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4. 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

6. Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Author

Nucci, A. M., Virtanen, S. M., Sorkio, S., Barlund, S., Cuthbertson, D., Uusitalo, U., Lawson, M. L., Salonen, M., Berseth, C. L., Ormisson, A., Lehtonen, E., Savilahti, E., Becker, D. J., Dupre, J., Krischer, J. P., Knip, M., Akerblom, H. K., Mandrup-Poulsen, T., Arjas, E., Laara, E., Lernmark, A., Schmidt, B., Hyytinen, M., Koski, K., Koski, M., Pajakkala, E., Shanker, L., Bradley, B., Dosch, H. -M., Fraser, W., Lawson, M., Mahon, J. L., Sermer, M., Taback, S. P., Becker, D., Franciscus, M., Nucci, A., Palmer, J., Pekkala, M., Catteau, J., Howard, N., Crock, P., Craig, M., Clarson, C. L., Bere, L., Thompson, D., Metzger, D., Kwan, J., Stephure, D. K., Pacaud, D., Ho, J., Schwarz, W., Girgis, R., Thompson, M., Catte, D., Daneman, D., Martin, M. -J., Morin, V., Frenette, L., Ferland, S., Sanderson, S., Heath, K., Huot, C., Gonthier, M., Thibeault, M., Legault, L., Laforte, D., Cummings, E. A., Scott, K., Bridger, T., Crummell, C., Newman, S., Houlden, R., Breen, A., Carson, G., Kelly, S., Sankaran, K., Penner, M., White, R. A., Hardy Brown, K., King, N., Popkin, J., Robson, L., Coles, K., Al Taji, E., Aldhoon, I., Mendlova, P., Vavrinec, J., Vosahlo, J., Brazdova, L., Venhacova, J., Venhacova, P., Cipra, A., Tomsikova, Z., Paterova, P., Gogelova, P., Einberg, U., Riikjarv, M. -A., Tillmann, V., Hirvasniemi, M., Kleemola, P., Parkkola, A., Suomalainen, H., Jarvenpaa, A. -L., Hamalainen, A. -M., Haavisto, H., Tenhola, S., Lautala, P., Salonen, P., Aspholm, S., Siljander, H., Holm, C., Ylitalo, S., Lounamaa, R., Nuuja, A., Talvitie, T., Lindstrom, K., Huopio, H., Pesola, J., Veijola, R., Tapanainen, P., Alar, A., Korpela, P., Kaar, M. -L., Mustila, T., Virransalo, R., Nykanen, P., Aschemeier, B., Danne, T., Kordonouri, O., Krikovszky, D., Madacsy, L., Khazrai, Y. M., Maddaloni, E., Pozzilli, P., Mannu, C., Songini, M., de Beaufort, C., Schierloh, U., Bruining, J., Basiak, A., Wasikowa, R., Ciechanowska, M., Deja, G., Jarosz-Chobot, P., Szadkowska, A., Cypryk, K., Zawodniak-Szalapska, M., Castano, L., Gonzalez Frutos, T., Oyarzabal, M., Serrano-Rios, M., Martinez-Larrad, M. T., Hawkins, F. G., Rodriguez Arnau, D., Ludvigsson, J., Smolinska Konefal, M., Hanas, R., Lindblad, B., Nilsson, N. -O., Fors, H., Nordwall, M., Lindh, A., Edenwall, H., Aman, J., Johansson, C., Gadient, M., Schoenle, E., Daftary, A., Klein, M. B., Gilmour, C., Malone, P., Tanner-Blasiar, M., White, N., Devaskar, U., Horowitz, H., Rogers, L., Colon, R., Frazer, T., Torres, J., Goland, R., Greenberg, E., Nelson, M., Schachner, H., Softness, B., Ilonen, J., Trucco, M., Nichol, L., Harkonen, T., Vaarala, O., and Luopajarvi, K.

Subjects
Canada, endocrine system diseases, infant feeding, breastfeeding, type 1 diabetes, breastfeeding duration, complementary feeding, infant formula, Infant, Article, United States, Diet, Nutrition Policy, Europe, Diabetes Mellitus, Type 1, Milk, Nutrition Assessment, Double-Blind Method, Surveys and Questionnaires, Animals, Humans, Infant Food, Prospective Studies, Infant Nutritional Physiological Phenomena
Abstract

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double-blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D-associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first-degree relative with T1D and increased human leukocyte antigen-conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.

Published
2017

10. Increase in the Incidence of Type 1 Diabetes Mellitus in Children in Three Cities in Poland, 1987-1999

Author

H Trippenbach-Dulska, Wasikowa R, Hanna Dziatkowiak, Ciechanowska M, Zbigniew Szybiński, A Symonides-ławecka, Bieniasz J, and Korniszewski L

Subjects
Male, Rural Population, Pediatrics, medicine.medical_specialty, Adolescent, Urban Population, Endocrinology, Diabetes and Metabolism, Population, Newly diagnosed, Endocrinology, Humans, Medicine, Prospective Studies, Child, education, Prospective cohort study, education.field_of_study, Type 1 diabetes, business.industry, Incidence, Incidence (epidemiology), medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Christian ministry, Poland, business, Rural population
Abstract

The aim of this study was to evaluate the trends in the incidence of type 1 diabetes mellitus (DM) in children aged 0-14 years between 1987 and 1999 in three cities in Poland. The study area comprised the provinces of Cracow and Wroclaw and the city of Warsaw. The data were collected prospectively on the basis of the register within the framework of the EURODIAB study up till 1997 and then within the project of the Ministry of Health. During the 13 years of the study period, 766 children (380 girls, 386 boys) with newly diagnosed type 1 DM were identified. The overall age-standardized incidence rates were 8.4/100,000 standardized population/year (95% CI 7.4-9.3) for Cracow province, 6.5/100,000/year (95% CI 5.6-7.4) for Wroclaw province and 7.9/100,000/year (95% CI 6.9-8.8) for Warsaw. A significant trend of increase for children aged 0-14 years was found in the three cities. The analysis of the trend in age subgroups showed a significant increase in incidence in all three age subgroups in Warsaw and Cracow province (0-4 year-old children, p

Published
2002

12. The Central Effect of β-Endorphin and Naloxone on The Biosynthesis of Gn RH and Gn RH Receptor (Gn RHR) in The Hypothalamic-Pituitary Unit of Follicular-Phase Ewes.

