Pyrvinium pamoate inhibits proliferation and invasion of human endometriotic stromal cells.

Endometriosis is characterized by the presence of functional endometrial tissue in other pelvic organs. This gynecologic problem occurs in 35-50% of women with pain and infertility. Endometriotic cells share some characteristics such as proliferation, migration, and invasion with tumor cells. Pyrvinium pamoate, an anthelmintic drug approved by the Food and Drug Administration, could inhibit the Wnt/ß-catenin signaling pathway and its anticancer effects were examined by several researchers. In this study, 12 ectopic and eutopic endometrial biopsies from females with ovarian endometrioma and 12 endometrial biopsies from nonendometriotic females were obtained. Ectopic (EESCs), eutopic (EuESCs), and control (CESCs) endometrial stromal cells were isolated. Then, the effect of pyrvinium pamoate on the proliferation and invasiveness of in vitro cultured cells was evaluated. The proliferation of CESCs, EuESCs, and EESCs was significantly decreased after treatment with pyrvinium pamoate. In addition, treatment with pyrvinium pamoate significantly inhibited the invasiveness of CESCs, EuESCs, and EESCs compared to nontreated groups. The results of the present research showed that pyrvinium pamoate inhibits the proliferation and invasion of human endometriotic stromal cells in vitro, further investigations on the therapeutic potential of this compound in endometriosis are required.

Could T cells be involved in lung deterioration and hyperglycemia in cystic fibrosis?

Cystic fibrosis-related diabetes (CFRD) is the most frequent complication of cystic fibrosis (CF) and associated with increased mortality. Why patients have an accelerated loss of lung function before the diagnosis of CFRD remains poorly understood. We reported that patients with or without CFRD had increased glucose excursions when compared to healthy peers. Studies have demonstrated that patients with CF have increased glucose fluctuations and hyperglycemia and that this may affect the clinical course of CF and lead to lymphocyte dysfunction. T-helper 17 (Th17) lymphocytes produce and secrete the pro-inflammatory cytokine IL-17. The Th17 pathway is involved in CF lung inflammation, ß-cell destruction in type 1 diabetes (T1D) and Th17 cells of patients with type 2 diabetes have increased production of IL-17 when compared to healthy peers. Also, regulatory T-cells (Tregs) have been shown to be dysfunctional and produce IL-17 in T1D. Furthermore, vitamin D can affect inflammation in CF, diabetes and the differentiation of lymphocytes. In this review, we discuss the potential roles of hyperglycemia on Th17 cells, Tregs and IL-17 as a potential cause for accelerated lung function decline before CFRD and how this could be modulated by vitamin D or by directly intervening in the IL-17A pathway.

Agreement of bioelectric impedance analysis and dual-energy X-ray absorptiometry for body composition evaluation in adults with cystic fibrosis.

Malnutrition in cystic fibrosis (CF) is associated with increased mortality and can lead to fat-free (FFM) and fat mass (FM) loss. Dual-energy X-ray absorptiometry (DXA) is used and validated to measure FFM and FM. DXA's high cost has led to the utilization of less costly techniques such as bioelectrical impedance analysis (BIA). The aim of this study was to determine the agreement of FFM, FM and %FM measurements taken with DXA and BIA in adults with CF. We measured FFM, FM and %FM in 34 adults with CF with a leg-to-leg BIA and an iDXA and determined agreement using Bland-Altman analysis. While DXA and BIA measurements were well correlated (r > 0.8), mean biases between both methods were between 8 and 11%. BIA underestimated FM and %FM and overestimated FFM. In a clinical research setting where these measurements are used to phenotype patients, BIA cannot replace DXA.

The association between leptin and insulin levels in adults with cystic fibrosis.

