Methods for chemical determination of ChE activity are as follows: titration, manometric, microdiffusion etc. Well-estabilished and commonly-used is Ammon's method using Warburg's manometric technique. Although this method is useful to follow proceeding reactions, the measurement evolves during 30-60min starting only 10min after the reaction is initiated by addition of substrate. Initial reaction states thus go unobserved. In this paper, a method for determination of the initial state of ChE activity was newly developed using pH-electrode. ChE activities in rabbit brain and liver and in human blood cells and serum were studied and a comparison with the manometric method was made.
An Acetic Acid Ulcer was produced by injection of 0.05ml into the stomach walls of rats using Takagi's method. This ulcer has been so-called “Intractable Ulcer” by Takagi et al. The rats were sacrificed, on days 5, 10, 20, 40 and 80 after injection of 10% acetic acid solution. The mucosa of the stomach was separated from the stroma, which contained submucosa, muscule and serosa, for determination of hexosamine or hydroxyproline content. General patterns of response were as follows ; On sides of the ulcer, there was always a group of glands containing newly formed PAS and alcian blue positive mucus. An early rise in hexosamine content, found as a peak on day 10, was followed by a decline in a later sample. These results suggest the importance of increased mucus content at the crater of the Acetic Acid Ulcer in the early stages of healing. In addition, significance of these results in the proliferation of collagen and mucus behavior in the healing process has been discussed.
Mechanism and site of action of chlorphentermine on the hypothalamic feeding center of the rat were investigated. Chlorphentermine is mose effective in depressing food intake in rats with ventromedial hypothalamic lesions compared with those in normal rats and less effective in rats with lateral hypothalamic lesions. The effect of chlorphentermine was decreased by pretreatment with tetrabenazine, a monoamine depleter. A single administration of 5-hydroxytryptophane (80mg/kg i. p.) depressed the food intake in normal rats. A microinjection of serotonin into the lateral part of the hypothalamus in normal rat produced a depression in food intake, while a microinjection of dopamine or noradrenaline produced facilitation. Results suggest that the action site of chlorphentermine could be the lateral part of the hypothalamus with serotonin possibly playing a role in the mechanism of action of chlorphentermine.
Influence of p-sulfate on the analgesic effect and acute toxicity of aminopyrine was studied with the following results: 1) Analgesic effect of o-, m- and p-sulfate was not observed in the pressure and acetic acid method. 2) In the pressure and acetic acid method, p-sulfate markedly augmented the analgesic effect of aminopyrine (p. o. administration). 3) The effect of simultaneous use of p-sulfate on the toxicity of aminopyrine was increased more than the toxicity of aminopyrine alone. 4) The analgesic effect of aminopyrine was always augmented out of relation to the dose of p-sulfate. 5) Analgesic effect and acute toxicity of phenacetin, NAPAP, morphine and acetyl salicylic acid was not augmented by p-sulfate.
Effect of estradiol on metabolism of phospholipid in rat myometrial membrane and influence of phospholipase C on phospholipid metabolism in rat uterus were examined. Results were as follows. 1) Phospholipid in the rat myometrial membrane was strongly increased by estrogen administration. Action of the hormone was particularly observed in phosphatidylethanolamine. 2) Incorporation of 32P-orthophosphate into phospholipids in rat myometrial membrane was notably accelerated by estrogen treatment. 3) Phospholipase C treatment of rat uterus under slight conditions did not influence phospholipid biosynthesis in the uterus, but extensive treatment by the enzyme extremely inhibited it.
Behavioral effects of doxepin, imipramine and amitriptyline, were investigated in rats trained on fixed ratio (FR 30) and fixed interval (FI 1) schedules of food reinforcement, continuous (Sidman-type) and discriminated avoidance as well as escape schedules. Effect of these drugs on conditioned emotional responses (CER) under FR and FI schedules developed by stimulus presentation associated with electric shock was simultaneously observed. When 10mg/kg of doxepin was given orally, no change was observed in FR- and FI-respondings. At higher doses (20-60mg/kg P. O.), response decreased in proportion to the dosage. CER was not attenuated in all the cases. The three drugs all showed suppressive effects on response and were arranged according to potency as, imipramine, doxepin and amitriptyline. When 50mg/kg of doxepin was administered orally, no marked change was detected in either avoidance behavior. At the dose of 100mg/kg, doxepin and amitriptyline showed a decrease in response with a corresponding increase in the number of shocks delivered, while imipramine showed no change. It is suggested that doxepin mainly revealed suppressive chlorpromazine like effects in all the schedules, but no attenuating effect of CER, when single large doses were administered orally. Thus diazepam-like effect was not confirmed.
