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192 XXXVI Annual Conference of XXXVI Annual Conference of XXXVI Annual Conference of XXXVI Annual Conference of XXXVI Annual Conference of the Indian Pharmacological Society the Indian Pharmacological Society the Indian Pharmacological Society the Indian Pharmacological Society the Indian Pharmacological Society New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 Abstract of resear Abstract of resear Abstract of resear Abstract of resear Abstract of research papers (Part-II) ch papers (Part-II) ch papers (Part-II) ch papers (Part-II) ch papers (Part-II) Abstracts GUFIC PRIZE 51.Beneficial effects of Zingiber officinale on experimentally-induced hyperlipidemia Sanjay KV, Goyal RK Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad. E-mail: [email protected] Objective: To evaluate the beneficial effects of standardized extracts of Zingiber officinale on elevated glycemic levels in experimentally induced hyperlipidemia and its correlation with 5-HT actions of Zingiber officinale. Methods: Wistar rats of either sex were divided into four groups, Group I served as control, Group II were hyperlipidemic rats which was induced by administering 10% fructose in drinking water, Group III were hyperlipidemic rats treated with methanolic extract of dried rhizomes of Zingiber officinale (250 mg/kg, b.w.), Group IV were hyperlipidemic rats treated with ethyl acetate extract of dried rhizomes of Zingiber officinale (250 mg/kg, b.w.) The drugs were administered orally for 3 weeks, at the end of which blood samples were analyzed for serum glucose, insulin, cholesterol, triglycerides, HDL- cholesterol, LDL and VLDL. Results: There was a significant increase in fasting serum glucose levels, serum insulin levels, serum lipid profile and increased body weight gain in hyperlipidemic control rats as compared to normal control rats. There was a significant reduction in fasting serum glucose levels, serum lipid profile and body weight and no changes in serum insulin levels in methanolic extract treated rats as compared to hyperlipidemic control rats. There was a significant reduction in fasting serum lipid profile and body weight and no changes in serum glucose and insulin levels in ethyl acetate extract treated rats as compared to hyperlipidemic control rats. Conclusion: Methanolic extract of Zingiber officinale was found to have better activity in controlling the elevated glycemic levels and elevated lipid profile in hyperlipidemic animals as compared to ethyl acetate extract of Zingiber officinale. P. C. DANDIYA PRIZE 52.Effect of curcumin on kainic acid-induced sei- zures and oxidative stress in rats Sharma M, Briyal S, Gupta YK Department of Pharmacology, All India Institute of Medi- cal Sciences, New Delhi - 110029. E-mail: [email protected] Objective: To study the effect of curcumin, a potent polyphenolic antioxidant, against kainic acid-induced seizures, and on a marker of oxidative stress in brain in rats. Methods: Male Wistar rats were used for the study. Rats were administered kainic acid at a dose 10 mg/kg, i.p. Animals were then observed for behavioral changes (grooming, rearing, hind limb scratching, urination, defecation, wet dog shakes, jaw movements, salivation, head nodding), incidence and latency of convulsions and mortality over the total period of 4 h. The rats were thereafter sacrificed for estimation of malondialdehyde (MDA). Curcumin was administered 30 min before kainic acid at doses of 100 and 200 mg/kg, i.p. Results: Kainic acid-induced long-lasting seizures and associated symptoms. The brain level of MDA was significantly raised after kainic acid administration (536 + 44 nmol/g wet tissue) as compared to control (200 + 36 nmol/g wet tissue). Pretreatment with curcumin (100 and 200 mg/kg, i.p.) in separate groups significantly increased the latency of onset of seizures and decreased mortality as compared to the vehicle treated kainic acid group. Curcumin (100 and 200 mg/kg, i.p.) significantly prevented the increase in MDA levels. Conclusion: Curcumin may have potential antiepileptic properties and requires further investigation. 53.Protective effect of endothelin antagonist (Tak- 044) against neuronal injury-induced by middle cerebral artery occlusion in rats Briyal S, Gupta YK, Gulati A* Neuropharmacology Laboratory, Department of Phar- macology, All India Institute of Medical Sciences, New Delhi-110029, India; * Department of Biopharmaceutical Sciences (M/C 865), University of Illinois at Chicago, Chicago, IL 60612, USA. E-mail: [email protected] Objective: To investigate the effect of endothelin antagonist (Tak-044) against middle cerebral artery occlusion model of stroke in rats. Methods: Male Wistar rats were pretreated with Tak-044 (5 mg/kg, i.p.) for 6 days and were thereafter subjected to focal Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203

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corrected_file.pmdXXXVI Annual Conference ofXXXVI Annual Conference ofXXXVI Annual Conference ofXXXVI Annual Conference ofXXXVI Annual Conference of the Indian Pharmacological Societythe Indian Pharmacological Societythe Indian Pharmacological Societythe Indian Pharmacological Societythe Indian Pharmacological Society
New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003 New Delhi, December 5-7, 2003
Abstract of researAbstract of researAbstract of researAbstract of researAbstract of research papers (Part-II)ch papers (Part-II)ch papers (Part-II)ch papers (Part-II)ch papers (Part-II)
Abstracts
51.Beneficial effects of Zingiber officinale on experimentally-induced hyperlipidemia Sanjay KV, Goyal RK Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad. E-mail: [email protected]
Objective: To evaluate the beneficial effects of standardized
extracts of Zingiber officinale on elevated glycemic levels in
experimentally induced hyperlipidemia and its correlation with
5-HT actions of Zingiber officinale.
Methods: Wistar rats of either sex were divided into four
groups, Group I served as control, Group II were hyperlipidemic
rats which was induced by administering 10% fructose in
drinking water, Group III were hyperlipidemic rats treated with
methanolic extract of dried rhizomes of Zingiber officinale (250
mg/kg, b.w.), Group IV were hyperlipidemic rats treated with
ethyl acetate extract of dried rhizomes of Zingiber officinale
(250 mg/kg, b.w.) The drugs were administered orally for 3
weeks, at the end of which blood samples were analyzed for
serum glucose, insulin, cholesterol, triglycerides, HDL-
cholesterol, LDL and VLDL.
Results: There was a significant increase in fasting serum
glucose levels, serum insulin levels, serum lipid profile and
increased body weight gain in hyperlipidemic control rats as
compared to normal control rats. There was a significant
reduction in fasting serum glucose levels, serum lipid profile
and body weight and no changes in serum insulin levels in
methanolic extract treated rats as compared to hyperlipidemic
control rats. There was a significant reduction in fasting serum
lipid profile and body weight and no changes in serum glucose
and insulin levels in ethyl acetate extract treated rats as
compared to hyperlipidemic control rats.
Conclusion: Methanolic extract of Zingiber officinale was found
to have better activity in controlling the elevated glycemic levels
and elevated lipid profile in hyperlipidemic animals as compared
to ethyl acetate extract of Zingiber officinale.
P. C. DANDIYA PRIZE
52.Effect of curcumin on kainic acid-induced sei- zures and oxidative stress in rats Sharma M, Briyal S, Gupta YK
Department of Pharmacology, All India Institute of Medi- cal Sciences, New Delhi - 110029. E-mail: [email protected]
Objective: To study the effect of curcumin, a potent
polyphenolic antioxidant, against kainic acid-induced seizures,
and on a marker of oxidative stress in brain in rats.
Methods: Male Wistar rats were used for the study. Rats
were administered kainic acid at a dose 10 mg/kg, i.p.
Animals were then observed for behavioral changes
(grooming, rearing, hind limb scratching, urination,
defecation, wet dog shakes, jaw movements, salivation, head
nodding), incidence and latency of convulsions and mortality
over the total period of 4 h. The rats were thereafter
sacrificed for estimation of malondialdehyde (MDA).
Curcumin was administered 30 min before kainic acid at
doses of 100 and 200 mg/kg, i.p.
Results: Kainic acid-induced long-lasting seizures and
associated symptoms. The brain level of MDA was significantly
raised after kainic acid administration (536 + 44 nmol/g wet
tissue) as compared to control (200 + 36 nmol/g wet tissue).
