Regional differences in the levels of biogenic amines and their metabolites in rat brain after tricyclic antidepressant treatments

Changes in the levels of biogenic amines in different brain regions and the cerebrospinal fluid in rats were measured after acute or chronic treatment with tricyclic antidepressants. After single or 3 weeks' treatment with imipramine or desipramine, blocks of tissues were obtained from seven regions of the brain (frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum) immediately after collection of the cerebrospinal fluid (CSF) from the cisterna magna. The concentrations of biogenic amines and their metabolites (norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA)) in brain tissues and the CSF were measured using the high performance liquid chromatography-electrochemical detection system (HPLC-ECD). Treatment with desipramine or imipramine caused major alterations in the concentrations of central norepinephrine or 5-HT and its metabolite, respectively. Brain regional responses were variable according to the kind of tricyclic antidepressants and the duration of treatment. It is noteworthy that chronic treatment with both desipramine and imipramine caused altered hippocampal concentrations of norepinephrine and/or 5-HT and its metabolites. Striatal DOPAC concentrations were also changed after acute or chronic treatment with both drugs. These results suggest that tricyclic antidepressants altered neurotransmission according to the brain region, and the hippocampal norepinephrine and 5-HT and/or the striatal dopamine may have a significant role for the expression of antidepressant action of tricyclic antidepressants.

Ethanol-induced Back-Diffusion of H+ in Rat Stomach

Ethanol causes mucosal injury to the stomach and which accompanied by back-diffusion of H+. Using several drugs known to modify the gastric acid secretion and to provide cytoprotection the effect of back-diffusion of H+ by ethanol was examined. Following 48 hours of starvation rats were anesthetized with urethane, and their stomachs were filled with 4 ml of 20% ethanol solution containing 1.8 mM HCI (7.2 microEq/4 ml) every 15 min. H+ content of the collected perfusates was determined by back-titration to pH 6.0. The presence of ethanol in the stomach for 1 hour caused a loss of luminal H+ at a rate of 4.8 +/- 0.4 microEq/15 min. Pretreatment of rats with atropine (2 mg/Kg, i.v.), pirenzepine(2 mg/Kg. i.v.), cimetidine (10mg/Kg i.v.), cromolyn sodium (20mg/Kg/hr, i.v.) or domperidone (1 mg/kg. i.v.) did not affect the ethanol-induced H+ back-diffusion. Similarly, no effect was seen in rats treated with prostaglandin E2 (100 microgram/Kg i.v.) or indomethacin (5 mg/Kg, s.c). The addition of procaine (10(-5)~10(-3) M) or propranolol (10(-9)~10(-5) M) to the perfusate did not cause any changes in the ethanolinduced H+ back-diffusion. However, pretreatment of rats with acetazolamide (100 mg/Kg i.v.) or ethoxzolamide(50 mg/Kg/day, p.o. for 6 days), carbonic anhydrase inhibitors, markedly suppressed the ethanol-induced loss of luminal H+. Based on these results, it is suggested that ethanol-induced back-diffusion of H+ is mediated, at least in part, by the activity of carbonic anhydrase, and that cholinergic, histaminergic and dopaminergic mechanisms are not involved. Moreover, the implications of prostaglandins and membrane stability are not suggested.

Enhancements of Mouse Hepatic Cytosol Enzyme Activities Involved in UDP-Glucuronic Acid Synthesis, Glutathione Reduction and Conjugation with Butylated Hydroxyanisole (BHA) and Its Structural Analogs

Activities of hepatic cytosol enzymes involved in UDP-g1ucuronic acid synthesis as well as in glutathione reduction and conjugation systems were determined following administrations of butylated hydroxyanisole (approximately 5 mmol/kg body weight/day) and of equimolar intake doses of its structural anglogs. These compounds included the multi-functional group side chain compounds (t-butyl hydroquinone, 4-hydroxy- anisole, hydroquinone, benzoquinone) and the mono-functional side chain compounds (t-butyl benzene, anisole, phenol). They were administered to mice for 10 days either by mixing them in the diet or by oral intubations. Results showed that glutathione Stransferase activities were markedly increased by all tested compounds except for the t-butyl benzene. Activities of glutathione reductase and glucose 6-phosphate dehydrogenase were increased together on1y by BHA and t-butyl hydroguinone. UDP-glucose dehydrogenase and NADH:quinone reductase activities were significantly elevated by the multi-functional side chain compounds, but not by the mono-functional analogs. The relations between chemical structures of tested BHA analogs and elevations of the measured hepatic cytosol conjugation (detoxification) system enzyme activities for the metabolism and excretion of BHA analogs are discussed.

