ICMR BULLETIN VOL. 28-No.-6-JUNE-1998.pdf
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Vol. 28, No. 6
June, 1998
HEALTH HAZARDS OF FUMONISIN MYCOTOXINS
AND ITS PREVENTION
Safe, adequate and nutritious food intake is an essential
pre-requisite for maintaining good health. A variety of
naturally occurring food contaminants like mycotoxins
constantly pose a threat to human health. Mycotoxins, the
secondary metabolites produced by fungi have gained
considerable health and economic significance during the
last four decades. Application of the risk analysis approach
to food safety issues revealed the need for assessing the
occurrence of mycotoxins in various food items,
particularly in staple cereals. The National Institute of
Nutrition (NIN), Hyderabad, has been investigating
outbreaks of food-borne disease due to the consumption
of mycotoxin-contaminated food commodities. These
include aflatoxic hepatitis in parts ofGujarat and Rajasthan,
enteroergotism in Rajasthan and acute deoxynivalenol
mycotoxicosis in the Kashmir Valley due to the
consumption of mouldy maize, ergoty bajra and rain
damaged wheat respectively1*3.
Fumonisin Mycotoxins
Fumonisins are a group of mycotoxins produced by
species ofFusarium, mainly F. moniliforme*. The discov
ery of fumonisins in 1988 by researchers from the South
African Medical Research Council received world-wide
attention5. Chemically, fumonisins are diesters of propane
1,2,3 tricarboxylic acid and are structurally similar to
sphingosine produced by F. moniliforme and related spe
cies in agricultural commodities, in the field as well as
during storage. Although different fumonisins viz
fumonisin Ap A2, B,, B2, B3, B4 and C( have been reported,
only fumonisin Bp B2 and B3 were found to occur natu
rally in foods6. Among the different varieties, fumonisin
B, is the major metabolite occurring naturally, mostly in
maize. Fumonisins have been shown to be hepatotoxic,
hepatocarcinogenic and nephrotoxic to rats, atherogenic
to monkeys and also lead to poor weight gain, diarrhoea
and rickets in broiler poultry7. Fumonisins are shown to
cause developmental toxicity in rats, mice and hamsters,
and are toxic to chick embryos8. Studies have shown that
fumonisins are cytotoxic to different mammalian cell lines
in vitro, although the sensitivity differs between different
cell lines9. Fumonisin B( has been found to inhibit the de
novo sphingolipid synthesis both in vitro and in vivo10*11.
The International Agency for Research on Cancer (I ARC)
has classified fumonisin Bj under the 2B group of car
cinogens, ie, “possibly carcinogenic”. In view of its po
tential toxic effects12, a study has been initiated to find out
the relevance of fumonisins in the Indian context.
Natural Occurrence
Fumonisins have been shown to occur naturally in
maize and maize-based animal feeds throughout the world
Division of Publication & Information, ICMR, New Delhi - 110029
S3S
general, Fusarium isolates from maize produced higher
fumonisin B( than the isolates from sorghum.
in levels ranging from a few nanograms to a few hundred
micrograms7. In general, maize and its products meant for
animal consumption, contain higher levels of fumonisin
Br Maize has been shown to be a good substrate for many
ofthe mycotoxins. Maize is not only consumed as a staple
by certain segments of the Indian population, but also used
as an important ingredient in animal feed.
Substrate Specificity
Studies carried out on the production of fumonisin B{
in maize14 in the laboratory by different workers’5 revealed
that maximum fumonisin Bt production occurs when in
oculated maize is incubated at 25°C for 7 to 9 weeks. How
ever, considerable growth and fumonisin B( production
was seen in the first week of inoculation itself. As high as
15 pg/g of fumonisin B( production by F. moniliforme
strain MRC 826 in maize has been reported under similar
conditions. In order to study the fumonisin production in
different cereal substrates such as maize, rice, sorghum
and wheat in the laboratory, sterilized substrates were
A total of 157 samples consisting of maize, sorghum,
poultry feeds and horse feeds collected from northern and
southern parts of India, were analysed using high perfor
mance liquid chromatography (HPLC) for the possible
presence of mycotoxins like fumonisin BI and aflatoxin
Br Detection limits were 20 ng/g for fumonisin Bt and 1.5
ng/g for aflatoxin Br Their levels in maize, sorghum and
poultiy feeds are given in the Table. Maize showed higher
Table: Incidence and levels of fumonisin B, and aflatoxin Bt in different commodities.