Pretreatment with curcumin (100 and 200 mg/kg, i.p.) in
separate groups significantly increased the latency of onset of
seizures and decreased mortality as compared to the vehicle
treated kainic acid group. Curcumin (100 and 200 mg/kg, i.p.)
significantly prevented the increase in MDA levels.
Conclusion: Curcumin may have potential antiepileptic
properties and requires further investigation.
53.Protective effect of endothelin antagonist (Tak- 044) against neuronal injury-induced by middle cerebral artery occlusion in rats Briyal S, Gupta YK, Gulati A* Neuropharmacology Laboratory, Department of Phar- macology, All India Institute of Medical Sciences, New Delhi-110029, India; *Department of Biopharmaceutical Sciences (M/C 865), University of Illinois at Chicago, Chicago, IL 60612, USA. E-mail: [email protected]
Objective: To investigate the effect of endothelin antagonist
(Tak-044) against middle cerebral artery occlusion model of
stroke in rats.
Methods: Male Wistar rats were pretreated with Tak-044 (5
mg/kg, i.p.) for 6 days and were thereafter subjected to focal
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
193
intraluminal thread for two hours. Twenty-four hours later the
rats were subjected to motor performance tests and were
subsequently sacrificed for estimation of markers of oxidative
stress malondialdehyde (MDA), glutathione (GSH) and
superoxide dismutase (SOD). Control group received vehicle
and similar protocol was followed.
Results: Significant motor impairment, with elevated levels
of MDA (611.6 + 13.5 nmol/g wet tissue) was observed in the
vehicle-treated middle cerebral artery-occluded rats. Levels
of GSH (57.5 + 2.1 µg/g wet tissue) and SOD (7.8 + 0.27
units/mg protein) were significantly decreased in vehicle
treated MCAo rats. Treatment with Tak-044 for 6 days
prevented the motor impairment and decreased the raised
levels of MDA (475.6 + 13.8 nmol/g wet tissue) and increased
levels of GSH (100.8 + 4.9 µg/g wet tissue) and SOD (12.1 +
0.5 units/mg protein) significantly as compared to vehicle-
treated rats.
Tak-044 in focal ischemia most probably by virtue of its
antioxidant property.
54.Supersensitivity to angiotensin II involves functional coupling of AT1 receptor and dihydropyridine sensitive L- type calcium channel in diabetic rat thoracic aorta Arun KHS, Kaul CL, Ramarao P Cardiovascular and Receptorology Lab, Departments of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab - 160062. E-mail: [email protected]
Objective: To study the role of dihydropyridine sensitive L-
type calcium channels in supersensitivity to angiotensin II (Ang
II) in diabetic rat thoracic aorta.
Methods: Ang II, phenylepherine (PE) and potassium chloride
(KCl) cumulative concentration response curves in presence or
absence of various calcium channel blockers were determined
in endothelium intact (E+)/denuded (E-) thoracic aortic rings
isolated from 8 weeks post streptozotocin (STZ) induced diabetic
and age matched control male Sprague-Dawley rats.
Results: Supersensitivity (increased pD 2 ) to Ang II and PE but
not KCl was observed in aortic rings from diabetic over control
rats, while maximal contraction (E max
) was significantly
enhanced to all the three spasmogens in aortic rings from
diabetic rats. Nimodipine but not verapamil or diltizam dose
dependently blocked ang II and KCl contractions in a
noncompetitive manner. -Log IC 50
of nimodipine against Ang II
but not PE or KCl-induced contractions -was significantly lower
in aortic rings from diabetic than control rats. [3H] Ang II (AT 1
receptors) and [3H] PN200110 (L-type calcium channels)
saturation binding revealed significantly higher K d and B
max but
,
control rats.
Conclusion: Our results suggest enhanced functional coupling
of AT 1 receptors and DHP sensitive L-type calcium channels in
supersensitivity to Ang II in diabetic rat thoracic aorta.
POSTER PRESENTATION
55.Effects of ACE/NEP dual inhibitor on blood pressure, vascular dysfuntion and cardiac hypertrophy in DOCA - salt rats Hegde P, Datla SR, Alikunju S, Rajagopal S, Rao YK, Chakrabarti R Cardiovascular Group; Dr. Reddy’s Lab - Discovery Research, Miyapur, Hyderabad - 500049. E-mail: [email protected]
Objective: To compare the antihypertensive effect of
sampatrilat, enalapril and amlodipine in DOCA-salt (DS) rats.
Methods: In vitro ACE and NEP activity was measured in rat
lung and rabbit kidney cortex extracts. Hypertensive DS rats
were treated with the drugs for 3 weeks. Periodical BP, final
day plasma electrolytes, urine volume, vascular functions and
cardiac weights were estimated.
Results: Sampatrilat inhibited ACE and NEP with an IC 50
of 66
nM and 640 nM, enalaprilat inhibit ACE with an IC 50
of 1.1 nM.
amlodipine, but not with the enalapril. Only sampatrilat
treatment normalized the elevated plasma sodium levels
accompanied by 3 fold increase in urine output. DS rats showed
reduced aortic relaxation to acetylcholine as compared to
control rats. Treatment with sampatrilat, enalapril and
amlodipine normalized this abnormality. DS rats showed
significant (40 ± 5 %) increase in heart to body weight ratio.
Sampatrilat treatment significantly attenuated this ratio (53 ±
6 %), but enalapril and amlodipine failed to show significant
effect.
pressure, reno-vascular dysfunction and cardiac hypertrophy.
56.Effect of bromocriptine and pyridoxine in patients of premenstrual syndrome Gupta R, Kulshreshtha S, Sharma AL, Singh S, *Sharma P Departments of Pharmacology, Gynaecology and *Ob- stetrics, SNMC, Agra. E-mail: [email protected]
Objective: To study the efficacy of bromocriptine and pyridoxine
in patients of pre menstrual syndrome.
Methods: Patients with premenstrual syndrome (n=60) were
divided into three groups- control, bromocriptine and pyridoxine
group. The control group patients received placebo (ferrous
sulphate 100 mg orally). In bromocriptine group, patients
received bromocriptine 2.5 mg BD orally and in pyridoxine
group, patients were given pyridoxine 100 mg orally. Total
number of premenstrual symptoms were 20. Grading of
symptoms was done to obtain a premenstrual score. All patients
were treated for three consecutive menstrual cycles. Every
month their premenstrual score was reevaluated to compare
the score before and after treatment.
Results: In control group, there was no significant change in
the score after treatment. In bromocriptine group, significant
reduction in mean pre-menstrual score was observed after 3
Abstracts
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
194
months of treatment (P<0.001). 65% patients had side effects
like nausea, vomiting, constipation and dizziness. In pyridoxine
treated patients, mean pre-menstrual score was significantly
reduced after 2 months (P<0.001) and 3 months of treatment
(P<0.001). 20% patients had side effects i.e. nausea, diarrhea
and dizziness.
pyridoxine showed better efficacy and was better tolerated as
compared to bromocriptine.
57.Antiinflammatory activity of a herbal formulation: Tilwadi ghrita Ramteke PR, Charde MS, Fulzele SV, Satturwar PM, Dorle AK Department of Pharmaceutical Sciences, Nagpur University Campus, Nagpur - 440033. E-mail: [email protected]
Objective: To study the in vivo antiinflammatory activity of
herbal formulation, tilwadi ghrita.
as an active constituents. The present study investigate
antiinflammatory activity of tilwadi ghrita, a herbal formulation.
The effect of antiinflammatory action of experimental
formulation was studied by increasing vascular permeability
induced by carrageenan in rat hind paw edema model. Ibuprofen
was taken as the standard drug.
Results: The herbal formulation showed maximal
antiinflammatory effect in the carrageenan induced rat paw
edema. This formulation showed significant antiinflammatory
activity when compared with that of Ibuprofen as standard.
Conclusion: The results demonstrate that the test formulation
exhibit significant antiinflammatory activity against carrageenan
induced rat hind paw edema. The percentage of protection was
found to be effective as comparable to standard drug Ibuprofen.
