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PA38 THE NATURAL HISTORY OF CELIAC DISEASE
XVII National Congress SIGENP Abstracts / Digestive and Liver Disease 42S (2010), S321–S376 found. Among these, two females no-responders to im vitamin K, one with deficiency of XI factor, another with lupus anticoagulant antibodies, were found. All children but the three previously described, improved after im vitamin K administration. Conclusions: The results of our study, performed in a large series of coeliac children and adolescents, demonstrate a prevalence of prolonged INR and prolonged PTT of 6% and 7%, respectively. However, no patient showed any clinical signs of altered coagulation. Coagulation disorders should be related to malabsorption, as suggested by improvement after intramuscular vitamin K administration. This study suggests that there is need for coagulation disorders screening among patients with coeliac disease before performing the intestinal biopsies, in order to correct vitamin K impairment and exclude deficit of specific coagulation factors.
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Methods: Equimolar sodium butyrate (100 mg/kg) and BuToRo (212 mg/kg) doses were administered orally 30 min before formalin or acetic acid injection. Results: Acute administration of sodium butyrate or BuToRo resulted ineffective in reducing pain both in acute or visceral models. Repeated treatments (once a day for three days) of BuToRo, but not of sodium butyrate, resulted effective in reducing the first phase of paw licking (48% inhibition vs control, p<0.01, n=12), whereas it was ineffective in reducing the second phase. In the model of visceral pain both drugs resulted active in reducing acetic acid-induced writhing. Although BuToRo resulted more effective if compared with sodium butyrate (-68% vs -33% respectively, p<0.01, n=12). Conclusions: Our results support the hypothesis that butyrate is involved in pain signalling. In particularly single administration are non effective in both pain models, whereas the increase of plasmatic levels of butyrate due to repeated treatment, results in an analgesic effect on acute phase of formalin and acetic acid-induced visceral pain. Our results strongly suggest the involvement of butyrate in the control of acute sensorial pain initiation whereas the inflammatory pain seems to be not controlled by butyrate levels. Further studies will need to better understand this peculiar effect.
A. Pacilio, E. Piccolo, M.G. Scala, R. Auricchio Università degli Studi di Napoli Federico II Background and aims: Celiac disease is a multifactorial disorder that results from environmental factors and a genetic predisposition. The aim of this study is to describe the natural history of celiac disease to evaluate the role of environmental factors. Methods: A retrospective case/control study was performed on 278 children from 6 to 48 months of age (139 celiacs and 139 age matched healthy controls) in order to evaluate the weight of breast-feeding, gluten’s weaning, month of birth and prevalence of clinical events in the first years. Results: The majority of celiacs presented with atypical clinical manifestation also in this age range (unexplained iron-deficiency anemia, fatigue, arthritis, bone loss or osteoporosis, dermatitis, failure to thrive) or were asymptomatic. Female sex and other autoimmune disorders were more frequent in cases than in controls. Among the 278 children, 30 (21.6%) celiacs and 13 (9.8%) controls weren’t breastfed; 36 (26.3%) celiacs and only 1 (0.8%) controls were weaned before the 4th month or after the 7th month of age. Among celiac children, 76 (54.7%) were born in the autumn season and this correlates with an increase of the risk of infections that modify the intestinal permeability; in fact, the analysis of the first year of life showed that celiac children had earlier gastrointestinal infections. In our cohort, failure to thrive, diarrhea and anorexia in the first year of life (independently of the symptoms at diagnosis) were more frequent in the celiacs than in the controls: failure of thrive: 33 (6%) vs 1 (1%); diarrhea: 8 (1.4%) vs 4 (0.7%); anorexia: 12 (2.2%) vs 0 (0%). Conclusion: This study confirms that atypical forms of this disorder became more frequent than in the recent past and that the environmental risk factors can influence the phenotype and the clinical aspects of CD especially regarding an early exposure to infections.
