PANTOTHENIC SECRETION

THE EFFECT OF PANTOTHENICACID DEFICIENCY ON GASTRICSECRETIONAND MOTILITY

By GEORGEH. M. THORNTON,WILLIAM B. BEAN, ANDROBERTE. HODGES

(From the Metabolism Ward of the Department of Medicine, College of Medicine and Uni-versity Hospitals, State University of Iowa, Iowa City, Ia.)

(Submitted for publication January 13, 1955; accepted March 16, 1955)

Reports of animal experiments and results ofpreliminary studies by Bean and Hodges (1) inman indicated that the metabolic effects of panto-thenic acid deficiency in human subjects would bewidespread and profound. Such was the case(2). Insofar as it was possible to predict themetabolic changes in this experiment it seemedlikely that one feature would be a suppression ofadrenal cortical function and that this might leadto a secondary reduction of gastric secretion. Onthe other hand, following Lipmann's (3) demon-stration that pantothenic acid is the active principleof coenzyme A, it has been shown that many meta-bolic processes involve acetylation reactions inwhich coenzyme A is essential (4). This led tothe hypothesis that coenzyme A might play a fun-damental part in the metabolism of parietal cellsand that pantothenic acid deficiency would, there-fore, have a direct inhibitory effect on their pro-duction of hydrochloric acid. These were thetheoretical considerations which led to the specialstudy of gastric function during pantothenic aciddeficiency in the hope of obtaining information ofphysiological and possibly therapeutic interest.This paper reports the results of these studieswhich were undertaken concurrently with thosereported by Bean, Hodges, and Daum (2).

MATERIALS AND METHODS

The subjects of the experiment were three normalyoung adult men who had no previous history of gastro-intestinal disease. During the experiment there werefive different dietary periods. Since a palatable diet de-ficient in pantothenic acid cannot be prepared fromnatural foods, a synthetic liquid formula was preparedand this was administered directly into the stomachthrough a plastic tube 5 mm. in diameter. This formula,which contained an adequate supply of all essential foodfactors, including pantothenic acid, was given for an ini-tial control period of 12 days. For a second period of 25days the same formula was used but pantothenic acidwas omitted and omega-methylpantothenic acid, a meta-bolic antagonist to pantothenic acid, was substituted.

In the third phase of the experiment both pantothenicacid and the antagonist were administered with the ob-ject of correcting the deficiency. After six days of thisregimen the expected improvement in the manifestationsof deficiency had not occurred and it became necessaryto allow a general diet by mouth supplemented by panto-thenic acid and other vitamins. At this stage there weremanifestations of insufficiency of the adrenal cortexand cortisone was administered in small daily doses forfour days (2). Three days after terminating cortisonetherapy tube feeding was resumed and continued fornine days as a final control period. The original formulacontaining pantothenic acid, but not the antagonist, wasadministered during this final period.

Three tests were selected to compare gastric secretoryand motor function during the development of deficiencywith the normal function during the initial control pe-riod and during the final recovery period. These testswere a modification of the serial test meal devised byHunt and Spurrell (5, 6), the secretory response tohistamine, and the secretory response to insulin. Forall these tests plastic tubes 5 mm. in diameter and havingone terminal and four lateral holes were used. Salivawas collected throughout each test by an oral catheterattached to an electric suction pump.

Test meals were considered essential to the investiga-tion because they provide a physiological stimulus togastric secretion and supply information about the empty-ing pattern of the stomach. Neither basal secretion norhistamine nor insulin tests provide direct chemical andmechanical stimulation of the stomach mucosa and wall.However, since the concentration of hydrochloric acidin gastric contents is dependent both on the rate of secre-tion and the rate of emptying of the stomach, fractionalmethods are of little value where quantitative informa-tion about secretion is required (7). In the techniquedevised by Hunt a series of meals of constant volume andcomposition and containing phenol red are completelywithdrawn after different intervals of time on differentdays. Complete emptying of the stomach at the be-ginning and end of each meal is ensured by lavage witha known volume of distilled water. From the resultsof a series of meals composite graphs of the secretionand emptying during the whole digestive phase can beconstructed. Hunt has shown that viscosity is unim-portant in a test meal and that the pectin in his originalformula is unnecessary. He has found that a meal con-sisting of 750 ml. of sucrose solution containing 75 gm.sucrose and approximately 60 mgm. phenol red per liter