58.Comparative evaluation of wound healing action of topical Tridax procumbens and VEGF in mice Yaduvanshi B, Mathur R, Velpandian T,* Gupta SK Departments of Pharmacology, *Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029. E-mail: [email protected]
Objective: To prepare a topical formulation of aqueous extract
of Tridax procumbens and compare its activity with VEGF in
murine model of wound healing.
Methods: Topical formulation of the lyophilized aqueous extract
of the fresh leaves of tridax (0.1% and 0.4%, w/w) and VEGF
(0.0001% w/w) was made. Two dermal wounds (4 mm id) were
punched on the depilated back of twenty male albino mice (25-
40 g) under pentobarbitone anesthesia (30 mg/kg, i.p.). The
mice were randomly divided into four groups (n=5) and treated
with 50 mg of either concentration of tridax or VEGF ointment
or just ointment base for four days. On the fifth day the mice
were sacrificed and assessed for (i) re-epithelization,
collagenation, vascularity and fibroblast by histopathological
examination of one wound (ii) collagen content in other healed
wound (iii) total leukocyte count and haemoglobin from blood
withdrawn by cardiac puncture.
Results: As compared to the control group (normal re-
epithelization, collagen-47.33 µg, TLC-17.20 X 106 /ml, Hb 10.9
g/dl), 0.1% ointment of tridax was less effective in healing the
dermal wound (normal re-epithilization, collagen-32.97 µg, TLC
3.2 X 106 /ml, Hb-10.8gm/dl). 0.4% ointment elicited
inflammatory response (ulcerous, edematous epithelium, TLC-
147.125 X 106 /ml, Hb-9.94 g/dl) along with poor wound healing
(collagen-15.70 µg). VEGF ointment was most effective in
healing the wound (normal epithilization, collagen-50.266 µg,
TLC-1263.6 x 106 ml, Hb- 10.5 gm/dl).
Conclusion: In contrast to few reports on the wound healing
potential of tridax, the present study showed, its topical aqueous
extract was less effective than VEGF in the doses investigated
(0.1 and 0.4 % w/w).
59.Standardization of four marketed preparations of Ashwagandha using HPLC with photodiode array detection Mathur R, Velpandian T,* Gupta SK Departments of Pharmacology, *Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110029. E-mail: [email protected]
Objective: To standardize four marketed preparations of
Ashwagandha using high performance liquid chromatography
with photodiode array detection.
Methods: Four Ashwagandha preparations (two tablets {A, B},
one powder {C} and one syrup {D}) were purchased from the
local Ayurvedic pharmacy. Coating of 2-3 tablets were scraped
off and triturated to give a powder from which 1 g was weighed.
3 ml of the liquid formulation was lyophilised and 1 g of
lyophilised powder weighed. Each 1 g of powder was refluxed
with 100 ml of methanol for 2 h. The refluxate was filtered,
concentrated and lyophilised. Standard withanoloid and
withaferin were purchased and used to set the standard curve
using following HPLC conditions: NovapakC18 column, 0.05 M
KH 2 PO
4 : ACN (6:4 v/v, 1 ml/min) mobile phase and detected
using photodiode array detection. The test samples were
injected and concentration of withanoloid and withaferin,
calculated from the standard curve plotted at 229 nm.
Results: As no claim had been made for withanoloid or “marker
compound” content in the label of the preparations, an
evaluation of the conformity with label was not possible and
we report the concentrations contained in the formulations.
There was a wide variation in the withanoloid (A-32.17µg/tab,
B-147.03 µg/tab, C-574.5 µg/g powder, D-14.4 µg/ml of syrup)
and withaferin (A-2.8 µg/tab, B-1.5 µg/tab, C-1.75 µg/gm of
powder, D-not detectable) concentration in the different
formulations.
detection and quantitation of “marker compound” to maintain
the chemical standards of polyherbal preparations.
60.Nonprotein toxins of snake venom and their neutralization by chemical antagonists
Abstracts
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
195
Gomes A, Archita S Department of Physiology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata - 700009. E-mail:[email protected]
Objective: To identify the nonprotein snake venom toxins and
their implications in snake envenomation.
Methods: (Ophiophagus hannah) venom was subjected to TLC
followed by column chromatography to isolate the nonprotein
toxins. Spectroscopy studies (UV, IR, NMR and MS),
Pharmacological and Neutralization studies were done in animal
models.
Results: Two nonprotein toxins (NPT I and II) from the Indian
King Cobra venom was isolated and purified through TLC and
silica gel column chromatography. Both the toxins were low
molecular weight (256 and 282 daltons) and are likely to be
long chain aliphatic compound. Both the toxins were lethal,
cardiotoxic and neurotoxic in nature. Polyvalent snake venom
antiserum failed to antagonize NPT I and II induced lethality in
mice. Anisic acid effectively antagonized lethal action of both
the toxins.
venom poisoning shall be discussed.
61.Effect of different doses of nimesulide on platelet aggregation in healthy volunteers Kotwani A, Kapoor U, Bhattacharjee J,* Gupta U Department of Pharmacology, Maulana Azad Medical College, New Delhi. *Department of Biochemistry, Lady Hardinge Medical College, New Delhi. E-mail: [email protected]
Objective: To find out the effect of low doses of nimesulide on
platelet aggregation and compare the effect with that of low
dose of aspirin.
and whose bleeding time and clotting time was normal. There
were five treatment groups (ten volunteers in each), four for
each dose of nimesulide and one for aspirin. Aspirin (Acetyl
salicylic acid) was given in the dose of 100 mg daily for 7 days
and nimesulide was given in the dose of 100, 50, 20 and 10 mg
daily for 7 days. Blood samples were collected, processed and
platelet aggregation was induced by adenosine diphosphate and
the effect of aspirin and different doses of nimesulide on platelet
aggregation was studied on day 1, 2, 3, 5 and 7.
Results: Aspirin significantly decreased platelet aggregation
on day 3, 5 and 7 (P<0.001), whereas nimesulide had no
significant effect on platelet aggregation at any of the given
four doses.
platelet aggregation even at sub therapeutic doses.
62.The effect of nutritional status on isoniazid pharmacokinetics in children suffering from tuberculosis Gupta D, Roy V, Sethi GR,* Mishra TK,** Singh B Department of Pharmacology, Maulana Azad Medical
College, New Delhi, *Department of Pediatrics, Lok Nayak Hospital, New Delhi, **Department of Biochem- istry, Maulana Azad Medical College, New Delhi - 110002. E-mail: [email protected]
Objective: To study the effect of nutritional status on isoniazid
pharmacokinetics in children suffering from tuberculosis.
Methods: A prospective, controlled, open label study was
conducted in twenty children (5–12 years of age) suffering from
tuberculosis. They were divided into two groups of 10 patients
each. Group I consisted of normal nourished children and Group
II undernourished children. Isoniazid was administered orally
(5 mg/kg) before breakfast. Serial venous blood samples were
collected at 0, 1, 2, 4, 6, 8 and 24 h. Isoniazid levels were
estimated spectrofluorometerically. Pharmacokinetic
parameters C max
constant and clearance were calculated.
Results: Area under time concentration curve for INH was
significantly higher in Group II (P<0.05). Volume of distribution
and plasma clearance decreased significantly (P<0.05) in
malnourished children. There was no statistically significant
difference in other parameters.
parameters of isoniazid in children.
63.Hepatoprotective potential of cimetidine in in- duced hepatotoxicity Bhupinder S, Usha G, Sarita A, Nita K, Devesh G Department of Pharmacology, Department of Biochem- istry and Department of Pathology. Maulana Azad Medi- cal College, New Delhi - 110002. E-mail: [email protected]
Objective: To study the hepatoprotective potential of cimetidine
in hepatotoxicity induced by isoniazid and rifampicin
combination in albino rabbits
Methods: Cimetidine (50 and 120 mg/kg, i.p.) was administered
for 7 days to two groups (n=6 in each) of rabbits. Hepatotoxicity
was induced in rabbits by administering isoniazid (50 mg/kg)
and also in combination with rifampicin (100 mg/kg) orally for
7days. On day 8, rabbits were sacrificed by cervical dislocation
and liver was removed for histopathological examination. Blood
samples were taken for assessment of liver injury by estimation
of liver function tests at baseline i.e. before administering the
drug and on day 8 i.e. after 7 days of drug administration.
