (HO) and, based on the results and weaknesses observed, proposed a simplified system with addition of objective criteria. Six observers classified radiographs of 169 total hip arthroplasties, using the Brooker classification and a modified system consisting of i) absence of HO or islands measuring <1 cm in length, ii) islands >1 cm or spurs leaving at least 1 cm between femur and pelvis, and iii) spurs leaving <1 cm between opposing surfaces or bony ankylosis. Reproducibility was calculated using kappa statistics. For the Brooker classification, interobserver kappa averaged 0.43 (range, 0.74-0.18) (poor). Intraobserver kappa averaged 0.74 (fair). For the modified classification, interobserver kappa averaged 0.59 (range, 0.51-0.76) (fair). Intraobserver kappa averaged 0.78 (good). Interobserver differences were significant (P=.0085). Interobserver consistency to detect severe HO (Brooker 3 and 4, or grade C) improved from 52% to 76% with the modified system. The new classification showed adequate interobserver reproducibility, less variability, and improved consistency for classification of significant HO.