Biomedical subjects

Cristina Ripoll

Publications and source records attributed to Cristina Ripoll.

15 recordsLinked to original sources

PubMed2006

Rapid endocrine disruption: environmental estrogen actions triggered outside the nucleus.

An exogenous substance is defined as an endocrine disrupter chemical (EDC) if it alters the function of the endocrine system provoking adverse health effects. Environmental estrogens are the most studied EDCs. They follow the same mechanisms of action as the gonadal hormone 17beta-estradiol. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to estrogen receptors (ERs), either ERalpha or ERbeta, and to act subsequently as transcription factors when binding to the estrogen response element (ERE) in the DNA. All the estrogenic bioassays currently used are based on this mechanism of action. New evidence indicates that the definition of estrogenicity for a chemical should take into account other estrogen receptors as well as new signaling pathways. These include the activation of additional transcription factors as well as the action of xenoestrogens through estrogen receptors located outside the nucleus: in the plasma membrane, mitochondria and probably the cytosol. Therefore, new estrogenic bioassays should be developed to include the novel concept of rapid endocrine disruption.

Animals↗

PubMed2006

The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis.

BACKGROUND: In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture. AIM: To examine the effect of the extent of the collateral circulation on the postprandial increase in portal pressure observed in cirrhosis. PATIENTS AND METHODS: The hepatic venous pressure gradient (HVPG), hepatic blood flow and azygos blood flow were measured in 64 patients with cirrhosis before and after a standard liquid meal. RESULTS: Peak increases in HVPG (median+14.9%), hepatic blood flow (median+25.4%), and azygos blood flow (median+32.2%) occurred at 30 min after the meal. Compared with patients with marked postprandial increase in HVPG (above the median, n = 32), those showing mild (<15%, n = 32) increase in HVPG had a higher baseline azygos flow (p<0.01) and underwent a greater postprandial increase in azygos flow (p<0.02). Hepatic blood flow increased similarly in both groups. Postprandial increases in HVPG were inversely correlated (p<0.001) with both baseline azygos flow (r = -0.69) and its postprandial increase (r = -0.72). Food intake increased nitric oxide products in the azygos (p<0.01), but not in the hepatic vein. Large varices (p<0.01) and previous variceal bleeding (p<0.001) were more frequent in patients with mild increase in HVPG. CONCLUSIONS: Postprandial hyperaemia simultaneously increases HVPG and collateral flow. The extent of the collateral circulation determines the HVPG response to food intake. Patients with extensive collateralisation show less pronounced postprandial increases in HVPG, but associated with marked flares in collateral flow. Collateral vessels preserve their ability to dilate in response to increased blood flow.

Adult↗

PubMed2006

Does interferon improve portal hypertension?

Chronic hepatitis C is the leading cause of advanced liver disease in the Western world. Most patients with liver cirrhosis develop portal hypertension (PHT) (i.e. an abnormal gradient between portal and inferior vena cava pressures), responsible for the most frequent and severe complications of liver disease and, as a consequence, the main cause of death and liver transplantation in those patients. The existence of a potential beneficial effect of antiviral therapy (AVT) on liver inflammation and fibrosis, partially independent of the degree of virological response, has been recently reported. However, the possible influence of these histological changes on PHT has not been evaluated. In this article, we summarize the available findings regarding the effect of AVT on PHT in patients with advanced chronic hepatitis C, as well as its possible implications for clinical practice and future avenues of investigation.

Antiviral Agents↗

PubMed2006

Cannabinoid receptors regulate Ca(2+) signals and insulin secretion in pancreatic beta-cell.

Insulin is the main hormone involved in the regulation of glycaemia, its impaired secretion is a hallmark of type I and type II diabetic individuals. Additionally, insulin is involved in lipogenesis and weight gain, provoking an anorexigenic action. The endocannabinoid system contributes to the physiological regulation of energy balance, food intake and lipid and glucose metabolisms. Despite that, an experimental link between the endocannabinoid system and the endocrine pancreas has not yet been described. Using quantitative real-time PCR and immunocytochemistry, we have demonstrated the existence of both CB1 and CB2 receptors in the endocrine pancreas. While the CB1 receptor is mainly expressed in non-beta-cells, the CB2 type exists in beta- and non-beta-cells within the islet. The endocannabinoid 2-arachidonylglycerol (2-AG) through CB2 receptors regulates [Ca(2+)](i) signals in beta-cells and as a consequence, it decreases insulin secretion. This effect may be a new component involved in the orexigenic effect of endocannabinoids and constitutes a potential target for pharmacologic manipulation of the energy balance.

Animals↗

PubMed2006

Prevalence of portal hypertensive duodenopathy in cirrhosis: clinical and haemodynamic features.

