Correlation between urinary catecholamine (CA) and various endocrine diseases has been reported by many authors. The effect of cold stress on the sympathetic nervous system (particularly tissue CA levels) under patho-physiological stage, however, is not well known. This experiment dealt with the effect of cold stress on tissue norepinephrine (NE), plasma NEFA, glucose and colonic temp. in alloxan diabetic rats in order to investigate the role of the sympathetic nervous system in diabetes mellitus. Cardiac NE of diabetic rats was decreased to about one half that of control, however, brain NE was not statistically altered. When diabetic rats were exposed to cold for several hr, cardiac NE was even more decreased. On the contrary, brain NE was increased significantly all the periods. Plasma NEFA and glucose of diabetic rats were significantly increased compared to control values. When these animals were exposed to cold, both were increased markedly for the first 30min, but thereafter showed a tendency of decrease and in particular plasma glucose showed a lower value than diabetic control value after 6hr. Absolute values of both substrates, however, were still higher than control values after 6hr periods. Colonic temp. fell markedly, but showed a tendency to recover within 3 to 6hr. These results indicate that the sympathetic nervous system in alloxan diabetes is stimulated and the decreased cardiac NE may reveal an attempt to remedy the low intracellular glucose level. More marked changes were observed in diabetic rats exposed to cold.
Respiratory resistance in dogs treated with reserpine or tyramine revealed that clorprenaline produced an increased of respiratory resistance but metaproterenol and trimetoquinol showed a decrease. Observations on the blood pressure of rats treated with tyramine were similar to the above. Increase of airway resistance provoked by histamine or acetylcholine, clorprenaline and metaproterenol had a long lasting action while that of trimetoquinol was temporary.
Pharmacological properties of butoxybenzyl hyoscyamine bromide (BHB) on isolated smooth muscle organs; stomach, intestine, gall-bladder, urinary bladder and uterus of animals (mice, rats, guinea pigs and rabbits) were investigated and compared to atropine sulfate (Atr), hyoscin N-butyl bromide (HBB) and prifinium bromide (PB). The tonus and spontaneous motility of isolated smooth muscles were decreased by BHB at the concentration of 1×10-4_??_10-5g/ml and the effects of BHB were more potent than those of Atr, PB and HBB. Anticholinergic and antinicotinic actions of BHB were observed at a concentration over 1×10-9g/ml and these effects of BHB were almost equivalent to those of Atr and PB, and more potent than that of HBB. BHB showed relatively potent anti-BaCl2 action in the ileum and stomach, and Atr, PB and HBB were less potent than BHB in this regard. Antihistaminic and antiserotonic actions were also observed in a relatively high concentration of BHB.
Effects of butoxybenzyl hyoscyamine bromide (BHB) on gastro-intestnal motility and secretion, salivary secretion and pupilis in animals were investigated. BHB inhibited the contraction of nictitating membrane during stimulation of cervical sympathetic preganglionic fiber in the dog. BHB inhibited spontaneous motility, motor activity elicited by bethanechol and the contraction during vagal stimulation in the gastro-intestinal tract of dogs, and also propulsion of charcoal meal in the intestine of mice. BHB reduced the basal or bethanechol stimulated acid secretion in rats and feeding or bethanechol stimulated acid secretion in Heidenhein pouch dogs, but not tetragastrin stimulated acid secretion in rats. BHB did not exhibit the inhibitory effect on the pancreatic and biliary serection in rats. BHB prevented the ulcer formation in the pylorus ligated or stress rats. BHB inhibited the chorda tympani nerve stimulated salivary secretion in dogs and the duration of this effect of BHB was shorter than that of inhibitory effects on gastro-intestinal motor activity. Mydriasis was observed in dogs and mice at large doses of BHB.
This study was conducted in order to ascertain the effects of vitamins on various malformations in the Wistar albino rat fetus caused by administration of vitamin K3 to the mother during pregnancy. Maternal rats were given an oral administration of vitamin K3 0.15mg/day/rat (control group). Experimental groups were given vitamin K3 15mg/day/rat group and another group 150mg/day/rat. Results are as follows. 1. As for increase in mother's body wt., pregnancy rate, and total number of delivered fetuses, no differences were observed. 2. Resorption was evident in the dead fetuses of the 15mg/day/rat group and the 150mg/day/rat group. There was no difference regarding number of surviving fetuses in each group. 3. Retardation of ossification of occipital bone and sternebrae was slightly observed in the fetus of the 15mg/day/rat group and markedly in the fetus of the 150mg/day/rat group. 4. Abnormalities in appearance and skelton were not induced. 5. Effect of vitamin K3 was induced slightly in the fetus of the 15mg/day/rat group and markedly in the fetus of the 150mg/day/rat group. There were abnormalities in appearance.