1085

GEORGEH. M. THORNTON, WILLIAM B. BEAN, AND ROBERT E. HODGES

is satisfactory (8). It has been confirmed in this labora-tory in eight normal subj ects and patients with pepticulcers that a meal of this composition will give remark-ably constant results from day to day with regard toboth secretion and motility. By estimating the concen-tration of phenol red in the original meal and in thestomach contents on each occasion it is possible to calcu-late the volume of the original meal remaining in thestomach. By assuming that the concentration of dyeleaving the stomach through the pylorus during each in-terval is equal to the mean of the initial and final con-centrations, the volume of gastric contents passing thepylorus during each time interval can be calculated.Penner, Hollander, and Saltzman (9) have shown thatphenol red is suitable for this purpose as it is neitheraltered nor absorbed by the stomach. By a similar tech-nique if the concentrationis of hydrochloric acid, totalchloride and pepsin in the gastric contents are estimatedin each of the series of meals, the quantity of these sub-stances which has passed the pylorus in between the timeof withdrawal of each meal cani be calculated. Since thevolume of gastric contenits at each time is known theamount of each constituenit secreted at various stages ofthe digestive period can he estimated. In a series of 19normal subjects Hunt found that the gastric secretory andemptying pattern of each individual remained remarkablyconstant from day to day. He also showed that if thevolume of the original meal remaining in the stomach(calculated from the volume of gastric contenits and theconcentration of phenol red) is plotted against time fora series of meals an exponenitial curve is obtained.

In this laboratory exponenitial curves of gastric empty-ing have been obtained in 17 experiments oIn 15 normalsubjects and patients witlh peptic ulcer, using a mealcontaining either pectin and sucrose 35 gm. per liter or:sucrose 75 gm. per liter wvithout pectin. The technique-was, therefore, considered suitable for the demoinstrationof the effect of pantotheniic acid deficiency oni gastricmotility. AnIy alteration of the emptying pattern duringdeficiency might be expectedI to alter the exponentialcurve obtained for each subject during the control period.

The results of the studies of gastric secretion in re-sponse to the test meals, to histamine and to insulin havebeen expressed as volumes of parietal and non-parietalcomponenit of gastric juice. These volumes may becalculated from the amount of hydrochloric acid andtotal chloride secreted during a given period by using:a formula evolved by Hunt (10) from Hollander's (11)(concept of two componenit secretion of gastric juice in,dogs, and from Ihre's (12) figures for the composition,of pure gastric juice in man. This method has the ad--vantage of taking into account neutralization of hydro-clhloric acidl by the alkaline componetnt of gastric secre--tion.

In the present experiment the volume of gastric juicesecreted changed to such a degree that construction ofa composite graph for the volumes of parietal and non-parietal component was not possible. These volumeswere therefore calculated for each individual meal fromtimne :zero to the time of withdrawal. Since gastric

secretion is generally rapid and constant for the first 30minutes after ingestion of the meal, this interval wasselected for the comparison of test meal data obtained atdifferent phases of the experiment. Where the actualtime of withdrawal of the meal was close to 30 minutesthis forms a sound method of comparison. Normal gas-tric secretion has been found to become slower after 30minutes and there is Ino way in which meals of longerduration can be compared xvith those of 30 minutes whenthe values for each are calculated from time zero, insteadof being incorporated in a serial graph. Meals of longerduration were included in the present experiment so thatdata on gastric emptyiing could be obtained, and so thatany rise in secretory rate at a late stage in the digestiveperiod would not be overlooked. The result of each ofthese meals was plotted oIn a graph of time against vol-ume of gastric juice and a straight line was drawn fromthis poiInt to time zero volume zero. The volume wasread from the point at which this straight line crossedthe line representing 30 minutes. It is realized that thismethod gives an approximate estimate only of the ac-tual secretion at 30 minutes but since the figures ob-tained were not inconisisteint with those obtainied wlhenthe actual duration of the meal was 30 minutes, theyhave been included in the graphs of the results. Thismethod would reflect any gross chainges in secretioIn dulr-ing the latter part of the digestive phase from one pe-riod of the experiment to another. WN!here the actualtime of withdrawal was less than 30 minutes the samemethod of expressing the results was used. Since gastricsecretioIn generally remIainls coInstaInt in rate for the first30 minutes the method is probably more accurate in thisinstaince. If some slowviIng of secretory rate did occurbefore 30 minutes this method would tendl to produceunduly high readings for 30-minute secretion. The pep-sin secretion was treated in the same way, graphs beingdrawn to determine the estimated total pepsin secretionat 30 minutes.

