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   2006| January-February  | Volume 38 | Issue 1  
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Screening of antimalarial drugs: An overview
BS Kalra, S Chawla, P Gupta, N Valecha
January-February 2006, 38(1):5-12
Efforts to discover and develop new antimalarial drugs have increased dramatically in recent years mainly because of resistance to existing antimalarial drugs. Selection of candidate drugs for clinical trials in man and the design of clinical protocols are based upon consideration of data from a battery of preclinical test systems. All compounds are assessed initially in one or more primary screening models. A compound which is considered 'active' by well established criteria in primary screening test is considered for further evaluation in successively more clinical tests. At the end of each stage of testing, a decision is taken to advance the compound to the next stage or discontinue it. Primary screening tests should have optimal sensitivity, a high degree of reproducibility, high throughput, requiring a minimum quantity of test compound and should bear low cost. As there is growing need for newer and more efficacious antimalarial drugs especially in tropical countries, more sensitive and economical screening models are needed. This review is an update of various conventional and latest in vitro and in vivo screening methods being used for evaluation of antimalarial compounds.
  44 18,365 1,090
Antihyperglycemic activity of aqueous extract of leaves of Cocculus hirsutus (L.) Diels in alloxan-induced diabetic mice.
S Badole, N Patel, S Bodhankar, B Jain, S Bhardwaj
January-February 2006, 38(1):49-53
Objective: To evaluate the antihyperglycemic activity of aqueous extract of leaves of Cocculus hirsutus (L.) Diels in alloxan-induced diabetic mice. Materials and Methods: Alloxan-induced (70 mg/kg, i.v.) diabetic mice were given aqueous leaf extract (250, 500, and 1000 mg/kg, p.o., n= 6) of C. hirsutus or vehicle (distilled water, 10 ml/kg, p.o.) or standard drug glyburide (10 mg/kg, p.o.) for 28 days. Blood samples were withdrawn by retro-orbital puncture and were analyzed for serum glucose on 0th, 7th, 14th, 21st, and 28th days by glucose oxidase/peroxidase method. In oral glucose tolerance test, glucose (2.5 g/kg, p.o.) was administered to nondiabetic control, glyburide (10 mg/kg, p.o.), and aqueous extract of C. hirsutus (1000 mg/kg, p.o.) treated mice. The serum glucose level was analyzed at 0, 30, 60, and 120 min after drug administration. Results: The aqueous leaf extract of C. hirsutus (250, 500, and 1000 mg/kg, p.o.) showed significant ( P< 0.01) reduction of serum glucose level in alloxan-induced diabetic mice at 28th day. In oral glucose tolerance test, aqueous extract of C. hirsutus increased the glucose tolerance. Conclusion: It is concluded that C. hirsutus has significant antihyperglycemic activity as it lowers serum glucose level in diabetic mice and significantly increases glucose tolerance.
  35 16,677 1,002
Effect of Pongamia pinnata flowers on blood glucose and oxidative stress in alloxan induced diabetic rats
R Punitha, K Vasudevan, S Manoharan
January-February 2006, 38(1):62-63
  29 10,608 760
Hepatoprotective activity of Pterocarpus santalinus L.f.,an endangered medicinal plant
BK Manjunatha
January-February 2006, 38(1):25-28
Objective: To evaluate the hepatoprotective activity of crude aqueous and ethanol stem bark extracts of Pterocarpus santalinus (Fabaceae) using CCl4 induced hepatic damage in male Wistar albino rats. Materials and Methods : The aqueous (45 mg/ml) and ethanol (30 mg/ml) extracts of stem bark in 1% gum tragacanth was administered orally for 14 days and the hepatoprotective activity studied in CCl4 induced hepatic damage model. The hepatoprotective activity was assessed using various biochemical parameters like serum bilirubin, protein, alanine transaminase, aspartate transaminase and alkaline phosphatase along with histopathological studies of liver tissue. Results : There was a significant increase in serum levels of bilirubin, alanine transaminase, aspartate transaminase and alkaline phosphatase with a decrease in total protein level, in the CCl4 treated animals, reflecting liver injury. In the aqueous and ethanol extracts treated animals there was a decrease in serum levels of the markers and significant increase in total protein, indicating the recovery of hepatic cells. Histological study of aqueous extract treated group exhibited moderate accumulation of fatty lobules and cellular necrosis where as ethanol extract treated animals revealed normal hepatic cords without any cellular necrosis and fatty infiltration. Conclusion: The ethanol and aqueous stem bark extract of P. santalinus afforded significant protection against CCl4 induced hepatocellular injury.