Aflatoxin B,
Fumonisin B,
Commodity
Range
(Hg/kg)
Geometric
mean
(Hg/kg)
9/44
0.18 -30.34
1.97
0.48
24/25
2.0 - 830.00
24.01
0*01 - 4.74
0.62
31/35
0.11 - 4030.47
2.60
19/19
0.04 - 64.7
1.17
••
19/19
5.0 - 126.00
14.38
5/14
0.02 - 0.26
0.10
14/14
0.38 - 108.61
37.88
Geometric
mean
(Mg/g)
Incidence
(positives/
total)
Range
Normal
sorghum
2/44
0.15- 0.51
0.27
Rain affected
sorghum
25/25
0.07 - 7.80
Normal
maize
26/35
Rain affected
maize
■Poultry feeds
fumonisin Bt contamination than sorghum13. All the rain
affected maize and sorghum samples showed fumonisin
B1 contamination, whereas 74% of the normal maize and
4.5% ofthe normal sorghum samples contained fumonisin
Br Highest fumonisin B, level was seen in a rain-affected
maize sample (64.7pg/g). Though aflatoxins were found
to co-occur, no correlation was observed between
fumonisin BI and aflatoxin Bt indicating that both the tox
ins exist independently in the samples.
In comparison with sorghum, maize samples showed
higher contamination with Fusarium sp. In addition, high
est number (16/26) of Fusarium species belonging to the
section Liseola were isolated from the maize samples.
Majority of the isolates (19/26) belonged to F. moniliforme.
Most of the isolates from maize (15/16) produced
fumonisin Br Highest fumonisin Bj production was seen
with F. moniliforme isolate from feed (234pg/g). In
56
Incidence
(positives/
total)
inoculated with fumonisin producing strain of F.
moniliforme and incubated in the dark for various inter
vals upto 60 days at 25°C. Results revealed that all the
substrates supported good fungal growth, although they
varied greatly in their capacity to support fumonisin
production. The Figure shows the production of fumonisin
BI on different substrates at the end of 60 days of incuba
tion. Highest fumonisin Bj production (2101 pg/g) was
seen in maize followed by rice (1448 pg/g), sorghum (125
pg/g) and least in wheat (31 pg/g). Rapid production of
fumonisin Bt was seen from 10 days onwards in maize, 20
days onwards in rice and was tardy throughout in wheat
and sorghum. Although production of fumonisin B, in rice
was seen to be tardy during the first 10 days of incubation,
its production increased rapidly by the end of 60 days of
incubation. The reported variation in the production of
fumonisin may be due to the differential availability of
various intermediates required in the bjosynthetic path
way or the presence of inhibiting compounds in wheat and
sorghum14.
Fig. Fumonisin B, production on different substrates.
Health Implications
Though consumption of maize contaminated with fun
gus F. moniliforme has been traditionally associated with
human and animal health hazards, the toxin responsible
for these effects was not identified till the discovery of
fumonisins. The two major diseases associated with
fumonisins are leukoencephalomalacia in horses and pul
monary oedema in pigs. Leukoencephalomalacia is char
acterized by degeneration of white matter of the brain.
