Hepatotoxicity of copper: studies on the developing animals.
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Biomedical subjects
Publications and source records attributed to P Tandon.
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The clastogenic effect of cis-dichlorodiammine platinum(II) (cis-platin) on mouse bone-marrow chromosomes has been studied. Cis-platin was injected at 3 different doses. Cells were fixed at different time intervals after treatment. Different types of aberrations together with the percent of mitotic index and frequency of abnormal metaphases were studied. The aberrations observed were primarily chromatid breaks, although isochromatid breaks, interchanges, and multiple breaks were also observed. A dose- and time-dependent effect was observed for both inhibition of mitotic index and frequency of abnormal metaphases. Trypsin-Giemsa staining of bone-marrow metaphase chromosomes from normal mice was compared with the bands of metaphase chromosomes obtained after Giemsa staining of chromosomes from platinum-treated mice and they were observed to be identical. Bands were present up to 120 h and aberrations were also induced in such plates.
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Co-cultivation of splenocytes with cis-dichlorodiamine platinum (II) treated tumor cells generate cytotoxic splenocytes, which when injected into normal mice, render them resistant to tumor challenge. Significant increases in mean survival time and 33% of tumor free survivals were observed in mice exposed to a tumor challenge on the 10th day after injection of sensitized splenocytes. Splenocytes peritoneal exudate cells obtained after in vivo immunization of mice with cis-dichlorodiamine platinum(II) treated cells retarded tumor growth in vivo when injected in different combinations in tumor bearing mice. Maximum survival time of tumor bearing mice and 20% tumor free survivals were observed when the animals were injected with a combination of immune splenocytes and normal peritoneal exudate cells. The increase in the number of macrophages of immunotherapeutically treated mice suggests that host macrophages have been activated. Splenocytes and macrophages obtained from immunotherapeutically treated mice showed an increase in cytotoxicity against tumor cells in vitro.
Newly synthesized triazoles were evaluated for their anti-inflammatory and antiproteolytic activities. These derivatives possessed potent anti-inflammatory and antiproteolytic activities. In addition, these compounds were relatively less toxic.
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The effect of medroxyprogesterone acetate (MPA) on brain monoamine levels and monoamine oxidase (MAO) activity was studied in adult, healthy, non-pregnant female rats. MpA was injected in a single dose of 100 mg/kg i.m. Dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT) levels and MAO activity were estimated fluorometrically in rat brian. No change in DA, NA, 5-HT or MAO activity was observed after 7 days of MPA treatment while a significant decrease in DA levels along with a significant increase in MAO activity was observed after 21 days of MPA treatment. However, there was no change in NA and 5-HT levels after 21 days of MPA administration. The selective reduction of DA by MPA could be due to an increase in MAO-B activity. MPA does not appear to increase MAO-A activity because neither of the specific substrates (NA and 5-HT) of MAO-A was found to be decreased inspite of the increase in MAO activity as estimated by the kynuramine method. These findings suggest the importance of MAO-B also in DA metabolism in rat brain.
Levonorgestrel which binds with high affinity to SHBG, is suggested as a new radioligand for estimation of SHBG in human plasma. Using 3H-levonorgestrel as a ligand, a number of samples from men, women pregnant and non-pregnant were analysed. The SHBG content was lowest in men, low in women and rose to higher level during pregnancy. The results of the present study suggest that levonorgestrel appears to be a better ligand than dihydrotestosterone for measuring SHBG.
Eighteen novel acetyl salicyloyl/butyroyl mercapto 1,3,4-thiadiazoles have been synthesized and characterized by their elemental analyses, IR and PMR spectral studies. Their efficacy against carrageenin induced paw oedema was tested in albino rats of either sex at a dose of 100 mg/kg p.o. In vitro antiproteolytic activity of the compounds was assessed by determining their ability to inhibit trypsin induced hydrolysis of bovine serum albumin. Active anti-inflammatory compounds were tested for their analgesic activity against aconitine induced writhing in albino mice. Approximate LD50 values were also determined in albino mice.
The role of catecholamines in the mechanism of antiovulatory and other central effects of medroxyprogesterone acetate (MPA) has been studied in adult healthy, non-pregnant female albino rats. It has been observed that a single dose of MPA (100 mg/kg) given intramuscularly did not cause any significant change in brain catecholamine levels after 7 days of treatment. However, there was a significant reduction in brain dopamine levels after 15 days of MPA administration. This reduction in brain dopamine levels may be responsible for the anti-ovulatory activity of MPA. Certain side effects of MPA such as amenorrhoea, galactorrhoea, breast tenderness, breast tumors, inactivity and depression may also be due to decrease in brain dopamine levels.
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