Administration Of INH Research Articles

Effects of Isoniazid on Psychomotor Skills Related to Driving

The effects of single oral dose of 751 mg INII, alone or in combination with 0.5 Gm/kg of alcohol, on psychomotor skills related to driving were investigated. Volunteer cadets (100) were tested with a battery of a choice reaction test, two coordination tests, and an attention test. Further, 50 drivers from motorized troops drove a simulator for 40 minutes. the experiments were double blind. Both INII and alcohol slightly elevated the subjective feeling of performance. At 30 minutes after the ingestion of the drugs, both INII and alcohol shortened reaction time, and INH also improved coordination at 90 and 150 minutes after drug intake. Both alcohol and INH impaired attention. No major interaction was observed between INH and alcohol in psychomtor tests. In simulated driving, INH antagonized the deleterious effect of alcohol on attention. The numbers of collisions at emergency were slightly increased after either drug. The numbers of drivers driving off the road were increased after alcohol and INH given together. After this combination, the small movements of the steering wheel characteristic of drunken drivers were significantly increased. Administration of INH, 10 mg/kg might cause some extra risks for driving in the very beginning of the treatment and in combination with alcohol. /Author/

A correlation between changes in GABA metabolism and isonicotinic acid hydrazide-induced seizures

Summary The intramuscular administration of INH (2.2 mmoles/kg) to chicks caused striking changes in brain GABA metabolism during a 16 h period following the injection. A sequential decrease and increase in brain GABA levels was observed. Both GAD and GABA-T enzyme systems were inhibited. Although GAD was inhibited more quickly following the INH treatment, the decrease in GABA-T activity continued for a much longer period of time and eventually the GABA-T system was inhibited to a greater extent than that of GAD. Seizure activity in the chicks was not related to changes in GABA levels nor to changes in the activities of GAD or GABA-T but did bear a relationship to a function which incorporated changes in both GABA levels and GAD activity. The possible significance of this correlation was discussed.

Isoniazid Toxicosis in Ducklings: Studies on Pyridoxine, Niacin, Glutamic Acid, and Arginine Supplementation

Isoniazid (isonicotinic acid hydrazide, INH), used widely in the prevention and treatment of tuberculosis of man and animals, has been found to have marked neurotoxic activity in Pekin ducks (3). Birds poisoned by dietary administration of the drug exhibit tremor and ataxia and are observed to have marked morphologic alterations in the brain, especially severe in the cerebellar medulla. Although lesions have not been described in human patients treated with the drug, several reports (13) have appeared on the occurrence of peripheral neuritis. Early studies by Biehl and Vilter (1) established that peripheral neuritis associated with INH therapy could be prevented by the administration of pyridoxine. However, as a supplement to the diet it was found in a preliminary study not to be effective in counteracting the toxic effects induced in ducks by dietary administration of INH (3). Convulsions, stupor, and somnolence have been observed in human patients after INH therapy; these clinical manifestations of toxicity occurred more frequently when INH was combined with pyridoxine (8,13). Glutamic acid has been found to be effective in preventing neurotoxic symptoms of INH toxicosis. Roberts and as-

The effect of isonicotinic acid hydrazide on the development of tumors.

AbstractIsonicotinic acid hydrazide (INH) was administered as a 0.1% solution in the drinking water for the life span of adult AKR inbred mice. The treatment resulted in no significant inhibitory effect on the development of malignant lymphomas which are characteristic of these animals, nor did it induce other tumors.Similar administration of INH as 0.05 and 0.15% solutions to adult randomly bred Swiss mice enhanced the formation of pulmonary adenomas, while it had no apparent inhibitory influence on the progression of other types of tumors.Single doses of 500, 400, 300, 250, 200 and 100 μg of INH were injected subcutane‐ously on the day of birth to Swiss mice, without significant tumorigenic effect.The problem of tumor induction versus inhibition is discussed.

実験動物の皮膚と四肢および内臓における抗酸菌の分布

Detailed observation of the distribution of acid-fast bacilli in the various parts of the healthy mouse is important as a measure for obtaining knowledge on the route of invasion of the organism into the animal and by the summation of the findings in numerous investigations, it may become possible to clarify the mechanism of infection of the murine leprosy bacillus under natural conditions.In relation to the above, the distributuion of acid-fast bacilli following administration of DDS and INH and bacillary distribution in animals other than the mouse were also examined.The acid-fast bacilli were collected by the Dharmendra's method using chloroform and ether. The skin was depilated and washed, the organs were cleansed well to eliminate all bacteria which may be adhering to the surface. The bacteria count was made by the formula given below.×quantity of bacterial suspension No. of organisms per 1 loop quantity per loop (0.002 ml) x=No. of samplesThe specimens were prepared by smearing one loopful of bacterial suspension on a glass slide, covering with phenol gelatin water and staining with Ziehl-Neelsen stain.The results are shown in the table. As may be seen, a considerable number of bacilli was present in the skin and foot pad of the mouse and in the organs, a somewhat larger number was found in those organs connected with the outside. There was no pronounced differnce according to the site of the skin. No difference in bacterial count was found between the 6-months DDS and INH treated mice and the untreated control.It is notewarthy that acid-fast bacilli were isolated from the foot pad of the guinea pig, rabbit and cat and from the skin nerve of the monkey. Studies must be carried out in the properties of these organisms in the future

EXPERIMENTAL RE-EVALUATION STUDIES ON ISONICOTINIC ACID HYDRAZIDE lN VITRO AND IN VIVO Ⅳ. Experimental Studies on Comparisons of Therapeutic Effects by Administration Modes of Isonicotinic Acid Hydrazide (lNH) in Mice Infected with the H37Rv Strain.