Horses are the most sensitive animals for the fumonisin
toxicity and levels as low as 8 pg/g in the feed may be
fatal. Pulmonary oedema and hydrothorax,* a fatal syn
drome in pigs has been reported from different parts of the
world16. Of late, field outbreaks of leukoencephalomalacia
and pulmonary oedema have also been reported from
USA16. However, so far such incidences have not been re
ported from India.
belonging to 6 districts of Andhra Pradesh and Karnataka
states of southern India. The disease was characterized by
borborygmy, abdominal pain and diarrhoea. The problem
has been traced to the consumption of food prepared from
mouldy sorghum and maize. The disease persisted as long
as mouldy grains were consumed. However, those who
had access to alternative foods, did not show the symptoms
of disease. Fortunately the disease was self-limiting, noncontagious and not fatal. Though people were aware of
the cause of the disease, they continued to consume mould
affected grains as its consumption was not considered by
them to be life endangering. Besides, they did not have
any alternative food source. The disease occurred in the
poorest segments of the population such as marginal
farmers and agricultural labourers. High levels of
fumonisin B( was found in the maize (upto 65 pg/g) and
sorghum (8 pg/g) collected from the affected households,
whereas these levels were comparatively lower in the
unaffected households. Samples did not contain any other
fusarium mycotoxins and had low levels of aflatoxin B,17.
Disease Outbreak in Poultry
During the study period, it was observed that rain af
fected mouldy maize was purchased by middlemen to be
used as poultry feed ingredient after mixing with normal
grains. Hence, a few farms in the region were visited to
find out the possibility of disease outbreak which occurred*
only in two layer poultry farms. The disease was charac
terized by black sticky diarrhoea, reduced weight gain,
drastic drop in egg production, lameness and mortality.
Antibiotic and vitamin supplementation had no effect. Feed
withdrawal showed improvement. The cause for the dis
ease outbreak was traced to a fresh batch of feed contain
ing high levels of fumonisin B( (8.5 pg/g). Some of the
symptoms were reproduced by giving the incriminated feed
to cockerels and fumonisin B, containing culture material
to layer hens in the laboratory18.
Disease Outbreak in Humans
Oesophageal Cancer and Fumonisins
During October 1995, there were unseasonal rains in
certain parts ofthe Deccan Plateau at the time of harvesting
the Kharifcrops ofmaize and sorghum. Heaps of harvested
maize and sorghum were left in the field for about 10 days.
Due to improper storage, these crops got affected by
moulds and when food items prepared from these mouldy
grains were consumed by animals as well as humans,
disease outbreaks were reported. There were reports of
deaths ofdomestic animals and ofan acute disease outbreak
in humans living in the affected region. A rapid
epidemiological survey was conducted in 50 villages
Fumonisins have been epidemiologically correlated
with the high incidence of human oesophageal cancer in
certain parts of the world such as South Africa19 and
China20. The highest incidence of human oesophageal
cancer has been reported from the lower Assam region of
India. This region comes under the Dibrugarh Hospital
Cancer Registry21. To find out whether fumonisin has any
role in the etiology of oesophageal cancer in the region, a
survey was conducted with the cooperation of the Regional
Medical Research Centre, Dibrugarh. However, none of
the food samples tested contained detectable fumonisin
57
B1 indicating that fumonisin may not have any role in the
etiology. Other possible etiological factors' investigated
include a special food ingredient called Kalakhar, a highly
alkaline coffee-decoction like liquid made from the charred
banana false stem. This product is frequently used in the
lower Assam region. Being highly alkaline and a charred
product, it may play a role in the etiology of the
oesophageal cancer. This problem required further study.
During the study, the role of food and domestic
environment in the etiology was studied by investigating
the incidence of oesophageal tumours in the domestic
poultry population in the region. Interestingly, 9 of 680
oesophagi collected from the region showed visible
tumours. Histopathological study of the samples revealed
that they were pseudo tumours. While samples collected
from the Hyderabad region did not show any visible
tumours, the oesophagi from the lower Assam region
showed histopathological changes such as basal cell
hyperplasia, glandular hypertrophy, acanthosis and reactive
changes. Hence, these results suggest that food and
domestic environment might play a major role in the
etiology of human oesophageal cancer in the region
(unpublished observation).
Detection Methods
There are a number of methods available for the de
tection and quantitation of fumonisins in food samples.
