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111.
CONTEXT: Human decidual stromal cells (DSC) are myofibroblast-like cells that express alpha-smooth muscle (alpha-SM) actin, a protein associated with cell contractility. Several lines of experimental evidence in humans and mice show that antiinflammatory cytokines favor normal pregnancy, whereas Th1 and inflammatory cytokines play a role in abortion. We previously demonstrated that IL-2, a Th1 cytokine, increased the contractility of human DSC. OBJECTIVE: We studied the effect of the antiinflammatory cytokines IL-10 and IL-4 on the contractility of DSC from first-trimester pregnancy. SETTING AND PATIENTS: We studied 10 healthy women who underwent elective vaginal termination of first-trimester pregnancy at Clínica El Sur, Málaga, and Clínica Ginegranada, Granada. MAIN OUTCOME MEASURE(S): After isolation of DSC, cell contractility was measured with the collagen gel contraction assay. alpha-SM actin was detected with Western blotting and immunofluorescence. RESULTS: We found that IL-10, but not IL-4, increased the volume of the collagen gel matrixes in which the cytokine-treated DSC were cultured, showing that IL-10 decreased DSC contractility. By Western blotting we demonstrated that this effect was not related to an alteration in the synthesis of alpha-SM actin. Nevertheless, we observed by immunofluorescence microscopy that DSC treated with IL-10 exhibited stress fibers with a lower content of alpha-SM actin than untreated control DSC. CONCLUSIONS: IL-10 relaxes DSC by reducing the incorporation of alpha-SM actin into their stress fibers. This relaxing activity may be of relevance for the maintenance of pregnancy.  相似文献   
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Primary cystic pancreatic neoplasms are rare tumors, with an approximate prevalence of 10% of cystic pancreatic lesions. Most of these lesions correspond to mucinous cystic neoplasm, serous cystoadenoma and intraductal papillary mucinous tumor (IPMT). IPMT is characterized by diffuse dilatation of the main pancreatic duct and/or side branches with inner defects related to mucin or tumor, or mucin extrusion from a patent ampulla. IPMT has a low potential for malignancy, with a low growth rate, a low rate of metastatic spread and postsurgical recurrence. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this tumor.  相似文献   
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INTRODUCTION AND OBJECTIVES: Some authors have described seasonal variations in the incidence of acute myocardial infarction. The aim of this study was to determine the existence of seasonal rhythms in admissions for acute myocardial infarction to coronary care units, and in mortality, and to analyze the influence of age on environmental factors. PATIENTS AND METHOD: The study included a total of 8400 consecutive patients with acute myocardial infarction admitted to 12 coronary care units in the PRIMVAC registry from January 1995 to December 1999. Seasonal rhythms were analyzed with the time series method and the Cosinor regression equation. The influence of age was analyzed with the chi 2 test. RESULTS: The total number of admissions increased in winter and decreased in summer. The highest peak (acrophase) occurred in winter, with 2183 cases (r2=0.91), specifically in February, with 742 cases (r2=0.66). The age of the patients conditioned seasonal variations (P=.006), and the influence was statistically significant for patients over 65 years of age. Changes in mortality with time did not reach statistical significance. CONCLUSIONS: A seasonal rhythm in admissions for acute myocardial infarction was found, with an increase in winter and a decrease in summer. Age conditioned the effect of environmental factors on acute myocardial infarction, and patients aged 65 years or older were more sensitive to mechanisms that led to increases in admissions in winter.  相似文献   
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Lenalidomide combined with dexamethasone has significant clinical activity in the treatment of multiple myeloma (MM). In previous clinical trials lenalidomide-induced neutropenia was a frequent side-effect, often leading to treatment delays and dose reductions. We describe three MM patients treated with lenalidomide plus dexamethasone, which developed grade 3/4 neutropenia during the initial cycles, but without serious infection. Administration of granulocyte-colony stimulating factor (G-CSF) for 3 d prevented further neutropenia, treatment delays, dose reductions, or infectious complications during the following cycles. Consequently, G-CSF could be effective in preventing further neutropenia-related complications without compromising treatment efficacy in MM patients with lenalidomide-induced neutropenia.  相似文献   
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Inflammation Research - The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion...  相似文献   
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Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m2) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Methods

Assessment of the occurrence of weight change ≥3% at week 12 was prespecified in the statistical analysis plan.

Findings

In 120 patients with weight data available, weight gain ≥3% was observed in 2 of 39 patients (5.1%) taking placebo TID, 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss ≥3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.

Implications

Up to 32.5% of patients treated with telotristat ethyl experienced significant, dose-dependent weight gain, associated with reduced diarrhea severity and improved biochemical and metabolic parameters. Improved nutritional status could be an additional aspect of telotristat ethyl efficacy among patients with functioning metastatic neuroendocrine tumors. ClinicalTrials.gov identifier: NCT01677910.  相似文献   
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