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Biomedical subjects

V Silano

Publications and source records attributed to V Silano.

At least 19 recordsLinked to original sources

Mannan and oligomers of N-acetylglucosamine protect intestinal mucosa of celiac patients with active disease from in vitro toxicity of gliadin peptides.

Wheat flour and other cereals toxic for celiac patients contain an alcohol-soluble protein fraction that, under experimental conditions simulating in vivo protein digestion, yields peptides that agglutinate undifferentiated K 562(S) cells. In contrast, cereals well tolerated in celiac disease (i.e., rice and maize) do not. Furthermore, purified A-gliadin peptides that damage in vitro-cultured flat celiac mucosa are powerful agglutinins for K 562(S) cells, whereas A-gliadin peptides that do not show any adverse in vitro effect on celiac intestine lack agglutinating activity. Mannan, acetylglucosamine, and its oligomers (N,N'-diacetylchitobiose and N,N',N"-triacetylchitotriose) were able to prevent and reverse cell agglutination induced by peptides from all the toxic cereals. Moreover, mannan and N,N',N"-triacetylchitotriose exhibited a protective effect on intestinal mucosa specimens of patients with active celiac disease cultured with wheat protein-derived peptides. These data are consistent with the hypothesis that the agglutinating and toxic peptides are bound by carbohydrates.

Acetylglucosamine

Intestinal mucosa of celiacs in remission is unable to abolish toxicity of gliadin peptides on in vitro developing fetal rat intestine and cultured atrophic celiac mucosa.

Subfraction 2R of fraction 9 from a peptic-tryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1-0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction 2R, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission.

Animals

Animal species and strains used to test chemical carcinogens: results of a preliminary study.

The selection of animal species sufficiently representative of human physiological processes and sensitive to a wide spectrum of toxic agents is one of the major problems in toxicology. The aim of this study, based on animal experimental carcinogenesis data available from the literature, was the identification of animal strains most often used in experimental carcinogenesis. The analysis was limited to experiments on chemicals or groups of chemicals classified by IARC under Group 1 of carcinogenic risk (sufficient evidence). For each experiment considered in the study, data concerning animal species, strains, and substrains (whenever possible) were collected. The data analysis has shown that approximately 83 and 61% of the considered carcinogens were tested positively in mouse and rat, respectively, and that A, Swiss, and C3H mouse strains and Sprague-Dawley and Wistar rat strains were used most often. The study has shown that practically all decisions regarding the carcinogenicity of substances are based on the response of only two animal species (mouse and rat). Therefore, a clear and complete understanding of carcinogenicity mechanisms in these species becomes essential in order to extrapolate results to man.

Animals

Prevention by mannan and other sugars of in vitro damage of rat fetal small intestine induced by cereal prolamin peptides toxic for human celiac intestine.

Peptic-tryptic-cotazym and peptic-tryptic digests were obtained, simulating in vivo protein digestion, from pure "bread" wheat gliadins and from rye, barley, and oats prolamine and tested on small intestine cultures from fetal rats. When tested at a concentration of 0.1 mg of peptides/ml of culture medium the peptic-tryptic-cotazym and peptic-tryptic digests of gliadin and prolamines were very active in slowing in vitro development of fetal rat intestine and in increasing the occurrence and severity of degenerative changes. The ability of some sugars to interfere with inhibition of fetal intestinal morphogenesis induced by these peptides was also tested. Mannan at a concentration of 0.1 mM was effective in allowing intestinal morphogenesis to take place in the presence of prolamine peptic-tryptic-cotazym and prolamine peptic-tryptic digests of the four toxic cereals. Some oligomers of N-acetyl-glucosamine were also effective in blocking the inhibitory effect of "bread" wheat gliadin peptides. These data are compatible with the hypothesis that some sugars may exert a protective effect on the toxic activity of cereal prolamin peptides on the human celiac intestine.

Animals

Biochemical, nutritional and toxicological aspects of alpha-amylase inhibitors from plant foods.

This paper is a critical review of the available data on plant protein inhibitors active either on animal or endogenous plant alpha-amylases. The First Section is a review of available data on molecular properties of the purified inhibitors from cereals, legumes, colocasia and yam. The Second Section deals with properties of amylase-inhibitor complexes and parameters controlling the interaction between amylases and inhibitors. The Third Section discusses possible roles of these inhibitors in the plant, whereas Section Four focuses on nutritional and toxicological significance of amylase inhibitors for human beings and other mammals. Lastly Section Five examines some applications in medicine of alpha-amylase inhibitors from plants.

Amino Acid Sequence

The chemical risk management process in Italy. A case study: the Seveso accident.

This paper describes, by means of a unique case study, i.e. the ICMESA accident at Seveso, the process of chemical risk management in Italy under emergency conditions which involved more than 200,000 people and about 1800 ha of a densely populated area. The paper also deals with the aims, the results, and the organizational aspects of the medium- and long-term activities that were carried out to rehabilitate the affected ecological and social systems. Problems of co-ordination at different levels (national, regional, provincial and local), as well as of interaction of decision-makers with scientific and technical experts and local staff responsible for action, have also been addressed.

