A N N A L E S A C A D E M I A E M E D I C A E S T E T I N E N S I S , 2 01 0, 5 6, 3
R O C Z N I K I
P O M O R S K I E J A K A D E M I I M E D Y C Z N E J W S Z C Z E C I N I E
A N N A L E S
A C A D E M I A E M E D I C A E S T E T I N E N S I S
ISSN 1427-440X
P O M O R S K I U N I W E R S Y T E T M E D Y C Z N Y W S Z C Z E C I N I E
SZCZECIN 2010, 56, 3
Annales Academiae Medicae Stetinensis – Roczniki Pomorskiej Akademii Medycznej w Szczecinie ukazują się od 1951 roku.
Są wydawnictwem naukowym, ciągłym, recenzowanym i cytowanym m.in. w Index Medicus (Medline), Biological Abstract, Chemical Abstract. Dostępne w ponad 150 bibliotekach krajowych i zagranicznych.
Do druku przyjmowane są prace oryginalne i poglądowe oraz prezentujące ważną kazuistykę z zakresu nauk podstawowych, kli- nicznych oraz humanistyki medycznej autorów z Pomorskiej Akademii Medycznej oraz z innych ośrodków w kraju i za granicą.
Zamieszczony materiał publikowany jest według przyjętego schematu wydawniczego, w języku polskim i/lub angielskim, z krótkimi streszczeniami odpowiednio dla języka polskiego – po angielsku, a dla języka angielskiego – po polsku. Każdy tom obejmuje części stałe: przemówienie rektora na inaugurację roku akademickiego, oryginalne prace naukowe o objętości 1–1,5 arkusza wydawniczego, w tym skondensowane rozprawy doktorskie, doniesienia naukowe itp. W suplemencie publikowana jest kronika PAM za poprzedni rok wraz ze spisem jednostek naukowo-dydaktycznych oraz bibliografią dorobku piśmienniczego uczelni.
REGULAMIN PUBLIKOWANIA PRAC*
w Annales Academiae Medicae Stetinensis – Roczniki Pomorskiej Akademii Medycznej
Redakcja Annales Academiae Medicae Stetinensis – Roczniki Pomorskiej Akademii Medycznej przyjmuje oryginalne prace naukowe, w trybie ciągłym. Można publikować materiały ze wszystkich dziedzin nauk medycznych, również te, które są zbyt obszerne na zamieszczenie w czasopismach specjalistycznych.
Materiał powinien mieć nie więcej niż 20–25 stron maszynopisu formatu A-4, łącznie z rycinami, tabelami, podpisami i pi- śmiennictwem tylko cytowanym w tym dziele (ograniczonymi do minimum) oraz streszczeniami.
Manuskrypt napisany w języku polskim i angielskim, na białym papierze, bez wyróżnień. Zadrukowana może być tylko pierw- sza strona kartki, druga pozostaje niezadrukowana (czysta). Używać należy 12-punktowej czcionki, z zachowaniem podwójnego odstępu między wierszami. Strony numerować kolejno, zaczynając od tytułowej. Numery stron umieszczać w dolnym, prawym rogu każdej strony. Zachować kolejność układu: strona tytułowa, tekst podstawowy, materiał ilustracyjny, piśmiennictwo.
Strona tytułowa
Imię i nazwisko autora (autorów); tytuł pracy w dwóch językach; miejsce uzyskania stopnia naukowego (dotyczy doktoratów) lub pracy autora (nazwa i adres placówki naukowej, tytuł i stopień naukowy jej kierownika); słowa kluczowe w dwóch językach wymienianych w katalogu MeSH; miejsce i nazwa instytucji, gdzie wykonano pracę; szczegółowe dane dotyczące dysertacji (do- tyczy prac doktorskich – promotor, liczba: stron, rycin, tabel i piśmiennictwa).
Tekst podstawowy
S u m m a r y: streszczenie pracy w języku angielskim i/lub innym. Powinno się w nim znaleźć: cel badania lub próby, podsta- wowe procedury (wybór badanych w doświadczeniu, metody obserwacji lub analizy), główne wyniki (istotne dane i ich statystyczne znaczenie) oraz wnioski. Należy podkreślić nowe i istotne aspekty pracy. W s t ę p: podać cel artykułu i podsumować uzasadnienie wykonanego badania lub obserwacji z możliwością przywołania piśmiennictwa. M e t o d y: opisać w sposób łatwo zrozumiały dobór materiału badawczego oraz zastosowanych metod i statystyki. W y n i k i: przedstawić w tekście w logicznej kolejności. Nie powtarzać danych z tabel i rycin, podkreślić i podsumować tylko ważne obserwacje. D y s k u s j a: podkreślić należy nowe oraz ważne aspekty badania i wynikające z nich wnioski, nie powtarzać szczegółowo danych przedstawionych w rozdziałach Wstęp i Wyniki. Porównać własne obserwacje z innymi autorami, którzy wykonali zbliżone badania. W n i o s k i: powiązać z celami badania i przedstawić w sposób zwięzły. S t r e s z c z e n i e s t r u k t u r a l n e (wstęp, materiał i metody, wyniki, konkluzje): w ję- zyku podstawowym pracy, zawierające kwintesencję tego, co jest w tekście, od 200 do 250 słów. S k r ó t y użyte w tekście po raz pierwszy należy podać w pełnym brzmieniu. Nie należy rozpoczynać zdania od skrótu. L i c z b o w e w a r t o ś c i i s y m b o l e wszystkich wielkości winny być podane wg międzynarodowego układu jednostek SI. S ł o w a k l u c z o w e: 3–6 terminów, nie powinny powtarzać słów zawartych w tytule pracy, wymienianych w katalogu MeSH.
Materiał ilustracyjny
Obejmuje ryciny (kreski – wykresy, diagramy oraz siatki – zdjęcia), tabele, tablice, opatrzone tytułami (pod rycinami, nad tabe- lami). Powinny być dostarczone na oddzielnych kartkach, z oznaczeniem góra–dół i kolejności numeracji wg cytowania w tekście.
Osobną numerację posiadają ryciny i osobną tabele. Fotografie mikroskopowe powinny posiadać wewnętrzną skalę, a stosowane symbole, strzałki lub litery – wyraźnie uwidocznione na tle. Kolorów używać tylko wtedy, jeśli barwa czarno-biała nie odda isto- ty przekazu. Tytuły oraz inne informacje wewnętrzne na rycinach i w tabelach należy podać w języku polskim i angielskim. Na marginesie maszynopisu zaznaczyć numery tabel i rycin w miejscu, gdzie mają być wstawione.
Piśmiennictwo
Numerując, należy podawać w kolejności cytowania. Każdy numer piśmiennictwa należy zapisywać od nowej linii. Pozycji nie należy dublować. Cytowane w tekście piśmiennictwo podać w nawiasach kwadratowych, ze spacją między numerami. Podajemy nazwisko autora/-ów z pierwszymi literami imion. Przytaczamy wszystkich autorów, jeśli jest ich sześciu. Powyżej tej liczby – sze- ściu z dopiskiem et al. Tytuły periodyków powinny być skracane zgodnie ze sposobem przyjętym w Index Medicus (Medline).
Redakcja wymaga przedłożenia pracy w dwóch egzemplarzach wraz z wersją elektroniczną (dyskietka lub CD-ROM) z za- znaczeniem programu zapisu. Tekst powinien być zapisany w programie Word.
* Opracowany na podstawie wytycznych Międzynarodowego Komitetu Wydawców Czasopism Medycznych, opublikowanych w Problemach Medycyny Nuklearnej 1997, 11 (21), 67–87.
