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Metalation of 3,5-diethylanisole with carbon-14 labelled ethyllithium has demonstrated that an adduct of EtLi to the ring is not an intermediate in the process; an alternative radical and radical anion route involving capture of a hydrogen atom by R (from RLi) from is not ruled out by the labelling experiments, but negative CIDNP results did not support the idea of the intermediacy of radical species in the metalation reaction with six different substrates. A number of metalation results were obtained with n-BuLi and t-BuLi in no-polar solvents in the presence and in the absence of N,N,N′,N′-tetramethyl- etlylenediamine (TMEDA) on substrates selected for showing different steric environments in the same molecule. The large majority of the data could be correted with the concept that the steric requirement of the RLi was related to tholigomer size and that the decreasing order of steric requirement was n-BuLi in hydrocarbon > t-BuLi in hydrocarbon > n-BuLi in ether > n-BuLiTMEDA in hydrocarbon. A case of particularly facile dimetalation was observed with a substrate in which the second lithium atom substituted in a methyl group adjacent to the portion of substitution on the ring by the first lithium, e.g., This reaction outcome seemed to correlate with the association of the product of the first metalation with the RLi oligomer which brought the nearby methyl group into close association with the oligomer surface, thus facilitating a second attack with introduction of the lithium atom at thatpoint. Metalation in the presence of TMEDA did not allow this facile dimetalation probably because of the absence of the oligomer in the presence of the chelating amine. Several observations point to heretofore unrealized possibilities for synthetic utility of RLi metalations under certain conditions.

Iodination of red blood cells under optimal conditions by the Phillips-Morrison method leads to the iodination of two surface proteins. Modification of these conditions leads to the labeling of additional membrane proteins; labeling of hemoglobin can also occur. These results lead to the conclusion that, depending on the conditions of iodination, proteins located at various depths of the membrane can be labeled. This information was used in establishing an assay for the optimal iodination conditions of HeLa cells. Such iodinated HeLa cells grow at the same rate as control HeLa cells; most of these iodinated surface proteins can be removed by subsequent treatment with pronase.

The molecular weights of the five iodinatable surface membrane proteins of HeLa cells were determined to be 170 000, 145 000, 130 000, 93 000 and 53 000. The proteolytic digestion of these proteins with pronase, trypsin and chymotrypsin was also studied. Metabolic studies showed that these iodinated surface proteins are released into the medium in both acid-soluble and acid-insoluble forms. Antibodies prepared towards these released membrane fragments as well as antibodies prepared towards whole membrane inhibit the growth of HeLa cells.

Summary The acute subcutaneous and oral toxicities of two commonly used antihistaminic drugs, chlorpheniramine and diphenhydramine, were determined in newborn and young rats. The resistance of rats to both drugs increased with increasing age. The greatest change in resistance appeared between the ages of 16 and 25 days. There was no apparent difference in the activity of the enzymes concerned with the metabolism of both drugs in the livers of 15- and 40-day-old rats. The development of greater resistance to both drugs with increasing age can be explained, insofar as the subcutaneous route is concerned, by a decrease in the amount of absorption.

IT HAS been realized that anesthesia becomes important in poultry surgery. Due to the particular structure of their respiratory organs, birds inhale the volatile anesthetic agents into the air sacs through the respiratory system. It is then difficult to control the depth of the depression and the dosage of these agents. Consequently, the use of inhalation anesthesia is not recommended in poultry. The studies reported herein were conducted to compare the actions of five different anesthetics in four kinds of species of domestic fowls. METHODS Healthy, native Chinese geese, ducks, chickens and pigeons were used. Five anesthetics, ether, 3 chloroform, 3 chloral hydrate, 3 sodium amytal 4 (sodium isoamyl ethyl barbiturate) and sodium pentothal 5 (sodium ethyl [1-methyl-butyl] thiobarbiturate), were chosen for this study. Ether or chloroform was inhaled from a mouth mask containing a piece of cotton saturated with the anesthetic. Chloral hydrate was administered orally as a 1 to 2% solution by a …

MANY cases of cobalt deficiency, both natural and experimental, have been reported in ruminants. All attempts to produce a cobalt deficiency have failed with such small laboratory animals as rats (Houk et al., 1946; Underwood and Elvehjem, 1938) and rabbits (Thompson and Ellis, 1947). The hypothesis that, in the ruminants, cobalt acts primarily through some mechanism involving the microorganisms in the rumen, led to metabolic studies in these animals (Comar and Davis, 1947a, b; Comar et al., 1946a, b; Becker and Smith, 1951). Metabolic studies on cobalt have also been reported from rabbits and swine (Comar and Davis 1947b), from rats (Comar et al., 1946a: Greenberg et al., 1943), and from dogs (Sheline et al., 1946; Lee and Wolterink, 1955a, b, c). Since the microorganisms found in the caeca of poultry may have nutritional significance, analogy with the ruminant suggests that their relationship to cobalt metabolism should be investigated. The …