  20 18,526 1,094
P-glycoprotein: Pharmacological relevance
Vishal R Tandon, B Kapoor, G Bano, S Gupta, Z Gillani, S Gupta, D Kour
January-February 2006, 38(1):13-24
P-glycoprotein (P-gp) is a 170 kDa membrane-bound protein, an energy-dependent efflux transporter driven by ATP hydrolysis. It is responsible for multidrug resistance of many drugs. Physiologically, it is involved in limiting the harmful exposure of toxins, drugs, and xenobiotics to the body by extruding them out of cells. It is increasingly recognized to play an important modulating role in the pharmacokinetic properties of many clinically important therapeutic agents and because of its importance in pharmacokinetics, its screening has to be incorporated into the drug discovery process. The modulation of drug transporters through inhibition or induction by various drugs or herbs can lead to significant drug-drug or drug-herb interactions by affecting various pharmacokinetic parameters of the drug. In addition, genetic polymorphism of P-gp has also been reported, which may affect drug disposition, produce variable drug effects, and may change disease risk susceptibility. As drug interactions and genetic polymorphism are important factors to be considered during drug development, P-gp may have an impact on drug development in future.
  18 16,684 1,307
Antiinflammatory and antinociceptive activities of zingiber officinale roscoe essential oil in experimental animal models
A Vendruscolo, I Takaki, LE Bersani-Amado, JA Dantas, CA Bersani-Amado, R K.N Cuman
January-February 2006, 38(1):58-59
  18 12,842 1,316
Anticestodal efficacy of Psidium guajava against experimental Hymenolepis diminuta infection in rats.
Temgenmogla V Tangpu, Arun K Yadav
January-February 2006, 38(1):29-32
Objective: To investigate the anticestodal efficacy of Psidium guajava L. leaf extract. Materials and Methods: Anticestodal efficacy was evaluated using experimental Hymenolepis diminuta infection in rats. The leaf extract was administered orally to different groups of experimentally infected H. diminuta infections in rats. The efficacy was adjudged in terms of parasite eggs/g (EPG) of faeces count before and after treatment, direct count of surviving worms remaining in small intestines after completion of treatment and by host clearance of parasite. In all the experiments, the effect of leaf extract was compared with a standard anticestodal drug, praziquantel (PZQ). Results: The leaf extract showed reduction in parasite EPG of faeces count in a dose-dependent manner. It further showed comparatively low recovery of worms including scolices in the small intestine and host clearance of parasite in a dose dependent manner. In all the experimental models the anticestodal efficacy of leaf extract was significantly comparable with that of PZQ. Conclusion: The leaf extract of P. guajava possesses anticestodal efficacy. Study supports its folk medicinal use in the treatment of intestinal-worm infections in northeastern part of India.
  17 12,576 354
Antipromastigote activity of an ethanolic extract of leaves of Artemisia indica
S Ganguly, S Bandyopadhyay, A Bera, M Chatterjee
January-February 2006, 38(1):64-65
  15 5,819 268
In vivo antioxidant activity of hydroalcoholic extract of Taraxacum officinale roots in rats
Meera Sumanth, AC Rana
January-February 2006, 38(1):54-55
  12 10,102 739
Effects of Mondia whitei extracts on the contractile responses of isolated rat vas deferens to potassium chloride and adrenaline
P Watcho, D Fotsing, F Zelefack, TB Nguelefack, P Kamtchouing, E Tsamo, A Kamanyi
January-February 2006, 38(1):33-37
Objective: To investigate the effects of the methylene chloride:methanol (CH2Cl2:MeOH, 1:1) extract of the dried roots of Mondia whitei Linn and its hexane and methanol fractions on potassium chloride (KCl) and adrenaline (Adr)-induced contractions of rat vas deferens. Materials and Methods: Isolated strips of normal adult rat vas deferens were mounted in a Ugo Basile single-organ bath containing Krebs solution. Cumulative concentration-response curves of KCl (1-7 x 10-2 M ) and adrenaline (1.21-8.45 x 10-7 M ) were established in the absence and presence of M. whitei (50-400 g/ml). In separate experiments, after obtaining a stable plateau of contractions with KCl (60 m M ), M. whitei samples (50-400 g/ml) were added cumulatively to relax the preparation. In KCl (60 m M ), containing depolarizing medium, cumulative concentration-contraction curve to CaCl2 (2-14 x 10-2 M ) was elicited in the absence and presence of the hexane fraction of M. whitei (50-400 g/ml). Results: All the M. whitei samples produced rightward shift of the concentration-response curves to KCl and Adr. At high concentration of the plant extracts (400 g/ml), a decrease of the maximal response to the contractile agents was observed compared with that obtained with the control. All the three extracts produced concentration-dependent relaxation of the plateau of contraction induced by KCl and the hexane fraction appeared to be the more potent. In calcium-free physiological salt solution, the hexane fraction of M. whitei produced rightward shift to the concentration-response curve to CaCl2 and completely abolished the contractile effect of calcium at high concentration (400 g/ml). Conclusion: It is concluded that M. whitei extracts antagonized the contractile responses to KCl and Adr in isolated rat vas deferens, which could be due to the blockade of voltage-operated calcium channels.
