Injection Of Salicylate Research Articles

Changes in liver tryptophan and tryptophan pyrrolase activity after administration of salicylate and tryptophan to the rat

The tryptophan content and tryptophan pyrrolase activity of rat liver were measured after the intraperitoneal administration of a range of doses of l-tryptophan and salicylate. The injection of salicylate increased both the total and the free concentration of tryptophan in the liver. It is suggested that salicylate induces tryptophan pyrrolase by releasing tryptophan from its binding sites on serum and liver proteins.

The effects of salicylate on the activity of rat liver tryptophan pyrrolase in vitro and in vivo

1. Salicylate, in concentrations of 0.05mm and above, inhibits the basal activity of tryptophan pyrrolase in homogenates of rat liver and the activity induced by cortisol but not that induced by tryptophan. The inhibition is abolished by adding haematin to the reaction mixtures. 2. The intraperitoneal injection of 400mg of sodium salicylate/kg in the rat causes a decrease in the tryptophan pyrrolase activity in the liver at 30min, the activity is restored to normal at 2h, increases to sixfold after 5h and returns to the basal value at 12h. The activation of the enzyme by salicylate is prevented by the administration of cycloheximide but not by pretreatment with actinomycin D. The effects of the combined injection of salicylate and cortisol are additive, whereas those of salicylate plus tryptophan are not. The injection of salicylate causes a progressive increase in the holo-/apo-enzyme ratio and an increased content of tryptophan in the liver over a period of 3h. 3. It is suggested that salicylate inhibits tryptophan pyrrolase activity in vitro and in vivo by interacting with iron protoporphyrins and causes a later enhancement of the enzyme activity in vivo by a mechanism involving the release of tryptophan from its binding sites on circulating albumin and on other proteins.

Influence of the duration of experimental fever on salicylate antipyresis in the rabbit.

1. Steady state fever has been produced in rabbits with a priming injection followed by a sustaining infusion of homologous plasma containing endogenous pyrogen (EP). This fever appears to last as long as the infusion continues.2. Intravenous salicylate given 1 h after the start of the EP infusion produced only a small antipyretic effect. The same dose of salicylate given 4 h after the start of an EP infusion resulted in rapid and progressive defervescence. Intermediate antipyretic responses were obtained when salicylate was administered intravenously 2 and 3 h after the start of an EP infusion.3. Less than 1% of the systemic dose, when injected into a lateral cerebral ventricle, produced a significantly smaller response at 1 h than at 4 h after the start of an EP infusion. At both these times the fall in temperature following the intraventricular salicylate injection was dose dependent, but the slope of the dose-response line was significantly steeper at 4 h than at 1 hour.4. It is suggested that salicylates produce their antipyretic effects by antagonizing the action of EP within the nervous system, and that the hypothalamic EP concentration falls during the course of an EP infusion.

The effects of salicylate on temperature regulation in the rabbit.

1. A stable pyrexia has been produced in rabbits by intravenous injection of leucocyte pyrogen followed by a continuous infusion.2. Intravenous sodium salicylate, given 4 hr after the start of pyrogen infusion, induced rapid and progressive defervescence. The rate of fall of temperature was dose dependent.3. Intravenous injection of sodium salicylate had no effect on the temperature of afebrile rabbits.4. The intraventricular injection of small doses of sodium salicylate, given 4 hr after the start of a pyrogen infusion, caused a rapid, dose-dependent defervescence, but had no significant effect on the temperature of afebrile rabbits.5. Salicylates exert at least part of their antipyretic activity through an action on the central nervous system.

Effect of Sodium Salicylate on Conditioned Absolute Threshold in the Guinea Pig

By means of an automated single-lever shock-avoidance procedure, guinea pigs were conditioned to track absolute thresholds to a thermal noise stimulus. Threshold measurements were made under control conditions and 1–2 h following a single intraperitoneal injection of sodium salicylate. A temporary threshold-shift function was obtained for dose levels from 50 to 250 ms/ks of salicylate. Contrary to expectation, threshold shifts were not produced when salicylate doses below lethal amounts were cumulated over 4 days' time. Failure to demonstrate drug-induced TTS under chronic-dose conditions is discussed in terms of blood salicylate levels. Data are presented that suggest that the analgesic property of salicylate can account in part for the hearing-loss function obtained with avoidance-conditioning procedures. [Work supported in part by the National Institute of Neurological Diseases and Blindness, U. S. Department of Health, Education, and Welfare.]

