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We have observed statistically significant elevation of urinary mucoprotein
levels in stone formers as compared to normal population. These results
suggest that mucoprotein is one of the important risk factors in the
etiology of urinary calculus disease in Udaipur region. Cystone, a
formulation of indigenous medicines has been found to progressively
reduce the mucoprotein excretion in thirty eight stone formers. Three
months therapy in seven patients significantly reduced it and brought
down its excretion to almost within normal range.
Keywords: Mucoproteins; Stone formers; Indigenous drug;
Cystone; Therapy.
In the last decade increasing attention has been
given to urinary excretion of mucoproteins. They contain a relatively
larger content of carbohydrates (Harper, 1979) and have a specific
property of inducing calcium phosphate and calcium oxalate crystalluria
and crystal aggregation (Pinto et al., 1980). Although excreted
only in small amounts, these are considered to exert a substantial
influence on the etiopathogenesis of stones.
Boyce and Swanson (1955) were the first to report the increased
urinary mucoprotein excretion in calculus disease, but major interest
arose only recently with the reports of Bichler et al., (1976) and
Hallson and Rose (1979). Their work was further supported by Pinto
et al., (1980) and Scurr et al., (190). Very recently Rose and Sulaiman
(1982) presented lucid proof of the stone promoting behaviour of
mucoproteins.
Various studies indicate that urinary mucoproteins behave as double
risk factors. Firstly, they increase the process of crystal formation
and aggregation which may serve as a "seed" for stone
formation and, secondly they provide an architectural frame-work
on which crystalloids hasten the process of stone growth.
Cystone*, a patent herbal drug formulation manufactured by The
Himalaya Drug co., Mumbai, India, is claimed to maintain crystalloid-colloid
balance and to dissolve the stone matrix, thereby disintegrating
the stone.
(*Cystone composition: Didymocarpus pedicillata 65mg; Sexifrage
legulata 40mg; Rubia cardefolia 16mg; Cyperus scariosus 16mg;
Achyranthes aspera 16mg; Onosma bracteatum 16mg; Vernonia cineria
16mg; Shilajeet purified 13mg and hajrul yahood bhasma 16mg)
We have been examining the usefulness of various indigenous drugs
in urolithiasis. In this project, we have also undertaken clinical
trials on Cystone and have observed that it decreases the concentration
of some of the stone promoting crystalloids (Singh et al., 1983
and Pendse et al., 1984). In the present paper we report urinary
mucoprotein excretion in normal men and stone formers and the effect
of Cystone therapy on the latter.
In the present
study 18 healthy persons and 115 radiologically proven stone formers
were selected. The normal men took their routine diet and patients
were given standard hospital diet. During the period of study oxalate
rich foods were avoided and only vegetarian food was permitted. In
the stone former group urine samples were collected before and after
Cystone therapy. In all the patients Cystone was given at a dose of
2 tablets three times a day for conservative treatment. The patients
were advised to report back for further check-ups after a specified
period unless they developed any serious complication requiring urgent
attention.
Forty five patients were advised to report after 12 and 24 weeks for
follow-up. Only seven patients turned up after 12 weeks and none of
them returned after 24 weeks despite repeated reminders.
Therefore, we could not ascertain their clinical or biochemical profile
thereafter. Another group of 70 patients were placed on the same therapy
and were advised to return for check-ups after 4 and 8 weeks. Thirty
eight patients turned up for both of these follow-ups.
Two 24 hours urine samples were collected from all the normal subjects
and seven stone formers who came for check-ups after 12 weeks. A single
24 hours urine sample was collected from the other 38 stone formers
who came for follow-ups after 4 and 8 weeks.
The urine samples were collected in 2.5 litre bottles containing sodium
azide as preservative. The samples were sent to the biochemistry laboratory
immediately after collection. The urinary output was measured. The
samples were mixed and analysed for creatinine (Natelson, 1971) and
mucoproteins. The procedure for determination of seromucoids by tyrosine
content as described by Natelson (1971) was suitably modified for
the determination of urinary mucoproteins.
Kachmar and Grant (1976) reported that
in man, urinary mucoprotein excretion is about 79mg/24 hours. Bichlet
et al. (1976) reported it to be 55.9 ± 6.2mg/24 hours in males
and 42.2 ± 8.2mg/24 hours in females. Anderson and Maclagon (1955)
reported higher normal values (146 ± 7.5mg mucoprotein in 24 hours
in males and 106 ± 6.4mg/24 hours in females). In our series the
mucoprotein excretion in normal subjects ranged from 21.45 to 112.8
mg/24 hours with a mean excretion of 59.01 ± 5.20mg/24 hours (Table
1). In stone formers the excretion ranged from 24.2 to 399.0mg/24
hours with a mean excretion of 103.53 ± 11.72mg/24 hours. The excretion
in stone formers was significantly higher than that in normal subjects
(p<0.05).
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Table 1: 24 hour urinary output
and mucoprotein excretion in 18 normal subjects and 45 stone
formers
|
|
Parameter
|
Normal subjects
(Mean ± SE)
|
Stone formers
(Mean ± SE)
|
| Volume
(ml/day) |
1,059 ± 120
|
1,394 ± 106
|
| Mucoprotein
(mg/day) |
59.0 ± 5.2
|
*103.5 ± 117
|
| *p<0.05 |
No significant difference
was observed in urinary output of the two groups. These observations
suggest that mucoprotein might be one of the etiological factors
in stone formation in the local population.