In order to determine the response of the parietal cellsto direct chemical stimulation the volume of gastricjuice secreted in response to the subcutaneous injectionof histamine was measured during the initial control pe-riod, during the deficient diet and during the final con-trol period. WVangensteens apparatus was used to col-lect gastric secretion by continuous suction for 30 miin-utes before and 90 minutes after histamine. In additioni,manual suction with a syringe was used at intervals of 30minutes to check the patency of the tube. Blockage, wlhenit occurred, was cleared by injecting small quantities ofair. In view of the role pantothenic acid is believed toplay in the metabolism of histamine (4) and the reduc-tion of histaminase in the alimentary canal in adrenal in-sufficiency, (13) small doses (0.5 or 1.0 mgm.) of hista-mine phosphate were used. In addition each test waspreceded by an injection of 2 ml. of the antihistamine,Thenfadil®g, given intramuscularly, 30 minutes before thehistamine dose to prevent untoward reactions. From thevolume of gastric juice collected and the concentrationi ofhydrochloric acid, total chloride and pepsin, the totalamount of these constituenits secreted in response to his-

1086

GASTRIC FUNCTION IN PANTOTHENICACID DEFICIENCY

tamine was calculated. Using the same formula as in theserial test meals, these figures were converted into vol-umes of parietal and non-parietal components of gastricjuice.

The gastric response to insulin was included in theinvestigation since this provides an indication of thesensitivity of the receptor-conductor mechanism for neuro-genic stimuli to gastric secretion. It may thus serve todifferentiate factors acting directly on the parietal cellsfrom those acting on the psychic or reflex secretion ofgastric j uice. Since pantothenic acid deficiency sup-presses adrenal cortical function in animals it was ex-pected that the subj ects of the experiment would de-velop some hypersensitivity to insulin. Small doses (5or 10 units) of insulin were, therefore, used and thesewere given subcutaneously instead of intravenously.This made it necessary to collect gastric juice for a pe-riod of 150 minutes after insulin instead of 60 or 90minutes. The technique of collection of gastric juicewas the same as in the histamine tests, the insulin in-jection being preceded by collection of basal secretion for30 minutes. Finger-tip blood samples were collected forblood sugar estimation once before insulin and at in-tervals of 30 minutes thereafter. The lowest readingof blood sugar was usually obtained at 60 minutes andoccasionally at 90 minutes after insulin. The averagefall of blood sugar was 36 mgm. per 100 ml. and on onlytwo occasions was the fall less than 30 mgm. per 100 ml.A level of 50 mgm. per 100 ml. in venous blood is gen-erally considered a satisfactory hypoglycemia. As theconcentration of sugar in capillary blood is approximately10 mgm. per 100 ml. higher than in venous blood, and asthe capillary blood sugar level fell to 60 mgm. per 100 ml.or less in every test in this experiment, the hypoglycemiainduced by the method used was considered adequate.The volumes of parietal component and non-parietalcomponent and the quantity of pepsin secreted in re-sponse to hypoglycemia were calculated in the same wayas in the histamine tests and the test meals.

The hydrochloric acid concentration in all specimenswas determined by electrometric titration against 0.1 Nsodium hydroxide with pH 6.5 as the end-point (12), thesucrose solution used in the test meals having been ad-justed to pH 6.5 before administration. Phenol red doesnot have a sufficiently sharp end-point for use as 'thetitration indicator, but its presence in the test meal speci-mens obscures Topfer's reagent and phenolphthalein.

Total chloride was also estimated by electrometrictitration against 0.5 N silver nitrate solution using asilver-silver chloride electrode (12). This method isconvenient, accurate and not affected by the presence ofphenol red in the specimens.

Pepsin concentrations were estimated by the methodof Bucher, Grossman, and Ivy (14). The substrate wasprepared from commercial dried bovine hemoglobinpowder (15). Anson's (16) curve was used to convertthe results to pepsin units.

