Author: "Bizzarri C" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

Author: Knip M., Akerblom H. K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H. -M., Dupre J., Fraser W. D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J. P., Lawson M. L., Ludvigsson J., Madacsy L., Mahon J. L., Ormisson A., Palmer J. P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N. H., Virtanen S. M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S. P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D. W., Brown C., Craig M., Johnston A., Bere L. J., Clarson C. L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J. -P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D. K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H. J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E. A. C., Woo V., Boland A., Clark H. D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J. C., Sauro V., Tawagi G. F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M. J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M. -C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E. A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J. C., Dawson C., Joyce C., Newhook L. A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M. J., Penner M., Sankaran K., Hardy-Brown K., King N., White R. A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M. -A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H. -M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A. -L., Hamalainen A. -M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A. S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S. -L., Selvenius J., Siljander H., Haanpaa P. -L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A. -M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A. R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M. -L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M. -L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G. B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y. M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M. B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J. A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J. R., Chueca M., Cortazar A., Echarte G., Frutos T. G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M. T., Hawkins F. G., Hernandez R., Herranz L., Pallardo L. F., Deibarra L. S., Fernandez B. H., Luis J. L., Ortiz-Quintana L., Recarte P. P., Arnau D. R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A. -M., Konefal M. S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A. -K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A. -B., Lyden G. -B., Nilsson N. -O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T. O., Andersson A. -C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I. -B., Strigard E., Svensson B. -L., Aman J., Breivik G. -E., Detlofsson I. -L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M. E., Gilmour C., Klein M. B., Lain C., Salerno D., Smith M. E., Vats K., Pfaff D. J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., Pediatrics, Knip M., Akerblom H.K., Altaji E., Becker D., Bruining J., Castano L., Danne T., De Beaufort C., Dosch H.-M., Dupre J., Fraser W.D., Howard N., Ilonen J., Konrad D., Kordonouri O., Krischer J.P., Lawson M.L., Ludvigsson J., Madacsy L., Mahon J.L., Ormisson A., Palmer J.P., Pozzilli P., Savilahti E., Serrano-Rios M., Songini M., Taback S., Vaarala O., White N.H., Virtanen S.M., Wasikowa R., Mandrup-Poulsen T., Arjas E., Lernmark A., Laara E., Schmidt B., Hyytinen M., Koski K., Koski M., Merentie K., Pajakkala E., Reunanen A., Salonen M., Terhonen T., Virkkunen S., Cuthbertson D., Gainer B., Hadley D., Malloy J., Nallamshetty L., Shanker L., Bradley B., Lough G., Fraser W., Sermer M., Taback S.P., Franciscus M., Nucci A., Palmer J., Alahuhta K., Barlund S., Korhonen T., Kovanen L., Lehtonen E., Niinisto S., Pekkala M., Sorkio S., Toivanen L., Vahatalo L., Uusitalo U., Ohman T., Bongiorno R., Catteau J., Fraser G., Lloyd M., Crock P., Giles M., Siech K., See D.W., Brown C., Craig M., Johnston A., Bere L.J., Clarson C.L., Jenner M., McManus R., Renato N., Lovell M., Higo D., Kent N., Kwan J., Marshall C., Metzger D., Chanoine J.-P., Stewart L., Thompson D., Edwards A., Lange I., Mercer J., Pacaud D., Josephine H., Schwarz W., Stephure D.K., Boer J., Chatur T., Chick C., Couch B., Demianczuk N., Girgis R., Marks S., Ryan E., Thompson M., Dean H.J., Grant L., Hamelin K., LaForte J., Murphy L., Catte D., Schneider C., Sellers E.A.C., Woo V., Boland A., Clark H.D., Cooper T., Gruslin A., Karovitch A., Keely E., Malcolm J.C., Sauro V., Tawagi G.F., Andrighetti S., Arnold G., Barrett J., Blumer I., Daneman D., Donat D., Ehrlich R., Feig D., Gottesman I., Gysler M., Karkanis S., Kenshole A., Knight B., Lackie E., Lewis V., Martin M.J., Maxwell C., Oliver G., Panchum P., Shilletto N., Simone A., Skidmore M., Turrini T., Wong S., Allen C., Belanger L., Bouchard I., Ferland S., Frenette L., Garrido-Russo M., Leblanc M., Imbeault J., Morin V., Olivier G., Weisnagell J., Costain G., Dornan J., Heath K., MacSween M.-C., McGibbon A., Ramsay C., Sanderson F., Sanderson S., Benabdesselam L., Gonthier M., Huot C., Thibeault M., Laforte D., Legault L., Perron P., Armson A., Canning P., Cummings E.A., Ivanko V., McLeod L., Mokashi A., Scott K., Bridger T., Crane J., Crummell C., Curtis J.C., Dawson C., Joyce C., Newhook L.A., Newman S., Druken E., Begum-Hasan J., Breen A., Houlden R., Woods M., Carrson G., Kelly S., Martel M.J., Penner M., Sankaran K., Hardy-Brown K., King N., White R.A., Park M., Popkin J., Robson L., Coles K., Al Taji E., Cerna M., Cerny M., Francova H., Hainerova I., Kothankova H., Koukalova R., Krakorova V., Mendlova P., Sitova R., Stechova K., Vavrinec J., Vosahlo J., Zlatohlavkova B., Brazdova L., Faksova P., Gregorova D., Kantor L., Malkova K., Venhacova J., Venhacova P., Cipra A., Skvor J., Budejovice C., Tomsikova Z., Botkova-Krauseova H., Mockova A., Paterova P., Gogelova P., Kandrnalova J., Einberg U., Jakovlev U., Posiadlo S., Rannaste E., Raukas R., Riikjarv M.-A., Valla K., Astover V., Kirss A., Retpap J., Taht E., Tillmann V., Vahtra S., Heikkila M., Hirvasniemi M., Luopajarvi K., Johansson S., Kleemola P., Laukkanen E., Parkkola A., Pigg H.-M., Puttonen H., Renlund M., Salonen K., Suomalainen H., Tenkula T., Teramo K., Jarvenpaa A.-L., Hamalainen A.-M., Jussila R., Kiiveri S., Haavisto H., Holopainen S., Kupiainen H., Leeve T., Lumme K., Nironen T., Tenhola S., Tiilikainen T., Keinonen H., Lautala P., Salonen P., Vesanto M., Aspholm A.S., Asunta P., Ikavalko H., Jason E., Jaminki S., Kekki P., Koskinen M., Lehtimaki S., Lahde J., Makela M., Peltoniemi S., Poutiainen L., Ranta K., Salonsaari T., Sarviharju-Tujula S.-L., Selvenius J., Siljander H., Haanpaa P.-L., Holm C., Juutilainen A., Jarvelainen V., Kangaskolkka-Keskilohko A.-M., Laino E., Marjamaki L., Suominen E., Ylitalo S., Hokkanen M., Lounamaa R., Matikainen M., Nuuja A., Paalanen I., Puupponen A.R., Salo-Edwards H., Alanne S., Kultti T., Linjama H., Muhonen K., Vaaraniemi M., Talvitie T., Backman M., Hanhijarvi R., Koivula P., Lindstrom K., Martikainen A., Nurmi P., Bjork A., Huopio H., Komulainen J., Lehtomaki S., Muikku E., Pesola J., Sankilampi U., Arkkola T., Hekkala A., Jurvakainen S., Koivikko M.-L., Kahonen M., Leinonen E., Mykkanen T., Pohjola H., Riikonen K., Niittyvuopio A., Stenius A., Tapanainen P., Veijola R., Alar A., Jovio S., Korpela P., Makinen E., Hietanen L., Kivisto J., Kaar M.-L., Lehtimaki P., Mustila T., Popov E., Saatela S., Taittonen L., Ahtiainen K., Laaksonen N., Luoto M., Viitala J., Virransalo R., Nykanen P., Paajanen S., Parkkinen S., Pyrhonen H., Sarkka T., Aschemeier B., Bektas S., Biester T., Datz N., Deiss D., Fath M., Lupke K., Muller B., Nestoris C., Rothes S., Sadeghian E., Semler K., Arato A., Krikovszky D., Nobilis A., Szenasi J., Benevento D., Anguissola G.B., Biagioni M., Bizzarri C., Cherubini V., Ferrito L., Giordano C., Giorgetti C., Khazrai Y.M., Kyanvash S., Maddaloni E., Napoli A., Piergiovanni F., Pitocco D., Suraci T., Tabacco G., Valente L., Visalli N., Carboni M.B., Cavallo R., Cau V., Isola C., Ledda A., Loddo M., Mannu C., Pettinau M., Pisano S., Porceddu M., Putzu C., Rita A., Peters D., Schierloh U., Bisschoff M., Blonk L., Lappenschaar T., Manai B., Seesink M., Sperling-Conrad M., Verhagen M., Zoethout J.A., Basiak A., Chalas M., Chesiak M., Gramza A., Iwankiewicz J., Sieradzan E., Wikiera B., Ciechanowska M., Dziatkowiak H., Futona B., Gorska A., Glowacka-Wony M., Kaim I., Klich B., Starzyk J., Wolanin M., Tokarska L., Chucherco D., Deja G., Firek-Pedras M., Jarosz-Chobot P., Kalina M., Kutrowska-Adamusiak K., Minkina-Pedras M., Muchaka-Bianga M., Bodalski J., Mlynarski W., Szadkowska A., Cieslak A., Cypryk K., Dziatosz K., Jastzebowska J., Krysiak A., Szymanska U., Wilcznski J., Zawodniak-Szalapska M., Aguay A., Bilbao J.R., Chueca M., Cortazar A., Echarte G., Frutos T.G., Jimenez P., Martul P., Moreno A., Oyarzabal M., Rica I., Salgado Y., Martinez-Larrad M.T., Hawkins F.G., Hernandez R., Herranz L., Pallardo L.F., Deibarra L.S., Fernandez B.H., Luis J.L., Ortiz-Quintana L., Recarte P.P., Arnau D.R., Aronsson L., Boden S., Fredriksson J., Isacsson E., Johansson I., Karlsson E., Lock C., Sandstrom A.-M., Konefal M.S., Andreasson C., Dahlstrom U., Hanas R., Lundqvist K., Windell L., Jansson I., Karlsson A.-K., Lindbladh B., Odenman I., Pettersson C., Sundberg F., Sundqvist M., Aronsson S., Bellman I., Bengtsson A.-B., Lyden G.-B., Nilsson N.-O., Soderblom M., Unt C., Augustsson M., Bengtsson M., Fors H., Helmrich A., Johansson T.O., Andersson A.-C., Boiard-Stomlid A., Hellgren G., Kallsholm H., Lindqvist J., Nilsson M., Nordwall M., Stromstedt C., Ahsberg C., Lindh A., Lindhe C., Samuelsson C., Wiik A., Edenwall H., Ljumgcrantz M., Persson I.-B., Strigard E., Svensson B.-L., Aman J., Breivik G.-E., Detlofsson I.-L., Kroon M., Sarnblad S., Johansson C., Ilvered R., Lundberg A., Akesson K., Beccarelli A., Gadient M., Rappold-Amrein C., Schoenle E., Daftary A., Damagro-Elias M.E., Gilmour C., Klein M.B., Lain C., Salerno D., Smith M.E., Vats K., Pfaff D.J., Malone P., Mansfield P., Munns M., Nickel K., Pompilio K., Siemion W., Taculad R., Van Horn K., Zdanadewic M., Chambliss C., Jones J., Sadler M., Tanner-Blasiar M., Bell C., Camper N., Devaskar S., Devaskar U., Horowitz H., Rogers L., Shannahan R., Silk K., Bermudez Z., Colon R., Frazer T., Martinez-Nieves B., Torres J., Vega J., Chan M., Cook S., Goland R., Greenberg E., Jules N., Montes J., Nelson M., Parra-Valencia Z., Schachner H., Softness B., Kiviniemi M., Suomenin R., Alexander A., Hyrckowian E., Nichol L., Trucco M., Karjalainen E., Louhio T., Sarnesto A., Valtonen E., Davydova B., Helander S., Hamalainen J., Harkonen T., Joutsjoki L., Kararic M., Latva-Koivisto M., Lonn E., Nurmi T., Ollila I., Rinkinen J., Ronkainen M., Tukiainen H., Cederlof A., Kiikeri M., Tsupari S., Cheng R., Bryant K., Chan Y., Maezawa Y., Paltser G., Rasavi R., Tsui H., Winer S., Wu P., Yantha J., University of Zurich, and Knip, Mikael
Subjects: Male, Risk, medicine.medical_specialty, Casein, Breastfeeding, 030209 endocrinology & metabolism, 610 Medicine & health, 2700 General Medicine, Endocrinology and Diabetes, Disease-Free Survival, law.invention, Follow-Up Studie, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, SDG 3 - Good Health and Well-being, law, Internal medicine, Diabetes mellitus, medicine, Humans, Cumulative incidence, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Original Investigation, 2. Zero hunger, Type 1 diabetes, business.industry, Hazard ratio, Absolute risk reduction, Infant, Newborn, Caseins, General Medicine, ta3121, medicine.disease, Infant Formula, 3. Good health, Diabetes Mellitus, Type 1, Infant formula, 10036 Medical Clinic, Endokrinologi och diabetes, Female, business, Human, Follow-Up Studies
Abstract: IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF
Published: 2018