Methods include TLC, HPLC, GC and ELISA22*23. The
HPLC procedure with the ophthaladehyde derivatization
is widely used. During the epidemiological survey of hu
man disease outbreak, the need of a method for the detec
tion and quantitation of fumonisin B1 in human urine was
recognised as there is no sensitive method available. A
two-step HPLC clean up method was developed with an
additional non-ionic polymeric absorbant resin Amberlite
XAD-2 clean up before the strong anion exchange (SAX)
cartridge clean up. The presently available method’involved
a single step SAX cartridge clean up and was not found to
be suitable for human urine with large volume at low toxin
levels due to salt interference. The newly developed method
had detection limit of less than 8 ng/ml with a high recov
ery and reproducibility24.
Prevention and Control Strategies
Effect ofcooking
Effect of household cooking processes such as prepa
ration of unleavened Indian bread (roti) and porridge made
out of naturally contaminated maize and sorghum on
fumonisin levels was studied by simulating household
58
cooking conditions in the laboratory. During preparation
of unleavened Indian bread upto 29% reduction in toxin
was seen in maize and no reduction was observed in sor
ghum based preparation. No reduction in fumonisin B, was
noticed in porridge prepared from maize although a little
(12%) reduction was observed during sorghum porridge
preparation25.
Decontamination
Density seggregation of fumonisin-contaminated
maize kernels in water and with different concentrations
of sodium chloride was studied. Results showed that the
buoyant kernels separated in water alone contained upto
74%.of the total fumonisin Br With the increasing con
centration of sodium chloride in water, more fumonisin
B, was removed. The maximum effectiye removal was
upto 86% with saturated NaCL solution. Removal of
fumonisin B, in 30% NaCL was optimal, as it was not
significantly different from the saturated NaCL solution26.
Varietal differences
To assess the susceptibility to fumonisin Bp 10 geno
types of maize consisting of 5 inbred and 5 hybrid variet
ies were screened. A large variation was seen among dif
ferent varieties with respect to fungal growth and fumonisin
B, production in the laboratory. Two inbreds viz Trishula
and Harsha and one hybrid, 5015x5016 supported very
low production of fumonisin B1 (<200 pg/g) and all the
remaining genotypes supported production of high level
of fumonisin Bt (>1200 pg/g)27.
Conclusions
Maize is the high risk commodity for fumonisin Bb
contamination. Although low levels of fumonisin B, were £)
found in sorghum, high levels may accumulate under con
ditions favourable for mould growth. Fumonisin produc
ing capacity of the Indian isolates indicates the need for
control of fungal contamination in the field and at the post
harvest level. Naturally occurring fumonisin B1 levels in
maize and sorghum also can cause health disorders in hu
mans and poultry. Cooking does not result in considerable
loss of fumonisin Br However, fumonisin levels can be
effectively controlled by the available procedures of de- .
contamination.
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1.
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Bryden, W.L. Leukoencephalomalacia in horses. Aust Vet J 70:
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Bhat, R.V., Beedu, S.R., Ramakrishna, Y. and Munshi, K.L. Out
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Ross, P.F., Rice, L.G., Osweiler, G.D., Nelson, P.E., Richard, J.L.
and Wilson, T.M. A review and update of animal toxicoses asso
ciated with fumonisin-contaminated feeds and production of
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Gelderblom, W.C.A., Jaskiewicz, K., Marasas, W.F.O., Thiel, P.G.,
Horak, R.M., Vleggaar, R. and Kriek, N.P. Fumonisins-novel my
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Bhat, R.V., Shetty, P.H., Amruth, R.P. and Sudarshan, R.V. A
food-bome disease outbreak due to the consumption of mouldy
sorghum and maize containing fumonisin mycotoxin. J Toxicol
Clin Toxicol 35:249, 1997.
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Bezuidenhout, S.C., Gelderblom, W.G.A.; Gorst-Allman, C.P.,
Horak, R.M., Marasas, W.F.O., Spiteller, G. and Vleggaar, R. struc
ture elucidation of the fumonisins, mycotoxins from Fusarium
moniliforme. J Chem Soc Chem Commun 743, 1988.