RESULTS

These are expressed graphically as volumes ofparietal and non-parietal component and quantityof pepsin secreted in response to equal stimuli atdifferent stages of the experiment. Figures 1, 2,and 3 show the results obtained in each of thethree subjects. The whole shaded area representsthe total volume of gastric juice, the dark shadedarea shows the volume of parietal component, andthe light shaded area shows the volume of non-parietal component.

The first graph in each figure shows the secre-tory response to the test meals. Above the re-sults of each test the time of withdrawal of themeal is shown. In all three subjects at least onemeal in each control period is comparable in dura-tion with a meal or meals during the second andthird periods when the symptoms of deficiencywere present. In many instances the duration ofthe test meals was sufficiently near to 30 minutesto justify direct comparison. This applies to meals1, 6, 8, 9, and 10 in subject M. C. (Figure 1); tomeals 1, 5, 6, 8, 9, and 10 in the subject L. N.(Figure 2); to meals 1, 5, 8, and 9 in subjectE. D. (Figure 3). On the basis of these mealsalone it can be seen that in the subjects M. C. andL. N. (Figures 1 and 2) there was a profoundfall in the gastric secretion, both of parietal andnon-parietal components, during the period whenthe pantothenic acid deficient diet was being ad-ministered, with recovery during the final controlperiod. The estimated 30-minute volumes of se-cretion derived from the meals of less than 30minutes are probably valid also, since these wereall during the deficient period and the methodtends to produce a value above the actual 30-min-ute secretion. The figures obtained from themeals of more than 30 minutes' duration are con-sidered to show that no significant gastric secre-tory response occurred during the later stages ofthe digestive period. The subject E. D. (Figure3) shows a slight but much less significant fallduring the period on the deficient diet. None ofthe three subjects showed a significant fall in thesecretion of pepsin in response to a test meal,though the response to histamine and insulin isseverely affected.

In the second graph of Figures 1, 2, and 3 thesecretory response to histamine is indicated. The

1087


I Tube Fed -Control Diet a ( _ d"-Dof Icient Dieti Anteolet

me -U+Pontothen AcWid NON-MRTALCOMPONE

Mb Mouth Fed -Generol Diet MRIETAL COMPONENT

Se Tube Fed -Control Diet

U .M ..U . : .~ ~ . * .37.5

SERIAL TEST MEL (voLGostric Juice in ml.)AroftiWof VA55 3o __6 _s.______6. 5- 5__-___ J._.___ 4W

100,- '

HISTAMINE TEST (vol. Gastric Juice in ml.)Nfstmine -----------.a as-- o.5

100i

0.

INSULIN TEST (vol. GastrIc Juice In ml.)DOsWIOf10Mb .0- J0 ---5------ 5----5--------- 5

MhsIibdSc9uv40___0_ _- 4 _ 55-_--55 -55

200~

150

100

7 14 21 28 35 42 49 56 63 70DAYS

FIGURE 1

1 Tube Fed - Control Diet ndsofunit)

Deficient Diet+ Antagonistme * -11 + Pontothenic Acid NON-PAETALCOMPONENTMb Mouth Fed-Generol Diet MPARIETAL COMPONENTmc Tube Fed -Control Diet

1K Mo. Nb Nc

L.N. I

* CORTISON¢§"mO1E',

~

SERIAL TEST NEAL (vol. Gastric Juice in ml.)AVAW00 s29-59_44_ /553030- 60 30 32 30 48

*O'1'°°L.L

HISTAMINE TEST (vol. Gastric Juice in ml.)HI~ie Pbhosphee-- 0.5 10- 0.5 0.5 -------- 0.5 a5

100

INULIN TEST (vol. Gtric Juice in nt)Amsof Ir^n-- 0 5- 5 -5 -------5AfkSAdSugq 35 50 5253-60

250 i

150 _

1 7 14 21 2 5 4 9 56

FIGURE 2

I Tube Fed- Control Dietla * -Deficient Diet+ Antogonist

Mo a Fontoth*enI Acid

mbMouth Fed- General DietMc Tube Fed -Control Diet

II

HISTAMiNE TEST (vol. Gastric Juice in ml.)Pfhwinhosohotc _- 1.0- 5

1501 i: .