Behavioral effects of repeated administration of doxepin were investigated in rats trained on fixed ratio (FR 30) and fixed interval (FI 1) schedules of food reinforcement, continuous (Sidman-type) and discriminated conditioned avoidance schedules. Effect on conditioned emotional responses (CER) under FR and FI schedules developed by stimulus presentation associated with electric shock was simultaneously observed. A qualitative difference between single and repeated doses of doxepin in various effects was demonstrated. Small doses of doxepin (10-20mg/kg/day P. O. for 10 days) increased FR and FI-respondings according as, daily successive administrations. Furthermore, marked attenuation of CER was observed after several days' administration. Intermediate dose (40mg/kg/day P. O. for 11 days) signifcantly enhanced the inhibitory effect of FR-respondings shown in single dose administration, while marked attenuation of CER was confirmed. These effects persisted continuously for more than 10 days after withdrawal. When 50mg/kg/day was administered for 15 days, the inhibitory effect on continuous and discriminated avoidance schedules was enhanced within the initial few days, then returned to baseline level. A large dose of doxepin (100mg/kg/day P. O. for 8-12 days) showed progressive one-sided suppression of respondings with corresponding increase in the number of shocks delivered in both schedules, and no tolerance was observed in this effect. The rates of responding and avoidance returned to baseline level immediately after withdrawal. Amitriptyline revealed similar effects but these were less potent. It should be noted that repeated administration of doxepin exhibited complex effects mixing selective enhancement or differential tolerance according to dosing and experimental parameters.
Doxepin, one of tricyclic antidepressants was examined as to whether or not it possesses a diazepam-like effect. Water-deprived rats were tested in an apparatus where they drank water under two kinds of conflict schedules. A clear diazepam-like effect was observed after long term administration of doxepin in the approach-withdrawal conflict schedule, although the potency was weaker than that of diazepam. In approach-avoidance conflict schedule a slight effect only was exhibited after doxepin. No marked sign was detected in the experiments after withdrawal of daily administration of doxepin.
When anti-rat kidney serum obtained from rabbits by Heymann's method was administered intravenously (1.4ml/100g B. W.×1/3×3 days) to rats, the following syndrome was induced. 1) Strong proteinuria was produced immediately and continued for 30 days at a high level. Excretion of alkaline phosphatase (AP) and lactic dehydrogenase (LDH) in urine significantly increased, while Na+ excretion decreased. 2) In addition to the appearance of hypoproteinemia and decrease of AP activity in blood, hyperlipemia and the elevations of blood urea nitrogen, creatinine and LDH activity were observed at an early stage. 3) On the other hand, protein concentration and AP activity in whole kidney homogenate diminished, whereas a significant increase of glucose-6-phosphate dehydrogenase activity was recognized for 20 days while that of LDH activity was weakly. 4) Considerable retention of ascites and kidney hypertrophy were observed as serious at autopsy.
Experiments were carried out to ascertain the effect of milk food (whole milk powder 80%, dextrin 20%) and cereal food (only cereal) to which arsenite had been added on the absorption of the arsenite from the digestive tract (residues in feces and excretion in urine) as well as accumulation in the organs. 1) The arsenite had a tendency to remain in the feces, the quantity gradually increasing. By the fifth week, the arsenite had been excreted approx. 50 percent in the case of cereal and 100 percent in the case of milk. 2) With milk, the quantity of arsenite in the brain and liver did not increase after the second week in whole organ and per g of organ, while the quantity in the kidney increased a little in whole organ, but did not increase per g. In the spleen, the quantity increased a little in whole organ and per g of organ. With cereal, the quantity in the brain, liver and kidney increased in whole organ and per g of organ, while in the spleen the increase was little. In the fifth week quantity in the brain, liver, kidney and spleen of rats raised on milk was relatively little as compared with those on cereal. 3) When rats were raised on arsenite added food, occurrence of arsenic tolerance in the digestive tract was recognized. Milk showed a considerable promotive effect to this occurrence of arsenic tolerance.
N-Acetyl-L-glutamine aluminum complex (KW-110) was studied with regard to the effects on various experimental ulcers. As a result, KW-110 showed antiulcerogenic action against all of the ulcers studied. Preventive effects against stress ulcer and Shay rat ulcer were especially remarkable. Moreover curative effect was also confirmed in acetic acid ulcer. From the studies of the other pharmacological properties, KW-110 showed inhibition of gastrointestinal motility, rise of gastric juice pH, and decrease of spontaneous movement. No other pharmacological action was observed.