Results: Rabbits administered with isoniazid and rifampicin
combination showed statistically significant increase in ALT and
AST levels (P=0.005, 0.02) after 7days of drug administration
compared to baseline. In the group administered with only
isoniazid, although levels of ALT and AST were raised but were
statistically not significant. No statistically significant increase
in levels of AST and ALT were observed in rabbits administered
with cimetidine in both high and low doses. However,
histopathological examination of liver showed necrosis in 16.6%
of rabbits in group administered with 50 mg/kg of cimetidine
but none of the rabbits in high dose cimetidine (120 mg/kg)
showed necrosis.
hepatotoxicity induced by isoniazid and rifampicin combination.
Abstracts
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
196
64.Effect of antiprogestins on steroids metabolizing enzymes-17βββββ OH steroid dehydrogenase and 20ααααα OH steroid dehydrogenase in rabbit uterus Vij U, Sharma K, Raj M, Kumar A Departments of Reproductive Biology and Anatomy, All India Institute of Medical Sciences, New Delhi - 110029, India. E-mail: [email protected]
Objective: To investigate the influence of progestin and
antiprogestin on the conversion of estradiol and progesterone
to their metabolites.
Methods: Rabbit was used as the animal model. The animals
were treated with different progestins, antiprogestins and
antiestrogens. The activity of steroid metabolizing enzymes 17β-
OH steroid dehydrogenase (OHSD) and 20α-OHSD was
estimated from the conversion of tritiated estradiol to estrone
and progesterone to 20α-OH progesterone respectively.
Results: The percent estrone formed was much higher under
the influence of progesterone and norgestrel. This suggested
that 17β-OHSD is a progestin dependent enzyme. RU486
antagonised its activity and percent estrone formed in rabbit
uterus treated with progesterone + RU486 was much lower
due to the influence of RU486 than in animals treated with
progesterone alone. RU486 alone reduced 17β -OHSD activities
still further. Estradiol + tamoxifen showed higher 17β-OHSD
activity than estrogen alone. 20α- OHSD activity under the
influence of different hormonal conditions was estimated from
the conversion of progesterone to 20α-OH progesterone. It was
much higher in progesterone treated group as compared with
estradiol treated group. 20α-OHSD is progesterone dependent
and increases under the influence of progesterone leading to
higher biotransformation of progesterone to 20α-OH
progesterone. However, RU486 depressed the effect of
progesterone thereby decreasing the biotransformation of
progesterone to 20α-OH progesterone.
of progesterone is highest under the influence of estrogen while
under the effect of progesterone more of progesterone remained
unconverted. RU486 facilitated biotransformation decreasing
the biologically active amount of progesterone in uterus.
65.Effect of mitomycin-C on alpha chymotrypsin induced glaucoma in rabbits Syed AA, Jha MC,* Haque SE, Pillai KK Department of Pharmacology, Faculty of Pharmacy,* Majeedia Hospital, Jamia Hamdard (Hamdard Univer- sity) Hamdard Nagar, New Delhi - 110062. E-mail: [email protected]
Objective: To study the effect of mitomycin C on glaucoma in
rabbits.
Methods: Normal healthy, albino rabbits of either sex weighing
1.5-2 kg were divided in to five groups. Five animals were
used in each group. Group I: Normal Control, Group ll: α-
chymotrypsin I.C. Group lll: α-chymotrypsin I.C.+ 0.1 ml of 4
µg/ml of mitomycin C I.C, Group lV: α-chymotrypsin I.C.+
0.1 ml of 8 µg/ml of mitomycin C I.C, Group V: α-chymotrypsin
I.C.+Timolol maleate (0.5%) eye drops, the intraocular
pressure (IOP) was recorded using Schiotz tonometer for each
rabbit of group 1 to 5 for 30 days. The in vitro assay of
cholinesterase enzymes was also done after the drug
treatment.
Results: The IOP was raised in the alpha chymotrypsin treated
group as compared to normal group measured with 10 gm wt
with Schiotz tonometer. The normal group has a IOP of 16.95
± 0.53 mm Hg and the toxic group had IOP 37.55 ± 0.95 mm
Hg. The mitomycin C treated groups showed a reduction in IOP
with both the concentration 4 µg/ml and 8 µg/ml (14.63 ±
1.96 and 14.95 ± 0.74 mm Hg) respectively. The timolol eye
drops treated animals showed less reduction in IOP (28.35 ±
1.02 mm Hg) as compared to the mitomycin C treated groups.
In the in vitro assay of cholinesterase enzymes physostigmine
produced a dose dependent inhibition of the enzyme
cholinesterases, while mitomycin C produced a mild inhibition
of the enzymes.
offers protection against alpha chymotrypsin induced glaucoma
in rabbits.
66.CYP2D6 phenotyping in North Indian subjects from Delhi Ahmed T,* Malik H,** Kakkar S,*** Varshney B,*** Singh TP,*** Rao MVS,*** Sagar J,*** Gautam A,*** Paliwal JK,*** Pillai KK,** Sharma PL* Departments of Pharmaceutical *Medicine and **Phar- macology, Faculty of Pharmacy, Jamia Hamdard, New Delhi - 110062. ***Metabolism and Pharmacokinetics Department, Ranbaxy Research Laboratories, Gurgaon - 122001.
Objective: To evaluate the percentage of poor and extensive
metabolisers in North Indian subjects from Delhi and at the
same time find a suitable bioanalytical method for CYP2D6
phenotying.
Methods: In this study, 75 (40 males, 35 female) healthy human
adult Indian subjects were phenotyped with respect to their
ability to metabolize dextromethorphan to dextorphan. Subjects
were requested to take 30 mg of dextromethorphan. Urine was
collected at 9.5 h after dosing. Dextromethorphan and
dextorphan excreted in urine were quantitated using a LC-MS/
MS (Liquid chromatography Mass Spectrometry) method. A
thermo hypersil column was used with a mobile phase
composition of ammonium formate:acetonitrile (15:85). Urine
samples were processed by using solid phase extraction
procedure. Standard curves from 0.01-10 µg/ml were
developed.
Results: The antimode value of 0.3 was calculated by plotting
a frequency histogram of the log metabolic ratios
(dextromethorphan/dextorphan). The population in this study
showed bimodal distribution with respect to metabolism of
dextromethorphan. Of the 75 subjects, 2 were found to be poor
metabolizers.
Conclusion: It can be inferred from this study that the
frequency of occurrence of poor metabolizers in North Indian
subjects from Delhi is 2.6%. The incidence of poor metabolizers
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67.Influence of grape juice and orange juice on pharmacokinetics and pharmacodynamics of diltiazem Karim S, Ahmed T,* Sajid M,** Monif T,*** Saha N, Pillai KK** Medical Services and Clinical Research Department, Dabur Research Foundation, Sahibabad, Ghaziabad - 201010. Departments of *Pharmaceutical Medicine and **Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi - 110062. ***Department of Clinical Phar- macology and Pharmacokinetics, Ranbaxy Research Laboratories, Gurgaon - 122001.
Objective: To study the effect of grape juice and orange juice
on pharmacokinetics (PK) and pharmacodynamics (PD) of
diltiazem in healthy volunteers.
of 12 healthy, adult, male human volunteers received a single
oral dose of Diltiazem 180 mg extended release capsule on
three different occasions: with 200 ml of water, with 200 ml of
grape juice and with 200 ml of orange juice. A wash out period
of seven days was kept between each study period. Serial blood
samples were collected till 24 h post dose and assayed for
diltiazem by specific HPLC method. Blood Pressure (BP) and
ECG measurements were done at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16
and 24 h post dose.
Results: There was no significant change in heart rate, BP or
any of the mean pharmacokinetic parameter i.e. C max
, T max
with water.