Author

Ciechanowska, M, Łapot, M, Mateusiak, K, Paruszewska, E, Malewski, T, Krawczyńska, A, and Przekop, F

Subjects
*LUTEINIZING hormone releasing hormone receptors, *ENDORPHINS, *NALOXONE, *BIOSYNTHESIS, *CEREBRAL ventricles, *HYPOTHALAMIC-pituitary-adrenal axis
Abstract

Contents The effects of prolonged, intermittent infusion of β-endorphin or naloxone into the third cerebral ventricle of follicular-phase ewes on the expression of genes encoding Gn RH and Gn RHR in the hypothalamus and Gn RHR in the anterior pituitary gland (AP) were examined by an enzyme-linked immunoabsorbent assay. Activation or blockade of μ-opioid receptors significantly decreased or increased the Gn RH concentration and Gn RHR abundance in the hypothalamus, respectively, and affected in the same way Gn RHR quantity in the AP gland. The changes in the levels of Gn RH and Gn RHR after treatment with β-endorphin as well as following action of naloxone were reflected in fluctuations of plasma LH concentrations. On the basis of these results, it is suggested that β-endorphinergic system in the hypothalamus of follicular-phase ewes affects directly or via β-endorphin-sensitive interneurons Gn RH and Gn RHR biosynthesis leading to suppression in secretory activity of the hypothalamic-pituitary axis. [ABSTRACT FROM AUTHOR]

Published
2016
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14. Rapid increase in the incidence of type 1 diabetes in Polish children from 1989 to 2004, and predictions for 2010 to 2025

Author

Jarosz-Chobot, P., primary, Polanska, J., additional, Szadkowska, A., additional, Kretowski, A., additional, Bandurska-Stankiewicz, E., additional, Ciechanowska, M., additional, Deja, G., additional, Mysliwiec, M., additional, Peczynska, J., additional, Rutkowska, J., additional, Sobel-Maruniak, A., additional, Fichna, P., additional, Chobot, A., additional, and Rewers, M., additional

Published
2010
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21. Polish multicenter study on diabetes type 1 incidence in the age group 0-14 between 1998 and 1999,Wieloośrodkowe badania nad zapadalnościa̧ na cukrzycȩ typu 1 w grupie wiekowej 0-14 lat w Polsce w latach 1998-1999

Author

Szybiński, Z., Dziatkowiak, H., Wa̧sikowa, R., Kinalska, I., Korman, E., Grzywa, M., Korniszewski, L., Trippenbach, H., Bandurska-Stankiewicz, E., Pach, D., Płaczkiewicz, E., Ciechanowska, M., Bieniarz, J., Irina Kowalska, Stankiewicz, W., Sobel-Maruniak, A., Orłowska-Florek, R., Staniszewski, A., Symonides-Ławecka, A., Dziubińska-Kolender, E., Kiełtyka, A., and Walczycka, L.

24. Targeting sgRNA N secondary structure as a way of inhibiting SARS-CoV-2 replication.

Author

Baliga-Gil A, Soszynska-Jozwiak M, Ruszkowska A, Szczesniak I, Kierzek R, Ciechanowska M, Trybus M, Jackowiak P, Peterson JM, Moss WN, and Kierzek E

Subjects
Humans, Antiviral Agents pharmacology, Antiviral Agents chemistry, Coronavirus Nucleocapsid Proteins genetics, Coronavirus Nucleocapsid Proteins antagonists & inhibitors, Coronavirus Nucleocapsid Proteins metabolism, Coronavirus Nucleocapsid Proteins chemistry, Sulfuric Acid Esters pharmacology, Sulfuric Acid Esters chemistry, COVID-19 virology, RNA, Small Interfering genetics, RNA, Small Interfering pharmacology, RNA, Small Interfering chemistry, Oligonucleotides, Antisense pharmacology, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense chemistry, Genome, Viral, Phosphoproteins genetics, Phosphoproteins metabolism, Phosphoproteins chemistry, SARS-CoV-2 drug effects, SARS-CoV-2 genetics, Virus Replication drug effects, RNA, Viral genetics, Nucleic Acid Conformation
Abstract

SARS-CoV-2 is a betacoronavirus that causes COVID-19, a global pandemic that has resulted in many infections, deaths, and socio-economic challenges. The virus has a large positive-sense, single-stranded RNA genome of ∼30 kb, which produces subgenomic RNAs (sgRNAs) through discontinuous transcription. The most abundant sgRNA is sgRNA N, which encodes the nucleocapsid (N) protein. In this study, we probed the secondary structure of sgRNA N and a shorter model without a 3' UTR in vitro, using the SHAPE (selective 2'-hydroxyl acylation analyzed by a primer extension) method and chemical mapping with dimethyl sulfate and 1-cyclohexyl-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate. We revealed the secondary structure of sgRNA N and its shorter variant for the first time and compared them with the genomic RNA N structure. Based on the structural information, we designed gapmers, siRNAs and antisense oligonucleotides (ASOs) to target the N protein coding region of sgRNA N. We also generated eukaryotic expression vectors containing the complete sequence of sgRNA N and used them to screen for new SARS-CoV-2 gene N expression inhibitors. Our study provides novel insights into the structure and function of sgRNA N and potential therapeutic tools against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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25. Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis-A Systematic Review.

Author

Brodzikowska A, Ciechanowska M, Kopka M, Stachura A, and Włodarski PK

Subjects
Humans, Inflammation metabolism, Lipopolysaccharides pharmacology, Pulpitis metabolism
Abstract

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

Published
2022
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26. Increased prevalence of celiac disease and its clinical picture among patients with diabetes mellitus type 1 - observations from a single pediatric center in Central Europe.

Author

Wędrychowicz A, Minasyan M, Pietraszek A, Centkowski J, Stręk M, Różańska J, Chełmecka K, Zdzierak B, Wilk M, Czekańska P, Pacut P, Grzenda-Adamek Z, Małek J, Ciechanowska M, Stelmach M, Nazim J, and B Starzyk J

Subjects
Adolescent, Child, Child, Preschool, Europe, Female, Humans, Male, Prevalence, Retrospective Studies, Celiac Disease complications, Celiac Disease epidemiology, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 epidemiology
Abstract

Introduction: The aim of our study was to analyze the incidence and the clinical characteristic of celiac disease (CD) in pediatric population with type 1 diabetes mellitus (T1DM)., Material and Methods: The data of 880 patients with T1DM, 429 girls, mean age 12.14 ±4.0 years was retrospectively retrieved from medical records. Patients with T1DM and CD were selected and a detailed analysis of CD prevalence and its clinical characteristic at the time of CD diagnosis was performed. The data were compared with the previous data from our center published a decade ago., Results: CD was suspected in 85/880 patients (9.65%) on the base of results of serological tests, but finally CD was diagnosed in 73/880 patients with T1DM (8.3%), in 53/429 girls (12.3%) and in 20/451 boys (4.4%). Most patients (71%) had CD diagnosed after T1DM onset. The majority of CD patients (72%) was asymptomatic. The CD diagnosis was not associated with inappropriate metabolic control of diabetes. The onset age of diabetes in children with CD was significantly lower than in those without CD (5.8 ±3.6 years vs. 7.56 ±4.0 years, p = 0.04). The prevalence of CD is significantly higher than a decade ago in our center (8.3% vs. 5.7%, p = 0.001)., Conclusions: In light of increasing prevalence of mainly asymptomatic CD in patients with T1DM, CD screening is necessary. However positive serological tests, which are currently used in screening, and are the first step of diagnostics, in some patients allow only to suspect the CD and further diagnostic steps should be performed.

Published
2021
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27. Assessment of exogenous melatonin action on mouse liver cells after exposure to soman.

