Conversion in vitro of pregnenolone to progesterone by the ovaries from immature rats after treatment of PMS and HCG was inhibited by addition of PGE₂ (1.4×10^-7M) or PGF_2α (1.4×10^-7M). Result of conversion in vitro of pregnenolone to progesterone and estradiol-17β by ovary of adult rat in estrus showed that the progesterone biosynthesis in the ovary was inhibited by PGF_2α (1.4×10^-7M) but the releasing rate of progesterone from the ovary into the medium increased by about 1.25 fold. Progesterone in the medium decreased dramatically following incubation. Estradiol-17β in the ovarian tissue and in the medium did not differ from the control rate with addition of PGF_2α. When the effect of PGF_2α (1.4×10^-7M) in vitro on the conversion of testosterone to estrone and estradiol-17β by the ovary from adult rat in estrus was studied, we found that the releasing rate of estrone from the ovary into the medium was increased by addition of PGF_2α; the rate was significantly different from control level after addition of PGF_2α 30 min of incubation (p<0.01). Thus a minute amount of PGE₂ and PGF_2α influences steroid biosynthesis in the rat ovary.

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Neurophysiological properties of the peripheral nerves of alloxan-induced diabetic rats and effects of vitamin B complex (V) were studied. Alloxan monohydrate was administered to Wistar (38 mg/kg, i.v.) and Sprague-Dawley (SD, 45 mg/kg, i.v.) rats. In Wistar diabetic rats (blood sugar level: more than 400 mg/dl for 6-8 weeks), nerve potentials with 2 peaks were recorded from the tibial and peroneal nerves. The late component had a higher threshold, longer time of recovery from excitation and slower conduction velocities. Large doses of V (B₁: 100, B₆: 100 and B₁₂: 1 mg/kg, i.p.) administered daily until the experiment inhibited the appearance of the late component. In SD diabetic rats(the same blood sugar content for 6 ?? 8 months), the ventral root potentials had a longer duration, higher threshold and longer time of recovery from excitation. In V administered rats, particularly along with insulin, these changes were prevented. Most efferent fibers of non-treated rats had a refractory period of less than 3.0 msec. The number of fibers with this refractory period was greatly reduced in the diabetic rats. Although rats administered each component of V₁₀₀ and V₅₀ had efferent fibers with similar refractory periods to that of rats in A-S group, those administered V₁₀₀ had efferent fibers with significantly shorter refractory periods. Thus, efferent fibers seem to be more sensitive than the afferent ones at the early stages of the long term diabetic state and a large dose of V, particularly along with insulin, depressed these changes.

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The discharge in afferent nerves of cat soleus muscle was recorded in Nembutal anesthetized animals. The frequency of discharges in the soleus muscle nerve was found to increase after tetanic contraction of the muscle either under ischemic or non-ischemic conditions. Two cases which had been associated with the augmentation of the discharge followed by tetanic contractions of soleus muscle exhibited excitation, i. e., increase in discharge frequency, due to an intraarterial injection of 10% NaCl solution, whereas no such excitation with the injection of 10% NaCl, was observed in two other cases which showed no post-tetanic potentiation. Increase in discharge frequency recorded from single nerve fibres, after tetanic contractions of soleus muscle under an ischemic condition, was demonstrated in one out of 11 fibres of group I, 2 fibres out of 20 in group II and one fibre out of 11 in group III. The increase seen in groups I and II were of a transient type, and that in group III was a lasting type which continued for more than 8 min. Although a vitamin B complex (the combination of thiamine monophosphate disulfide 107.3 mg, pyridoxine hydrochloride 100 mg and cyano-cobalamine 1 mg), dissolved in 20% glucose solution, tended to enhance spontaneous discharge in the soleus muscle nerve, the post-tetanic potentiation of the discharge was significantly suppressed by this combined administration. The vitamin B complex dissolved in Ringer's solution also showed actions similar to, but weaker than, those of the complex dissolved in the glucose solution. These results suggest that vitamin B complex may effectively be used for the relief of muscular pain under ischemic conditions.

