Nghien CLFU - Ky thuat
vi khuan 6 ndng do thude pha lodng nhy ddi vol chiing vi khudn miu (1/150); fl' nflng do thudc pha loang 1/200 thudc khflng cfl kha nang ii-e chd vi khuan phdt tridn.
- VOI tryc khudn E. coli: thudc cfl kha nang ii-c chd 90 % vi khudn phdt tridn fl* ndng do thudc pha lodng 1/50; 76,66 % chung vi khuan phdt tridn fl' ndng do thudc pha loang 1/75; & ndng dfl thudc pha loang nhu ddi vol chung vi khudn mdu (1/100) thudc cd khd ndng yc chd 66,66 % ehiing vi khudn; fl' ndng dfl thudc pha lodng 1/150 vd 1/200 thudc khong co khd ndng ire chd vi khudn phdt tridn.
+ 6" ndng dfl thudc pha loang nhu cde chiing vi khuan mau: khd ndng khdng khuan cua thudc C T.K giira cdc chung E coli va tu cau khuan vdng phdn lgp dygc Id nhy nhau (p > 0,05)
Thudc CO xu hu'dng idm giam pH dm dao dgng vgt thi nghiem trong qua trinh dgt thudc
Viem nhiem dyfl'ng sinh dye dyoi thyong Id sy phdi hgp cua cae tde nhdn, can nghien ciru bd sung vdo thudc mflt sd hogt chdt chdng nam,
trichomonas, de cfl the mfl' rflng phgm vi ehi djnh ciia thude.
Tai lieu tham khSo
1. Phan Thj Kim Anh (1994). "Nghien cCru hudc ddu danh gia tdn sudt mdc bSnh nhilm khuin di/dng sinh due du'oi a phu nO ddn kham tai B§nh vi#n bao v$Ba me va Tre so smh'. Luan van Bac sT chuydn khoa II, Truong 0ai hpc Y Ha Noi
2. Phan Thl Kim Anh (1995), "Vi khuin gay b^nhvd tinh nhay cam vol khang smh cua cSc chung vi khuin phan lap du'oc tai Benh vien Bao ve Ba me vd Tre so smh trong 2 nam 1994-1995", Cong trinh nghien cOv khoa hoc Benh vien Bdo vd Ba me va Tre sa sinh. tr 85-92
3- Nguyen Huy Can, Lu-angThi Bich (1971), "Dilu tri viem §m dao blng thudc nam", Ky ydu cdng trinh nghien cOv khoa hoc y dwac. Tap 1, Nhd xuat ban Y hoc. tr-162-168
4 Duong Thi Cuang (1994), Viem dwdng smh due nif, Bach khoa thu b^nh hoc, I g p II, tr. 452-455
5. Nghiem Thl Thanh Hudng (1996), "OSnh gia tac dung cua vien nen C T K ddi v6i b#nh vi&m am dgo, cb tip cung do vi khuin tai tuyin c6ng ding", Kyyeu cac cong trinh nghien c&u khoa hoc, Vi^n Y hgc c6 truyin Viet Nam, tr 224-234
{Ngdy nhdn bdi: 25/3/2015 - Ngdy duydt ddng: 04/05/2015)
jThir nghiem tac dung kfch thich mien dich ciia pidotimod tong hop tren dong vat thi nghiem
NguySn Van Ru^, Quach Thi Ha Van^
'Tnt&ng Dgi hoc Dirac Ha Xoi -Hoc I ip« Oudn Y
*E-mail.quachhavan(agniail com
Summary
TTie bioactive influences of the pidotimod recently synthetized in Vietnam on some biological processes were investigated in mice. Experimental animals were divided into four groups: a control (G1), negative control (G2), pidotimod 200 mg/kg treated (G3), and pidotimod 400 mg/kg treated group (G4). On the first day of testing, the mice of G3 and G4 were given orally pidotimod (dose 200 mg / kg and 400 mg / kg) 1 time a day, for 12 consecutive days. On the 3^, 4'^ and 5" day (from ffje start of oral pidotimod), groups G2, G3, G4 were subjected to peritoneal injection with cyclophosphamide (120 mg/kg/day) to cause immunosuppmssion. On day 13, all mice were injected intravenously glue Pelikan ink 4001 (carbon) diluted at a dose of 0.1 ml/10 g body w/eight The decrease in relative spleen v\^ight along with the increase in the v/eight of mice, relative thymus weight, the number of leukocytes was higher than G2 wffth obvious statistical significance (p <0.05) The tested pidotimod exhibited the immunostimulating effects on some organs and immune system cells, influencing the macrophage function in reticuloendothelial of mononuclear cells.
