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Biomedical subjects

M M Esteban

Publications and source records attributed to M M Esteban.

At least 19 recordsLinked to original sources

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.

Adipose Tissue↗

Validity of specific IgE antibodies in children with egg allergy.

BACKGROUND: The demonstration of specific IgE antibodies to egg supports the existence of allergy to this food, but a correct diagnosis can only be obtained after a challenge test. Several studies have assessed different cut-off points in the level of these antibodies as predictors of clinical reactivity. OBJECTIVE: Validation of the specific IgE antibodies measured by the CAP System Fluorescence enzyme immunoassay (FEIA) technique in the diagnosis of egg allergy in children under 2 years of age. METHODS: A prospective study of 81 children with suspected egg allergy was performed. Specific IgE antibodies was quantified for egg white, egg yolk, ovoalbumin and ovomucoid. The diagnostic challenge test was carried out following the previously established criteria. The validity of the specific IgE antibodies was analysed using children with a negative diagnostic challenge test as control group. RESULTS: The prevalence of egg allergy in the group studied was 79% and egg white was the allergen that showed the greatest diagnostic efficacy. The sensitivity and positive predictive value of the prick test and of the CAP to egg white were excellent and the specificity and the negative predictive value had lower values. A level of > or = 0.35 KU(A)/L for specific IgE antibodies to egg white predicted the existence of reaction in 94% of the cases. CONCLUSIONS: Quantification of the specific IgE antibodies to egg white is useful in the diagnosis of egg allergy. In children under 2 years of age with a background of immediate hypersensitivity after egg ingestion and presence of specific IgE antibodies to egg white of > or = 0.35 KU(A)/L, diagnostic challenge test is not necessary to establish the diagnosis of allergy to this food.

Antibody Specificity↗

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.

Adipose Tissue↗

Identification of bovine IgG as a major cross-reactive vertebrate meat allergen.

BACKGROUND: Although beef is a main source of protein in Western diets, very little has been published on allergic reactions to beef or the main allergens implicated in these reactions. The aim was to evaluate the IgE antibody response to beef in suspected meat-allergic subjects and assess cross-reactivity of beef with other vertebrate meats. METHODS: Fifty-seven sera from suspected meat-allergic subjects were tested by grid blot for specific IgE antibodies to vertebrate meats (beef, lamb, pork, venison, and chicken), and the patterns of recognition of meat proteins were assessed by immunoblot studies. RESULTS: A 160-kDa band, identified as bovine IgG, was detected in raw beef in 83% (10/12) of beef-allergic subjects but in only 24% of the beef-tolerant subjects. IgE reactivity to a band of similar mol. mass was detected also in lamb and venison, but rarely in pork or chicken. Complete inhibition of the IgE reactivity to the bovine IgG was obtained with lamb, venison, and milk. IgE reactivity to this band also completely disappeared when beef or lamb extracts were separated under reducing conditions, indicating conformational epitopes. CONCLUSIONS: Bovine IgG appears to be a major cross-reacting meat allergen that could predict beef allergy. Further studies with oral IgG challenges should be performed to document the conclusion that in vitro reactivity correlates with clinical hypersensitivity. The role of bovine IgG in other bovine products such as milk, dander, or hair must also be studied, and the hypothesis that it is a cross-reacting allergen with other mammalian products validated.

Adolescent↗

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.

Adolescent↗

Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus.

We have previouslyreported that low doses of melatonin inhibit apoptosis in both dexamethasone-treated cultured thymocytes (standard model for the study of apoptosis) and the intact thymus. Here we elucidate the mechanism by which this agent protects thymocytes from cell death induced by glucocorticoids. Our results demonstrate an effect of melatonin on the mRNA for antioxidant enzymes in thymocytes, also showing an unexpected regulation by dexamethasone of these mRNA. Both an effect of melatonin on the general machinery of apoptosis and a possible regulation of the expression of the cell death related genes bcl-2 and p53 are shown not to be involved. We found melatonin to down-regulate the mRNA for the glucocorticoid receptor in thymocytes (glucocorticoids up-regulate their own receptor). The decrease by melatonin of mRNA levels for this receptor in IM-9 cells (where glucocorticoids down-regulate it) demonstrates that melatonin actually down-regulates glucocorticoid receptor. These findings allow us to propose the effects of melatonin on this receptor as the likely mediator of its thymocyte protection against dexamethasone-induced cell death. This effect of melatonin, given the oxidant properties of glucocorticoids, adds another mechanism to explain its antioxidant effects.