Conclusion: It can be concluded that there is no significant
influence of grape juice or orange juice on the PK and PD of
diltiazem. Hence there is no need for dose adjustment and no
risk of dysrrythmias.
68.Effect of lacidipine in streptozotocin-induced diabetic neuropathy in rats Suruchi A, Singh J, Sood S, Lal H Departments of Pharmacology, Physiology and Biochemistry, PGIMS, Rohtak. E-mail: [email protected]
Objective: To evaluate preventive effect of lacidipine (aDHP
type CCB) on motor nerve conduction velocity (MNCV) and
nociception in streptozotocin (STZ) diabetic rats.
Methods: In albino rats (250-300 g) diabetic neuropathy was
produced by injecting STZ (50 mg/kg, i.v.). MNCV was
determined in sciatic posterior tibial conducting system of ether
anesthetized animals by EMG. Body weight, blood/urine sugar
levels. Urine volume and nociception were studied at 2 week
intervals. Protocol for preventive study was (n=10) in each
group) Group I: Control, Group II: STZ (50 mg/kg, i.v.) single
injection, Group III: Lacidipine (1 mg/kg, i.p., daily) 5 days prior
to STZ and continued for 12 weeks + STZ, Group IV: Insulin (4
U/kg, s.c. bid) +STZ.
preventing diabetic complications including neuropathic
changes in rats. MNCV in diabetic rats was significantly
reduced af ter 6 weeks of STZ. MNCV was markedly
improved in lacidipine pretreated group. Antinociceptive
effect of lacidipine was obser ved in diabetic rats.
Lacidipine had no significant effect on body weight, blood/
urine sugar levels.
associated with STZ diabetes in rats.
69. Plasma cortisol level as a predictor of response to standard treatment in acute attack of bronchial asthma in pediatric age group? Upender K, Girish T, Mittal SK,* Sharma VK,** Uma T Department of Pharmacology, Maulana Azad Medical College, New Delhi - 110002. *Department of Pediatrics, Lok Nayak Hospital, New Delhi - 110002. **Department of Microbiology, Maulana Azad Medical College, New Delhi - 110002.
Objective: To correlate the initial plasma cortisol level and
severity of asthma attack and the response to standard
treatment for acute exacerbation of bronchial asthma in
pediatric age group.
patients included in the present study was on steroids. Venous
blood sample for determination of plasma cortisol level was
taken and patients were nebulized with salbutamol every 20
min, upto 1 h. The patients who failed to respond even after
three nebulizations were labeled as nonresponders and repeat
venous blood sample for plasma cortisol estimation was taken
before giving injection hydrocortisone. In responders sample
was taken 1hour after last nebulization.
Results: The mean plasma cortisol value at the time of
admission in responders (12.42 ± 1.9 µg/dl) was not found to
be significantly different from that in non-responders (13.1 ±
2.74 µg/dl). Children with severe attack of asthma had
significantly higher plasma cortisol levels both at the time of
admission (P=0.03) and at the end of study (P=0.001), as
compared to patients with moderate attack. The mean
percentage change in plasma cortisol levels in nonresponders
was an increase of 80.65 ± 60.64%, whereas, in responders it
decreased by 16.49 ± 21.7% and this difference was statistically
significant (P<0.05).
normally in asthmatic patients, producing a rise in cortisol levels
corresponding to degree of stress; and from initial cortisol level
alone, it cannot be predicted, whether a patient will respond to
β-2 agonist (salbutamol) nebulization alone or will require
exogenous corticosteroids.
70.Effects of antioxidants in stress-induced neurobehavioral changes in rats Pal R, Masood A, Banerjee BD, Vijayan VK, Ray A
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198
Departments of Pharmacology and Clinical Research Centre, V. P. Chest Institute, University of Delhi and Department of Biochemistry UCMS and GTB Hospital, Delhi. E-mail: [email protected]
Objective: To evaluate the possible role of free radicals in
stress-induced neurobehavioural changes in rats.
Methods: The male Wistar rats (150-200 g) were treated with
L-ascorbic acid (100 mg/kg), alpha tocopherol (30 mg/kg), alone
and in combination, whereas the control group received
appropriate vehicle. All the treatment groups were exposed to
restraint stress (RS), and their behaviour in the elevated plus
maze and open field tests were assessed.
Results: In the elevated plus maze test, RS reduced open entries
and time spent as compared to no RS controls. L-Ascorbic acid
and alpha tocopherol increased the open arm entries and time
spent as compared to the RS group, the combination therapy
being most effective. In the open-field test, RS increased entry
latency and decreased ambulation and rearings. In the L-
Ascorbic Acid and alpha tocopherol treated groups, the changes
were reversed by differential degrees.
Conclusion: The results are suggestive of possible involvement
of role of free radicals in stress-induced neurobehavioral
changes.
71.Exploring antiinflammatory and wound healing effects of Piper betle leaf extract in experimental animal models Rakes R, Chattopadhyay S, Bhattacharyya D, Bandyopadhyay SK, Chatterjee U* Departments of Pharmacology and *Pathology, Institute of Postgraduate Medical Education and Research [IPGME&R], Kolkata - 700020. E-mail: [email protected]
Objective: To investigate the antiinflammatory and wound
healing profile of methanol extract of Piper betle leaf in
experimental animal models.
evaluated in rats in the following models: a) Carrageenan and
dextran induced hind paw edema (acute inflammation) b) Cotton
pellet granuloma (subacute inflammation) and c) Freund’s
adjuvant induced arthritis (chronic inflammation). Piper betle
was administered orally in a dose of 300 mg/kg and oral
indomethacin (10 mg/kg) was the standard for comparison.
The topical wound healing profile was assessed on 4 mm punch
wounds inflicted in rats, in comparison to povidone iodine.
Parameters evaluated were a) time taken to complete healing
b) protein content of wound tissue and c) demonstration of
epithelialization and collagenesis.
Results: In carrageenan induced rat paw edema model,
percentage inhibition of paw volume, after 3 h, in Piper betle
treated group was 24.35% (P<0.05), a figure comparable to
indomethacin 32.11% (P<0.05). Similar results were obtained
with dextran. Piper betle reduced dry weight of cotton pellet
granuloma by 28.90% (P<0.05) which also compared well with
indomethacin 44.41% (P<0.001). In the model of chronic
inflammation, primary lesion inhibition by Piper betle was 9.61%
(P<0.05) while secondary lesions were inhibited by 8.23%
(P>0.05). Time taken for complete healing of wound was 10.33
± 0.11 days, compared to 9.50 ± 0.24 days with povidone
iodine. Regarding wound healing, total protein, the indicator of
cytokinesis, was 22.17 mg/g of tissue (P<0.05) in Piper betle
group, which was comparable to povidone iodine 27.53 mg/g
(P<0.005). Histopathology of wound tissue on day 7 revealed
definite synthesis of collagen in both groups. However, neither
showed significant synthesis of epithelial tissue that was
abundant in control group.
primary lesions of chronic inflammation in standard animal
models, to an extent comparable to indomethacin. It also
promotes wound healing though to a lesser extent than povidone
iodine.
72.Evaluation of immunomodulatory properties of tea decoction Chatterjee C, Mandal G, Bandyopadhyay S,* Mandal C,* Chatterjee M,* Bhattacharyaa D Department of Pharmacology, Institute of Postgradu- ate Medical Education and Research [IPGME&R], Kolkata - 700020. *Department of Immunobiology, Indian Institute of Chemical Biology [IICB], Kolkata - 700032. E-mail: [email protected]
Objective: To determine the antiinflammatory and
immunomodulatory properties of tea decoction in experimental
animals.
were screened in a Freund’s adjuvant-induced model of chronic
inflammation. Subsequently, the immunomodulatory activity of
tea was evaluated by examining the cell-mediated response by
the blastogenesis assay and delayed type hypersensitivity
response; the humoral response was evaluated by the
hemagglutination assay and hemolytic plaque assay.