TAP CHi DirgfC HOC - 5/2015 (S6 469 NAM 55)
Nghien CIFU - Ky thuat
Keywords: Pidotimod, biological processes, weight, leukocytes.
D|t vdn 6k
Pidotimod Id mgt hgp ehat efl tdc dyng dieu hfla midn djch dang d y g c T r y i n g Dgi hgc D y g c Hd Ngi tien hanh nghien eiru tdng hgp. Nhflm nghien ciru ehiing tfli tien hdnh thir mgt sd tdc dyng sinh hgc ciia che phdm tren dgng vat t h y c nghigm nhdm mye tieu khdo sat d y g c dnh hud'ng cua pidotimod den mflt sd qud trinh sinh hgc tren chuflt thi nghiem theo quy dinh cua Bg Y te ''i nhy thdn trpng, trgng lugng t y o n g ddi cua Idch, ire;
sd lygng bach cau vd ddnh gid tae dung kich thich mien djeh tren chirc ndng dgi thyc bdo vol h§ lydi nfli mfl.
N g u y e n l i e u , cTdi t u ' O ' n g v a p h u ' O ' n g p h a p n g h i e n c i P u
Nguyen liflu:
Pidotimod do Bg mfln Hod D y g e - Tnrong Dgi hgc D y g c Ha Ngi tdng hgp.
immunostimulating, weight of mice, relative thymus
Doi t u ' o n g :
Chugt nhdt trdng do Vien Vg sinh Djeh te Trung y o n g cung cap'^l
Phu'O'ng phdp nghien cu>u:
Chugt d y g e ehia thanh 4 Id, moi Id 8 eon nhy sau:
- Lfl chu'ng sinh hge (G1): chugt d y g c udng n y o c mudi + khflng gdy suy giam mien djch;
Lfl chirng am (-) (G2)' N y o c mudi + cyclophosphamid (CY);
- Lfl thir lieu 200 (mg/kg) (G3): ehugt d y g e tiem pidotimod 200 mg/kg + CY;
- Ld thir lieu 400 (mg/kg) (G4): chuflt d y g c tiflm pidotimod 400 mg/kg + CY.
Cdc ehi tiflu nghien ciru: S y bien ddi trgng lygng co the, trgng lugng Idch tuong ddi, trgng lygng tuyen ire t y o n g ddi, cfl lygng bgch cau ngoai vi, ehf sd thyc bdo'^'.
S o dd thi nghidm
CY (120 mg/kg) i.p. Carbon (Myc)
(0,1 ml/10 g)i.v.
Pidotimod (200 - 400 mg/kg, p.o.), 1 lan/ngay x 12 ngay
Lay mau hoc mat, can, can lach, iic.
Hinh 1 ; S o d S quy trinh Cdch tiin hdnh
Theo dfli cdn ngng cua chugt trong sudt qua trinh eho udng thudc, cho chugt udng diing lieu vd theo ddi phdn irng ben ngodi eiia ehudt.
Ngdy t h y nhat eiia thir nghigm, ede lo G3 vd G4, chuflt d y g c udng pidotimod (lieu 200 mg/kg vd 400 mg/kg) 1 Idn/ngdy va udng trong 12 ngdy lien tye. Cdc ngay t h y 3, thir 4 vd ngdy thir 5 tinh tir khi bdt dau cho udng pidotimod, cac Ifl G2, G3, G4 d y g c tiem phiic mgc cyclophosphamid (lieu 120 mg/kg/ngdy) dd gdy suy gidm mien djch. Vdo ngdy thir 13 tdt
tidn hdnh thO nghidm
ea ede cd the chuflt d y g c tiem ttnh mach keo m y c Pelikan 4001 (carbon) da pha loang vfl'i lieu 0,1 ml/lOg the trgngi^l
Tai thoi didm 0 vd 15 phiit sau khi tiflm m y c , lay mau mau tir hde mdt 6' mdi ehugt eho vdo tirng dng chdng dong d y n g riflng biflt, cd ddnh ddu t y o n g irng; mdu thu d y g e mang ddm bgch eau bdng may dem t y dflng vd do quang dd xdc djnh dg thanh thai carbon.
