Theophylline Poisoning And Its Interaction With Some H-2 Receptor Antagonists
Ola G. Haggag, Ph. D., Marcelle R. Haroun, Ph.D., Mohamed K. Ahmed, PhD. and Ragaey R. Fahmy MD
Departments of Forensic and toxicology and pathology, Benha faculty of medicine
a b s t r a c t
Theophylline poisoning is becoming more common, as a result of the increased therapeutic uses and due to plenty of drug interactions that affect theophylline clearance. The objective of this study was to assess theophylline poisoning and to determine the effect of three H-2 receptor antagonists (cimetidine, ranitidine and famotidine) on theophylline toxicity. Sixty-five patients with acute theophylline poisoning (mean serum level was 58.42±31.74) and twenty healthy individuals were selected. Significanct elevation in blood sugar, serum creatine phosphokinase and kidney function tests, significant lowering in serum potassium and insignificant changes in liver function tests were found. The experimental studies were conducted on 400 male adult albino rats. In the acute toxicity study, 240 rats were classified into eight groups. The first four groups were given the LD50 0of theophylline (Theo), cimetidine C, rantidine R, and famotidine F respectively. The 5 th, 6th and 7th grouos were given 1/2 LD50 of theo+C, theo+R and theo+F while 8th group was served as a control. In short-term chronic study, 160 rats were divided into the same eight groups and were given a daily oral doses of 1/10 the LD50of p27,p35, Bax and CD44 was investigated in 30 papillary thyroid carcinoma (PTC) with or without cervical nodal metastasis to determine the role of immunohistochemical marker for prediction of neck metastasis in these patients.
P27 expression in non-metastasizing PTC was lower than normal thyroid tissue (P≤ 0.01) and higher than metastasizing PTC (P≤ 0.01), p53 immunoreactivity was present, faint (grade 1) in 2 cases (11%) and moderate (grade 2) in one case ( 5.5%) of non-metastasizing PTC, while 15 (83.5%) cases on non-metastasizing PTCs and all of metastasizing PTCs and normal thyroid tissue had no immunoreactivity for p53. There was no statistically significanct difference among all groups of immunoreactivity for p53. Expression of Bax in patients with PTC was more than normal thyroid tissue ( P≤ 0.01). However, non-metastasizing and metastasizing PTC was similar. The results indicate that the metastasizing PTC showed significantly low CD44 expression than the non-metastasizing PTC (p ≤ 0.05), also the metastasizing and non-metastasizing PTC showed significantly less CD44 expression than the normal tissue (p≤ 0.05).
The immunohistochemical evaluation of p27 and CD44 expression in patients with PTC may be useful to predict for metastasis risk of the PTC to regional lymph nodes.
Research in J.Egypt. Pharmacol. Exp.Ther. 21 (1)(2002): 437–467