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Shetty, P.H., Sudarshan, R.V., Rao, J.P.K. and Bhat, R.V. Dis
ease outbreak in layer hens due to consumption of fumonisin con
taminated feed. Br Poult Sci 38:475, 1997.
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Thiel, P.G., Marasas, W.F.O., Sydenham, E.W., Shephard, G.S.
and Gelderblom, W.C.A. The implications of naturally occurring
levels of fumonisins in corn for human and animal health.
Mycopathologia 117:3, 1992.
Rheeder, J.P., Marasas, W.F.O., Thiel, P.G., Sydenham. E.W.,
Shephard, G.S. and Van Schalkwyk, D.J. Fusarium moniliforme
and fumonisins in com in relation to human oesophageal cancer
in Transkei. Phytopathology 82 : 353, 1992.
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Marasas, W.F.O. Fumonisins: History, world-wide occurence and
impact. In : Fumonisins infood; Advances in Experimental Medi
cine and Biology. Eds. L.S. Jackson, J.W. De Vries and L.B.
Bullerman, Plenum Press, New York, p 1, 1996.
Chu, F.S. and Li, G.Y. Simultaneous occurrence of fumonisin B4
and other mycotoxins in mouldy com collected from the People's
Republic of China in regions with high incidence of oesophageal
cancer. Appl Environ Microbiol 60 : 847, 1994.
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Zacharias, C., Van Echten-Deckert, G., Wang, E., Merrill, A.H.
Jr. and Sandhoff, K. The effect of fumonisin B( on developing
chick embryos: Correlation between denovo sphingolipid biosyn
thesis and gross morphological changes. Glycoconjugate J 13 :
167,1996.
National Cancer Registry Programme. Indian Council of Medical
Research, New Delhi, p 84, 1989.
22.
Sydenham, E.W., Gelderblom, W.C.A., Thiel, P.G. and Marasas,
W.F.O. Evidence for the natural occurrence o.f fumonisin B,, a
mycotoxin produced by Fusarium moniliforme in com. J Agric
Food Chem 38:285, 1990.
23.
Chu, F.S., Huang, X. and Maragos, C.M. Production and charac
terization of anti-idiotype and anti- anti-idiotype antibodies against
fumonisin B,. JAgric Food Chem 43 :261, 1995.
9.
Wang, E., Norred, W.P., Bacon, C.W., Riley, R.T. and Merrill
A.H. Jr. Inhibition of sphingolipid biosynthesis by fumonisins.
Implications for diseases associated with Fusarium moniliforme.
J Biol Chem 266: 14486, 1991. *
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Norred, W.P., Wang, E., Yoo, H., Riley, R.T. and Merrill, A.H.
Jr. In vitro toxicology of fumonisins and the mechanistic implica
tions. Mycopathologia 117: 73, 1992.
24.
Shetty, P.H. and Bhat, R.V. Sensitive method for detection and
quantitation of fumonisin B( in human urine. J Chromatogr B:
Biomed Appl 705 : 171, 1998.
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Stevene, V.G. and Tang, J. Fumonisin B,-induced sphingolipid
depletion inhibits vitamin uptake via the glycosyl'phosphotidyl
inositor-anchored folate receptor. J Biol Chem 272:18020,1997.
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Shetty, P.H. Relevance of fumonisin mycotoxins in Indian con
text Ph.D. Thesis, National Institute ofNutrition, Hyderabad, 1997.
26.
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IARC. Toxins derived from Fusarium moniliforme : fumonisins
B, and B2 and fusarin C. In : IARC Monogr Eval Carcinog. Risks.
Hum., International Agency for Research on Cancer, Lyon, France.
56:p445, 1993.
Shetty, P.H. and Bhat R.V. Effect of density seggregation on
fumonisin Bt content in naturally contaminated maize. FoodChem,
(In Press), 1998.
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Shetty, P.H. and Bhat R.V. Differential production of fumonisin
B( in maize inbreds and hybrids in laboratory. Cereal Res Commun
25:1011,1997.
13.
Shetty, P.H. and Bhat, R.V. Natural occurrence of fumonisin B,
and its co-occurrence with aflatoxin B* in Indian sorghum, maize
and feeds. J Agric Food Chem 45 : 2170,1997.
