Diagnóstico y tratamiento de las exacerbaciones
T RATAMIENTO INTEGRAL DE LA EEPOC
(molar %)
40
40
20
30
20
10
- 1.0
40
o.o
/r---,r---,?---,r---�7
6.0
7. 0
8.0
A
(pH)
1.0
FIGURE 4 . 14 Predi cted 7-Ketodeoxycholate Yield
74
- 1.0,
N2-co2
N2
(Gas)
The model from which this figure is drawn i s pre s ented in Appendix 2 , Tab le A2 . 1
L. M.
C.
t
8. 6
8.2
1.0
o.o
/�---,�---�,�---,r---�7
6.0
--!$
8.0
A
(pH)
(Gas)
1 . 0
FIGURE 4 . 15 Predicted Ce l l Yield ( as L . M . C . , of maximum observed number o f ce lls mi llili tre o f culture )
7 5
The model from which this figure i s drawn i s presented in Appendix 2 , Table A2 . 5 .
TABLE 4 . 4
c DC L . M. C .
Matrix o f Correlation Coe f fi cients for the P airs of
Vari ab les in 1
7KD c D
- 0 . 876 * * *
0 . 266 - 0 . 6 9 8 *
0 . 772 * * * - 0 . 8 84 * * * 0 . 6 20 * * * * - s tatistically s igni fi cant at the 1% leve l
* - s tatistically s i gni fi cant at the 5 % level
4 . 5 DI SCUSS ION OF EXPERIMENT l
The expe rimental de sign approach adopted i s empi ri cal , and as s uch i t is s ui ted to the proj e ct aim. Th is me ans that any mechanistic dis cus s ion indulged in i s speculative , but may ass is t in the i dentifi cation of areas worthy o f further res earch .
The regress i on mode l s con fi rm what i s intui tive ly obvious from the raw data ; the pre fe rred conditions for dehydroxylation lie very c lose to pH 7 with an atmosphe re of N 2 - co2 , 9 : 1 , whe re as for de hydrogenation , an atmo sphe re o f nitrogen , close to pH 7 is optimum.
7 6
I f an experimental des i gn with only two levels ( i . e . a 2 2 factorial ) had been s e lecte d , the dehydroxylation optimum might not have been dete cte d , since the s igni fi cant negative main e ffe cts for both vari ables would le ad to the con c lus i on that greatest deoxycholate yields lay in the dire ction o f low pH and hydrogen gas . The three
leve l design adopted allowed the e l ucidation of much curvature in b oth variables , reflected in the s i z e of quadratic terms in all mode ls , and e vi denced by .the ability o f a logari thmic trans formation to des cribe deoxycholate yield. The h i gh pe ak for dehydroxylation at pH 7/Nz-COz i s mani fest mai n ly in inte ractions involving quadratic terms . Thi s p eak i s o f great infl uence i n the mode l , yet comprises only a s ingle data point . The regression techniques us ed tend to weight s uch large outlying points , and in this case the apparent statistical signi fi -
cance is enhanced by c lose agreement of the repl icates . Moreove r , this high value arose i n the very fi rs t run , whe re di ffe rent random in fluences may have been acting .
To check this value , and t o sub stantiate the predicted maximum deoxycholate yield (wh i ch corresponded clos e ly to run 1 condi tions ) , run 1 was repeated. The results are depi cted in Figure 4 . 16 . The total degree o f t ran s formation was as predic te d ( 50 . 6 % , p rediction 50 . 0 % ) and growth yield on ly a little high ( L . M. C . 8 . 80 , predi ction 8 . 60 ) . Howeve r , the yield of deoxycholate was lowe r than predicted
via
the logari thmi c t rans formation ( 10 . 9 % , predi ction 20 . 3 % ) and7-ketodeoxycholate yield correspondingly higher ( 38 . 5 % , predicted 3 1 . 0 % ) . The diffe rence between the two pH 7/N 2 -c02 runs may reflect
" a change in the random in fluence s affecting any experiment . Thi s i s parti cularly like ly s ince the 1 1- run des ign was performed a s a s i ngle
randomi sed block ove r 3 months , and the repe at some weeks late r on its own . De spite the di ffe rence , the repeat run s till showed a highe r deoxychol ate yield than any of the othe r ten t rials . Thus the bas i c conclus ion still holds : dehydroxylation was gre atest at pH 7 unde r the N2 -C02 mixture .
Most lite rature reports concerning dehydroxylation as a function of pH have de alt with rates o f trans formation . The current work has
' been concerned with yie lds , which are more relevant to the e arly
\stages of proce ss deve lopment , and requi red fewer data points for adequate calculation . Only when deoxychol i c acid yields be come fav ourable will rates become of intere s t from a p rocess viewpoint . This di fference between yie ld optima and rate optima mus t be borne in mind when cons ide ring p revi ous ly reported pH " optima" .
7 7
The l iterature s hows some dis agreement concerning the dependence of dehydroxylation on pH . Dras ar and Hi l l ( 19 74 ) reviewed thei r own extensi ve faecal-isolate screening experiments , and simi lar expe riments of thei r col le ague s , all of whi ch emp loye d T . L . C . to detect 7a-dehyd roxylation by harvested and res uspended ce l l s of anae robically grown organisms . They conc luded that i f the pH o f the culture medium fe l l below p H 6 . 5 , very l i ttle dehydroxylation could b e detected. Midtvedt and Norman ( 1968) investigated growing c ultures of thei r lactobacillus-
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