Results: In the immunologically mediated chronic inflammatory
model of Freund’s adjuvant-induced arthritis, tea decoction (10
and 20%) showed a profound dose dependent antiinflammatory
activity in both the primary and secondary phase, thus reflecting
its activity on acute and immunologically mediated inflammation
respectively. This was corroborated by an enhanced cell
mediated response evident by a marked proliferation of
peripheral blood mononuclear cells.
Conclusion: Tea possesses antiinflammatory and
immunomodulatory activity in experimental animals.
73.Efficacy and safety of the controlled release formulation of erythromycin in respiratory tract infections Badyal DK, Dhanoa J,* Dadhich AP Departments of Pharmacology and *Medicine, Chris- tian Medical College, Ludhiana - 141008. E-mail: [email protected]
Objective: To evaluate the efficacy and safety of erythromycin-
CR (controlled release) in respiratory tract infections.
Methods: The study was conducted in 44 patients suffering
from mild to moderate upper respiratory tract infections.
Patients who fulfilled inclusion and exclusion criteria were
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enrolled after they signed a written informed consent. Patients
were given erythromycin-CR tablet 500 mg twice a day for 5-7
days. Efficacy was evaluated based on clinical assessment.
Safety evaluation was based on treatment emergent adverse
effects and laboratory investigations.
signs and symptoms at post therapy visit. A satisfactory clinical
response (complete cure and improvement) was achieved in
all the patients (100%). Erythromycin was well tolerated with a
low incidence of drug related adverse events.
Conclusion: The findings of this study indicate that
erythromycin-CR is a suitable option for the treatment of
patients with mild to moderate upper respiratory tract
infections.
74. Role of Delphinium denudatum Wall. in heroin addicted patient : Case Reports Rahman SZ, Khan RA, Kumar A Department of Pharmacology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh - 202002. E-mail: [email protected]
Objective: To verify the efficacy and beneficial role of
Delphinium denudatum Wall. (Jadwar, family; Ranunculaceae)
in the heroin dependent patients.
Methods: A pilot clinical trial was carried out in three patients
to verify the efficacy of Jadwar and its beneficial role in heroin
dependent patients. Detailed in-take record before and after
drug administration was taken according to the planned
protocol.
withdrawal symptoms.
aggregate scores for all parameters in morphine withdrawal
syndrome and may be studied further as an alternative remedy
in morphine de-addiction.
75.Spontaneous reporting of adverse drug reactions in Mumbai Patwardhan GA, Kulkarni RA, Shinde VJ, Thatte UM Department of Clinical Pharmacology, TNMC and BYL Nair Ch. Hospital. E-mail: [email protected]
Objective: To study and encourage spontaneous reporting of
adverse drug reactions (ADRs) among practitioners at a tertiary
care hospital and in the private sector.
Methods: ADR report forms were prepared as per the WHO
format and distributed to all the clinical departments within
the hospital and 250 private practitioners in order to encourage
reporting since July 2002. Timely reminders were also given.
ADRs occurring with herbal medications were also
documented.
Results: 138 ADRs have been reported in the last one year. Of
these, 34% of the reports were obtained from the hospital and
66% from private practitioners. Four of these ADRs resulted in
death and 19 resulted in hospitalization. Cutaneous reactions
(54%), gastrointestinal disturbances (13%) and ADRs affecting
the nervous system (13%) made up a large proportion of
reported ADRs. Antimicrobial agents were responsible for
51.44% of the events. Drugs acting on CNS (25%) and
antineoplastics were the other drugs implicated. 20 cases of
ADRs due to herbal drugs were also reported.
Conclusion: Spontaneous reporting of ADRs is an important
tool to assess drug safety.
76.Evaluation of in vitro effect of selected food items on platelet aggregation Kalekar SA, Deshmukh AS, Thatte NM, Rao SA, Kulkarni RA, Thatte UM Department of Clinical Pharmacology, TN Medical Col- lege and BYL Nair Ch. Hospital, Mumbai Central, Mumbai. E-mail: [email protected]
Objective: To evaluate whether common food items like orange,
sweet lime, cucumber and lemon have antiplatelet effects.
Methods: 16 healthy male volunteers aged between 18-23 years
fulfilling the eligibility criteria were recruited into the study.
Platelets harvested from these volunteers were initially
subjected to a viability assay with different concentrations of
the juices of the selected agents. Concentrations not affecting
platelet viability were then selected for platelet aggregation
study, which was performed by turbidimetric method of Born
using automated platelet aggregocorder. Maximum platelet
aggregation induced by ADP (5 µM) was recorded and
percentage inhibition of aggregation was calculated. Distilled
water was the vehicle control and 0.05 mg/ml aspirin acted as
positive control.
Results: All the test agents showed varying degree of inhibition
of platelet aggregation. Maximal effect was observed with
undiluted cucumber (37.65 ± 13.86 %), which was comparable
to aspirin (35.17 ± 9.39 %). When given in combination with
aspirin, there was enhanced inhibition of platelet aggregation,
indicating potentiation of antiplatelet effect of aspirin by
cucumber. This is true only for n = 2 cases.
Conclusion: The above study demonstrates that common food
items like cucumber exert antiplatelet activity, which may be
due to the presence of flavonoids.
77.Development of modern techniques for the quality control of bhasmas Parab SM, Uchil DA,* Navalakhe RM, Bhalerao SS, Deshmukh AS, Kulkarni RA, Thatte UM Department of Clinical Pharmacology, TN Medical Col- lege and BYL Nair Ch. Hospital, Mumbai Central, Mumbai, *Department of Pharmacology, KEM Hospi- tal, Mumbai. E-mail: [email protected]
Objective: To confirm the quality of Suvarnabhasma, a
commonly used formulation, prepared by the Ayurvedic
methodology using modern techniques.
Ayurvedic processes and at different stages of preparation was
procured from a reputed pharmacy. Process I had 12 stages
while process II had 6 stages of preparation. All samples were
subjected to physicochemical characterisation such as
a) particle size distribution, b) Inductively coupled plasma-
Atomic emission spectroscopy, c) Thermal analysis d) X-ray
diffraction pattern. The samples were also subjected to
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200
using Suvarnabhasma prepared by process II also demonstrated
no toxicity as compared to that prepared from using process I.
Conclusion: Thus, it can be concluded that Suvarnabhasma
prepared by process II conformed to Ayurvedic standards of
quality and was a safer product. The study thus demonstrates
that modern techniques can be used to validate Ayurvedic
quality control parameters so as to promote acceptability from
modern pharmaceutical viewpoint.
ORAL PRESENTATION
78.Botulinum toxin type A in prophylactic treatment of migraine Sangeeta S,1 Anand KS,2 Atul P,3 Singh MM,4
Kiran B5
Departments of 1Neuropsychopharmacology and 3,5Neurology, Institute of Human Behaviour and Allied Sciences, 2Ram Manohar Lohia Hospital, 4Departments of Preventive and Social Medicine, Maulana Azad Medical College, New Delhi. E-mail: [email protected]
Objective: To assess the efficacy and safety of Botulinum toxin
type A (BTX-A) as prophylactic agent in patients with migraine.
Methods: A randomised, double blind, vehicle-controlled,
parallel group study was conducted in 32 patients with a history
of 2 to 8 migraine attacks per month. The patients were
randomised to receive single administrations of 50-U BTX-A or
vehicle, injected into multiple sites of pericranial muscles at
the same visit. Patients kept daily diaries in which they recorded
outcome measures like migraine frequency, migraine severity,
and the occurrence of migraine-associated symptoms. Patients
graded symptoms on a 4 point scale ranging from grade 0 to 3
before and upto 3 months after treatment. The assessments
were made at 0, 1, and 3 months. The primary efficacy
parameters included frequency of headache, number of
headaches resolved (grade 3/2 to grade 0) and alleviation of
other accompanying symptoms of migraine. The supplementary
endpoint included improvement in quality of life (QOL).
