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The development of testes and genital accessory organs, the plasma testosterone concentration and the reactivity of seminal vesicles to catecholamines were studied in rats rendered cryptorchid at the time of prepubertal growth. The wet weights of the accessory organs and the testosterone concentrations were reduced and corresponded to those observed after castration. The response of the seminal vesicle to adrenaline and noradrenaline, but not to methoxamine, showed a reduction in sensitivity. It is suggested that an enhancement of neuronal catecholamine uptake may have occurred. The results also reinforce the idea that development, plasma testosterone concentration and reactivity of seminal vesicles are independent phenomena. In cryptorchidism, despite the consequences arising from the maintenance of the testes at body temperature rather than at the lower temperature of the scrotum, the age that the rat is rendered cryptorchid is also of fundamental importance. Copyright 1993, 1999 Academic Press

Background & Aims: Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease. Methods: Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. Results: CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm^2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm^2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody. Conclusions: In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease. GASTROENTEROLOGY 1998;115:564-572

Secretory activity induced by stimulation of alpha-adrenergic, beta-adrenergic, and muscarinic cholingeric receptors and by dibutyryl cAMP and 8-bromo cGMP has been investigated in rat submandibular tissue slices. Isoproterenol produced a sialic acid secretion from the acinar cells that was inhibited by propranolol, but not by phenoxybenzamine or atropine. Dibutyryl cAMP produced a sialic acid secretion from the acinar cells that was not inhibited by propranolol, phenoxybenzamine, or atropine. Both norepinephrine and acetylcholine produced significant secretion of sialic acid but at a reduced efficacy. Norepinephrine stimulated both peptide hydrolase secretion from the granular duct cells and a release of K+ from the acinar cells. Both actions were inhibited by phenoxybenzamine, but not by propranolol or atropine. Acetylcholine stimulated a minimal secretion of peptide hydrolase from the granular duct cells and a significant release of K+ from the acinar cells. The norepinephrine- and acetylcholine-stimulated release of K+ was increased after the addition of 1 mM ouabain. High concentrations of 8-bromo cGMP induced a K+ efflux that was not inhibited by phenoxybenzamine or atropine. Vacuolation of the acinar cells was correlated with K+ release.

A bleeding syndrome induced by contact with Lonomia achelous caterpillars was first described in Venezuela in 1967. It was reported in the early eighties in North Brazil among rubber latex collectors. From 1989 a very high incidence has been observed in South Brazil due to contact with L. obliqua. Symptoms are similar in all accidents, starting with a burning pain after contact followed by erythema, edema and heat; blisters, headache, nausea, and vomit may also appear. The onset of a hemorrhagic syndrome one to twelve hours later manifests as hematoma throughout the body, epistaxis, bleeding from mucosa and from healing scars, with low plasma fibrinogen concentrations. An intense fibrinolytic activity has been detected in the blood of the patients.Contact of Swiss rats with Lonomia obliqua caterpillars or intradermal injections of Lonomia hair extracts into rats induced blood incoagulability within one to two hours. Studies with these extracts demonstrated a dose-dependent procoagulant activity, higher on rat than on human plasma and potentiated by calcium. On purified fibrinogen, the extracts are weakly active only when calcium is present. The procoagulant activity of the extract was slightly inhibited by heparin and better inhibited by hirudin.The mechanism of the overwhelming fibrinolytic state observed in patients has still to be elucidated since it is not explained by in vitro tests with Lonomia obliqua hair extracts on a chromogenic substrate specific for plasmin and there is hardly any plasminogen activator-like activity in these extracts.

Summary: Cystic fibrosis (CF) and heterozygote sera stimulate a significant K+efflux from rat submandibular gland fragments in the presence of 1 mM ouabain. This sensitive parameter can be maximally stimulated by as little as 0.5% CF serum and is inhibited by the calcium channel blocker D600 and EGTA. Specific receptor blockers propranolol, phenoxybenzamine or atropine do not inhibit the CF serum-stimulated K+efflux and agonists do not supramaximally stimulate K+efflux when added with serum. CF serum-induced K+efflux did not result in the leakage of lactic dehydrogenase into the bathing media nor did it mimic the action of the calcium ionophore A23187 when added in the presence of D600. In addition, ultrafiltrates of CF serum (less than 10,000 daltons) also stimulated K+efflux from rat submandibular gland tissue fragments.Speculation: Cystic fibrosis serum factor(s) may be altering membrane permeability to calcium which results in the release of K+from rat submandibular gland fragments.

