Montserrat Gil

Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test

The effects of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test were studied. When tested immediately or 24 h after 1 h exposure to noise, restraint in tubes or tail shock, no changes in either defecation rate or activity in the holeboard were observed. In contrast, immediately after 1 h immobilization in wood-boards, a reduction of the number of areas crossed and the number of head-dips was found. The inhibitory effect of immobilization on head-dips persisted 24 h later. The behavior of the rats in the forced swim test was classified into three categories: struggling, mild swim and immobility. The changes in behavior were critically dependent on the type of stressor, and more specifically on its intensity, that was evaluated with three different physiological parameters (serum prolactin, corticosterone and glucose levels). Thus, if tested immediately after stress, noise did not alter the response of the rats, restraint in tubes and tail shock-reduced immobility, and the latter stressor increased mild swim. In the second experiment, immobilization in wood-boards reduced struggling. Twenty-four hours after stress, noise, restraint in tubes or tail shock were without effect, but immobilized rats showed increased immobility and reduced mild swim activity. The present data clearly indicate that behavior of rats in a holeboard and in a forced swim situation are not related, and that acute stress could have a differential effect on the various categories of behavior in a forced swim situation.

The serum glucose response to acute stress is sensitive to the intensity of the stressor and to habituation

The reliability of serum glucose concentrations as an index of habituation to chronic stress was evaluated in adult male rats. The glucose response to immobilization was attenuated by six days of previous chronic exposure to the same stressor, the degree of reduction being related to the duration (15 min, 1 hr or 4 hr) of the daily exposure to immobilization. In another experiment, three groups of rats were exposed to one of three stressors (handling plus change of room, restraint in tubes, or immobilization by wood boards), 1 hr daily for 27 days. On day 28, when faced with the same acute stressor to which they were chronically exposed, the rats showed a consistent reduction in glucose response, regardless of the type of stressor used. In addition, in stress-naive rats serum glucose levels were related to the intensity of the stressor as assessed by three independent measures (food intake, body weight changes, and adrenal weight after chronic exposure to the stressor). These data indicate that, under appropriate conditions, glucose levels can be a good index of both the intensity of acute stress experienced by the rats and their habituation to repeated stress.

Behavioral and neurochemical changes in response to acute stressors: Influence of previous chronic exposure to immobilization

The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence, prevalence and clinical course of primary biliary cirrhosis in a Spanish community

Background and aims Primary biliary cirrhosis (PBC) is characterized by the autoimmune inflammatory response of small intrahepatic bile ducts. Prevalence in Spain is estimated as 61.9 cases per million inhabitants, whereas Northern Europe rates over 200 cases/million. Our objective was to determine the incidence and prevalence of PBC in our health area. Material and methods PBC was defined by the presence of abnormal liver tests (dissociated cholestasis) with positive antimitochondrial antibodies and/or compatible liver histology. Medical records from patients diagnosed between 1990 and 2002 were reviewed retrospectively. The following data were collected: diagnostic data, demographic and analytic data, liver histology and stage and treatment and disease outcome. Results In a population of 389 758 inhabitants, 87 patients were diagnosed with PBC. Mean age at diagnosis was 63.9±12.6 years. Eighty-four (96.6%) were women. Mean annual incidence was 17.2 per 106 inhabitants and the prevalence at the end of study was 195 per 106. Biopsy was performed in 71 (81.6%) patients, 61 of whom (86%) did not have fibrosis. Time of follow-up was 63.6±43.2 (2.28–153.9) months. Conclusion Incidence and prevalence in our reference area are higher than in some Spanish areas, as per the results previously published; however, they are comparable with those obtained in Northern Europe and the US.