O- . ' _ _

nPEp1N (thouendiofuwts)_oN-META COMONn

_ PARWT COMPONET

me b lMe

_----- 0.5 --0.5

* I

I-. i-

INSULIN TEST (vol. Gastric Juice in ml.)Ibe off-WI /0 ---/0 ---S 5---5 ---------- 5Afk7.AvodSuvWr52__30M__60 -_-__ 52- 53 __- 53

250

200

50 .1

I 7 14 21 28 5 Il 4a9s6 63

FIGURE 3

FIGS. 1, 2, AND 3. TIIE GASTRIC SECRETORYCHANGESDURING THE DEVELOPMENTOF PANTOTHENIC ACID DE-FICIENCY IN THE SUBJECTS M. C., L. N., AND E. D.

The figures for the serial test meals show the esti-mated secretion at 30 miniutes. Those for the histamiinetests and insulin tests show the actual secretion during90 and 150 minutes, respectively, after the test dose.

dose of histamine phosphate in mgm. is indicatedabove each test. Subjects M. C. (Figure 1) andL. N. (Figure 2) again show a striking fall insecretory response both of parietal and non-parietalcomponent and of pepsin during the induction ofpantothenic acid deficiency, Nith recovery duringthe final control period. The subject E. D. showsno significant change since the dose of histanminewas greater in the first test than in the otherthree tests and there is no appreciable rise duringrecovery. The first histamine test in this sub-ject was not obtained until seven days after be-ginning the deficient diet because of an attack ofpharyngitis which made retention of a tube for120 minutes impossible.

The third graph in each figure shows the secre-

tory response to subcutaneous insulin. The doseof insulin and the lowest capillary blood sugar

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ED I | --

oo ~ ~j

SERIAL TEST MEAL (vol. Gostric Juice In ml.)rSonof TMT.37--- 55- 71- 72--30I5---50 - ___ 30 32 47

100- .aa50 l

0

II

ii

63 70


reading obtained are indicated above the resultsof each test. As might be expected when there isa marked fall in response to histamine there is alsoa fall in response to hypoglycemia in subjectM. C. (Figure 1) and L. N. (Figure 2). Thesubject E. D. (Figure 3) shows a definite thoughless marked fall in his gastric response to hypo-glycemia.

The test meal results were used to determinethe effect of pantothenic acid deficiency on gastricmotility. The number of meals obtained duringeach phase of the experiment was not sufficientto prepare separate graphs for the initial and finalcontrol periods and for the period of the defi-cient diet. However, the logarithms of the vol-umes of the meals remaining in the stomach wereplotted against time for each subject throughoutthe experiment. The results are shown in Figures4, 5, and 6. In spite of gross changes in thevolume of gastric juice secreted into the stomachthe same exponential emptying pattern is retainedby the subjects M. C. (Figure 4) and L. N. (Fig-ure 5) throughout the experiment. The dis-crepant volumes found at 71 and 72 minutes inthe subject E. D. (Figure 6) coincided with thepharyngitis already mentioned. His psychologicalreaction to the discomfort of being subjected to atest meal under these circumstances may explainthe delay in gastric emptying (17). If they areexcluded from the graph he also appears to haveretained the same exponential emptying pattern.

DISCUSSION

The results of this experiment suggest that anadequate intake of pantothenic acid is essential to

PATTERNOF EMPTYINGOF THE STOMACH

6

E2

._56

'sEbf

M.C.

3.0-

2.8-

2.6-

2.4-

2.2-

2.0-

1.8-41.6 -

LOGARITHMOF INITIAL VOLUMEOF MEAL (750ml.)

\ Initial Control PeIx Deficient Dieto Final Control Pe

x

x

PATTERNOF EMPTYINGLN. OF THE STOMACH

,

0

E

0~0-j

E D.

3.0-

2 8-

2.6-

E 2.4-E

o 2.2-

-- 2.0-

1.8

FIGURE 5

PATTERNOF EMPTYINGOF THE STOMACH

_ LOGARITHMOF INITtAL VOLUMEOF MEAL (750ml.)----------------------___

*Initiol C\ ~~~~~xDeficien

\x ~ ~~~oFinol Cc

x\

20 40 60Durotion of Test Meol in minutes

FIGURE 6

0

:ontrol Periodnt Dietontrol Period

xx

80

FIGS. 4, 5, AND 6. LOGARITHMSOF THE VOLUMESOFTHE TEST MEAL REMAINING IN THE STOMACHAT VARI-OUS TIME INTERVALS AFTER INGESTION PLOTTED AGAINSTTIME OF WITHDRAWALFOR THE SUBJECTS M. C., L. N.,ANDE. D.