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ACh response in the isolated duodenum from SART stressed (repeated cold stressed) mice was remarkably decreased in comparison to normal mice 5 days after onset of loading SART stress, and maximal contraction in SART stress mice duodenum was about 37% of that in non-stressed mice. Pilocarpine and KCl responses were also considerably decreased, but BaCl₂ response was much the same as in the controls. Thus, the contraction system of the muscle is apparently not damaged by SART stress. Though body weights decreased, the daily intake of food increased in SART stressed mice. Length of small intestine from SART stressed mice was much the same as in controls, but wet weights of small intestines were larger than in controls. Autonomic agonists, antagonists, tranquilizers and other drugs were given intraperitoneally to mice once daily during SART stress, and the ACh responses in the isolated duodenum were investigated. Pretreatment with adrenergic and anticholinergic drugs inhibited the decrease of ACh response, but antiadrenergic and cholinergic drugs had no effects. Pretreatment with tranquilizers such as reserpine, chlorpromazine, carpipramine and imipramine inhibited the decrease of ACh response in the isolated duodenum, but diazepam, meprobamate and benadryl had no influence. Pretreatment of neurotropin, a neurosedative had good inhibitory effects. Our results suggest that SART stressed mice may be in a state of unbalance regarding sympathetic and parasym pathetic nerves, particularly with regard to abnormal tension in the parasympathetic nervous system, in part of the duodenum. Pretreatment with most of the above drugs had no influence on loss of body weight in SART stressed mice while pretreatment with neurotropin inhibited body weight to a considerable extent.

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SL-573 (1-cyclopropylmethyl-4-phenyl-6-methoxy-2(1H)-quinazolinone) was tested for its effect on the chemotaxis, phagocytosis, phagocytosis-stimulated oxygen uptake and lysosomal enzyme release of rat polymorphonuclear leucocytes and the histamine release from rat mast cells. In phagocytosis, SL-573 did not show significant inhibitory activity (less than 25% even at a high concentration of 200 μM). The effects of other nonsteroidal anti-inflammatory agents on phagocytosis were also insignificant as follows: indomethacin (IM): no effect at 400 μM and 50 ?? 80% inhibition at 800 μM, mepirizole(MP) : about 25% inhibition at 1000 μM, aspirin (AS): no effect at 1000 μM, and ibuprofen (IP) : no effect at 1000 μM. SL-573, on the other hand, apparently inhibited other functions of polymorphonuclear leucocytes and mast cells at concentrations below 100 μM. Particularly, SL-573 was a potent inhibitor of phagocytosis-stimulated oxygen uptake (IC₅₀: 23 μM). The inhibitory activity of SL-573 was 17 times that of IM and more than 40 times those of IP, MP and AS. In chemotaxis, SL-573 showed 50% inhibition at 58 μM, while IC₅₀ values of IM, IP, MP and AS were 31 μM, 68 μM, 370 μM and 460 μM, respectively. The inhibitory effect of SL-573 on lysosomal enzyme release was 49.5% at 100 μM. The inhibitory activity was more potent than those of IM (100 μM: 11.8% inhibition) and IP (100 μM: 20.2%). AS and MP did not significantly affect the lysosomal enzyme release at 100 μM. In histamine release from mast cells, SL-573 showed more potent inhibitory activity (100 μM: 35-58% inhibition) than IM (300μM: 43 ?? 58%), IP (1000μM: 49 ?? 51%), AS (1000 μM: 1 ?? 5%) and MP (1000 μM: 1 ?? 41%).

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N-Ethyloxycarbonylaminomethyl-L-isoleucine (A-145), a novel antitumor amino acid derivative, is an antitumor agent effective in cases of Ehrlich ascites rather than against Sarcoma-180. The chemotherapeutic index of A-145 was 14.9 for Ehrlich ascites carcinoma and 4.2 for ascites Sarcoma-180. Experimental studies on ddy mice regarding the difference in susceptibility of these two tumor cell lines to A-145 gave the following results. In in vivo experiments, the uptake of ¹⁴C-A-145 by Ehrlich ascites carcinoma was greater than by Sarcoma-180, i. e. the uptake ratio of Ehrlich ascites carcinoma/Sarcoma-180 was 1.52 at 30 min and 2.7 at 24 hr after injection. In in vivo experiments, there was no remarkable difference between Ehrlich ascites carcinoma and Sarcoma 180 in the subcellular distribution of ¹⁴C-A-145, and the majority of the radioactivity taken up was distributed in nuclei and cytosol fractions. In in vitro experiments, the uptake of ¹⁴C-A-145 by both cell lines was found to be temperature sensitive, glucose dependent, and decreased on addition of KCN, 2, 4-dinitrophenol or iodoacetic acid. In in vitro experiments, competitive inhibition by L-isoleucine on ¹⁴C-A-145 uptake into tumor cells was observed in both cell lines, however, in vitro experiments, the inhibitory effect of A-145 on cell growth in cultured Sarcoma-180 was not reversed by L-isoleucine.

