Radoslaw Motkowski

Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome.

Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.

Karmienie naturalne w żywieniu niemowląt z wybranych miast Polski Centralnej i Wschodniej

Wstep Karmienie naturalne jest optymalnym sposobem zywienia niemowląt, jednak nadal zbyt mala liczba dzieci lub przez zbyt krotki okres jest karmiona piersią. Cel Celem pracy byla ocena sposobu zywienia, ze szczegolnym uwzglednieniem karmienia naturalnego niemowląt, pochodzących z wybranych miast Polski Centralnej i Wschodniej oraz analiza czynnikow wplywających na karmienie piersią. Material i metody Praca jest cześcią projektu „Nawyki zywieniowe a stan odzywienia niemowląt w Polsce”, realizowanego w latach 2003–2005 jako prospektywne, wieloośrodkowe badanie obserwacyjne. W ocenie sposobu zywienia posluzono sie metodą ankietową. Wyniki Badaniem objeto 134 niemowleta 6-miesieczne, w 2 etapie uczestniczylo 98 dzieci 12-miesiecznych (73%). Realizacja zadan odbywala sie wg opracowanego protokolu badawczego, wszystkie dzieci spelnialy kryteria wlączenia/wylączenia do badania. Analiza zywienia wykazala, ze bezpośrednio po porodzie 97,7% matek rozpoczelo karmienie piersią, ale tylko 50% noworodkow bylo karmionych wylącznie piersią. W 6 miesiącu zycia (m.z.) 68,6% niemowląt nadal byla karmiona naturalnie, jednak tylko 3,7% wylącznie piersią. W grupie niemowląt 12-miesiecznych 41,8% dzieci bylo karmionych naturalnie, pozostale 58,2% – sztucznie. Stwierdzono roznice w czestości i czasie karmienia piersią noworodkow i niemowląt pochodzących z Polski Centralnej i Wschodniej. Analiza roznych czynnikow mogących miec związek z tym sposobem zywienia wykazala, ze wiekszą szanse na karmienie naturalne w 6 m.z. mialy niemowleta matek niepalących, w wieku powyzej 25 lat, a w 6. i 12. m.z. – niemowleta, ktore nie byly dokarmiane w pierwszych 3 miesiącach zycia. W analizie regresji krokowej postepującej stwierdzono, ze czas zakonczenia karmienia naturalnego oceniany w 6. i 12. m.z. wiązal sie z czasem wprowadzania dokarmiania, z wiekiem matki i wylącznym karmieniem piersią w okresie noworodkowym, a w 6. m.z. dodatkowo z pracą zawodową matki. Wnioski 1. Na oddzialach noworodkowych nadal czesto nie są przestrzegane zasady wylącznego karmienia piersią i niedopajania zdrowych dzieci. 2. Stwierdzono znaczącą poprawe w zakresie czestości karmienia naturalnego noworodkow, jak rowniez niemowląt 6- i 12-miesiecznych, jednak w pierwszym polroczu zycia zdecydowanie zbyt malo niemowląt jest karmionych wylącznie piersią. Zbyt wcześnie wprowadzane jest dokarmianie i/lub poszerzanie diety niemowląt. 3. Istnieje potrzeba kontynuacji dzialan promocyjnych dotyczących karmienia naturalnego oraz korygujących sposob zywienia dzieci w 1. roku zycia.

Bonn Risk Index Based Micromethod for Assessing Risk of Urinary Calcium Oxalate Stone Formation

PURPOSE The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on a 200 ml urine sample taken from a 24-hour collection. We evaluated whether the Bonn Risk Index can also be effectively determined in small urine samples. MATERIALS AND METHODS We studied 190 children and adolescents with nocturia and calcium oxalate urolithiasis. Initially Bonn Risk Index was determined according to the original method of Laube. Subsequently Bonn Risk Index was calculated using a computer program controlling a specially designed system to define the time point of induced crystallization based on consecutive urine samples of 1.5, 2.0 and 3.0 ml. RESULTS No significant differences were found in Bonn Risk Index between values obtained from 200 ml samples and those based on the micromethod with urine samples of 2 and 3 ml. CONCLUSIONS Assessment of risk of urinary calcium oxalate stone formation with Bonn Risk Index in small urine volumes, based on prototype equipment controlled by specialized computer software, is comparable to the original method. This finding facilitates the procedure and improves Bonn Risk Index determination in children.

