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Application of isotopic techniques in the
study of Protozoal and Helminthic drug
development research
J.C.Samantaray
Department of Microbiology,
All India Institute of Medical Sciences,
Ansari Nagar, NEW DELHI.
PARASITE
COMMENTS
P. falciparum*
CHLOROQUINE
WIDE SPREAD
MEFLOQUINE
Plasmodium vivax
CHLOROQUINE
PAPUA NEW-GUINEA
Leishmania*
GLUCANTINE
PENTOSTAM
Toxoplasma gondii
ATOVAQUINE
UNCOMMON
Giardia lamblia
METRONIDAZOLE
UNCOMMON
Trichomonas vaginalis
METRONIDAZOLE
UNCOMMON
ANTIPARASITIC DRUG SCREENING PROTOCOL
(I) PARASITE:
(ii) DRUG / COMPOUND:
(b) Morphology:
(iii) PARAMETERS:
(a) Rate of Growth:
(c) Metabolism:
SCREENING OF ANTIPARASITIC AGENTS
PARASITE
OBSERVATION
E. HISTOLYTICA
AXENIC CULTURE
SPIROARSNOME
INHIBITION
MULTIPLICATION
DEVELOPMENMT
GOLDEN HAMSTER
METRONIDAZOLE
ABSCESS
HEALING

HEPATIC ABSCESS
TINIDAZOLE BIOPSY
PANIDAZOLE &

OTHER COMPOUNDS
ACANTHAMOEBA
GUINEA PIG
NEOMYCIN
ULCER HEALING
CYSTICIDAL
KERATITIS
PARAMOMYCIN
1 & 2 ADDITIVE
PROPAMIDINE
RECURRENCE
ISOTHIONATE
GIARDIA LAMBLIA
AXENTIC CULTURE
METRONIDAZOLE
ADDITIVE EFFECT
CELL CULTURE
FURAZOLIDONE
ATTACHMENT
SCREENING OF ANTIPARASITIC AGENTS
PARASITE
OBSERVATION
MOUSE PERITO.m Ø.
PENTOSTAM
INHIBITION
DEVELOPMENT
MONOCYTE LINE
GLUCANTIME
AND ATTACMENT
RESISTANCE
LEISHMANIA
HUMAN MONOCYTE
LEUKEMIA CELL
LINE

PROMASTIGOTE,
TUBULAZOLE
NNN MEDIUM,
(MICROTUBLE
MOTILITY
DEVELOPMENT
MICROPLATE
INHIBTOR)
INHIBITION
14

LIQUID MEDIUM
C ESTIMATION
HAMSTER, S/C,
GLUCANTIME
PARASITE LOAD,
RESISTANCE
L. panamensis
FOOT PAD,
(IM/ORAL)
SKIN ULCER,
5 X 106 ORGANISM
LYMPH NODE
ALLOPURINOL
DIAMIDINE
T. cruzi
AXENTIC CULTURE
SINEFOMYCIN
TRYPANOSTATIC
DRUG
SCREEN

SCREENING OF ANTIPARASITIC AGENTS
PARASITE
OBSERVATION
MICE MODEL
ATOVAQUINE
SURVIVAL/
DRUG SCREEN
T. brucei
MRC FIBROBALST
ATOVAQUINE
QUNTITATIVE ELISA
DRUG SCREEN
T. gondii
ALONE OR WITH
PYRIMETHAMINE
RESISTANCE
MICE(TACHYZOITE, IP,
SDZ, CLARITHROMYCIN
104 CYSTS
2 DAYS OLD CALF
SINEFUMYCIN
MORTALITY
CRYPTO-
IMMUNOSUPRESSED RAT
HALAFUGINONE
OOCYST SHREDING
SPORIDIUM
SCREENING OF ANTIPARASITIC AGENTS
NEMATODES
SPIROARSONOMES
MOTILITY
DRUG SCREEN
INHIBITION
MICROFILARIA
INHIBITION
NIPOSTRONGYLUS
NIPOSTRONGYLUS
SPIROARSONOMES
DRUG SCREEN
INHIBITION
ECTOPARASITES
ECTOPARASITES
PIG,PIGEON
FALLING OF TICKS
SCREENING
(TICK,LOUSE,FLEA)
MORTALITY INSECTS
HUMANSAFETY
EFFECT ON SYSTEMIC
ADMINSTRATION

In vitro and in vivo activities of three Acridine
Thioethers against Leishmania donovani
(Mesa C et al, Pharmacology, 65, 74-82, 2002)
(i) PARASITE:
(ii) DRUG/COMPOUND:
(iii) OBSERVATIONS:
(a)Growth Rate

Metabolism
(b)Morphology
(c)Metabolism
CONCLUSION: (i) Macromolecular synthesis inhibited (++) (ii) Alteration in
activity of enzymes (iii) Alterations in production of end metabolites
(iv) interference with carbohydrate energy production.
SCREENING OF ANTIPARASITIC AGENTS
ISOTOPIC TECHNIQUE
ORGANISM
APPLICATION
1. Isotopic techniques have been mostly used in antiprotozoal 2. Commonly studied protozoa are Plasmodium, Leishmania, Trypanosome and 3. Metabolic labeling with 3H Nucleotides ( Uracil, Thymine), Amino acids ( leucine, serine etc), sugars ( glucose, galactose)are the commonest protocols used 4. Labeling of macromolecules 125I transferin, lactoferin, albumin, 59Fe apotransferin, apolactoferin and other molecules have been used for specific protocols 5. Isotopic techniques have been commonly used to study metabolic pathways (proteins, glycoproteins, phospholipid synthesis, sugar, amino acid and ion transport), drug screening and resistance studies of parasites

Source: http://tc.iaea.org/tcweb/abouttc/strategy/thematic/pdf/presentations/CommunicableDiseases/AppliIsotopicTechStudyofProtozoalandHelminthicDrugDevRes-DrugResistParasites.pdf

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1. In the patient with a blood glucose of 300mg/dL or higher without signs or symptoms of dehydration should receive how much normal saline? Pg 61 2. The adult dose of Zofran is _____. Pg 69 a. 4mg over 30 seconds IV/IO b. 4mg over 1 minute c. 2mg over 1 minute IV/IO d. 2 mg IM 3. Zofran may be given all of the following routs except_____. Pg 69 4. The pediatric dose of Zofran is _____. P

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