Studies on Alkaline Phosphatase Isoenzyme in the Serum and Organs of the Rat

Isoenzymes of alkaline phosphatase from purified extracts of liver, intestine, pancreas and bone of rats were determined by their isoelectric points and compared with those from serum. 1) The extracts obtained from homogenized tissues were centrifuged at 65,000xg and filtered through an Ultrogel AcA 34 column. Among the three major peaks obtained by gel filtration, the second peak fractions were further separated by isoelectric focusing. Isoenzymes of alkaline phosphatase were found only in the second peak. 2) Isoenzymes of alkaline phosphatase were distinguishable with pH 3.5-10 ampholytes. When pH 3-6 ampholytes were used, isoenzymes were more clearly separated, e.g., 4in serum, 5 in intestine and 2 each in the liver, pancreas, and bone. 3) Comparing the bands of the isoenzymes of alkaline phosphatase to those of serum, only the band with 5.04 pI was the same between serum and intestine. These results indicate that several forms of alkaline phosphatase, even though all are from the rat, may exist; and some of the isoenzymes of alkaline phosphatase found in the serum originated from the intestine.

Variation of Pituitary Responsiveness to Synthetic LH-RH and T-RH during Different Phases of the Menstrual Cycle

The LH and FSH responses to synthetic LH-RH and the prolactin response to synthetic T-RH were evaluated during different phases of the mentrual cycle in order to understand secretory capacity of the pituitary during the menstrual cycle. Eleven regularly menstruating women between 22 and 35 years of age with a usual cycle length of 27 to 31 days volunteered for this Study. Volunteers received an intra-venous injection of 100 microgram synthetic LH-RH and 200 microgram synthetic T-RH during the early and the late follicular phases and during the early and midluteal phases of the menstrual cycle. LH-RH induced a prompt increase in circulating LH, reaching the peak concentration at 30 minutes following LH-RH administration in all phases of the cycle studied. A change in responsiveness with greater and more sustained LH release from the early to the late follicular phases was observed. The response during the luteal phase was significantly greater than the responses in both the early and the late follicular phases. A concomitant but a much smaller FSH response was observed. T-RH elicited a prompt increase in circulating prolactin within 30 minutes and decreased gradually thereafter, reaching the baseline level by 2 hours after T-RH administration. Maximum concentration of prolactin was reached in 30 minutes following T-RH during all phases of the menstrual cycle. No variation in pituitary responsiveness to T-RH, however, was observed during different phases of the menstrual cycle. These data indicate that the sensitivity of the pituitary gonadotrophs to LH-RH varies during different phases of the menstrual cycle.

The Effect of Ketamine on the Isolated Smooth Muscle of the Rabbit / 대한마취과학회지

Ketamine hydrochlaride, chemically related to both pencyclidine and cyclohexamine, is a new nonbarbiturate intravenous anesthetic agent. Clinical investigations were begun in 1965 by Domino and associates, who first used the term "dissociative anesthesia" . Anesthesia induced by ketamine dissimilar to that resulting from the more widely used intravenous or gaseous componds. Because of its minimal depressant effect on the cardiovascular and respiratory systems as well as its dissociative effect on the central nervous system ketamne bas achieved widespread use. However there have been few reports on its effect an intestinal motility. The present study was undertaken to determine the effect of ketamine on doudenal motility and on other smooth muscles of the rabbit. Strips of various isolated smooth muscle, 2 cm long from adult rabbits weighing about 2 kg, were suspended in a muscle chamber containing Tyrode's solution, which was bubbled with oxygen gas, and the solution was kept constant at 38C. Contraction of the preparations was recorded on polygraph (Grass, mode17). After being washed several times with fresh solution, the smooth muscle strips attained constant motility and tonus. Ketamine and other drugs were added in various concentrations to the chamber. The results areas follows: 1) Ketamine relaxed the isolated rabbit duodenag strip and potentiated the relaxing effect of epinephrine, norepinephrine and isoproterenol. 2) The relaxing effect of ketamine on isolated duodenal strip of rabbits was not abolished by the adrenergic blocking agents, but ketamine antagonized histamine or serotonin-induced contra ction. 3) Ketamine did not exert any effect on the isolated auricle, aorta, trachea, trigone and detrusor muscle strips of rabbit. From the results described above, it may be concluded that ketamine exerts a depressant effect on the isolated duodenal smooth muscle of rabbits without relation to adrenergic receptors.