A specially built inhalation chamber is described for inhalation toxicity studies of trifluoroamine oxide (AMOX). AMOX was introduced into the chamber through a calibrated micrometer valve. Desired AMOX concentrations were reached within 5 minutes after closure of the chamber and were monitored by a continuous infrared scanning technique. The concentrations were relatively constant and reproducible between 10 and 100 ppm.

l -β-Aspartamido-carbohydrate was prepared from the egg-white ovalbumins of duck, turkey, Western gull, and genetically homogeneous chickens, demonstrating the general nature of their linkage of carbohydrate to protein. In each case, the carbohydrate was paucidisperse; and the compositions of the fractions for duck and turkey were such that it is likely that more than one oligosaccharide residue per polypeptide chain is present. The results further support the hypothesis that the series of carbohydrate fractions represents the result of biosynthesis, and not that of genetic heterogeneity or subsequent degradation of one or more oligosaccharides.

Five components of l -β-aspartamido-carbohydrate, prepared from crystalline chicken ovalbumin by digestion with pronase, have been isolated and purified by a combination of ion-exchange chromatography and zone electrophoresis. Their sequences may be represented: homology being demonstrated by enzymic hydrolysis with α- d -mannosides (E.C.3.2.1.24) or N-acetyl-β- d -glucosaminidase (E.C.3.2.1.30). The molecular dispersity of ovalbumin is discussed in the light of these results.

Five components of asparaginyl-carbohydrate, prepared from crystalline chicken ovalbumin by digestion with pronase, have been isolated and purified. The homology of their structures has been demonstrated by enzymatic hydrolysis, using α- D -mannosidase and N -acetyl-β- D -glucosaminidase.

Acute inhalation and intraperitoneal toxicities of trifluoroamine oxide (AMOX) were determined in rats and mice. The LC50's after exposing male rats or mice for 4 hours (deaths within 7 days) were 24.2 ppm and 17.5 ppm, respectively. The LC50's after exposing male rats for 60, 30, or 15 minutes were between 87 and 104 ppm, 119 and 149 ppm, or 202 and 240 ppm, respectively. The intraperitoneal LD50's for male rats or mice (deaths within 7 days) were 51.6 mg/kg and 32.1 mg/kg, respectively. After intraperitoneal injection, females were more susceptible to the lethal effects of AMOX than the males. AMOX produced strong irritations resulting in pulmonary edema and hemorrhage after inhalation, and local denatured changes and accumulation of clear exudate after intraperitoneal injection. AMOX was quickly absorbed after intraperitoneal injection to rats. Fluoride increased quickly in the blood and concentrated in various tissues, especially in the thyroid, bone, and teeth. Most of the fluoride was excreted in the urine, and a considerable amount was recovered also in the feces.

Pyrimethamine, in oral doses averaging 5–6.2 mg/kg/day for 10–21 days, produced a distinctive pattern of toxicity in healthy beagles. This toxicity resembled that produced by antifolate agents and was characterized by emesis, anorexia, diarrhea (occasionally bloody), and weakness followed by malaise, cachexia, and marked body weight loss. Leukopenia, reticulocytopenia, and intestinal degeneration and atrophy indicated that the target organs were the hematopoietic system and the digestive tract. Administration of folinic acid (0.3 mg/kg/day, im) but not folic acid (7.5 mg/kg/day, po) simultaneously with pyrimethamine protected beagles against the toxicity produced by pyrimethamine.

Summary1. Serum, bile, and liver total cholesterol levels of 9 species of laboratory animals and 4 species of amphibians are reported. 2. Dogs, monkeys, hamsters, and mice have relatively higher serum total cholesterol concentration than cats, rats, rabbits, and guinea pigs. 3. Total cholesterol concentration in liver varies only slightly among these species. 4. Gall-bladder bile of monkeys contains large amounts of total cholesterol. Guinea pigs excrete very small amounts of total cholesterol in bile. 5. Serum and liver total cholesterol concentrations of the pigeon are very high. 6. Total cholesterol concentration in liver varies slightly among the 4 species of amphibians used. Frogs excrete significant amounts of cholesterol in bile. 7. Serum total cholesterol concentrations of both species of toads are higher than those of both species of frogs.