  7 8,858 258
Effect of an unani formulation on lipid profile in rat
Tajuddin , M Nasiruddin, N Ahmad
January-February 2006, 38(1):56-57
  4 6,422 297
Prevention of multiple drug allergy by histaglobulin
M Mohanty, S Mohapatra, KP Pattnaik, TR Swain
January-February 2006, 38(1):68-69
  3 8,989 213
Effect of trolox and quercetin on sulfur mustard-induced cytotoxicity in human peripheral blood lymphocytes
R Bhattacharya, RK Tulsawani, R Vijayaraghavan
January-February 2006, 38(1):38-42
Objective: To evaluate the protective activity of antioxidants, viz. trolox and quercetin, against sulfur mustard (SM)-induced cytotoxicity. Materials and Methods: Cytotoxicity of various concentrations (20-640 M) of SM, in the presence or absence of 10 M trolox or quercetin (-0.5, 0, or +0.5 h) was determined in human peripheral blood lymphocytes after 6-h exposure. Cell viability was measured by Trypan blue dye exclusion (TBDE). Further, a cytotoxic concentration of SM (80 M) was challenged by the two antidotes (-0.5 h) and cell viability was measured by TBDE and leakage of intracellular lactate dehydrogenase (LDH). Mitochondrial integrity and peroxide levels were measured by 3-4,5-dimethyl thiazol- Z -yl)-2,5-diphenyltetrazolium bromide and 2',7'-dichlorofluoroscin diacetate assay, respectively. Morphological changes of cells exposed to 320 M SM (with or without antidotes) were also visualized under light microscope. Results: On the basis of TBDE , SM caused cell death of approximately 50% at 80 M and 100% at 640 M, respectively. Pretreatment of trolox conferred significant protection compared with quercetin. Also, pretreatment of trolox significantly reduced cell death and LDH leakage caused by 80 M SM but did not prevent the loss of mitochondrial integrity. Trolox significantly reduced the levels of peroxides generated by SM. The better protection offered by trolox was evidenced in cell morphology studies too. Conclusion: Pretreatment (-0.5 h) of trolox afforded significant protection against SM-induced cytotoxicity in human lymphocytes. The protection was related to the antioxidant property of trolox, a water soluble analog of a-tocopherol.
  3 6,941 245
Unethical publication practices: How should we deal with them?
R Raveendran
January-February 2006, 38(1):3-4
  2 6,300 250
Exenatide: An incretin-mimetic agent
S Kaushal, SC Chopra, S Arora
January-February 2006, 38(1):76-78
  2 8,293 481
Imatinib mesylate-induced generalized hypopigmentation in patients with chronic myeloid leukemia
Sunita , DK Gupta, S Saluja, S Bhasin, M Sharma
January-February 2006, 38(1):66-67
  2 5,628 150
Inhibition of chondrogenic differentiation in chick limb-bud mesenchyme microcultures treated with cyclosporine
Soghra Bahmanpour, Douglas F Paulsen
January-February 2006, 38(1):43-48
Objectives: To explore the effects of cyclosporine (CsA) on skeletal development (chondrogenesis). Materials and Methods: Mesenchymal cells obtained from stage-23 to stage-24 chick-embryo limb buds were grown in 96-well plates using chemically defined tissue-culture medium. Cultures were treated with CsA (0.01-5.0 g/ml) and incubated (37C, 5% CO2) with daily medium changes for 4 days. After incubation of the cells in multiwell plate, cartilage differentiation (chondrogenesis) was assessed by selectively staining sulfated glycosaminoglycans (GAGs) in the cartilage matrix with Alcian blue, extracting the GAGs with 4 M guanidinium HCl, and spectrophotometric analysis of the extracts. Results: CsA treatment had concentration-dependent effects on chick limb-bud mesenchymal cell cultures. At 5 g/ml, CsA caused cell loss, as judged microscopically by the paucity of cells remaining at the end of the culture period. CsA concentrations between 0.1 and 1 g/ml caused a marked, dose-dependent decrease in chondrogenesis. At 0.01 g/ml, CsA had no significant effect on chondrogenesis. At concentrations above 0.01 g/ml, normalized data showed significant chondrogenic inhibition at 0.5 and 1.0 g/ml CsA. Conclusions: The findings suggest a possible biological basis for CsA-associated effects on mesenchyme-derived tissues and provide a model system for further studies.
  1 7,319 157
Book review
Arun Nanivadekar
January-February 2006, 38(1):81-81
  - 3,897 163
Book review
CH Shashindran
January-February 2006, 38(1):82-82
  - 3,425 130
Patent laws must be in the national interest.
V Thawani, K Gharpure, M Thawani
January-February 2006, 38(1):70-72
  - 6,224 240
Patent holder deserves monopolistic rights
M Qaiser, Mohan P Chandran
January-February 2006, 38(1):73-75
  - 6,547 182
Gatifloxacin-induced prolongation of QTC interval
VN Shah, NR Karavadara, DS Shah, BK Shah
January-February 2006, 38(1):60-61
  - 5,212 202
Clinical Trial Results
J Singh
January-February 2006, 38(1):79-80
  - 4,884 256
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