R O C Z N I K I
P O M O R S K I E J A K A D E M I I M E D Y C Z N E J W S Z C Z E C I N I E
A N N A L E S
A C A D E M I A E M E D I C A E S T E T I N E N S I S
P O M O R S K I U N I W E R S Y T E T M E D Y C Z N Y W S Z C Z E C I N I E
SZCZECIN 2010, 56, 3
R e d a k t o r n a c z e l n y E d i t o r - i n - C h i e f
prof. dr hab. n. med. IRENEUSZ KOJDER
M i ę d z y n a r o d o w a R a d a N a u k o w a I n t e r n a t i o n a l S c i e n t i f i c C o u n c i l
Prof. Dr. Raymond Ardaillou (Paryż, F), prof. dr hab. n. med. Andrzej Cretti, Prof. Dr. Antonio J.G. Ferreira (Lizbona, P), prof. dr hab. n. med. Janusz Fydryk, Prof. Dr. Alan Gewirtz (Filadelfia, USA), Prof. Dr. Yücel Kanpolat (Ankara, TR),
prof. dr hab. n. med. Irena Karłowska, Prof. Dr. Koichi Kono (Osaka, J), prof. dr hab. n. med. Ireneusz Kojder, prof. dr hab. n. med. Tadeusz Marcinkowski,
Prof. Dr. Falk Oppel (Bielefeld, D), Prof. Dr. Mary Osborn (Getynga, D), prof. dr hab. n. med. Andrzej Paradowski, Prof. Dr. Wolfgang Straube (Rostok, D),
prof. dr hab. n. med. Eugeniusz Szmatłoch
K o m i t e t r e d a k c y j n y E d i t o r i a l c o m m i t t e e
prof. dr hab. n. med. Dariusz Chlubek, prof. dr hab. n. med. Maria Jastrzębska, prof. dr hab. n. med. Anhelli Syrenicz, prof. dr hab. n. med. Andrzej Żyluk, dr hab. n. med., prof. PAM Mariusz Lipski, dr hab. n. med. Anna Machoy-Mokrzyńska,
dr hab. n. med. Alicja Walczak, dr hab. n. hum. Aleksandra Żukrowska, mgr Dagmara Budek, mgr Bożena Opiela
T ł u m a c z r e d a k c j i E d i t o r i a l t r a n s l a t o r dr n. med. Tomasz Dutkiewicz
R e d a k c j a t e c h n i c z n a i k o r e k t a T e c h n i c a l e d i t o r a n d p r o o f r e a d e r
Hubert Czekała Wojciech Markowski
Bożena Opiela Ryszard Sędkiewicz
S k ł a d i ł a m a n i e P u b l i s h i n g l a y o u t
Waldemar Jachimczak
© Copyright by Pomorski Uniwersytet Medyczny w Szczecinie, 2010
A d r e s r e d a k c j i E d i t o r i a l o f f i c e a d d r e s s Pomorski Uniwersytet Medyczny w Szczecinie
70-204 Szczecin, ul. Rybacka 1 www.pum.edu.pl/uczelnia/wydawnictwo
wydawnictwo@pum.edu.pl
Wydanie publikacji dofinansowane przez Ministerstwo Nauki i Szkolnictwa Wyższego This publication was partly financed by the Ministry of Science and Higher Education
WYDAWNICTWO POMORSKIEGO UNIWERSYTETU MEDYCZNEGO W SZCZECINIE Wydanie I. Nakład 520 egz. Format A-4. Objętość: ark. druk. 19,0.
Druk i oprawa: PPH ZAPOL, Dmochowski, Sobczyk, Spółka jawna, Szczecin, tel. 91 435 19 00, e-mail: zarzad@zapol.com.pl
1. Joanna Bober, Karolina Kędzierska, Ewa Kwiatkowska, Ewa Stachowska, Edyta Gołembiewska, Olech Mazur, Zdzisław Staniewicz, Kazimierz Ciechanowski, Dariusz Chlubek
Czy stres oksydacyjny może wpływać na aktywność wymieniacza sodowo-protonowego? . . . . 5 2. Bogumiła Elbl, Bożena Birkenfeld, Jadwiga Szymanowicz, Hanna Piwowarska-Bilska, Tomasz Urasiński,
Maria Listewnik, Aleksandra Gwardyś
Zależność między odpływem żołądkowo-przełykowym a nawracającymi zakażeniami dolnych dróg oddechowych i astmą oskrzelową u dzieci . . . . 13 3. Sylwia Wieder-Huszla
Monitorowanie zakażeń szpitalnych na oddziale intensywnej terapii medycznej . . . . 20 4. Ewa Stachowska, Dominika Jamioł, Dariusz Chlubek
Kwasy tłuszczowe trans i ich rola w zapaleniu i chorobach układu krążenia . . . . 30 5. Ewa Lewandowska, Bożena Birkenfeld, Bartosz Kaczmarek, Piotr Zorga, Maria Listewnik
Wartość diagnostyczna scyntygrafii perfuzyjnej serca SPECT z użyciem 99m TC-MIBI u kobiet z podejrzeniem choroby wieńcowej . . . . 39 6. Mariusz Molenda, Joanna Bober, Dobrosława Stańkowska-Walczak, Małgorzata Stańczyk-Dunaj
Palenie papierosów czynnikiem sprzyjającym powstawaniu nieswoistych chorób zapalnych jelit . . . . 50 7. Grzegorz Ptaszkiewicz, Włodzimierz Majewski
Urazy w kolarstwie – opis przypadku i przegląd piśmiennictwa . . . . 55 8. Ewa Sobolewska
Wpływ materiałów nowej generacji stosowanych w protetyce odtwórczej na środowisko jamy ustnej . . . . 66 9. Wojciech Kaczmarek
Stan zmineralizowanych tkanek zębów u młodzieży uprawiającej zawodowo pływanie . . . . 81 10. Arkadiusz Kazimierczak, Marcin Śledź, Renata Guzicka-Kazimierczak, Piotr Gutowski, Miłosław Cnotliwy
Wczesny zgon w chirurgii naczyniowej. Aktualny problem prognostyczny . . . . 87 11. Jacek Materny, Irena Mazurkiewicz, Elżbieta Gawrych, Bożena Birkenfeld, Piotr Zorga
Czy poprawa czynności nerki po operacji Hynesa–Andersona jest możliwa? . . . . 95 12. Danuta Miklaszewska, Aleksandra Gawlikowska-Sroka, Florian Czerwiński,
Edyta Dzięciołowska-Baran, Ewa Adamiec
Przedurodzeniowy rozwój krtani płodów ludzkich – badania morfometryczne . . . . 103 13. Beata Karakiewicz, Celina Stala, Elżbieta Grochans, Iwona Rotter, Bożena Mroczek, Liliana Zaremba-Pechmann,
Maria Laszczyńska, Marta Giezek
Ocena wpływu wybranych czynników socjodemograficznych na jakość życia osób chorujących na stwardnienie rozsiane. . . . 107 14. Ewelina Żyżniewska-Banaszak, Hanna Mosiejczuk, Paweł Cichocki
Fizjoterapia i odnowa biologiczna – czy dla wszystkich?. . . . 113 15. Jadwiga Kuciel-Lewandowska, Malwina Wierzchowska, Małgorzata Paprocka-Borowicz,
Andrzej Kierzek, Andrzej Pozowski, Roman Heider, Michał Guła, Wojciech Tomasz Laber
Skuteczność kompleksowej fizjoterapii w zespołach bólowych barku . . . . 121 16. Remigiusz Jarosław Tritt
Wprowadzenie w tematykę LGBT – aparat pojęciowy, wybrane fakty historyczne i ewolucja myślenia w dobie HIV/AIDS – nadzieje i wyzwania . . . . 126 17. Marcin Kolwitz
Polski system ochrony zdrowia – perspektywy i możliwości zastosowania systemów ochrony zdrowia innych państw Unii Europejskiej. . . . 131 18. Andrzej Kierzek, Jadwiga Kuciel-Lewandowska, Andrzej Pozowski, Małgorzata Paprocka-Borowicz, Marek Rej
Izydor Nahumowicz (1800–1842) i jego dzieło o druskiennickich wodach . . . . 144
SPIS TREŚCI
CONTENTS
1. Joanna Bober, Karolina Kędzierska, Ewa Kwiatkowska, Ewa Stachowska, Edyta Gołembiewska, Olech Mazur, Zdzisław Staniewicz, Kazimierz Ciechanowski, Dariusz Chlubek
Does oxidative stress affect the activity of the sodium-proton exchanger?. . . . 5 2. Bogumiła Elbl, Bożena Birkenfeld, Jadwiga Szymanowicz, Hanna Piwowarska-Bilska, Tomasz Urasiński,
Maria Listewnik, Aleksandra Gwardyś
The association between gastroesophageal reflux and recurrent lower respiratory tract infections and bronchial asthma in children . . . . 13 3. Sylwia Wieder-Huszla
Monitoring of nosocomial infections in intensive care units . . . . 20 4. Ewa Stachowska, Dominika Jamioł, Dariusz Chlubek