1) This study was undertaken to ascertain the difference between, the control group (0.75mg/day/rat) and experimental groups (7.5 and 75mg/day/rat) regarding the effect of vitamin E. 2) Mother's body wt. was remarkably decreased in the 75mg/day/rat-group. Pregnancy rate was slightly lower in the 7.5mg/day/rat-group and was 50% in the 75mg/day/rat-group. 3) Implantation condition of pregnant mothers was slightly less in the experimental group. 4) Slight ossification retardation in fetus of occipital bone and sternebrae was generally observed in the experimental group. 5) Abnormalities in appearance and skeleton were not observed. 6) Effect of vitamin E on the fetus was induced in the 75mg/day/rat-group, but abnormalities in appearance were not observed.
The actions of title compounds on acute inflammation were examined and compared to such structural analogous as mefenamic acid (MA) and flufenamic acid (FA) or such antiinflammatory agents as phenylbutazone (PB) and indomethacin (IM). In the anti-inflammatory effects tested in oral administration, no significant difference was observed between free and sodium compounds. In the inhibitory effects on increased vascular permeability and acute edema, No. 1 compound showed a more potent activity than MA, FA and PB, while No. 2 compound had an activity similar to MA. The inhibitory effect of test compounds on carrageenin edema did not decrease in adrenalectomized rats. Both No. 1 and No. 2 compounds revealed a markedly inhibitory action on ultraviolet erythema as well as fenamates. Neither showed antagonistic effects on the mediators (except for serotonin) and urine volume was not increased. The test compounds were considered to have a similarly specific anti-inflammatory activity to the known anti-inflammatory agents and compound (No. 1) which substituted carbonic acid of anthranilic acid to acetic acid was found to have a more potent anti-inflammatory action than the original compound (No. 2).
It was reported in a previous paper that No. 2 compound had a similar effect to flufenamic acid (FA) on acute experimental inflammation and the No. 1 compound which was substituted carbonic acid of No. 2 to acetic acid had a more potent effect than FA. In this paper, the effects of title compounds on subacute experimental inflammation are described in comparison with such known anti-inflammatory agents as FA, mefenamic acid (MA), phenylbutazone (PB) and indomethacin (IM). On sustained mustard edema, granuloma tissue formation (cotton pellet, granuloma pouch and wound healing) and adjuvant arthritis, No. 2 showed a similarly inhibitory effect to FA and PB, while No. 1 showed a more potent effect than No. 2 and FA and similar to IM. Both No. 1 and No. 2 compounds had a more potently inhibitory effect on subacute infiammation than on the acute. In these anti-inflammatory activities, no significant difference was observed between free and sodium salt, but No. 1 was several times more potent than No. 2 as on acute inflammation as well. Neither compound showed a direct analgesic or uricosuric effect, but indirectly an analgesic effect was observed, due to an anti-inflammatory action. From the potent effect on subacute inflammation and in addition, a markedly inhibitory effect on carrageenin edema and ultraviolet erythema, test compounds, in particular No. 1, may be considered effective on such chronic inflammation as rheumatic disease, while toxicity and ulcerogenic action were found to be stronger than FA and PB.
It is presumed that the central nervous system play a role in inflammation. Some reports have been made on the anti-inflammatory action of morphine and chlorpromazine, therefore anti-inflammatory and analgesic effects of benzodiazepine derivatives, a kind of tranquillizer, were examined. On the acute and subacute various experimental inflammations, benzodiazepines showed an inhibitory effect in some cases and not in others depending on the phlogist and method. In order for benzodiazepine to inhibit inflammation, a greater dose than the effective tranquillizing dose was required even so, the anti-inflammatory activity was slight. There was no derivative which had consistent anti-inflammatory effect among the benzodiazepines. All benzodiazepines tested showed no analgesic effect, but rather a synergistic effect in combination with morphine. The potentiation of benzodiazepines to morphine was found in a less than effective tranquilizing dose. From the above results, it may be considered that benzodiazepines do not have anti-inflammatory and analgesic effects, but rather potentiate the analgesic effect of morphine.
1. Weanling rats were orally administered 1.5mg/day/rat of vitamin K3 (×10 group), 15mg/day/rat of vitamin K3 (×100 group) and 150mg/day/rat of vitamin K3 (×1, 000 group). The experimental group was treated for 12 wk. Increase in body wt. of weanling rats was low in the 150mg/day/rat group, and an enlarged spleen in the males was also observed in the same group. 2. Mother rats were fed on the same diets as the 3 experimental groups for about 20 days before the pregnancy and then through the gestation and natal periods. The offspring were fed a normal diet during the 12wk. after being weaned. Increase in body wt. of weanling rats did not differ among the subjects, and abnormalities in organs were also absent. 3. Mother rats were fed on the same experimental method No. 2 through the gestation, neonatal and lactation periods. The offspring were fed on a normal diet for 12 wk. after being weaned. As for the increase in body wt. of weanling rats, there was no difference found in any group, and abnormalities of organs were absent. 4. Mother rats about 20 days before pregnancy and through the gastation period, and weanling rats for 12 wk. after being weaned were given 150mg/day/rat of vitamin K3. These subjects were normal as to the number of RBC and WBC, values of hematocrit and hemoglobin, bleeding time and prothrombin time, blood sugar, hemoglobin urea. 5. Mother and weanling rats fed on the same experimental method No. 4 revealed high values for Icterus Index and bilirubin. The experimental offspring of mother rats fed on a normal diet after neonatal and lactation periods had normal values for Icterus Index and bilirubin.
