ICMR BULLETIN VOL. 27-No.-4-APRIL-1997
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- ICMR BULLETIN VOL. 27-No.-4-APRIL-1997
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ISSN 0377-4910
PATHOPHYSIOLOGY OF DIARRHOEA DUE TO GIARDIA LAMBLIA
There seems to be a considerable impact of diarrhoeal
diseases on the health of world population. An estimated
3-5 billion cases of diarrhoea are reported each year
resulting in 3-5 million deaths per year1’2. Despite serious
global concern, diarrhoeal diseases are a continuing threat
to developing countries, 80 per dent of the deaths in these
countries occurring in children below two years of age.
A wide assortment of enteropathogens are incrimi
nated as causative agents of infective diarrhoeas. These
are mainly Vibrio cholerae, Escherichia coli, Shigella
sp. Rotaviruses, Giardia lamblia, Entamoeba histo
lytica and Cryptosporidium.
Amongst the parasites causing infective diarrhoeas,
there are less prevalent ones also like Isospora sp. Dien
tamoeba fragiles, Trichuris trichura, Strongyloides
stercoralis and Ancylostoma duodenale. However, G.
lamblia is the most common protozoan parasite of the
human intestinal tract and a potential causative agent of
diarrhoea. It infects about 2-15 per cent of the population
in various parts of the world. In developing countries the
incidence is higher, ranging from 5-50 per cent. It is well
established that G. lamblia is an important cause of
significant morbidity, localized water-borne outbreaks of
epidemic proportions and traveller’s diarrhoea.
There have been major developments over the last
decade in our understanding of the biology of G. lamblia
and pathophysiology of the diarrhoea caused. As late as
the mid 1970s there was no universal agreement that this
parasite was indeed an important pathogen. This was partly
on account of the broad clinical spectrum seen with this
infection; ranging from asymptomatic cyst passage to
acute or chronic diarrhoea with malabsorption. A multiplic
ity ofsigns and symptoms have been associated and a broad
spectrum ofmorphological and functional intestinal changes
accompany this infection. Why some patients become
acutely ill while others remain virtually asymptomatic needs
investigation. Though it is still not fully understood it
appears that both the parasite as well as the host factors
are responsible for the spectrum of clinical manifestations
associated with this infection.
Age seems to be an important pre-disposing factor
since children are more susceptible and frequently present
with symptomatic giardiasis. Protein calorie malnutrition in
the host enhances the susceptibility to infection. Severe
malnutrition increases the risk of infection through its
deleterious effect on the host’s humoral and cellular
responses. This decreases the host’s ability to resolve the
infection thereby indreasing the parasite’s effect and
increased malabsorption. In experimental moderately
malnourished mice the'parasite causes severe infection as
compared to their pair fed controls. However, in severely
malnourished m ice the number oftrophozoites is decreased;
possibly due to lack of nutrition. A significant increase in
the lymphocyte population of intraepithelium and lamina
; Division of Publication & Information, ICMR, New Delhi - 110 029
propria in normal and moderately protein deficient animals
has been observed. It was,however, less marked in severely
malnourished group3. This could be because of severe
protein deficiency in this group.
not itself enough to account for malabsorption but couid
contribute to a cascade ofabnormalities that together impair
the absorptive mechanism ofthe gut to cause diarrhoea with
malabsorption.
Patients with hypogammaglobulinemia are at increased
risk ofsevere giardiasis characterised by malabsoprtion and
chronic abdominal pain4.
The mucosal injury inflicted by Giardia appears to be
the-major factor in the pathophysiology ofthis infection. The
earliest suggestion that Giardia formed a mechanical barrier
to absorption by covering the intestinal surface is no longer
acceptable. Some individuals with only a few detectable
parasites can have severe symptoms whereas others with
massive numbers of parasites may have slight or no
symptoms. Moreover effective competition between host
and parasite for nutrients would require enormous number
of parasites. The large absorptive surface area of the small
intestine would seem to compensate readily for such a
possibility.