Each graph includes results obtained during the initialand final control periods as well as during the periodof pantothenic acid deficiency.

normal gastric secretory function, but not to nor-mal motility. The conditions of the experimentwere abnormal in that the three subjects were re-ceiving a synthetic diet directly into the stomachinstead of a natural diet by mouth. There is noreport in the literature on the effect of prolongedtube feeding on gastric secretion but it is commonexperience that the use of a milk drip, in the treat-ment of peptic ulcer, causes a temporary neutrali-zation of acid in the stomach rather than any sup-pression of secretion. If the results obtained were

20 40 60Durotion of Test Meol in minutes

FIGURE 4

1089

er od

triod


caused by tube feeding alone some fall of secre-tion should have become apparent during the ini-tial control period of 12 days and improvement ofgastric function during the final control periodwould be most unlikely. In addition, the pepsinsecretion in response to the test meals would beexpected to undergo suppression to an extentsimilar to the other constituents of gastric juice.It is believed, therefore, that pantothenic acid de-ficiency was in fact responsible for the secretorychanges. Though there are many reports (4) ofthe effects of pantothenic acid deficiency on othertissue in animal experiments, there are no re-ports of the effects on the stomach of man or ani-mals.

Pantothenic acid deficiency might bring about adepression of secretion of gastric juice by two pos-sible mechanisms. Since coenzyme A is essentialto the formation of cortisone by the adrenal cortexin rats ( 18) and since the subjects of the ex-periment showed evidence of adrenal cortical dys-function, (1, 2), it is possible that the effects weredue to a deficient supply of cortisone. Since itwas necessary to administer cortisone and restorevitamins to the diet simultaneously, because ofsevere symptoms, it is not possible to say whichfactor was responsible for restoring normal secre-tion. The diminished hydrochloric acid secretioncommonly found in Addison's disease is in keep-ing with such a mechanism. The absence of afall in pepsin secretion in the test meals in thepresent experiment is inconsistent with the find-ing of Spiro, Reinfenstein, and Gray (19) thaturopepsin is absent from the urine of patients withAddison's disease and could be restored by givingcortisone. There is, however, insufficient evidenceto establish whether or not the diminished gastricsecretion was mediated through the adrenal cortex.

Alternatively coenzyme A might be essential tothe metabolic processes whereby the parietal cellssecrete hydrochloric acid. The "electron-cycle"mechanism described by Crane, Davies, andLongmuir (20) postulates the enzyme substrate

+2Hsystem oxaloacetate L-malate to accotunt for

the transfer of hydrogen atoms across the peri-canalicular zone of the parietal cells. Coenzvme Apresumably plays a part in this mechanism. De-ficiency of pantothenic acid could theoreticallyblock the mechanism of secretion at this point, if

the electron-cycle mechanism is the true processby which hydrochloric acid is produced. Since theprecise mechanism of hydrochloric acid secretionand the precise metabolic functions of pantothenicacid have not been established, any theory as tothe relationship between the two must, at present,remain purely speculative. The results of thepresent experiment merely show that such a rela-tionship does exist. Further work is now beingundertaken with the obj ect of investigating themeans bv which pantothenic acid deficiencv in-hibits gastric secretion.

The results of the experiment do not suggesta reason for the relatively minor effect on thegastric secretion in one of the three subjects(E. D.). In this particular subject the centralnervous system manifestations of deficiency andevidence of insufficiency of the adrenal cortex weremore severe than in the other two subjects. Thismay be a manifestation of the variations ob-served in many deficiency states where a group ofindividuals are all affected by the same deficiency.Individual subjects of the present experimentshowed considerable variation in the degree andrate of change in the system or tissue predomi-nantlv involved (2).

SUMI'MARY ANDCONCLUSIONS

1. Pantothenic acid deficiency was induced ina group of three normal human volunteers, bydiet and the administratioln of a metabolic an-tagonist.

2. Two of three subjects developed severe de-pression of gastric secretion which returned tonormal after the experiment had been terminated.