Trans fatty acids and their role in inflammation and cardiovascular disease. . . . 30 5. Ewa Lewandowska, Bożena Birkenfeld, Bartosz Kaczmarek, Piotr Zorga, Maria Listewnik
Diagnostic value of 99m TC-MIBI myocardial perfusion SPECT in women with suspected coronary artery disease . . . . 39 6. Mariusz Molenda, Joanna Bober, Dobrosława Stańkowska-Walczak, Małgorzata Stańczyk-Dunaj
Cigarette smoking as a promoting factor for nonspecific inflammatory bowel disease . . . . 50 7. Grzegorz Ptaszkiewicz, Włodzimierz Majewski
Trauma in cycling – case report and review of the literature . . . . 55 8. Ewa Sobolewska
The effect of new generation materials used in reconstructive dentistry on the oral cavity environment. . . . 66 9. Wojciech Kaczmarek
The status of mineralized dental tissues in young competitive swimmers . . . . 81 10. Arkadiusz Kazimierczak, Marcin Śledź, Renata Guzicka-Kazimierczak, Piotr Gutowski, Miłosław Cnotliwy
Early death in vascular surgery: an ongoing prognostic problem. . . . 87 11. Jacek Materny, Irena Mazurkiewicz, Elżbieta Gawrych, Bożena Birkenfeld, Piotr Zorga
Does Hynes-Anderson pyeloplasty improve renal function? . . . . 95 12. Danuta Miklaszewska, Aleksandra Gawlikowska-Sroka, Florian Czerwiński,
Edyta Dzięciołowska-Baran, Ewa Adamiec
A morphometric study of prenatal development of the human larynx . . . . 103 13. Beata Karakiewicz, Celina Stala, Elżbieta Grochans, Iwona Rotter, Bożena Mroczek, Liliana Zaremba-Pechmann,
Maria Laszczyńska, Marta Giezek
Assessment of the impact of some sociodemographic factors on the quality of life of patients with multiple sclerosis . . 107 14. Ewelina Żyżniewska-Banaszak, Hanna Mosiejczuk, Paweł Cichocki
Physiotherapy and biological regeneration: for everyone? . . . . 113 15. Jadwiga Kuciel-Lewandowska, Malwina Wierzchowska, Małgorzata Paprocka-Borowicz,
Andrzej Kierzek, Andrzej Pozowski, Roman Heider, Michał Guła, Wojciech Tomasz Laber
The effectiveness of a comprehensive program of physiotherapy in shoulder pain syndromes . . . . 121 16. Remigiusz Jarosław Tritt
Introduction to LGBT: definitions, some historical facts, and evolution of thinking in the era of HIV/AIDS – hopes and challenges . . . . 126 17. Marcin Kolwitz
The Polish healthcare system: perspectives and possibilities for adoption of healthcare systems from other countries of the European Union . . . . 131 18. Andrzej Kierzek, Jadwiga Kuciel-Lewandowska, Andrzej Pozowski, Małgorzata Paprocka-Borowicz, Marek Rej
Izydor Nahumowicz (1800–1842) and his work on the salt springs of Druskininkai. . . . 144
A N N A L E S A C A D E M I A E M E D I C A E S T E T I N E N S I S
R O C Z N I K I P O M O R S K I E J A K A D E M I I M E D Y C Z N E J W S Z C Z E C I N I E 2010, 56, 3, 5–12
JOANNA BOBER, KAROLINA KęDZIERSKA1, EWA KWIATKOWSKA1, EWA STAChOWSKA2, EDYTA GOłEMBIEWSKA1, OLECh MAZuR3, ZDZISłAW STANIEWICZ3, KAZIMIERZ CIEChANOWSKI1, DARIuSZ ChLuBEK4
DOES OxIDATIvE STRESS AffECT ThE ACTIvITY Of ThE SODIuM-PROTON ExChANGER?
CZY STRES OKSYDACYJNY MOżE WPłYWAć NA AKTYWNOŚć WYMIENIACZA SODOWO-PROTONOWEGO?
Zakład Chemii Medycznej Pomorskiego Uniwersytetu Medycznego w Szczecinie al. Powstańców Wlkp. 72, 70-111 Szczecin
Kierownik: dr hab. n. med., prof. PUM Joanna Bober
1 Klinika Nefrologii, Transplantologii i Chorób Wewnętrznych Pomorskiego Uniwersytetu Medycznego w Szczecinie al. Powstańców Wlkp. 72, 70-111 Szczecin
Kierownik: prof. dr hab. n. med. Kazimierz Ciechanowski
2 Zakład Biochemii i Żywienia Człowieka Pomorskiego Uniwersytetu Medycznego w Szczecinie ul. Broniewskiego 24, 71-460 Szczecin
Kierownik: dr hab. n. med., prof. PUM Ewa Stachowska
3 Stacja Dializ Szpitala Wojewódzkiego w Koszalinie im. Mikołaja Kopernika ul. T. Chałubińskiego 7, 75-581 Koszalin
Kierownik: lek. med. Olech Mazur
4 Katedra Biochemii i Chemii Medycznej Pomorskiego Uniwersytetu Medycznego w Szczecinie al. Powstańców Wlkp. 72, 70-111 Szczecin
Kierownik: prof. dr hab. n. med. Dariusz Chlubek
Streszczenie
Wstęp: U pacjentów z przewlekłą niewydolnością nerek (CRF) występuje akumulacja wolnych rodników tlenowych (ROS). Stres oksydacyjny powoduje zaburzenia aktywności wymieniacza sodowo -protonowego (NHE). Badania nad aktywnością NHE u pacjentów z CRF dawały sprzeczne rezultaty, trudne do interpretacji.
Celem pracy było udowodnienie, że stres oksydacyjny może wpływać na aktywność NHE.
Metody: W badaniu udział wzięło 87 osób, które przydzielono do 4 grup: pacjenci z CRF leczeni zachowa- wczo, pacjenci hemodializowani z płynem nie zawierają- cym glukozy – HD -g(−), pacjenci hemodializowani z pły- nem zawierającym glukozę – HD -g(+) i grupa kontrolna (C). Oceniano aktywność NHE, prędkość wypływu proto- nów (Vmax) i stałą Michaelisa–Mentena (Km) oraz stężenie TBARS (jako wykładnika stresu oksydacyjnego) w osoczu, a także stężenie zredukowanego glutationu we krwi.
Wyniki: Stężenie TBARS u pacjentów hemodializo- wanych przed i po dializie oraz w grupie pacjentów z CRF leczonych zachowawczo było znacząco wyższe niż u pacjen- tów z grupy kontrolnej. Stężenie TBARS w osoczu wykazało ujemną korelację z VpHi6.4 w grupie kontrolnej oraz z Vmax
i VpHi6.4 po HD w grupie HD -g(−). Stwierdzono także zależność pomiędzy stężeniem kreatyniny a stężeniem TBARS (p < 0,0001; r = +0,51) u pacjentów z CRF leczo-
nych zachowawczo.
Wniosek: Płyn dializacyjny pozbawiony glukozy powo- dował duży stres oksydacyjny i obniżoną aktywność NHE w przeciwieństwie do płynu zawierającego glukozę, który powodował względnie niewielkie nasilenie stresu oksyda- cyjnego.
H a s ł a: stres oksydacyjny – wymieniacz sodowo- -protonowy – hemodializa – schyłkowa niewy-
dolność nerek.
6 JOANNA BOBER, KAROLINA KĘDZIERSKA, EWA KWIATKOWSKA ET AL.
Summary
Introduction: Accumulation of reactive oxygen species (ROS) takes place in patients with chronic renal failure (CRF). Oxidative stress causes disorders in the activity of the sodium -proton exchanger (NHE). Studies on NHE in CRF produced results that are discrepant and difficult to interpret.
The aim of this study was to demonstrate that oxidative stress had an effect on the activity of NHE.
Methods: We enrolled 87 subjects divided into 4 groups:
patients with CRF treated conservatively; patients with CRF hemodialyzed without glucose – HD -g(−); patients with CRF hemodialyzed with glucose – HD -g(+); controls (C). The activity of NHE, the rate of proton efflux (Vmax), Michae- lis constant (Km), and the concentration of thiobarbituric acid -reactive substances (TBARS, an indicator of oxidative stress) in plasma, as well as the concentration of reduced glutathione in blood were determined.