The concept of cooperative action between G.lamblia
and bacteria, fungi and viruses has been postulated by
several investigators5,6 It is possible that endosymbiosis is
responsible for the apparent differences of virulence seen
with different Giardia strains. Children with giardiasis who
require hospitalisation for rehydration have been shown to
carry Rotavirus more frequently as compared to other
pathogens and this synergistic action might result in symp
tomatic infection. Proteolytic enzyme activity has been
demonstrated in Giardia1. Two major cysteine proteases of
40 and 50 kDa have been characterised. The 40 kDa
protease which cleaves haemoglobin and IgA has been
proposed as a virulence determinant. Strain variations also
might be responsible for various pathogenesis associated
with this infection. Trophozoite counts have been demon
strated to be higher in mice infected with strains isolated from
symptomatic patients as compared to those who are asymp
tomatic. Lymphocyte subset analysis showed an early sig
nificant increase in T,B and CD4+cells and a slight increase
in CD8* cells in animals infected with strains isolated from
asymptomatic patients than in those infected with isolates
from symptomatic patients8. Further, isoenzyme analysis of
G. lamblia isolates obtained from symptomatic and asymp
tomatic patients showed phosphoglucomutase (PGM) and
hexokinase (HK) enzymes as differentiating markers.
Both luminal as well as mucosal factors are important
in the development of diarrhoea and even malabsoprtion in
giardiasis. Giardia trophozoites consume bile salts in vitro
by an apparently carrier mediated active transport process9.
Consumption of host bile salts in chronic infection could
theoretically deplete the bile salt pool and thus contribute to
the fat malabsorption by impairing the micellar solubilisation
of ingested fats and by decreasing the effectiveness of
pancreatic lipase. Abnormal pancreatic exocrine function in
patients with symptomatic giardiasis has also been reported.
Tryptic activity in duodenal aspirates has been noticed to be
reduced in infected patients which returned to normal after
eradication ofthe parasite10. Stimulated lipase activity is also
reduced in infected children and this correlated with fat
excretion11. Given the large pancreatic functional reserve,
the magnitude of the reduction observed in these studies is
36
G. lamblia adheres to the epithelial cell surface by
means of its ventral adhesive disc. With scanning electron
microscopy, several investigations have demonstrated circu
lar marks of various depths left on the microvillous surface
by detached trophozoites. These marks were most likely due
to alteration/destruction of brush border of microvilli12.
However, it seems unlikely that this relatively mild destruc
tion of the surface epithelium is sufficient in itself to cause
diarrhoea.
Direct association between invasiveness and pathogen
esis of Giardia infection has been the subject of varied
opinions. Electron microscopic studies in animals have shown
that mucosal penetration could only occur in areas where
necrosis or mechanical trauma was present13.
Malabsorption ofcarbohydrates, vitamin B , D-xylose
and vitamin A are frequently observed during Giardia
infestation. The mechanical barrier mechanism is not suf
ficient to explain this altered functional physiology of the
intestine. It has been reported that during giardiasis the brush
border membrane enzymes and transport of monosaccha
rides and amino acids are reduced14. However, uptake of
nutrients did not alter significantly with different inoculum
size of the organism.
Conflicting reports are available as regards the toxic
effects of viable trophozoites or its sonicates. Though no
potent toxin has been isolated so far but Nash etalls isolated
and characterised excretory secretory (ES) products of G.
lamblia. Over 70 per cent of cell surface cysteine rich
proteins were released by 24 h into the culture medium. The
major ES products released were of225-94000 molecular
weight. Samra et al'6 demonstrated that the uptake of
nutrients was decreased in the brush border membrane
vesicles treated with ES products. Further, exposure of
intestinal tissue to ES products resulted in net secretion
of Na+, Cl- and 3-0-methyl-D-glucose.
Chen et al11 have reported a CRP gene (CRP136) from
G.duodenalis which has a repeat sequence homologous to
the gene encoding a small class of snake toxins from the
burrowing adder—the sarofotoxins.The initial symptoms
caused by sarofotoxins ie stomach cramps, nausea, vomiting
and diarrhoea are similar to those observed in giardiasis
infection. It has been suggested that a change in gene
regulation of a specific CRP with toxin properties could be
the mechanism which changes a non-pathogenic asymptom
atic infection to a pathogenic severe giardiasis.