Author

Król T, Trybus W, Trybus E, Kopacz-Bednarska A, Kowalczyk M, Brytan M, Paluch M, Antkowiak B, Saracyn M, Król G, and Ciechanowska M

Subjects
Animals, Autophagy drug effects, Hepatocytes metabolism, Hepatocytes ultrastructure, Lipid Peroxidation drug effects, Lysosomes metabolism, Male, Mice, Inbred BALB C, Chemical Warfare Agents toxicity, Cholinesterase Inhibitors toxicity, Hepatocytes drug effects, Melatonin pharmacology, Protective Agents pharmacology, Soman toxicity
Abstract

Melatonin is a hormone with many different biological activities and therefore seems to be an important factor reducing the harmful effects caused by toxic organophosphorus compounds. In this study, we attempted to evaluate the protective effect of melatonin on liver cells of mice challenged with chemical warfare agent-soman. The study was conducted at the level of ultrastructural and biochemical changes (analysis of the activity of model lysosomal enzymes and assessment of the level of lipid peroxidation). Significant biochemical and ultrastructural changes were found in the studied mouse hepatocytes after administration of soman alone, and soman in combination with melatonin, and the scope of the disclosed changes was dependent on the time of action of the examined factors. Melatonin has shown protective action, shielding liver cells from toxic effects of soman, which may result from its antioxidant properties and stimulation of the lysosomal compartment, the system coordinating the isolation and removal of cell-threatening processes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
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28. Effect of corticotropin releasing hormone and corticotropin releasing hormone antagonist on biosynthesis of gonadotropin relasing hormone and gonadotropin relasing hormone receptor in the hypothalamic-pituitary unit of follicular-phase ewes and contribution of kisspeptin.

Author

Ciechanowska M, Kowalczyk M, Lapot M, Malewski T, Antkowiak B, Brytan M, Winnicka I, and Przekop F

Subjects
Animals, Female, Follicular Phase metabolism, Hydrocortisone blood, Hypothalamus drug effects, Kisspeptins genetics, Luteinizing Hormone blood, Receptors, Kisspeptin-1 genetics, Sheep, Corticotropin-Releasing Hormone antagonists & inhibitors, Corticotropin-Releasing Hormone pharmacology, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamus metabolism, Receptors, LHRH metabolism
Abstract

This study aimed to determine the mechanisms governing Gonadotropin releasing hormone (GnRH) biosynthesis and luteinising hormone (LH) secretion in follicular-phase sheep after infusion of corticotropin releasing hormone (CRH) and/or CRH antagonist corticotropin releasing hormone nist (CRH-A) into the third cerebral ventricle. The study included two experimental approaches: first, we investigated the effect of CRH or CRH-A (α-helical CRH 9-41) on GnRH and GnRH receptor (GnRHR) biosynthesis in the preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VMH), stalk/median eminence (SME), and on GnRHR in the anterior pituitary (AP) using an enzyme-linked immunosorbent assay (ELISA); second, we used real-time PCR to analyse the influence of CRH and CRH-A on the levels of kisspeptin (Kiss1) mRNA in POA and VMH including arcuate nucleus (VMH/ARC), and on Kiss1 receptor (Kiss1r) mRNA abundance in POA-hypothalamic structures. These analyses were supplemented by radioimmunoassay (RIA) and ELISA methods for measurement of LH and cortisol levels in the blood, respectively. Our results show that administration of CRH significantly decreased GnRH biosynthesis in the POA/hypothalamus. CRH also decreased GnRHR abundance in the hypothalamus and in the AP, but increased it in the POA. Furthermore, administration of CRH decreased plasma LH concentration and levels of Kiss1 mRNA in the POA and VMH/ARC as well as Kiss1r mRNA in these structures and in the SME. Significant increase in plasma cortisol concentration in the group treated with CRH was also observed. For CRH-A, all analysed effects were opposite to those induced by CRH. The study demonstrates that intracerebroventricular (i.c.v.) infusion of both CRH and CRH-A affects the GnRH/GnRHR biosynthesis and LH secretion in follicular-phase sheep conceivably via either central and peripheral mechanisms including Kiss1 neurons activity and cortisol signals. It has also been suggested that CRH and CRH-A infusion probably had effects directly at the AP.

Published
2018
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29. Biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in hypothalamic-pituitary unit of anoestrous and cyclic ewes.

Author

Ciechanowska MO, Łapot M, Mateusiak K, Paruszewska E, Malewski T, and Przekop F

Subjects
Anestrus blood, Animals, Anterior Hypothalamic Nucleus metabolism, Estrous Cycle blood, Female, Luteinizing Hormone blood, Median Eminence metabolism, Pituitary Gland metabolism, Preoptic Area metabolism, Sheep, Ventromedial Hypothalamic Nucleus metabolism, Anestrus metabolism, Estrous Cycle metabolism, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamo-Hypophyseal System metabolism, Receptors, LHRH biosynthesis
Abstract

This study was performed to explain how the molecular processes governing the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit are reflected by luteinizing hormone (LH) secretion in sheep during anoestrous period and during luteal and follicular phases of the oestrous cycle. Using an enzyme-linked immunosorbent assay (ELISA), we analyzed the levels of GnRH and GnRHR in preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk-median eminence (SME), and GnRHR in the anterior pituitary gland (AP). Radioimmunoassay has also been used to define changes in plasma LH concentrations. The study provides evidence that the levels of GnRH in the whole hypothalamus of anoestrous ewes were lower than that in sheep during the follicular phase of the oestrous cycle (POA: p < 0.001, AH: p < 0.001, VM: p < 0.01, SME: p < 0.001) and not always than in luteal phase animals (POA: p < 0.05, SME: p < 0.05). It has also been demonstrated that the GnRHR amount in the hypothalamus-anterior pituitary unit, as well as LH level, in the blood in anoestrous ewes were significantly lower than those detected in animals of both cyclic groups. Our data suggest that decrease in LH secretion during the long photoperiod in sheep may be due to low translational activity of genes encoding both GnRH and GnRHR.

Published
2017
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30. Incidence of type 1 diabetes mellitus during 26 years of observation and prevalence of diabetic ketoacidosis in the later years.

Author

Wojcik M, Sudacka M, Wasyl B, Ciechanowska M, Nazim J, Stelmach M, and Starzyk JB

Subjects
Adolescent, Age Distribution, Age Factors, Child, Child, Preschool, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 complications, Diabetic Ketoacidosis blood, Diabetic Ketoacidosis etiology, Female, Humans, Incidence, Infant, Infant, Newborn, Longitudinal Studies, Male, Poland epidemiology, Prevalence, Retrospective Studies, Severity of Illness Index, Sex Distribution, Blood Glucose analysis, Diabetes Mellitus, Type 1 epidemiology, Diabetic Ketoacidosis epidemiology, Forecasting
Abstract

