Effect of treatment with different doses of 17-beta-estradiol on the insulin receptor.

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of sex hormones. However, the influence of these hormones on the early steps of insulin action has not been extensively studied, although the potentially beneficial effect of estradiol on glucose homeostasis has been reported. In this paper, we attempted to determine the effect of 17-beta-estradiol on the insulin receptor of ovariectomized rats treated with different doses of hormones. Our results showed a tissue-dependent response to estradiol. We found that low doses of estradiol increased the amount of insulin receptors in liver and muscle on days 6 and 11 of treatment but not in adipose tissue, and after 16 days only the muscle responsed in this way. On the other hand, high doses of estradiol significantly decreased the amount of insulin receptors, at least in muscle and adipose tissue. We believe that the low concentrations of 17-beta-estradiol (similar to early pregnancy) could be responsible for the increase in insulin sensitivity by increasing the amount of insulin receptors in peripheral tissues. When the hormone levels were high (similar to late pregnancy) the amount of insulin receptors decreased in peripheral tissues, and insulin sensitivity is diminished just as in late pregnancy. The specific molecular mechanism for this action is as yet unknown.

Reduced ethanol consumption during cyproheptadine administration in rats from a long-term alcohol-treated colony.

The influence of cyproheptadine (CPH) on forced and voluntary ethanol intake was studied in long-term alcohol-treated rats. Wistar rats from a colony (WAC) that have been drinking alcohol as their only liquid fluid for the 25 previous generations and from a genetically related colony (WN) that had never been given alcohol were used. In the first experiment, daily IP doses of 15 mg/kg CPH were found to reduce forced ethanol consumption during CPH treatment in both WAC and WN rats which had been drinking ethanol for six months. In two additional groups of WAC and WN rats which were not given ethanol, water intake was not affected by CPH administration. In a second experiment, alcohol preference was reduced both during and after CPH, but total fluid intake (ethanol + water) was not affected. These findings suggest that the effect of CPH could be specific to ethanol. The decrease in ethanol consumption was associated with a significant body weight loss; this result may support the hypothesis of a link between the serotoninergic system, food intake, and alcohol drinking behavior that has been considered by earlier investigators.

Food allergy and intolerance in children and adolescents, an update.

Epidemiological surveys demonstrate that rapid increase in allergic diseases is a real phenomenon. In developed countries they are about the commonest chronic diseases, reaching between 15% and 30% of the population. Adverse reaction to food can be divided into toxic reaction and non-toxic reactions. The non-toxic reactions are divided into non-immune mediated and immune mediated, these are considered food allergic reactions. We showed our experience in a 4 y survey, individualized by food allergens during the first two years of life. In Spain egg white protein is the most common allergen followed by cow's milk and peanuts. These three food items represent half of the sensitizations in children under 2 y of age. After 4 y sensitivities to vegetable allergens such as nuts, fruits and legumes are most frequent. The diagnosis of food allergy is still problematic, even in the case of atopy or IgE mediated hypersensitivity. There is a lack of standardized diagnostic procedures; the only test accepted as 'gold standard' for confirmation of food allergy and in general for food intolerance, is a properly performed double blind placebo-controlled oral food challenge. Negative results should be always followed by an open food challenge. This test should only be conducted in patients with a good medical condition and in a clinic or hospital setting, and only if trained personal and equipment for treating systemic anaphylaxis are present. Contraindications to a challenge test are limited to those situations that can be hazardous for the patient in relationship to the studied food. The treatment of food allergy and intolerance is avoiding the implicated food as long as necessary, until tolerance appears. Prevention of food allergy is the first goal of every pediatric allergologist. Controlled trials of food allergy prevention have been performed only in high allergic risk children.

Effect of treatment with different doses of 17-beta-estradiol on insulin receptor substrate-1.

CONTEXT: Ovarian hormones modulate insulin sensitivity, but their exact role remains unclear. OBJECTIVE: We tried to determine whether different doses of 17-beta-estradiol cause changes in the regulation of insulin receptor substrate (IRS-1) levels, and if so, the possible implications in insulin sensitivity. DESIGN: Ovariectomized rats were treated with different doses of 17-beta-estradiol at 6, 11 and 16 days. MAIN OUTCOME MEASURES: Immunoprecipitation and Western blotting for IRS-1 were performed in different tissues. RESULTS: We found that estradiol treatment has an influence on the amount of IRS-1 but that it acts in different ways depending on the tissue studied, on the length of treatment, and on the doses employed. CONCLUSIONS: Our results suggest that low concentrations of 17-beta-estradiol could be responsible for the upregulation of insulin receptor substrate 1, increasing insulin sensitivity in muscle and adipose tissue. However, insulin receptor substrate 1 is downregulated with high concentrations of 17-beta-estradiol, thus these high hormone plasma levels could favour insulin resistance in peripheral tissues. The role of 17-beta-estradiol seems to modulate insulin receptor substrate 1 levels in insulin dependent tissues, but in a different manner in each tissue. These novel findings are important for improving knowledge about the possible risk for insulin resistance in women taking oral contraceptives or receiving hormone replacement therapy at menopause.

