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
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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