Studies on the synthesis and biological activity of 3-(substituted anilinomethyl)-4-(5-substituted-2-furfurylidene)amino-1,2,4 -triazole-5- thiones and their Mannich bases.

A series of 3-(substituted anilinomethyl)-4-(5-substituted-2- furfurylidene)amino-1,2,4-triazole-5-thiones were synthesized as potential biologically active agents. They were converted to Mannich bases, by treating with suitable amine in the presence of formaldehyde in alcohol medium. The newly synthesized compounds were screened for their antibacterial and antifungal activities.

Effects of chronic oral administration in mice of the gut-stimulating crystals of Croton penduliflorus seed oil.

Crystals from Croton penduliflorus seeds (CPC) were administered at weekly intervals in two doses (7 mg/kg and 21 mg/kg) by gastric intubation to mice over 12 weeks. CPC induced purgation in the treated mice, with the higher dose having a more profound effect. Mice treated with CPC developed skin lesions with swollen scrotums. There were significant changes in the PCV, Hb and plasma proteins of treated mice. Gangrene of the tail with subsequent sloughing was observed, particularly in the low dose group. Mice in the low dose group also experienced retarded growth. A significant clinical finding in the treated mice was abortion during late pregnancy and 100% fetal mortality. It was concluded that, apart from its purgative effect, CPC can cause toxic effects in chronic administration. Use in pregnant women should be discouraged.

Effects of the gut-stimulating principle in Croton penduliflorus seed oil on the central nervous system.

The gut-stimulating principle in Croton penduliflorus seed oil isolated as white crystals (CP crystals) significantly reduced pentobarbitone-induced sleeping time in mice at doses of 3 and 6 mg/kg intraperitoneally. Indomethacin (4 mg/kg) and atropine (0.044 mg/kg) significantly reversed the action of CP crystals on pentobarbitone sleeping time with indomethacin having a profound reversal effect. CP crystals significantly reduced the mean onset of convulsions and the mean death time in mice treated with a surely convulsive dose of strychnine. CP crystals significantly reduced the intensity of morphine and pethidine analgesia and prolonged the duration of pethidine analgesia. Most actions of CP crystals suggest that it stimulates the CNS and reduces the intensity of opioids (except codeine) while prolonging their duration of analgesic action.

The toxic effects of a chronic administration of the gut-stimulating principle in Croton penduliflorus hutch. seeds in mice.

Albino mice (8-10 wks) weighing between 14 and 25 g were divided into 2 groups and dosed orally once per week with 2 doses (7 mg/kg and 21 mg/kg) of the gut-stimulating principle in Croton penduliflorus seeds (CP crystals) for 12 weeks. Some mice (3-4) from each group were killed at 10 days intervals for the first 6 wks of the experiment and at 20 days intervals for the last 6 weeks. Gross and histopathological changes in the brain, heart, liver, kidney, adrenal, spleen, testis, lung and various segments of the gastrointestinal tract including the stomach, duodenum, ileum and colon were observed. The relative weights of the visceral organs were also recorded. Significant weight change in the spleen was evident. The congestion of the lung was the most common gross pathological observation made. Other observations were splenomegaly, enlarged heart, swollen uterine horns, etc. Histopathological changes observed included haemorrhages in the lungs, myocardium, liver, kidney, testis, brain etc. Goblet cell hyperplasia with mucin present in the lumen were observed in the jejunum, ileum and colon. In conclusion, CP crystals produced severe lesions in the visceral organs and the brain after chronic oral administration at low and high dosage levels which should indicate caution in administering the extract to humans.

The interaction of aflatoxin B1 with vitamin K, phenylbutazone, and sulfamethoxine in rats.

The interactions of aflatoxin B1 (AFB1) with vitamin K, phenylbutazone, and sulfamethoxine were investigated in albino rats. Vitamin K (5 mg/kg) was able to completely suppress the increase in whole blood clotting time caused by AFB1 (25 micrograms/kg). Phenylbutazone (50 mg/kg) and sulfamethoxine (50 mg/kg) also significantly (P less than 0.05) lowered the increased clotting time caused by AFB1. Equilibrium dialysis was performed on rat plasma (4 mg/ml protein content) to investigate the displacement of AFB1 (3 micrograms) from its bound form by vitamin K (250 micrograms), phenylbutazone (2500 micrograms), and sulfamethoxine (2500 micrograms). Phenylbutazone and sulfamethoxine significantly (P less than 0.05) displaced AFB1 from rat plasma protein. Histopathological examinations performed on the liver, kidneys, and spleen of control and treated rats showed that none of the drugs used appeared to offer any significant organ protection against AFB1 except in the spleen.

The glucose tolerance of the West African dwarf goats.

Glucose tolerance tests conducted on 4 adult goats and 3 kids, injecting glucose intravenously (0.5 g/kg body weight), showed that the former required 180 min and the latter 45 min after injection, to restore blood glucose to normal. For the adult goats, the turnover rate (K) was 0.38 +/- 0.03/hr, turnover time (TT) 2.64 +/- 0.18 hr and half-time (T 1/2) 110.24 +/- 7.73 min for glucose clearance while for the kids, these were 1.59 +/- 0.12/hr, 0.64 +/- 0.04 hr and 26.05 +/- 4.36 min respectively. The higher glucose clearance in the kids than in the adults may be attributed to a more efficient insulin response and to greater glucose utilization than in the former. The dwarf goats appear to differ substantially from the cows in their homeostatic responses to induced hyperglycemia.