The antisecretory and antiulcerogenic activities of Bergenin were studied and the following results were obtained: Bergenin was shown to have a dose dependent antisecretory effect on gastric secretion in pylorus ligated rats for 3_??_6hr (s. c., 140_??_315mg/kg). LD50 for gastric secretion in pylorus ligated rats for 6hr was as follows; Free acidity 210mg/kg, total acidity 240mg/kg and gastric juice volume 260mg/kg. Bergenin was not only shown to have dose dependent antiulcerogenic activities in stressed rat ulcers, but also was found to have the same effect on experimental ulcers induced by serotonin, reserpine and fasting. LD50 for each experimental ulcer was as follows: Reserpine ulcer 64mg/kg, serotonin ulcer 32mg/kg, stress ulcer 38mg/kg and fasting ulcer 50mg/kg, however Bergenin had no antiulcerogenic effect in pylorus ligated rats for 18hr.
1) Weanling rats were individually administered vitamin E orally 0.5_??_0.75mg/day/rat (control group), 5.0_??_7.5mg/day/rat (×10 group) and 50_??_75mg/day/rat (×100 group). Period of experimental group was 12 wk. Increase in body wt. of weanling rats was low in the 50_??_75mg/day/rat (×100 group) and wt. of the adrenal gland, thymus, thyroid and testis did not vary among the subjects. 2) Mother rats were fed on the same diets as the said experimental 2 groups of vitamin E for about 20 days before pregnancy and then through gestation and the natal period. Their offspring were fed on a normal diet during 12 wk. after weaning. Increase in body wt. of weanling rats did not differ nor were abnormalities observed in the organs. 3) Mother rats were fed on the same experimental method of vitamin E through gestation, natal and lactation periods. Their offspring were fed on a normal diet during 12 wk. after weaning. Increase in body wt. of the weanling rats did not differ among the three groups nor were there abnormalities observed in the organs. 4) Mother rats and their weanlings fed on a 75mg/day/rat diet, the former for about 20 days before pregnancy and through gestation period, the latter during 12 wk. after weaning, were normal as to the number of RBC and WBC, the value of haematocrit and hemoglobin, bleeding time and prothrombin time and blood sugar and creatin urea. 5) From the viewpoint of development pharmacology, it may be concluded that vitamin E is a comparatively safe drug.
The present experiments were undertaken to investigate the mechanism of spasmolytic action of 4-methylumbelliferone (4-MU). It has been reported that the spasmolytic actions of trihydroxybenzene derivatives and trihydroxypropiophenone (THPP) in the biliary system are partially due to the inhibition of catechol-O-methyltrasferase (COMT) activity. On the other hand, resorcinol, a dihydroxybenzene isomer is used as a synthetic material for 4-MU. Utilizing epinephrine as a substrate and S-adenosylmethionine as a methyl donor, the effects of pyrogallol and 4-MU on rat liver COMT activity were determined. Pyrogallol showed inhibition of enzyme activity depending on the concentration added, however, 4-MU was ineffective at any concentration. Contractile responses of the isolated rabbit aorta to transmural electrical stimulation and exogenously applied epinephrine were potentiated by pretreatment with pyrogallol, but were rather inhibited at high concentrations of 4-MU. The phasic and tonic contractions in the isolated rabbit sphincter of Oddi induced by KCl in normal nutrient solution were little affected by either THPP or 4-MU in low concentrations, but were inhibited, in high concentrations. On the other hand, these contractions were inhibited by papaverine in any concentration, but not so by atropine. The contractile responses of the isolated rabbit sphincter of Oddi to CaCl2 and BaCl2 in Ca++ free medium were significantly inhibited by THPP, papaverine and 4-MU, but not so by atropine. The transmural electrical stimulation applied to the sphincter of Oddid caused contractions of the two components, the initial one during stimulation and the other following stimulation. These two components were inhibited by papaverine and 4-MU, depending on the concentration added, but were only slightly inhibited by THPP in high concentrations. It was observed, however, that atropine usually converted the initial component to a relaxation. The late component was unaffected by atropine. The mechanism of spasmolytic action of 4-MU has been discussed herein.