Seroprevalence and epidemiology of Helicobacter pylori infection in patients with cirrhosis

BACKGROUND Helicobacter pylori infection is the major pathogenic factor for peptic ulcer disease. Its epidemiology is not fully known; few data are available in patients with chronic liver disease. AIMS To investigate the seroprevalence and factors associated with Helicobacter pylori infection in a series of liver cirrhosis patients. METHODS Two hundred and twenty consecutive patients were prospectively included in a study aimed to evaluate the effect of dietary intervention on cirrhosis complications and survival. At inclusion, an epidemiological and clinical questionnaire was completed. Sera were obtained and stored at -70 degrees C until analyzed. They were tested for Helicobacter pylori antibodies using a commercial ELISA kit. RESULTS Eleven out of 220 patients had borderline anti-Helicobacter pylori IgG titers. Of the remaining 209 patients, 105 (50.2%) showed positive titers of Helicobacter pylori IgG. Univariate analysis showed that Helicobacter pylori infection was more frequent in older patients, those born outside Catalonia, and in patients with a low educational level. Past ethanol consumption and current smoking correlated negatively with Helicobacter pylori infection. Multivariate analysis selected age (OR 3.1. 95% CI 1.46-6.45), educational level (OR 2.2. 95% CI 1.18-4.2) and alcohol consumption (OR 0.7. 95% CI 0.45-0.99) as the variables independently related to Helicobacter pylori infection. CONCLUSIONS Helicobacter pylori infection in cirrhosis has the same epidemiological pattern as in the general population. Suggestions that the etiology or the severity of the liver disease could be related to Helicobacter pylori infection were not confirmed by our study.

Inhibition of catecholamine synthesis depresses behavior of rats in the holeboard and forced swim tests: Influence of previous chronic stress

Catecholaminergic pathways in the brain are activated during stress and are presumably involved in the control of physiological and behavioral changes triggered by stress. When repeatedly stressed, adaptive changes have been observed in catecholaminergic activity in the brain. In the present experiment, it was assessed whether or not chronic exposure to immobilization (IMO) altered the influence of catecholamines on behavior in the holeboard and forced swim test by administering alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis). Adult Sprague-Dawley rats were used. Chronic stress amortiguated the inhibitory effect of acute IMO on some but not all behaviors in the two tests. Whereas previous chronic IMO exacerbated the effects of the drug on struggling and immobility in the forced swim test, no change in response to the drug as a consequence of chronic IMO was observed in the holeboard test. The present data suggest that chronic IMO-induced changes in the catecholaminergic control of some behaviors might be related to depression-like states in rats. The actual physiological meaning of these changes and the specific receptors involved remain to be elucidated.

Chronic stress induced changes in LH secretion: The contribution of anorexia associated to stress

The effects of chronic intermittent immobilization (IMO) on serum LH levels of adult male rats were studied. Chronic IMO (2 h daily for 13 days) did not alter basal LH levels, but abolished the LH response to acute stressors (IMO and tailshock). The inhibition of LH caused by acute exposure to IMO for 4 or 18 h was similar in control and chronic IMO rats. Also the LH response to exogenous LHRH administration was normal in chronically stressed rats. When a group of rats eating the same amount of food as that eaten by immobilized rats was introduced (pair-fed), an inhibition of LH response to acute stressors quite similar to that found in chronic IMO rats was observed. These data indicate that chronic stress-induced inhibition of LH release caused by short-term exposure to acute stressors was located above the pituitary and was mainly due to anorexia accompanying daily exposure to the stressor.

Chronic immobilization stress appears to increase the role of dopamine in the control of active behaviour in the forced swimming test

Previously, we have demonstrated that chronic exposure to immobilization (IMO) did not modify the influence of catecholamines on active behaviour of rats in the holeboard, but clearly increased the role of these amines in the forced swimming test (FST). In the present experiment, it was studied whether or not chronic IMO altered the role of dopamine in the two tests. Adult male Sprague-Dawley rats were left either undisturbed or subjected daily to 2 h of IMO stress for 12 days. On the following day, half of the rats were administered saline and the others the dopamine antagonist haloperidol (0.5 mg/kg). Then the rats remained undisturbed in the animal room (controls) or were subjected to acute IMO for 2 h. Finally, all animals were exposed consecutively to the holeboard (4 min) and the FST (5 min). In non-chronically stressed rats, acute IMO depressed behaviour in the holeboard but not in the FST. In chronic IMO rats the inhibitory effect of acute IMO on holeboard activity was slightly reduced as compared to controls. Acute IMO increased struggling in rats previously exposed to chronic IMO but did not alter struggling in non-chronically stressed rats. Whereas the inhibition caused by haloperidol treatment in the active behaviour of rats in the holeboard was not altered by chronic IMO, the inhibitory effect of haloperidol in the active behaviour of rats in the FST was greater after chronic IMO, particularly in rats also subjected to acute IMO. These data suggest that chronic IMO stress potentiates the role of dopamine in a specific behavioural task such as the FST and adds support to the previously published data demonstrating enhanced behavioural and neurochemical responses to dopamine-related drugs after chronic stress.