Results: The concentration of TBARS was significantly higher in hemodialyzed patients before and after dialysis and in patients with CRF on conservative treatment in compari- son with group C. TBARS in plasma correlated negatively with VpHi6.4 in group C and with Vmax and VpHi6.4 after HD in group HD -g(−). We found that the concentration of creatinine correlated with TBARS (p < 0.0001; r = +0.51) in the conservatively treated group.
Conclusion: We observed a marked oxidative stress and decreased NHE activity when dialysis was done without glucose, whereas patients dialyzed with glucose demon- strated a relatively low intensity of oxidative stress.
K e y w o r d s: oxidative stress – sodium -proton exchanger – hemodialysis – end -stage kidney failure.
Introduction
The sodium -proton exchanger (NHE) is a transmem- brane transporting system carrying protons out of the cell and replacing them with sodium. The sodium -proton exchanger activity is affected by growth factors [1], osmotic stress [2], intracellular pH [1], and hormones [3]. It was also found that mitogen-activated protein kinases (MAPK) had an effect on NHE activity after its enhancement in response to osmotic stress [4] or growth factors [5]. Activa- tion of NHE in the presence of nanomole concentrations of aldosterone is suppressed by MAPK inhibitors [6]. Several isoforms of NHE have been discovered and their distribu- tion in cells has been studied. Erythrocytes (RBC) contain isoform 1 only.
Oxidative stress in vitro and in vivo leads to disorders in NHE activity. It was found that NHE activity in the aortic endothelium was inhibited in the presence of the hydroxyl radical [7, 8, 9] and that this effect was neutral- ized by reduced glutathione (GSH). Superoxides suppress
NHE activity in mesangial cells of kidneys [10, 11] and in cultured astrocytes [12]. Decreased activity in renal cells infected with Sandai virus was attributed to oxidative stress and to concurrently reduced concentration of GSH. Inhibi- tion of inflammation with accompanying increase in GSH concentration restored normal NHE activity [13].
Reactive oxygen species (ROS) responsible for oxida- tive stress are known to accumulate in patients with chronic renal failure – CRF (on conservative treatment or under- going regular hemodialysis). The concentration of TBARS (thiobarbituric acid -reactive substances) is the main indicator of oxidative stress. Plasma TBARS levels are increased in patients with renal failure treated either conservatively [14]
or undergoing hemodialysis (HD) [14, 15] and in patients with low hematocrit values [16].
Studies on NHE in chronic renal failure (treated con- servatively or with hemodialysis) have so far produced dis- crepant results or have been plagued with interpretation difficulties because the conditions of dialysis are not always given. The sodium -proton exchanger activity in lymphocytes of patients undergoing HD was reported to be decreased [17, 18] or unchanged [19]. Kovacic et al. [20] attributed the decline in NHE activity before HD to decreased activity of the sodium -potassium pump. Contradictory results were obtained in studies on the activity and amount of NHE in erythrocytes – both parameters were higher in hemodia- lyzed patients than in controls [21]. Patients with chronic renal failure treated conservatively or undergoing dialysis (HD or peritoneal dialysis) were found to have significantly higher activities of erythrocyte NHE compared to healthy subjects [22].
Material and methods
Material
The study was done in 87 subjects divided into 4 gro- ups: patients with CRF on conservative treatment; patients with chronic renal failure hemodialyzed with glucose -free fluid – HD -g(−); patients with chronic renal failure hemo- dialyzed with glucose -containing fluid – HD -g(+); control group (C). Patient and biochemical data are presented in table 1. The main causes of renal failure in patients on con- servative treatment were: glomerulonephritis (n = 8), pyelo- nephritis (n = 7), other or unknown (n = 6). Chronic renal failure in the HD -g(−) group was caused by glomerulone- phritis (n = 8), pyelonephritis (n = 9), other (n = 5). Cau- ses in the HD -g(+) group were: glomerulonephritis (n = 8), pyelonephritis (n = 9), other (n = 4). Among other causes of renal failure was either gout and kidney stones or the etiology was unknown. Patients with neoplastic disease, acute infection, and smokers were excluded. None of the patients underwent blood transfusion during some weeks preceding the study. Age, gender, and biochemical para- meters did not differ significantly between both groups of hemodialyzed patients. Patients were dialyzed three times
DOES OxIDATIVE STRESS AFFECT THE ACTIVITy OF THE SODIUM-PROTON ExCHANGER? 7
T a b l e 1. Biochemical parameters, age, and gender of patients with chronic renal failure (CRf) and patients hemodialyzed (hD) with or without glucose
T a b e l a 1. Parametry biochemiczne, wiek i płeć pacjentów z przewlekłą niewydolnością nerek (CRf) i pacjentów hemodializowanych (hD) z glukozą lub bez glukozy
Parameter Parametr
Without glucose / Bez glukozy With glucose / Z glukozą before HD CRF
przed HD after HD
po HD before HD
przed HD after HD po HD Urea (mmol/L)
Mocznik (mmol/L) 46.9 ± 13.7 20.4 ± 9.8 46.2 ± 9.9 19.4 ± 7.1 34.9 ± 30.3
Creatinine (μmol/L)
Kreatynina (μmol/L) 767.6 ± 252.0 396.2 ± 156.5 731.4 ± 176.9 359.1 ± 102.6 258.8 ± 124.7 Potassium (mmol/L)
Potas (mmol/L) 5.41 ± 0.83 4.13 ± 0.39 5.36 ± 0.85 3.94 ± 0.60 4.4 ± 0.3
Sodium (mmol/L)
Sód (mmol/L) 142.0 ± 4.42 142.8 ± 4.6 139.4 ± 3.24 140.5 ± 2.65 142 ± 2
Protein (g/L)
Białko (g/L) 72.4 ± 10.5 75.8 ± 12.4 63.3 ± 6.2 69.3 ± 10.4 62.9 ± 9.7
Albumin (g/L)
Albuminy (g/L) 48.3 ± 6.1 52.31 ± 8.12 42.7 ± 4.6 47.14 ± 5.83 38.4 ± 5.8
Diastolic pressure (mmHg)
Ciśnienie rozkurczowe (mmHg) 85.5 ± 14.6 87.1 ± 14.4 93.3 ± 15.1 86.1 ± 12.0 151.5 ± 18.0 Systolic pressure (mmHg)
Ciśnienie skurczowe (mmHg) 141.5 ± 22.9 142.9 ± 23.6 159.0 ± 27.6 139.8 ± 22.6 94.7 ± 11.8 Age (years)
Wiek (lata) 55.9 ± 14.8 64.3 ± 12.1 56.8 ± 16.0
Gender (F/M)
Płeć (K/M) 11/11 10/13 7/14
T a b l e 2. Data on hemodialysis using dialysate with or without glucose
T a b e l a 2. Dane hemodializy z dializatem zawierającym lub nie zawierającym glukozy
Parameter / Parametr
Dialysate with glucose
Dializat z glukozą
Dialysate without glucose Dializat bez
glukozy Duration of HD session (h)
Czas trwania HD (h) 3.91 ± 0.28 3.67 ± 0.47 Time since first HD (months)
Czas od pierwszej HD (miesiące) 9.45 ± 6.62 8.78 ± 6.42 Frequency of HD (per week)
Częstość HD (na tydzień) 2.95 ± 0.21 3.00 ± 0.32
KT/V 0.91 ± 0.22 0.93 ± 0.33
Surface of dialyzer membrane (m2) Powierzchnia membrany
dializacyjnej (m2) 1.42 ± 0.25 1.42 ± 0.19 Number of dialyzer uses
Ilość użyć dializatora 7.08 ± 7.46 7.90 ± 6.54 HD – hemodialysis / hemodializa, KT/V – dialysis index / wskażnik dializy
a week with the use of polysulfone dialyzers (Fresenius).
The composition of the dialysis fluid was: Na+ 138 mmol/L, K+ 0, 2.0 or 3.0 mmol/L, Ca2+ 1.75 mmol/L, Mg2+ 0.5 mmol/L, Cl− 107.5 mmol/L, HCO3− 32 mmol/L. Glucose was added to a concentration of 5.5 mmol/L. Table 2 shows other para- meters of hemodialysis.
The control group included 21 healthy subjects (10 women and 11 men) aged 56 ± 16.6 years (hospital personnel).