Lectin activity exhibited by Giar<7/# merits investigation
in the study of toxic mechanisms. Lectins may directly or
indirectly contribute to the microvillous damage .Plant lectins
are capable of directly damaging enterocytes in animal
models. Alternatively lectins may facilitate adherence ofthe
organisms to the mucosa. In G .lamblia two distinct lectins
have been demonstrated; a 57-78 kDa glucose/mannose
specific lectin18 and a 28-30 kDa mannose-PO4 specific
lectin19. Recently Sreenivas etaF° have identified a 148 kDa
lectin specific for oc-methyl-D-mannoside purified from the
membrane extract of G. lamblia. However, the role of these
lectins as potential targets for host immune defences or in
facilitating adherence and then producing the pathophysi
ological alterations in the host remains to be investigated.
An inflammatory response in the lamina propria is
frequent in giardiasis. The sensitised lymphocytes in the gut
might have an important role to play in the mucosal damage
in infected animals. Significant increase in T-cell population
ofintraepithelial lymphocytes (IEL) and ofboth T and B cells
in lamina propria have been observed by Kan war et al21.
The rise in the IEL to the same degree as is observed
in coeliac disease indicates immunological injury in the form
of villous atrophy. Evidence for the role of immune system
in producing mucosal injury has been implied from
experimental G.muris infection in immunodeficientathymic
mice. Despite prolongation of infection in these animals,
abnormalities ofvillus architecture were less severe than in
immunocompetent mice. When lymphocytes from spleens
of immunologically intact m ice were injected into athym ic
infected mice, histological abnormalities developed in the
mucosa22.
In the small intestine, the secretory function is confined
to crypt cells while abosrption occurs exclusively in the cells
ofthe villi. With appropriate stimulation, copious intestinal
secretion of water and electrolytes may result. The intra
cellular calcium concentration is a major regulator oftrans
membrane electrolyte transport. Recently there has been
rapid progress in understanding the receptors that generate
intracellular signals from inositol lipids. One ofthese lipids,
phosphatidyl inositol 4,5-bisphosphate (PIP2) is hydrolysed
to DAG (diacylglycerol) and inositol triphosphate (IP3) as
part of a signal transduction mechanism for controlling a
variety ofcellular processes including secretion, metabolism
and cell proliferation, etc. DAG operates within the plane
ofthe membrane to activate protein kinase C(PKC) whereas
IP3 is released into the cytoplasm to function as second
messenger for mobilising intracellular calcium. The acti
vated PKC phosphorylates the membrane proteins thereby
altering transport carriers or conductance channel23.
Though the detailed mechanism ofdiarrhoea in giardia
sis is not fully understood, similar mechanisms involving
complex interactions of various biochemical pathways as
proposed for other secretory diarrhoeas may be involved.
Prostaglandins E and F appear to play an important role,
possibly by stimulating the CAMP system. CAMP produces
its effect by mobilising Ca+2 from intracellular stores which
in turn regulates electrolyte transport. PGE/PGF levels have
been reported to be higher in infected animals as compared
to the controls24 (Table I).
Table I. Prostaglandins E and F levels in G. lamblia infected
and uninfected control mice (ng/100 mg of tissue)24.
Post
PGE
Infection
Day
Uninfected
Infected
0
PGF
Uninfectec1
Infected
241.12
243.0
32.89
34.12
3
240.33
259.33
33.05
39.33++
6
241.25
288.33**
33.98
53.3*
9
240.98
539.0+
33.12
58.6**
12
242.10
331.66+
33.0
119.66+
15
241.22
321.33+
32.75
84.66+
P*<0.05, •♦<0.01, +<0.001, ++<0.02
Superscript number refers to the sl.no. in the reference list
Calmodulin, a calcium binding protein, has been shown
to be increased in microvillar core during G. lamblia infec
tion. Calmodulin decreases Na* and Cl' absorption and leads
to hypersecretion. W7 is a specific inhibitor of calmodulin.
In control animals with W7 net absorption was observed but
in experimental animals already calmodulin was increased
and this resulted in net secretion (Fig.I)25.
□ Mucosal to Serosal Flux
H Serosal to Mucosal Flux
Table II. Intracellular free calcium levels in control and
experimental animals23.
Group
Intracellular free calcium
concentration (nmoles/1)
Control
101.150 ± 18.203
Experimental
212.201 ± 10.115*
♦P<0.01 as compared to control
Superscript number refers to the sl.no. in the reference list.