Accidents

Ecotoxicological profile of xylenes. Working Party on Ecotoxicological Profiles of Chemicals.

The xylenes (o, m, p), which are produced in large amounts and widely used, must be considered as environmental contaminants, as they have been identified in the atmosphere of many countries. Their acute and chronic toxicity in mammals is moderate. Mutagenic and teratogenic properties can be excluded. Carcinogenic potential has been at present inadequately studied. In man some disturbances are evident at the concentration of 45 ppm. Hepatic metabolism is a valid process of detoxification and its high rate limits the risk of accumulation of the xylenes in adipose tissue. Ecotoxicological data refer almost exclusively to water. No long-term tests have been made. However, the high volatility, elevated elimination, and the low factor of accumulation suggest the impact on aquatic environment should be limited. Xylenes are easily biodegraded by many microorganisms. Photoxydation is one of the main degradation processes, responsible for the disappearance of the xylenes from the atmosphere.

Animals

In vitro activation of adenylate cyclase of atrophic celiac intestinal mucosa by wheat gliadin-derived peptides.

In order to demonstrate that gliadin peptides may interact with cell membranes of celiac small intestinal mucosa, the capacity of these peptides to activate the cell membrane enzyme adenylate cyclase was tested. The addition of peptides from bread wheat purified A-gliadin and whole gliadin (proteins that are toxic for celiac patients) enhanced the adenylate cyclase activity of crude cell membrane preparations obtained from atrophic small intestinal mucosa of celiac patients. No activation of adenylate cyclase of this tissue was observed with peptides from proteins nontoxic for celiac patients (bread wheat albumin and maize prolamin). Gliadin peptides did not activate adenylate cyclase of morphologically normal small intestinal mucosa from normal subjects or from celiac patients in remission. These results, therefore, suggest that peptides from bread wheat gliadin may interact with cell membrane of atrophic small intestinal mucosa of celiac patients.

Adenylyl Cyclases

Toxicity mechanisms of wheat and other cereals in celiac disease and related enteropathies.

This paper is a critical appraisal of current theories on the mechanisms of toxicity of wheat and other cereals in celiac disease and some related enteropathies. The "peptidase deficiency," "primary immune defect," and "gluten-lectin" theories on celiac disease are examined and critically discussed on the basis of the relevant data available in 88 references. Special attention has been paid in this review to the nature of the cereal components triggering the appearance of toxic symptoms and signs in celiac disease as well as to underlying action mechanisms. The gluten-lectin theory is the one best able to explain, in addition to celiac disease, some secondary intolerances that may occur in temporarily predisposed individuals as a consequence of several causes, including viral hepatitis and intestinal infections, as well as the occurrence of intestinal lesions in healthy subjects administered very high amounts of gluten.

Animals

Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy.

This paper is a progress report of the epidemiologic work carried out under the supervision of the Lombardy Regional Authority during the two years elapsed from the accident in a TCP-producing factory (ICMESA) in Meda (Italy), which resulted in the contamination of several towns of a large, densely populated area called the Brianza di Seveso with a total population of 220,000 inhabitants. A wide follow-up program is in progress in the Seveso area; it includes a clinical screening of the population living in the contaminated area and longitudinal and systematic health control of different groups at risk; a long-term morbidity cohort study has been also undertaken. TCDD exposure following the ICMESA accident resulted in an increased chloracne frequency. Neurologic examinations showed both signs of idiopathic subclinical neurologic damage and cases of clinically detectable idiopathic polyneuropathy in adults. A limited percentage of idiopathic hepatomegaly was reported to be present on clinical investigation; no information, however, is given on the criteria by which the hepatomegaly was investigated. Some alterations were observed in some exposed people in one or more liver tests (mainly transaminases and gamma-GT). So far, immunologic investigations, cytogenetic examination and embryomorphology analysis on cases of therapeutical or spontaneous abortions have not given abnormal results.

Abortion, Spontaneous

Toxicity of wheat flour proteins and protein-derived peptides for in vitro developing intestine from rat fetus.

A peptic-tryptic-cotazym (PTC) digest of a crude wheat gliadin preparation was obtained under experimental conditions simulating in vivo protein digestion and then fractionated into 10 peaks by ion-exchange chromatography. PTC-gliadin digest and one of its subfractions (coded as fraction 9 according to its elution pattern) were very active in inhibiting in vitro development and morphogenesis of small intestine from 17- and 18-day-old rat fetuses, whereas they were harmless for the culture of jejunum from 21-day-old fetuses. PTC-digest also induced extensive tissue degeneration and necrosis of in vitro cultured small intestinal mucosa from patients with active celiac disease (gluten-induced entheropathy), but did not cause any detectable effect on histologically normal human small intestinal mucosa. Some wheat albumin and gliadin fractions were also tested on in vitro developing small intestine from 17-day-old rat fetus. Among all the tested protein fractions, only one gliadin fraction (coded as alpha 10-gliadin from its gel electrophoretic mobility) exhibited a toxic effect; morphologic alterations induced by alpha 10-gliadin were similar to those induced by PTC-digest and fraction 9.

Albumins