Erythrocytes obtained from 10 healthy subjects (not from the control group) were used to examine the influence of in vitro generated superoxides on NHE activity. The study protocol was approved by the Bioethics Committee of the Pomeranian Medical University in Szczecin and informed consent to participate was obtained from all subjects.
Methods
The activity of the sodium -proton exchanger was determined according to our modification of the method of Orlov et al. [23]. The sodium -proton exchanger activity was quantified as the amiloride -sensitive H+ efflux from acid -loaded cells. Measurements were performed at intra- cellular H+ concentrations equal to 1000, 631, 398, 251, 158, and 100 nmol H+/L. The sodium -proton exchanger acti- vity was expressed either as the rate of proton efflux at intracellular pH equal to 6.4 (VpHi6.4) or as the maximal rate (Vmax) calculated from the kinetics curve. Maximal rate and Michaelis constant (Km) for intracellular protons were computer -calculated [24] according to the Michaelis–
Menten formula with Hanes–Woolf modification [25]. The most common way of expressing NHE activity is to present it as the rate of proton efflux at intracellular pH of 6.4 [23].
However, the whole exchanger kinetics cannot be expressed in this way. We previously found (data not published) a cor- relation between Vmax and VpHi6.4 in healthy subjects and in patients with hypertension.
8 JOANNA BOBER, KAROLINA KĘDZIERSKA, EWA KWIATKOWSKA ET AL.
The concentration of TBARS in plasma was deter- mined with a spectrofluorimetric method [26]. Deprotei- nized plasma was heated with thiobarbituric acid and the products of the reaction were extracted with butanol. Fluo- rescence of the complex was measured using excitation and emission wavelengths of 529 nm and 547 nm, respectively.
The concentration of reduced glutathione was determined in whole blood a few minutes after collection according to the method of Beutler et al. [27]. Deproteinized blood reacted with dithio -bis(2 -nitrobenzoic acid) and the color inten- sity of the product was proportional to GSH concentration.
To study the effect of superoxides on the sodium -proton exchanger in vitro we incubated an erythrocyte suspension (Ht 0.05–0.07 L/L) for one hour in a solution containing glu- cose 0 or 5.5 mmol/L, NaCl 150 mmol/L, phosphate buffer 5 mmol/L (pH 7.4, 37°C) and t -butyl peroxide (t -BOOH) at concentrations of 0.005–1 mmol/L. Erythrocytes were incu- bated in parallel in the same solution without t -BOOH. The sodium -proton exchanger activity was determined imme- diately after incubation and separation of the cells from the incubation medium.
Statistical analysis
All results are presented as the arithmetic mean ± standard deviation (SD). Non -parametric tests were used because the Shapiro–Wilk’s test showed that the distribution of values deviated from normal. Wilcoxon’s paired test was used to assess statistical significance of differences before and after dialysis. Correlations between parameters in the groups were assessed with Spearman’s test. The Mann–
Whitney U test was used to determine the significance of differences in the groups. Wilcoxon’s paired and Mann–
Whitney U tests were used for statistical analysis of the results obtained in vitro.
Results
The sodium -proton exchanger activities in the groups are presented in table 3. Patients with CRF had very high values of Vmax and VpHi6.4 in comparison to controls and both groups of hemodialyzed patients. Comparing both groups of patients undergoing HD we found significant dif- ferences for Km before HD and proton efflux rate after HD.
Maximal rate, VpHi6.4, and Km values before HD in the group of patients dialyzed without glucose did not differ from values obtained in the control group. Maximal rate, VpHi6.4, and Km significantly decreased after HD. How- ever, Vmax and VpHi6.4 were significantly lower in com- parison to the control group. Michaelis constant after HD in the HD -g(+) group decreased significantly compared to the value before HD. We did not find any statistically significant correlations for VpHi6.4 before and after HD in the HD -g(+) and control groups. Maximal rate before HD was significantly higher in comparison to the control group and decreased during HD, but this change was not
statistically significant. After hemodialysis, Vmax did not differ significantly compared to the control group.
Plasma TBARS concentrations and TBARS to plasma protein ratios are presented in table 4. The intensity of oxi- dative stress given as TBARS concentration in the group of hemodialyzed patients before and after HD and in the group of patients with CRF on conservative treatment was higher than in controls. Plasma TBARS concentrations increased during HD in the HD -g(−) group but this increase was not caused by a decrease in plasma volume after HD as TBARS to plasma protein ratio was also increased. Plasma TBARS concentrations and TBARS to plasma protein ratios decreased after HD in the HD -g(+) group. In the HD -g(−) group, plasma TBARS concentrations and the TBARS to protein ratios were statistically significantly higher before and after HD in comparison to the CRF group. Plasma TBARS and TBARS to plasma protein ratios were signifi- cantly higher in the HD -g(+) group compared to the CRF group before HD. After HD, concentrations of TBARS in both groups were similar. There were significant differ- ences in plasma TBARS before HD and in plasma TBARS and TBARS to plasma protein ratio after HD between the groups of patients undergoing HD.
The concentration of reduced glutathione was higher in all patients than in controls (table 4). This relationship was statistically significant for all groups except for HD -g(+) before HD. The concentration of GSH showed significant changes after hemodialysis, decreasing in HD -g(−) and increasing in HD -g(+) groups. Compared to CRF patients, GSH concentrations were significantly higher in all groups except HD -g(+) before HD.
The intensity of oxidative stress measured as plasma TBARS concentration showed a negative correlation with
T a b l e 3. Parameters of the sodium -proton exchanger (mean ± SD) T a b e l a 3. Parametry wymieniacza sodowo -protonowego
(średnia ± SD) Group
Grupa
VpHi6,4 (mmol H+/L
RBC/h)
Vmax
(mmol H+/L RBC/h)
(nmol HKm +/L)
Control
Kontrolna 7.98 ± 2.09 12.09 ± 2.55 216.8 ± 129.8 CRF 13.39 ± 4.91 21.02 ± 7.46 228.0 ± 201.1 HD -g(−) before HD
HD -g(−) przed HD 9.10 ± 3.17‡ 11.60 ± 4.55* 195.6 ± 82.2*
HD -g(−) after HD
HD -g(−) po HD 6.59 ± 2.62 9.56 ± 3.88 153.0 ± 90.9 HD -g(+) before HD
HD -g(+) przed HD 8.43 ± 2.37 16.53 ± 6.09 317.8 ± 165.6†
HD -g(+) after HD
HD -g(+) po HD 8.95 ± 2.03 14.83 ± 6.56 217.8 ± 112.5 Vmax – maximal rate of proton efflux / maksymalna prędkość wypływu protonów;
Km – Michaelis constant / stała Michaelisa–Mentena; CRF – chronic renal failure / przewlekła niewydolność nerek; HD – hemodialysis / hemodializa; HD- -g( -) – hemodialyzed without glucose / hemodializa z płynem nie zawierającym glukozy; HD -g(+) – hemodialyzed with glucose / hemodializa z płynem zawierającym glukozę
Before HD vs after HD: / Przed HD vs po HD: * p < 0.05, † p < 0.01,
‡ p < 0.001.
DOES OxIDATIVE STRESS AFFECT THE ACTIVITy OF THE SODIUM-PROTON ExCHANGER? 9
VpHi6.4 in the control group and with Vmax and VpHi6.4 after HD in the HD -g(−) group. We also found a relationship between creatinine and TBARS concentrations (p < 0.0001;
r = +0,51) in patients on conservative treatment (fig. 1).
Results of in vitro studies
The results of in vitro studies are presented in figure 2.