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Shetty, P.H. and Bhat, R.V. Effect of different substrates on pro
duction of fumonisin Bt by Fusarium moniliforme MRC-826. Appl
Environ Microbiol (In Press), 1998.
This write-up has been adapted from the article entitled “Health
hazards of fumonisin mycotoxins and its prevention” by Sh. P.H.
Shetty, Senior Research Fellow and Dr. Ramesh V. Bhat, Dy.
Director (Sr.Grade), published in the Nutrition News 18(3), 1997.
59
ABSTRACTS
Some Research Projects Completed Recently
Effect of low level prenatal and neonatal irradiation on
the adult brain development and reproductive function
in mouse.
i
The study was carried out on inbred Swiss albino mice to
evaluate the effect of gamma irradiation at selected critical
developmental stages during gestation on the adult
neurophysiology and to see, if the neurophysiological effects
of prenatal irradiation persist to later part of life. Efforts were
also made to find out if prenatal irradiation would impair the
reproductive performance of mouse.
Pregnant mice were whole body irradiated with 0.25,0.35
•or 0.5 Gy of gamma radiation on days 11.5,12.5 (late orga
nogenesis days), 14.5 or 17.5 (foetal days) post coitus (pc)
and allowed to complete gestation and parturate. Behavioural
and'haematological changes were studied in the adults at 6,12
and 18 months of age. Reproductive performance was tested
at 6-8 months of age after mating the irradiated F1 males with
normal females of the same age. For neonatal exposure, pups
were whole body exposed to 0.5 Gy of gamma radiation on
days 4,5 or 6 post-partum.
Adult behaviour was not affected by prenatal irradiation
with 0.25 Gy. Exposure to 0.5 Gy on days 11.5,12.5 or 14.5
pc produced significant changes in the exploratory, locomotor
and learning and memory performances at 6 months of age.
The changes were more pronounced after irradiation on the
late organogenesis days (11.5 and 12.5 pc) than on the foetal
day (14.5 pc). Normal brain function was restored by 12
months in all animals, except those exposed on 11.5 day pc
in which the impaired locomotor activity and learning
deficiency persisted even at 12 months of age. Even 0.35 Gy
on day 11.5 pc produced a significant change in the locomotor
and learning performance of the young adult mice. Animals
bom to mice irradiated on day 17.5 pc were more resistant to
these effects. The peripheral RBC counts and haemoglobin
showed significant decrease at 6 months of age when the
pregnant mouse was exposed to 0.5 Gy on the foetal gestation
(14.5 or 17.5 pc) days, but not during the organogenesis
period. Post-partum exposure did not have any significant
effect on the adult behaviour or haematological parameters.
None of the hippocampal biogenic amines (noradrenaline,
dopamine, 5-hydrdxytryptomine and its metabolite - 5hydroxyindolacetic acid) studied showed any significant
change after any level of exposure on any of the gestation
days. *
The reproductive performance of the Fj males exposed
to different doses of irradiation did not show any significant
change from normal.
60
It is clear from the study that the late organogenesis pe
riod, especially day 11.5 pc is a particularly sensitive phase
in brain development and long lasting behavioural changes
can be produced in the adult by exposure at this stage to doses
below IGy.
R. Bhaskar
P. Uma Devi
Department of Radiobiology
Kasturba Medical College
Manipal.
Publications:
1.
Bhaskar, R., Uma Devi, P., Nalini, N. and Shivananda, B. Age
dependent changes in body weight, brain weight, behaviour and
biogenic amines in the hippocampus of mouse. Indian J Gerontol
9(3&4):
1955.
2.
Bhaskar, R, and Uma Devi, P. Long-term effect of prenatal expo
sure to low level of gamma radiation on neurophysiology of mouse.
Indian J Expt Biol 34: 887, 1996.
Lung specific liposomes as drug delivery vehicles.