Effect of beta-Adrenergic Blockers on Experimentally-induced Convulsion and Narcosis

Effects of beta-adrenergic blockers and related agents were investigated on experimental convulsions of chicks induced with strychnine, pentylenetetrazol or electroshock and on thiopental sleeping time of rabbits. Convulsions of chicks due to strychnine were significantly inhibited by all beta-adrenergic blockers except dichloroisopreterenol. Propranolol inhibited electroshock convulsion as well, but none of the blockers inhibited pentylenetetrazol convulsion. Furthermore, the mortality of chicks due to large dose of pentylenetetrazol was greatly increased by treatment of beta-adrenergic blockers. Pindolol alone showed diazepam-like anticonvulsive effect against low doses of pentylenetetrazol. Pretreatment with beta-adrenergic blockers caused a marked increase in thiopental sleeping time in rabbits. Prolongation of thiopental sleep due to propranolol was abolished by premedication of animals with reserpine or tranylcypromine. Thiopental sleeping time was prolonged by Zizyphus extract, though less effective than beta-adrenergic blockers. It is felt that the anticonvulsive or sleep enhancing effect of beta-adrenergic blocking agents has an intimate relationship with endogenous adrenergic amines and the receptors.

Study on the Fractionation of Synovial Fluid Protein

Fractionation of protein components of the human synovial fluid was carried out with paper and disc electrophoresis, and isoelectric focusing. The mean ranges of total protein content of synovial fluid obtained in the thirty patients suffering from nonspecific and traumatic synovitis, degenerative osteoarthritis or rheumatoid arthritis were 3.8 to 4.6g/dl. There was no significant difference between each from of arthritis. The pattern of protein fractionation of synovial fluid by paper electrophoresis was similar to that of serum protein. On disc electrophoresis, 20 fractions were identified in synovial fluid and the main fraction was albumin. Isoelectric focusing of the human serum with Ampholine carrier ampholyte in thin layer polyacrylamide gel revealed 27 protein fractions and five isoenzymes of amylase and two of them were the main fractions. In the synovial fluid 22 protein fractions and two isoenzymes of amylase, which had the same isoelectric points as the main fractions of serum, were noted. It is suggested that the isoamylases in the synovial fluid are a dialysate of plasma enzymes.

Inhibitory Effect of Tuberculo-protein Complex, Tubercin-3, on Three Cases of Lepromatous Leprosy

Three cases of leprosy were successfully treated with a tuberculo-protein complex, Tubercin-3, which was prepared from Mycobacterium tuberculosis by Chung( J. Korean Med. Ass. 17:427-431, 1974) and no noticeable side effects were observed. The three cases were brought to us without leprosy medication since their disease was recently diagnosed. Daily inoculations of Tubercin-3, 1.0 microgram on the forearm, subcutaneously for 8 months in Case 1, 7 months in Case 2, and 6 months in Case 3, cleared them of their lepromatous lesions.