The urinary output,
mucoprotein and creatinine excretion of seven stone formers before
and after 12 weeks of Cystone therapy are given in Table 2. Cystone
therapy decreased the mucoprotein excretion from 79.15 ± 8.04 to
55.40 ± 7.49mg/24 hours (p<0.05). Urinary output increased
but it was not statistically significant.
|
Table
2: Mean 24 hour urinary output, mucoprotein and creatinine
excretion of 7 stone formers before and after 12 weeks of
Cystone therapy
|
|
Parameter
|
Initial
(Mean ± SE)
|
3 month follow-up
(Mean ± SE)
|
| Volume
(ml/24 hours) |
1,302
± 195
|
1,598
± 172
|
| Mucoprotein
(mg/24 hours) |
79.1
± 8.0
|
*55.4
± 7.4
|
| Creatinine
(mg/24 hours) |
1,121.2
± 143.5
|
1,133.7
± 133.6
|
| *p<0.05 |
Even 4 and 8 weeks of Cystone therapy
progressively decreased the mucoprotein excretion (Table 3). In this
group urinary output was also significantly higher. The level of significance
(t and p values) can be seen from Table 4.
|
Table
3: Mean 24 hour urinary output, mucoprotein and creatinine
excretion in 38 stone formers before and after 4 and 8 weeks
of Cystone therapy
|
|
Parameter
|
Initial
(Mean ± SE)
|
I follow-up
(4 weeks)
(Mean ± SE)
|
II follow-up
(8 weeks)
(Mean ± SE)
|
| Volume
(ml/24 hours) |
1,357
± 20
|
1,518
± 92
|
1,745
± 93
|
| Mucoprotein
(mg/24 hours) |
108.0
± 14.6
|
75.2
± 8.5
|
55.7
± 3.6
|
| Creatinine
(mg/24 hours) |
971.8
± 83.0
|
993.1
± 69.9
|
1,219.9
± 78.0
|
|
Table 4: Statistical evaluation of urinary
output and mucoproteins before and after 4 and 8 weeks of
Cystone therapy in 38 stone formers
|
| Parameters |
|
t
|
p
|
| Volume: |
Initial vs I follow-up |
2.024
|
<0.05
|
| Initial vs. II follow-up |
6.080
|
<0.001
|
| I follow-up vs II
follow-up |
3.743
|
<0.001
|
| Mucoprotein: |
Initial vs I follow-up |
2.634
|
<0.01
|
| Initial vs II follow-up |
4.046
|
<0.001
|
| I follow-up vs II
follow-up |
2.277
|
<0.05
|
Among these 45 stone formers, one patient
with right ureteric calculus spontaneously voided it during the course
of treatment. We did not have any evidence that Cystone pulverised
the stone in any of these patients during the therapy period. However,
it should be mentioned that the desired effect of the drug on disintegration
of calculi is supposed to be achieved after 4-6 months (or even longer)
of therapy. Despite our best efforts we have found that clinical trials
of such a long duration are not feasible here.
- The urinary output, and mucoprotein
and creatinine excretion in 18 normal subjects and 45 stone formers
before and after Cystone therapy were measured.
- The urinary mucoprotein excretion
in normal subjects and stone formers was 59.01 ± 5.20 and 103.53
± 11.72mg/24 hours respectively. In the latter group the excretion
was significantly higher (p<0.05).
- In seven stone formers 12 weeks
of Cystone therapy significantly decreased the mucoprotein excretion
(p<0.05).
- In 38 stone formers, Cystone therapy
progressively decreased the urinary mucoprotein excretion and
increased urinary output. These differences were statistically
significant.
- Bichler, K.H., Kirchner, C.H. and Indler, V. (1976): Brit.
J. Urol. 47: 733.
- Boyce, W.H. and Swanson, M. (1955): J. Clin. Invest.
34: 1581.
- Hallson, P.C. and Rose, G.A. (1979): Lancet 1: 1000.
- Harper, A. (1979): Review of Physiological Chemistry. Langes
Medical Publications Singapore.
- Kachmar, J.F. and Grant, G.H. (1976): Fundamentals of Clinical
Chemistry (Editor: Tietz, W.N.) W.B. Sauders Co. Philadelphia
p. 335.
- Natelson, S. (1971): Techniques of Clinical Chemistry III Ed.
Charles C. Thomas. Publisher Springfield Illinois, U.S.A. p. 286.
- Pendse, A.K., Ghosh, R., Goyal, A. and Singh, P.P. (1984): Asian
Med. Jour. 27: 137.
- Pinto, B., Patermain, J.L. and Bernstham, J. (1980): Urolithiasis
(Editors Smith, L.H., Robertson, W.G. and Finlayson, B.) Plenum
Press, New York, London, p. 651.
- Rose, G.A. and Sulaiman, S. (1982): J. Urol. 127: 177.
- Scurr, D.S., Bridge, C.M. and Robertson, W.G. (1980): Urolithiasis.
Editors: Smith, L.H., Robertson, W.G. and Finlayson, B.: Plenum
Press, New York, London, p. 602.
- Singh, P.P., Pendse, A.K., Goyal, A., Ghosh, R., Srivastava,
A.K. and Kumawat, J.L. (1983): Indian Drugs 20: 264.
- Singh, P.P., Goyal, A., Kumawat, J.L., Ghosh, R., Srivastava,
A.K. and Pendse, A.K. (1983): Arch. Med. Prac. 1: 43.
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