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.
Acute Kidney Injury ; Amylases ; Animals ; Blood Pressure ; Blood Volume ; Capillaries ; Diagnosis ; Dogs* ; Femoral Vein ; Humans ; Hypercalcemia ; Hypotension ; Infusions, Intravenous ; Ligation ; Lipase ; Pancreas ; Pancreatic Diseases ; Pancreatic Ducts ; Pancreatic Juice ; Pancreatitis ; Prunus ; Research Personnel ; Rivers ; Trypsin ; Urinary Catheters

The influence of intravesica1 pressure on urine for-mation was studied in dogs and rabbits prepared with ureteral fistulae and in man following ureteral cathe-terization. Reduction of urinary output following distension of the bladder occurred in all except two dogs. The mean rate of reduction in sixteen dogs was 37.3 +/- 4.9 per cent. The response was not blocked by tetracaine applied to the bladder mucosa or by systemic hexamethonium. The renal blood flow showed a significant reduction following distension of the bladder. After denervation or celiac ganglionectomy, the reduction of urinary output or of renal blood flow was prevented in the ipsilateral kidney. Coloring of the renal cortex by intravenously injected indigo carmine does not occur in animals with distended bladders. Adrenaline and serotonin produced and enhanced the effect on the urinary response of the distended bladder. The injection of a small amount of blood or urine from animals with distended bladders into undistended animals produced a significant decrease in urine formation in the recipients. In five human subjects, a marked reduction of urine flow was noted following bladder distension. We conchlde that the intravesical pressure may regulate the formation of urine through a short vesico-renal reflex mediated by the celiac ganglion and through a long vesico-hypothalamic reflex which releases the antidiuretic hormone.
Animals ; Denervation ; Dogs ; Epinephrine ; Fistula ; Ganglia, Sympathetic ; Ganglionectomy ; Hexamethonium ; Humans ; Indigo Carmine ; Kidney ; Mucous Membrane ; Rabbits ; Reflex ; Renal Circulation ; Serotonin ; Tetracaine ; Ureter ; Urinary Bladder

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.
Adrenergic beta-Antagonists/pharmacology* ; Anesthesia ; Animal ; Anticonvulsants* ; Blood Pressure/drug effects ; Chickens ; Convulsions/chemically induced ; Heart Rate/drug effects ; Male ; Propranolol/pharmacology* ; Rabbits ; Strychnine/antagonists & inhibitors ; Thiopental

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.
Animal ; Dogs ; Dyes/metabolism* ; Pancreas/metabolism* ; Pancreatic Juice/secretion* ; Rosaniline Dyes/metabolism*

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.
Adult ; Female ; Follicle Stimulating Hormone/secretion ; Gonadorelin/pharmacology* ; Human ; Luteinizing Hormone/secretion ; Menstruation* ; Pituitary Gland/drug effects* ; Protirelin/pharmacology*

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.
Acetazolamide/administration & dosage* ; Alanine Transaminase/blood ; Amylases/blood ; Animal ; Aprotinin/administration & dosage* ; Aspartate Aminotransferases/blood ; Atropine/administration & dosage* ; Cortisone/administration & dosage* ; Female ; Hexamethonium Compounds* ; Lipase/blood ; Male ; Organ Weight ; Pancreas/drug effects* ; Pancreas/enzymology ; Procaine/administration & dosage* ; Rats ; Time Factors

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.
Animals ; Female ; Gastric Juice/drug effects ; Male ; Rats ; Serotonin/*pharmacology ; Stomach Ulcer/*prevention & control

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.
Alkaline Phosphatase/analysis* ; Alkaline Phosphatase/blood ; Animal ; Isoenzymes/analysis* ; Isoenzymes/blood ; Rats

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.
Animal ; Anisoles/metabolism* ; Butylated Hydroxyanisole/analogs & derivatives ; Butylated Hydroxyanisole/metabolism* ; Cytosol/enzymology* ; Glutathione/metabolism* ; Mice ; Uridine Diphosphate Glucuronic Acid/biosynthesis* ; Uridine Diphosphate Sugars/biosynthesis*

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.
Adult ; *Aircraft ; Animals ; Dogs ; Gastric Juice/*secretion ; Human ; Male ; *Noise ; Stomach/*physiology