1 To evaluate the role of prostaglandin I 2 (PGI 2 ) in allergic in¯ammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI 2 (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukocyte accumulation and cytokine (interleukin (IL)-4 and IL-5) production in the airway of sensitized mice. These airway in¯ammatory responses were signi®cantly greater in IP receptor de®cient mice than in wild-type mice.3 The vascular leakage caused by passive cutaneous anaphylaxis, substance P and 5-hydroxytryptamine was markedly increased in the skin of IP receptor de®cient mice, compared with comparably treated wild-type mice. 4 The inhalation of antigen in sensitized mice resulted in increased serum antigen speci®c IgE, total IgE and IgG levels. The magnitude of the elevations of each immunoglobulin level in IP receptor de®cient mice is notably higher than that in wild-type mice. To elucidate the mechanism of an enhancement of immunoglobulin production, the activity of T cells in sensitized and non-sensitized mice was studied by means of the production of cytokines. The antigen-induced IL-4 production by spleen cells from sensitized IP receptor de®cient mice was almost three times greater than that in wild-type mice. On the contrary, the anti-CD3 antibody-induced interferon-g production by CD4+ T cells from non-sensitized IP receptor de®cient mice was signi®cantly lower than that in wild-type mice. 5 The present data indicate that IP receptor de®ciency reinforced an allergic airway and skin in¯ammation by augmentation of vascular permeability increase and the T helper 2 cell function. These ®ndings suggest a regulatory role of PGI 2 in allergic in¯ammation.
These results indicate that some of the CASA estimates provide reliable estimation of the fertilizing ability of human sperm. There were significant differences of the two sperm movement characteristics, including VCL and Rapid (before and after swim-up), indicating that the total distance traveled by rapid sperm movement might be important in human sperm fertilizing abilities.
This study was performed to predict pregnancy by intrauterine insemination (IUI) using computer-aided sperm analysis (CASA) estimates and strict criteria in patients with male factor infertility. IUI was performed in 682 cycles on 160 male factor infertile patients. Semen examinations were carried out by CASA and strict criteria before and after sperm preparation using continuous-step density gradient centrifugation. Receiver operating characteristics (ROC) curves were constructed for assessment of the effectiveness of each individual parameter in predicting pregnancy by IUI. A clinically acceptable threshold was calculated when sensitivity plus specificity were maximum. The average cycle of IUI performed was 4.3 +/- 2.4. Pregnancy rate per cycle and per patient were 7.2% (49/682) and 28.1% (45/160), respectively. Using ROC curve, it was shown that normal sperm morphology assessed by the strict criteria before sperm separation and five parameters after sperm separation including rapid, progressive motility, average path velocity (VAP), curvilinear velocity (VCL), and straight line velocity (VSL) were able to predict pregnancy by IUI. Correlation between sperm parameters and pregnancy outcome was examined by the logistic regression model. In a multivariate analysis normal morphology before sperm separation >or=15.5% [odds ratio (OR) = 2.2, p = 0.02], rapid after sperm separation >or=25.5% [OR = 3.9, p = 0.029], and VCL after sperm separation >or=102.65 microm/sec [OR = 3.2, p = 0.002] were the parameters of predictive value for pregnancy outcome. Adjustment of the model for female age, female infertility factors, and the methods of ovulation induction did not change this finding, and the final model still had the same covariates. Pregnancy rates per cycle according to the number (0, 1, 2 and 3) of variables satisfied with the three parameters were 0% (0/110), 1.6% (3/183), 9.7% (21/217) and 15.1% (23/151), respectively. Three semen parameters including normal morphology before sperm separation, rapid and VCL after sperm separation were identified as predictors of pregnancy by IUI. These variables would be helpful when counselling patients before they make the decision to proceed with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-ET.