2. Growth hormone treatment improves final height and nutritional status of children with chronic kidney disease and growth deceleration

Author: Dello Strologo L, Cavallo L, Cappa M, Mario Giordano, Faienza Mf, Maurizio Delvecchio, Bizzarri C, and Lonero A
Subjects: Male, medicine.medical_specialty, Deceleration, Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, Physiology, Nutritional Status, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, Child, Growth Disorders, Growth retardation, Human Growth Hormone, business.industry, Human growth hormone, Final height, Case-control study, Nutritional status, Prognosis, medicine.disease, Body Height, Growth hormone treatment, Case-Control Studies, Female, Complication, business, Follow-Up Studies, Kidney disease
Abstract: Growth retardation is a common complication of chronic kidney disease (CKD) in children. Treatment with recombinant human growth hormone (rhGH) has been used to help short children with CKD to attain a height more in keeping with their age group, but the scientific evidence regarding the effect of rhGH on final height is scarce. Final heights of children with CKD receiving rhGH treatment (cases) were compared with final heights of a matched cohort of children with CKD that did not receive rhGH therapy (controls). Sixty-eight rhGH-treated cases (44 boys) were compared with 92 untreated controls (60 boys). Mean duration of rhGH therapy was 4.2 ± 0.9 years; rhGH dose was 0.3 ± 0.07 mg/kg/week. Height SDS at baseline was lower in rhGH-treated patients than in controls (−2.00 ± 1.02 versus −0.96 ± 1.11, p
Published: 2017
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3. Raised C-reactive protein levels in patients with recent onset type 1 diabetes

Author: Picardi, A., Valorani, M. G., Vespasiani Gentilucci, U., Manfrini, S., Ciofini, O., Cappa, M., Guglielmi, C., Pozzilli, P., Visalli, N., Fioriti, E., Valente, L., Anguissola Gb, Costanza F., Cipolloni, L., Merola, K. M., Montemari, A., Matteoli, M. C., Patera, P., Crino, A., Bizzarri, C., Lauria Pantano, P. A., Cavallo, Maria Gisella, Schiaffini, R., Spera, S., Suraci, C., Pitocco, D., and Ghirlanda, G.
Subjects: Adult, Male, Percentile, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Alpha (ethology), Orosomucoid, Endocrinology, cardiovascular disease, Internal medicine, Diabetes mellitus, alpha(1)-acid glycoprotein, high-sensitive c-reactive protein, type 1 diabetes mellitus, Internal Medicine, medicine, Humans, Child, Type 1 diabetes, biology, business.industry, Insulin, medicine.disease, C-Reactive Protein, Diabetes Mellitus, Type 1, Child, Preschool, Metabolic control analysis, biology.protein, Female, business, Body mass index
Abstract: Background To investigate serum concentrations of high-sensitive C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12). Methods CRP and AGP were measured in 44 recent onset T1DM patients (26M/18F, mean age 14.9 ± 9.1 years), and 44 age- and sex-matched controls, using a highly sensitive immunonephelometric assay. Results There were no significant differences in the concentrations of high-sensitive C-reactive protein (hs-CRP) and AGP between patients and controls. hs-CRP levels significantly increased in patients at T12 compared to the levels at diagnosis [0.69 (0.14–15.5) versus 0.43 (0.14–7.47) mg/L, p < 0.05; for males: 0.77 (0.14–15.5) versus 0.35 (0.14–7.47) mg/L, p < 0.05; for females the increase was not significant]. AGP levels were not different at T12 compared to diagnosis. No significant correlations were found between hs-CRP and body mass index (BMI), C-peptide, glycosylated haemoglobin, or insulin dose. A strong correlation was found between hs-CRP values at diagnosis and those at T12 (ρ = 0.73, p < 0.001); indeed, patients with hs-CRP levels above the 50th percentile at diagnosis showed significantly increased hs-CRP values at T12 compared to patients with baseline hs-CRP levels under the 50th percentile [1.61 (0.18–15.5) versus 0.16 (0.14–1.92) mg/L, p < 0.0001)], and to controls [0.55 (0.14–6.50), p = 0.001]. Conclusions This is the first report showing that, despite good metabolic control, 1 year of overt T1DM is sufficient to increase hs-CRP levels, especially in males. hs-CRP levels at diagnosis is a predictor for the values observed at 12 months, suggesting the possibility to select a subgroup of patients requiring strict follow-up for cardiovascular complications. Copyright © 2006 John Wiley & Sons, Ltd.
Published: 2007
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4. A New Homozygous Frameshift Mutation in the HSD3B2 Gene in an Apparently Nonconsanguineous Italian Family

Author: Bizzarri, C, Massimi, A, Federici, L, Cualbu, A, Loche, S, Bellincampi, L, Bernardini, S, Cappa, M, and Porzio, O
Subjects: Adult, Male, Frameshift HSD3B2 mutation, Classical congenital adrenal hyperplasia, Congenital, Structure-Activity Relationship, Adrenocorticotropic Hormone, Protein Domains, Renin, Humans, Family, 3β-Hydroxysteroid dehydrogenase mutations, Frameshift Mutation, Adrenal Hyperplasia, Adrenal Hyperplasia, Congenital, Progesterone Reductase, Settore BIO/12, 17-alpha-Hydroxyprogesterone, Congenital adrenal hyperplasia, Androstenedione, Infant, Newborn, Infant, Newborn, Female, Italy
Abstract: 3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia (CAH) caused by inactivating mutations in the HSD3B2 gene.We report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child born to apparently nonconsanguineous parents and presenting ambiguous genitalia and salt wasting. The steroid profile showed elevated concentrations of 17-hydroxyprogesterone, androstenedione, ACTH and plasma renin, but normal values of cortisol and dehydroepiandrosterone sulfate. Unexpectedly, plasma aldosterone was high. For structural and functional analyses, the three-dimensional structure of 3β-HSD2 was modeled using the crystal structure of the short-chain dehydrogenase Gox2253 from Gluconobacter oxydans as a template.The direct DNA sequence of the child revealed a new homozygous frameshift mutation in exon 4 of the HSD3B2 gene, a single nucleotide deletion at codon 319 [GTC(Val)x2192;GC], yielding premature stop codon in position 367. Molecular homology modeling and secondary structure predictions suggested that the variant sequence might both alter the substrate-binding cleft and compromise the overall stability of the enzyme.We have described the first HSD3B2 gene mutation in the Italian population and analyzed its effect in the context of the 3β-HSD2 structure and function.
Published: 2015

5. Early and progressive insulin resistance in young, non-obese cancer survivors treated with hematopoietic stem cell transplantation

Author: Bizzarri, C., Pinto, R. M., Ciccone, S., Brescia, L. P., Locatelli, F., and Cappa, M.
Subjects: Male, Transplantation Conditioning, Adolescent, Hematopoietic stem cell transplantation, Comorbidity, Hypothyroidism, Non-alcoholic Fatty Liver Disease, Risk Factors, Glucose Intolerance, Body Fat Distribution, Humans, Prospective Studies, Survivors, Obesity, cancer survivor, child, hematopoietic stem cell transplantation, insulin resistance, metabolic syndrome, obesity, Child, Anthropometry, Hypogonadism, Body Weight, Infant, Insulin resistance, Metabolic syndrome, Hormones, Causality, Cross-Sectional Studies, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Cardiovascular Diseases, Case-Control Studies, Child, Preschool, Hematologic Neoplasms, Cancer survivor, Disease Progression, Female, Whole-Body Irradiation
Abstract: It is unclear whether there is a causative relationship between the development of metabolic syndrome (MS) and increased risk of early cardiovascular morbidity in patients receiving hematopoietic stem cell transplantation (HSCT) during childhood. Early identification of risk factors associated with insulin resistance, MS, and abnormal glucose tolerance during childhood or adolescence in these patients could represent a useful tool for preventing cardiovascular disorders.In a single-center, prospective, descriptive, cross-sectional study, we studied 45 survivors of hematological malignancies (age: 13.9 ± 4.8 years) treated with HSCT before the age of 18 years and 90 matched healthy controls. We collected clinical, imaging, and laboratory data including oral glucose tolerance test (OGTT).7/45 patients (15.6%) showed abnormal glucose tolerance at OGTT, 1/45 (2.2%) was obese, and none fulfilled the criteria for MS. A waist/height ratio0.5 was associated with patients with abnormal glucose tolerance (85.7% of cases), compared to patients with normal glucose tolerance (42.1%) and controls (23.3%). In patients with abnormal glucose tolerance, use of total body irradiation (TBI) as conditioning regimen was more common, and time elapsed from HSCT was longer.Patients treated with HSCT may develop insulin resistance early after transplantation. They do not show overt obesity, but have redistribution of fat tissue with central fat accumulation. The main factors associated with increased metabolic risk are TBI and time from HSCT. Evaluation of MS and glucose tolerance should be part of hormonal follow-up, which should be routinely proposed to these patients.
Published: 2015