The influence of t -BOOH on NHE activity (VpHi6.4) was assessed at concentrations of 1, 3, 5, 7 and 10 μmol/L and 0.05, 0.1 and 1 mmol/L (fig. 2). Independently of the t -BOOH concentration used, NHE activity was always lower after incubation in glucose -free medium. There was a statistically significant increase in NHE activity at low t -BOOH concen- trations (up to 3 μmol/L) which decreased to baseline level at 50 μmol/L. With increasing concentrations of t -BOOH, NHE
Fig. 1. Correlation of plasma TBARS with creatinine concentrations in patients with chronic renal failure treated conservatively Ryc. 1. Korelacja osoczowego stężenia TBARS ze stężeniem kreatyniny u pacjentów z przewlekłą niewydolnością nerek leczonych zachowawczo T a b l e 4. Concentration of TBARS in erythrocytes and plasma and
TBARS plasma to total plasma protein ratio (mean ± SD) T a b e l a 4. Stężenie TBARS w erytrocytach i osoczu oraz wskaźnik
TBARS w osoczu do całkowitego białka w osoczu (średnia ± SD)
Group Grupa
TBARS in plasma (μmol/L)
TBARS w osoczu (μmol/L)
TBARS in plasma/protein
(μmol/g) TBARS w osoczu/białko
(μmol/g)
(nmol/g Hb)GSH
Control
Kontrolna 0.79 ± 0.12 0.012 ± 0.002 7.26 ± 1.50 CRF 1.05 ± 0.21 0.017 ± 0.004 8.26 ± 1.16 HD -g(+) before HD
HD -g(+) przed HD 1.36 ± 0.30† 0.022 ± 0.004† 8.76 ± 3.47‡
HD -g(+) after HD
HD -g(+) po HD 1.17 ± 0.31 0.017 ± 0.005 11.07 ± 3.28 HD -g(−) before HD
HD -g(−) przed HD 1.56 ± 0.27‡ 0.022 ± 0.004* 10.38 ± 1.81‡
HD -g(−) after HD
HD -g(−) po HD 2.01 ± 0.55 0.027 ± 0.009 8.82 ± 2.22 GSH – reduced glutathione / glutation zredukowany; CRF – chronic renal failure / przewlekła niewydolność nerek; HD – hemodialysis / hemodializa; HD -g(−) – hemodialyzed without glucose / hemodializa z płynem nie zawierającym glukozy; HD -g(+) – hemodialyzed with glucose / hemodializa z płynem zawierającym glukozę
Before HD vs after HD: / Przed HD wobec po HD: * p < 0.05, † p < 0.01,
‡ p < 0.001
RBC – erythrocytes / erytrocyty; t -BOOH – t -butyl peroxide / nadtlenek t-butynylu
Ryc. 2. The influence of superoxides on the sodium -proton exchanger (NHE) activity (VpHi6.4) in relation to the presence of glucose in the dialysate (white
bars: dialysate without glucose; grey bars: dialysate with glucose) Ryc. 2. Wpływ nadtlenków na aktywność wymieniacza sodowo -protonowego – NHE (VpHi6,4) w zależności od obecności glukozy w dializacie (słupki
białe: dializat bez glukozy, słupki szare: dializat z glukozą)
activity decreased in glucose -free solution and remained near the baseline level in the glucose -containing solution.
The activity of the sodium -proton exchanger with t -BOOH at concentrations ranging 1–7 μmol/L was 50% higher than in the control group.
Discussion
Changes in oxidative stress indicators are the conse- quence of changes in the anti -oxidative system. The concen- tration of plasma TBARS is the main indicator of oxidative stress. TBARS concentration was higher in all groups of patients with CRF treated conservatively or undergoing hemodialysis than in the control group. There was a posi- tive correlation between TBARS concentration and plasma creatinine concentration in the CRF group which may reflect increasing production of free radicals in the course of the disease. Similar results were obtained by Taccone -Gallucci et al. [28]. The highest TBARS concentrations were found in dialyzed patients. However, changes in TBARS concen- tration after hemodialysis were not uniform. In the HD -g(+) group, TBARS concentration significantly decreased after HD consistently with results obtained in patients dialyzed with polysulfone membranes [29, 30, 31, 32]. On the other hand, hemodialysis in the HD -g(−) group caused an increase in plasma TBARS concentration without any change in RBC.
Similar results were obtained using cuprophane dialyzers [33] and in our previous studies [31, 32].
Changes in TBARS concentration in both hemodia- lyzed groups reflect changes in the TBARS to plasma pro- tein ratio. The ratio in the HD -g(+) group was lower after HD than before HD and achieved the same value as in the CRF group. In the HD -g(−) group, this ratio was higher after HD than before HD in spite of decreased plasma vol- ume caused by HD.
10 JOANNA BOBER, KAROLINA KĘDZIERSKA, EWA KWIATKOWSKA ET AL.
Differences in TBARS concentrations and their changes during HD in both groups of hemodialyzed patients reflect the significant influence of glucose on the anti -oxidative system. Glucose easily passes through pores of the dialysis membrane causing a decrease in plasma glucose concen- tration when glucose -free solution is used. This decrease is not always seen clinically. The metabolism of glucose through the hexose monophosphate cycle (HMP) in eryth- rocytes increases up to approximately 40% during oxidative stress in comparison to approximately 15% in the basal state.
NADPH is an important product of this metabolic pathway being the source of “reductive equivalents” necessary for the reduction of oxidized glutathione (GSSG) to reduced glu- tathione (GSH), the main non -enzymatic free radical scaven- ger in erythrocytes. Under conditions of decreased glucose concentration and lack of GSH, this anti -oxidative role of erythrocytes is partially impaired. Our results (decreased GSH concentration in the HD -g(−) group and increased in the HD -g(+) group after hemodialysis) confirm the role of glucose in the anti -oxidative action of the HMP cycle.
Free radicals generated during glucose -free HD are not degraded through the non -enzymatic pathway at a sufficient rate and their sheer volume is not dialyzed quickly enough.
In the HD -g(−) group, this process is reflected by increased TBARS concentration after hemodialysis.
Differences in the activity of the sodium -proton exchanger are best observed between the group of patients with CRF on conservative treatment and the other groups.
Although Km did not change, Vmax and VpHi6.4 were undoubt- edly higher. The process of hemodialysis did not affect NHE activity in the HD -g(+) group but showed an apparent inhibi- tory action in the HD -g(−) group.
The influence of TBARS on NHE activity was equivocal.
We found a negative correlation with NHE kinetic param- eters in the control and HD -g(−) groups. In the remaining groups there was a positive correlation with proton efflux rate and a negative correlation with Km. Concerning inter- actions between NHE parameters and anti -oxidative sys- tems, there was a distinct difference between HD -g(+) and the other groups.
Reactive oxygen species generated in chronic renal fail- ure and hemodialysis show destructive properties against blood cells, affecting not only lipids but also transmembrane structures such as ion transporting systems (e.g. sodium- -proton exchanger). Although the exchanger is present in all human cells, mechanisms that regulate its activity are yet to be fully understood. Oxidative stress is one of the factors that can modify NHE activity [34, 35, 36, 37].
The inhibitory role of oxidative stress on NHE activity has been known for a long time [7, 11, 38]. The influence of hydroxyl radicals disappeared in the presence of anti- -oxidative factors such as glutathione or propofol [12, 13].
Free radical -mediated increase in NHE activity was found in rat myocytes exposed to superoxides. Mitogen activated protein kinases were activated by superoxides at low con- centrations (up to 100 μM), producing NHE stimulation
during reperfusion. This effect disappeared in the pres- ence of MAPK inhibitors and partially (up to 50%) in the presence of kinase C and thyrosine kinase inhibitors [39].
Cultured hepatic cells exposed to iron(III)nitrilotriacetate as a source of hydroxyl radicals revealed increased NHE activity associated with increased TBARS concentration.
Inhibition of cell proliferation and decreased collagen syn- thesis were observed in the presence of amiloride, an NHE inhibitor [40].
This paper presents new data found by us which link oxidative stress with NHE activity in hemodialyzed patients [31, 32, 41]. Previously, Matteucci and Giampietro [42]
observed a relationship between reduced glutathione con- centration, TBARS, erythrocyte osmotic resistance, and NHE activity in patients with diabetes (a disease with a free radical background). The activity of the sodium -proton exchanger can be regulated by many factors, especially by protein C kinases [43, 44], calcium ions [45, 46], G pro- teins, and MAPK [4, 5, 6]. One of the features of MAP kinases is their sensitivity to low concentrations of free radicals reflected by their activation leading to increased NHE activity [39]. The presence of MAPK in erythro- cytes was recently demonstrated [47] and is now helpful in explaining many processes which regulate the activity of the sodium -proton exchanger. The results of our in vitro study show that there is a very small range of concentrations of hydroxyl radicals in which significant NHE activation exceeding 50% of the baseline value can be observed. This model appears more likely in patients with renal failure.