OBJECTIVES: To estimate the prevalence of portal hypertensive duodenopathy (PHD) in patients with cirrhosis and portal hypertension, and to evaluate its relationship with clinical and haemodynamic parameters. PATIENTS AND METHODS: Endoscopy reports and clinical history of 549 consecutive patients with cirrhosis and portal hypertension were evaluated retrospectively. A diagnosis of PHD was obtained in those patients with a congestive vascular pattern of the duodenum. RESULTS: PHD was found in 46 patients (8.4%). Previous endoscopic band ligation and coexistence of severe gastropathy were significantly more frequent in PHD group. Systemic and hepatic haemodynamic evaluations were performed in 20 patients with PHD and 160 without PHD: the mean hepatic venous pressure gradient was higher in those cases with PHD (22.5 (5.4) vs. 19.8 (5.5) mmHg, P=0.045). Hypertensive colopathy was found in seven out of the 10 patients with PHD and a colonoscopic evaluation. In five of six patients PHD disappeared after liver transplant. CONCLUSIONS: PHD is an uncommon finding of portal hypertension in cirrhotic patients. It is associated with previous endoscopic band ligation, to manifestations of portal hypertension in other sites of the gastrointestinal tract and to greater values of hepatic venous pressure gradient. The clinical relevance of this syndrome remains to be determined.

Adult↗

PubMed2006

Antiviral therapy decreases hepatic venous pressure gradient in patients with chronic hepatitis C and advanced fibrosis.

BACKGROUND: Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown. AIM: This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension. METHODS: Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score. RESULTS: HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11). CONCLUSIONS: AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Adult↗

PubMed2006

The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance.

The function of the pancreatic beta-cell is the storage and release of insulin, the main hormone involved in blood glucose homeostasis. The results in this article show that the widespread environmental contaminant bisphenol-A (BPA) imitates 17beta-estradiol (E2) effects in vivo on blood glucose homeostasis through genomic and nongenomic pathways. The exposure of adult mice to a single low dose (10 microg/kg) of either E2 or BPA induces a rapid decrease in glycemia that correlates with a rise of plasma insulin. Longer exposures to E2 and BPA induce an increase in pancreatic beta-cell insulin content in an estrogen-receptor-dependent manner. This effect is visible after 2 days of treatment and starting at doses as low as 10 microg/kg/day. After 4 days of treatment with either E2 or BPA, these mice developed chronic hyperinsulinemia, and their glucose and insulin tolerance tests were altered. These experiments unveil the link between environmental estrogens and insulin resistance. Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia.

Animals↗

PubMed2005

Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era.

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00-1.06; P = .05) so that each 1-mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved.

Adult↗

PubMed2005

Comparison of transjugular intrahepatic portosystemic shunt dysfunction in PTFE-covered stent-grafts versus bare stents.

PURPOSE: The aim was to compare the clinical and hemodynamic outcome between polytetrafluoroethylene (PTFE)-coated stent-grafts and bare stents in patients who required both elective and emergency transjugular intrahepatic portosystemic shunt (TIPS) placement due to portal hypertension related complications. MATERIALS AND METHODS: Retrospective analysis of all seventy patients with portal hypertension related complications who required TIPS placement in a referral hospital from September 1998 to May 2002 was done. Follow-up was extended until May 2003. PTFE-covered stent-grafts were used in the latter 20. Demographic variables, cirrhosis etiology and Child-Pugh class, indication of TIPS placement and clinical outcome were recorded. The following TIPS-related outcomes were registered: recurrent variceal bleeding and/or ascites, hepatic encephalopathy and mortality. RESULTS: Baseline characteristics, portacaval gradient (PCG) after TIPS placement and at 1 month angiographic revision were similar in both groups. At 6 month follow-up, PCG was significantly lower in patients with stent-grafts (14.2 mmHg (5.6 mmHg) versus 7 mmHg (1 mmHg), p<0.001). Overall, there were no cases of clinically relevant TIPS dysfunction in the coated stent group while 22% of patients in the bare stent group had recurrence of portal hypertension related complications (p=0.085). Actuarial probability of TIPS dysfunction in bare stents was 82% at 12 months compared to no episode in covered stent-grafts (p=0.03). Mean increase in total serum bilirubin was higher in the PTFE-coated stent group (6.7 mg/dl (14.4 mg/dl) versus 0.5 mg/dl (2.4 mg/dl), p=0.01) without differences in encephalopathy nor mortality rate. CONCLUSION: One year shunt patency rate is improved with placement of ePTFE-covered stent-grafts without a higher rate of encephalopathy. Further prospective trials are required.

Chi-Square Distribution↗

PubMed2005

Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.

Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.

Animals↗

PubMed2004

Disentangling the molecular mechanisms of action of endogenous and environmental estrogens.

The gonadal hormone 17beta-estradiol is involved in numerous cellular processes. In many cases, 17beta-estradiol actions are imitated by synthetic and natural chemicals in the environment. Their actions differ depending on the target tissue, the receptors involved and the molecular pathways activated. The plethora of estrogenic actions is triggered by different receptors and other specific structures that activate different signalling pathways. This amount of information may lead to a maze of effects triggered by endogenous and environmental estrogens that we intend to clarify in this review. Understanding the variety of estrogen receptors, their different locations and the signalling pathways activated by estrogenic ligands is fundamental for understanding the diversity of actions that estrogens have in different tissues and cells.

Animals↗

PubMed2004

Oestradiol rapidly inhibits Ca2+ signals in ciliary neurons through classical oestrogen receptors in cytoplasm.