6. Cushing’s Syndrome in a 6-month-old Boy: A Rare Side-effect due to Inadequate use of Topical Corticosteroids

Author: Cappa M, Bizzarri C, Ciccone S, El Hachem M, and Romana Marini
Subjects: Male, Hypothalamo-Hypophyseal System, Pediatrics, medicine.medical_specialty, Hydrocortisone, Side effect, Treatment outcome, MEDLINE, Pituitary-Adrenal System, 030209 endocrinology & metabolism, Dermatology, Administration, Cutaneous, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Humans, Medicine, Cushing Syndrome, Betamethasone Valerate, S syndrome, business.industry, Infant, General Medicine, Treatment Outcome, business
Published: 2016
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7. Age at Diagnosis of Type 1 Diabetes and the Effect of Immunomodulatory Therapies on Residual Beta Cell Function

Author: Pitocco, D., Distasio, E., Crino, A., Manfrini, S., Guglielmi, C., Visalli, N., Suraci, C., Matteoli, M. C., Cavallo, Maria Gisella, Bizzarri, C., Pozzilli, P., and Group, Imdiab
Subjects: Male, Aging, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Age at diagnosis, Beta-cell Function, Biochemistry, Endocrinology, Text mining, Insulin-Secreting Cells, Internal medicine, medicine, Humans, Immunologic Factors, Age of Onset, Child, Type 1 diabetes, C-Peptide, business.industry, Biochemistry (medical), General Medicine, medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Female, business, Follow-Up Studies
Published: 2008
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8. Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes

Author: Napoli N, Strollo R, Pitocco, D, Bizzarri, C, Maddaloni, E, Maggi, D, Manfrini, S, Schwartz, A, Pozzilli, P, Collaborators, IMDIAB Group, Anguissola, Gb, Astorri, E, Barchetta, Ilaria, Benevento, D, Beretta Anguissola, G, Buzzetti, Raffaella, Capizzi, M, Cappa, M, Cassone Faldetta, Mr, Cavallo, Maria Gisella, Cipolloni, L, Cipponeri, E, Crinò, A, Di Stasio, E, Fioriti, E, Ghirlanda, G, Guglielmi, C, Lauria, A, Matteoli, Mc, Maurizi, Ar, Moretti, C, Napoli, N, Palermo, A, Portuesi, R, Spera, S, Strollo, R, Tuccinardi, D, and Valente, L.
Subjects: Male, medicine.medical_treatment, Bone remodeling, Endocrinology, Osteogenesis, Insulin-Secreting Cells, Insulin, Age of Onset, Vitamin D, Child, Multidisciplinary, biology, C-Peptide, Mitochondrial medicine Energy and redox metabolism [IGMD 8], Vitamins, Osteocalcin, Medicine, Female, Collagen, medicine.drug, Research Article, Peak bone mass, Adult, medicine.medical_specialty, Calcitriol, Adolescent, Clinical Research Design, Science, Bone and Mineral Metabolism, Bone resorption, Autoimmune Diseases, Rheumatology, Internal medicine, medicine, Humans, Bone Resorption, Retrospective Studies, Nutrition, Glycated Hemoglobin, Diabetic Endocrinology, Type 1 diabetes, Endocrine Physiology, business.industry, Diabetes Mellitus Type 1, medicine.disease, Peptide Fragments, Diabetes Mellitus, Type 1, Metabolic control analysis, biology.protein, Clinical Immunology, business, Follow-Up Studies
Abstract: Contains fulltext : 125353.pdf (Publisher’s version ) (Open Access) BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of beta-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve beta-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 microg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P
Published: 2012

9. Diabetes-related autoantibodies in children with acute lymphoblastic leukemia

Author: Bizzarri, C., Pinto, R. m., Pitocco, D., Astorri, E., Cappa, M., Hawa, M., Giannone, G., Palermo, A., Maddaloni, E., Leslie, Dr, Pozzilli, P., Altomare, M., Barchetta, Ilaria, Benevento, D., Beretta Anguissola, G., Buzzetti, Raffaella, Capizzi, M., Cappa, M. r., Cavallo, Maria Gisella, Cipolloni, L., Cipponeri, E., Costantino, F., Crino, A., Defeudis, G., Di Stasio, E., Fallucca, S., Fioriti, E., Ghirlanda, G., Guglielmi, C., Khazrai Yeganeh, M., Kyanvash, S., Lauria, A., Maggi, D., Manfrini, S., Maurizi, A. r., Moretti, C., Morviducci, L., Napoli, N., Patera, P., Portuesi, R., Schiaffini, R., Scrocca, R., Spera, S., Strollo, R., Suraci, C., Tubili, C., Tuccinardi, D., Valente, L., and Visalli, N.
Subjects: Male, medicine.medical_specialty, Diabetes Care Electronic Pages, Endocrinology, Diabetes and Metabolism, Glutamate decarboxylase, Radioimmunoassay, Pre B Lymphocyte, Internal medicine, Diabetes mellitus, Epidemiology, Internal Medicine, medicine, Diabetes Mellitus, Humans, Insulin, Online Letters: Observations, Child, Philadelphia 1 Chromosome, Autoantibodies, Acute Lymphoblastic Leukemia, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, Glutamate Decarboxylase, Thyroid, Autoantibody, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Leukemia, medicine.anatomical_structure, Child, Preschool, Immunology, Etiology, Female, business
Abstract: Acute lymphoblastic leukemia (ALL) is the most common subtype of leukemia in children. Although ALL and type 1 diabetes appear to be biologically unrelated, there are common threads in both epidemiology and etiology. Rising incidence rates of both ALL (1) and type 1 diabetes (2) observed over recent decades in many Western countries seem to support common etiological factors (3). In the current study, we report on diabetes-related autoantibodies (Abs) in a group of patients with ALL. Thirty-four consecutive children (19 males and 15 females, mean age 6.2 ± 4.6 years) were referred to our institution in 2004 for newly diagnosed ALL. Patients were tested for Abs to islet and thyroid antigens. After the initial investigation and treatment, 31/34 (91%) patients (3 died in the mean time) were followedup for 6 years to evaluate the evolution of the autoimmune markers and progression toward type 1 diabetes. Glutamic acid decarboxylase (GAD) Abs by direct …
Published: 2012

10. Type 1 diabetes and measles, mumps and rubella childhood infections within the Italian Insulin-dependent Diabetes Registry

Author: Ramondetti, F, Sacco, S., Comelli, M., Bruno, Graziella, Falorni, A, Iannilli, A., D'Annunzio, G., Iafusco, D., Songini, M., Toni, S., Cherubini, V., Carle, F., Cerutti, Franco, Novelli, Giulia, Bianchi, L., Piffer, S., Lorini, R., Minuto, N., Roncarolo, F., Tenconi, M. T., Predieri, B., Reali, M. F., Medici, A., Biagioni, M., Gesuita, R., Santeusanio, F., De Giorgi, G., Visalli, N., Bizzarri, C., Chiarelli, F., Tumini, S., Prisco, F., Confetto, S., Frongia, P., Marinaro, A. M., Ramondetti, F, Sacco, S, Comelli, M, Bruno, G, Falorni, A, Iannilli, A, D'Annunzio, G, Iafusco, Dario, Songini, M, Toni, S, Cherubini, V, and Carle, F.
Subjects: Registrie, Male, Mump, Type 1 diabete, Adolescent, incidenza, association study, infectious diseases, Antibodies, Viral, Diabete mellito di tipo 1, Body Mass Index, children, Measle, Humans, Registries, epidemiologia, association study, children, infectious diseases, Type 1 diabetes, Child, Mumps, Rubella, Infectious disease, Incidence, Infant, Newborn, Infant, Association study, Children, Infectious diseases, Type 1 diabetes, Diabetes Mellitus, Type 1, Italy, Child, Preschool, Female, malattie infettive dell'infanzia, Measles-Mumps-Rubella Vaccine, Human, Measles
Abstract: Diabet. Med. 29, 761-766 (2012) ABSTRACT: Aims Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. Methods This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used. Results The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). Conclusions According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility Diabet. Med. 29, 761766 (2012) Abstract Aims Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 19961997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results. Methods This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 19962001, analysing data of newly-diagnosed Type 1 diabetes children, aged 014 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated population at risk, represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearmans rank correlation was used. Results The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269). Conclusions According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility.
Published: 2011

11. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor

Author: Bertini, R, Barcelos, Ls, Beccari, Ar, Cavalieri, B, Moriconi, A, Bizzarri, C, DI BENEDETTO, Paola, Di Giacinto, C, Gloaguen, I, Galliera, E, Corsi, Mm, Russo, Rc, Andrade, Sp, Cesta, Mc, Nano, G, Aramini, A, Cutrin, Jc, Locati, M, Allegretti, M, and Teixeira, Mm
Subjects: Male, Models, Molecular, Anti-Inflammatory Agents, BINDING MODE, chemokine receptors, Inbred C57BL, Receptors, Interleukin-8B, Receptors, Interleukin-8A, Rats, Sprague-Dawley, Mice, Models, CXCR1/CXCR2, Receptors, CHEMOKINE RECEPTORS, Leukocytes, Site-Directed, NON-COMPETITIVE ALLOSTERIC INHIBITOR, Skin, Sulfonamides, CXC1-CXCR2 inhibitors, Neovascularization, Pathologic, Chemotaxis, inflammation, Research Papers, Medicina Básica, Chemotaxis, Leukocyte, Liver, LEUCOCYTE RECRUITMENT, Reperfusion Injury, non-competitive allosteric inhibitor, CIENCIAS MÉDICAS Y DE LA SALUD, Interleukin-8A, leucocyte recruitment, Inmunología, binding mode, Human Umbilical Vein Endothelial Cells, Animals, Humans, Interleukin-8B, Neovascularization, Cell Proliferation, Pathologic, Animal, experimental angiogenesis, Cell Membrane, Interleukin-8, Molecular, Leukocyte, Rats, Mice, Inbred C57BL, Disease Models, Animal, Mutagenesis, ISCHAEMIA REPERFUSION INJURY, Disease Models, ischaemia reperfusion injury, Mutagenesis, Site-Directed, Sprague-Dawley, EXPERIMENTAL ANGIOGENESIS
Abstract: Background and Purpose: DF 2156A is a new dual inhibitor of IL-8 receptors CXCR1 and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding mode, molecular mechanism of action and selectivity, and evaluated its therapeutic potential. Experimental Approach: The binding mode, molecular mechanism of action and selectivity were investigated using chemotaxis of L1.2 transfectants and human leucocytes, in addition to radioligand and [ 35S]-GTPγS binding approaches. The therapeutic potential of DF 2156A was evaluated in acute (liver ischaemia and reperfusion) and chronic (sponge-induced angiogenesis) experimental models of inflammation. Key Results: A network of polar interactions stabilized by a direct ionic bond between DF 2156A and Lys99 on CXCR1 and the non-conserved residue Asp 293 on CXCR2 are the key determinants of DF 2156A binding. DF 2156A acted as a non-competitive allosteric inhibitor blocking the signal transduction leading to chemotaxis without altering the binding affinity of natural ligands. DF 2156A effectively and selectively inhibited CXCR1/CXCR2-mediated chemotaxis of L1.2 transfectants and leucocytes. In a murine model of sponge-induced angiogenesis, DF 2156A reduced leucocyte influx, TNF-α production and neovessel formation. In vitro, DF 2156A prevented proliferation, migration and capillary-like organization of HUVECs in response to human IL-8. In a rat model of liver ischaemia and reperfusion (I/R) injury, DF 2156A decreased PMN and monocyte-macrophage infiltration and associated hepatocellular injury. Conclusion and Implications: DF 2156A is a non-competitive allosteric inhibitor of both IL-8 receptors CXCR1 and CXCR2. It prevented experimental angiogenesis and hepatic I/R injury in vivo and, therefore, has therapeutic potential for acute and chronic inflammatory diseases. Fil: Bertini, R.. Dompé; Italia Fil: Barcelos, L. S.. Universidade Federal de Minas Gerais; Brasil Fil: Beccari, A. R.. Dompé; Italia Fil: Cavalieri, B.. Dompé; Italia. Università di Torino; Italia Fil: Moriconi, A.. Dompé; Italia Fil: Bizzarri, C.. Dompé; Italia Fil: Di Benedetto, P.. Dompé; Italia Fil: Di Giacinto, C.. Dompé; Italia Fil: Gloaguen, I.. Dompé; Italia Fil: Galliera, E.. Università degli Studi di Milano; Italia Fil: Corsi, M. M.. Università degli Studi di Milano; Italia. Policlinico San Donato IRCCS; Italia Fil: Russo, R. C.. Universidade Federal de Minas Gerais; Brasil Fil: Andrade, S. P.. Universidade Federal de Minas Gerais; Brasil Fil: Cesta, M. C.. Dompé; Italia Fil: Nano, G.. Dompé; Italia Fil: Aramini, A.. Dompé; Italia Fil: Cutrin, Juan Carlos. Università di Torino; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: Locati, M.. Università degli Studi di Milano; Italia Fil: Allegretti, M.. Dompé; Italia Fil: Teixeira, M. M.. Universidade Federal de Minas Gerais; Brasil
Published: 2011