Effect of Ketamine on the Isolated Uterus of Guinea Pig / 대한마취과학회지

Postpartum bleeding of the uterus is an important cause of maternal death. It is thought that the inhibitory effect of the majority of potent inhalation anesthetics on uterine contraction is often responsible (Munson, 1970; Lim et al., 1971; Kim, 1972). There have been numerous reports that ketamine stimulates uterine contraction clinically Chodoff and Stella, 1966; Little et al, 1972; Galbert and Gardner, 1973; Corssen, 1974). Jawalekar and associates(1972) reported that ketamine increased resting tension, contractile amplitude and frequency of the uterine strips of pregnant mice. And Kim(1975) reported research on the effects of ketamine on the isolated uterus of rabbits. According to Kim(1975), ketamine exerted .a stimulatory action on the uterus under the influence of progesterone. This progesterone-depenent uterine stimulatory action of ketamine is not concerned with adrenergic and cholinergic mechanisms but appears to have a direct effect on the uterine muscle. The present study was undertaken to determine whether or not ketamine also exerted a stimlatory action on the uterus of the guinea pig and to follow up whether or not stimulatory action of ketamine also depends upon progesterone in the guinea pig. Adult female non-pregnant guinea pigs and rabbits weighing approximately 0, 5 kg and 2. 0 kg respectively were employed in this experiment. At the end of 10 to 14 days following bilateral oophorectomy, non-pregnant guinea pigs and rabbits were injected intramusculary with estradiol benzoate (2,000 I.U./kg) or progesterone (Smg/kg) once a day for four consecutive days, A uterine strip, about 1.5~2,0cm in length, was carefully isolated from the experimental animals and suspended in a muscle chamber containing 50 ml of Lockes solution, maintained at constant temperature of 38C. It was aerated with 100% oxygen bubbling through the bathing fluid by means of a sintered glass plate at the bottom of the muscle chamber. One end of the uterine strip was attached to the bottom of the muscle chamber and the other end to a lever. Motility and tonus were recorded on kymograph paper. After being washed several times with fresh Locke's solution, the uterine strip attained a constant motility and tonus. Ketamine then was added in various concentrations to the chamber. The results are as follows: 1. The uterine mctility of guinea pig shows a higher amplitude and lower frequency compared with that of rabbit. 2. Effects of ketamine on isolated uterine strips of guinea pig pre-treated with estrogen showed no change using 1~20 gamma/ml of ketamine, but with 50 gamma/ml or more, the amplitude of uterine contractions was depressed. 3. On isolated uterine strips of guinea pig pre-treated with progesterone, there was no effect with 1100 gamma/ml of ketamine, depressed amplitude of uterine contractions with 150 gamma/ml and markedly depressed amplitude of uterine contraction with 200 gamma/ml. 4. On isolated uterine strips of rabbit pre-treated with estrogen, there was no effect with 20 gamma/ml of ketamine, but depressed amplitude of uterine contraction using 50 gamma/ml. 5. On isolated uterine strips of rabbit pretreated with progesterone, there was an increase in amplitude and frequency of uterine contractions with up to 150 gamma/ml of ketamine, but depressed amplitude with 200 gamma/ml or more. From the above results it may be concluded that ketamine exerted a stimulatory action on the uterus of rabbit under the influence of progesterone but not on the uterus of guinea pig. The large amount of ketamine depressed the amplitude of uterine contraction in guinea pig and rabbit and this depressing dose is higher in the animals (guinea pig and rabbit) pre-treated with pr ogesterone than with estrogen.

Renal Excretion of Pancreatic Enzyme in Dogs / 대한비뇨기과학회지

It is generally accepted that in acute pancreatitis, the enzymes normally excreted by the pancreas are released from the disrupted parenchyma into the extraductal space and taken up by way of the lymphatics and capillaries. The enzymes in the blood stream may appear in high concentration in the serum. Therefore, serum amylase and lipase determinations has long been a mainstay in the diagnosis of acute pancreatitis and other pancreatic diseases. However, many investigators have claimed that the urinary output of amylase may be elevated more consistently in acute pancreatitis than in the serum concentration of either amylase or lipase, and urinary amylase measurement is a more sensitive reflection of the presence of pancreatitis and of its clinical course than is the measurement of serum amylase or lipase. Clinically, one of the ominous signs which may develop during the early course of acute pancreatitis is severe hypotension. But, no agreement has been reached among investigators as to the cause of the hypotension, although several investigators have implicated a blood volume deficiency resulting form inflammatory process, and hypercalcemia. Perhaps, the majority have attributed the hypotension to systemic effect of some of the pancreatic enzymes, especially trypsin. Nevertheless, the correction of these factors sometimes fail to restore a normal blood pressure clinically. The purpose of the present investigation was to observe the relationships between serum concentration and urinary output of pancreatic enzymes, and to determine the degree of hypotension resulting from the systemic administration of pancreatic enzymes. These experimental procedures, consisted of heteroinfusion of human pancreatic juice and homoinfusion of canine pancreatic emulsion intravenously, and pancreatic ductal ligation in dogs. Blood and urine samples for the enzyme analysis were collected serially thorough the femoral vein and ureteral catheter before and after the procedure. Blood pressure was measured consistently by the kymograph before and after infusion of pancreatic juice. Activities of amylase and lipase were determined by methods of Nelson and, Cherry and Crandall, respectively. The results obtained are summarized as follows; 1. Following intravenous infusions of pancreatic juice exogenously. serum and urine concentrations of amylase and lipase increased rapidly, but these enzymes decreased rapidly in urinary excretion and gradually in serum concentration. Urinary recovery of amylase was approximately 10% of the total infused amount of pancreatic juice at the end of 4 hours. 2. Following ligation of the pancreatic duct, the amylase and lipase levels of serum rose gradually and reached the maximum at 24-48 hours after ligation and then gradually fell. The output of these enzymes in the urine were relatively constant while serum enzymes were increased. 3. When the human pancreatic juice was infused, hypotension was pronounced, and it was deeper and more prolonged in hypotensive effect with infusion of highly concentrated juice in the enzyme activities. With human pancreatic juice, a more sustained hypotension occurred than was observed after infusion of canine pancreatic emulsion. As a result of this investigation, it is felt that the hypotension in acute pancreatitis is probably the result of pancreatic enzymes itself. 4. In postinfusion period, the urine volume was markedly decreased following hypotension, and the urine volume was increased following blood pressure to normal level. This suggests that urine volume may diminish resulting from transient acute renal failure due to hypotensive effect by pancreatic enzymes.