Unlabelled: The prevalence of type 1 diabetes (T1D) varies greatly between countries. However, over the past several decades, a global rise in the incidence of T1D in the pediatric population has been noted. The aim of our study was to investigate the incidence of T1D in children living in the Lesser Poland during the period of time from January 1, 1987, to December 31, 2012, and to analyze the demographic characteristics and occurrence of diabetic ketoacidosis (DKA) in patients with newly diagnosed T1D in the second part of the study (2006-2012). During 26 years, 636 children (331 boys, 305 girls) aged 0-14 years were newly diagnosed with T1D (0-4 years old, n = 131; 5-9 years old, n = 253, 10-14 years old, n = 252). The standardized incidence ratio (SIR) ranged significantly (p < 0.001) from 5.2/100,000/year in 1987 to 21.9/100,000/year in 2012. The highest SIR was observed in age group 5-9 years old (21.2) and the lowest in 0-4 years old (8.8). There was no association with sex or living in urban or rural area. On admission, DKA was diagnosed in 22.4 % of patients. There were no significant differences relating to the presence of DKA (p = 0.912) in subsequent years., Conclusions: The incidence of T1D among children is increasing rapidly with the highest SIR in the 5-9 years old age group. DKA is still an important problem in the pediatric population., What Is Known: • The incidence of pediatric type 1 diabetes mellitus in Europe is increasing. The initial manifestation of the type 1 diabetes mellitus is diabetic ketoacidosis. What is New: • This is the longest (26 years) continuous analysis of the incidence of type 1 diabetes in Poland and the first analysis focused on the incidence rate and also on presence of diabetic ketoacidosis.

Published
2015
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31. Antinociceptive effect of D-Lys(2), Dab(4)N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog.

Author

Antkowiak B, Paluch M, Ciechanowska M, Nawrocka M, Bańkowski K, Michalak O, Kocik J, Kowalczyk M, and Izdebski J

Subjects
Analgesics, Opioid chemistry, Analgesics, Opioid therapeutic use, Animals, Male, Mice, Inbred BALB C, Motor Activity drug effects, Oligopeptides chemistry, Oligopeptides therapeutic use, Pain Measurement, Pain Threshold drug effects, Peptides, Cyclic chemistry, Peptides, Cyclic therapeutic use, Rotarod Performance Test, Visceral Pain drug therapy, Analgesics, Opioid pharmacology, Nociceptive Pain drug therapy, Oligopeptides pharmacology, Peptides, Cyclic pharmacology
Abstract

Background: A preliminary evaluation of antinociceptive activity of a new cyclic dermorphin/deltorphin tetrapeptide analog restricted via a urea bridge and containing C-terminal ureidoethylamid {[H-Tyr-d-Lys(&(1))-Phe-Dab(&(2))-CH2CH2NHCONH2][&(1)CO&(2)]} (cUP-1) revealed a significant and long-lasting increase of pain threshold to thermal stimulation after systemic application. The current studies were aimed at further evaluation of cUP-1 activity in animal models of somatic and visceral pain. The influence of cUP-1 on motor functions was also investigated., Methods: The influence of cUP-1 (0.5-2mgkg(-1), iv) on nociceptive threshold to mechanical pressure and analgesic efficacy in formalin and acetic acid-induced writhing tests were estimated. The antinociceptive effect of cUP-1 was compared to that of morphine (MF). The influence of cUP-1 (1, 4 and 8mgkg(-1), iv) on locomotor activity, motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement., Results: Administration of cUP-1 in doses of 1 and 2mgkg(-1) elicited a significant increase of nociceptive threshold to mechanical pressure. MF applied in the same doses induced an antinociceptive effect only at the higher dose (2mgkg(-1)). There were no marked differences between the effect of cUP-1 and MF at each dose, at relative time points. In the writhing test and both phases of the formalin test, cUP-1 showed a significant, dose-dependent antinociceptive effect which did not markedly differ from that of MF. cUP-1 did not significantly affect motor functions of mice., Conclusions: Systemic application of cUP-1 elicited a dose-dependent antinociceptive effect. The analgesic efficacy of cUP-1 on mechanical nociception, visceral and formalin-induced pain was comparable to that of MF. cUP-1 did not impair motor functions of mice., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Published
2014
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32. Diabetes mellitus after allogeneic hematopoietic stem cell transplantation.

Author

Wędrychowicz A, Ciechanowska M, Stelmach M, and Starzyk J

Subjects
Adolescent, Comorbidity, Diabetes Mellitus drug therapy, Diabetes Mellitus epidemiology, Drug Therapy, Combination, Female, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Metformin therapeutic use, Transplantation, Homologous, Treatment Outcome, Diabetes Mellitus etiology, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
Abstract

Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are known to be at risk of developing endocrine abnormalities, but occurrence of diabetes mellitus (DM) is a relatively recent observation. We present a 17.5-year-old girl with DM after high-dose radio- and chemotherapy followed by allogeneic HSCT for the treatment of acute lymphoblastic leukemia, diagnosed when she was 10 years old. In the posttransplantation period, multiple acute and chronic complications occurred. Among them, we observed graft versus host disease requiring corticosteroid therapy, pancreatitis and some endocrine complications like primary hypothyroidism, growth hormone deficiency and hypergonadotropic hypogonadism. DM with some components of metabolic syndrome-like insulin resistance, high arterial blood pressure and dyslipidemia developed during the first year after HSCT. Five years later, a trend towards increased requirement of insulin with deterioration in metabolic control of DM was observed, despite a normal level of C-peptide and negative diabetes autoantibodies. After the addition of metformin to continuous subcutaneous insulin infusion in the therapy of DM, an improvement in metabolic control was observed. Due to the possible mechanism of insulin resistance which is associated with impaired insulin receptors after HSCT procedure, metformin with insulin appears to be effective in the treatment of this type of diabetes., (Copyright © 2013 S. Karger AG, Basel.)

Published
2013
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33. Immunolocalization of cytochrome P450 17alpha-hydroxylase/c17-20 lyase in the ovary of pregnant pigs and fetal gonads.

Author

Knapczyk-Stwora K, Ciechanowska M, Sternak M, Durlej M, and Słomczyńska M

Subjects
Androgens metabolism, Animals, Female, Fetus enzymology, Immunohistochemistry veterinary, Male, Ovary embryology, Pregnancy, Steroid 17-alpha-Hydroxylase genetics, Swine embryology, Testis embryology, Testis enzymology, Gene Expression Regulation, Developmental physiology, Gene Expression Regulation, Enzymologic physiology, Ovary enzymology, Steroid 17-alpha-Hydroxylase metabolism, Swine metabolism
Abstract

The study was designed to localize P450 17alpha-hydroxylase/c17-20 lyase (P450c17) in the ovaries of pregnant pigs and fetal gonads. Immunoexpression of P450c17 was investigated in the porcine ovaries (follicles and corpora lutea; CL) collected on days 10, 18, 32, 50, 70 and 90 post coitum (p.c.), and fetal gonads (testes and ovaries) on days 50, 70 and 90 p.c. The presence of P450c17 in ovarian follicles was demonstrated on all examined days of pregnancy but was restricted to theca interna cells. In CL, P450c17 was detected on all examined days of pregnancy but only in small luteal cells. In the female porcine fetuses, P450c17 immunostaining was found in oocyte nests and granulosa cells of primary ovarian follicles, while in the male fetuses in fetal Leydig cells. In conclusion, the immunolocalization of P450c17, detected in the ovaries of pregnant pigs and fetal porcine gonads, indicates the potential sites of androgen synthesis. We suggest that androgens may play a role in the maintenance of pregnancy and in the development of prenatal gonads in pigs.