3. The changes affected the volume of parietaland non-parietal components secreted in responseto a meal, to histamine and to insulin.

4. Pepsin secretion in response to insulin andhistamine was also diminished but pepsin responseto a meal was unaffected.

5. It is postulated that the parietal cells weredepleted of an essential metabolic factor, possiblycoenzyme A. The diminished secretion may, how-ever, have been an indirect result of depression offunction of the adrenal cortex.

6. There was no significant change in gastricmotility as a result of pantothenic acid deficiency.

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ACKNOWLEDGMENT

The authors wish to acknowledge with gratitude thetechnical assistance of Dr. A. P. Barer who carried outthe pepsin estimations for this study.

REFERENCES

1. Bean, W. B., and Hodges, R. E., Pantothenic aciddeficiency induced in human subjects. Proc. Soc.Exper. Biol. & Med., 1954, 86, 693.

2. Bean, W. B., Hodges, R. E., and Daum, K., Panto-thenic acid deficiency induced in human subjects.J. Clin. Invest., 1955, 34, 1073.

3. Lipmann, F., Acetylation of sulfanilamide by liverhomogenates and extracts. J. Biol. Chem., 1945,160, 173.

4. Krehl, W. A., Pantothenic acid in nutrition. Nutri-tion Rev., 1953, 11, 225.

5. Hunt, J. N., The secretory pattern of the stomach ofman. J. Physiol., 1951, 113, 169.

6. Hunt, J. N., and Spurrell, W. R., The pattern ofemptying of the human stomach. J. Physiol.,1951, 113, 157.

7. Hunt, J. N., The interpretation of fractional testmeals: some studies in a "glass stomach." Guy'sHosp. Rep., 1953, 102, 157.

8. Hunt, J. N., The inhibitory action of sucrose on

gastric digestive activity in patients with pepticulcer. Guy's Hosp. Rep., 1954, 103, 161.

9. Penner, A., Hollander, F., and Saltzman, M., Thegastric absorption of phenol red in humans. Am.J. Digest. Dis., 1938, 5, 657.

10. Hunt, J. N., An interpretation of histamine and in-sulin tests in patients with peptic ulceration.Lancet, 1950, 2, 397.

11. Hollander, F., Studies in gastric secretion. IV.Variations in the chlorine content of gastric juice

and their significance. J. Biol. Chem., 1932, 97,585.

12. Ihre, B., Human gastric secretion; a quantitativestudy of gastric secretion in normal and pathologi-cal conditions. Acta med. Scandinav., 1938, Suppl.,95.

13. Haeger, K., Jacobsohn, D., and Kahlson, G., Thelevel of histaminase in thoracic duct lymph as anindicator of adrenocortical activity. Acta physiol.Scandinav., 1953, 30, Supp. 111, p. 170.

14. Bucher, G. R., Grossman, M. I., and Ivy, A. C., Apepsin method: the r6le of dilution in the determi-nation of peptic activity. Gastroenterology, 1945,5, 501.

15. Orringer, D., Lauber, F. U., and Hollander, F., Useof dried bovine hemoglobin powder in the Ansonand Mirsky methods for pepsin and trypsin.Science, 1950, 111, 88.

16. Anson, M. L., The estimation of pepsin, trypsin,papain, and cathepsin with hemoglobin. J. Gen.Physiol., 1938, 22, 79.

17. Wolf, S., Experimental observations on changes inemotional state and physiologic disturbances inthe gastrointestinal tract in Postgraduate Gastro-enterology. Bockus, H. L., Ed., Philadelphia,Saunders, 1950, p. 225.

18. Krehl, W. A., Winters, R. W., and Schultz, R. B.,Adrenal function in pantothenic acid deficiency.Nutrition Symposium Series, National VitaminFoundation, Inc., 1952, 5, 39.

19. Spiro, H. M., Reinfenstein, R. W., and Gray, S. J.,The effect of adrenocorticotrophic hormone uponuropepsin excretion. J. Lab. & Clin. Med., 1950,35, 899.

20. Crane, E. E., Davies, R. E., and Longmuir, N. M.,Relations between hydrochloric acid secretion andelectrical phenomena in frog gastric mucosa. Bio-chem. J., 1948, 43, 321.

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PANTOTHENIC SECRETION