12. No protective effect of calcitriol on Î²-cell function in recent-onset type 1 diabetes: The IMDIAB XIII trial

Author: Bizzarri, C., Pitocco, D., Napoli, N., Di Stasio, E., Maggi, D., Manfrini, S., Suraci, C., Cavallo, Maria Gisella, Cappa, M., Ghirlanda, G., Pozzilli, P., and Group, Imdiab
Subjects: Adult, Male, Advanced and Specialized Nursing, Glycated Hemoglobin A, Adolescent, C-Peptide, Calcitriol, Child, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemic Agents, Insulin, Insulin-Secreting Cells, Young Adult, Internal Medicine, Endocrinology, Diabetes and Metabolism, Diabetes and Metabolism, Endocrinology, Diabetes Mellitus, Type 1
Published: 2010

13. Incidence of type 1 diabetes has doubled in Rome and the Lazio region in the 0- to 14-year age-group: A 6-year prospective study (2004-2009)

Author: Bizzarri, C., Patera, P. I., Arnaldi, C., Petrucci, S., Bitti, M. L. M., Scrocca, R., Manfrini, S., Portuesi, R., Buzzetti, Raffaella, Cappa, M., Pozzilli, P., and Immunotherapy Diabetes Imdiab Group
Subjects: Male, Pediatrics, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Rome, Group A, Settore MED/13 - Endocrinologia, Diabetes mellitus, Internal Medicine, medicine, Diabetes Mellitus, Humans, Prospective Studies, Prospective cohort study, Child, Preschool, Advanced and Specialized Nursing, American diabetes association, Settore MED/38 - Pediatria Generale e Specialistica, Type 1 diabetes, diabetes, business.industry, Incidence (epidemiology), Autoantibody, Infant, Newborn, Infant, Italy, Child, Preschool, Diabetes Mellitus, Type 1, Incidence, Female, medicine.disease, Newborn, Lazio region, incidence, business, Type 1
Abstract: Incidence of type 1 diabetes is rising, especially among younger children (1,2). We evaluated type 1 diabetes incidence in the years 2004–2009 among subjects
Published: 2010

14. The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI)

Author: Pitocco, D., Crino, A., Di Stasio, E., Manfrini, S., Guglielmi, C., Spera, S., Beretta Anguissola, G., Visalli, N., Suraci, C., Matteoli, M. C., Patera, I. P., Cavallo, Maria Gisella, Bizzarri, C., Pozzilli, P., and Group, Imdiab
Subjects: Blood Glucose, Male, Niacinamide, calcitriol, medicine.medical_specialty, Calcitriol, Adolescent, type 1 diabetes, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, nicotinamide, Pilot Projects, Bedtime, law.invention, chemistry.chemical_compound, Endocrinology, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Insulin-Secreting Cells, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Type 1 diabetes, Nicotinamide, business.industry, medicine.disease, B vitamins, Diabetes Mellitus, Type 1, chemistry, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Background A number of recent studies underline the importance of vitamin D in the pathogenesis of Type 1 diabetes (T1D). Aims The aim of this study was to investigate whether supplementation with the active form of vitamin D (calcitriol) in subjects with recent-onset T1D protects residual pancreatic β-cell function and improves glycaemic control (HbA1c and insulin requirement). Methods In this open-label randomized trial, 70 subjects with recent-onset T1D, mean age 13.6 years ± 7.6 sd were randomized to calcitriol (0.25 µg on alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year. Intensive insulin therapy was implemented with three daily injections of regular insulin + NPH insulin at bedtime. Results No significant differences were observed between calcitriol and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol group. Conclusions At the dosage used, calcitriol has a modest effect on residual pancreatic β-cell function and only temporarily reduces the insulin dose.
Published: 2006

15. Intradermal skin test with diabetes specific antigens in patients with type 1 diabetes

Author: Crino, A., Cavallo, Maria Gisella, Corbi, S., Mesturino, C. A., Ferrazzoli, F., Coppolino, G., Bizzarri, C., Cervoni, M., Monetini, L., Pozzilli, P., Visalli, N., Buzzetti, Raffaella, Parravano, C., Romeo, S., Perciaccante, A., Matteoli, M. C., Spera, S., Teodonio, C., Suraci, C., Multari, G., Sulli, N., Cantagallo, A., De Mattia, G., Cassone Faldetta, M. R., Manca Bitti, M. L., Marietti, G., Pitocco, D., and Ghirlanda, G.
Subjects: Adult, Male, medicine.medical_specialty, Cellular immunity, Adolescent, T cell, medicine.medical_treatment, Immunology, Immune system, Antigen, Internal medicine, Diabetes mellitus, medicine, Immunology and Allergy, Humans, Insulin, Hypersensitivity, Delayed, Child, Autoimmune disease, Type 1 diabetes, business.industry, Glutamate Decarboxylase, Caseins, Intradermal Tests, Middle Aged, medicine.disease, Isoenzymes, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 1, Endocrine Disease, Female, business
Abstract: SummaryCell mediated immune response in vitro to a number of antigens has been reported in patients with Type 1 diabetes. The aim of the present study was to develop an in vivo intradermal (delayed type hypersensitivity) skin test using antigens known to be recognized by lymphocytes of patients with Type 1 diabetes and to compare, where possible, the in vivo response to the in vitro T cell proliferation to the same antigens.The skin test was performed in the following group of patients: 55 with recent onset Type 1 diabetes; 16 patients with Type 1 diabetes of longer duration; 10 patients with autoimmune thyroid disease and 20 patients with Latent Autoimmune Diabetes in Adults (LADA). Type 1 diabetes specific antigens for the skin test included glutamic acid decarboxilase (GAD65), insulin and beta casein, whereas diabetes non specific antigens included tetanus toxoid, diphteria, proteus, tubercolin, streptococcus, and glycerol as control. A multitest device consisting of heads delivering intradermally 10 µl of solution containing the antigens was applied to the forearms; the specific antigens were injected in one forearm whereas the non specific antigens were injected in the other forearm. Reading of the reaction, which was considered positive in the presence of a nodule of 2 mm diameter was performed 48 h after the multitest application. The in vitro T cell response to diabetes specific antigens used in the multitest was studied using conventional proliferation assays in patients with recent onset Type 1 diabetes and in age matched normal subjects.Only recent onset Type 1 diabetes patients showed an in vivo positive response to GAD65, such response being detectable in 10 patients (18%). Two patients reacted also to beta casein and insulin, all other patient groups resulted negative but 2 patients with longer duration of Type 1 diabetes. There was no apparent link between the in vivo skin test and in vitro T cell proliferation to GAD65.We conclude that in vivo cell mediated immune reaction to GAD65, insulin and beta casein can be visualized in a minority of patients with recent onset Type 1 diabetes. Further studies are required to determine specificity and whether altering the dose can improve the sensitivity of the test.
Published: 2001

16. Inhibitory activity of IL-1 receptor antagonist depends on the balance between binding capacity for IL-1 receptor type 1 and IL-1 receptor type II

Author: Ruggiero P, Bossù P, Macchia G, Del Grosso E, Sabbatini V, Bertini R, Colagrande A, Bizzarri C, Maurizi G, Di Cioccio V, D'Andrea G, Di Giulio A, Frigerio F, Grifantini R, Guido Grandi, Tagliabue A, and Boraschi D
Subjects: Mice, Inbred C3H, Sialoglycoproteins, Immunology, Receptors, Interleukin-1, Recombinant Proteins, Cell Line, Interleukin 1 Receptor Antagonist Protein, Mice, Mutation, Immunology and Allergy, Animals, Humans, Female, Protein Binding
Abstract: A series of mutants of human IL-1 receptor antagonist (IL-1ra) has been designed by comparison of IL-1ra and IL-1beta structures in order to increase receptor antagonist capacity. Upon in vitro and in vivo assay of IL-1 antagonism, the IL-1ra mutants DoB 0039 (N91-->R), DoB 0040 (T109-->A) and DoB 0041 (N91/T109-->R/A) could inhibit IL-1beta effects more efficiently than wild-type IL-1ra, with DoB 0041 being the most active. Analysis of the receptor-binding capacity of the IL-1ra mutants showed that all three mutants could inhibit binding of IL-1alpha or IL-1beta to IL-1RI-bearing cells more efficiently than wild-type IL-1ra. Conversely, binding of IL-1beta to IL-1RII-bearing cells could be inhibited by DoB 0041 much less efficiently than by wild-type IL-1ra. It is known that the two types of IL-1 receptors (IL-1RI and IL-1RII) play different roles in the regulation of IL-1 activity, with IL-1RI being solely responsible for cell triggering upon IL-1 binding, whereas IL-1RII acts as a scavenger of IL-1 and can thus be considered as a natural IL-1 inhibitor. Thus, the enhanced inhibitory capacity of DoB 0041 as compared with wild-type IL-1ra is explained in terms of better binding to the activating receptor IL-1RI and poorer interaction with the inhibitory receptor IL-1RII.
Published: 1997

