Inhibition of growth of Leishmania donovani promastigotes by newly synthesized 1,3,4-thiadiazole analogs

Leishmania donovani, the causative agent of visceral leishmaniasis, is transmitted by sand flies and replicates intracellularly in their mammalian host cells. The emergence of drug-resistant strains has hampered efforts to control the spread of the disease worldwide. Forty-four 1, 3, 4-thiadiazole derivatives and related compounds were tested in vitro for possible anti-leishmanial activity against the promastigotes of L. donovani. Micromolar concentrations of these agents were used to study the inhibition of multiplication of L. donovani promastigotes. Seven compounds were identified with potential antigrowth agents of the parasite. Compound 4a was the most active at 50 micro M followed by compound 3a. These compounds could prove useful as a future alternative for the control of visceral leishmaniasis

Histopathological and biochemical toxic effect of amiodarone on thyroid gland in albino rat

Amiodarone AMD [Cordarone] was a benzofuran derivative, used in management of angina and refractory ventricular arrhythmia. Its effect on the thyroid gland structure and function was investigated in this study. Fifty adult male albino rats were used and divided into three groups. The first group was consisted of 10 rats which served as control, received distilled water orally [1ml]. The second group was consisted of 20 rats used as therapeutic dose treated group, received 40 mg/Kg b. w. of amiodarone while the third group was consisted of 20 rats used as a toxic dose treated group which received 60 mg/Kg b. w. of amiodarone orally daily for three months. Body weight of animals was determined. Serum concentration of tri-iodothyonine [T3], thyroxine [T4], thyrotrophin [TSH], interleukin 6 [IL6], tumour marker P53 and tissue residue for amiodarone in plasma, fat, liver, lung, thyroid gland and heart was determined. Specimens from thyroid gland were taken and prepared for light and electron microscope examination. Highly significant decrease in body weight [P<0.001] were observed in both therapeutic and toxic doses treated groups in comparison to the control one. A very highly significant increase [P<0.001] of serum [T4 and T3] with Concomitant suppression of [TSH] [P<0.001]. Serum levels of IL6 and P53 showed also a very highly significant increase [P<0.001]. Amiodarone concentration in plasma, fat, liver, lung, thyroid gland and heart showed significant increase in therapeutic dose treated group and highly significant increase in toxic dose treated group. Histopathological examination of thyroid gland of therapeutic dose treated group by light microscope showed marked evidence of thyotoxicosis in the form of microcystic follicular changes and peripheral scalloping, cellular degeneration with scanty cytoplasm and vesicular nuclei appeared. These changes became more severe in toxic dose treated group in the form of epithelial hyperplasia with atypical nuclear features. Thyroid tissue damage with haemorrhage and necrosis. Electron microscopic examination showed a remarkable cellular changes in the form of dilated rouph endoplasmic reticulum, inclusion lysosomes, dilated Golgi bodies, mitochondrial distension and nuclear degeneration. In both treated groups these changes were dose related