UNLABELLED: Cystic fibrosis (CF)-related diabetes is an important complication of CF caused by a decrease in insulin secretion that is associated with weight loss, poor nutritional status and increased mortality. Leptin, a hormone secreted from white adipose tissue, has an important role in energy homoeostasis by inhibiting food intake and increasing energy expenditure. Leptin secretion can be increased by nutrient signals such as insulin. AIMS: Considering that leptin plays a role in energy homoeostasis and that CF is associated to poor weight gain and decreased insulin secretion, leptin levels in CF patients with different glucose tolerances were investigated and compared with those of healthy control subjects. METHODS: Two-hour oral glucose tolerance tests (OGTT) were performed in 82 patients with CF and various glucose tolerances as well as in 17 healthy control subjects during which blood was withdrawn every 30 min to measure glucose and insulin. Fasting leptin, fibrinogen and fat mass were also measured, and body mass index (kg/m(2)) calculated for all participants. Early and late insulin secretion was separated by calculating the area under the curve from time 0 to 30 min and 30 to 120 min of the OGTT (AUC(0-30) and AUC(30-120)). RESULTS: Leptin levels were comparable between CF patients and healthy control subjects. Interestingly, correlations were observed between leptin levels and insulin (AUC(0-120) and AUC(30-120)) after adjusting for gender and fat mass (P<0.05). CONCLUSION: This study suggests a potential role of insulin in regulating leptin levels in adults with stable CF.

Normal total and high molecular weight adiponectin levels in adults with cystic fibrosis.

Cystic fibrosis related diabetes (CFRD) is an important complication of CF that increases mortality. Adiponectin, an adipokine secreted from adipose tissue, plays an important role in fatty acid and glucose metabolism. Lower total adiponectin (TA) levels have been linked to the risk of developing type 2 diabetes. However, studies show that the high molecular weight isoform (HMW), thought to be more active than TA, might be a better indicator of insulin sensitivity. Our aim was to determine the association between HMW and insulin sensitivity in CF subjects and determine if other factors might modulate its levels. Thirteen control subjects and 47 CF adults (16 with normal glucose tolerance, 16 prediabetic and 15 with CFRD) underwent an oral glucose tolerance test. Blood samples were taken at time 0, 30, 60, 90 and 120 min. Body mass index, fibrinogen, glucose and insulin, TA and HMW were measured in every subject. Regression analysis was used to determine the association between TA, HMW and glucose (fasting glucose, 2h glucose and glucose AUC) as well as insulin (fasting insulin, insulin AUC, and Stumvoll insulin sensitivity index) parameters. TA and HMW levels were similar between CF patients and controls and were not associated to insulin sensitivity. TA was negatively associated to insulin AUC (p=0.0108) and 2h glucose (p=0.0116) in controls while these relationships were either weakly negative (p=0.0208) or weakly positive (p=0.0105) in CF patients. Also, HMW was negatively associated to insulin (p=0.00301) and glucose AUC (p=0.0546) in controls whereas these associations were positive in CF patients (p=0.0388, p=0.0232 respectively). In conclusion, our exploratory study on HMW adiponectin demonstrated similar levels of TA and HMW between CF patients and controls and different relationships between forms of adiponectin to glucose metabolism and insulin in CF.

Similar associations of total adiponectin and high molecular weight adiponectin with cardio-metabolic risk factors in a population of overweight and obese postmenopausal women: a MONET study.

The aim of the study was to examine the association between total adiponectin and high molecular weight (HMW) adiponectin levels with cardio-metabolic risk factors in a population of sedentary, overweight, and obese postmenopausal women. Cross-sectional study was carried out on 55 nondiabetic sedentary overweight and obese postmenopausal women aged between 50 and 70 years. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp technique. Body composition and visceral fat were measured using dual X-ray absorptiometry and computed tomography, respectively. Other cardio-metabolic risk factors included: plasma lipids, hsC-reactive protein, energy expenditure (doubly labeled water), peak oxygen consumption, muscle strength (using weight training equipment) as well as total and HMW adiponectin. Correlations of total and HMW adiponectin with various cardio-metabolic risk factors were comparable. In addition, regression analysis results showed similar independent predictors of total and HMW adiponectin. Finally, the receiver operator characteristic (ROC) curves for total and HMW adiponectin to predict insulin sensitivity showed no difference between the areas under curve (AUC) (AUC total adiponectin=0.80 [95% CI: 0.66-0.95] versus AUC HMW adiponectin=0.76 [95% CI: 0.60-0.91], p=0.36). The present study indicates that HMW adiponectin does not seem to provide additional information than total adiponectin in relation to cardio-metabolic risk factors in overweight/obese postmenopausal women.