17. Mapping of receptor binding sites on IL-1 beta by reconstruction of IL-1ra-like domains

Author: Boraschi D, Bossù P, Ruggiero P, Tagliabue A, Bertini R, Macchia G, Gasbarro C, Pellegrini L, Melillo G, Ulisse E, Visconti U, Bizzarri C, Del Grosso E, Andrew Reay Mackay, Frascotti G, Frigerio F, Grifantini R, and Grandi G
Subjects: Mice, Inbred C3H, Binding Sites, Base Sequence, Sialoglycoproteins, Immunology, Molecular Sequence Data, Receptors, Interleukin-1, Peptide Mapping, Interleukin 1 Receptor Antagonist Protein, Mice, Structure-Activity Relationship, Mutagenesis, Site-Directed, Immunology and Allergy, Animals, Humans, Female, Sequence Alignment, Sequence Analysis, Interleukin-1
Abstract: Upon structure comparison between IL-1 beta and its antagonist IL-1ra, single or multiple residues along the IL-1 beta sequence were replaced with the corresponding amino acids present in the IL-1ra protein, in the attempt to identify sites important for receptor binding and for biologic activity on the two molecules. Ten of fifteen mutant proteins had activity comparable to that of wild-type IL-1 beta in three different biologic assays and in receptor binding, indicating that the introduced changes did not influence the functional structure of the protein. Conversely, three mutants (SMIL-9: 127/263 R/T-->W/Y; SMIL-10: 125/127/263/265 T/R/T/Q-->R/W/Y/E; SMIL-15:222/227 I/E-->S/S) showed an increased binding capacity for IL-1RI, not paralleled by increased agonist activity, indicating that the introduced IL-1ra residues could be involved in the nonagonist IL-1RI binding site. On the other hand, two mutants showed diminished binding capacity with concomitant decrease in biologic activity. Both mutants (SMIL-1, five substitutions in the loop 202-214; and SMIL-3, total replacement of the loop 164-173 with the IL-1ra stretch 52-55) included substitutions of residues allegedly important for agonist binding to IL-1RI. Mutant SMIL-3 showed the most profound reduction in binding capacity for IL-1RI (CDw121a) and a more than 1,000-fold reduced biologic activity both in vitro and in vivo, but it retained full capacity of binding to IL-1RII (CDw121b) and acted as a selective antagonist of IL-1RII. From these results the following conclusions can be drawn. IL-1 beta binds to IL-1RI and to IL-1RII through different sites, and the loop 164-173 appears as one of the areas involved in the selective interaction with IL-1RI. Agonist (IL-1 beta) and nonagonist (IL-1ra) binding to IL-1RI occur through distinct sites, with loops 164-173 and 202-214 of IL-1 beta identified as two of the sites selectively involved in agonist binding to the activating receptor.
Published: 1995

18. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus

Author: Crinò, A., Schiaffini, R., Ciampalini, P., Suraci, M. C., Manfrini, S., Visalli, N., Matteoli, M. C., Patera, P., Buzzetti, R., Guglielmi, C., Spera, S., Costanza, F., Fioriti, E., Pitocco, D., Pozzilli, P., Corbi, S., Cervoni, M., Manca Bitti, M. L., Bizzarri, C., Lauria Pantano, A., Cipolloni, L., Coppolino, G., Valente, L., Beretta Anguissola, G., Montemari, A. L., Cappa, M., Di Stasio, E., Lorenza Nisticò, Petrone, A., Cavallo, M. G., and Ghirlanda, G.
Subjects: Adult, Male, Niacinamide, Adolescent, nicotinamide, type 1 diabetes mellitus, c-peptide, intensive insulin therapy, Drug Administration Schedule, Diabetes Mellitus, Type 1, Humans, Hypoglycemic Agents, Insulin, Female, Child, Retrospective Studies
Abstract: A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis.We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis.In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years.Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

19. [Wolfram syndrome. Personal experience]

Author: Marietti G, Bizzarri C, Perrone F, Zampino G, Conti G, Benedetto Falsini, and Ricci B
Subjects: Hearing Loss, Sensorineural, Osmolar Concentration, Ophthalmic Nerve, Wolfram Syndrome, Sensorineural, Diabetes Mellitus, Type 1, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, Diabetes Mellitus, Humans, Female, Thiamine, Child, Preschool, Hearing Loss, Type 1, Autoantibodies
Abstract: We report on a young patient who suffered from diabetes mellitus and neurosensorial deafness from the age of two. One year later she was noted to have deteriorated vision and the diagnosis of optic atrophy was made, her visual acuity decreased progressively. At the age of six she was admitted to our hospital because of thiamine responsive megaloblastic anemia, a rare clinical feature of Wolfram's syndrome (only 13 cases have been reported to date). Thiamine (75 mg/day) was commenced at a single oral dose with a rapid increase of Hb level after a few days of therapy. The insulin requirement didn't decrease during thiamine therapy, the C-peptide level after glucagon remained almost indosable. No improvement was observed in the deafness and in the optic atrophy. These findings suggest that diabetes mellitus and optic atrophy, in Wolfram's syndrome are not related to thiamine metabolism.

20. Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Author: F. Bogazzi, Giorgio Radetti, Mariacarolina Salerno, B. Rees Smith, Stefano Masiero, L. de Sanctis, F. Presotto, Carla Giordano, Roberto Perniola, Valentina Camozzi, C. Betterle, Carla Scaroni, Antonella Meloni, Sarah Black, Francesca Pigliaru, Chiara Sabbadin, Alessandra Fierabracci, Carla Bizzarri, Marco Cappa, Garvin Weber, Donatella Capalbo, Susi Barollo, Jadwiga Furmaniak, Mariella Valenzise, Antonio Stigliano, A. Crinò, N. A. Greggio, Riccardo Scarpa, Silvia Garelli, Uberto Pagotto, M. Dalla Costa, A. De Bellis, Iacopo Chiodini, Shu Chen, Beatrice Rubin, Garelli, S., Dalla Costa, M., Sabbadin, C., Barollo, S., Rubin, B., Scarpa, R., Masiero, S., Fierabracci, A., Bizzarri, C., Crino, A., Cappa, M., Valenzise, M., Meloni, A., De Bellis, A. M., Giordano, C., Presotto, F., Perniola, R., Capalbo, D., Salerno, M., Stigliano, A., Radetti, G., Camozzi, V., Greggio, N. A., Bogazzi, F., Chiodini, I., Pagotto, U., Black, S. K., Chen, S., Rees Smith, B., Furmaniak, J., Weber, G., Pigliaru, F., De Sanctis, L., Scaroni, C., Betterle, C., Garelli S., Dalla Costa M., Sabbadin C., Barollo S., Rubin B., Scarpa R., Masiero S., Fierabracci A., Bizzarri C., Crino A., Cappa M., Valenzise M., Meloni A., De Bellis A.M., Giordano C., Presotto F., Perniola R., Capalbo D., Salerno M.C., Stigliano A., Radetti G., Camozzi V., Greggio N.A., Bogazzi F., Chiodini I., Pagotto U., Black S.K., Chen S., Rees Smith B., Furmaniak J., Weber G., Pigliaru F., De Sanctis L., Scaroni C., Betterle C., Garelli, S, Dalla Costa, M, Sabbadin, C, Barollo, S, Rubin, B, Scarpa, R, Masiero, S, Fierabracci, A, Bizzarri, C, Crinò, A, Cappa, M, Valenzise, M, Meloni, A, De Bellis, A M, Giordano, C, Presotto, F, Perniola, R, Capalbo, D, Salerno, M C, Stigliano, A, Radetti, G, Camozzi, V, Greggio, N A, Bogazzi, F, Chiodini, I, Pagotto, U, Black, S K, Chen, S, Rees Smith, B, Furmaniak, J, Weber, G, Pigliaru, F, De Sanctis, L, Scaroni, C, and Betterle, C
Subjects: Male, Transcription Factor, Endocrinology, Diabetes and Metabolism, Autoimmune hepatitis, Gene mutation, Gastroenterology, Chronic mucocutaneous candidiasis, Endocrinology, Addison Disease, Autoimmune Polyglandular Syndrome type 1 (APS-1), Prevalence, Medicine, Polyendocrinopathies, Autoimmune, Candidiasis, Chronic Mucocutaneou, Addison’s disease, AIRE gene mutations, Autoimmune Polyglandular Syndrome type 1 (APS-1), Autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED), Chronic hypoparathyroidism, Chronic mucocutaneous candidiasis, Interferon autoantibodies, Candidiasis, Chronic Mucocutaneous, AIRE gene mutations, Addison’s disease, autoimmune polyglandular syndrome type 1 (APS-1), autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED), chronic hypoparathyroidism, chronic mucocutaneous candidiasis, interferon autoantibodies, Autoimmune regulator, Autoantibodie, Italy, Interferon autoantibodie, Addison's disease, Interferon Type I, Original Article, Female, Chronic hypoparathyroidism, Human, Adult, medicine.medical_specialty, Autoimmune Gastritis, Hypoparathyroidism, Internal medicine, Interferon autoantibodies, Humans, Mortality, Autoantibodies, Autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED), business.industry, Chronic mucocutaneous candidiasi, AIRE gene mutation, Autoantibody, medicine.disease, Autoimmune polyendocrine syndrome type 1, Mutation, business, Transcription Factors
Abstract: Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.
Published: 2021

21. Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders

Author: Lorenzo Lenzi, Carla Bizzarri, Ivana Rabbone, Riccardo Bonfanti, Mohamad Maghnie, Maria Cristina Maggio, Giuseppe d'Annunzio, Dario Iafusco, Lorenzo Iughetti, Stefano Tumini, Giuseppina Salzano, Gabriella Pozzobon, Marco Marigliano, Stefano Zucchini, Silvia Vannelli, Valentino Cherubini, Andrea Scaramuzza, Zucchini, S, Iafusco, Dario, Vannelli, S, Rabbone, I, Salzano, G, Pozzobon, G, Maghnie, M, Cherubini, V, Bizzarri, C, Bonfanti, R, D'Annunzio, G, Lenzi, L, Maggio, Mc, Marigliano, M, Scaramuzza, A, Tumini, S, Iughetti, L., Zucchini, S., Iafusco, D., Vannelli, S., Rabbone, I., Salzano, G., Pozzobon, G., Maghnie, M., Cherubini, V., Bizzarri, C., Bonfanti, R., D'Annunzio, G., Lenzi, L., Maggio, M.C., Marigliano, M., Scaramuzza, A., Tumini, S., and Maggio, M. C.
Subjects: Male, medicine.medical_specialty, Adolescent, Growth hormone, Insulin therapy, GH deficiency, Type-1 diabetes, Turner syndrome, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, education, Dwarfism, TYPE I (INSULIN-DEPENDENT) DIABETES MELLITUS, Settore MED/38 - Pediatria Generale E Specialistica, Endocrinology, Insulin resistance, Pharmacotherapy, Surveys and Questionnaires, Internal medicine, Diabetes mellitus, growth hormone treatment, medicine, Humans, Hypoglycemic Agents, Insulin, Child, Dwarfism, Pituitary, Growth Disorders, Type 1 diabetes, Human Growth Hormone, business.industry, medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Pediatrics, Perinatology and Child Health, Drug Therapy, Combination, Female, Insulin Resistance, business
Abstract: Background/Aim: Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). Methods: A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Results: Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Conclusions: Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.
Published: 2014