[Determinants of poor mental health in people aged 16 to 64 residing in a large city]. / Factores que determinan la mala salud mental en las personas de 16 a 64 años residentes en una gran ciudad.

BACKGROUND: Know what factors determine the poor mental health in the city of Madrid. MATERIAL AND METHODS: Cross-sectional study Health Survey of the City of Madrid (ESCM'05), analyzed 5746, persons aged 16 to 64 years, in the years 2004-2005. Dependent variable was obtained from the General Health Questionnaire (GHQ-12), was considered score above 2. Independent variables included sociodemographic factors, lifestyle, health and environmental issues. The quality of life related to health (HRQOL) was measured with the questionnaire COOP / WONCA. RESULTS: The overall prevalence of poor mental health was 19.2%, p <0.05 for gender, age group 16 to 24 years and lower social classes. The predictors most strongly associated with poor mental health in the multiple regression are: women OR=1.48 (1.23-1.78), minors OR=3.21 (2.40-4.29), immigrant economic OR=1.33 (1.06-1.68), smoking or drinking alcohol OR=1.22 (1.02 -1.49) and 1.31 (1.09 -1.57), chronic disease OR=1.47 (1.21 -1.79), sleeping less 8 hours OR=1.41 (1.17 -1.68), having fair or poor health status perception OR=1.65 (1.22-2.22), self-perceived poor quality of life HRQOL OR=1.18 (1.15-1.22), and limited social activities OR=1.34 (1.07 -1.69) . CONCLUSIONS: The mental health problems are highly prevalent in this city. Being woman, young, economic migrant, worse lifestyles, poor quality of life refered or limited social activities are the factors that force to explain the association with poor mental health.

Frequency of food allergy in a pediatric population from Spain.

We evaluated the prevalence and characteristics of the principal foods implicated in 355 children diagnosed with IgE-mediated food allergy. Diagnosis was established on the basis of positive clinical history for the offending food, positive specific IgE by skin prick test and RAST, and open food challenge. Our results showed the principal foods involved in allergic reactions are: eggs, fish, and cow's milk. These are followed in frequency by fruits (peaches, hazelnuts and walnuts), legumes (lentils, peanuts and chick peas) and other vegetables (mainly sunflower seeds). The legumes demonstrated the highest degree of clinical cross-reactivity. Most patients with food allergy reacted to one or two foods (86.7%). Only 13.3% of patients reacted to 3 or more foods, mostly to legumes and fruits. We found that food allergy begins most frequently in the first (48.8%) and second (20.4%) years of life. Allergy to proteins of cow's milk, egg, and fish begins predominantly before the second year, demonstrating a clear relationship with the introduction of these foods into the child's diet. Allergy to foods of vegetable origin (fruits, legumes and other vegetables) begins predominantly after the second year.

Sensitization to inhalant allergens in children diagnosed with food hypersensitivity.

In order to characterize the profile of inhalant allergen sensitizations in patients with food hypersensitivity, we carried out a screening process using a standard panel of inhalant allergens by SPT. We screened 437 patients (mean age 5.4 years, 4.1 SD) who showed anti-allergen IgE to one or several foods, determined by both SPT and RAST. In each case in which a positive SPT to inhalant appeared, a new individualized search for these allergens was performed by both SPT and Phadezym RAST. We found sensitization to aeroallergens in 272 of the 437 children (62%) with sensitization to foods (52% of all patients were sensitized to pollens, 17% to dermatophagoides, and 26% to animal allergens). The number with sensitization to aeroallergens was proportionally increased in relation to the number of food sensitizations (p < 0.05). Sensitization to pollen allergen were found with higher frequency (p < 0.001) in patients with sensitization to fruits, legumes, and other vegetables (mainly walnuts, chestnuts, melons, or sunflower seeds) than in those sensitive to foods of animal origin. Sensitization to dermatophagoides and animal allergens did not show any special distribution relative to the kind of food sensitization. Seventeen patients with sensitization to egg showed sensitization to avian feathers. This type of sensitization did not appear in the remainder of patients evaluated.

Predominant right ventricular infarction in malignant renovascular hypertension in rats.

Malignant hypertension was induced in Wistar rats of both sexes by complete aortic ligature just above the origin of the left renal artery. An acute and a late phase of hypertension, 4 days and 28 days after the aortic ligature respectively, were defined to study the relationship between the severity of hypertension and injury of the small arteries and myocardial necrosis. The most frequent finding in the heart was the presence of right ventricular infarction. In acute-phase hypertension most of the animals showed acute infarction of the right ventricle, but only focal left ventricular infarction was found. Lesions in the large coronary arteries were not observed. However, the small arteries and arterioles of the right ventricle presented fibrinoid necrosis lesions. In late-phase hypertension, the intramyocardial small vessels showed proliferative endarteritis and fibrinoid necrosis lesions, but this time they appeared in both ventricles. The severity of the myocardial infarcts and the percentage of small arteries and arterioles injured in the right ventricle were significantly higher than in the left ventricle despite the maintenance of blood pressure almost to the same level. No changes in the right ventricular pressure were observed in either phase. These observations suggest that in malignant renovascular hypertension the intramyocardial arteriolar lesions appear to be an important factor in the production and the severity of myocardial infarcts with predominance in the right ventricle.

