The experiments reported were undertaken to investigate pharmacologically certain claims that some antihistaminics are antemetic in man and capable of inhibiting or preventing apomorphine-induced vomiting in animals. Diphenhydramine hydrochloride, diphenhydramine-8-chlorotheophyllinate, and diphenhydramine- 8-bromotheophyllinate, administered to cats in rotation, by mouth, in doses of from 0.5 to 20 mgm. per kgm. body weight 0.5 hr. before subcutaneous injection of 20 to 50 mgm, per kgm. of apomorphine hydrochloride, had no effect upon the vomiting syndrome. Doses of from 0.5 to 40 mgm. Per kgm. of the same three derivatives of diphenhydramine were administered orally to dogs in rotation and at intervals of 0.5, 1,2, and 4 hr. before intramuscular injection of 0.05 mgm. per kgm. of apomorphine hydrochloride, with no effect upon the incidence of vomiting and no effect upon the frequency of vomiting and retching except partial inhibition at convulsant and subconvulsant doses. Similar results were obtained from administration of promethazine hydrochloride orally to dogs in doses of from 0.5 to 40 mgm. per kgm. one hour before intramuscular injection of 0.05 mgm. per kgm. of apomorphine hydrochloride, and the same procedure, substituting methapyrilene hydrochloride and methapyrilene-8-chlorotheophyllinate for promethazine hydrochloride, did not affect the vomiting syndrome whatsoever. The results indicate that in amounts corresponding to usual human therapeutic doses, none of these antihistaminics has any ability to prevent apomorphine-induced emesis in dogs and cats.
THISHIS project was undertaken to find if water given by mouth has a pharmacological expectorant action in the sense that it is able to augment the output of demulcent respiratory tract fluid. Respiratory tract fluid is a secretion rich in soluble and insoluble mucus which can be collected through a cannula ligated into the trachea of an animal under certain conditions.1 An agent capable of increasing the output of this fluid may be said to have pharmacological expectorant activity.2 Therapeutic expectorant activity is present if the agent has the same properties at the dosage range and conditions of therapeutic use.Relatively few drugs reputed to be expectorants have been found to have pharmacological expectorant activity at doses near the range recommended in human therapy.2 This may be due in part to the fact that pharmacological expectorant activity has been found recently to vary with season.3 A drug studied in one season of the year might be found to have ex¬ pectorant activity which would be missed if studied in another season. Nevertheless, many pharmacologists and clinicians have concluded that expectorants are useless remedies. Statements to this effect appear in certain publications of organized medi¬ cine, for example that of the British Na¬ tional Formulary4 which concludes that "Cough mixtures . . . are probably (of) little more use than placebos." On the other hand, expectorants continue to be recommended particularly in the treatment of chronic cough, as in bronchial asthma,5·6 and of acute and chronic cough in infants and very young children,4 in which narcotic antitussives are contra¬ indicated and nonnarcotic antitussives may be ineffective.7The studies herein reported were prompted specifically by statements in the literature such as "Domestic remedies of honey in hot water with lemon juice . . . often give as much relief as more sophisti¬ cated mixtures." 4 Oral administration of aqueous solutions of sucrose 8 and volatile oils 9 had been previously found in this laboratory to have no effect in therapeutic doses on the volume output of respiratory tract fluid. This suggested that water itself might be an expectorant. Kendig " has stated that water is the most effective means of liquefying bronchial secretions in asthmatic children, and that it may be given by mouth or by steam inhalation. The inhalation of dry air into the trachea has been known for many years to dry the secretion of respiratory tract fluid, and this is remedied by substituting inhalation of humid air.2 No previous systematic study of the effect of oral administration of water has been reported. Materials and MethodsThe experiments were performed upon healthy male or nonpregnant female rabbits obtained from Canadian Breeding Laboratories, St. Con¬ stant, Quebec, Canada, and weighing 2 to 4 kg. They were fed rabbit pellets and water ad libitum and housed in animal cages, one rabbit per cage.Food was withdrawn for 48 hours to empty the stomach prior to administration of distilled water.The numbers of animals used are indicated ...
The objective of this investigation was to find at what stage in the growth of Walker carcinoma 256 appear the shifts in water and lipid levels of host carcass, skeletal muscle, and testicle, noted at or near death of the dual organism by Boyd, Connell, and McEwen (1952). Lipid and water estimations were made upon these tissues, at intervals of one, two, and three weeks of tumor growth, in 35 tumor-bearing and 34 littermate control albino rats. In host carcass, the decline in concentration, per 100 gm. dry weight, of total lipid, neutral fat, and total fatty acids appeared after two weeks of tumor growth, while at or about the same time a rise occurred in the levels of water, total cholesterol, free cholesterol, and phospholipid. In hind limb skeletal muscle of the host, the levels of total lipid, neutral fat, and total fatty acids were lowered, while those of water were elevated, after two and three weeks of tumor growth. In host testicle, the levels of water and lipids were essentially similar to those of the controls. The rise in concentration of water, phospholipid, total cholesterol, and free cholesterol of the host varied, in general, with increase in the T/RC coefficient. Maximal low levels of host total lipid, neutral fat, and total fatty acids were reached at T/RC coefficient values of 20 to 30. Maintenance of total body weight (tumor plus host) was due mainly to accumulation of water in both components. The host component lost dry weight, total lipid, neutral fat, and total fatty acids more rapidly than these accumulated in the tumor in total amount. The smaller loss of total amounts of water, phospholipid, total cholesterol, and free cholesterol in the host was offset by an approximately equal accumulation of these substances in the tumor.
The objective of this project was to find to what extent loss of weight in the digestive tract might affect tumor size and age in albino rats bearing Walker carcinosarcoma 256. Wet weight, dry weight, and water content were measured upon tongue, esophagus, cardiac stomach, pyloric stomach, jejunum, ileum, cecum, colon, and residual carcass (minus tumor). The animals bore tumors weighing 12 ± 6 (mean ± S.D.) % of host (minus tumor) weight after 18 ± 6 days of tumor growth (group I), 38 ± 12% after 24 ± 6 days (group II), and 93 ± 26% after 29 ± 5 days (group III) and controls were twins of the same sex. There were few significant changes in the animals of group I. In group II, there was loss of dry weight in all organs except pyloric stomach, losses being percentagewise the same as in residual carcass. Loss of dry weight of jejunum and ileum was less in rats of group III than in those of group II. In group III, loss of weight in other organs tended to be less than in residual carcass. Loss of dry weight in residual carcass was not significantly greater in the animals of group III than in those of group II. Water levels were increased in all organs of rats in groups II and III. This evidence indicates that rats of group III may have lived longer after tumor implantation, lost no more carcass weight, and bore larger tumors because they had lost weight in the small bowel at a lesser rate than had the rats of group II.Further studies revealed that lipid shifts were in general less marked in organs which had lost the least weight. In animals bearing large tumors, percentage loss of neutral fat was less in most organs of the digestive tract than in the residual carcass. Increases in the levels of cholesterol and phospholipid were less in pyloric stomach and small bowel than in other organs of the digestive tract. Shifts in the amount of nonlipid dry weight and in levels of lipids and water were in general less in pyloric stomach and small bowel than in other organs of the body. In these respects, pyloric stomach and small bowel resembled brain, heart, and lung. It is suggested that resistance of pyloric stomach and small bowel to the cachectic influence of the tumor may be a factor determining tumor size and length of survival of the host.
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