Esophageal epiphrenic diverticula are uncommon. Traditionally, thoracotomy has been the preferred surgical approach. Recently, minimally invasive approaches have been reported in a few series. However, the best surgical approach remains uncertain. In this study, we review the results of 25 articles discussing laparoscopic or thoracoscopic surgery. From January 1995 to December 2008, there were a total of 133 patients reported in English-language journals in PubMed. Nineteen patients (14 %) underwent thoracoscopic surgery, 112 (84 %) laparoscopic surgery and two patients (2 %) were treated using a combination approach. The diverticulectomy was performed using an endostapler device in all patients. A myotomy was added in 103 patients (83 %). A fundoplication was added in 106 patients (85 %). There were two deaths during surgery (2 %). The post-operative morbidity rate was 21 %. The most severe complication was suture-line leakage, which occurred in 20 patients (15 %). Recently, we successfully treated a patient with an epiphrenic esophageal diverticulum by performing a minimally invasive laparoscopic transhiatal resection and Heller myotomy with Dor fundoplication after observing its enlargement on radiological and endoscopic examinations over 2 years. We believe laparoscopic transhiatal resection and Heller myotomy with Dor fundoplication may therefore become the standard treatment modality for minimally invasive surgery for esophageal epiphrenic diverticulum.
These results suggest that C. trachomatis infection is highly associated with peritubal adhesion which is difficult to diagnose by HSG. Therefore, in C. trachomatis antibody-positive patients, exclusion of tubal pathology by THL or standard laparoscopy should be carried out to consider appropriate treatments. Although THL is not a substitute for laparoscopy, it can be proposed as a first line procedure in the early stages of the infertility investigation.
Bovine mycoplasmosis caused by Mycoplasma bovis results in pneumonia and mastitis in cattle. We previously demonstrated that the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) pathway is involved in immune dysfunction during M. bovis infection and that prostaglandin E 2 (PGE 2 ) suppressed immune responses and upregulated PD-L1 expression in Johne's disease, a bacterial infection in cattle. In this study, we investigated the role of PGE 2 in immune dysfunction and the relationship between PGE 2 and the PD-1/PD-L1 pathway in M. bovis infection. In vitro stimulation with M. bovis upregulated the expressions of PGE 2 and PD-L1 presumably via Toll-like receptor 2 in bovine peripheral blood mononuclear cells (PBMCs). PGE 2 levels of peripheral blood in infected cattle were significantly increased compared with those in uninfected cattle. Remarkably, plasma PGE 2 levels were positively correlated with the proportions of PD-L1 + monocytes in M. bovis-infected cattle. Additionally, plasma PGE 2 production in infected cattle was negatively correlated with M. bovis-specific interferon (IFN)-γ production from PBMCs. These results suggest that PGE 2 could be one of the inducers of PD-L1 expression and could be involved in immunosuppression during M. bovis infection. In vitro blockade Goto et al.PGE 2 -Induced Immunodysfunction During Bovine Mycoplasmosis assays using anti-bovine PD-L1 antibody and a cyclooxygenase 2 inhibitor significantly upregulated the M. bovis-specific IFN-γ response. Our study findings might contribute to the development of novel therapeutic strategies for bovine mycoplasmosis that target PGE 2 and the PD-1/PD-L1 pathway.
SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality.
Epidemiological studies have implicated lung inflammation as a risk factor for acute cardiovascular events, but the underlying mechanisms linking lung injury with cardiovascular events are largely unknown.Our objective was to develop a novel murine model of acute atheromatous plaque rupture related to lung inflammation and to investigate the role of neutrophils in this process.Lipopolysaccharide (LPS; 3 mg·kg(-1)) or saline (control) was instilled directly into the lungs of male apolipoprotein E-null C57BL/6J mice following 8 weeks of a Western-type diet. 24 h later, atheromas in the right brachiocephalic trunk were assessed for stability ex vivo using high-resolution optical projection tomography and histology. 68% of LPS-exposed mice developed vulnerable plaques, characterised by intraplaque haemorrhage and thrombus, versus 12% of saline-exposed mice (p=0.0004). Plaque instability was detectable as early as 8 h post-intratracheal LPS instillation, but not with intraperitoneal instillation. Depletion of circulating neutrophils attenuated plaque rupture.We have established a novel plaque rupture model related to lung injury induced by intratracheal exposure to LPS. In this model, neutrophils play an important role in both lung inflammation and plaque rupture. This model could be useful for screening therapeutic targets to prevent acute vascular events related to lung inflammation.
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