Animals↗

Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson's disease.

It was recently reported that low doses of 6-hydroxydopamine (6-OHDA) induce apoptosis of naive (undifferentiated) and neuronal (differentiated) PC12 cells, and this system has been proposed as an adequate experimental model for the study of Parkinson's disease. The mechanism by which this neurotoxin damages cells is via the production of free radicals. Given that the neurohormone melatonin has been reported 1) to be a highly effective endogenous free radical scavenger, 2) to increase the mRNA levels and the activity of several antioxidant enzymes, and 3) to inhibit apoptosis in other tissues, we have studied the ability of melatonin to prevent the programmed cell death induced by 6-OHDA in PC12 cells. We found that melatonin prevents the apoptosis caused by 6-OHDA in naive and neuronal PC12 cells as estimated by 1) cell viability assays, 2) counting of the number of apoptotic cells, and 3) analysis and quantification of DNA fragmentation. Exploration of the mechanisms used by melatonin to reduce programmed cell death revealed that this chemical mediator prevents the 6-OHDA induced reduction of mRNAs for several antioxidant enzymes. The possibility that melatonin utilized additional mechanisms to prevent apoptosis of these cells is also discussed. Since this endogenous agent has no known side effects and readily crosses the blood-brain-barrier, we consider melatonin to have a high clinical potential in the treatment of Parkinson's disease and possibly other neurodegenerative diseases, although more research on the mechanisms is yet to be done.

Animals↗

Allergic reactions associated with airborne fish particles in IgE-mediated fish hypersensitive patients.

We evaluated the clinical characteristics found in 21 children who showed allergic reactions upon incidental inhalation of fish odors or fumes, from 197 diagnosed with IgE-mediated fish hypersensitivity. Allergic reactions to fish via ingestion began in most patients (86%) within the first 24 months of life. The vast majority (19/21) of patients showed cutaneous symptoms, either alone or, less frequently, associated with other clinical manifestations. Hake and flounder were the species of fish most frequently implicated in eliciting clinical manifestations upon ingestion. After diagnosis, all these patients were placed on a strict fish-avoidance diet. During this period of avoidance, patients reported allergic reactions (mean age 7 years) after incidental exposure to airborne fish odors or fumes. Clinical manifestations through inhalation were respiratory (mainly wheezing) in 12 patients and cutaneous (mainly urticaria) in nine patients. Nineteen of 21 patients reported three or more episodes upon exposure to fish aerosols; in most cases, these episodes occurred at home when other people were eating fish. In conclusion, incidental inhalation of fish odors or fumes could play an important role in accidental and unknown encounters with fish in children on fish-avoidance diets for fish IgE-mediated hypersensitivity. Such exposures could elicit clinical symptoms and could have some effect in delaying the development of tolerance.

Air Pollutants↗

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.

Age Factors↗

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.

Amylases↗

Cultured neonatal islet transplants in alloxan-treated and spontaneously diabetic rats.

Neonatal Fischer-344 (FSH) islets isolated by a nonenzymatic method have been shown to survive indefinitely in Wistar/Furth (WF) recipients. We have applied this islet isolation method to six different donor strains and transplanted the resulting islets across 20 different strain combinations. We report the variable results obtained, with FSH being the most consistently successful donor strain and ACI being the best recipient strain. Based on the complete success of culture-derived FSH (Rt1lv1) and BN (Rt1n) transplants to WF (Rt1u) recipients, we used this system to test the MHC-restriction of autoimmune beta cell destruction in the BB/Wor rat (Rt1u). Culture-derived FSH and/or WF islets were transplanted to pre-diabetic BB/Wor recipients. Animals were sacrificed at the onset of disease or up to 33 days after disease onset. No immune response developed in FSH and WF grafts in non-diabetic animals. In diabetic animals, all FSH grafts and 12/14 WF grafts survived intact, although some grafts exhibited mild-moderate infiltration which was more pronounced in MHC-matched grafts. In two animals which developed severe hyperglycemia and ketosis, the FSH grafts were found to be intact while the WF grafts were destroyed by disease recurrence. In addition, FSH and BN islets were transplanted to diabetic BB/Wor recipients. Three of four FSH islet recipients and two of four BN islet recipients were reversed of their disease. Neither these nor the non-reversed animals showed signs of disease recurrence in the MHC-mismatched grafts. Therefore, in these studies, MHC-mismatched cultured grafts survived well and were capable of reversing the diabetic syndrome in spontaneously diabetic BB/Wor recipients.

Animals↗