Results: After 3 months in the study group, the mean number
of headache days per month in the study group decreased from
4-5 moderate-to-severe headaches to 1-2 (P<0.05) compared
to 3 to 4 in the control group. About 75% of patients reported
complete relief to mild headache (grade 0-1) with BTX-A after
3 months. Patient’s QOL parameters like energy/vitality, and
feelings and concerns about the treatment had shown
considerable improvement. However, normal day-to-day work
functioning and social interactions deteriorated. No adverse
effects were reported in both groups.
Conclusion: Pericranial injection of 50-U BTX-A showed good
efficacy and tolerability but is an expensive prophylactic therapy
and requires expertise in administering the drug.
79.Characterization of the acute inflammatory reactions stimulated by carrageenan and lipopolysaccharide
Bhargavi V, Suresh J, Chakrabarti R, Joshi VD Inflammation Biology, Discovery Research, Dr.Reddy’s Laboratories Ltd. Bollaram Road, Miyapur, Hyderabad - 500049. E-mail: [email protected]
Objective: To identify a suitable animal model for the screening
of cytokine modulating antiinflammatory agents.
Methods: In vitro experiments were performed on rat
peritoneal exudate cells for the expression of tumour necrosis
factor (TNFα) and interleukins (IL-1β, IL-6) with
lipopolysaccharide (LPS) treatment and their inhibition with
standard drugs was studied. Immunofluorescence studies were
performed for assessing the inflammation pathway induced by
LPS. In vivo experiments were performed in Wistar rats by LPS
induced paw edema model.
Results: Stimulation of isolated rat peritoneal exudate cells
(PEC) with 10 ng/mL LPS induced 3.04 + 0.2 ng/mL IL6 and
1.03 + 0.09 ng/mL TNFα but carrageenan (CAR) did not. Atleast
100 mg/mL CAR was necessary for detection of IL6 (2.03 +
0.1 ng/mL) and TNFα (0.6 + 0.09 ng/mL) in PEC. In vitro
experiment results were obtained from pooled PEC of 3 rats.
Subplantar administration of LPS in rats induced inflammatory
paw edema like CAR. LPS but not CAR induced 2.8 + 0.6 ng/
mL TNFα and 2.9 + 0.5 ng/mL IL-6 in serum at 1 and 3 h
respectively, which restored to basal levels by 5 h. LPS-induced
serum TNFα levels closely paralleled paw swelling and their
reduction by pentoxifylline correlated with inhibition of
inflammation.
and the in vivo model successfully assesses the cytokine
inhibitory activity of standard drugs. Hence LPS induced paw
edema model is a functional model for identification of cytokine
modulating antiinflammatory agents.
80.Role of nitric oxide in NIDDM with special refer- ence to hypertension Srinivasan BP, Gaurav B Department of Pharmacology, Delhi Institute of Phar- maceutical Sciences and Research (Previously: College of Pharmacy), New Delhi - 110017. E-mail: [email protected]
Objective: To determine the role of NO in diabetes and diabetic
complications with particular focus on hypertension in STZ
induced NIDDM model in rats.
Methods: Two days old neo-natal wistar rats were injected
with STZ (90 mg/kg) and allowed for 6 weeks to become
diabetic. Diabetic and control groups were then treated with L-
Arginine (1 g/l in drinking water), aminoguanidine (100 mg/
kg), metformin (500 mg/kg), rosiglitazone (50 µmol/kg), ramipril
(0.5 mg/kg) and amlodipine (3 mg/kg). The effect of each of
these drugs on elevated blood pressure, blood glucose, OGTT,
lipid profile, plasma nitrate and islet nitrite levels was
determined.
tolerance, significant reduction in (SBP), (DBP) and (MBP), a
significant increase in plasma nitrate and islet nitrite levels
and insignificant increase in HDL cholesterol levels.
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and plasma lipid profile. Metformin was observed to decrease
SBP, DBP and MBP, significantly increased plasma nitrate and
nitrite levels; increase glucose tolerance and significantly
increased HDL cholesterol levels. Rosiglitazone was found to
significantly reduce the SBP, DBP and MBP, improve glucose
tolerance, significantly enhanced plasma nitrate and nitrite
levels and increased the total cholesterol as well as HDL.
Cholesterol levels significantly. Ramipril treatment to diabetic
rats improved glucose tolerance, decreased glucose levels,
significantly decreased SBP, DBP and MBP, enhanced nitrate
and islet nitrite levels and significantly increased the HDL
cholesterol levels. The increase of total cholesterol and TG levels
was found insignificant. Amlodipine significantly decreased SBP,
DBP and MBP, significantly reduced serum TG levels, and the
effect on glucose tolerance, plasma nitrate and nitrite levels
was found to be insignificant.
Conclusion: L-Arginine, metformin, rosiglitazone, ramipril
and amlodipine have a significant protective role in diabetic
hypertension. Aminoguanidine has a mixed role on other
parameters though it has no signif icant role in
hypertension.
81.Snake bite treatment : A challenge to herbal antagonists Gomes A Laboratory of Toxinology and Experimental Pharma- codynamics, Department of Physiology, University of Calcutta, 92, A.P.C. Road, Kolkata - 700009. E-mail: [email protected]
Objective: To identify herbal antagonists from Indian medicinal
plants for snake venom neutralization in experimental animals.
Methods: Root extracts of Hemidesmus indicus (Sarsaparilla)
and Pluchea indica (Kukrunda) was subjected to column
chromatography to isolate the snake venom neutralizing factor.
Structural elucidation (UV, IR, NMR and EIMS), snake venom
neutralization, mechanism of venom neutralization by the pure
compounds were done in animal models.
Results: Two pure compounds (2-OH-4-MeO-benzoic acid and
lupeol acatate) were identified from the root extract of H. indicus
and one compound (β-sitosterol) from the root extract of P.
indica having snake venom neutralization properties (lethal,
haemorrhage, oedema, PLA 2 , cardiotoxic and neurotoxic). These
herbal antagonists potentiated the action of the polyvalent snake
venom antiserum in experimental animals. These compounds
also showed antioxidant property through lipid peroxidation
and SOD activity.
activity may be an alternative therapeutic measure against
snake bite in the near future.
82.Topical phenytoin suspension in the treatment of leprosy tropic ulcers: A randomised double blind pilot study Bhatia A, Nanda S,* Gupta U, Gupta S,* Reddy BSN*
Departments of Pharmacology and *Dermatology, Maulana Azad Medical College and LN Hospital, New Delhi - 110002. E-mail: [email protected]
Objective: To evaluate and compare two strengths of topical
phenytoin sodium suspension (2% and 4%) with normal saline
in the healing of acute trophic ulcers in leprosy patients.
Methods: It was a prospective, parallel, double-blind
randomized study. 45 in-patients with acute trophic ulcers of
leprosy were randomized to receive 2%, 4% or normal saline
dressing on their ulcers once daily for 4 weeks. Parameters
such as reduction in wound surface area, bacterial culture,
appearance of healthy granulation tissue, cessation of discharge,
overall grading of clinical healing and safety were assessed at
weekly intervals.
Results: Wound area reduction was greater in 2% and 4%
phenytoin groups compared to normal saline group (P<0.001).
Appearance of healthy granulation tissue and cessation of
discharge was also observed earlier in the two phenytoin groups.
At the end of 4 weeks, 11 ulcers each had healed completely in
2% and 4% phenytoin groups versus none in the control group.
However, there were no statistical differences between the 2%
and 4% phenytoin groups. No side effects were reported by any
patient.
and cheap therapeutic option for the healing of trophic ulcers
in leprosy patients.
83.Correlation between alteration in trace elements, psychomotor performance and learned memory on long term tobacco use: An experimental study Farida A, Anil K, Singhal KC Department of Pharmacology, J.N. Medical College, A.M.U. Aligarh - 202002.
Objective: To study the correlation between long term tobacco
use, alternations in serum zinc copper levels and its effect on
psychomotor performance and learned memory.
Methods: The effect of chronic self-administration of tobacco
on serum trace-elements (Zn, Cu), forced locomotor activity
and learned memory was studied in Charles-foster rats of either
sex weighing between 150-250 g fed with chow diet ad lib.