Oestrogen plays a key role in a great variety of actions in the nervous system, either through classical or alternative pathways. The classical pathways are initiated after oestrogen binding to the oestrogen receptors ERalpha or ERbeta, which translocate from the cytoplasm to the nucleus and act there as transcription factors. Alternative pathways are initiated at the plasma membrane and cytoplasm, via binding to classical or non-classical ERs. Using isolated ciliary ganglion neurons from the chick embryo and Ca2+ imaging, we demonstrated that a 10-min exposure to 17beta-oestradiol reduces Ca2+ influx through the plasma membrane. This effect was not reproduced by oestradiol conjugated to bovine serum albumin, which does not cross the plasma membrane, indicating that 17beta-oestradiol was acting intracellularly. ERalpha was detected in the cytoplasm by immunostaining and its involvement in the regulation of Ca2+ influx by ICI182,780 inhibition. The phosphatidylinositol-3 kinase (Pi3-kinase) inhibitor wortmannin and the nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) both blocked the oestradiol effect. The oestradiol effect was reproduced by 8Br-cGMP and abolished in the presence of the cGMP-dependent protein kinase (PKG) inhibitor KT5823. Our study indicates that 17beta-oestradiol can regulate Ca2+ influx via PI3-kinase, NOS and PKG after activation of cytoplasmic ER.

Animals↗

PubMed2004

Estrogen and xenoestrogen actions on endocrine pancreas: from ion channel modulation to activation of nuclear function.

17beta-Estradiol elicits a rapid opposite effect on [Ca2+]i in alpha- and beta-cells within intact islets of Langerhans. In beta-cells, physiological concentrations of the gonadal hormone decreases KATP channel activity in synergy with glucose, leading to a membrane depolarization that opens voltage-gated Ca2+ channels, potentiating Ca2+ signals. As a consequence insulin release is enhanced and transcription factor CREB is activated in a Ca(2+)-dependent manner. In glucagon-containing alpha-cells, 17beta-estradiol provokes the abolishment of Ca2+ oscillations generated by low glucose, a situation that should decrease glucagon release. In both types of cells the second messenger involved is cGMP. The estrogen receptor involved is located in the plasma membrane and has a pharmacological profile unrelated to classical estrogen receptors ERalpha and ERbeta. For that reason, it has been named non-classical membrane estrogen receptor (ncmER). Although the physiological roles of this receptor are still unknown, it may be implicated in the responses of the endocrine pancreas to the physiological and pathological changes of 17beta-estradiol.

Animals↗

PubMed2004

Comparison of transcatheter arterial embolization and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure.

PURPOSE: To compare the outcomes of embolotherapy and surgery as salvage therapy after therapeutic endoscopy failure in the treatment of upper gastrointestinal peptic ulcer bleeding. MATERIALS AND METHODS: Retrospective analysis of 70 cases of refractory peptic upper gastrointestinal hemorrhage was performed. Thirty-one cases were managed with embolotherapy and 39 were managed surgically. Demographic variables, underlying conditions, clinical findings, endoscopic treatment, transfusion requirements before and after alternative therapeutic approach, length of hospital stay, and outcomes including recurrent bleeding, need for surgery after initial alternative treatment, and in-hospital death were recorded. RESULTS: Patients who received embolotherapy were older (75.2 years +/- 10.9 vs 63.3 years +/- 14.5; P <.001) and had greater incidences of heart disease (67.7% vs 20.5%; P <.001) and previous anticoagulation treatment (25.8% vs 5.1%; P =.018). There were no differences in the rest of the pretreatment variables. No differences were found between the embolotherapy and surgery groups in the incidence of recurrent bleeding (29% vs 23.1%), need for additional surgery (16.1% vs 30.8%), or death (25.8% vs 20.5). CONCLUSIONS: The lack of differences between these two treatment alternatives, despite the more advanced age and greater prevalence of heart disease in the embolotherapy group, provides support for future prospective randomized studies aimed to evaluate the role of embolotherapy in the management of refractory peptic ulcer bleeding.

Age Distribution↗

PubMed2002

Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta-estradiol rapidly activate transcription factor CREB.

Endocrine-disrupting chemicals (EDCs) are hormone-like agents present in the environment that alter the endocrine system of wildlife and humans. Most EDCs have potencies far below those of the natural hormone 17beta-E2 when acting through the classic estrogen receptors (ERs). Here, we show that the environmental estrogen Bisphenol-A and the native hormone 17beta-E2 activate the transcription factor, cAMP-responsive element binding protein (CREB) with the same potency. Phosphorylated CREB (P-CREB) was increased after only a 5-minute application of either BPA or 17beta-E2 in a calcium-dependent manner. The effect was reproduced by the membrane-impermeable molecule E2 conjugated to horseradish peroxidase (E-HRP). The increase in P-CREB was not modified by the anti-estrogen ICI 182,780. Therefore, low-dose of BPA activates the transcription factor CREB via an alternative mechanism, involving a non-classical membrane estrogen receptor. Because these effects are elicited at concentrations as low as 10(-9) M, this observation is of environmental and public health relevance.

Animals↗