SOME FACTORS INFLUENCING URINARY EXCRETION OF 3-HYDROXYANTHRANILIC ACID.

SummaryExcretion of a metabolite of tryptophan, 3-hydroxyanthranilic acid (3HAA), was studied in rabbits under varying conditions (immunization with gram negative bacteria, starvation, tryptophan loading, injection of 3HAA, sodium salicylate or cortisone). Starvation for 3 days resulted in a significant decrease in excretion of 3HAA, and injection of 500 mg of tryptophan (I.V.) was followed by an approximate doubling of 3HAA excretion. Immunization and injection with either salicylate or 3HAA (1000 fig) were not accompanied by significant changes in excretion of the metabolite. Administration of hydrocortisone, an agent known to increase liver tryptophan pyrrolase in other species, resulted in the maximal output of 3HAA observed. By inference, it is suggested that the higher excretion of 3HAA and other metabolites of tryptophan observed in some patients with rheumatoid arthritis may result from the preferential shunting of tryptophan metabolism into the kynurenine pathway. Although the basis for such a sh...

VASCULAR REFLEX RESPONSES INDUCED BY AN INTRAARTERIAL INJECTION OF AZAAZEPINOPHENOTHIAZINE, ANDROMEDOTOXIN, VERATRIDINE, BRADYKININ AND KALLIKREIN AND BLOCKING ACTION OF SODIUM SALICYLATE.

The cross circulation technique was applied for perfusing the innervated hindlimb and kidney preparation for analysing the reflex response in the systemic blood pressure and the respiratory movement, when dimethylaminopropyl-tetrahydro-azaazepino-phenothiazine (RPP 201), andromedotoxin, veratridine, bradykinin and kallikrein were injected into the femoral artery of hindlimb preparation.The pressor reflex response was constantly observed by use of RPP 201, andromedotoxin and veratridine but the depressor, or the pressor or the combined reflex was obtained by use of bradykinin and kallikrein. The depressor reflex induced by bradykinin disappeared when the skin of leg was removed, while the pressor reflex was reversed to the depressor one by preceding injection of sodium salicylate into the femoral artery. The pressor reflex with respiratory excitation induced by RPP 201 was also blocked by sodium. salicylate. The afferent fibers in the sciatic nerve were principally responsible to the reflex, and anticholinergic, antiadrenergic, antihistamic, antiserotonic, neuromusclar blocking and ganglion blocking agents did not block the reflex but procaine did it. Authors conclude that the depressor reflex response is probably induced by the excitation of afferent fiber from the skin while the pressor one is originated from the muscle, joint and other parts than the skin, and that sodium salicylate blocks peripherally these nociceptive or pseudoaffective reflex responses, especially originated from the muscle and joint but not from the skin.

INFLUENCE OF ACETYLSALICYCLIC ACID ON THE BODY-TEMPERATURE OF HEAT-STRESSED CHICKENS.

THE oral administration of acetylsalicylic acid or the intra-muscular injections of sodium salicylate were found by me1 to have no influence on the pituitary-adrenal axis of chickens. High levels of acetylsalicylic acid (0.58 per cent) depressed body-weight while low levels (0.07 and 0.15 per cent) did not influence body-weight or pro-thrombin time. A later report by Hutchins et al.2 confirmed that sodium salicylate did not influence the pituitary-adrenal axis in chickens. These workers also reported that immature chicks acclimatized to 105° F and fed sodium salicylate had lower body-temperatures than controls not fed sodium salicylate. The purpose of this investigation was to determine the influence of acetylsalicylic acid on the body-temperature of heat-stressed birds.

Effect of salicylate on the biliary excretion of thyroxine in rats.

In rats in which the plasma thyroxine is labeled with I131, injections of salicylate cause an increase in the ratio of the concentrations of radioactivity in bile and plasma (B/P ratio) and a fall in plasma radioactivity. It is suggested that both effects are due to displacement of thyroxine from the main thyroxine- binding protein of the plasma by salicylate. The greatest effect produced by salicylate on the B/P ratio is not as great as the effect of injections of exogenous thyroxine. This finding is considered in relation to the mechanism whereby the biliary excretion of thyroxine increases at high plasma thyroxine concentrations.

Use of Amine Buffer (THAM) in Treatment of Acute Salicylate Intoxication.