Phmmg phdp ddnh gid dg thanh thai Mdi m i u d y g c them HCI 0,1 N de ly gidi vol ty Ifl 10 pi mau/3 ml HCI. Sau do dem ly tdm
TAP CHI DlTQC HOC-5/2015 (S6 469 NAM 55)
• Nghien ciru - Ky thuat
vgi tdc do 4000 vflng trong 5 phut, logi bfl edn va Idy phan nyfl'c dd do quang, xde djnh ndng do carbon trong mau. Tien hdnh quet phd de xdc djnh byoc song tai dd ed dg hap thy eye dgi (fl' byfl'c sdng 657 nm), sau dfl do mat do quang tgi byfl'c sflng dfl (mdu trdng la mdu chuflt khflng tiflm myc, va tien hdnh ly giai, ly tdm nhy cae mdu khde).
Xac djnh trgng iw^g lach va tuyen IFC
Chuflt sau khi lay mau, gidt chdt, md byng de bflc lfl Idch, tuyen ire. Bflc nhe nhdng cat lay todn bg tuydn ire, lach ciia tirng eon ehugt, diing ggc thdm khd nyoc vd mdu tryoc khi cho cae td ehu-e ndy Ifln dTa can'^i.
Phuvng phap xir iy s6 ii$u
Cac sd lieu nghien ciru dyge xy ly thdng ke theo phyong phap t - test Student. So lieu dyoc dien dat dyoi dang X^^ ± SD Sy khdc biet ed y nghTa thdng ke khi p < 0,05
K i t qua nghien CLPU
Theo doi su> bidn d6J trgng iu'g'ng co> thl trong qua trinh thu> nghiflm
Kdt qua ve trgng lygng chugt tryde, sau khi tiem cyclophosphamid vd sy bidn ddi trgng lygng chuflt = trgng lygng sau thir - trgng lygng trygc khi tiflm CY trinh bdy tren bdng 1.
Lo chugt
Chung sinh hoc Chijng im ThCr liiu 200 Thir liiu 400
Bang 1: KStqu^
Ngay thirl 33,6311,33 34,00*1,39 33,75*2,60 31,78*2,58
v^ sy biSn ddi tn?ng luvng chudt thl nghISm
Tp^ng lining (giNgay thir 3 35 + 2,00 34,75*1,49 34,88*2,59 33,38*2,50
Ngaythi>13 42,1312,17""
27,1313,68"
30,6312,50"' 28,25 + 1,75"
— Slf biin doi trgng luong (g)
*7,13*2,17 -76213,02 4,2510,46 -5,11*1,09 Dau (-) the hi$n sw gidm khSi Iwong, dau (+) thi hi$n sw tang khoi luvng.
'. p< 0,05, **, p < 0,01 so vol nhom chCmg Sm.
''• p<0, 05:'^ p<0,01 so V&I tn?ng tw<?ng ban diu.
Kdt qud bang 1 eho thdy tnr&c khi tiflm CY, trgng lygng ehugt fl' cdc nhdm khdc nhau khdng ddng kd, nhyng sau khi gay suy giam midn dich, trgng lygng eiia cdc nhflm ehugt da cd sy thay ddi, trong khi nhflm chyng sinh hge tang, thi eac nhdm khae deu gidm so vd'i ban dau. Nhy vgy, pidotimod Idm tang trgng lygng chuflt so vol nhdm chyng am, ddc biet fl' lidu 200 mg, sy tdng ndy cfl y nghTa thdng ke so vfl'i chirng dm.
Xac djnh trgng lu'O'ng lach tu*ong ddi Trgng lygng laeh tyong ddi (%) = Trgng lygng Idch x 100/Trgng lygng chugt,
Chung tfli sir dung trgng lygng Idch tyong ddi de Idm gidm sy phy thugc eiia Idch vao trgng lygng ehuflt. Viing tiiy trdng eiia Idch Id noi trii ngy ciia ede te bao lympho nfln bj dnh hyd'ng nhidu ciia CY. Sau day Id kdt qud trgng lygng Idch tyong ddi ciia cdc nhdm chugt.