It would seem that oxidative stress which intensifies in the course of the disease should either activate or inhibit NHE activity. However, the activity of the exchanger was high in patients with an intermediate stage of the disease, normal in patients with ESRD before dialysis, and low in patients dialyzed with a glucose -free fluid. This discrep- ancy can probably be explained by the action of superox- ides on MAPK. Patients with CRF, like patients with dia- betes [42], are exposed to relatively weak oxidative stress, although strong enough to activate MAP kinases. It is known that increased ROS concentrations lead to inhibi- tion of MAP kinases. This situation was confirmed by us in the control group and in hemodialyzed patients. High oxidative stress and decreased NHE activity were seen when dialysis was done with the glucose -free fluid. On the other hand, there was relatively low stress when glucose was present in the fluid, reflected by unchanged Vmax of the exchanger and reduced Km as a form of activation of this protein [31, 32].
Conclusion
We observed marked oxidative stress and decreased NHE activity when dialysis was done without glucose, whereas patients dialyzed with glucose demonstrated rela- tively low intensity of oxidative stress.
DOES OxIDATIVE STRESS AFFECT THE ACTIVITy OF THE SODIUM-PROTON ExCHANGER? 11
References
1. Wakabayashi S., Fafournoux P., Sardet C., Pouysségur J.: The Na+/H+
antiporter cytoplasmic domain mediates growth factor signals and con- trols “H(+) -sensing”. Proc Natl Acad Sci USA. 1992, 89, 2424–2428.
Grinstein S., Woodside M., Sardet C., Pouyssegur J., Rotin D.
2. : Activa-
tion of the Na+/H+ antiporter during cell volume regulation. Evidence for a phosphorylation -independent mechanism. J Biol Chem. 1992, 267, 23823–23828.
Winkel G.K., Sardet C., Pouyssegur J., Ives H.E.
3. : Role of cytoplasmic
domain of the Na+/H+ exchanger in hormonal activation. J Biol Chem.
1993, 268, 3396–3400.
Gillis D., Shrode L.D., Krump E., Howard C.M., Rubie E.A., Tibbles L.A.
4.
et al.: Osmotic stimulation of the Na+/H+ exchanger NHE1: relation- ship to the activation of three MAPK pathways. J Membr Biol. 2001, 181, 205–214.
Bianchini L., L’Allemain G., Pouyssegur J.
5. : The p42/p44 mitogen-
-activated protein kinase cascade is determinant in mediating activation of the Na+/H+ exchanger (NHE1 isoform) in response to growth factors.
J Biol Chem. 1997, 272, 271–279.
Gekle M., Freudinger R., Mildenberger S., Schenk K., Marschitz I., Schra- 6.
mek H.: Rapid activation of Na+/H+ exchange in MDCK cells by aldoste- rone involves MAP -kinase ERK1/2. Pflugers Arch. 2001, 441, 781–786.
Cutaia M., Parks N.
7. : Oxidant stress decreased Na+/H+ antiport activity in bovine pulmonary artery endothelial cells. Am J Physiol. 1994, 267, L649–659.
Demaurex N., Romanek R.R., Orlowski J., Grinstein S.
8. : ATP dependence
of Na+/H+ exchange. Nucleotide specificity and assessment of the role of phospholipids. J Gen Physiol. 1997, 109, 117–128.
Hu Q., Xia Y., Corda S., Zweier J.L., Ziegelstein R.C.
9. : Hydrogen pero-
xidase decreased pHi in human aortic endothelial cells by inhibiting Na+/H+ exchange. Circ Res. 1998, 83, 644–651.
Kaufman D.S., Goligorsky M.S., Nord E.P., Graber M.L.
10. : Perturba-
tion of the cell pH regulation by H2O2 in renal epithelial cells. Arch Biochem Biophys. 1993, 302, 245–254.
Shaw S., Naegeli P., Etter J.D., Weidmann P.
11. : Inhibition of rat glome-
rular mesangial cell sodium/hydrogen exchange by hydrogen peroxide.
Clin Exp Pharmacol Physiol. 1995, 22, 817–823.
Daskalopoulos R., Korcok J., Farhangkhgoee P., Karmazyn M., 12.
Gelb A.W., Wilson J.X.: Propofol protection of sodium -hydrogen exchange activity sustains glutamate uptake during oxidative stress.
Anesth Analg. 2001, 93, 1199–1204.
Ciriolo M.R., Palamara A.T., Incerpi S., Lafavia E., Buè M.C., De Vito P.
13.
et al.: Loss of GSH, oxidative stress, and decrease of intracellular pH as sequential steps in viral infection. J Biol Chem. 1997, 272, 2700–2708.
Lin T.H., Chen J.G., Liaw J.M., Juang J.G.
14. : Trace elements and lipid
peroxidation in uremic patients on hemodialysis. Biol Trace Elem Res. 1996, 51, 277–283.
Soejima A., Matsuzawa N., Miyake N., Karube M., Fukuoka K., Naka- 15.
bayashi K. et al.: Hypoalbuminemia accelerates erythrocyte membra- ne lipid peroxidation in chronic hemodialysis patients. Clin Nephrol.
1999, 51, 92–97.
Ludat K., Sommerburg O., Grune T., Siems W.G., Riedel E., Hampl H.
16. :
Oxidation parameters in complete correction of renal anemia. Clin Nephrol. 2000, 53, S30–35.
Tepel M., Klaus T., Laukemper S., Schlüter H., Zidek W.
17. : Increased
lymphocytic Na+/H+ exchange activity after hemodialysis: evidence for an endogenous inhibitor of Na+/H+ exchange in patients with end- -stage renal failure. Life Sci. 1996, 59, 1545–1552.
Rombolà G., Colussi G., Guastoni C., Civati G., Minetti L.
18. : Lympho-
cytic intracellular pH and Na+/H+ exchanger activity in hemodialysis patients. Am J Physiol. 1995, 15, 24–30.
Poli de Figueiredo C.E., Ng L.L., Garrido M.C., Davies J.E., Ellory J.C., 19. Hendry B.M.: Leukocyte intracellular pH and Na/H antiporter activity
in uraemia and type I diabetes mellitus. Nephrol Dial Transplant. 1991, 6, 615–620.
Kovacic H., Gallice P., Brunet P., Berland Y., Crevat A.
20. : Sodium pump
and Na+/H+ activities in uremic erythrocytes. A microcalorimetric and pH -metric study. Clin Chim Acta. 1997, 259, 31–40.
Corry D.B., Tuck M.L., Nicholas S., Weinman E.J.
21. : Increased Na/H
antiport activity and abundance in uremic red blood cells. Kidney Int.
1993, 44, 574–578.
De Franceschi L., Olivieri O., Girelli D., Lupo A., Bernich P., Corro- 22.
cher R.: Red cell cation transport in uremic anaemia: evidence for an increased K/Cl co -transport activity. Effects of dialysis and erythro- poietin treatment. Eur J Clin Invest. 1995, 25, 762–768.
Orlov S.N., Postnov I.Y., Pokudin N.I., Kukharenko V.Y., Postnov Y.V.
23. :
Na+ -H+ exchange and other ion -transport systems in erythrocytes of essential hypertensives and spontaneously hypertensive rats: a com- parative analysis. J Hypertens. 1989, 7, 781–788.
Leatherbarrow R.J.
24. : Enzfitter, a non -linear regression data analysis program for the IBM PC. Sigma 2000.
Canessa M.
25. : Kinetic properties of Na+/H+ exchange and Li+/Na+, Na+/
Na+, and Na+/Li+ exchanges of human red cells. Methods Enzymol.
1989, 173, 176–191.
Wasowicz W., Neve J., Peretz A.
26. : Optimized steps in fluorometric de-
termination of thiobarbituric acid -reactive substances in serum: im- portance of extraction pH and influence of sample preservation and storage. Clin Chem. 1993, 39, 2522–2526.
Beutler E., Duron O., Mikuskelly B.
27. : Improved method for the determi-
nation of blood glutathione. J Lab Clin Med. 1963, 61, 882–888.
Taccone -Gallucci M., Giardini O., Lubrano R., Bandino D., Mazzarella V., 28.
Mannarino O. et al.: Red blood cell lipid peroxidation in predialysis chronic renal failure. Clin Nephrol. 1987, 27, 238–241.
Biasioli S., Schiavon R., Petrosino L., Cavallini L., Cavalcanti G., 29.