The effectiveness of tris (hydroxymethyl) aminomethane (THAM) in increasing salicyluria after intravenous injection of sodium salicylate was tested in experiments on 4 dogs. A marked drop of salicylate in plasma and increase in its excretion in urine was demonstrated. These experiments also indicate that maximum excretion of salicylate by the kidney will occur when an elevation of body fluid pH and urine pH are accompanied by a marked diuresis. THAM, which promotes these changes, may be useful in treatment of salicylate poisoning in man.

Effect of salicylate on the activity of plasma enzymes in the rabbit.

ELEVATIONS of glutamic-oxaloacetic and glutamic-pyruvic transaminases have been reported to occur in sera from more than 50 per cent of children with rheumatic fever treated with either aspirin or sodium salicylate1. The injection of sodium salicylate in the rat caused an increased activity of xanthine dehydrogenase in the blood but a decreased activity of the enzyme in the liver, and it was suggested that the salicylate caused liver and other tissue damage leading to an increased rate of release of enzyme protein into the circulation2. We have therefore studied the effects of prolonged oral administration of salicylate on the activities of five plasma enzymes and on tissue histology in the rabbit.

The effects of sodium salicylate on the oxygen consumption of rats.

The effects of sodium salicylate on oxygen consumption of intact rats and rats treated with tubocurarine have been studied. Intraperitoneal injections of sodium salicylate in untreated rats produced varying results which depended on both the dose and the concentration used. Intravenous injections in rats treated with curare gave rise to an increase in oxygen consumption which was proportional to the log dose over a range of 0.0625 mg./g. to 0.5 mg./g. body weight. It was concluded that sodium salicylate stimulated the oxygen consumption of rats when the concentration of the drug in the plasma was high.

The antagonism of salicylate to diethylstilbestrol upon liver glycogen in the rat.

Since salicylate has been reported to antagonize liver glycogenesis after cortisone, an experiment was designed to test the antagonism of salicylate to diethylstilbestrol upon liver glycogen in normal, fasted, female rats. Liver glycogen levels, elevated by estrogen treatment for two weeks, were found to be lowered by a subsequent injection of sodium salicylate, 5–8 hours before sacrifice. The action of the estrogen in producing liver and adrenal enlargement, moderate depletion of adrenal ascorbic acid,and maximal depletion of adrenal cholesterol was confirmed. Salicylate alone produced only a moderate depletion of adrenal ascorbic acid, while the combined effect of the drugs was seen in a marked depletion of this substance. Diethylstilbestrol and sodium salicylate were synergistic with regard to the stimulation of activity in the rat adrenal cortex under these conditions (probably by release of ACTH), but their actions on liver glycogen levels were in the opposite directions. The estrogen stimulated glycogen accumulation while salicylate was glycogenolytic; in combination, the substances were antagonistic in this respect. It is concluded that the mechanism is a salicylate-glucocorticosteroid antagonism.

Studies on water excretion following intravenous hydration and the administration of pitressin or nicotine in congestive heart failure.

The diuretic response to intravenous infusions of 5 per cent glucose in water and the antidiuretic response to intravenous injections of nicotine salicylate and aqueous Pitressin, during maximal water diuresis, were studied in normal subjects and patients in congestive failure of varying severity. Patients in moderately severe congestive failure exhibited normal diuretic responses during the periods of intravenous hydration and normal antidiuretic responses following nicotine or Pitressin injections. Patients in more severe congestive failure failed to achieve comparable diuretic responses, following intravenous hydration; in the course of this, signs of increasing congestive failure developed, which were associated with further decrease in urine flows, at times, without any further decrease in renal hemodynamics. These studies confirm the impression that patients in moderate congestive failure have neither increased sensitivity to, nor reduced ability to, inactivate endogenous or exogenous antidiuretic hormone. In addition, the observation, that patients in more severe failure do not achieve adequate water diuresis during intravenous hydration, suggests that sustained production of antidiuretic production, independent of normal osmoreceptor control, may be contributing to their fluid retention.

Vestibular and Acoustic Reactions Induced in Guinea-Pigs by Subcutaneous Injection of Quinine, Pilocarpine and Salicylate

Vestibular and Acoustic Reactions Induced in Guinea-Pigs by Subcutaneous Injection of Quinine, Pilocarpine and Salicylate

Treatment and cure of seventy-six cases of hydrocele by one twin-injection of lithium salicylate and quinine hydrochloride and urethane

Seventy-six patients with hydrocele have been treated and cured by the method of one twin injection of lithium salicylate and quinine hydrochloride and urethane. The average loss of time was two to three days. No hospitalization was necessary in any one case of this series. No complications occurred and there was no setback in any of the patients who suffered from myocardial or pulmonary conditions. This method, if used in carefully selected cases, may do away with the hazard of surgery and save money and time for the patient.