Elimination of Basic Fuchsin and Other Dyes from the Pancreas

Twenty dyes which previously have been claimed to be excreted in pancreatic juice were reinvestigated to determine to what extent they could be eliminated through the pancreas. Exogenous secretin or cholecysto-kinin-pancreozymin(CCK-PZ) stimuli were used in dogs which had been given intravenous dye solutions at the rate of 1mg/min. In this experiment among the twenty dyes, only six were found to be eliminated through the pancreas. The intensity of dye color in pancreatic juice was estimated photometrically or macroscopically. The dye color intensity decreased as follows; basic fuchsin, acridine red, new fuchsin, rhodamin B, phenol red and rhodamin 6G. Basic fuchsin consistently appeared in CCK-PZ stimulated juice. However, it was seen in only a scant amount or not at all in juice stimulated by purified Vitrum (Sweden) secretin. Similar findings were observed in cats and conscious pigs. The content of basic fuchsin in pancreatic juice was more related to changes in the enzyme concentration than to other components. The chloride content of the juice was related to the amylase or basic fuchsin secretion. However, the chloride content was inversely related to the secreted volume. Vagal stimulation or the administration of parasympathomimetics produced a juice rich in enzyme content, but the dye response to vagal stimulation was weak. Usually the volume of secreted pancreatic juice following stimulation by Boots (England) secretin is greater than stimulated by purified Vitrum preparation. Basic fuchsin was slightly reduced during its elimination from pancreas or when present in alkaline pancreatic juice. Adding acid and formaldehyde revived the color. The acridine red and other pyronine dyes caused the juice to fluorescence. This effect lasted over 24 hours.

Effect of Bile Acids on Biliary Excretion of Cholesterol in Rabbits

The effects of cholic acid and eight related cholanic acid analogs on bile flow and biliary excretion of bile salts and cholesterol were studied in rabbits. Bile acids were infused intravenously in anesthetized rabbits. In all except hyodeoxycholic or lithocholic acid treated animals increases in bile flow were recorded within 10 minutes during infusion of bile acid-The increase in bile f1ow associated with an increase in bile salt level in bile after cholic acid infusion was observed, however, there were little changes in biliary, cholesterol levels. Bile salt level in bile was not associated with bile flow after chenodeoxycholic acid infusion but the cholesterol level in bile was significantly increased. Ursodeoxycholic acid similarly increased cholesterol but to a lesser extent. Keto-forms of chenodeoxycholic acid were without action. These results indicate that both cholic and chenodeoxycholic acids have the capacity to alter specific biliary excretion of bile components, the former on bile salts and the latter on cholesterol-a precursor of bile acids in bile.