*P < 0.01 as compared to control
**P < 0.01 as compared to the same group without W7.
Figi. Effect of W 7 on Na* transport in control and G.lamblia
infected mice jejunum (Gorowara et al 1991).
A two fold increase in intracellular calcium and IP3 levels
was observed in enterocytes isolated from G. lamblia
infected mice. This causes intestinal ion Secretion in
G. lamblia infection (Table II)25. Application of G. lamblia
trophozoites could bring about a rise in IP3 levels in mouse
enterocytes (Fig.2)26. PKC acts in synergism with Ca+2 to
induce fluid secretion in giardiasis (Table III)27. A proposed
mechanism of diarrhoea in giardiasis is depicted in Fig.3.
Fig.3. Proposed mechanism of diarrhoea in giardiasis
Table III. Effect of PMA on unidirectional fluxes of Na* and
Cl' in the small intestine of control and G. lamblia
infected animals27.
Group/Fluxes
Control
(p equiv.cnr’h’’)
No addition
Na* fluxes
Mucosal-toserosal
Serosal-tomucosal
Net flux
Cl* fluxes
Mucosal-toserosal
Serosal-tomucosal
Net flux
with G.lamblia trophozoites (Gorowara et al 1994)
38
PMA
Experimental
(p equiv.cm’2h'1)
No addition
PMA
2.79±0.04
2.70*0.36 1.81*0.21**
1.76±0.1^|
1.20*0.19*
4.06*0.40 3.40*0.25**
3.37*0.22
1.58*0.17* -1.36*0.14 ■1.59*0.19** -1.61*0.14
1.80*0.19
1.60*0.15 1.45*0.20**
1.41*0.21
2.61*0.29*
5.67*0.38
6.58*0.30
-0.81*0.07* -3.99*0.29
6.48±0.59f
-5.03±0.39t -5.17*0.19
•P<0.01 as compared to the same group with PMA
P’^O.Ol, t < 0.001 as compared to control
Values are mean ± SE of six determinations
PMA: Phorbol-12-myristate-13-acetate
Superscript number refers to the si. no. in the reference list.
Much has been learnt about the biology ofthis parasite
in the recent years. It seems likely that Giardia causes
diarrhoea and malabsorption by a number of mechanism
although the relative importance and relevance of each is
unclear and incomplete. Further, exploration of the nature
of interaction between the parasite and the host factors
warrants more information to answer the queries
regarding the pathophysiology of giardiasis.
References
14.
Samra, H.K., Garg, U.C., Ganguly, N.K. and Mahajan, R.C. Effect
of different Giardia lamblia inocula on glucose and amino acid
transport in the intestinal brush border membrane vesicles of
infected mice. Ann Trop Med Parasitol 81: 367, 1987.
15.
Nash, T.E., Gillin, F.D. and Smilth, P.D. Excretory-secretory
products of Giardia lamblia. J Immunol 131: 2004, 1983.
16.
Samra, H.K., Ganguly, N.K., Garg, U.C., Goyal, J. and Mahajan,
R.C. Effect of excretory-secretory products of Giardia lamblia
on glucose and phenyl alanine transport in the small intestine of
Swiss albino mice. Biochem Int 17: 801, 1988.
17.
Chen, N., Upcroft, J.A. and Upcroft, P. A Giardia duodenalis
gene encoding a protein with multiple repeats of a toxin ho
mologue. Parasitology 111: 423, 1995.
I
Giannella, R.A. Enteric infections : 50 years of progress. Gas
troenterology 104: 1589, 1993.
2.
UNICEF. Diarrhoeal disease : back to basics. In: The State of
World’s Children. Oxford University Press for UNICEF, New
Delhi, p.6, 1994.
18.
Farthing, M.J.G., Pereira, M.E.A. and Keusch, G.T. Description
and characterisation of a surface lectin from Giardia lamblia.
Infect Immun 51: 661, 1986.
3.
Upadhyay, P, Ganguly, N.K., Walia, B.N.S. and Mahajan, R.C.
Kinetics of lymphocyte subpopulation in intestinal mucosa of
protein deficient Giardia lamblia infected mice. Gut 27: 386,
1986.
19.