22. Biological clock and heredity in pubertal timing: what is new?

Author: Manuela Caruso Nicoletti, Luisa De Sanctis, Anna Grandone, Alessandra Cassio, Carla Bizzarri, Flavia Barbieri, Elena Inzaghi, and Barbieri F, Inzaghi E, Caruso Nicoletti M, Cassio A, Grandone A, DE Sanctis L, Bizzarri C.
Subjects: Epigenomics, Heredity, Epigenomic, Biological clock, Ubiquitin-Protein Ligases, media_common.quotation_subject, Central precocious puberty, Puberty, Precocious, Fertility, Environment, Affect (psychology), Bioinformatics, medicine.disease_cause, Genetic, Biological Clocks, Genetics, Humans, Medicine, Sexual maturity, Genes, Tumor Suppressor, Epigenetics, Gonadotropins pituitary, Endocrine disruptors, media_common, business.industry, Puberty, Endocrine disruptor, Genes, Pediatrics, Perinatology and Child Health, Precocious, business, pubPuberty, Tumor Suppressor
Abstract: Puberty represents a milestone during a person's life and is characterized by several physical and psychological changes which end with the achievement of sexual maturation and of fertility. Puberty onset depends on a series of sophisticated, not completely understood, mechanisms certainly involving Gonadotropin-Releasing Hormone (GnRH) and its effects on pituitary gonadotropins. As recent evidence has demonstrated that pubertal timing deeply affects future adult health life, many efforts have been performed in order to clarify the exact actors involved in the onset and progression of puberty. Genetic factors are undoubtedly essential players in the regulation of pubertal development, accounting for approximately 50-80% of its variability. Mutations in genes such as KISS1, MKRN3, and DLK1 have been associated with central precocious puberty. Interestingly, a possible involvement of epigenetic mechanisms has been proposed as additional element able to affect pubertal phase. Environmental factors have recently attracted much attention. Indeed, an overall decrease in the age of puberty has been observed in the last decades. As genetic factors require long time to exert their effect, other players, such as environmental ones, may be involved. Special focus has been posed on nutritional status, endocrine-disrupting chemicals with non-conclusive results. Pubertal timing deeply affects future life, suggesting the need to clarify mechanisms driving pubertal onset and progression, in order to identify tailored therapeutic strategies and targets.
Published: 2022
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23. Differences between Transient Neonatal Diabetes Mellitus Subtypes can Guide Diagnosis and Therapy

Author: Riccardo Bonfanti, Dario Iafusco, Ivana Rabbone, Giacomo Diedenhofen, Carla Bizzarri, Patrizia Ippolita Patera, Petra Reinstadler, Francesco Costantino, Valeria Calcaterra, Lorenzo Iughetti, Silvia Savastio, Anna Favia, Francesca Cardella, Donatella Lo Presti, Ylenia Girtler, Sarah Rabbiosi, Giuseppe D’Annunzio, Angela Zanfardino, Alessia Piscopo, Francesca Casaburo, Letizia Pintomalli, Lucia Russo, Valeria Grasso, Nicola Minuto, Mafalda Mucciolo, Antonio Novelli, Antonella Marucci, Barbara Piccini, Sonia Toni, Francesca Silvestri, Paola Carrera, Andrea Rigamonti, Giulio Frontino, Michela Trada, Davide Tinti, Maurizio Delvecchio, Novella Rapini, Riccardo Schiaffini, Corrado Mammì, Fabrizio Barbetti, Monica Aloe, Simona Amadeo, Claudia Arnaldi, Marta Bassi, Luciano Beccaria, Marzia Benelli, Giulia Maria Berioloi, Enrica Bertelli, Martina Biagioni, Adriana Bobbio, Stefano Boccato, Oriana Bologna, Franco Bontempi, Clara Bonura, Giulia Bracciolini, Claudia Brufani, Patrizia Bruzzi, Pietro Buono, Roberta Cardani, Giuliana Cardinale, Alberto Casertano, Maria Cristina Castiglione, Vittoria Cauvin, Valentino Cherubini, Franco Chiarelli, Giovanni Chiari, Stefano Cianfarani, Dante Cirillo, Felice Citriniti, Susanna Coccioli, Anna Cogliardi, Santino Confetto, Giovanna Contreas, Anna Corò, Elisa Corsini, Nicoletta Cresta, Fiorella De Berardinis, Valeria De Donno, Giampaolo De Filippo, Rosaria De Marco, Annalisa Deodati, Elena Faleschini, Valentina Fattorusso, Valeria Favalli, Barbara Felappi, Lucia Ferrito, Graziella Fichera, Franco Fontana, Elena Fornari, Roberto Franceschi, Francesca Franco, Adriana Franzese, Anna Paola Frongia, Alberto Gaiero, Francesco Gallo, Luigi Gargantini, Elisa Giani, Chiara Giorgetti, Giulia Bianchi, Vanna Graziani, Antonella Gualtieri, Monica Guasti, Gennaro Iannicelli, Antonio Iannilli, Ignaccolo Giovanna, Dario Ingletto, Stefania Innaurato, Elena Inzaghi, Brunella Iovane, Peter Kaufmann, Alfonso La Loggia, Rosa Lapolla, Anna Lasagni, Nicola Lazzaro, Lorenzo Lenzi, Riccardo Lera, Gabriella Levantini, Fortunato Lombardo, Antonella Lonero, Silvia Longhi, Sonia Lucchesi, Lucia Paola Guerraggio, Sergio Lucieri, Patrizia Macellaro, Claudio Maffeis, Bendetta Mainetti, Giulio Maltoni, Chiara Mameli, Francesco Mammì, Maria Luisa Manca-Bitti, Melania Manco, Monica Marino, Matteo Mariano, Marco Marigliano, Alberto Marsciani, Costanzo Mastrangelo, Maria Cristina Matteoli, Elena Mazzali, Franco Meschi, Antonella MIgliaccio, Anita Morandi, Gianfranco Morganti, Enza Mozzillo, Gianluca Musolino, Rosa Nugnes, Federica Ortolani, Daniela Pardi, Filomena Pascarella, Stefano Passanisi, Annalisa Pedini, Cristina Pennati, Angelo Perrotta, Sonia Peruzzi, Paola Peverelli, Giulia Pezzino, Anita Claudia Piona, Gavina Piredda, Carmelo Pistone, Elena Prandi, Barbara Pedieri, Procolo Di Bonito, Anna Pulcina, Maria Quinci, Emioli Randazzo, Rossella Ricciardi, Carlo Ripoli, Rosanna Roppolo, Irene Rutigliano, Alberto Sabbio, Silvana salardi, Alessandro Salvatoni, Anna Saporiti, Rita Sardi, Mariapiera Scanu, Andrea Scaramuzza, Eleonardo Schiven, Andrea Secco, Linda Sessa, Paola Sogno Valin, Silvia Sordelli, Luisa Spallino, Stefano Stagi, Filomena Stamati, Tosca Suprani, Valentina Talarico, Tiziana Timapanaro, Antonella Tirendi, Letizia Tomaselli, Gianluca Tornese, Adolfo Andrea Trettene, Stefano Tumini, Giuliana Valerio, Claudia Ventrici, Matteo Viscardi, Silvana Zaffani, Maria Zampolli, Giorgio Zanette, Clara Zecchino, Maria Antonietta Zedda, Silvia Zonca, Stefano Zucchini, Bonfanti, R., Iafusco, D., Rabbone, I., Diedenhofen, G., Bizzarri, C., Patera, P. I., Reinstadler, P., Costantino, F., Calcaterra, V., Iughetti, L., Savastio, S., Favia, A., Cardella, F., Presti, D. L., Girtler, Y., Rabbiosi, S., D'Annunzio, G., Zanfardino, A., Piscopo, A., Casaburo, F., Pintomalli, L., Russo, L., Grasso, V., Minuto, N., Mucciolo, M., Novelli, A., Marucci, A., Piccini, B., Toni, S., Silvestri, F., Carrera, P., Rigamonti, A., Frontino, G., Trada, M., Tinti, D., Delvecchio, M., Rapini, N., Schiaffini, R., Mammi, C., and Barbetti, F.
Subjects: Proband, Male, Pediatrics, Potassium Channels, Endocrinology, Diabetes and Metabolism, Datasets as Topic, Diagnosis, Differential, Diagnostic Techniques, Endocrine, Female, Humans, Infant, Infant, Newborn, Italy, Mutation, Potassium Channels, Inwardly Rectifying, Remission Induction, Retrospective Studies, Sulfonylurea Receptors, Diabetes Mellitus, Infant, Newborn, Diseases, Diseases, Gastroenterology, Diabetes mellitus genetics, Endocrinology, Settore MED/13, Retrospective Studie, Diagnosis, Medicine, Endocrine pancreas, Transient Neonatal Diabetes Mellitus, 6q24 TNDM, KATP TNDM, Sulfonylureas, Sulfonylureas, Sulfonylurea Receptor, biology, Diabetes Mellitu, General Medicine, Metformin, Inwardly Rectifying, Settore MED/03, 6q24 TNDM, medicine.symptom, Endocrine, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Human, endocrine system, medicine.medical_specialty, KATP TNDM, ABCC8, Transient Neonatal Diabetes Mellitus, Internal medicine, Diabetes mellitus, Macroglossia, Endocrine pancreas, business.industry, medicine.disease, Newborn, Diagnostic Techniques, Transient neonatal diabetes mellitus, Differential, biology.protein, Sulfonylurea receptor, business
Abstract: Objective Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design Retrospective analysis of the Italian data set of patients with TNDM. Methods Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
Published: 2021

24. Hypogonadism in male and female: which is the best treatment?

Author: Mariacarolina Salerno, Luisa De Sanctis, Carla Bizzarri, Marco Cappa, Enrica Bertelli, Marianna Di Frenna, Malgorzata Wasniewska, Bertelli, E., DI Frenna, M., Cappa, M., Salerno, M., Wasniewska, M., Bizzarri, C., and DE Sanctis, L.
Subjects: Delayed puberty, Male, Pediatrics, medicine.medical_specialty, Adolescent, Hormone Replacement Therapy, media_common.quotation_subject, Fertility, Young Adult, Hypergonadotropic hypogonadism, Medicine, Humans, Testosterone, Young adult, media_common, Gonadotropin, Puberty, Delayed, business.industry, Hypogonadism, Testosterone (patch), medicine.disease, Hypogonadotripic and hypergonadotropic hypogonadism, Transgender hormone therapy, Pediatrics, Perinatology and Child Health, Etiology, Female, medicine.symptom, business, Psychosocial, Gonadotropins, Human
Abstract: INTRODUCTION: Subjects with hypo- or hypergonadotropic hypogonadism need hormone replacement therapy (HRT) to initiate puberty and maintain it with a normal hormonal status. While general recommendations for the management of HRT in adults have been published, no systematic suggestions focused on adolescents and young adults. The focus of this review is the HRT in males and females with hypogonadism, from puberty to late reproductive age, covering the different management options, encompassing sex steroid or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatments. EVIDENCE ACQUISITION: We conducted an extensive search in the 3 major scientific databases (PubMed, EMBASE and Google Scholar) using the keywords "hormonal replacement therapy," "hypogonadism," "bone mineral density," "estradiol/testosterone," "puberty induction," "delayed puberty." Case-control studies, case series, reviews and meta-analysis published in English from 1990 to date were included. EVIDENCE SYNTHESIS: By considering the available opportunities for fertility induction and preservation, we hereby present the proposals of practical schemes to induce puberty, and a decisional algorithm to approach HRT in postpubertal adolescents. CONCLUSIONS: A condition of hypogonadism can underlie different etiologies involving the hypothalamic-pituitary-gonadal axis at different levels. Since the long-terms effects of hypogonadism may vary and include not only physical outcomes related to sex hormone deficiencies, but also psychological problems and implications on fertility, the initiation, maintenance and consolidation of puberty with different pharmaceutical options is of utmost importance and beside pubertal development, optimal uterine and testicular growth and adequate bone health should consider also the psychosocial wellbeing and the potential fertility.
Published: 2021

