Search

Background : Interleukin-8 (IL-8) is a pro-inflammatory cytokine highly expressed in inflammatory bowel diseases, but whose effects on intestinal motility are unknown. Aim : To characterize the role of IL-8 in the contraction of rat intestinal segments. Methods : Contractile response to acetylcholine (ACh 10-6 M) in terminal ileal segments (including mucosa) from Wistar rats was measured before and after incubation (15, 30, 60 or 90 min) with IL-8 (1 ng/mL), and after 60 min of incubation with different doses of IL-8 (0, 0.1, 0.5, 1, 10 and 100 ng/mL). The effects of blocking neural transmission with tetrodotoxin (TTX) and inhibiting protein synthesis (cycloheximide) were tested. The contractile response of longitudinal muscle–myenteric plexus preparations (i.e. without mucosa) was measured after 60 min of incubation with 0.1 and 1 ng/mL of IL-8. Results : IL-8 increased ileal contraction induced by ACh 10-6 M. This augmentation was significant after 60 min of incubation (58%, P=0.01) and persisted after 90 min (18%, P=0.04). A 60-min incubation period showed a dose-related effect, beginning at 0.5 ng/mL (30%, P=0.003) and reaching a peak at 1 ng/mL (58%, P=0.01). The same effect was also observed on colonic segments. TTX did not affect the IL-8 increase of ACh-induced contractions, which was completely abolished by cycloheximide. IL-8 had no significant effect on longitudinal muscle–myenteric plexus preparations. Conclusion : In vitro, IL-8 increases contractile response of the ileum to ACh in a dose-dependent manner. This effect is not neurally mediated, but seems to involve protein synthesis by intestinal mucosa. [ABSTRACT FROM AUTHOR]

Focuses on study which characterized prostaglandin dehydrogenase (PGDH) mRNA expression in critical intrauterine tissues of pregnant baboons in late gestation and at spontaneous labor. Information on PGDH; Methodology; Effect of gestation and labor on cervical PGDH mRNA expression; Data on PGDH mRNA abundance in intrauterine tissues from the uterus.

Background: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis.Methods: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls.Results: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1).Conclusions: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause. [ABSTRACT FROM AUTHOR]

To better understand the molecular mechanisms involved in pathological development of placenta in preeclampsia, we used LC-MS/MS to construct a large-scale comparative proteome profile of human placentas from normal and preeclamptic pregnancies. A total of 2636 proteins were detected in human placentas, and 171 different proteins were definitively identified between control and preeclamptic placentas. Further bioinformatics analysis indicated that these differentially expressed proteins correlate with several specific cellular processes which occur during pathological changes of preeclamptic placenta. 6 proteins were randomly selected to verify their expression patterns with Western blotting. Of which, 3 proteins’ cellular localizations were validated with immunohistochemistry. Elucidation of how protein-expression changes coordinate the pathological development would provide researchers with a better understanding of the critical biological processes of preeclampsia and potential targets for therapeutic agents to regulate placenta function, and eventually benefit the treatment of preeclampsia. [ABSTRACT FROM AUTHOR]

Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) remains a significant cause of postoperative morbidity and mortality. There are few reports on acute symptomatic pulmonary embolism (PE) following urogynaecological surgery. [ABSTRACT FROM AUTHOR]

Controversy still exists regarding the involvement of relaxin (RLX) in cervical reorganization throughout parturition in the human, despite its well-known role in facilitating extensive extracellular matrix (ECM) remodeling in diverse organs. Therefore, the aim of the present study was to examine the influence of RLX and estrogen (E2) on the cervical tissue of the common marmoset monkey. Two experimental designs were used: 1) in vivo analysis of the intracervical diameter under locally applied RLX and 2) ovariectomized (ov) marmosets were treated systemically with either recombinant human (rh) RLX, E2 or rhRLX+E2 to examine their action on the cervix. In vivo-locally applied rhRLX induced a distinct and significant widening of the cervix (before: 4.8±1.1 mm versus after: 5.7±0.9 mm in diameter; P<0.030, MV±S.E.M.). This widening effect was most pronounced in animals without previous pregnancies. In vitro investigation of cervical tissue showed significantly increased wet weights after all three hormone treatments (E2: 0.27±0.07 g, RLX: 0.25±0.04 g, E2+RLX: 0.30±0.11 g; all P<0.05; MV±S.E.M.) versus controls (0.10±0.04 g). Furthermore, morphological changes such as loosening of the connective tissue structure and decline in collagen content, an increase in the number of eosinophils, increased the expression of matrix metalloproteinases (MMP1) and MMP2, as well as gene and protein expression of the RLX receptor RXFP1 could be detected in the cervical tissue after all hormone treatments, compared with controls. In summary, RLX has a potent widening effect on the cervix of the common marmoset monkey. Although E2 is not required for this RLX effect, a combined application of E2 and RLX induced the most prominent cervical ripening. [ABSTRACT FROM AUTHOR]

Around 20% of all deliveries are preceded by labour induction, a proportion that has not varied dramatically over recent years. Fetal death was the only indication for labour induction centuries ago, while this is now a very rare indication, with prolonged pregnancy and maternal hypertensive disorders being the major indications for the last 50-60 years. Techniques for inducing labour have also changed from dietary delicacies and verbal threats giving way to physical stimulation mainly achieved by cervical stretching and amniotomy and more recently to sophisticated pharmacological manipulation using oxytocin and prostaglandins, based on our expanding knowledge of the physiological processes involved in spontaneous parturition. Relaxin, antiprogestins, nitric oxide as well as complementary medicines have also been explored in recent years. Successful induction is, however, still not guaranteed and there has been increasing emphasis during the past decade on exploring strategies for identifying the probability of success. Measurement of fetal fibronectin in cervical mucus, maternal serum nitrite/nitrate concentrations, ultrasound delineation of cervical form and electrical impedance measurements across the cervix are all being investigated. Safety, success, and patient satisfaction continue to be the major objectives with economic evaluations now becoming a significant factor in the search for the ideal induction method. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling [...]