Published
2011
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34. Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

Author

Ciechanowska M, Łapot M, Malewski T, Mateusiak K, Misztal T, and Przekop F

Subjects
Analysis of Variance, Animals, Corticotropin-Releasing Hormone agonists, DNA Primers genetics, Female, Luteinizing Hormone blood, Peptide Fragments pharmacology, Radioimmunoassay, Real-Time Polymerase Chain Reaction, Corticotropin-Releasing Hormone pharmacology, Follicular Phase metabolism, Gene Expression Regulation drug effects, Gonadotropin-Releasing Hormone metabolism, Hypothalamus metabolism, Pituitary Gland, Anterior metabolism, Receptors, LHRH metabolism, Sheep metabolism
Abstract

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit., (© CSIRO 2011 Open Access)

Published
2011
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35. Neuroendocrine regulation of GnRH release and expression of GnRH and GnRH receptor genes in the hypothalamus-pituitary unit in different physiological states.

Author

Ciechanowska M, Lapot M, Mateusiak K, and Przekop F

Subjects
Afferent Pathways physiology, Anestrus, Animals, Brain physiology, Cloning, Molecular, Endorphins physiology, Estrus, Female, Gene Expression Regulation, Humans, Hypothalamus physiology, Neurons, Pituitary Gland, Anterior physiology, Gonadotropin-Releasing Hormone genetics, Gonadotropin-Releasing Hormone metabolism, Hypothalamo-Hypophyseal System physiology, Receptors, LHRH genetics
Abstract

This review is focused on the relationship between neuroendocrine regulation of GnRH/LH secretion and the expression of GnRH and GnRH receptor (GnRHR) genes in the hypothalamic-pituitary unit during different physiological states of animals and under stress. Moreover, the involvement of hypothalamic GABA-ergic, Beta-endorphinergic, CRH-ergic, noradrenergic, dopaminergic and GnRH-ergic systems in the regulation of expression of the GnRH and GnRHR genes as well as secretion of GnRH/LH is analyzed. It appears that the neural mechanisms controlling GnRH gene expression in different physiological states may be distinct from those regulating GnRH/LH release. The hypothalamic GnRHR gene is probably located in different neural systems and may act in a specific way on GnRH gene expression and GnRH release.

Published
2010
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36. [Disorders of lipid metabolism in adolescents with simple obesity].

Author

Wójcik M, Januś D, Maślanka A, Olchawa-Czech A, Radwańska M, Dylag K, Dolezal-Ołtarzewska K, Roztoczyńska D, Tyrawa K, Zygmunt-Górska A, Kumorowicz-Czoch M, Kalicka-Kasperczyk A, Ciechanowska M, Stelmach M, Nazim J, and Starzyk J

Subjects
Adolescent, Atherosclerosis epidemiology, Causality, Child, Cholesterol, HDL metabolism, Comorbidity, Dyslipidemias diagnosis, Female, Humans, Hypertension epidemiology, Incidence, Insulin Resistance, Male, Risk Factors, Triglycerides metabolism, Dyslipidemias epidemiology, Dyslipidemias metabolism, Obesity epidemiology, Obesity metabolism
Abstract

Background: Obesity affects approximately 45 millions of children worldwide. Some of them present with secondary dyslipidemia that leads to premature atherosclerosis., Aim of the Study: 1) Assessment of the frequency and type of dyslipidemia in obese adolescents. 2) An attempt at defining risk factors of atherogenic lipid profile in obese adolescents., Material and Methods: In 146 (84 girls/62 boys) obese (mean BMI SDS 4.95, 95% CI 4.62-5.29) adolescents (age 10-18, mean 14.7 years), the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglicerydes (TG) were measured. Atherogenic dyslipidemia was defined as a high TG level with a concomitant low HDLc level. Standard oral glucose tolerance test was performed with the assessment of fasting and after 120' post-load of 75 g of glucose and insulin levels; the insulin resistance index HOMA-IR was calculated., Results: The mean values of the lipid fractions were in normal ranges: TC 4.64 mmol/L (95% CI 4.48-4.8), LDLc 2.86 mmol/L (95% CI 2.73-2.99), TG 1.4 mmol/L (95% CI 1.3-1.5), and HDLc 1.16 (95% CI 1.1-1.2). However, in 50.69% of the patients (45.24% girls and 58.06% boys), elevated levels of TC, LDLc, and TG were observed respectively in 23.29%, 17.81% and 37.67%, and low HDLc in 15.07% of patients. A total of 10.96% of the patients presented with coexistence of a low HDLc and a high TG. In 26.7%, dyslipidemia was followed by arterial hypertension. There was a reverse correlation between a low HDLc value and BMI SDS [R (-) 0.22, p < 0.05] and not with TC, LDLc, and TG. The relative risk of abnormal lipid profile occurrence was higher in obese patients with insulin resistance (OR 1.72; 95% CI 0.8-3.4; p = 0.12), being significant only for boys (OR 3.67; 95% CI 1.1-12.1; p = 0.03). There was a reverse correlation between fasting insulin level, HOMA-IR and HDLc [R (-) 0.2; p < 0.05; R (-) 0.2; p < 0.05) respectively], as well as TG (R 0.26 ; p < 0.05; R 0.26; p < 0.05, respectively), and between post-load insulin level and TG (R 0.24; p < 0.05)., Conclusions: 1) Lipid disorders occur in about one-half of obese adolescents, of which 10% presents with atherogenic lipid profile. 2) One of the most important risk factors of atherogenic lipid profile occurrence is insulin resistance, especially in boys. The severity of the obesity (BMI-SDS) is of lesser importance.

Published
2010

37. [Autoimmune thyroid disease and type 1 diabetes mellitus in a 2-year-old girl with Down syndrome and congenital hypothyroidism--a case presentation].

Author

Wójcik M, Kumorowicz-Czoch M, Ciechanowska M, and Starzyk J

Subjects
Child, Preschool, Congenital Hypothyroidism diagnosis, Diabetes Mellitus, Type 1 diagnosis, Female, Humans, Infant, Newborn, Thyroiditis, Autoimmune diagnosis, Congenital Hypothyroidism complications, Diabetes Mellitus, Type 1 complications, Down Syndrome complications, Thyroiditis, Autoimmune complications
Abstract

Autoimmune thyroid disease (AITD) and type 1 diabetes mellitus (DM1) are much more common in Down Syndrome (DS) in comparison to the general population. The onset of DM1 may occur earlier than in the general population, often before age of 2 years, but AITD presents usually in the 2-3 decade of life, only sporadically before 10 years of age. The authors present a rare, unusual course of coincidence of AITD and DM1 in a 2-year-old girl with DS and congenital subclinical hypothyroidism.

Published
2010

38. Effects of GABA(A) receptor modulation on the expression of GnRH gene and GnRH receptor (GnRH-R) gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland of follicular-phase ewes.