25. Growth Trajectory and Adult Height in Children with Nonclassical Congenital Adrenal Hyperplasia

Author: Carla Bizzarri, Rita Ortolano, Silvia Einaudi, Mariangela Chiarito, Tommaso Aversa, Mariacarolina Salerno, Federico Baronio, Laura Guazzarotti, Angela Alibrandi, Maria Felicia Faienza, Domenico Corica, Donatella Capalbo, Barbara Baldini Ferroli, Enrica Abrigo, Malgorzata Wasniewska, Anna Grandone, Antonio Balsamo, Antonietta Spinuzza, Gianni Russo, Letteria Morabito, Wasniewska, M. G., Morabito, L. A., Baronio, F., Einaudi, S., Salerno, M., Bizzarri, C., Russo, G., Chiarito, M., Grandone, A., Guazzarotti, L., Spinuzza, A., Corica, D., Ortolano, R., Balsamo, A., Abrigo, E., Baldini Ferroli, B., Alibrandi, A., Capalbo, D., Aversa, T., and Faienza, M. F.
Subjects: Adult, Male, medicine.medical_specialty, Hydrocortisone, Pediatric endocrinology, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 21-hydroxylase deficiency, Models, Biological, Adult height, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Congenital adrenal hyperplasia, Child, Retrospective Studies, 030219 obstetrics & reproductive medicine, Adrenal Hyperplasia, Congenital, business.industry, 21-hydroxylase deficiency, Adult height, Growth and puberty, Nonclassical 21-hydroxylase deficiency, Severity of phenotype, Bone age, Stepwise regression, medicine.disease, Body Height, Child, Preschool, Pediatrics, Perinatology and Child Health, Bone maturation, Nonclassical 21-hydroxylase deficiency, Population study, Growth and puberty, Female, business, Severity of phenotype, medicine.drug
Abstract: Background: Children with nonclassical congenital adrenal hyperplasia (NCCAH) often present increased growth velocity secondary to elevation of adrenal androgens that accelerates bone maturation and might compromise adult height (AH). Objective: The aim of the study was to analyze prognostic factors affecting growth trajectory (GT) and AH in children with NCCAH. Methods: The study was a retrospective, multicentric study. The study population consisted of 192 children with a confirmed molecular diagnosis of NCCAH, followed by pediatric endocrinology centers from diagnosis up to AH. Clinical records were collected and analyzed. AH (standard deviation score; SDS), pubertal growth (PG) (cm), GT from diagnosis to AH (SDS), and AH adjusted to target height (TH) (AH-TH SDS) were evaluated as outcome indicators using stepwise linear regression models. Results: The stepwise linear regression analysis showed that AH and AH-TH were significantly related to chronological age (CA) (p = 0.008 and 0.016), bone age (BA)/CA ratio (p = 0.004 and 0.001), height (H) (p < 0.001 for both parameters) at NCCAH diagnosis, and TH (p = 0.013 and p = 0.002), as physiologically observed, and was positively related to height (p = 0.027), negatively to BMI (p = 0.001) and BA/CA ratio (p = 0.001) at NCCAH diagnosis. Gender, genotype, biochemical data, and hydrocortisone treatment did not significantly impair height outcomes of these NCCAH children. Conclusions: The results of this study suggest that AH and GT of NCCAH patients are mainly affected by the severity of phenotype (CA, BA/CA ratio, and H) at the time of diagnosis.
Published: 2020

26. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

Author: Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani, G Aimaretti, M Altobelli, M R Ambrosio, M Andrioli, G Angeletti, F Arecco, G Arnaldi, M Arosio, A Balsamo, M Baldassarri, L Bartalena, N Bazzoni, L Beccaria, P Beck-Peccoz, G Bellastella, M Bellizzi, F Benedicenti, S Bernasconi, C Bizzarri, G Bona, S Bonadonna, G Borretta, M Boschetti, A Brunani, V Brunelli, F Buzi, C Cacciatore, B Cangiano, M Cappa, R Casalone, A Cassio, P Cavarzere, V Cherubini, T Ciampani, D Cicognani, A Cignarelli, M Cisternino, P Colombo, S Corbetta, N Corciulo, G Corona, R Cozzi, C Crivellaro, I Dalle Mule, L Danesi, A V D’Elia, E degli Uberti, S De Leo, E Della Valle, M De Marchi, N Di Iorgi, A Di Mambro, A Fabbri, C Foresta, G Forti, A R Franceschi, A Garolla, M Ghezzi, C Giacomozzi, M Giusti, E Grosso, G Guabello, M P Guarneri, G Grugni, A M Isidori, F Lanfranco, A Lania, R Lanzi, L Larizza, A Lenzi, S Loche, P Loli, V Lombardi, M C Maggio, G Mandrile, C Manieri, G Mantovani, S Marelli, M Marzullo, M A Mencarelli, N Migone, G Motta, G Neri, G Padova, G Parenti, B Pasquino, A Pia, E Piantanida, E Pignatti, A Pilotta, B Pivetta, M Pollazzon, A Pontecorvi, P Porcelli, G B Pozzan, G Pozzobon, G Radetti, P Razzore, L Rocchetti, R Roncoroni, G Rossi, E Sala, A Salvatoni, F Salvini, A Secco, M Segni, R Selice, P Sgaramella, F Sileo, A A Sinisi, F Sirchia, A Spada, A Tresoldi, R Vigneri, G Weber, S Zucchini, Bonomi, Marco, Vezzoli, Valeria, Krausz, Csilla, Guizzardi, Fabiana, Vezzani, Silvia, Simoni, Manuela, Bassi, Ivan, Duminuco, Paolo, Di Iorgi, Natascia, Giavoli, Claudia, Pizzocaro, Alessandro, Russo, Gianni, Moro, Mirella, Fatti, Letizia, Ferlin, Alberto, Mazzanti, Laura, Zatelli Maria, Chiara, Cannavò, Salvo, Isidori Andrea, M., Pincelli Angela, Ida, Prodam, Flavia, Mancini, Antonio, Limone, Paolo, Tanda Maria, Laura, Gaudino, Rossella, Salerno, Mariacarolina, Francesca, Pregnolato, Maghnie, Mohamad, Maggi, Mario, Persani, Luca, Italian Network on Central, Hypogonadism., Zatelli, Maria Chiara, Cannavã², Salvo, Isidori, Andrea M., Pincelli, Angela Ida, Tanda, Maria Laura, Aimaretti, G., Altobell, M., Ambrosio, M. R., Andrioli, M., Angelett, G., Arecco, F., Arnald, G., Arosio, M., Balsamo, A., Baldassarr, M., Bartalena, L., Bazzon, N., Beccari, L., Beck-Peccoz, P., Bellastella, G., Bellizz, M., Benedicent, F., Bernasconi, S., Bizzarri, C., Bona, G., Bonadonna, S., Borrett, G., Boschetti, M., Brunani, A., Brunelli, V., Buz, F., Cacciatore, C., Cangiano, B., Cappa, M., Casalone, R., Cassio, A., Cavarzere, P., Cherubini, V., Ciampani, T., Cicognan, D., Cignarell, A., Cisternin, M., Colombo, P., Corbetta, S., Corciul, N., Corona, G., Cozzi, R., Crivellaro, C., Dalle Mule, I., Danesi, L., Eli, A. V. D., Degli Uberti, E., De Leo, S., Della Valle, E., De Marchi, M., Di Iorgi, N., Di Mambr, A., Fabbri, A., Foresta, C., Forti, G., Franceschi, A. R., Garolla, A., Ghezzi, M., Giacomozzi, C., Giusti, M., Grosso, E., Guabello, G., Guarneri, M. P., Grugni, G., Isidori, A. M., Lanfranco, F., Lania, A., Lanzi, R., Larizza, L., Lenzi, A., Loche, S., Loli, P., Lombardi, V., Maggi, M. C., Mandrile, G., Manieri, C., Mantovani, G., Marelli, S., Marzullo, M., Mencarelli, M. A., Migone, N., Motta, G., Neri, G., Padov, G., Parenti, G., Pasquino, B., Pia, A., Piantanida, E., Pignatti, E., Pilotta, A., Pivett, B., Pollazzon, M., Pontecorvi, A., Porcelli, P., Pozza, G. B., Pozzobon, G., Radetti, G., Razzore, P., Rocchett, L., Roncoron, R., Rossi, G., Sala, E., Salvatoni, A., Salvini, F., Secc, A., Segni, M., Selice, R., Sgaramella, P., Sileo, F., Sinisi, A. A., Sirchia, F., Spada, A., Tresoldi, A., Vigneri, R., Weber, G., Zucchini, S., Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani, Italian Network on Central Hypogonadism […, A. Cassio, …, S. Zucchini, ], Isidori, Andrea M, Weber, Giovanna, and Italian Network on Central, Hypogonadism
Subjects: 0301 basic medicine, Male, Pediatrics, Synkinesis, Kallmann syndrome, diagnosis, genotype, Endocrinology, Diabetes and Metabolism, Gonadal Steroid Hormone, Cohort Studies, Olfaction Disorders, 0302 clinical medicine, Endocrinology, Olfaction Disorder, Young adult, Age of Onset, Gonadal Steroid Hormones, Gonadotropin, Pituitary Hormone, Isolated hypogonadotropic hypogonadism, General Medicine, isolated hypogonadotropic hypogonadism, pubertal delay, genetic-basis, gonadotropin-deficiency, Diabetes and Metabolism, Phenotype, Italy, Cohort, Female, complex, Cohort study, Human, Adult, medicine.medical_specialty, Adolescent, Gonadotropins, Humans, Hypogonadism, Obesity, Overweight, Pituitary Hormones, Young Adult, 030209 endocrinology & metabolism, NO, 03 medical and health sciences, Hypogonadotropic hypogonadism, Adolescent, Adult, Age of Onset, Cohort Studies, Female, Gonadal Steroid Hormones, Gonadotropins, Humans, Hypogonadis, Italy, Male, Obesity, Olfaction Disorders, Overweight, Phenotype, Pituitary Hormones, Synkinesis, Young Adult, Endocrinology, Diabetes and Metabolism, Endocrinology, Internal medicine, medicine, Isolated hypogonadotropic hypogonadism, Kallmann syndrome, Observational cohort study, gnrh deficiency, disease, business.industry, Settore MED/13 - ENDOCRINOLOGIA, isolated Hypogonadotropic hypogonadism, kallmann syndrome, medicine.disease, body regions, 030104 developmental biology, Sex steroid, linked kallmann-syndrome, heterogeneity, phenotype, Observational cohort study, Synkinesi, Age of onset, Cohort Studie, business
Abstract: Objective Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Conclusions Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.
Published: 2018

