Background: Affymetrix microarrays have become increasingly popular in gene-expression studies; however, limitations of the technology have not been well established for commercially available arrays. The hybridization signal has been shown to be proportional to actual transcript concentration for specialized arrays containing hundreds of distinct probe pairs per gene. Additionally, the technology has been described as capable of distinguishing concentration levels within a factor of 2, and of detecting transcript frequencies as low as 1 in 2,000,000. Using commercially available arrays, we assessed these representations directly through a series of 'spike-in' hybridizations involving four prokaryotic transcripts in the absence and presence of fixed eukaryotic background. The contribution of probe-target interactions to the mismatch signal was quantified under various analyte concentrations.

1 The effect of the prostaglandin synthesis inhibitors aspirin and indomethacin (Ind) was investigated upon contractions of the perfused isolated terminal ileum of the rat to bradykinin (Bk) or potassium chloride (KCI). The release of a prostaglandin-like substance (PGLS) from the ileum was simultaneously assayed on the rat fundus strip (RFS).2 Aspirin (610 gM) or Ind (28 1kM) reduced contractions of the ileum to Bk perfused over the mucosal surface but not to Bk perfused over the serosal surface.3 After perfusion of either ileal surface the effluent potentiated the contractions of the RFS to Bk.No potentiation was observed in the presence of either Ind or aspirin.

I t i s e s t a b l i s h e d t h a t most, if n o t a l l , n o n -s t e r o i d a l a n t i -i n f l a m m a t o r y d r u g s (NSAID) induce g a s t r o i n t e s t i n a l damage (Menguy 1 9 7 2 ) . The development of a s i m p l e i n v i t r o method f o r q u a n t i f y i n g t h i s mucosal e p i t h e l i a l damage i s d e s c r i b e d . The t e r m i n a l ileum was removed from m a l e Wistar r a t s (180-250 9 . ) and p e r f u s e d through i t s lumen a t 3 m l /min f o r 3 h o u r s w i t h Krebs s o l u t i o n a t 37OC. bubbled w i t h 5 % co e f f l u e n t from t h e ileum and weighing t h e r e s i d u a l m U C O S a l C e l l s . t e s t was added t o the r e s e r v o i r p r i o r t o p e r f u s i o n Of the i k u m and the r e s u l t was compared w i t h an a d j a c e n t s e c t i o n o f t i s s u e p e r f u s e d w i t h Krebs s o l u t i o n a l o n e . t i s s u e .The mucosal damage induced by indomethacin, a known i n t e s t i n a l i r r i t a n t (Fang e t a1 1 9 7 6 ) , w a s feud t o be dose dependent. ( F i a . 1 ) . Fig. 1 : Mucosal e p i t h e l i a l loss and 02' MucOSal damage w a s determined by f i l t e r i n g t h e 2 The drug under A l l r e s u l t s are e x p r e s s e d a s a p e r c e n t a g e of t h e w e t w e i g h t of t h e I II 111 due t o indomethacin, i. Indomethacin 7pM (n=9) ii. Indomethacin 14pM (n=9) iii, Indomethacin 28pM (n=6) Ir A s p i r i n (330pM) and phenylbutazone (129uM) also caused a s i g n r f i c a n t mucosal loss o f 3.8 _+ 0.7% (n = 5, p < 0.01) and 6.2 _+ 1.1% (n = 11, p < 0.001) r e s p e c t i v e l y . However, n e i t h e r p a r a c e t a m o l (660uM), a drug w i t h minimal g a s t r o i n t e s t i n a l i r r i t a n c y , nor d i c l o f e n a c ( 2 1 0 u M ) , a new NSAID, caused any s i g n i f i c a n t mucosal l o s s . p r e s e n c e of indomethacin (28uM), p r e v e n t e d t h e mucosal loss produced by indomethacin a l o n e . An e x p l a n a t i o n f o r t h e r e s u l t s i s t h a t i n h i b i t i o n o f p r o s t a g l a n d i n s y n t h e s i s i n t h e g a s t r o i n t e s t i n a l t r a c t may be t h e mechanism i n v o l v e d i n mucosal loss, w h i l s t t h e p r e v e n t i o n of mucosal l o s s by PGE i s c o n s i s t e n t w i t h t h e known c y t op r o t e c t i v e a c t i o n of p r o s t a g l a n d i n s ( h o b e r t The c o r r e l a t i o n between the r e s u l t s o f t h i s s t u d y and t h e known i n t e s t i n a l i r r i t a n c y of t h e d r u g s s t u d i e d ( R a i n s f o r d 1975; Yanagi e t a 1 1978) i n d i c a t e s t h e v a l i d i t y o f t h e method as a simple s c r e e n f o r g a s t r o i n t e s t i n a l i r r i t a n t s . ROW. i s an S.R.C. s t u d e n t . W e thank D r . J. Pike (Upjohn C o . ) f o r p r o s t a g l a n d i n s and Geigy f o r d i c l o f e n a c ( " V o l t a r o l " ) .R a i n s f o r d , K.D. (1975) Agents A c t i o n s 5: 326-344 Robert, A. (1975) G a s t r o e n t e r o l o g y 69: 1045-1047 Yanagi, Y. e t a1 (1978) ...

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