There are two kinds of tryptamine receptor in the guinea‐pig ileum, namely the M receptors which can be blocked with morphine and the D receptors which can be blocked with dibenzyline. Atropine, an atropine‐like drug, cocaine, and methadone inhibit effects due to the M receptors, even after dibenzyline, but have no additional effect after morphine. Lysergic acid diethylamide, dihydroergotamine and 5‐benzyloxygramine inhibit effects due to the D receptors, even after morphine, but have no additional effect after dibenzyline. The M receptors are probably in the nervous tissue and the D receptors are probably in the muscles.

To investigate the prevalence and clinical and genetic patterns of celiac disease (CD) among siblings of CD patients, 103 siblings and one twin of 80 celiac children were evaluated by means of their clinical history, physical examination, blood indices of nutritional status, and antigliadin antibodies (AGA). Antiendomysium antibody (AEA) levels were determined in 70 patients and 85 subjects were human leucocyte antigen (HLA) typed. On the basis of clinical or laboratory data or both, 21 siblings (20.2%) were submitted to intestinal biopsy, whereas intestinal biopsy in six siblings with positive serologic screening (AGA lgA or AEA or both) was not performed because of parental refusal. In a high percentage of cases (18%), all on a gluten‐containing diet, the intestinal mucosa was atrophic, and CD was subsequently diagnosed. Because we could not submit all the siblings to intestinal biopsy, this figure could underestimate the real prevalence of the disease in our series; consequently, it was not possible to calculate accurately the sensitivity and specificity of AGA and AEA. Nevertheless, AEA (positive in all the nine siblings with mucosal atrophy), followed by AGA IgA, proved to be the best screening for CD. Eighteen of 19 CD siblings showed HLA‐predisposing antigens. Among the 19 CD siblings, one showed a typical form with gastrointestinal symptoms, two had short stature, one suffered from recurrent vomiting, and in 15, the disease was clinically silent. On the contrary, among siblings who were first diagnosed (index cases), the majority (73.7%) had a typical from of CD, and no clinically silent cases were observed. We did not find any difference between index cases and CD siblings in food habits and distribution of HLA antigens. In 15 of 18 cases, the sibling diagnosed subsequently was the older one. Finally, the typical form of CD was significantly more frequent among the younger brother than the older. In conclusion, the high prevalence of the silent form of CD in our cases indicates that siblings of CD subjects should always be screened for CD. The combination of AGA IgA and AEA represent a good screening method to use in selecting children for the intestinal biopsy.

The authors propose a relactation technique to be used with mothers of children readmitted to the Campinas Maternity, to the Clinics of the Medical School (UNICAMP) and to the Institute of Pediatrics (UNICAMP) who were not nursing their babies at the breast for several reasons. The authors put into practice a simple method consisting of stimulating breast suction by means of an adult type naso-gastric catheter, adapted to the nipple, through which complementary feeding is provided using milk from a human-milk bank or cow milk, while the lactic production is not restored. The technique is mainly based in intense psychological help and counseling, frequent and repeated suctions of the nipple to stimulate the production of prolactin, as well as complementary feeding to reinforce suction.

It has been confirmed that cryptorchidism may affect the control mechanism of gonadotrophin secretion. This has been based on morphological aspects of the adenohypophysis of cryptorchid rats which have shown an increase in basophilic and vacuolated basophilic cells, an increase known to be related to the production of gonadotrophin. The morphological alterations observed in the testes, prostates, seminal vesicles and ductus deferentes of these cryptorchid animals, the quiescence and the responses of their seminal vesicles and ductus deferentes to sympathomimetic and parasympathomimetic drugs indicated that these cryptorchid animals may be somewhere between normal and castrated rats, although not equidistant from either. Comparison of wet weights and of occurrence of spontaneous contractions, and determination of drug parameters in seminal vesicles and ductus deferentes taken from normal, castrated or cryptorchid rats, suggested that the development and the spontaneous or the pharmacological responses of male accessory organs of reproduction are independent phenomena.