The study was carried out to formulate liposomes with
increased affinity for lung tissues and decreased uptake by
liver and spleen and to evaluate the chemotherapeutic effi
cacy of antitubercular drugs encapsulated in these liposomes,
against experimental tuberculosis in mice.
Surface modification of stealth liposomes by tagging Ostearyl amylopectin (O-SAP) resulted in increased affinity
towards lung tissue of mice. Liposomes containing egg phosphatidyl-choline (ePC) and cholesterol (CH) in a molar ratio
of 2:1.5 were found to be stable in serum. Inclusion of
dicetylphosphate (DCP), O-SAP and monosialoganglioside
(GM^/distearyl phosphatidylethanolamine-poly (ethylene
glycol) 2000 (DSPE-PEG 2000) in PC: CH liposomes ftirf ,
ther increased the stability in serum.
Tissue distribution of different formulations of liposomes
rfevealed that lung specific stealth liposomes (PC:CH:OSAP:DCP:GMj/DSPE-PEG 2000) accumulated more in the
lungs than the reticuloendothelial system of mice. The
preadministration of PC and CH (2:1.5) liposomes or
injections of dextran sulphate (DS) before the administration
of lung specific stealth liposomes further enhanced their
uptake in the lungs. The behaviour ofthese liposomes in mice
infected with Mycobacterium tuberculosis H37Rv was similar
to that in normal mice. In vivo stability of these liposomes
demonstrated slow and controlled release of their
encapsulated contents.
Isoniazid and rifampicin encapsulated in liposomes were
less toxic to peritoneal and alveolar macrophages compared
to free drugs in spite of their uptake being equal in both the
macrophages. Further, the encapsulated drugs, were less hepatotoxic as compared to free drugs.
against tuberculous infection in mice and seems to be a
promising therapeutic approach for the chemotherapy of
tuberculosis.
The chemotherapeutic efficacy of isoniazid and rifampi
cin entrapped in lung specific stealth liposomes was evalu
ated by injecting the liposomal and free drugs intravenously
twice a week, for six weeks to tuberculous mice. Liposome
encapsulated drugs at and below therapeutic concentrations
were more effective than free drugs on the basis of colony
forming units (CFUs). The organomegaly and histopatho
logical studies also demonstrated that liposomal drugs cleared
the mycobacteria more efficiently compared to free drugs.
Liposomal drugs had marginal hepatotoxicity as seen by the
levels of total bilirubin and serum glutamate pyruvate tran
saminase and alkaline phosphatase.
G.K. Khuller
Department of Biochemistry
Postgraduate Institute of
Medical Education and Research
Chandigarh,
Publications:
1.
Parampal Deol, I., Khuller, G.K., and Joshi, K. Therapeutic effi
cacies of isoniazid and refampicin encapsulated in lung-specific
stealth liposomes against Mycobacterium tuberculosis infection
induced in mice. Antimicrob Agents Chemother 41: 1211,1997.
2.
Parampal Deol, I. and Khuller, G.K. Lung specific stealth lipo
somes: Stability, biodistribution and toxicity of liposomal antitu
The study thus demonstrated that lung specific stealth
liposome encapsulated antitubercular drugs are more effective
bercular drugs in mice. Bicohim Biophys Acta 1334: 161,1997.
ICMR NEWS
Meetings
Meeting ofthe Project Advisory Committee on ICRC Lep
rosy Vaccine Trial was held at New Delhi (May 25,1998);
Participation of ICMR Scientists in Scientific Events:
Dr. G.P. Chhotray, Asstt. Director, Regional Medical
Research Centre, Bhubaneswar, participated in the VIII
International Congress on Infectious Diseases at Boston
(May 15-18, 1998).
Dr. Dipika Mohanty, Director, Institute of
Immunohaematology, Mufnbai, participated in the XXIII
International Congress of the World Federation of
Haemophilia at The Hague (May 17-22,1998).
Dr. Y. Venkataramana, Research Officer, National
Institute of Nutrition, (NIN), Hyderabad, participated in
the XXVI FIMS World Congress of Sports Medicine at
Orlando (May 30-June 3,1998).
