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Skeletal changes induced by treatment of pregnant rats with four potent teratogens, busulfan, acetazolamide, vitamin A palmitate, and ketoconazole, were evaluated using Alizarin Red S and Alcian Blue double-staining to investigate the relationship between drug-induced skeletal malformations and cartilaginous changes in the fetuses. Pregnant rats (N = 8/group) were treated once or twice between gestation days (GDs) 10 to 13 with busulfan at doses of 3, 10, or 30 mg/kg; acetazolamide at 200, 400, or 800 mg/kg; vitamin A palmitate at 100,000, 300,000, or 1,000,000 IU/kg; or ketoconazole at doses of 10, 30, or 100 mg/kg. Uterine evaluations and fetal external and skeletal examinations were conducted on GD 20. Marked skeletal abnormalities in ribs and hand/forelimb bones such as absent/ short/bent ribs, fused rib cartilage, absent/fused forepaw phalanx, and misshapen carpal bones were induced at the mid- and high-doses of busulfan and acetazolamide and at the high-dose of vitamin A palmitate and ketoconazole. Increased incidences of discontinuous rib cartilage (DRC) and fused carpal bone (FCB) were observed from the low- or mid-dose in the busulfan and acetazolamide groups, and incidences of FCB were increased from the mid-dose in the vitamin A palmitate and ketoconazole groups. Therefore, DRC and FCB were detected at lower doses than those at which ribs and hand/forelimb malformations were observed in the four potent teratogens.

Summary We hove sought to verify the possible role of the amygdala effecting on the renal function and urinary bladder movements by investigating the changes of the renal volume, urinary secretion, movements of urinary bladder, blood pressure, heart rate and respiration induced by stimulation on the basal telencephalon and diencephalon, especially on the amygdaloid nuclear complex and obtained following results: 1) I Decrease in the renal volume and retardation of the urine outflow were recognized by electrical and chemical stimulations of the medial principal nucleus (T of Völsch or medial small‐celled part of the basal nucleus of Johnston) and perhaps also by stimulation of the cortical nuclens 'B of Völsch), but not by stimulation or, the cortex of the piriform lobe or periamygdaloid cortical area (Rose's area periamygdalaris). Since isolated stimulation of the lateral or intermediate principal nucleus (M or T'. was difficult and in our stimulation experiments all another adjadent nuclear structures were injured, any definite conclusion could not be determined upon these nuclei. 2) Responses in the renal volume can be classified in several types. These, however, seem to have no correlation with the stimulated subnuclei, but seemingly stand in an intimate relationship with the types of change in the blood pressure caused by amygdalar stimulation. 3) Stimulation experiments of the arnygdala after severing various neighboring regions revealed that the impulse concerned may be conveyed immediately through the fibers passing across the optic tract to reach the hypothalamic nuclei on the same side. 4) Splanchnicotomy cusses generally increase in the urine dropping from the ureter. Stimuliaton on the‐ medial part of the amygdala after splanchnicotomy did also result in a decrease in the renal volume, while the urine secretion showed in one example a tendency toward increasing, but in another examples on remarkable alteration. 5) Experiments on hypophysectomized dogs produced also a slight diminution of the renal volume and an increasing effect upon the urine secretion. No remarkable effects were found after thyroidectomy. 6) Inhibitory effects upon the bladder movements may be elicited by stimulation of the medial principal nucleus (T of Völsch) as well as of the cortical nucleus (B). After cessation of stimulation, an abnormally strong contraction of the bladder can be occasionally observed or in some case;, mainly in repeated stimulations, a long inhibitory period was seen. Accelerated effects was recognized on the contrary by stimulation of the intermediate principal nucleus (T') with some after effects as diminution of some successive contractions. 7) Stimulations on another subnuclei of the amygdala and on the periamygdaloid cortical area were not effective upon urinary bladder movements, while stimulation of a certain part of the hippocampus cause micturition or a remarkable contraction of the urinary bladder. 8) Stimulation of the posterior orbital area of the frontal lobe produces an inhibitory effect upon re...