Usefulness of indirect noninvasive methods in predicting progression to cirrhosis in chronic hepatitis C.

Background and aims The ability of noninvasive methods to predict the development of cirrhosis has not been established. We evaluated the ability of three noninvasive methods [the Forns index, the aspartate aminotransferase-to-platelet ratio index (APRI), and the Non-Invasive Hepatitis-C-related Cirrhosis Early Detection (NIHCED) score] to determine the risk of developing cirrhosis in chronic hepatitis C. Methods Consecutive patients with chronic hepatitis C who had undergone liver biopsy between 1998 and 2004 were eligible. We used the three methods to evaluate patients at baseline and at follow-up (4–10 years later). When these methods yielded discordant or indeterminate results, a second liver biopsy was performed. Logistic regression models were fitted for each method to predict whether cirrhosis would appear and to predict long-term mortality from cirrhosis. Results We included 289 patients in our study. The mean scores at baseline and at follow-up, respectively, were as follows: Forns, 5.47±1.95 and 6.56±2.02; APRI, 1.1±2.33 and 1.4±1.53; and NIHCED, 7.79±11.45 and 15.48±15.28. The area under the receiver operating characteristic curve for predicting cirrhosis was 0.83 for Forns, 0.79 for APRI, and 0.76 for NIHCED. The sensitivity and specificity for predicting cirrhosis, respectively, were 75 and 71% for Forns (cutoff 4.7), 86 and 42% for APRI (cutoff 0.48), and 41 and 82% for NIHCED (cutoff 0). The area under the receiver operating characteristic curve for predicting mortality was 0.86 for Forns, 0.79 for APRI, and 0.84 for NIHCED. Conclusion Indirect noninvasive markers could help identify patients with chronic hepatitis C at risk of progression to cirrhosis.

Punción biopsia hepática ambulatoria (PBHA) guiada por ultrasonografía: descripción técnica y complicaciones

Objetivos Describir la tecnica y las complicaciones de la puncion biopsia hepatica ambulatoria (PBHA) realizada siguiendo un protocolo propio y compararlas con las biopsias con ingreso hospitalario. Comparar los costes de las dos modalidades de biopsia. Material y metodos Desde enero de 2000 a enero de 2002, se han realizado 320 PBH en nuestro hospital, 250 de forma ambulatoria (PBHA). Para esta ultima modalidad, todos los pacientes cumplieron una serie de criterios minimos de salud y de entorno social previamente establecidos. Se han registrado las complicaciones posprocedimiento. Se han calculado los costes economicos de las PBHA y PBH con ingreso. Resultados La PBHA se realizo en 250 pacientes, 164 varones y 86 mujeres, con una edad media de 46 anos. No existieron complicaciones en 160 (64%) pacientes. Existio dolor controlado con medicacion en 78 (31,2%) y cuadro vagal en 8 (3,2%). Cuatro pacientes requirieron ingreso: dos hematomas subcapsulares autolimitados, un cuadro vagal prolongado y otro por no cumplir los criterios del protocolo. Se ha realizado PBH con ingreso en 50 varones y en 20 mujeres, con una edad media de 48 anos. De las 70 PBH ingresadas, hubo cuatro complicaciones graves: un fallecimiento, dos hemoperitoneos y un hematoma subcapsular autolimitado. El coste unitario de las PBHA fue de 393,66 #E y de las PBH con ingreso fue de 528,71 €. Conclusiones Si se siguen unas condiciones sociosanitarias minimas, la PBHA es una prueba segura, que evita ingresos hospitalarios, lo que se traduce en una mayor confortabilidad de los pacientes y en un ahorro economico.