Bdng 2: Kit qud vi trong luxyng Idch twang ddi
Lo chuot ChLFng smh hoc ChLpng am (-) ThCf lilu 200 mg/kg ThCr lieu 400 mg/kg
N 8 8 8 8
Trgng Itfgng lich tlmng ddi 0,52310,118"
0,770*0,148"
0,65410,112*
0,557 * 0,036"
pi) Tyl^ so vin (•) (lin) 0,68 1,00 0,85 0,72
:p< 0,05, "
;p<0,05, "
p<0,01 so vdl 16 chCeng am p < 0.01 so voi Id chOng sinh hoc
Kdt qua trfln bang cho thdy: CY Idm tang ddng ke trgng lygng laeh tyong ddi (khodng 32 %) so vd'i nhom chyng sinh hgc. Cdc nhdm su" dung pidotimod cung ed tdng nhyng tdng it hon so v&\
chyng am, chu'ng to pidotimod efl tde dyng lam hgn ehe sy gia tang trgng lygng Idch ciia CY.
Dge biflt pidotimod 400 Idm gidm trgng lygng Ideh dang kd (khodng 28 %) so vd'i chirng dm,
TAP CHI DU'OC HOC-5/2015 (56469 NAM 55)
Nghien ctpu - Ky thuat
trd" ve gan mye binh thyfl'ng eiia nhflm chyng sinh hgc
Anh hu'fl'ng cua pidotimod len trgng lu'O'ng tuydn U'C tuiong ddi cua chudt thi nghiem
Tyong ty nhy Ideh, tinh trgng lygng tuyen ire
Bdng 3: Kdt qud vd trong Iwgng tuyin wc twang ddi
tyong ddi eua ede nhflm ehugt de ddnh gid tac dung eua pidotimod theo cong thyc:
Trgng lw(;mg tuyin wc tuong <Rii(%) = Trong luang tuyin wc^lOO/ Trgng Iwgng diudt
id chugt Chirng smh hoc
Chijng am (-) Thif lieu 200 ThiJ lilu 400
N 8 8 8 8
Trgng lirgng tuy4n ijpc tifong ddi (%) 0,14310,049"
0,042*0,029"
0,135*0,049"
0,134*0.025"
Tfl&sov6i(-)(lin}
3,40 1,00 3,21 3,19
•; p < 0,05, ** p<0,01 so vai Id ch&ng dm: " • Ket qua ehi ra rang, trgng lygng tuydn ire eiia chirng dm, chi gan bdng 1/3 ehirng sinh hgc vd 2 nhflm sir dung pidotimod cfl trgng lygng tuyen ire, xap xi bdng nhdm ehyng sinh hgc. Nhy vdy efl thd nfli, pidotimod g cd 2 mirc lieu giiip khoi
' < 0,05; '^- p<0,01 so vol 16 ch&ng S//J/J hoc.
phyc trgng lygng Ideh tyong ddi fl' ehuflt bj suy giam midn djch vd mu-c binh thyfl'ng.
Anh hu'fl'ng cua pidotimod len sd lygng bgch cdu ngogi vi
Bang 4; Kdt qud vi dnh hw&ng cOa pidotimod din s6 lugng bsich cdu ngoai v
Nh6m chuotLd chiing smh hoc L6 Chung am (-) Lo thu tieu 200 Lo thu lilu 400
N 8 8 8 8
So lu'gng b^ch ciu (itliy ti bao/ml) 1711318,994 4,638 11,036"
10,775 13,541"' 12,912 15,780"
Tyle so voi (-) (tin) 3,69 1,00 2,32 2,78
*. p < 0,05, **. p<0,01 so vol 16 chung am; '^
Kdt qua trfln bang chi ra rdng CY Idm giam sd lygng bgch cau xudng khodng 3,5 Idn so vol nhflm chyng sinh hgc vd pidotimod d' cd 2 mu'c lidu dd Idm tang sd lyong baeh eau len khoang 2 lan so vd'i chirng am, tuy nhien vin chya the dat nhy mire binh thyong va viec dimg lieu 400 Idm tdng bgch cdu cao hon so vgi Ifl 200, sy khdc nhau ve sd lygng baeh eau giira 2 Ifl nay khong efl y nghTa thdng kfl (p > 0,05).