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It has been reported that an increase in dopaminergic activity in the striatum can induce gnawing compulsion, a stereotyped behavior. Apomorphine, amphetamine and L-DOPA also produce such effects, particularly in the rat. However, it has been reported that the gnawing compulsion in the guinea pig cannot be induced with L-DOPA and is not related to the levels of catecholamine in the brain. It is of essential importance in this kind of research to clarify whether or not a dopaminergic mechanism is equally involved in gnawing compulsion of the rodent in general. The present study dealt with the mechanism of gnawing compulsion with L-DOPA administration to guinea pigs. Gnawing compulsion was amplified by crystal pick-up and amplifiers and was continuously recorded by an inkwriting-oscilloscope. The recorded data were scored for quantitative and objective analysis. Certainly, L-DOPA alone did not induce continuous gnawing, but the gnawing was obviously induced by pretreatment with benserazide, a peripheral decarboxylase inhibitor. The induced gnawing compulsion was inhibited by pimozide and haloperidol which are both dopamine receptor blockers. When catecholamine synthesis was inhibited by pretreatment with α-methyl-p-tyrosine, the amphetamine induced gnawing compulsion alone was markedly inhibited, but the apomorphine or L-DOPA induced gnawing compulsion following the pretreatment with benserazide was not inhibited. Therefore, it was deduced that gnawing compulsion was induced with amphetamine indirectly by dopamine release, with apomorphine by its direct stimulation of the dopamine receptor, and with L-DOPA by its action on the dopamine ieceptor, after having been converted to dopamine. Based on these results, it was concluded that the dopaminergic mechanism is closely involved in gnawing compulsion seen in the guinea pig as well as in the rat.

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Mechanical contraction of the dorsal sacro-cocygeus muscle and electrical stimulation of spinal cord elicited tail elevation such as straub tail reaction(STR). When morphine, 0.25 ?? 0.5 μg, was injected into the lumbothecal space, STR was produced dose-dependently and such was the same as that produced by systemic injection of morphine. STR was not observed, when morphine was injected into the lumbo-thecal space in spinal mice. STR was antagonized by tubocurarine given subcutaneously and by naloxone injected into the lumbothecal sapce. STR was not antagonized by the right, left or both dorsal spinal lesion at C_{5 ?? 6} as well as by the right or both dorsal spinal lesion at T_{11 ?? 12}. However, STR was antagonized by the spinal transection at T_{11 ?? 12}. The lesion of spinal serotonergic neurons enhanced STR. These results suggest that morphine acts on both the lumbo-sacral nerve cell bodies and the nerve terminals descending via the spinal ventral horn, by which the morphine-induced contraction of dorsal sacro-coccygeus muscle tendons produce STR.

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Rats were provided a normal laboratory diet or a low Ca-vitamin D-deficient diet. After the administration of 1α-hydroxycholecalciferol, mitochondria, microsomes and slices were prepared from kidney cortex of both control and treated rats. When 1α-hydroxycholecalciferol was given to normal and low Ca·vitamin D-deficient rats, Ca accumulation in mitochondria was stimulated during 30 minutes and the high calcium content was maintained at the subsequent incubation. There was a significant decrease of mitochondrial Ca²⁺-ATPase and Mg²⁺-ATPase activities with low Ca·vitamin D depletion, but both enzyme activities were restored by 1α-hydroxycholecalciferol treatment of the depleted rats. Ca²⁺-ATPase and Mg²⁺-ATPase activities of microsomes were not altered with the administration of 1α-hydroxycholecalciferol. In contrast to results of mitochondrial Ca transport, changes in Ca influx and efflux of slices were not significant in response to the treatment of low Ca·vitamin D-deficient rats with 1α-hydroxycholecalciferol. The results of the present study suggest that 1αhydroxycholecalciferol plays a role in the process of Ca accumulation and ATP hydrolysis of mitochondria in kidney cortex.

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