Assessment of Lithogenic Risk in Children Based on a Morning Spot Urine Sample

PURPOSE The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on 24-hour urine collection. We studied whether the Bonn Risk Index could be measured in spot urine samples and which part of the day is most suitable for this purpose. MATERIALS AND METHODS We collected total and fractionated 24-hour urine (in a 6-hour nocturnal portion and 9 consecutive 2-hour diurnal samples) in 42 children and adolescents with calcium oxalate urolithiasis and 46 controls. Bonn Risk Index values determined from each of the urine fractions were compared to those obtained from related 24-hour urine collections. RESULTS Both groups exhibited similar circadian patterns of Bonn Risk Index values. Median Bonn Risk Index for the nighttime portion of urine in the stone group was 1.4 times higher than that obtained from the total 24-hour urine. The morning hours between 08:00 and 10:00 showed the peak lithogenic risk, and this fraction had the highest sensitivity and selectivity regarding discrimination between stone formers and healthy subjects. The afternoon hours demonstrated lower and less fluctuating crystallization risk. Despite diurnal fluctuations in Bonn Risk Index, there was still a well-defined cutoff between the groups. CONCLUSIONS Bonn Risk Index determined from urine samples collected between 08:00 and 10:00 appears optimal in separating stone formers from healthy subjects, and appears as useful as the value determined from 24-hour urine collection. Investigation of this diurnal sample simplifies diagnosis in pediatric stone disease without loss of clinical information.

Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia-Telangiectasia and Nijmegen Breakage Syndrome

This study compared the antioxidant status and major lipophilic antioxidants in patients with ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS). Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and concentrations of coenzyme Q10 (CoQ10) and vitamins A and E were estimated in the plasma of 22 patients with AT, 12 children with NBS, and the healthy controls. In AT patients, TAS (median 261.7 μmol/L) was statistically lower but TOS (496.8 μmol/L) was significantly elevated in comparison with the healthy group (312.7 μmol/L and 311.2 μmol/L, resp.). Tocopherol (0.8 μg/mL) and CoQ10 (0.1 μg/mL) were reduced in AT patients versus control (1.4 μg/mL and 0.3 μg/mL, resp.). NBS patients also displayed statistically lower TAS levels (290.3 μmol/L), while TOS (404.8 μmol/L) was comparable to the controls. We found that in NBS patients retinol concentration (0.1 μg/mL) was highly elevated and CoQ10 (0.1 μg/mL) was significantly lower in comparison with those in the healthy group. Our study confirms disturbances in redox homeostasis in AT and NBS patients and indicates a need for diagnosing oxidative stress in those cases as a potential disease biomarker. Decreased CoQ10 concentration found in NBS and AT indicates a need for possible supplementation.

Neutrophil Phenotypic Characteristics in Children with Congenital Asplenia and Splenectomized for Hereditary Spherocytosis

The spleen plays an important role in the granulocyte homeostasis due to such mechanisms as pooling, elimination of senescent cells and regulatory effects on granulocyte renewal in the bone marrow. The expression profile of granulocyte receptors was tested in children with congenital asplenia, and splenectomized for spherocytosis. Receptors tested included those appearing with maturation (CD16, CD11b, CD11c, TREM-1), disappearing (CD54, CD49d, CD64) and maintained during maturation (CD11a, CD45). In general, we found that the circulating granulocyte pool in the asplenic patients had phenotypical features of highly matured but not apoptotic neutrophils with a significantly elevated expression of CD16 (CD16high), tendency to a lower expression of CD45 (CD45low) and an unchanged expression of CD64 (and other markers indicating systemic inflammatory reactions). The high fluorescence intensity of CD11b,c, and TREM-1 in the congenital asplenia may indicate a potentially elevated pro-inflammatory status of granulocytes, possibly due to the low activity of vagus nerve and spleen-dependent cholinergic anti-inflammatory pathway.

Realizacja zaleceń żywienia uzupełniającego w grupie niemowląt uczestniczących w projekcie badawczym „Nawyki żywieniowe a stan odżywienia niemowląt w Polsce” ☆ ☆☆