De Fanti E. et al.: Role of cellulosic and noncellulosic membranes in hyperhomocysteinemia and oxidative stress. ASAIO J. 2000, 46, 625–634.
Luciak M., Trznadel K.
30. : Free radical species metabolism during ha- emodialysis with different membranes. Nephrol Dial Transplant. 1991, Suppl. 3, 66–70.
Bober J., Kwiatkowska E., Kędzierska K., Olszewska M., Dołęgow- 31.
ska B., Domański L. et al.: Does glucose present in the dialysate limit oxidative stress in patients undergoing regular hemodialysis? Blood Purif. 2005, 3, 219–225.
Bober J., Kwiatkowska E., Kędzierska K., Olszewska M., Gołembiew- 32.
ska E., Stachowska E. et al.: Influence of glucose in the dialysate on the activity of erythrocyte -glutathione -peroxidase and blood se- lenium concentration in hemodialyzed patients. Arch Med Res. 2007, 3, 330–336.
Toborek M., Wasik T., Drózdz M., Klin M., Magner -Wróbel K., 33. Kopieczna -Grzebieniak E.: Effect of hemodialysis on lipid peroxi- dation and antioxidatant system in patients with chronic renal failure.
Metabolism. 1992, 41, 1229–1232.
Avkiran M.
34. : Protection of the ischaemic myocardium by Na+/H+ exchan- ge inhibitors: potential mechanisms of action. Basic Res Cardiol. 2001, 96, 306–311.
Karmazyn M.
35. : Role of sodium -hydrogen exchange in cardiac hypertro- phy and heart failure: a novel and promising therapeutic target. Basic Res Cardiol. 2001, 96, 325–328.
Matteucci E., Di Bello V., Giampietro O.
36. : Integrated analysis of erythro-
cyte Na+/H+ antiport activity and left ventricular myocardial function in type I insulin -dependent diabetes mellitus. J Diabetes Complications.
1995, 9, 208–211.
Trevisan R., Viberti G.
37. : Sodium -hydrogen antiporter: its possible role in the genesis of diabetic nephropathy. Nephrol Dial Transplant. 1997, 12, 643–645.
Tsai K.L., Wang S.M., Chen C.C., Fong T.H., Wu M.L.
38. : Mechanism of
oxidative stress -induced intracellular acidosis in rat cerebellar astro- cytes and C6 glioma cells. J Physiol. 1997, 502, 161–174.
Sabri A., Byron K.L., Samarel A.M., Bell J., Lucchesi P.A.
39. : Hydrogen
peroxide activates mitogen -activated protein kinase and Na+/H+ exchan- ge in neonatal rat cardiac myocytes. Circ Res. 1998, 82, 1053–1062.
12 JOANNA BOBER, KAROLINA KĘDZIERSKA, EWA KWIATKOWSKA ET AL.
Svegliati -Baroni G., Di Sario A., Casini A., Ferretti G., D’Ambrosio L., 40. Ridolfi F. et al.: The Na+/H+ exchanger modulates the fibrogenic ef- fect of oxidative stress in rat hepatic stellate cells. J Hepatol. 1999, 30, 868–875.
Bober J., Kwiatkowska E., Ciechanowski K., Kędzierska K., Dołęgow- 41. ska B., Olszewska M. et al.: Do trace elements modify the activity of erythrocyte sodium -proton exchanger in hemodialyzed patients? Biol Trace Elem Res. 2005, 2, 107–120.
Matteucci E., Giampietro O.
42. : Oxidative stress in families of type 1
diabetic patients. Diabetes Care. 2001, 24, 167–168.
Sauvage M., Mazière P., Fathallah H., Giraud F.
43. : Insulin stimulates
NHE1 activity by sequential activation of phosphatidylinositol 3 -kinase
and protein kinase C zeta in human erythrocytes. Eur J Biochem.
2000, 267, 955–962.
Wakabayashi S., Shigekawa M., Pouyssegur J.
44. : Molecular physiology
of vertebrate Na+/H+ exchanger. Physiol Rev. 1997, 77, 51–74.
Lijnen P., Fagard R., Petrov V.
45. : Activation by calcium of erythrocyte
Na+/H+ exchange in men. J Hypertens. 1998, 16, 305–310.
Lijnen P., Echevaria -Vázquez D., Fagard R., Petrov V.
46. : Protein kinase
C induced changes in erythrocyte Na+/H+ exchange and cytosolic free calcium in humans. Am J Hypertens. 1998, 11, 81–87.
Sartori M., Ceoletto G., Semplicini A.
47. : MAPKinase and regulation
of the sodium -proton exchanger in human red blood cell. Biochim Biophys Acta. 1999, 1421, 140–148.
A N N A L E S A C A D E M I A E M E D I C A E S T E T I N E N S I S
R O C Z N I K I P O M O R S K I E J A K A D E M I I M E D Y C Z N E J W S Z C Z E C I N I E 2010, 56, 3, 13–19
BOGuMIłA ELBL, BOżENA BIRKENfELD, JADWIGA SZYMANOWICZ¹, hANNA PIWOWARSKA-BILSKA, TOMASZ uRASIńSKI¹, MARIA LISTEWNIK, ALEKSANDRA GWARDYŚ
ZALEżNOŚć MIęDZY ODPłYWEM żOłąDKOWO-PRZEłYKOWYM A NAWRACAJąCYMI ZAKAżENIAMI DOLNYCh DRóG ODDEChOWYCh
I ASTMą OSKRZELOWą u DZIECI
ThE ASSOCIATION BETWEEN GASTROESOPhAGEAL REfLux AND RECuRRENT LOWER RESPIRATORY TRACT INfECTIONS
AND BRONChIAL ASThMA IN ChILDREN
Zakład Medycyny Nuklearnej Pomorskiego Uniwersytetu Medycznego w Szczecinie ul. Unii Lubelskiej 1, 71-252 Szczecin
Kierownik: dr hab. n. med., prof. PUM Bożena Birkenfeld
¹ Klinika Pediatrii, Hematologii i Onkologii Dziecięcej Pomorskiego Uniwersytetu Medycznego w Szczecinie ul. Unii Lubelskiej 1, 71-252 Szczecin
Kierownik: dr hab. n. med., prof. PUM Tomasz Urasiński
Summary
Introduction: It is well known that gastroesophageal reflux (GER) coincides with chronic diseases of the lower respiratory tract. However, the impact of effective manage- ment of gastroesophageal reflux on the course of coexisting pathologies of the lower respiratory tract has not been une- quivocally evaluated. This study was undertaken to assess the impact of treatment of gastroesophageal reflux on the course of recurrent lower respiratory tract infections and bronchial asthma in children.
Material and methods: We enrolled 76 children, 38 boys and 38 girls, aged 1–204 months (median: 66.5 months). All children had clinical symptoms of gastroesophageal reflux.
The children were allocated to three groups: Group I: recur- rent lower respiratory tract infections (33 children); Group II: bronchial asthma (23 children); Group III: no chronic respiratory tract disease (20 children). Groups were similar with respect to age and gender. Upper gastrointestinal tract scintigraphy and endoscopy were performed in all chil- dren. The children were followed for 1–23 months (mean: 7 months). In most cases, GER was managed conservatively, except for four children who were operated.
Results: Complete or partial resolution of GER symp- toms was seen in 89% of patients, no change was noted
in 9%, and progression was seen in the remaining 2% of children. Treatment of GER was accompanied by alleviation of respiratory symptoms in 84% of children (group I and II).
Conclusions: Effective therapy of gastroesophageal reflux decreases the frequency of recurrent lower respira- tory tract infections and improves asthma control.
K e y w o r d s: gastroesophageal reflux – bronchial asthma – recurrent lower respiratory tract infec-
tions – children.
Streszczenie
Wstęp: Współwystępowanie odpływu żołądkowo- -przełykowego i przewlekłych chorób dolnych dróg oddechowych jest zjawiskiem znanym od dawna, nato- miast nie oceniono dotychczas jednoznacznie wpływu skutecznego leczenia odpływu żołądkowo -przełykowego na przebieg współistniejących schorzeń dolnych dróg oddechowych.
Celem pracy była ocena wpływu leczenia odpływu żołądkowo -przełykowego na przebieg nawracających zakażeń dolnych dróg oddechowych i astmy oskrzelowej u dzieci.