27. 2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors

Author: Francesco Colotta, Rosa Di Bitondo, Riccardo Bertini, Maria Candida Cesta, Piercarlo Fantucci, Nicoletta Di Bello, Valerio Berdini, Nicolini Luca, Marcello Allegretti, S. Florio, Giuseppe Nano, Vito Di Cioccio, Alessandra Topai, Massimo Locati, Vincenzo Russo, Cinzia Bizzarri, Emanuela Galliera, Giuseppe Zampella, Allegretti, M, Bertini, R, Cesta, M, Bizzarri, C, Di Bitondo, R, Di Cioccio, V, Galliera, E, Berdini, V, Topai, A, Zampella, G, Russo, V, Di Bello, N, Nano, G, Nicolini, L, Locati, M, Fantucci, P, Florio, S, and Colotta, F
Subjects: Models, Molecular, musculoskeletal diseases, Lymphoma, Ligands, CXCR3, Receptors, Interleukin-8A, Mice, Structure-Activity Relationship, Chemokine receptor, Cell Movement, Cell Line, Tumor, Drug Discovery, Animals, Humans, CXC chemokine receptors, CXCL14, Binding Sites, Chemistry, hemic and immune systems, Recombinant Proteins, Chemotaxis, Leukocyte, CXCL2, Biochemistry, Ketoprofen, molecular modelling, molecular mechanics, molecular dynamics, ligand, binding pocket, CXCR1, reperfusion injury, repertaxin, Macrophages, Peritoneal, Mutagenesis, Site-Directed, Molecular Medicine, XCL2, CXCL9, Female, Propionates, Chemokines, CXC, CCL21
Abstract: The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCLS-induced human PMNs chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury. © 2005 American Chemical Society.
Published: 2005
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28. Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene

Author: Fabrizio Barbetti, Stefano Tumini, Riccardo Bonfanti, D. Iafusco, Franco Meschi, Carla Bizzarri, Marco Cappa, F. Cerutti, Francesco Prisco, E. Ciacco, C. Torelli, Maurizio Vanelli, E. Faleschini, V. Cauvin, G. Tonini, Tonini, G, Bizzarri, C, Bonfanti, R, Vanelli, M, Cerutti, F, Faleschini, E, Meschi, F, Prisco, F, Ciacco, E, Cappa, M, Torelli, C, Cauvin, V, Tumini, S, Iafusco, Dario, Barbetti, F, EARLY ONSET DIABETES STUDY GROUP OF THE ITALIAN SOCIETY OF, Paediatric, ENDOCRINOLOGY AND, Diabetology, and Iafusco, D
Subjects: Blood Glucose, Potassium Channels, diabetes control, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, diarrhea, antidiabetic agent, glibenclamide, glipizide, insulin, sulfonylurea, clinical article, clinical trial, diabetes mellitus, gene mutation, gestational age, human, letter, missense mutation, newborn, newborn period, priority journal, Amino Acid Substitution, Child, Diabetes Mellitus, Humans, Hypoglycemic Agents, Infant, Infant, Newborn, Infant, Newborn, Diseases, Insulin, Mutation, Potassium Channels, Inwardly Rectifying, Sulfonylurea Compounds, Treatment Outcome, Diseases, Settore MED/13 - Endocrinologia, Diabetes mellitus genetics, Neonatal diabetes mellitus, neonatal diabetes mellitus, KCNJ11, Kir6.2, Permanent neonatal diabetes mellitus, Inwardly Rectifying, endocrine system, medicine.medical_specialty, medicine.drug_class, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, business.industry, nutritional and metabolic diseases, medicine.disease, Sulfonylurea, Endocrinology, Sulfonylurea receptor, business
Abstract: To the Editor, Activating missense mutations in the gene encoding potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) represent the most common cause (40 to 64%, depending on populations) of permanent neonatal diabetes mellitus in patients diagnosed in the first 6 months of life [1, 2]. In addition, KCNJ11 activating mutations can lead to transient/relapsing neonatal diabetes [3, 4]. The KCNJ11 gene encodes the pore-forming subunit (also known as KIR6.2) of the pancreatic beta cell ATP-sensitive potassium channel (KATP), which exerts a pivotal role in glucose-regulated insulin release. In the beta cell, KIR6.2 forms a hetero-octameric complex (4:4) with the sulfonylurea receptor subtype 1 (SUR1); binding to SUR1 by sulfonylureas determines channel closure and insulin secretion [2]. In previously published cases, seven patients have been reported to respond well to the transfer from insulin to oral hypoglycaemic agents [4–8]. Here we report on the replacement of insulin with sulfonylureas in ten Italian children who have mutations in KCNJ11 (R50P, V59M [x4], K170R, R201C and R201H [x3]) and were followed in nine Diabetologia (2006) 49:2210–2213 DOI 10.1007/s00125-006-0329-x
Published: 2006

29. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury

Author: Cinzia Bizzarri, Maria Neve Cervellera, Massimo Locati, Emanuela Galliera, Pia Villa, Giuseppe Poli, Daniela Corda, Gaetano D'Anniballe, Maria Di Girolamo, Fabrizio Mainiero, Raffaele Strippoli, Giuseppe Zampella, Fernando O. Martinez, Franck Martin, Riccardo Bertini, Gentile Marco, Marcello Allegretti, Vilma Sabbatini, Angela Santoni, Rosa Di Bitondo, Vito Di Cioccio, Pietro Ghezzi, Maria Candida Cesta, Roberto Anacardio, Alessio Moriconi, Francesco Colotta, Alberto Mantovani, Giulia Troiani, B Cavalieri, Juan Carlos Cutrin, Bertini, R, Allegretti, M, Bizzarri, C, Moriconi, A, Locati, M, Zampella, G, Cervellera, M, Di Cioccio, V, Cesta, M, Galliera, E, Martinez, F, Di Bitondo, R, Troiani, G, Sabbatini, V, D'Anniballe, G, Anacardio, R, Cutrin, J, Cavalieri, B, Mainiero, F, Strippoli, R, Villa, P, Di Girolamo, M, Martin, F, Gentile, M, Santoni, A, Corda, D, Poli, G, Mantovani, A, Ghezzi, P, and Colotta, F
Subjects: Models, Molecular, Chemokine, Protein Conformation, Allosteric regulation, C-C chemokine receptor type 6, Biology, Pharmacology, CXCR3, Receptors, Interleukin-8A, Chemokine receptor, Structure-Activity Relationship, Allosteric Regulation, Animals, Humans, Interleukin 8, CXC chemokine receptors, Settore MED/04 - Patologia Generale, Inflammation, Sulfonamides, Multidisciplinary, Binding Sites, Liver Diseases, Biological Sciences, Rats, Biochemistry, Reperfusion Injury, biology.protein, molecular modelling, CXCR1, chemokine, GPCR, 7TM receptor, reperfusion injury, Signal transduction, Signal Transduction
Abstract: The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling. Repertaxin is an effective inhibitor of polymorphonuclear cell recruitmentin vivoand protects organs against reperfusion injury. Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors.
Published: 2004

30. Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births

Author: D. Lo Presti, S. Brescianini, T. Suprani, Riccardo Schiaffini, Colin G. Nichols, Riccardo Bonfanti, Lucia Russo, B. Pasquino, D. Iafusco, Ornella Massa, Lorenzo Iughetti, Carla Bizzarri, Corrado Mammì, Valeria Grasso, Carlo Colombo, Fabrizio Barbetti, Franco Meschi, Iafusco, Dario, Massa, O, Pasquino, B, Colombo, C, Iughetti, L, Bizzarri, C, Mammì, C, Lo Presti, D, Suprani, T, Schiaffini, R, Nichols, Cg, Russo, L, Grasso, V, Meschi, F, Bonfanti, R, Brescianini, S, Barbetti, F, and The Early Diabetes Study Group of, Isped
Subjects: Male, Pediatrics, medicine.medical_specialty, Neonatal diabetes, Short Communication, Endocrinology, Diabetes and Metabolism, KCNJ11 gene, ABCC8 gene, INS gene, neonatal diabetes, Reference laboratory, Infant, Newborn, Diseases, ABCC8, Settore MED/13 - Endocrinologia, Neonatal diabetes mellitus, Endocrinology, Diabetes mellitus, medicine, Internal Medicine, Humans, Transient neonatal diabetes mellitus, Permanent neonatal diabetes mellitus, biology, business.industry, Incidence, Incidence (epidemiology), Infant, Newborn, Infant, General Medicine, medicine.disease, Diabetes Mellitus, Type 1, Italy, Mutation, biology.protein, Female, business, Live Birth
Abstract: Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000–1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005–2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000–1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.
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30 results on '"Bizzarri C"'

1. Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

2. Growth hormone treatment improves final height and nutritional status of children with chronic kidney disease and growth deceleration

3. Raised C-reactive protein levels in patients with recent onset type 1 diabetes

4. A New Homozygous Frameshift Mutation in the HSD3B2 Gene in an Apparently Nonconsanguineous Italian Family

5. Early and progressive insulin resistance in young, non-obese cancer survivors treated with hematopoietic stem cell transplantation

6. Cushing’s Syndrome in a 6-month-old Boy: A Rare Side-effect due to Inadequate use of Topical Corticosteroids

7. Age at Diagnosis of Type 1 Diabetes and the Effect of Immunomodulatory Therapies on Residual Beta Cell Function

8. Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes

9. Diabetes-related autoantibodies in children with acute lymphoblastic leukemia

10. Type 1 diabetes and measles, mumps and rubella childhood infections within the Italian Insulin-dependent Diabetes Registry

11. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor

12. No protective effect of calcitriol on Î²-cell function in recent-onset type 1 diabetes: The IMDIAB XIII trial

13. Incidence of type 1 diabetes has doubled in Rome and the Lazio region in the 0- to 14-year age-group: A 6-year prospective study (2004-2009)

14. The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI)

15. Intradermal skin test with diabetes specific antigens in patients with type 1 diabetes

16. Inhibitory activity of IL-1 receptor antagonist depends on the balance between binding capacity for IL-1 receptor type 1 and IL-1 receptor type II

17. Mapping of receptor binding sites on IL-1 beta by reconstruction of IL-1ra-like domains

18. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus

19. [Wolfram syndrome. Personal experience]

20. Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

21. Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders

22. Biological clock and heredity in pubertal timing: what is new?

23. Differences between Transient Neonatal Diabetes Mellitus Subtypes can Guide Diagnosis and Therapy

24. Hypogonadism in male and female: which is the best treatment?

25. Growth Trajectory and Adult Height in Children with Nonclassical Congenital Adrenal Hyperplasia

26. Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

27. 2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors

28. Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene

29. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury

30. Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births

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