Wstep Żywienie uzupelniające to proces przechodzenia od wylącznego karmienia piersią do diety bardziej urozmaiconej, rodzinnej. Aktualne rekomendacje zalecają wprowadzanie bezpiecznych pokarmow uzupelniających po 6 m.z. z jednoczesną kontynuacją karmienia naturalnego. Cel Celem pracy jest ocena praktycznej realizacji zalecen dotyczących wprowadzania do diety niemowląt pokarmow uzupelniających. Material i metody Praca jest cześcią projektu badawczego „Nawyki zywieniowe a stan odzywienia niemowląt w Polsce” realizowanego w latach 2003–2005 jako prospektywne, wieloośrodkowe badanie obserwacyjne. W ocenie sposobu zywienia posluzono sie metodą ankietową. Realizacja zadan odbywala sie wg opracowanego protokolu badawczego, wszystkie dzieci spelnialy kryteria wlączenia/wylączenia do badania. Wyniki Badaniami objeto 134 niemowleta 6-miesieczne, w 2 etapie uczestniczylo 98 dzieci 12-miesiecznych (73%). Analiza zywienia wykazala, ze w 6 m.z. tylko 3,7% niemowląt bylo karmionych wylącznie piersią, a 86,6% spozywalo juz pokarmy uzupelniające. Najcześciej pierwszym pokarmem wprowadzanym do diety innym niz mleko matki bylo mleko modyfikowane. Średni czas wprowadzenia dokarmiania oceniono na 3,95 m.z.; spośrod uwzglednionych czynnikow, mogących miec wplyw na wczesne ( Wnioski Analiza zywienia niemowląt wykazala rozbiezności pomiedzy obowiązującymi zaleceniami a ich realizacją w codziennej praktyce. W celu optymalizacji warunkow rozwoju i zdrowia dzieci istotna jest wlaściwa edukacja rodzicow oraz wdrazanie zasad prawidlowego zywienia.

Ocena realizacji zaleceń żywieniowych oraz profilu lipidowego w surowicy krwi dzieci chorych na fenyloketonurię

Streszczenie Cel badania Ocena realizacji zalecen dotyczących spozycia bialka, weglowodanow, tluszczow i energii w diecie dzieci chorych na fenyloketonurie oraz profilu lipidowego surowicy tych dzieci w odniesieniu do grupy kontrolnej. Material i metody Do grupy badanej wlączono 107 dzieci (46 dziewcząt i 61 chlopcow) w wieku średnio 8,8 lat (SD 2,06) chorych na fenyloketonurie rozpoznaną w okresie noworodkowym na podstawie skryningu populacyjnego. U wszystkich dzieci przeprowadzono analize wywiadu zywieniowego, ocene stezenia cholesterolu, cholesterolu lipoprotein HDL i trojglicerydow, w surowicy krwi. Grupe kontrolną stanowilo 62 zdrowych dzieci (31 dziewcząt i 31 chlopcow) w wieku średnio 8,6 lat (SD 1,1) ktore nigdy nie wymagaly leczenia dietetycznego. Wyniki Przeprowadzone badania wykazaly, ze dieta badanych dzieci chorych na fenyloketonurie prawidlowo zbilansowana w zakresie podazy bialka i Phe moze wiązac sie z nieprawidlową realizacją zapotrzebowania na tluszcze i energie. Profil lipidowy dzieci z PKU odniesiony do norm dla dzieci zdrowych, poza podwyzszonym stezeniem trojglicerydow, jest korzystniejszy z punktu widzenia prewencji procesu miazdzycowego. Wniosek Dieta dziecka chorego na fenyloketonurie poza odpowiednią podazą bialka i Phe wymaga takze prawidlowego zbilansowana pod wzgledem ilości spozywanych kalorii i tluszczow.

Low Milk Consumption in Childhood and Fragility Fractures

protein) might have affected skeletal status. Assuming that a low calcium intake is a result of cow’s milk allergy, it seems reasonable to infer that a milk-free diet is associated with fragility fracture risk. The question arises, how much dietary calcium would be expected in this patient to satisfy his metabolic needs and to prevent new fractures. There are a variety of calcium intake recommendations from expert groups in different countries; however, approximately half of prepubertal children worldwide have intakes of ! 600 mg calcium/day (45–57% of the RDIs) [4, 5] . Although a large proportion of children do not meet the RDI for calcium intake, these children do not experience fractures associated with low-energy trauma. Dr. Monti and colleagues did not mention other risk factors, e.g. trauma associated with sport activities and leisure time, silent celiac disease or rare metabolic disorders. Was a genetic investigation carried out to consider rare clinical manifestations of osteogenesis imperfecta? It is also not known whether prolonged medication was used in this patient (e.g. steroids for the management of urticaria and atopic dermatitis). Furthermore, methodological objections appear regarding the fractured nasal septum which should not be included in the analysis as a fragility fracture (or an osteoporosis-related fracture) in this boy. Dear Sir, An interesting case report concerning the associations between a low calcium intake and increased fracture occurrence was recently published in the Annals of Nutrition and Metabolism . Dr. Monti and colleagues described an 8-year-old Caucasian boy with severe allergy, including cow’s milk protein hypersensitivity, and multiple fractures who had a restrictive milk-free diet [1] . The problem is vital due to a commonly held notion that milk and dairy products are essential for bone health during growth. However, there are certain substantive issues and methodological points that should be discussed in the article. In the introduction the authors cited comprehensive positive studies about nutrition and growth, but they ignored some important key position papers and updated reviews providing little evidence of a low milk intake and an increased fracture rate [2, 3] . Indeed, milk and dairy products are the main source of calcium but the level of calcium in diets is not the only nutritional factor involved in fracture risk or ‘osteoporosis’. In the presented patient, it remains uncertain whether cow’s milk allergy itself, chronic diarrhea (likely to cause micronutrient deficiency and malabsorption of vitamin D despite appropriate supplementation) or a long-term deprivation of milk and the therewith associated deficits (i.e. Published online: January 28, 2008