Reduction of the prenatal hypoxic-ischemic brain edema with noscapine.

Cytotoxic free radicals and release of several neurotransmitters such as bradykinin contribute to the pathogenesis of hypoxic-ischemic brain damage. We have studied the efficacy of noscapine, an opium alkaloid and a bradykinin antagonist, in reducing post-hypoxic-ischemic damage in developing brain of 7-d-old rat pups. Hypoxic-ischemic injury to the right cerebral hemisphere was produced by legation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before hypoxia the rat pups received noscapine (dose = 0.5-2 mg/kg) or saline. Pups were scarified at 24 h post recovery for the assessment of cerebral damage by histological methods. Our results showed that noscapine was an effective agent in reducing the extent of brain injury after hypoxic-ischemic insult to neonatal rats. Therefore, it is concluded that noscapine may be a useful drug in the managements of patients after stroke.

Correlation between ACE activity and mean blood pressure in Iranian normotensive subjects after oral administration of a single dose of enalapril.

Relationship between serum ACE activity and mean blood pressure (MAP) after administration of a single oral dose of the ACE inhibitor enalapril 10 and 20 mg tablets was investigated in 19 Iranian normotensive male subjects. Enalapril at doses, which maximally inhibit ACE activity, reduced MAP dose dependently. The t(max) of ACE inhibition decreased significantly by increasing the enalapril doses, but t(max) of MAP reduction did not change by increasing the dose. The AUC (area under the curve) of ACE inhibition versus time was significantly larger in 20 mg enalapril group compare to 10mg enalapril group (p<0.001). A significant correlation was found between log of residual ACE activity and MAP (r=0.4927; p<0.001). It is concluded that in Iranian normal subjects, after administration of a single oral dose of enalapril, MAP related to residual ACE activity.

Effects of trypan blue on the action of adrenergic agonists in the guinea-pig isolated atrium.

It has been reported that trypan blue, a diazo dye with polyamphipathic structure, can inhibit the coupling of receptors to G-proteins. The present study was carried out to investigate the effect of trypan blue on the actions of adrenoceptor agonists in the guinea-pig atrium. Trypan blue (10 and 100 microM) antagonized the positive inotropic effects of isoprenaline and dobutamine by shifting their concentration-response curves to the right. With the selective beta 2-adrenoceptor agonist, salbutamol, there was a reduction of response in the presence of trypan blue. Therefore, we concluded that trypan blue diminish the response to beta-adrenoceptor agonists possibly via decoupling receptors from Gs. Trypan blue and similar agents, due to their unique mode of action, can be used as tools for the investigation of the mechanism of receptor-G protein coupling in the whole tissue preparation.

Specific polypeptide markers in chronic B cell malignancies detected by two-dimensional gel electrophoresis.

Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis of silver stained polypeptides was used to discriminate the cell protein profiles in chronic B cell malignancies. We identified 5 distinct polypeptides (H1 to H5) present in hairy cell leukemia (HCL) (14 cases) and absent in most chronic lymphocytic leukemia (CLL) and normal B lymphocytes. Two polypeptides, H2 and H5, were absolutely specific of HCL. The 2-D PAGE profiles found in 3 splenic lymphoma with villous lymphocytes (SLVL) and 2 HCL variants (HCL-V) were similar to HCL with a unique additional peptide present in 3/3 SLVL and 1/2 HCL-V. When HCL and SLVL were assessed for the CLL stage-specific 2-D PAGE patterns, HCL was related to stage A/B while SLVL was related to stage C. In conclusion, 2-D PAGE analysis of the molecular pattern of B lymphocytes provides a new means to recognize the leukemic origin of the sample and distinguish HCL from CLL and SLVL.