PROSTIGMIN AS AN AID IN THE DIAGNOSIS OF MYASTHENIA GRAVIS

Our object in this communication is to demonstrate the value of prostigmin as an aid in the diagnosis of myasthenia gravis. In the course of the study this drug was used with immediate but transient improvement in nine cases of the disease, and with neither subjective nor objective changes in fourteen cases of various neurologic disorders. The value of this drug in the treatment of these patients will also be discussed. In recent years interest in myasthenia gravis has been stimulated by the discovery of new therapeutic agents and by metabolic studies. Walker 1 in 1934 reported the improvement that resulted from the subcutaneous injection of physostigmine salicylate. This drug was tried because it was thought that the disease might be due to a curare-like poisoning of the motor nerve endings or the myoneural junctions. Feb. 8, 1935, Walker demonstrated before the Clinical Section of the Royal Society of Medicine

L'année thérapeutique: Médications et procédés nouveaux

This volume, like its predecessors, is replete with interesting abstracts from the current literature, giving special prominence, of course, to innovations reported in French medical periodicals. A few of the items of interest are the treatment of chronic alcoholism and delirium tremens by injections of emetine hydrochloride (0.02 Gm.); the analgesic value of intradermal injections of distilled water into tender areas; atropine in large doses (2 mg. and more) in the treatment of parkinsonism, and the treatment of fistulas by sclerosing injections of quinine ethyl carbamate or sodium salicylate. It is stated that hemorrhages in the mouth can be promptly checked by application of meat from a bird such as a pigeon or a chicken, slaughtered at the time of use. The antidotal value of sodium nitrite against potassium cyanide poisoning is discussed. Gelatinothorax, in the treatment of empyema, is the injection of 2 per cent of gelatin in physiologic

Studies of Experimental Streptococcus Arthritis. IV. Effect of Sodium Salicylate on Skin Allergy.

The effect of sodium salicylate on the development of dermal allergy in the presence of hemolytic streptococcal arthritis was studied because this drug is commonly employed in the treatment of acute rheumatic fever, and because the studies of Swift concerning the pathogenesis of this disease support the idea that allergy to streptococci of various kinds is a factor in its production. As previously reported by us, the production of arthritis in rabbits by the inoculation into a knee joint of 0.1 cc. of 24 hour broth culture of hemolytic streptococcus will be followed, in 6 days, by the appearance of a strongly positive local reaction to intradermal injection of a filtrate of a 5 day culture in Harley's medium. This skin reaction takes 12 to 24 hours to develop. All rabbits were tested previous to the experiment and found to give no such reaction. In this study 24 rabbits were employed, 12 of which received sodium salicylate and 12 were used as controls. Of those which received sodium salicylate, 6 received the drug for a considerable period before receiving an intra-articular injection of 0.1 cc. of culture of hemolytic streptococcus; and 6 rabbits received the drug and the culture at the same time. The dose of sodium salicylate was 0.2 gm. per kilo in 4% solution and was given intravenously. The first series of 6 received 8 daily injections of salicylate and after an interval of 12 days, during which the animals were in good health, received 6 more injections given at 2 day intervals. After the injection of streptococci into the knee joint, 3 more daily injections of sodium salicylate were used and 3 days later skin tests were made.

PARIS

<h3>Improvement in the Treatment of Epidemic Encephalitis and Parkinson's Disease</h3> By means of intravenous injections of sodium salicylate, Carnot and Blamoutier have secured remarkable results in the acute period of epidemic encephalitis. The injections sometimes produce painful shock, although never causing serious accidents. Such injections affect the inner tunic of the vein and cause the vein to become blocked. Dr. René Bénard's simple modification, recently introduced, consists in administering sodium salicylate in a dextrose solution, following which neither shock nor reactions on the wall of the vein are observed. One of his assistants was able to apply sixty-three injections of this solution in the same vein. A slender needle must be employed, and, in puncturing the wall, laceration must be avoided. In introducing the needle, care must be taken to prevent the solution from adhering to its surface. It is sufficient to immerse the needle for a few seconds in