SummaryThe renal clearance of erythromycin is slightly less than the glomerular filtration rate in dogs. Benemid appears to inhibit the reabsorption of erythromycin by the renal tubules.

Two separate areas which are located in the southern portion of the Coppermine River area were surveyed by the author during the summer of 1957. The area under investigation is underlain by the upper part of the Epworth Series and the lower part of the Coppermine River Series. Because of the lack of fossils in these series, they are presumed to be of late Precambrian age. The upper part of Epworth Series is represented by dolomite and interbedded quartzite. The lower part of the Coppermine River Series is represented by a series of basalt flows which are typical tholeiites, and interbedded sandstone in its upper part. A monzonite dyke crosses the basalt flows and sandstone at a high angle and is parallel to the main basaltic dyke swarm seen in the Takiyuak Lake area. The common structural feature is a series of tension faults trending from N10°E to N45°E and N10°W to N20°W, This is believed to have originated by the compressive force from the north induced by the Caledonian movement. The ore minerals, mainly chalcocite, occur in quartz-carbonate veins in feeder dykes and flow tops of basalt. Flakes of native copper are occasionally found in the fractures of the basalt flows.

SummaryBrain chromatin isolated from morphine-treated rats exhibited a significantly lower capacity to promote RNA synthesis than chromatin from control rats. The effect was not caused by either ribonuclease or an RNA polymerase inhibitor extracted during the isolation of chromatin. Removal of protein from chromatin DNA abolished the effect. The in vitro addition of morphine to brain chromatin from untreated animals produced no effect.

SummaryCrystalline papain and crude bromelin preparations stimulate erythropoiesis, whereas other proteolytic enzymes are ineffective. Sialic acid, measured by direct Ehrlich reaction, has been detected in crystalline papain preparations.

The characteristics of the absorption of prednisolone were studied both in intact dogs and in ligated segments of the intestinal tract. Absorption of uncoated prednisolone was essentially complete in 2 hours. Following the administration of copolymer-coated pellets, absorption was extended over a period of 10-12 hours.

SummaryThe usefulness of duodenal fistula dogs as test animals for acid-stable or -labile compounds is demonstrated and the practical application is discussed.

A diet containing 65 per cent sucrose with added cholesterol resulted in hypercholesteremia and increased tissue cholesterol deposition in rats. Ten per cent corn oil with added cholesterol in Purina laboratory chow had no apparent effect on the serum total cholesterol but increased cholesterol deposition in tissues. Ovariectomy was without significant effect. Thyroidectomy or hypophysectomy aggravated the hypercholesteremia and the increased tissue cholesterol deposition induced by the sucrose diet. The effect of hypophysectomy was not due to the loss of thyrotrophic hormone alone. Addition of vitamin D aggravated hypercholesteremia and increased liver cholesterol deposition in normal, thyroidectomized or hypophysectomized rats fed the sucrose diet. In ovariectomized rats, the tissue cholesterol deposition was also augmented. When corn oil diet was fed, the supplementary vitamin D increased the serum total cholesterol level of the thyroidectomized rat.

Vancomycin was administered intramuscularly to dogs at dose levels of 25, 50, 100, and 200 mg/kg in 50% PEG 200 every day for one month. Kidney function, as indicated by creatinine and PAH clearances, was normal. The venous CO 2 contents were not significantly changed. The renal clearance of vancomycin was 40% to 68% of the glomerular filtration rate based on total plasma concentration. At termination, none of the dogs showed gross or microscopic abnormality in the kidney, hematopoietic organs, and other tissues. PEG 200 was given to dogs, 1.0 ml/kg/day for 8 days intramuscularly, or 0.5, 1.0, 2.5, and 5.0 ml/kg i.v. singly. No toxic effects were apparent in any of the dogs. Venous CO 2 content, blood NPN, and blood alkaline phosphatase were normal. No gross or microscopic abnormality was found in the kidneys, circulation, and various tissues.

Acute inhalation, intraperitoneal and/or oral toxicities of AMOX and TAMA were determined in rats and mice. IP absorption was studied in rats. AMOX produced strong irritation resulting in pulmonary edema and hemorrhage after inhalation; and local denatured changes and accumulation of clear exudate after intraperitoneal injection. TAMA was less toxic on the weight basis. Both AMOX and TAMA were quickly absorbed after IP injection. Fluoride increased quickly in the blood and concentrated in various tissues especially in the thyroid, bone and teeth. Most of the administered fluoride was excreted in the urine and a considerable amount was also recovered in the feces.