Anh hu'ong cua pidotimod Ifln chiix nang
dai thiFC bdo cua \IPCF\ ngi mdDgi thyc bdo lyd'i ngi md cfl nhiflm vy quan trgng Id thyc bdo vd tiflu hoa khdng nguyen, sau dd truydn thflng tin di truyen khdng nguyfln eho
p < 0.05:'". p < 0,01 so vol 16 ch&ng smh hpc
ede te bdo lympho dd tgo tri nhd* mien djch. Vi vdy, ehung tfli danh gia ehire nang thye bdo eiia cac td bdo don nhdn lygi nfli mo thflng qua chl sd thyc bdo sau khi dya khdng nguyfln Ig Id carbon vdo mdu.
Cflng thirc tinh chi sd thyc bdo nhy sau:
K = (Ln OD, - Ln OD^) / (T, - T,) trong dfl: OD, vd ODj Id mgt dfl quang do tgi thd'i diem T, (0 phiit) va T^ (15 phiit) tuong irng.
Ndng dfl carbon trong mdu cao (OD cao) sau 15 phLJt thi chi sd thyc bdo edng thap, tue Id khd ndng bat giir cac hat carbon cua cdc td bdo don nhdn cdng thap. Ket qud thi nghigm tren eae 16 ehuflt dyoc ghi nhdn trong bdng 5.
Bdng 5: Kit qud vi dnh hw&ng cOa pidotimod ldn chi s6 dai thwc bdo cOa Iw&i ndi md
Lo chuotChOng sinh hoc Chtmg im {•)
VliHliu200 Thu biu 4(XI
N 8 8 8 8
Mat do quang t^O phat 0,082 10,048 0,120 10,030 0,123 10.039 0,111 * 0,020
mt
do quang t^i 15 phut 0,041 • 0,026 0,093 10,024 0,069 10,015 0,067 10,018Chi s6 thgc bao 0,053*0,026 0,017 10,009"
0,037 * 0,013*
0,03610,018
Tyle so voi (•) 3,12 1.00 2.18 2.12
";p < 0,05, " . p < 0,07 so voi 16 chirng am , ^ ' p< 0,05, " p < 0,01 so v6i 16 chwng smh hoc.
TAP CHi Diroc HOC - 5/2015 (SO 469 NAM 55)
• Nghien CLPU - Ky thuat
Chi sd t h y e bdo cua Ifl ehung dm ehi bdng khoang 1/3 so v o l chu-ng sinh hgc. Pidotimod fl- nhflm t h y lieu 200 mg/kg lam tdng ehi sd ndy Ifln khodng 2 ldn so voi chyng dm va co y nghta thdng ke (p < 0,05).
B a n l u a n Vfl t r g n g I v g ^ g c h u o t :
CY gay (re chd midn djch, y c che s y tang sinh cua hau het cac td bdo, dae biflt Id td bdo tiiy xuong va te bao niem mae dyfl'ng tiflu hfla, do dfl gay ra nhieu tdc dyng phy trfln duong tieu hfla vd cac mfl, eo quan khae. Qua quan sdt, cho thay ede id ehugt cd s y dyng CY cdc phan ii-ng t h y a n g ngdy cham chap hon, thuong ndm tgp ehung mgt ehd, it hoat dgng vd dn it hon so voi Ifl chirng sinh hge, mflt sd chuflt cfln efl biflu hien tieu chdy d* nhirng ngdy cudi cua dot diing thudc.
Cfl le vi vdy md khdi lygng chuflt fl' nhirng nhom ndy gidm nhieu so vol ban dau, nhat Id 16 ehyng am, trong khi Ifl chirng sinh hgc, khdi lygng ehuflt van tang sau 13 ngay didu tri.
Ve t r g n g lipong lach tu'cmg ddi Lo chu'ng am cfl gid tri Ion nhat, cfln lo chyng sinh hgc co gia tri be nhat, tire la CY tang trong lygng lach t y o n g ddi a chuflt nhdt trdng. Cd the do CY Idm suy giam m i l n dich nen con vdt dd bi nhiem cac tdc nhdn gay benh (vi khuan, virus, ky sinh trung...) vd tang sd lugng eae td bdo chdt, efl thd day ehinh Id nguyen nhan Idm tang khdi lygng Idch. Ldch d u g c cau tao bfll tuy trdng vd tiiy ad. Trong do tuy do chidm 4/5 khdi lu'gng Idch, Id "md chon' eua cdc td bao hdng cau gid hay tfln thyong vd cdc mdnh te bdo chdt. Day cung cd the id nguyen nhan lam tang khdi lygng lach fl' nhirng 16 dilng CY. Tiiy trdng ehinh Id noi chya cde nang lympho.