Reflex pressor response to gastric mechanical stimulation in rats.

Neural and humoral mechanisms involved in the reflex pressor response during mechanical stimulation of the stomach of rats were investigated. The arterial blood pressure response was prevented by inhibition of alpha-adrenergic vasoconstriction using either an alpha-adrenergic blocker or a ganglionic blocker. In addition, there was a small decrease in the response after nephrectomy. However, there were no alterations in the response after beta-adrenergic blockade, bilateral adrenalectomy, inhibition of converting enzyme activity with enalapril or bilateral cervical vagus nerve transection. The heart rate was not modified after either intervention. After vagotomy the time of recovery of the basal blood pressure was significantly prolonged. It can be concluded that the blood pressure response to mechanical stimulation of the stomach wall is of neural rather than of humoral origin and mainly involves activation of alpha-adrenergic receptors. Vagal efferent pathways could be also involved.

Normalization of the altered liver function tests after islet transplantation in diabetic rats.

The purpose of our study was to determine if streptozotocin induced diabetes (SID) in rats produces alterations in hepatic function, as described in poorly controlled diabetic patients, and if islet transplantation (islet-Tx) would subsequently ameliorate this status. Hepatocellular dysfunction was evaluated by the aspartate aminotransferase (SGOT) and the alanine aminotransferase (SGPT) activities in plasma. For the evaluation of cholestasis the plasma alkaline phosphatase (APase) activity was used. These determinations were performed in normal, SID, SID with Islet-Tx, and SID Wistar rats with sham-Tx. Also, glucose was measured in plasma samples, as well as histological studies of the liver were performed. More than 1,000 isogeneic islets (islet-Tx group) or non viable insular tissue (sham-Tx group) were transplanted via mesenteric ileal vein three weeks after SID. The results showed that SID in rats produces alterations in the hepatic function as well as in the structure of the hepatocytes, and the normalization of carbohydrate metabolism by islet transplantation restores normal hepatic function and morphology.

Islet transplantation restores normal serum amylase levels in diabetic rats.

Diabetes is associated with a diminution in exocrine pancreatic function. The goal of our study was to investigate whether the altered exocrine pancreatic function of streptozotocin-induced diabetic rats could be ameliorated by islet transplantation. Diabetic rats received either more than 1,000 syngeneic islets intraportally (islet transplantation group) or pancreatic, nonviable insular tissue (sham transplantation group). Plasma amylase and insulin levels in diabetic rats were significantly lower than in normal rats. The exocrine pancreas of streptozotocin-induced diabetic rats showed alterations (decrease of zymogen granules, diminution of endoplasmic reticulum, clusters of ribosomes without organization) in the structure of acinar cells at the electron microscopic level. After islet transplantation, plasma glucose levels were restored to normal values, and those of amylase and insulin gradually increased to normal values. A positive correlation between plasma levels of amylase and insulin was found. Three months after islet transplantation, the islet-transplanted rats did not show morphologic alterations of the acinar cells which were still found in the sham-transplanted rats. It is concluded that alterations of exocrine pancreas in streptozotocin-induced diabetic rats are ameliorated by islet transplantation.

Blood pressure changes after gastric mechanical and electrical stimulation in rats.

The effect of different stimuli applied in several parts of the digestive tract on blood pressure was studied in unconscious Wistar rats. Gastric distension and electrical and pinching stimuli produced a significant increase in both systolic and diastolic arterial blood pressure. When different gastric zones were stimulated by either electrical or pinching stimuli, the highest pressor response was found in the antropyloric zone. The stimuli applied to the small intestine, outside the duodenum, did not modify the blood pressure. The pinching of the abdominal peritoneum caused a pronounced (P less than 0.001) blood pressure decrease. These data suggest that the pressor response to gastric distension could be mediated by gastric mechanoreceptors. The pressor response observed after stimulation of the gastric antropyloric zone suggests that this area has a greater number of mechanoreceptors.

Oral disodium cromoglycate in food allergy. An open trial in four patients.

The effect of DSCG olution per os was studied in four infants with immediate hypersensitivity reaction to cow's milk and egg, manifested by digestive and cutaneous symptoms. Previous administration of a 1 per cent DSCG solution by mouth resulted in diminution of both the digestive and cutaneous symptoms associated with allergen challenge. The best time interval between oral DSCG and the allergen challenge was about 30 min. The drug lost effectiveness when the solution was prepared more than a week in advance of its administration. A 2-year follow-up in two of the patients revealed the reappearance of cutaneous and digestive symptoms and, for the first time, the onset of wheezing while continuing to administer the allergens and despite continuous oral DSCG. The characteristics of these cases raise questions about the means of sensitization, and the possible mechanism of action of oral DSCG in the inhibition of non-digestive symptoms. Clinical indications for its use are discussed.