Author

Ciechanowska M, Lapot M, Malewski T, Mateusiak K, Misztal T, and Przekop F

Subjects
Animals, Bicuculline pharmacology, Female, Follicular Phase drug effects, GABA Agonists pharmacology, GABA Antagonists pharmacology, Gene Expression Regulation drug effects, Gonadotropin-Releasing Hormone genetics, Hypothalamus drug effects, Luteinizing Hormone blood, Luteinizing Hormone physiology, Muscimol pharmacology, Pituitary Gland, Anterior drug effects, RNA, Messenger biosynthesis, RNA, Messenger genetics, Random Allocation, Receptors, GABA-A genetics, Receptors, LHRH genetics, Reverse Transcriptase Polymerase Chain Reaction veterinary, Sheep metabolism, Statistics, Nonparametric, Follicular Phase genetics, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamus physiology, Pituitary Gland, Anterior physiology, Receptors, GABA-A metabolism, Receptors, LHRH biosynthesis, Sheep genetics
Abstract

The effect of prolonged, intermittent infusion of GABA(A) receptor agonist (muscimol) or GABA(A) receptor antagonist (bicuculline) into the third cerebral ventricle on the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland was examined in follicular-phase ewes by real-time PCR. The activation or inhibition of GABA(A) receptors in the hypothalamus decreased or increased the expression of GnRH and GnRH-R genes and LH secretion, respectively. The present results indicate that the GABAergic system in the hypothalamus of follicular-phase ewes may suppress, via hypothalamic GABA(A) receptors, the expression of GnRH and GnRH-R genes in this structure. The decrease or increase of GnRH-R mRNA in the anterior pituitary gland and LH secretion in the muscimol- or bicuculline-treated ewes, respectively, is probably a consequence of parallel changes in the release of GnRH from the hypothalamus activating GnRH-R gene expression. It is suggested that GABA acting through the GABA(A) receptor mechanism on the expression of GnRH gene and GnRH-R gene in the hypothalamus may be involved in two processes: the biosynthesis of GnRH and the release of this neurohormone in the hypothalamus.

Published
2009
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39. Expression of the GnRH and GnRH receptor (GnRH-R) genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland of anestrous and luteal phase ewes.

Author

Ciechanowska M, Lapot M, Malewski T, Mateusiak K, Misztal T, and Przekop F

Subjects
Animals, Female, Gene Expression, Gonadotropin-Releasing Hormone genetics, Hypothalamus metabolism, Luteinizing Hormone blood, Luteinizing Hormone physiology, Pituitary Gland, Anterior metabolism, RNA chemistry, RNA genetics, Receptors, LHRH genetics, Reverse Transcriptase Polymerase Chain Reaction veterinary, Seasons, Sheep metabolism, Estrous Cycle physiology, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamus physiology, Pituitary Gland, Anterior physiology, Receptors, LHRH biosynthesis, Sheep physiology
Abstract

Data exists showing that seasonal changes in the innervations of GnRH cells in the hypothalamus and functions of some neural systems affecting GnRH neurons are associated with GnRH release in ewes. Consequently, we put the question as to how the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland is reflected with LH secretion in anestrous and luteal phase ewes. Analysis of GnRH gene expression by RT-PCR in anestrous ewes indicated comparable levels of GnRH mRNA in the preoptic area, anterior and ventromedial hypothalamus. GnRH-R mRNA at different concentrations was found throughout the preoptic area, anterior and ventromedial hypothalamus, stalk/median eminence and in the anterior pituitary gland. The highest GnRH-R mRNA levels were detected in the stalk/median eminence and in the anterior pituitary gland. During the luteal phase of the estrous cycle in ewes, the levels of GnRH mRNA and GnRH-R mRNA in all structures were significantly higher than in anestrous ewes. Also LH concentrations in blood plasma of luteal phase ewes were significantly higher than those of anestrous ewes. In conclusion, results from this study suggest that low expression of the GnRH and GnRH-R genes in the hypothalamus and of the GnRH-R gene in the anterior pituitary gland, amongst others, may be responsible for a decrease in LH secretion and the anovulatory state in ewes during the long photoperiod.

Published
2008
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40. Changes in the GnRH mRNA and GnRH receptor (GnRH-R) mRNA levels in the hypothalamic-anterior pituitary unit of anestrous ewes after infusion of GnRH into the third cerebral ventricle.

Author

Lopot M, Ciechanowska M, Malewski T, Mateusiak K, Misztal T, and Przekop F

Subjects
Animals, Cerebral Ventricles drug effects, Female, Gonadotropin-Releasing Hormone administration & dosage, Injections, Intraventricular, Luteinizing Hormone blood, Sheep, Anestrus physiology, Gonadotropin-Releasing Hormone biosynthesis, Hypothalamus metabolism, Pituitary Gland, Anterior metabolism, RNA, Messenger metabolism, Receptors, LHRH biosynthesis
Abstract

In the present paper the role of GnRH in the ultrashort loop of the negative feedback action on GnRH secretion was evaluated on the molecular level by the Real-time PCR technique. Specifically, the effect of GnRH infused into the third cerebral ventricle on the expression of GnRH and GnRH receptor (GnRH-R) genes was analyzed in the hypothalamic-pituitary unit of anestrous ewes. GnRH did not significantly affect GnRH mRNA levels in the preoptic/anterior hypothalamic area but drastically increased its level in the ventromedial hypothalamus. In addition, GnRH infusion augmented GnRH-R mRNA level in the entire hypothalamus. In the GnRH-treated animals, anterior pituitary GnRH-R mRNA level and plasma LH concentration were also elevated. The changes in GnRH mRNA and GnRH-R mRNA levels in the hypothalamus in response to treatment with GnRH suggest that GnRH acts differently on the stability of these transcripts. On the basis of presented results it seems that GnRH may affect GnRH and GnRH-R biosynthesis and, consequently, GnRH/LH release.

Published
2008
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41. The central effect of beta-endorphin and naloxone on the expression of GnRH Gene and GnRH receptor (GnRH-R) gene in the hypothalamus, and on GnRH-R gene in the anterior pituitary gland in follicular phase ewes.

Author

Ciechanowska MO, Lapot M, Malewski T, Mateusiak K, Misztal T, and Przekop F

Subjects
Animals, Breeding, Estrous Cycle, Female, Gene Expression drug effects, Hypothalamus chemistry, Luteinizing Hormone metabolism, Pituitary Gland, Anterior chemistry, Polymerase Chain Reaction, RNA, Messenger analysis, Receptors, LHRH genetics, Seasons, Gonadotropin-Releasing Hormone genetics, Hypothalamus drug effects, Naloxone administration & dosage, Pituitary Gland, Anterior drug effects, Sheep metabolism, beta-Endorphin administration & dosage
Abstract

The effect of prolonged intermittent infusion of beta-endorphin or naloxone into the third cerebral ventricle in ewes during the follicular phase of the estrous cycle on the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland was examined by Real time-PCR. Activation of micro opioid receptors decreased GnRH mRNA levels in the hypothalamus and led to complex changes in GnRH-R mRNA: an increase of GnRH-R mRNA in the preoptic area, no change in the anterior hypothalamus and decrease in the ventromedial hypothalamus and stalk/median eminence. In beta-endorphin treated ewes the levels of GnRH-R mRNA in the anterior pituitary gland also decreased significantly. These complex changes in the levels of GnRH mRNA and GnRH-R mRNA were reflected in the decrease of LH secretion. Blockade of micro opioid receptors affected neither GnRH mRNA and GnRH-R mRNA nor LH levels secretion. These results indicate that beta-endorphin displays a suppressive effect on the expression of the GnRH gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland, but affects GnRH-R gene expression in a specific manner in the various parts of hypothalamus; altogether these events lead to the decrease in GnRH/LH secretion.