Vfl t r g n g I v g n g tuyen IFC t v o m g ddi Nhflm ehirng dm cfl gid tn thap hon dang ke so vd'i nhdm chirng sinh hgc, chu'ng td CY lam teo nhfl CO quan lympho nay. Tuyen ire Id eo quan lympho trung y o n g , la noi chin va biet hoa eiia lympho T. Tuydn ii-c teo nhd anh hu'fl'ng den chuc ndng mifln dich, dae biflt Id ddng baeh eau iympho T vd dap yng tao khang the phy thuflc te bdo T (T-^ependent antibody response) eiia ddng td bdo lympho B. Cac to s y dung pidotimod ed khdi lugng tuydn ire Ifln hon ddng ke so vgi 16
chu'ng dm vd efl s y khac biet khflng dang ke so v o l Ifl chirng sinh hgc. N h y vay, cfl the noi rdng, pidotimod cfl tdc dyng bao ve tuyen y c d y o i tdc dyng cua CY, gflp phan Idm tang OLFMD d' nhO'ng ea thfl bi suy gidm m i l n dich.
v d s d liFO'ng bach c d u
Cung thay rd s y gidm bgch cdu fl' Ifl chyng dm do s y u'c chd tiiy x y o n g ciia CY. O cac 15 didu tri bdng pidotimod Idm hgn che ddng kd sy giam ndy. Co the giai thich rdng, pidotimod eo tac dung ngdn chgn s y y c chd tuy x y o n g ciia CY, bdo ve cac td bdo nay nhdm duy tri ehire ndng eua ehung trong he mifln djch nfli ehung va hfl tao mau ndi chung.
D d i vifi c h i s d t h v c bao
Ndng do carbon trong mau ciia Id ehirng dm gidm it hon (chl sd t h y c bdo thdp) so voi cdc 16 cfln lai, chu'ng tfl r i n g hoat dgng ciia cdc td bao don nhdn eua he thdng lyd'i ngi mfl o' nhdm ndy cfl suy gidm. O cac 15 thfr diing pidotimod, d i i sd thye bdo tang ddng kd so vol Ifl ehirng am da chi ra rdng thudc cfl tdc dyng tren he thdng lyfll ngi mfl, kich thieh hoat dflng eua eae te bdo thye bdo don nhdn, c^dng Igi cde tdc nhdn ig cfl hgi cho CO thd. Trong t h y nghiflm nay trfln pidotimod sdn xuat tgi Viet Nam, ehf sd t h y c bdo id chirng am chl bang 32,08 % so v ^ i chirng sinh hgc (p <
0,05), d' eae 16 su" dung pidotimod (lieu 200 mg/
kg vd 400 mg/kg, p.o.) tdng hon so voi chirng dm 117,65 % va 111,16 %, dat 69,8 % va 67,9 % so vfl'i Id chung sinh hgc. S y khdc biet ndy ed thd do viec sir dyng hfla chat khdc nhau, tidn hanh trong eae mfli tnrong va dieu kien khac. Nhu vgy, CO the khdng djnh r i n g , neu c o the cdng bj suy giam mifln dich thi pklotimod kich thich Idm tang midn djeh cdng manh.
K i t luan
- Da khao sdt dnh hyfl'ng ciia pidotimod ddn mgt sd qua trinh sinh hgc ve: m y c dfl tang trgng lygng chuflt, 36 giam trgng lygng lach tyong ddi, mire do tang trgng lygng tuydn y e tyong ddi, mu'c do tang sd lugng bgch edu cao hon 16 chirng dm (G2) cfl y nghTa thdng ke (p < 0,05).
- Da ddnh gid d u g c tac dyng kieh thich midn djeh tren mgt sd c o quan vd td bdo ciia hfl mien djch tren diugt thi nghiem nhy c h y e ndng dai t h y c bao tren l y f l i ndi mfl cua td bao don nhan.
TAP CHi Diroc HOC - 5/2015 (SO 469 NAM 55)