PA39 ANALGESIC PROPERTIES OF N-(1-CARBAMOYL-2-PHENYL-ETHYL)BUTYRAMIDE, A NEW SYNTHETIC BUTYRATE PRODRUG IN AN ANIMAL MODEL OF ACUTE PERIPHERAL AND VISCERAL PAIN R. Russo a , O. Sasso a , G. D’Agostino a , A. Iacono a , G. Mattace Raso a , M. Palomba a , R. Meli a , R. Berni Canani b,c , A. Calignano a
PA40 EFFECTS OF N-(1-CARBAMOYL-2-PHENYL-ETHYL)BUTYRAMIDE, A NEW SYNTHETIC BUTYRATE PRODRUG ON GASTROINTESTINAL TRANSIT TIME MODULATION R. Russo a , O. Sasso a , G. D’Agostino a , A. Iacono a , G. Mattace Raso a , M. Palomba a , R. Meli a , R. Berni Canani b,c , A. Calignano a a Department
of Experimental Pharmacology, Naples; b Department of Pediatrics and University of Naples “Federico II”, Naples; c European Laboratory for the Investigation on Food Induced Diseases, University of Naples “Federico II”, Naples Introduction and aims: Butyrate is the most important short chain fatty acid produced by colonic microflora. Butyrate is considered a promising drug for the treatment of many gastrointestinal diseases but the extremely unpleasant taste and odour make the oral administration of currently available butyratebased products extremely difficult. We have tested the effects of a new butyrate derivate synthesized in our laboratory in comparison to equimolecular doses of sodium butyrate on in intestinal transit time in mice. Methods: Equimolar sodium butyrate (100 mg/kg) or N-(1-carbamoyl-2phenyl-ethyl)butyramide (BuToRo) (212 mg/kg) doses were administered orally 30 min before a charcoal meal. Thirty minutes after mice were sacrificed and the length travelled by the charcoal meal was measured. Acute treatment of sodium butyrate or BuToRo were equally able to reduce intestinal motility (-38% vs -43%, NS). Then we investigated the effects on intestinal transit time in a model of castor oil–induced diarrhea in mice. Results: The effect of BuToRo on intestinal transit time was more pronounced compared to that observed using sodium butyrate (-75% vs -27%, p<001). In addition, the effect of BuToRo on total stool volume in the first 24 h was more pronounced if compared to that seen with sodium-butyrate (64% vs -20% of reduction in total stool volume respectively, p<0.001). Conclusions: Our results indicate that in basal condition sodium butyrate and BuToRo are equally active, whereas in the presence of an intestinal inflammatory state BuToRo was more active in reducing peristalsis and stool volume. These data support a potential therapeutic role for this new compound in the treatment of inflammatory diarrhea.
a Department
of Experimental Pharmacology, Naples; b Department of Pediatrics and University of Naples “Federico II”, Naples; c European Laboratory for the Investigation on Food Induced Diseases, University of Naples “Federico II”, Naples Background and aims: Evidences suggests a potential role elicited by short chain fatty acids (SCFAs) in regulating visceral pain. We comparatively tested the effects of a new synthetic butyrate derivative, N-(1-carbamoyl-2-phenylethyl)butyramide (BuToRo), and of sodium butyrate (one of the main SCFAs produced by the colonic microflora) in two animal models of acute peripheral pain perception (formalin-induced paw licking in mice) and visceral pain (acetic acid-induced writhing in mice).
PA41 USE OF AN AMINO-ACID-BASED FORMULA IN THE TREATMENT OF COW’S MILK PROTEIN ALLERGY PRESENTING AS ALLERGIC PROCTOCOLITIS R. Francavilla, R. Sardaro, C. Fontana, S. Fico, F. Indio Università degli Studi di Bari Background: Food allergy to cow’s milk proteins (APLV) is frequently found in young infants and may present as proctocolitis. Treatment is by starting
PA38 THE NATURAL HISTORY OF CELIAC DISEASE
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Methods: Equimolar sodium butyrate (100 mg/kg) and BuToRo (212 mg/kg) doses were administered orally 30 min before formalin or acetic acid injection. Results: Acute administration of sodium butyrate or BuToRo resulted ineffective in reducing pain both in acute or visceral models. Repeated treatments (once a day for three days) of BuToRo, but not of sodium butyrate, resulted effective in reducing the first phase of paw licking (48% inhibition vs control, p<0.01, n=12), whereas it was ineffective in reducing the second phase. In the model of visceral pain both drugs resulted active in reducing acetic acid-induced writhing. Although BuToRo resulted more effective if compared with sodium butyrate (-68% vs -33% respectively, p<0.01, n=12). Conclusions: Our results support the hypothesis that butyrate is involved in pain signalling. In particularly single administration are non effective in both pain models, whereas the increase of plasmatic levels of butyrate due to repeated treatment, results in an analgesic effect on acute phase of formalin and acetic acid-induced visceral pain. Our results strongly suggest the involvement of butyrate in the control of acute sensorial pain initiation whereas the inflammatory pain seems to be not controlled by butyrate levels. Further studies will need to better understand this peculiar effect.