Published
2008
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42. The effect of stress on the expression of GnRH and GnRH receptor genes in the discrete regions of the hypothalamus and pituitary of anestrous ewes.

Author

Łapot M, Ciechanowska M, Malewski T, Misztal T, Mateusiak K, and Przekop F

Subjects
Animals, Female, Gonadotropin-Releasing Hormone genetics, Luteinizing Hormone metabolism, RNA, Messenger metabolism, Receptors, LHRH genetics, Sheep, Gonadotropin-Releasing Hormone metabolism, Hypothalamus metabolism, Pituitary Gland, Anterior metabolism, Receptors, LHRH metabolism, Stress, Physiological metabolism
Abstract

Using the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) technique, the gonadotropin releasing-hormone (GnRH) mRNA and GnRH receptor (GnRH-R) mRNA were analyzed in the preoptic area (POA), anterior (AH) and ventromedial (VM) hypothalamus, stalk/median eminence (SME) and anterior pituitary gland (AP) of anestrous ewes subjected to short or prolonged footshock stimulation. No GnRH gene expression was detected in the SME and AP. The comparable levels of GnRH mRNA were found in the POA, AH and VM in control ewes. Short and prolonged footshock stimulation significantly increased GnRH mRNA in all analyzed tissue. The highest responses in GnRH mRNA to the short stress occurred in the POA whereas to the prolonged stress in the POA and VM. In non-stressed ewes the GnRH-R mRNA were detected in tissue continuum throughout the POA, AH, VM, SME and AP. The highest concentration of GnRH-R mRNA was detected in the SME. Short as well as prolonged stress stimuli caused an increase in GnRH-R mRNA levels in all analyzed tissue. The highest responses in GnRH-R mRNA expression were found in the VM. In spite of profound up-regulation of GnRH mRNA and GnRH-R mRNA under the short and prolonged stress conditions, the increase of luteinizing hormone (LH) secretion was noted only during acute stress. It is suggested that the increase of expression of GnRH and GnRH-R genes in anestrous ewes are not directly related to GnRH level and GnRH-R activity.

Published
2007

43. Effect of stress on the expression of GnRH and GnRH receptor (GnRH-R) genes in the preoptic area-hypothalamus and GnRH-R gene in the stalk/median eminence and anterior pituitary gland in ewes during follicular phase of the estrous cycle.

Author

Ciechanowska M, Lapot M, Malewski T, Misztal T, Mateusiak K, and Przekop F

Subjects
Animals, Female, Gene Expression Regulation physiology, Gonadotropin-Releasing Hormone genetics, RNA, Messenger biosynthesis, Radioimmunoassay methods, Receptors, LHRH genetics, Reverse Transcriptase Polymerase Chain Reaction methods, Sheep, Stress, Physiological metabolism, Follicular Phase metabolism, Gonadotropin-Releasing Hormone metabolism, Median Eminence metabolism, Pituitary Gland, Anterior metabolism, Preoptic Area metabolism, Receptors, LHRH metabolism, Stress, Physiological pathology
Abstract

The RT-PCR (reverse transcription polymerase chain reaction) technique was used to analyze GnRH mRNA and GnRH-R mRNA in the preoptic area, anterior and ventromedial hypothalamus, and GnRH-R mRNA in the stalk/median eminence and anterior pituitary gland of follicular ewes subjected to short (3 h during one day) or prolonged (5 h daily during four consecutive days) footshock stimulation. To analyze relationship between expression of GnRH and GnRH-R genes with LH secretion the blood samples were collected at 10 min intervals to determine LH levels in control and stressed animals. The concentration of GnRH mRNA increased significantly in the preoptic area, anterior and ventromedial hypothalamus of ewes subjected to short stress. The prolonged stressful stimuli significantly decreased GnRH mRNA levels in all analyzed structures. In short stressed ewes the significant augmentation of mRNA encoding GnRH-R was detected in the preoptic area, entire hypothalamus, stalk/median eminence and anterior pituitary gland. The GnRH-R mRNA was significantly reduced in all tested structures of animals subjected to prolonged footshocking except for the preoptic area, where GnRH-R mRNA did not differ from control values. The changes in GnRH mRNA and GnRH-R mRNA levels under short or prolonged stress were associated with an increase or decrease of LH concentration in blood plasma, suggesting the existence of a direct relationship between GnRH mRNA and GnRH-R mRNA expression with LH secretion. The results indicate that the expression of both GnRH gene and GnRH-R gene, as well as LH secretion in ewes during the follicular phase of the estrous cycle, are dependent upon the kind of stress.

Published
2007
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44. [Polish multicenter study on diabetes type I incidence in he age group 0-14 between 1998 and 1999].

Author

Szybiński Z, Dziatkowiak H, Wasikowa R, Kinalska I, Korman E, Grzywa M, Korniszewski L, Trippenbach H, Bandurska-Stankiewicz E, Pach D, Płaczkiewicz E, Ciechanowska M, Bieniarz J, Kowalska I, Stankiewicz W, Sobel-Maruniak A, Orłowska-Florek R, Staniszewski A, Symonides-Ławecka A, Dziubińska-Kolender E, Kiełtyka A, and Walczycka L

Subjects
Adolescent, Age Distribution, Age Factors, Chi-Square Distribution, Child, Child, Preschool, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Poland epidemiology, Prevalence, Prospective Studies, Registries, Risk Factors, Sex Distribution, Sex Factors, Diabetes Mellitus, Type 1 epidemiology
Abstract

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to present the incidence rates of type 1 diabetes in the age group 0-14 in 7 distinct regions of Poland (Krakow, Wroclaw, Warsaw, Bialystok, Poznan, Rzeszow and Olsztyn centers) with over 30% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from paediatric hospital wards and diabetes outpatient units. The incidence rates calculated in 1998 showed the highest value of 14.6 and 14.5/100,000 for Olsztyn and Warsaw, and the lowest (8.4/100,000) for Poznan center. In 1999 the highest value of 14.7/100,000 was noted in Krakow and the lowest (9.3/100,000) in Poznan center. The differences in diabetes type 1 incidence rates between age groups 0-4, 5-9 and 10-14 were found to be significant (p < 0.0005) and were also significant when incidence rates were compared between males and females in these age groups in the whole study area in 1998-1999 (p = 0.002 and p = 0.015 respectively).

Published
2001

45. [Risk of incidence of diabetes mellitus in relatives of patients with diabetes type I in retrospective questionnaire study].

