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Biomedical subjects

K B Masani

Publications and source records attributed to K B Masani.

5 recordsLinked to original sources

A simple quantitative in vitro macrophage migration assay.

An in vitro macrophage chemotaxis model using mouse peritoneal non-elicited resident macrophage cells and chemotaxins containing mediators of non-specific elicitors such as oyster glycogen or sodium caseinate has been described. Macrophage cells accumulation in mouse peritoneal cavity was maximum at 48 hr after injecting (i.p.) oyster glycogen (2.5%) or sodium caseinate (12%), 0.5 ml/mouse. Chemotaxins containing mediators were prepared from these mice by peritoneal lavage and termed as routine 'diluted' cocktail and 'concentrated (3 times)' cocktail. Chemotaxis assays were carried out in a modified Boyden chamber using a 48-well microchemotaxis assembly. In vitro results showed higher macrophage chemotaxis response against the 'concentrated' cocktails as compared to routine 'diluted' cocktail. Macrophages exhibited cell density dependent increase in the responsiveness to chemoattractant and macrophage cell density of 4 x 10(6) per ml concentration in the upperwell was found to be optimum. Macrophage responsiveness was seen better with sodium caseinate cocktail as compared to oyster glycogen in vitro as well as in vivo. DMSO (Dimethyl Sulphoxide) solvent (0.25% conc.) did not interfere with normal macrophage chemotaxis. Both CO2 incubator (5% CO2 in air) and BOD incubator with humidified chamber favoured chemotaxis. In vitro test system described can be used as a model to study the effect of anti-inflammatory compounds directly on the macrophage chemotaxis.

Animals↗

A comparative study of experimental caecal amoebiasis and the evaluation of amoebicides.

Caecal amoebiasis models (mouse, hamster and rat) were compared for amoebic infection and chemotherapeutic evaluation using a pathogenic strain of Entamoeba histolytica of human origin. Caecal infection in the hamster was of the acute type, with a large number of amoebae in the caecal tissue, whereas the amoebae in rats were seen in the lumen, on the mucosal surface. Amoebic lesions in the mouse caecum were of moderate severity. The mouse model responded to both metronidazole (tissue amoebicide) and diloxanide furoate (luminal amoebicide), whereas the hamster model only responded well to metronidazole and the rat model only to diloxanide furoate. Using the mouse as a primary screening model, a new oxadiazole compound, BTI 2405E, was found to have tissue and luminal amoebicidal activity. In rodent caecal models, a single dose of BTI 2405E was found to be more effective than one of metronidazole or diloxanide furoate. The mouse model appears to be the most useful for primary screening of anti-amoebic compounds.

Amebicides↗

Activity of a new oxadiazole compound, against experimental infections with Entamoeba histolytica and Giardia lamblia in animal models.

BTI 2286E(+/-)-E-3-(4-methylsulphinylstyryl)-1,2,4-oxadiazole has demonstrated potent amoebicidal activity in a single-dose treatment against Entamoeba histolytica infection in the livers of golden hamsters and the caeca of mice, hamsters and rats. It has intra luminal activity against Entamoeba criceti, a natural infection in golden hamster, and anti-giardial activity against Giardia lamblia infection in suckling mice. BTI 2286E is more potent than metronidazole in extra intestinal, intra luminal amoebiasis models and has significant advantages in that it is non-mutagenic in the Ames test and has a shorter duration of effective treatment.

Amebicides↗

Comparative pharmacokinetics and amoebicidal activity of metronidazole and satranidazole in the golden hamster, Mesocricetus auratus.

The pharmacokinetic properties of metronidazole and satranidazole were studied in the golden hamster (Mesocricetus auratus), at a dose of 80 mg/kg po. Blood and liver samples were collected at frequent time intervals and assayed for metronidazole and satranidazole by HPLC. Satranidazole exhibited significantly higher plasma concentrations than metronidazole at 1 and 2 h post-dose, but the comparative Cmax values were not significantly different. The satranidazole plasma elimination half-life of 1.01 h was significantly shorter than the corresponding metronidazole half-life of 3.62 h. The comparative liver pharmacokinetic parameters Cmax, Tmax and T1/2 did not differ significantly. Satranidazole however exhibited significantly higher liver concentrations at 1 h post-dose and Cmax and AUC0-infinity values were approximately 35% higher. The in-vivo amoebicidal activity of both compounds was evaluated in the acute hamster hepatic model of amoebiasis. Both metronidazole and satranidazole were administered as single graded doses po, and their dose-response profiles were characterized. Satranidazole demonstrated significantly greater amoebicidal activity than metronidazole with an ED50 value of 19.5 mg/kg, compared to an ED50 value of 45 mg/kg for metronidazole. These data suggest that higher plasma and liver concentrations of satranidazole and greater intrinsic potency probably contribute to superior amoebicidal activity in the hamster model of hepatic infection.

Administration, Oral↗