A. Pacilio, E. Piccolo, M.G. Scala, R. Auricchio Università degli Studi di Napoli Federico II Background and aims: Celiac disease is a multifactorial disorder that results from environmental factors and a genetic predisposition. The aim of this study is to describe the natural history of celiac disease to evaluate the role of environmental factors. Methods: A retrospective case/control study was performed on 278 children from 6 to 48 months of age (139 celiacs and 139 age matched healthy controls) in order to evaluate the weight of breast-feeding, gluten’s weaning, month of birth and prevalence of clinical events in the first years. Results: The majority of celiacs presented with atypical clinical manifestation also in this age range (unexplained iron-deficiency anemia, fatigue, arthritis, bone loss or osteoporosis, dermatitis, failure to thrive) or were asymptomatic. Female sex and other autoimmune disorders were more frequent in cases than in controls. Among the 278 children, 30 (21.6%) celiacs and 13 (9.8%) controls weren’t breastfed; 36 (26.3%) celiacs and only 1 (0.8%) controls were weaned before the 4th month or after the 7th month of age. Among celiac children, 76 (54.7%) were born in the autumn season and this correlates with an increase of the risk of infections that modify the intestinal permeability; in fact, the analysis of the first year of life showed that celiac children had earlier gastrointestinal infections. In our cohort, failure to thrive, diarrhea and anorexia in the first year of life (independently of the symptoms at diagnosis) were more frequent in the celiacs than in the controls: failure of thrive: 33 (6%) vs 1 (1%); diarrhea: 8 (1.4%) vs 4 (0.7%); anorexia: 12 (2.2%) vs 0 (0%). Conclusion: This study confirms that atypical forms of this disorder became more frequent than in the recent past and that the environmental risk factors can influence the phenotype and the clinical aspects of CD especially regarding an early exposure to infections.
PA39 ANALGESIC PROPERTIES OF N-(1-CARBAMOYL-2-PHENYL-ETHYL)BUTYRAMIDE, A NEW SYNTHETIC BUTYRATE PRODRUG IN AN ANIMAL MODEL OF ACUTE PERIPHERAL AND VISCERAL PAIN R. Russo a , O. Sasso a , G. D’Agostino a , A. Iacono a , G. Mattace Raso a , M. Palomba a , R. Meli a , R. Berni Canani b,c , A. Calignano a
PA40 EFFECTS OF N-(1-CARBAMOYL-2-PHENYL-ETHYL)BUTYRAMIDE, A NEW SYNTHETIC BUTYRATE PRODRUG ON GASTROINTESTINAL TRANSIT TIME MODULATION R. Russo a , O. Sasso a , G. D’Agostino a , A. Iacono a , G. Mattace Raso a , M. Palomba a , R. Meli a , R. Berni Canani b,c , A. Calignano a a Department
of Experimental Pharmacology, Naples; b Department of Pediatrics and University of Naples “Federico II”, Naples; c European Laboratory for the Investigation on Food Induced Diseases, University of Naples “Federico II”, Naples Introduction and aims: Butyrate is the most important short chain fatty acid produced by colonic microflora. Butyrate is considered a promising drug for the treatment of many gastrointestinal diseases but the extremely unpleasant taste and odour make the oral administration of currently available butyratebased products extremely difficult. We have tested the effects of a new butyrate derivate synthesized in our laboratory in comparison to equimolecular doses of sodium butyrate on in intestinal transit time in mice. Methods: Equimolar sodium butyrate (100 mg/kg) or N-(1-carbamoyl-2phenyl-ethyl)butyramide (BuToRo) (212 mg/kg) doses were administered orally 30 min before a charcoal meal. Thirty minutes after mice were sacrificed and the length travelled by the charcoal meal was measured. Acute treatment of sodium butyrate or BuToRo were equally able to reduce intestinal motility (-38% vs -43%, NS). Then we investigated the effects on intestinal transit time in a model of castor oil–induced diarrhea in mice. Results: The effect of BuToRo on intestinal transit time was more pronounced compared to that observed using sodium butyrate (-75% vs -27%, p<001). In addition, the effect of BuToRo on total stool volume in the first 24 h was more pronounced if compared to that seen with sodium-butyrate (64% vs -20% of reduction in total stool volume respectively, p<0.001). Conclusions: Our results indicate that in basal condition sodium butyrate and BuToRo are equally active, whereas in the presence of an intestinal inflammatory state BuToRo was more active in reducing peristalsis and stool volume. These data support a potential therapeutic role for this new compound in the treatment of inflammatory diarrhea.
a Department
of Experimental Pharmacology, Naples; b Department of Pediatrics and University of Naples “Federico II”, Naples; c European Laboratory for the Investigation on Food Induced Diseases, University of Naples “Federico II”, Naples Background and aims: Evidences suggests a potential role elicited by short chain fatty acids (SCFAs) in regulating visceral pain. We comparatively tested the effects of a new synthetic butyrate derivative, N-(1-carbamoyl-2-phenylethyl)butyramide (BuToRo), and of sodium butyrate (one of the main SCFAs produced by the colonic microflora) in two animal models of acute peripheral pain perception (formalin-induced paw licking in mice) and visceral pain (acetic acid-induced writhing in mice).
PA41 USE OF AN AMINO-ACID-BASED FORMULA IN THE TREATMENT OF COW’S MILK PROTEIN ALLERGY PRESENTING AS ALLERGIC PROCTOCOLITIS R. Francavilla, R. Sardaro, C. Fontana, S. Fico, F. Indio Università degli Studi di Bari Background: Food allergy to cow’s milk proteins (APLV) is frequently found in young infants and may present as proctocolitis. Treatment is by starting