Tobacco was given with sweetened drinking water in 3 different
doses of 50, 100 and 200 mg/kg for 12 weeks. Separate identical
control groups were provided with simple sweetened drinking
water. Weekly blood samples were collected and estimated by
Atomic Absorption Spectrophotometer for serum Zn and Cu
levels. Learned memory was tested on Hebbs-William’s T-maze
and forced locomotor activity on Rota-Rod.
Results: A significant decrease (P<0.05) in the serum Zn levels
and an increase (P<0.05) in the serum Cu levels were observed
in tobacco treated groups as compared to controls after 4
weeks. A significant reduction (P<0.01) in Maze traversing time
and Forced locomotor activity was also observed in tobacco
treated rats.
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memory.
84.Sub-chronic effect of alfa-cypermethrin in rats Manna S, Bhattacharyya D, Mandal TK* Department of Pharmacology, University College of medicine, Calcutta University, Kolkata -700020. *Departments of Pharmacology and Toxicology, WBUAFS, Belgachia, Kolkata - 700037. E-mail: [email protected]
Objective: To investigate the sub-chronic effect of alfa-
cypermethrin (α-CP) on antioxidant status, cytochromeP 450
content in liver, tissue residual concentration of α-CP, and brain
GABA level in rats.
dissolved in dimethyl sulfoxide (DMSO-1 ml) was given daily
orally for 60 days at 1/10LD 50
(14.5 mg/kg) after determination
of oral LD 50
CytochromeP 450
tissue residual concentration of α-CP, and brain GABA level
were studied.
glycogen level significantly in liver. It increased the
malondialdehyde (MDA) level, while decreased the activities of
catalase (CAT) and superoxide dismutase (SOD). α-CP was
present in considerable amount in tissues. The GABA level in
cerebellum and whole brain (without cerebellum) was reduced
significantly.
alters the antioxidant status. The reduction in brain GABA level
may be the possible mechanism of action of pyrethroids in
mammals. So injudicious use of α-CP may cause health hazards
in human as well as animal health.
85.A comparative study of ramipril plus amlodipine versus ramipril plus hydrochlorothiazide in mild to moderate essential hypertension Ghosh A, Hazra A, Kar AK* Department of Pharmacology, Institute of Postgradu- ate Medical Education and Research [IPGME&R], Kolkata - 700020. *Department of Cardiology, IPGME&R and SSKM Hospitals, Kolkata - 700020. E-mail: [email protected]
Objective: To compare the antihypertensive efficacy and
tolerability of ramipril plus amlodipine with ramipril plus
hydrochlorothiazide in Indian subjects with mild to moderate
essential hypertension (as per JNC VI criteria).
Methods: A prospective, single blind, randomized controlled
trial, with two parallel treatment groups as above, was carried
out at the cardiology OPD of SSKM Hospitals, Kolkata. Subjects
included consenting adult men between 18 and 75 years, as
well as women of similar age not having any imminent possibility
of pregnancy, with sitting resting diastolic blood pressure (DBP)
between 90 - 110 mmHg. Major exclusion criteria were
secondary, severe or complicated hypertension, serious
systemic disease and concomitant use of confounding
medication. Eligible subjects were randomized to receive either
ramipril 2.5 mg and amlodipine 2.5 mg, one of each, orally,
once daily, or ramipril 2.5 mg and hydrochlorothiazide 12.5
mg, one of each. They were followed up every 2 weeks for 8
weeks. BP was recorded (24 h after a dose of study drug) at
each visit. In subjects not responding adequately (i.e. DBP >
90 mmHg), doses were doubled at 4 weeks. Routine blood tests
and ECG were done at screening and at study end. Adverse
events reported spontaneously or detected at clinical
examination, or gathered from trial diaries, were recorded to
assess safety, all subjects enrolled being evaluated. Efficacy
analyses was restricted to subjects reporting for at least one
follow-up visit.
Results: There were 15 evaluable patients in the first group
and 12 in the latter. Mean reductions in SBP and DBP were
11.8 and 8.47 mmHg respectively (P<0.001) in the first group
and 7.67 (P<0.01) and 9.5 mmHg (P<0.001) respectively in
the latter. Between group differences were not significant.
Adverse events were generally mild and similar in both groups,
no withdrawal being attributable to them. Tolerability of both
was also excellent with respect to biochemical parameters.
Conclusion: Ramipril combined with amlodipine is a well-
tolerated regimen, comparable in efficacy and safety to ramipril
plus hydrochlorothiazide, in the treatment of mild to moderate
essential hypertension.
86.Correlation of salivary with serum concentrations of antiepileptic drugs Shinde VJ, Kulkarni RA, Goyal P, Parab SM, Kule PG, Thatte UM Department of Clinical Pharmacology, TNMC and BYL Nair Ch. Hospital, Mumbai Central, Mumbai - 400008. E-mail: [email protected]
Objective: To correlate the salivary and serum
concentrations of commonly used antiepileptic drugs like
phenytoin sodium (EPT), phenobarbitone (PBT) and
carbamazepine (CBZ).
Methods: 150 patients of either sex between 12-65 years,
attending the therapeutic drug monitoring (TDM) OPD for drug
analysis were included in the study. Recruited patients were
those receiving the same dose of one or more AED(s) for at
least one month and compliant with therapy. Both blood and
unstimulated saliva were collected for drug estimation which
was carried out using a HPLC method.
Results: Out of 150 recruited patients, 128 patients were on
monotherpy and 22 patients were on combination of two or
more AEDs. Good correlation (r>0.7) was observed between
serum and salivary levels of EPT and CBZ mainly when the
levels were in the therapeutic range. Poor to moderate
correlation (r<0.5) was however observed between serum and
salivary levels of PBT.
alternative to serum estimation in case of phenytoin and
carbamazepine, however not so in case of phenobarbitone.
87.In vitro effect of aloe vera on neutrophil and monocyte phagocyte function in relation with prakriti Mahale MK, Patil MJ, Deshmukh AS, Bhalerao SS,
Abstracts
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
203
Thatte UM Department of Clinical Pharmacology, TN Medical Col- lege and BYL Nair Ch. Hospital, Mumbai Central, Mumbai. E-mail: [email protected]
Objective: To assess the in vitro effect of aloe vera (Av) on
polymorphonuclear leucocytes (PMN) and monocyte phagocyte
function and to investigate the effect of the prakriti on these
parameters.
Methods: 28 volunteers i.e 10 volunteers each of Pitta and
Kapha prakriti and 8 volunteers of Vata prakriti were identified
using a standardized questionnaire and recruited into the study.
Peripheral venous blood was collected and polymorphonuclear
leucocyte and monocytes were separated. In vitro effect of
extract of Av (0.1, 0.2 and 0.4 µg/ml) on PMN and monocyte
phagocyte function was assessed using Candida albicans as a
test organism.
Results: Aloe vera stimulated PMN and monocyte phagocytosis
in all the groups in a dose dependent manner with maximum
increase in % phagocytosis of PMN and monocyte at 0.1 µg/ml
(P=1.95x10-15) and 0.4 µg/ml (P=1.44X10-11) respectively.
Interestingly, the stimulation in terms of percentage increase
in phagocytosis with Av was maximum in individuals with Kapha
prakriti (46.22% in PMN and 31.38% in monocyte as compared
to control).
response in Kapha prakriti individuals, which is in accordance
with Ayurvedic concepts.
Indian J Pharmacol | June 2004 | Vol 36 | Issue 3 | 192-203
Date : 14th-16th January, 2005
Venue : Science City, Kolkata
Organized by: Organizing Vice-Chairperson: West Bengal Branch S. K. Bandopadhyay
Indian Pharmacological Society Head–Department of Pharmacology,
IPGME&R, Kolkata - 700020.
Institute of Postgraduate Medical T. K. Mondal
Education & Research (IPGME&R), Reader & Head–Department of Pharmacology,
244B Acharya J. C. Bose Road, West Bengal University of Animal&
Kolkata - 700020. Fisheries Sciences,
E-mail: [email protected] Kolkata - 700037.