• Toxicological Research
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• v.13 no.1_2
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• pp.167-173
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• 1997

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rabbits (New Zealand White strain) from day 6 to 18 of gestation at dose levels of $0.35 \times 10^6$, $0. 69 \times 10^6$, and $1.38 \times 10^6$ I.U./kg/day. Hydrocortisone sodium succinate (0.3 mg/kg/day) was also given in the same way. Teratological effects of the test agents on the organogenesis of fetuses and the development of offsprings (F1 rabbits) were investigated. The results were as followings: (1) No significant changes by the treatment of LBD-001 or hydrocortisone sodium succinate were observed in the body weights, the food and water consumption, the lactating or nurshing behaviors, and the autopsy of the pregnant rabbits. (2) No significant changes in the resorption rate, the fetal organogenesis, and the normal develpoment of offsprings (F1) by the treatment of LBD-001 or hydrocortisone sodium succinate were detected. The results show that LBD-001 at the dose of $1.38 \times 10^6$ I.U./kg/day or less and hydrocortisone sodium succinate at the dose of 0.3 mg/kg/day are neither teratogenic in the organogensis of the fetuses and the development of the offsprings (F1) nor toxic to the mother rabbits.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.301-309
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• 1996

LBD-001, a recombinant human interferon ${\gamma}$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rats (Sprague-Dawley) from day 7 to 17 of gestation at dose levels of 0.35$\times$10$^{6}$ , 0.69$\times$10$^{6}$ , and 1.38$\times$10$^{6}$ I.U./kg/day. As the control groups, hydrocortisone sodium succinate (5 or 10 mg/kg/day) was also similarly administered. Teratological effects of the test agents on fetuses and development of offsprings (F1 rats) were investigated. (1) No significant changes by the treatment of LBD-001 were observed in body weight, food and water consumption, feeding and nursing behaviors, and autopsy of pregnant or lactating mother rats. However, in hydrocortisone sodium succinate (10 mg/kg/day)-treated group, significant decreases of body weight on day 16, 18, and 20 of gestation and food consumption on day 20 of gestation and outstanding atrophy of thymus and adrenals were observed in two rats autopsied on day 20 of gestation. (2) No significant changes in resorption rate, skeletal or visceral development of fetuses, and physical or sensory development of offsprings (Fl) by the treatment of LBD-001 were detected. In hydrocortisone sodium succinate (10 mg/kg/day)-treated group, however, there were significant decreases of body weight of fetuses, delay of ossification, temporary delay of body weights of offsprings (F1) on day 1 and 3 of lactation, and increased tendency of stillborn rate and malformation rate of bone. The results show that LBD-001 at the dose of 1.38$\times$10$^{6}$ I.U./kg/day or less is not teratogenic in organogenesis of fetuses and the development of offsprings (F1). Meanwhile, hydrocortisone sodium succinate (10 mg/kg/day) seems to delay ossification of fetuses and temporarily retard the development of offsprings (Fl).

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.568-573
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• 1994

Corticosteroids are widely used in the treatment of various diseases because of its potent antiinflammatory effect. According to recent knowledge, bronchial asthma is also chronic inflammatory disease. Therefore antiinflammtory agent such as cromoyln sodium and corticosteroid is highly recommended for treament of chronic bronchial asthma. Especially hydrocortisone succinate (Solu-Cortef) is commonly used for treament to acute asthmatic attack via intravenous injection due to have rapid therapeutic onset and short duration. Since Sunaga et al. reported acute asthma attack after hydrocortisone injection in 1973, several cases of bronchospam with or without angioedema and urticaria after intravenous injection of hydrocortisone have been reported. We experienced a case of severe bronchospasm and acute respiratory failure after intraveous injection of hydrocortisone succinate in 64 year-old female asthmatic patient who visited to emergency room for acute asthmatic attack. About 5 minites after Solu-Cortef injection, a severe bronchospasm with arterial hypoxemia was developed. In order to confirm the suspected relationship between the offending drug(Solu-Cortef) and acute bronchospasm, we examed intravenous and inhalation provocation test by hydrocortisone succinate and methylprednisolone(control). After administration of hydrocortisone succinate via intravenous and inhalation route, severe asthmatic attack occurred. But administration of intravenous methylprednisolone and orall triamcinolone and saline were not provoke bronchospasm. Skin test using hydrocortisone sodium succinate was also positive. Administration of hydrocortisone is very serious to asthmatic patient with hydrocortisone hypersensitivity. Therefore, the clinician must be have history taking about previous adverse reaction of steroid before its clinical use. And methylprednisone may be useful and safe drug to the treatment of acute asthmatic patient with hydrocortisone hypersensitivity.