Effect of Cold and Hot Environments on the Exocrine Pancreas of Rats

Male albino rats fed 8 or 25% casein as a source of protein (designated here as low and high protein diet) were exposed to cold(4-5 degrees C) or heat (36-38 degrees C) environment for 21 days. Another series of rats were exposed alternately between cold and hot environments every other day. The weight of the liver, pancreas, kidneys and testis were increased in rats exposed to the cold environment on both low and high protein regimen. Histologically the pancreatic section from cold and alternating temperature rats showed enlargement of the pancreatic acini, cellular hypertrophy and increase in zymogen granules. The weight of the spleen in hot environment and of pancreas in alternating environment were also increased in rats given high protein diet. In the rats exposed to cold, the volume of the biliary-pancreatic secretion was significantly increased, which may reflect the hypertrophy and weight increase of both liver ,and pancreas, however, the content of amylase and lipase were decreased and trypsin was little changed or increased in case of high protein regimen. In rats exposed to hot environment, in contrast, the amylase content of the juice was Increased in high protein regimen. Little change of pancreatic enzymes were seen in the alternating group. The serum protein of all experimental groups was elevated and the serum amylase was elevated only in rats exposed to the alternating environment. The mortality of rats fed low protein diet was 33.3% in both cold and alternating environments and 25.0% in the hot environment. The mortality of rats fed a high protein diet was lower than low protein regimen, and furthermore, none died in the alternating environment with the high protein regimen. The data indicate that exposure to either cold or hot environment bring about danger to life, and also functional and morphological alterations of digestive viscera. The increased organ weight and digestive secretion in cold environment is suggestive of pituitary-adrenal participation in cold adaptation while no such involovement is apparent in heat adaptation. The higher protein regimen demonstrated protective effect for either cold or hot environmental stress.

Influence of Corticosteroids on the Hepatic Cell and Bile Secretion (1)

Daily administration of glucocorticoids for 10 days to dogs resulted in a significant increase in the hepatic bile secretion in response to secretory stimulants. The response of hepatic bile in testosterone-treated animals was not changed and the response was increased in DOCA--treated animals. A significant increase of liver weight was induced by the animals receiving glucocorticoids. Other organ weight was not changed; however, a slight reduction of kidney weight was seen in prednisolone, dexamethasone, and DOCA treated animals and also in animals supplemented with cortisone following adrenalectomy. The presence of large areas of ballooning and vesicular changes of liver cells was seen in glucocorticoid treated animals, particularly in cases of dexamethasone and prednisolone. Both vesicular changes of liver cell and its glycogen content were increased by the repeated administration of prednisolone and reduced by the cessation of treatment. Special stain and liver glycogen determination demonstrated the material distending the liver cell was glycogen. These findings indicate that long term administration of glucocorticoids results in an increase of liver weight and hepatic glycogen content as well as increased bile secretion.

Effect of Long-Term Administration of Secretory Suppressives on Rat Pancreas (1)

Atropine (2.5 mg/kg), hexamethonium (1 mg/kg), Trasylol (1,000 u/kg), acetazolamide (100 mg/kg), cortisone (5 mg /kg) or procaine (5 mg/kg) were injected intraperitoneally once a day for 21 days into rats (both sexes) fed a low protein diet. The rats were fasted and sacrificed 24 hr after the last injection. Atropine and cortisone, but not the other agents, cause a significant increase in both pancreatic weight and enzymes. Serum amylase increased markedly in the cortisone group and serum GOT and GPT increased but slightly in the atropine group. Enlargement of the pancreatic acini, cellular hypertrophy and increases of zymogen granules were observed in all the groups except the procaine and normal control group. The hypertrophy of acini was more prominent in the atropine and cortisone groups. None of drugs used could induce decrease or depress the enzyme formation and weight of pancreas. This data indicates that long-term administration of these drugs, particularly atropine, cortisone or even other Ragents may induce preferential formation of pancreatic enzymes to exocrine secretions and consequently may cause enlargement of the pancreatic acini.

The Influence of Rotatory Movement on the Tissue Catecholamines in Rats

The present study was designed to examine the possible relationship between the function of the labyrinth and the role of the sympathetic nervous system In experimental motion sickness produced by rotatory movement(8O r.p.m.). The catecholamines in the brain, the heart and the adrenal gland of rats were rapidly reduced to one half of normal values following exposure to rotatory movement. The pretreatment with streptomycin and dramamine completely prevented the depletion by the rotatory movement of the catecholamines in the brain, the heart and the adrenal gland, but scopolamine did not prevent the decrease. Bretylium or chlorpromazine signifcantly inhibited reduction of the catechol-amines in both of the brain and the heart. However they did not influence the decrease in the adrenal gland. The reduction of the tissue catecholamines in rotatory movement is presumed to be caused largely by activation of the sympathetic nervous system mediated through labyrinthine stimulation.