Author

Bieniasz J, Wasikowa R, Dziatkowiak H, and Ciechanowska M

Subjects
Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 2 epidemiology, Female, Genetic Predisposition to Disease, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Poland epidemiology, Retrospective Studies, Risk, Surveys and Questionnaires, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 genetics
Abstract

It is commonly known that there is a higher risk of diabetes type 1 in relatives of patients with diabetes type 1. According to some reports in families of these patients the incidence of diabetes type 2 is also higher. The aim of our study was the evaluation of incidence of diabetes type 1 and 2 in 1st and 2nd degree relatives of patients with diabetes type 1. Our study was conducted in the years 1993-2000 in the Department of Endocrinology for Children and Adolescents in Wrocław and in the Department of Endocrinology of Jagiellonian University in Cracow among relatives of all the patients in the age of 0-19 years with newly diagnosed diabetes type 1. Special prepared questionnaires were used in which patients were asked about: number of relatives of 1st and 2nd degree, age, sex and diagnosis of diabetes in the relatives. Data from families of 332 patients were obtained. They concerned 4080 relatives. Diabetes occurred in 121 relatives (2.96%). 20 of them were 1st degree relatives and 101--2nd degree relatives. In 31 relatives (0.76%) diabetes type 1 was diagnosed and in 88 relatives (2.16%) diabetes type 2 was diagnosed. Except for one individual (patient's mother) diabetes type 2 occurred in 2nd degree relatives. Diabetes type 1 was diagnosed in 16 1st degree relatives and 15 2nd degree relatives. They were: 1st degree relatives: 9 fathers, 3 brothers, 2 mothers and 2 sisters. 2nd degree relatives: in 8 cases siblings of patient's parents, in 7 grandparents. In families of diabetic children and adolescents relatives with type 1 and type 2 diabetes were observed, with a dominance of relatives with diabetes type 2 in 2nd degree relatives.

Published
2001

46. Effect of immunization on nocturnal NAT activity in chicken pineal gland.

Author

Markowska M, Bialecka B, Ciechanowska M, Koter Z, Laskowska H, Karkucinska-Wieckowska A, and Skwarlo-Sonta K

Abstract

OBJECTIVES: The effect of a single immunization with sheep red blood cells (SRBC) on the nocturnal NAT activity in the pineal gland and serum anti-SRBC agglutinin titer was examined in the young, sexually immature ASTRA S chickens. METHODS: 3-, 4-, and 5-week-old birds of both sexes, hatched in long (Spring) and short (Autumn) day, were housed from hatching in controlled light (L:D = 12:12) and temperature conditions. Quantity of produced 14C-labeled N-acetyltryptamine was used as a measure of the nocturnal NAT activity in the pineal gland. Serum anti-SRBC agglutinins were determined by microhemagglutination test. RESULTS: In experimental conditions applied, a sexual dimorphism in both pineal gland function and immune system activity was observed. NAT activity was dependent on the season, sex and age of chickens examined and was modified by the single immunization with SRBC. CONCLUSION: Results obtained confirmed once again the existence of the reciprocal functional connection between the pineal gland and immune system in chickens and demonstrated that even in well controlled experimental conditions the influence of the seasonal factor(s) on immunity must be taken into consideration.

Published
2000

47. [Level of glycosylated hemoglobin in children with newly diagnosed diabetes during their hospitalization].

Author

Dziatkowiak H, Adamczyk A, Kamińska E, and Ciechanowska M

Subjects
Adolescent, Child, Child, Preschool, Diabetes Mellitus diagnosis, Female, Hospitalization, Humans, Infant, Male, Diabetes Mellitus metabolism, Glycated Hemoglobin analysis
Abstract

Percent of HbA1 was determined in 60 children with newly diagnosed diabetes mellitus at the beginning and end of their first hospitalization. High levels of HbA1 (over 15%) were found in the majority of children at the admittance which means late diagnosis. A decrease in HbA1 by 0.5-7.5% was noted in 76% of all diabetic children treated at the hospital for 7-24 days. In 54% out of these children HbA1 levels decreased by 1.5-4.5%. Mean HbA1 value was 3.6% following a two-week hospitalization, and 3.7%--after 3 weeks. Mean decrease in HbA1 for all treated children was 0.18% per week. Positive correlation between HbA1 and its percentage and mean glycaemia at the beginning of hospitalization was seen. No correlation between HbA1 values measured at the end of hospitalization and blood glucose levels determined during the whole hospitalization period was found.

Published
1993

48. [Analysis of changes in concentration of glycosylated hemoglobin and fructosamine during the first three weeks of treatment of children with newly diagnosed insulin-dependent diabetes].

Author

Adamczyk A, Ciechanowska M, Dziatkowiak H, and Szafran Z

Subjects
Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1 therapy, Female, Fructosamine, Humans, Male, Diabetes Mellitus, Type 1 metabolism, Glycated Hemoglobin metabolism, Hexosamines metabolism
Abstract

Blood serum fructosamine and blood glycosylated hemoglobin (HbA1) concentrations were determined in 47 children with newly diagnosed insulin-dependent diabetes during their first stay in the hospital. Three determinations at week's intervals were carried out in each patient. The mean values of concentration decrement after the first, second and third week of treatment were 0.47, 0.37 and 0.26 mmol/l, respectively, (median values 0.56, 0.33 and 0.17 mmol/l) for fructosamine concentration, and 1.8, 2.9 and 1.0% (median 1.5, 2.3 and 0.8%) for HbA1. No correlation was found between the weekly decrement values in fructosamine and HbA1 concentrations when all the values were taken into consideration, and only a slight positive correlation when the decrement after two weeks of treatment was considered (r = 0.57, p < 0.05). Very high rate of decrease in the concentration of glycosylated hemoglobin was noted in some children, reaching the values from 4 to even 8.6% per week.

Published
1993

49. [Evaluation of the results of the treatment of children with insulin-dependent diabetes mellitus fully or partially trained in self care].

Author

Ciechanowska M, Dziatkowiak H, Boduch G, Adamczyk A, and Wisłocka E

Subjects
Adolescent, Age Factors, Child, Child, Preschool, Diabetes Mellitus, Type 1 blood, Female, Glycated Hemoglobin analysis, Humans, Male, Self Administration methods, Blood Glucose Self-Monitoring methods, Diabetes Mellitus, Type 1 drug therapy, Health Education methods, Hyperglycemia prevention & control, Insulin administration & dosage
Abstract

The study was aimed at assessing the results of diabetes mellitus therapy in 162 children, who underwent 1) the full programme of diabetes education (114 children) and 2) only the part of it (48 children). The first group was under care of Cracow Medical School Pediatrics Institute since the disease and had 2 weeks of formal diabetes mellitus teaching. The second group was treated in a less unified way in different hospitals and did not have the chance of regular teaching programme. The degree of metabolic control was assessed by series of Hb A1c determinations in whole 1987 year. The levels of Hb A1c were also compared with the children age, diabetes mellitus duration and the period elapsing from the time of last teaching. Children who were fully educated in the problems of their disease achieved significantly better results. In all group a deterioration of diabetes control during puberty was however observed. In children not fully educated such a deterioration was also noted in correlation with diabetes mellitus duration.

Published
1992

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