In this experiment the writers studied various modes of INH oral administration to the SM-strain mice infected with the H<sub>37</sub>Rv strain. The results were as follows 1. When doses of INH less than 1.8mg per kg were administered orally to experimental tuberculosis mice, daily twice administration of INH was less effective than daily once administration of the same amount of INH in the antibacterial efficacy and also in development of INH-resistant tubercle bacilli 2. When doses of INH larger than 18mg per kg were administered orally to experimental tuberculosis mice, there was no difference in anti-bacterial effects of INH between daily twice and daily once administration of the same amount of INH, In the mice treated twice daily with INH resistant tubercle bacilli developed more frequently. 3. Intermittant every other day administration of high doses of INH (18mg per kg and 72 mg per kg) were less effective and induced more frequently INH-resistant tubercle bacilli than daily once administration of the same amount of INH in experimental tuberculosis mice. Intermittent impact doses of INH(72mg per kg) were toxic to mice as well as daily once administration of the same doses of INH. 4. The frequency and grade of development of INH-resistent tubercle bacilli in vivo depended on the amount of administration doses, the length of time in contact with the drug and the grades of multiplication of tubercle bacili. 5. Impact therapy with the maximum administrable dose of INH(72mg per kg) is not to be recommended in tuberculosis. 6. We suggest further studies on the modes of administration and suitable effective doses of INH for man.

Studies on Methods of Administration of INH from the Viewpoint of Concentration of Active INH in Human Serum

Studies on Methods of Administration of INH from the Viewpoint of Concentration of Active INH in Human Serum

BCG接種モルモツトの・アレルギーと免疫力とに及ぼすINHの影響

BCG接種モルモツトの・アレルギーと免疫力とに及ぼすINHの影響

TREATMENT OF TUBERCULOUS PLEURAL EFFUSIONS WITH PARTICULAR REFERENCE TO ADRENAL CORTICOSTEROIDS

On the basis of our own experience with tuberculous pleural effusions in children as well as on the more extensive experience of other clinicians working with adult patients, we believe that adrenal corticosteroids, given simultaneously with adequate antituberculous drug therapy, not only exert no deleterious effect on the underlying tuberculous infection, but frequently hasten clinical and roentgenographic improvement. Six consecutive patients with tuberculous pleural effusions are here presented. Diagnosis was established with the aid of tuberculin test, cultures of gastric washings and pleural fluid, and pleural biopsy. Treatment included administration of INH, PAS and prednisone. The clinical and roentgenographic response was unusually prompt in the five patients with early effusions. On the basis of this experience we recommend the following treatment: INH (20 mg/kg/24 hr) for a period of at least a year, PAS (0.5 gm/kg/24 hr) for the same length of time; and prednisone (1.0 mg/kg/24 hr) for a period of about 4 to 6 weeks, with diminishing doses during the ensuing 2 weeks. The general care should be that given to any child with early active tuberculosis, including bed rest during the febrile period but rarely beyond it. If such treatment can be instituted early, the incidence of pleural adhesions, with ventilatory impairment and development of scoliosis, is probably lessened. The sixth patient, who was suffering from fibrocaseous pleurisy at the time of admission to our hospital, recovered slowly; in this case adrenal corticosteroid therapy appeared to exert no effect on the course of the disease.

SERUM LEVEL AND URINARY OUTPUT OF URIC ACID IN PATIENTS OF PULMONARY TUBERCULOSIS RECEIVING SM, PAS AND INH

In 137 patients of pulmonary tuberculosis serum uric acid level was determined by Newton's method. The mean value in 100 male patients was 3.74±0.98mg per dl, and the mean value in 37 female patients was 3.04±0.87mg per dl. This difference in sex is statistically significant. Between age and serum uric acid level there was not a significant correlation. On the other hand there was found a correlation between the pathological findings in chest X-ray and the serum level of it; i.e. severer the pathological findings in chest X-ray was, lower the uric acid level in serum was. It was also lower in the patients with positive culture in sputum than the patients with negative culture.The administration of PAS, SM or INH showed no appreciable influence on the uric acid level of patients.Urinary output of uric acid was mesured in 28 patients taking ordinary diet of author's sanatorium and the mean daily output was estimated as 497(122-872)mg and there was found no correlating factor with this value, with the exceptin of PZA administration, which will be discussed in next paper.