Ward, H.D., Lev, B.I., Kane, A.V., Keusch, G.T. and Pereira,
M.E.A. Identification and characterisation of taglin, a mannose6-phosphate binding, trypsin activated lectin from Giardia lam
blia. Biochemistry 26: 8669, 1987.
4.
Perlmutter, D.H., Leichtner, A.M., Goldman, H. and Winter, H.S.
Chronic diarrhoea associated with hypogamma-globulinemia and
enteropathy in infants and children. Dig Dis Sci 30: 1149, 1985.
20.
Sreenivas, K., Ganguly, N.K., Ghosh, S., Sehgal, R. and Mahajan,
R.C. Identification of a 148-kDa surface lectin from Giardia
lamblia with specificity for p-methyl-D-mannoside. FEMS
Microbiol Lett 134: 33, 1995.
5.
Feely, D.E, Chase, D.G., Hardin, E.L. and Erlandsen, S.L. Ultrastructural evidence for the presence of bacteria, virus like particles
and mycoplasma like organisms associated with Giardia spp. J
Protozool 35: 151, 1988.
21.
Kanwar, S.S., Ganguly, N.K., Walia, B.N.S. and Mahajan, R.C.
Enumeration of small intestinal lymphocyte population in Gia
rdia lamblia infected mice. J Diar Dis Res 2: 243, 1984.
6.
Miller, R.L., Wang, A.L. and Wang, C.C. Purification and
characterisation of the Giardia lamblia double stranded RNA
virus. Mol Biochem Parasitol 28: 189, 1988.
22.
Roberts-Thomson, I.C. and Mitchell, G.F. Giardiasis in mice. I.
Prolonged infections in certain mouse strains and hypothymic
(nude) mice. Gastroenterology 75: 42, 1978.
7.
Hare, D.F., Jarroll, E.L. and Lindmark, D.G. Giardia lamblia:
Characterisation of proteinase activity in trophozoites. Exp
Parasitol 68: 168, 1989.
23.
Berridge, MJ. and Irvine, R.F. Inositol phosphates and cell signal
ling. Nature 341: 197, 1989.
24.
8.
Mahajan, S., Kaur, S., Sehgal, R., Ganguly, N.K. and Mahajan, R.C.
T-lymphocyte subsets in Balb/c mice infected with different strains
of Giardia lamblia. J Protozool Res 4: 105, 1994.
Ganguly, N.K., Garg, S.K., Vasudev, V., Radhakrishna, V., Anand,
B.S. and Mahajan, R.C. Prostaglandins E and F levels in
mice infected with Giardia lamblia. Indian J Med Res 79: 755,
1984.
9.
Halliday, C.E.W., Clark, C. and Farthing, M.J.G. Giardia bile salt
interaction in vitro and in vivo. Trans R Soc Trop Med Hyg 82:
428, 1988.
25.
Gorowara, S., Ganguly, N.K., Mahajan, R.C., Goyal, J. and Walia,
B.N.S. Role ofcalcium and calmodulin in Giardia lamblia induced
diarrhoea in mice. J Diar Dis Res 9: 111, 1991.
10.
Chawla, L.S., Sehgal, A.K., Broor, S.L., Verma,R.S. and Chuttani,
P.N. Tryptic activity in the duodenal aspirate following a standard
meal in giardiasis. Scand J Gastroenterol 10: 445, 1975.
26.
Gorowara, S., Ganguly, N.K., Mahajan, R.C. and Walia,
B.N.S. Involvement of intracellular calcium stores in Giardia
lamblia induced diarrhoea in mice. FEMS Microbiol Lett 120:
231, 1994.
11.
Katelaris, P., Seow, F. and Ngu, M. The effect of Giardia lamblia
trophozoites on lipolysis in vitro. Parasitology 103: 35, 1991.
27.
12.
Erlandsen, S.L. and Chase, D.G. Morphological alterations in the
microvillus border ofvillous epithelial cells produced by intestinal
microorganisms. Am J Clin Nutr 27: 1277, 1974.
Gorowara, S., Ganguly, N.K., Mahajan, R.C. and Walia, B.N.S.
Study on the mechanisms of Giardia lamblia induced diarrhoea in
mice. Biochim Biophys Acta 1138: 122, 1992.
13.