Vasopressor and steroidogenic effects of synthetic angiotensin [Asn1, Val5] AII and Bothrops jararacacrude renin were compared in anesthetized Bothrops jararacasnakes. While the intravenous infusion of [Asn1, Val5] AII (2.0 μg/kg/min) promoted an arterial blood pressure elevation of 18.2 ± 2.7 mmHg but had no detectable steroidogenic effect, Bothrops jararacacrude renin (0.4 ml/kg/min) induced an increase of both, mean arterial blood pressure (12.8 ± 2.0 mmHg) and plasma corticosterone concentration (85.8 ± 20.1 ng/ml). In vitroexperiments indicated that the relative potencies of synthetic angiotensins were [Asn1, Val5] AII < [Asp1, Ile5] AII = (Asp1, Val5] AII in B. jararacauterus, but [Asn1, Val5] AII > (Asp1Ile5] AII in the guinea-pig ileum. The results indicate that the renin-angiotensin system may be important for the control of blood pressure and steroidogenesis in the snake, although some differences in the structural requirements for angiotensin action occur in this animal when compared to mammals.

BACKGROUND & AIMS: Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens and possibly showing milder changes of mucosal architecture. Ten patients with symptoms suggesting celiac disease and serum antiendomysium antibodies with normal mucosal architecture were studied. METHODS: Immunohistochemical detection of mucosal immune activation and HLA typings were performed. RESULTS: Mucosal immune activation, with normal mucosal architecture and normal gamma/delta+ intraepithelial lymphocytes counts, was found on a gluten-containing diet. In 3 of 6 patients, multiple biopsy specimens showed one sample with severe villous atrophy. Clinical and immunomorphologic features were strictly gluten dependent. The mucosal immune activation was elicited in vitro by gliadin. Only 4 patients had the typical HLA typing of celiac disease. CONCLUSIONS: Gluten-sensitive celiac-like symptoms may occur in patients with serum antiendomysium antibodies, apparently normal intestinal mucosa, and HLA typing not commonly associated with celiac disease. These patients should undergo multiple biopsies, and signs of immunologic activation should be sought accurately; in the presence of mucosal immune activation, a trial with a gluten-free diet should be encouraged to detect gluten dependency. In vitro immunologic response of small intestinal mucosa to gliadin may support the diagnosis of gluten-sensitive enteropathy. (Gastroenterology 1996 Sep;111(3):608-16)

An Entic Haplorthod, cropped for many years to potatoes, was used for plant pot and chemical studies involving the effects of pH increases by liming on the availability of B and P to Zea maysL. and Medicago sativaL.

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio <31 as index of intestinal atrophy. It is noticeable that a selective IgA deficiency was present in only 9 of 18 EMA IgG1 positive children. In addition, clinical symptoms, EMA IgG1, and mucosal atrophy disappeared after 8–10 mo on a gluten-free diet. Neither EMA IgA nor EMA IgG1 were detected in the children in the control groups. The other 12 children in study group showed no histologic abnormalities and were EMA IgG1 negative. In this study, we reveal a group of EMA IgG1 CD children without IgA deficiency. The diagnosis was based on the presence of gluten-dependent typical serological and histologic features of CD. Our data suggest that EMA IgG1 determination could be a new tool in the diagnostic workup of CD, useful in avoiding possible misdiagnosis.

A 15-month-old infant with a systolic cardiac murmur developed an episode of nonsustained ventricular tachycardia during transthoracic echocardiography. A large intracardiac mass, which widened the interventricular septum causing right ventricular outflow tract obstruction, was seen and confirmed by magnetic resonance imaging. A cardiac fibroma was suspected, and because of the risk of life-threatening arrhythmias, surgery was rapidly considered. Despite the challenging location, the tumor was completely and successfully resected. Microscopic examination confirms the diagnosis of ventricular fibroma.

Accidental induction of convulsions by using repetitive transcranial magnetic stimulation (rTMS) has been reported to have occurred in 6 normal voluntary subjects, in 1 patient with depression and in 1 patient who had temporal lobe epilepsy, with secondary generalization. In addition, 3 other cases have been published relating its use with seizure induction and in 1 case, using 1-Hz stimulation. In this paper, we report a patient who was participating in a protocol for the use of rTMS in chronic pain, with stimulation in the motor cortex, who developed a generalized seizure in the fifth application. Intertrain interval was within safety guidelines, but the combination of 10 Hz for 10 seconds was excessive and must be considered the main cause for the episode. No further complication has been noted after she was withdrawn from the study protocol.