Acknowledgement to the 2007 Reviewers

T. Decsi, Pécs, Hungary K.A. Dewaal, Zwolle, The Netherlands I. Dostalova, Prague, Czeck Republic C.P. Earthman, St. Paul, USA P. Eckl, Salzburg, Austria K. Eder, Halle/Saale, Germany I. Elmadfa, Vienna, Austria G. Emil, Bratislava, Republic of Slovakia M. Faber, Tygerberg, South Africa E. Fabian, Vienna, Austria L. Ferguson, Auckland, New Zealand A. Flynn, Cork, Ireland S.D. Freedman, Boston, USA J. Freeland-Graves, Austin, USA H. Freisling, Vienna, Austria J. Frohlich, Vancouver, Canada D. Fuchs, Innsbruck, Austria N. Fuller, London, UK P. Galassetti, Calif., USA K. Gedrich, Freising-Weihenstephan, Germany D. Genser, Vienna, Austria H. Goldenberg, Vienna, Austria R. Grossklaus, Berlin, Germany F. Guillon, Nantes, France P. Haber, Vienna, Austria J.E. Haddow, Providence, USA M.H. Hamdaoui, Tunis, Tunisia J.C. Hansen, Aarhus, Denmark H. Hauner, Munich, Germany S. Hercberg, Bobigny, France M. Hershfinkel, Be’er-Sheva, Israel H. Heseker, Paderborn, Germany M. Hiesmayr, Vienna, Austria E.C. Hinton, Cambridge, UK M. Hohenegger, Vienna, Austria B.J. Holub, Guelph, Canada N. Houalla, Beirut, Lebanon G. Hu, Helsinki, Finland M. Huettinger, Vienna, Austria T. Inagawa, Izumo, Japan C. Invitti, Milan, Italy S. Jackson, London, UK G. Jahreis, Jena, Germany A. Kafatos, Heraklion, Greece H. Karlic, Vienna, Austria C.L. Keen, Davis, USA M.J. Keenan, Baton Rouge, USA R. Kelishadi, Isfahan, Iran D. Kelley, California, USA E.T. Kennedy, Boston, USA V.G. Athyros, Thessaloniki, Greece S. Lee, Seoul, Korea W. Aberer, Graz, Austria F.B. Aksungar, Istanbul, Turkey L. Allen, Davis, USA S.B. Astley, Colney, UK P. Athias, Dijon, France K.T. Augusti, Thalassery, India F. Azizi, Tehran, Iran P. Balagopal, Jacksonville, USA D.E. Barre, Sydney, Canada R.L. Batterham, London, UK I. Bautista, Las Palmas de Gran Canaria, Spain H. Bays, Louisville, USA R. Benamouzig, Bobigny, France A. Berg, Freiburg, Germany J. Berger, Vienna, Austria E. Oerich Berghofer, Vienna, Austria R. Bergmann, Berlin, Germany L.M. Bermejo López, Madrid, Spain V. Boehm, Jena, Germany H. Boeing, Nuthetal, Germany A. Bordoni, Bologna, Italy C.L. Bowlus, Sacramento, USA J. Bradbury, London, UK M.A. Brehm, Amsterdam, The Netherlands J. Briedé, Maastricht, The Netherlands T.L. Broderick, Glendale, USA C. Brombach, Wädenswil, Switzerland D.L. Brown, Ithaca, USA R.S. Bruno, Storrs, USA W. Bursch, Vienna, Austria P.C. Calder, Southampton, UK J. Campion, Pamplona, Spain M. Caroli, Brindisi, Italy R. Cermak, Leipzig, Germany N. Chang, Seoul, Korea J.-M. Chardigny, Clermont-Ferrand, France M.-F. Chen, Taipei, Taiwan S. Claeyssens, Rouen, France F. Correia, Porto, Portugal T. Crowe, Melbourne, Australia E. Curis, Paris, France S. Czernichow, Bobigny, France H. Dabadie, Pessac, France S. Dalton, New York, USA U. Das, Willemstad, Curacao, Neerlandaises Antilles M. Daniel Vaz de Almeida, Porto, Portugal J. de la Osada, Zaragoza, Spain D. de Luis, Simancas, Spain