Owen, R.L., Nemanic, P.C. and Stevens, D.P. Ultrastructural ob
servations in giardiasis in a murine model. I. Intestinal distribu
tion, attachment and relationship to the immune system of Gia
rdia muris. Gastroenterology 76: 757, 1979.
This write-up has been contributed by Dr. R.C. Mahajan,
Department of Parasitology, and Dr. N.K. Ganguly and Dr. H.
Sandhu, Department of Experimental Medicine and
Biotechnology, Postgraduate Institute of Medical Education
and Research, Chandigarh.
39
ABSTRACTS
Some Research Projects Completed Recently
Evaluation of the incidence of postoperative
pulmonary complications in relation to preopera
tive status
A total of 836 patients undergoing major surgical
procedures were studied to find out the incidence of
postoperative pulmonary complications, evaluate the
effect of pre-existing lung diseases and other risk factors
on the incidence of these complications and compare
the incidence of complications under different types of
anaesthesia. The effect of efficient postoperative pain
relief on incidence of pulmonary complications was also
evaluated.
Of the 728 patients who were preoperatively as
sessed on the basis of history, clinical examination and
bedside pulmonary function tests, 516 patients had noram 1
lung functions while 85, 87 and 40 patients (total 212)
had mild, moderate and severe pulmonary disease. Post
operative pulmonary complications developed in 7.69 per
cent (56 of the 728) of patients. Pneumonia and atelecta
sis were the most common postoperative pulmonary
complications. The incidence of postoperative pulmo
nary complications was higher in patients with moderate
and severe preoperative lung diseases (26.43 and 37.5%
respectively) compared to those with normal lung func
tions or mild disease (2.9 and 3.5% respectively). The
postoperative complications were more frequent in
smokers compared to nonsmokers. The incidence was
greater following thoracic and upper abdominal surger
ies (12.5%) and musculoskeletal and miscellaneous
surgeries including operations like hip replacement,
thyroidectomy, radicle mastectomy and Harrington-rod
insertion for scoliosis (8.75%) compared to those un
dergoing lower abdominal surgery (2.59%). The inci
dence was also higher following exposure to general
anaesthesia (8.52%) compared to regional anaesthesia
(4.54%). Duration of surgery exceeding 4 h was as
sociated with higher incidence of complications; age of
the patients had no bearing on the complication rate.
In the second part of the study the effect of efficient
postoperative pain relief on the incidence of pulmonary
complications was assessed on 108 patients undergoing
oesophagectomy. These patients were given analgesia
through the epidural route using either a local anaesthetic
or narcotics. All these patients were given aggressive
preoperative and postoperative breathing exercises and
physiotherapy. Fifty five patients receiving conventional
opiate analgesia by parenteral route served as controls.
Th j incidence of complications in control group was
40
significantly higher (75.3%) compared to patients re
ceiving epidural anaesthesia (35.29%). This study es
tablishes the role of aggressive chest physiotherapy and
breathing exercises in reducing the pulmonary compli
cation rate.
L.
H.
Kaul
Department of Anaesthesiology,
All India Institute of Medical Sciences,
New Delhi
Publication:
Kaul, H.L., Kashyap, L., Khoshoo, M.. Pandc, J.N., and
Sundaram, K.R. Postoperative pulmonary complications in patients
with preoperative lung diseases. Indian J Med Res 98: 55, 1993.
Chemical and biological effects of oxygen radicals
produced by exposure to benzene and antioxidant
potentials in liver and serum during oxidative stress
The efficiency of hydroquinone (HQ) and 1, 2, 4benzene-triol (BT) iron chelates to act as prooxidants
was studied in Wister strain albino rats. Evaluation was
done by studying (i).the potential of HQ and BT to
release iron from ferritin and whether the iron released
could catalyze oxidative reaction; (ii) efficiency of HQ
and BT in catalysing bleomycin-dependent DNA deg
radation, glutathione degradation and lipid peroxidation
in vitro; and (iii) the antioxidant potentials in serum and
liver of rats exposed to benzene.