Effect of Air-Craft Noise on Gastric Function

Thirty three healthy young men and six dogs equipped with gastric fistulae were stimulated by noise of 100 to 120 phons emanating from a F-86F jet engine. The basal secretion of gastric juice in the dogs was little changed, but in human subjects the secretion of gastric juice was altered as follows; 30.3% of 33 subjects showed an increased acid output, 63.6% showed a decrease and the remaining showed no change. Furthermore, the basal resting secretion of those showing decreased acidity from noise exposure was higher than that of those showing increased acidity. Gastric motility was greatly inhibited by exposure to noise in both dogs and humans but the inhibition was more sensitive and more prolonged in humans. Rats fed synthetic diet were placed under conditions of repeated noise for either short or long periods and the occurrence of gastric ulcers by the procedure described by Shay et al was observed. The prevalence of ulcer lesions was increased and the severity of the lesion was enhanced in rats exposed to noise for either short or long periods. The above results indicate that the influences of air-craft noise were not remarkable, but the noise to a considerable degree, is responsible for the occurrence of gastric disorders in man. Sound fields surrounding air-craft engines are thought to be the cause of physical or mental disturbances experienced by persons at close range. Laird (1932) reported that 60 decibels of noise decreased the normal secretion of gastric juice in four of five human subjects who previously had been given an Ewald meal and also caused a decrease in the normal secretion of saliva by about 40 per cent. Previously Laird and Smith (1930) had observed that 80 to 90 decibels of noise caused a decrease in gastric motility in human beings. Vaughan and Van Liere (1940) reported a significant reduction in acid secretion in dogs with Pavlov pouches from a noise of l00 decibels and 2,000 frequency. However, noise frequency of 600 was ineffective. The present study was undertaken to determine in humans and animals whether digestive function or other disorders occurred readily with either single or repeated exposure to air-craft noise.

Effect of Serotonin on Experimentally Induced Gastric Ulcer in Rats

Ulcerative gastric lesions in rats were produced by the procedure of Shay et al. The lesion develops uniformly in the rumen, less often in the antrum, and least frequently in the body of the stomach. Administration of serotonin (8 mg/kg) was effective in preventing the occurrence of gastric lesions and the effect is distinct particularly in the group which had 48 hrs of starvation and 10 hrs of pyloric ligation. Bilateral vagotomy was completely effective and pretreatment of atropine or morphine was moderately effective in preventing the gastric lesions. The acidity of gastric juice was considerably lower, however, the mucin content was higher in the animals treated with serotonin than nontreated control animals. Histobgically, mucus secretion was greater in the animals that were given serotonin. In summary, it is concluded that serotonin is effective in preventing ulceration in the stomach by its action of increasing mucin secretion and inhibitory gastric acid secretion.

Effect of Serotonin on Gastric Secretion in the Dog

Heidenhain pouch secretion in response to small dose of serotonin was studied in conscious dogs. A single subcutaneous injection of 0.5 to 2.0 mg of serotonin produced no changes in spontaneous fasting secretion; however, the milk-induced secretion was greatly inhibited by the same dose. This inhibition was abolished by treatment of dibenzyline or LSD(d-lysergic acid die- thylamide). LSD alone enhanced the response of gastric secretion to milk. Constant intravenous infusion of serotonin, at levels of 3 to 10 microgram/kg/min was associated with a significant increase in the volume of gastric juice aspirated from three anesthetized dogs, but the acidity of juice varied very slightly. However, when histamine is given as much as 0.8 to 3 microgram/kg/min, a marked increase in both the volume and acidity was observed. A significant elevation of mucin content in the juice obtained from the Heidenhain pouch was seen in dogs receiving a single subcutaneous injection of 1.0 mg of serotonin. In case of histamine, the mucin content of pouch juice was not relatively increased and merely an increase in the total amount of mucin secondary to the volume increase was seen. The observed increase in mucin by serotonin was inhibited by LSD, BOL (2-bromo-d-lysergic acid diethylamide) or dibenzyline, and mildly by morphine. Atropine or hexamethonium did not block the response of mucin production to serotonin. The gastrointestinal motility elicited by serotonin was not affected by these agents. It is felt that the receptor(s) responsible for the mucin production in the dog belongs to the D-receptor types postulated by Gaddum and Picarelli.