간디스토마 감염에 있어서의 Vitamin A 대사에 관한 연구

Abstract

[한글]

[영문]

Department of Parasitology, College of Medicine, Yonsei University, Seoul, Korea

(Director: Professor Chin-Thack Soh)

Since the Chinese liver fluke, clonorchis sinensis, was first described by

Mcconnel(1875). it has been established that the adult fluke lives in the biliary

passages of many mammalian hosts, including human body.

Concerning pathogenicity, a multitude of symptoms has been described in patients

with clonorchiasis. Based on reports by Inouye (1903), Mayer (1916), Oldt (1927),

Becrovitz (1931), Otto (1937), of decreasing frequency: fatigue, weakness, weight

loss, abdominal pains, indigestion, ascites, increased or decreased appetitie,

nausea and vomiting, diarrhea, constipation, jaundice, paresthesia, edema, night

blindness, dizziness, pyrosis, gaseousness, importence, headaches, paplitations,

and hot-cold sensations.

It is commonly asumed that severe illnesses are due to haavier worm loads, and

that in light infestations the symptoms are usually negligible, though it might be

deeply related with the duration of the infestation. However, the nutritional

disturbances, including weak vision or night blindness aree not uncommon among the

people with clonorchis infestation in endemic areas, and it is recognized that the

disease is due to the functional and pathological changes of the liver itself.

though such signs could be closely related with vitamin A deficiency,there have

been no reliable experimental reports covering vitamin A metabolism in liver fluke

infestation. The purpose of this study is to add new information to this field.

Materials and Methods

Male rabbits 1.5-2.0 kg in weight were used as the experimental animal. From

February thru April they were fed mainly with hay, and from May thru September with

fresh grass leaves and remnants of bean curd. Both control and infested groups were

observed for a seven month period.

The metacercariae of clonorchis sinensis from fresh water fish were cfollected by

the digestion medthod:

Control (B group)………………………………Not infested, healthy.

Mild infestation (C group)………………… 100 metacercariae were given.

Moderate infestation (D group)…………… 300 metacercariae were given.

Heavy infestation (E group)…………………600 metacercariae were given.

Extra……………………2,000 metacercariae were fed for short term observation.

The plasma level of vitamin A was determined by the Dann & Evelyn's Cyorgy

modified method with the blood which was drawn at 6:00 a.m. each day. At the same

time, examinations of body weight, liver function tests(thymol turbidity test,

prothrombin test, total protein calculation) and hemoglobin and red cell

determinations were made. Along with this experiment, patho-histological

examinations of the liver and of the eye of rabbits which were sacrificed or which

died of malnutrition were carried on.

Summary

Three groups of 30 rabbits were infested with the metacercariae of clonorchis:

100,300, 600 for each. Biologicaland histochemical studies have been carried on

over a seven month period.

1. Plasmal level of vitamin A and β-carotene: Although the B group (control) had

been maintained above 50 γ% for seven months, the infested groups showed a

tendency to decrease from the time of two to four weeks after the infestation and

continued below the normal line until seven months, except during August (the 6th

month), when diet was ample in vitamin A. The order of decreasing frequency were

the control, light, moderate, and heavy infestation groups. β-carotene was 0-9% of

normal range, both in the control and in the infested animals.

2. Absorption of vitamin A from intestine: 2,0000 I.U. of vitamin A was given

orally to each group six months after infestation, and observations were made for

eight hours. The rate of absorption was accelerated according to the grade of worm

burden, especially in heavy infestation. The peak of the curve appeared 4-5 hours

after administration.

3. Body weight: Generally, the weight showed an increasing curve until seven

months after the infestation, though the degree was different according tot he worm

burden; in order were the B, C, D, and E groups.

4. Liver function tests: There were practically no significant differences

between infested and unifested groups. Only the globulin showed a slight increase

several weeks after the infestation; there was no reversal of A/G ratio.

5. Histopathology of liver: One week after the infestation, peribiliary

inflammation appeared and developed into thickening of the bile duct wall,

enlargement of bile ducts, proliferation of the biliary epithelium and somethimes

desquamation and new formation of bile capillaries with crypt formation in the bile

ducts. Infestations of several months duration, the periportal tissue developed

fibrosis in varying degrees in many portions of the parenchyma. In some areas the

hepatic cells were destroyed, and cirrhosis and fatty metamorphosis were sometimes

observed. The degree of change almost paralleled the degree and duration of

infestation.

6. Histopathology of eye: No histologic changes were detectable for about two

months, except in the group with the extra heavy infestaion by 2,000 metacercariae.

In general, pathological manifestations were observed five months after infestaion.

Some of the rabbits showed a slight focal desquamation of the limbal bulbar

conjunctive and epidermidalization, slight rete peg formation and keratinization of

the corneal epithelium. In most cases, there was moderate large and small round

cell infiltration beneath the epithelium and the rods and cones layer showed

vacuolation and disinteegration with rarefication of the outer nuclear layer.

The reason for the low level of vitamin A plasma value in clonorchiasis

infestations is still dubious for final conclusion, so long as the ability of

vitamin A absorption and liver function have been within normal range. But the

following factors would give an appropriate answer for the puzzle.

a. The chronic inflammatory condition of the liver will consume more vitamin A.

b. Desquamation of the bile duct wall and damage to liver cells will cause

outflow of vitamin A from the Cytoplasm.

c. Indirectly, vitamin A shall serve as one of the nutritional sources for the

liver fluke.

Conclusion

1. The plasma level of vitamin A in infested groups continued at a lower level

than in the uninfested group.

2. The ability to absorb vitamin A was accelerated according tot he loads of

infestations.

3. The body weight in the infested group stayed at a lower level for seven months

observation period.

4. No significant disturbances of liver function were observed.

5. The liver showed inflammatory changes within one week after infestation, and

this converted gradually to the cirrhotic stage.

6. During the several months after the infestation, there appeared epithelial

changes in the cornea and degenerative signs in the retinal rods and cones layer.