Administration of benzene consecutively for 10 days
to rats of either sex resulted in decrease in antioxidant
potentials in serum. Serum uric acid and albumin showed
significant decrease in all groups exposed to benzene.
oc-tocopherol in serum and liver did not exhibit significant
change compared to control. Exposure to benzene also
led to increase in lipid peroxidation and decrease in free
sulph-hydryl groups. Serum ferroxidase activity, total
iron content (TIC) and total iron binding capacity (TIBC)
measured in female rats exposed to benzene showed
significant decrease in ferroxidase activity without any
change in TIC or TIBC. The decrease in antioxidation
potentials observed may be due to the oxidation reaction
exhibited by the benzene metabolites, particularly HQ
and BT resulting in oxidative stress in benzene treated
rats.
Lower concentrations of BT resulted in the release
of iron from ferritin which was able to induce lipid
peroxidation and catalyze bleomycin-dependent DNA
degradation. The presence cf oxyradical scavengers ie
albumin, catalase or superoxide dismutase significantly
inhibited iron release from ferritin by BT. It was also
found that iron complexes with HQ and BT catalyzed
bleomycin-dependent degradation of DNA.
tion of adducts with DNA which is one of the prereq
uisites of benzene toxicity and carcinogenesis.
Iron catalyzed bleomycin-dependent degradation of
DNA was enhanced 12-fold in the presence of
glutathionyl hydroquinone (GHQ) and three-fold in the
presence of glutathione (GSH). The degradation of
DNA was linear with the increase in concentrations of
GHQ or GSH, other factors being constant. The pres
ence of oxyradical scavengers viz thiourea, mannitol,
albumin, superoxide dismutase, catalase and dimethyl
sulphoxide caused significant inhibition of degradation
by GHQ and iron.
G. Sambasiva Rao
Industrial Toxicology
Research Centre
Lucknow
It is concluded that the polyphenolic metabolites of
benzene enhance the availability of Fe (II) to bleomycin.
Such Fe (II) was possibly made available due to reduc
tion of Fe (III) by polyphenols thus protecting the Fe
(II) from hydrolysis to hydroxides and further oxidation.
It is also concluded that GHQ is a potent prooxidant,
capable of enhancing iron dependent formation of
superoxide radical and also due to its faster autooxidation
to glutathionyl benzosemiquinone may facilitate forma
Publications:
1.
Ahmad, S., Singh, V. and Rao, G.S. Antioxidant potential in
serum and liver of albino rats exposed to benzene. Indian J Exp
Biol 32: 203, 1994.
2.
Singh, V., Ahmad, S. and Rao, G.S. Prooxidant and antioxidant
properties of iron-hydroquinone and iron-1, 2, 4-benzenetriol
complex. Implications for benzene toxicity. Toxicology 89: 25,
1994.
3.
Ahmad, S., Singh, V. and Rao, G.S. Release of iron from ferritin
by 1,2, 4-benenetriol. Chemico-Biol Interac 96: 103, 1995.
4.
Singh, V., Ahmad, S. and Rao, G.S. Release of aldehydic
products from glutamate or deoxyuridine by 8-aminolevulinic
acid in presence of copper ions. Indian J Exp Biol 34:208,1996.
5.
Rao, G.S., Glutathionyl hydroquinone: a potent prooxidant and
a possible toxic metabolite of benzene. Toxicology 106: 49,
1996.
ICMR NEWS
The following meetings of various technical committees/groups were held:
Meetings of the Task Forces (TFs)/Project Review
Committees (PRCs)/Scientific Advisory Committee
(SAC) held at New Delhi:
TF on the study of the normal
range of important lymphocyte
sub-population in India
March 21, 1997
PRC on Anatomy, Haematology,
Human Genetics, Immunology and
Physiology
April 1, 1997
TF on the monitoring of adverse
drug reactions in India
April 8,1997
PRC on Pharmacology
April 9,1997
SAC on Food Contaminants
in India
PRC on Cardiovascular Diseases,
Neurology and Mental Health
Dr. Kamala Krishnaswamy took over as the Director
of the National Institute of Nutrition, Hyderabad w.e.f.
April 11,1997.
Honours/Awards:
Dr. Kalyan Banerjee, Director, National Institute of
Virology, Pune, has been awarded the prestigious Shri Om
Prakash Bhasin Award for the year 1996 in recognition of
his scientific contributions.
