gramicidin-a and Body-Weight

Investigations were carried out on the immunosuppressive effect of gramicidin S (GrS), a cyclic peptide antibiotic produced by Bacillus brevis, on the onset of experimental ocular neuritis and allergic encephalomyelitis in Lewis rats immunized with rat brain homogenates. The criteria for evaluation of the drug effect were changes in body weight, activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), clinical manifestations such as paralysis of lower extremities and histopathological changes. Clinical symptoms and body weight reduction were effectively prevented by GrS treatment of immunized animals. The activity of the myelin marker enzyme CNPase was markedly decreased in the lumbar spinal cord of encephalitogen-immunized animals on day 16 (ie 16 days after immunization) and the decrease of enzymatic activity was partially prevented by GrS administration. On the other hand, the CNPase activity of the retrobulbar optic nerve of inoculated animals remained essentially the same as that of healthy control animals, although inflammatory changes were prominent in the optic nerve. Histopathological changes observed in the optic nerve and spinal cord of diseased animals were virtually absent in GrS-treated animals. A possible mechanism of the immunosuppressive activity of GrS is discussed.

Topics: 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Body Weight; Encephalomyelitis, Autoimmune, Experimental; Female; Gramicidin; Immunization; Immunosuppressive Agents; Optic Nerve; Optic Neuritis; Phosphoric Diester Hydrolases; Rats; Rats, Inbred Lew; Spinal Cord

The troches "Meiji" contain fradiomycin (neomycin), an aminoglycoside antibiotic, and gramicidin S, and are effective against gram-negative and -positive bacteria. In this paper the safety evaluation of the troches is reported. In this study male guinea pigs of Hartley strain were used, and fradiomycin (FRM) and gramicidin S (GRMN) were administered orally for 35 days consecutively except Sunday. The PRYER'S reflex test was carried out with frequency range of 10,000 approximately 15,000 Hz before, during and after the administration. After the last administration the animals underwent vital perfusion with physiological saline and then with Wittmack's fixative. Bilateral temporal bones were removed and fixed in the same fixative for several days. Using a conventional method, serial celloidin horinzontal sections were prepared and stained with hematoxyline-eosine to observe histopathological effect of the medicines on the organs of CORTI. The results were as follows: 1) There were no remarkable differences in the treated animals from the initial states. No animal died at all the doses tested. 2) All of the guinea pigs received 10 and 50 mg/kg of FRM and 4 and 20 mg/kg of GRMN for 35 days indicated positive pinna reflex in the extensive frequency range of 10,000 approximately 15,000 Hz. There was no remarkable damage in the organ of CORTI on histopathological examination. 3) It was concluded from these results that the troches are highly safe.

Topics: Animals; Body Weight; Dosage Forms; Drug Combinations; Drug Evaluation, Preclinical; Gramicidin; Guinea Pigs; Hearing; Male; Neomycin; Organ of Corti; Reflex