Dr. K. Vijayafaghavan, Dy. Director (Sr.. Grade), NIN,
Hyderabad, undertook a Short-term WHO Consultancy on
Nutritional Emergencies in Papua New Guinea (May 15Junel5, 1998).
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Symposium/Seminar/Workshop/
Course/Conference
-
Date & Place
Contact Address
National Workshop of Medical Editors and Reviewers
in Medical Communication: Peer Review, Ethics and
Internet
June 16-18,1998;
(at Pondicherry)
Dr. C. Adithan, Organising Secretary of the Work
shop, Department of Pharmacology, Jawaharlal
Institute of Postgraduate Medical Education and
Research, Pondicheny-605006.
National Conference on Molecular Diagnostics
June 27-29,1998:
(at Thiruvananthapuram)
Dr. P.R. Sudhakaran, Organising Secretary of the
Conference, Department of Biochemistry, Univer
sity of Kerala, Thiruvananthapuram-695581.
International Symposium oh. Frontiers of Genetics and
Development
July 7-8, 1998;
(at Bangalore)
Dr. U. Vijayaraghavan, Convenor of the Sympo
sium, Department of Microbiology and Cell
Biology, Indian Institute of Science, Bangalore560012.
International Symposium on Temporomandibular Joint
Disorders and Chronic Orofacial Pain
October 30-31,1998;
(at Mangalore)
Prof. P.K. Dayal, Organising Secretary ofthe Sym
posium, KMC College of Dental Surgery, Man
galore-575001.
61
COUNCIL’S TRAINING PROGRAMMES FOR 1998-99
Leprosy
•
At the Central JALMA Institutefor Leprosy, Agra:
•
Multidrug Therapy Orientation Course in Leprosy for
Medical Officers (August 17-28, October 26-November 6;
and December 7-18,1998).
Training Course for Laboratory Animal Technicians (June
16-July 31,1998).
•
Occupational Health
At the National Institute of Occupational Health, Ahmedabad:
•
Virology
Training Course on Environmental Hygiene Practice (No
vember 16-20, 1998).
At the National Institute of Virology, Pune:
•
Medical Entomology
Diploma in Medical Virology (July 1998-May 1999).
Reproductive Biology
At the Vector Control Research Centre, Pondicherry:
At the Institutefor Research in Reproduction, Mumbai:
•
•
Workshop on Andrology for Clinicians (November 16-30,
1998)
Postgraduate Diploma Course in Medical Entomology (from
August 10, 1998).
Biomedical Statistics
Endocrinology
At the Institutefor Research in Medical Statistics, Chennai:
At the National Institute of Nutrition, Hyderabad:
•
Basic Course in Statistics for Postgraduate Medical Students
(July 1998).
•
Basic Course in Statistics for Medical Officers (November
1998).
•
Annual Certificate Course on Endocrinological Techniques
and their Applications (August 1-September 15,1998).
Nutrition
Haematology .
At the National Institute of Nutrition, Hyderabad:
•
•
M.Sc. in Applied Nutrition (June 1, 1998-February 28,
1999).
Postgraduate Certificate Course in Nutrition (December 1,
1998-February 28,1999).
At the Institute of Immunohaematology, Mumbai:
•
Training Course in Transfusion Medicine for Blood Bank
Medical Officers (August 11-October 9,1998).
•
Training Course in Blood Group Serology and Blood Bank
Methodology’for Blood Bank Technicians (August 11September 10, 1998).
•
Training Course in Advanced Haematology and
Immunohaematology (September 21-October 9,1998).
Laboratory Animal Technology
At theNational Centrefor Laboratory Animal Science, National
Institute ofNutrition, Hyderabad:
EDITORIAL BOARD
Chairman
Dr. N.K. Ganguly
Director-General
Members
Dr. Padam Singh
Dr. Bela Shah
Dr. Lal it Kant
Dr. R. Ravi
Dr. V. Muthuswamy
Editor
Dr. N. Medappa
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Research, New Delhi
at the ICMR Offset Press, New Delhi-110 029
R.N. 21813/71
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