♦♦♦
April 10-11,1997
April 15,1997
Participation of ICMR Scientists in Scientific Events:
Dr. A. Gajanana, Dy. Director, Centre for Research
in Medical Entomology, Madurai, participated in the IV
International Symposium on Dengue Fever at Tahiti,
Society Island (April 14-17, 1997).
Appointments:
The Regional Occupational Health Centre (Eastern),
Calcutta ofthe Council moved in the new building complex
of the Centre at Salt Lake, Calcutta on January 29,1997.
The Council’s Regional Medical Research Centre, Port
Blair, moved in the new permanent building of the Centre
at Dollygunj on March 29, 1997.
***
♦**
♦♦♦
The ICMR received a generous donation of an
endowment from His Majesty Sultan Qaboos Bin Said AlSaid, the Ruler of Oman. His Excellency Mr. Yahaya Bin
Mahfudh Al-Mantheri, Minister of Higher Education,
Sultanate of Oman, handed over the endowment donation
to Director-General, ICMR at a function held at the Institute
of Pathology, New Delhi on April 3, 1997.
41
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Date & Place
Symposium/Seminar/Workshop/
Course/Conference
Contact Address
National Conference of Gerontology and Symposium on
Molecular Markers of Aging
April 7-9, 1997;
(at Gwalior)
Dr. Y.K. Jaiswal, Organising Secretary of the
Conference, School of Studies in Biochemistry,
Jiwaji University, Gwalior-474011.
I National Convention of Association for the Promotion
of DNA Finger Printin; and other DNA Technologies
April 12-13, 1997;
(at Hyderabad)
Dr. K.P.C. Gandhi, Organising Secretary of the
Convention, Forensic Science
Laboratory,
Hyderabad-500004.
Training Workshop on Biomedical Communication
June 2-3, 1997;
Dr. C.M. Habeebullah, Director, Decan College
(at Hyderabad)
of Medical Sciences, Hyderabad-500258.
COUNCIL’S TRAINING PROGRAMMES FOR 1997-98
Leprosy
•
At the Central JALMA Institute for Leprosy, Agra:
•
Training Course on National Leprosy Eradication
Programme for Medical Officers (September 15-26,1997).
Virology
At the National Institute of Virology, Pune:
•
Diploma in Medical Virology (July 1997-May 1998).
Occupational Health
At the National Institute of Occupational Health,
Ahmedabad:
•
Orientation Course on Occupational Health for Industrial
Medical Officers (September 30-October 11, 1997).
•
Training Course on Environmental Hygiene Practice
(November 10-14,1997).
Reproductive Biology
At the Institute for Research in Reproduction, Mumbai:
Postgraduate Certificate Course in Nutrition (December
1,1997-February 28,1998).
Laboratory Animal Technology
•
Training Course on Research Methods in Clinical Trials
of Newer Contraceptives (April 14-25,1997).
At the National Centre for Laboratory Animal Science,
National Institute of Nutrition, Hyderabad:
•
Workshop on Genotoxicity (August 28-29, 1997).
•
•
Workshop on Basic Molecular Biology for Clinicians
(December2-11,1997).
Training Course for Laborator)' Animal Technicians (June
16-July 31,1997).
•
Training Course for Laboratory Animal Supervisors (Sep
tember 1-November 29,1997).
Endocrinology
Haematology
At the National Institute of Nutrition, Hyderabad:
•
Annual Certificate Course on Endocrinological Tech
niques and their Applications (August 1-September 15,
1997).
At the Institute of Immunohaematology, Mumbai:
•
Training Course in Transfusion Medicine for Blood Bank
Medical Officers (August 27-October 24, 1997).
•
Training Course in Blood Group Serology and Blood
Bank Methodology for Blood Bank Technicians (August
27-September26,1997).
•
Training Course in Advanced Haematology and
Immunohaematology (October 6-24,1997).
Nutrition
At the National Institute of Nutrition, Hyderabad:
•
M.Sc. in Applied Nutrition (June 1, 1997-February 28,
1998).
EDITORIAL BOARD
Dr.G.V.Satyavati
... Chairperson
Dr. BadriN. Saxena ... Member
Dr. Bela Shah
... Member
Dr. N. Medappa
... Editor
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Research, New Delhi
at the ICMR Offset Press, New Delhi-110029
RN.21813/71
Position: 2331 (13 views)