J. Edward King

Studies on olfactory discrimination in dogs: (3) ability to detect human odour trace

Abstract Dogs failed to find human odour trace on glass slides weathered outdoors for three weeks, and were beginning to make some unreliable responses with 1 and 2 week old samples. Similar slide material kept indoors for the same length of time was readily and significantly detected. In fact, high performance scores were recorded up to 6 weeks. There was little correlation between records kept on temperature and climatic changes and the actual work performance scores.

Studies on nicotine absorption during pregnancy

Abstract Pregnant and nonpregnant rats of the Osborne-Mendel strain were injected subcutaneously with heavy doses of a 2 per cent solution of pure nicotine for the purpose of determining the LD 50 for females of this strain. Pregnant rats received drug on the twenty-first day, one day before expected delivery. The LD 50 for neonates of this strain was also determined within 6 to 24 hours of normal birth. The following values were obtained:Osborne-Mendel rats LD 50 (mg./Kg.)Pregnant adults, 140 to 150 days of age27.4Nonpregnant females, 140 to 150 days of age33.5Neonates, 6 to 24 hours old14.55 Pregnant rats tend to die significantly later than nonpregnant rats, but their tolerance for nicotine is considerably less. The significance of these facts is discussed in terms of maternal-fetal relationships in drug detoxification. Pregnant versus nonpregnant differences in respect to tolerance for nicotine were the reverse of those consistently encountered with barbiturates.

Intrauterine respiration in the rat fetus 1. Direct observations—comparison with the guinea pig

Abstract 1. 1. Guinea pig fetuses in intact uterine horns do not engage in intrauterine respiratory-like efforts according to our observations of water bath preparations. We cannot speak with as much certainty about rat fetuses in intact uterine horns. 2. 2. Both species can be induced to make intrauterine respiratory movements under conditions of hypoxic stress. 3. 3. The pattern of these movements differs in the two species. 4. 4. This behavior occurs only after the hypoxic stimulus has been operant for a definite interval of time, and it runs its course for a very fixed period of time. It is not a thing that is seen in some fetuses by chance and not in others, but in all fetuses subjected to stress under the terms of our experiment. 5. 5. Initiation is longer delayed and its duration increases the more the fetus approaches term age. 6. 6. The development of the responsiveness of the fetal respiratory center in rats of different gestational ages was discussed and compared with similar findings in other species. 7. 7. Neither the rat nor the guinea pig fetus behaved at all like rabbit fetuses are reported to behave in utero. 8. 8. The question as to whether fetuses are normally apneic in utero or engage spontaneously in intrauterine respiratory-like behavior cannot be settled on the basis of observational techniques alone.

Experimental studies on nicotine absorption during pregnancy: IV. The postmature neonate

Abstract This report deals with 55 pregnant rats assigned randomly, 5 each, to 11 study groups. Three groups were untreated controls delivered either spontaneously on the twenty-second day of gestation (term), or by cesarean section on the twenty-first and twenty-second day. Four groups were rendered postmature by prolonging gestation with chorionic gonadotropin and were delivered by section on days 21, 22, 23, and 24. Four other experimental groups producing postmature young were delivered by section on these same days after having been treated chronically with nicotine throughout pregnancy. While gestation had been equally prolonged in the two experimental groups, hormone-induced postmaturity yielded young with many of the characteristics that have been ascribed to the postmaturity syndrome in man. However, nicotine-exposed young were underweight, virtually fetal in appearance, had narrower transverse head diameters, shorter vibrissae, shorter claws or none at all, and ossification in the long bones had not progressed as far as it had in term young of equal weights. Both groups of experimental animals would have delayed delivery even longer had sectioning not intervened. The nicotine-treated off spring could have passed for premature and were somewhat comparable to the peculiar, small, malnourished infants with prolonged gestations described recently in the human literature.

INTRAUTERINE RESPIRATION IN THE RAT FETUS. II. ANALYSIS OF ROENTGENOLOGICAL TECHNIQUES.

Abstract Pregnant rats and guinea pigs of varying gestational ages were prepared for roentgenological examination after injecting Thorotrast (or Diodrast) in amnio. Sometimes Calcodur blue dye was mixed with Thorotrast to color the fetus in order to ascertain that the injection had been carried out successfully. Injections were made through the abdominal wall directly in some specimens. After periodic roentgenograms were taken they were allowed to deliver their own young. In others the abdomen was opened surgically amniotic sacs were injected and the abdomen was closed, only to be reopened prior to term to study fetuses in a water bath preparation. These were called chronic water bath studies. In an acute water bath study, injection was made immediately upon exposure of the uterus and a clamp was applied to the uterine vessels of one uterine horn to render fetuses in that horn hypoxic. The fetuses in the opposite, unclamped horns served as oxygenated controls. In all water bath studies, neck clamps were applied to the fetuses before removal to prevent their aspirating amniotic contents during cesarean delivery. These fetuses were x-rayed and the roentgenograms were studied for evidence of aspirated contrast medium in the fetal lung. If such aspiration occurred routinely in the control groups, it could be said that the fetuses normally practiced intrauterine respiration. If it occurred chiefly in the hypoxic horn, it could be ruled that such fetal behavior was normally induced only under conditions which fostered intrauterine hypoxia. The data presented support the last thesis in the main. We have pointed out how critical one must be in evaluating studies of this nature.

Intrauterine respiration in the rat fetus III. Aspiration and swallowing of Calcodur blue dye

Abstract 1. 1. The data presented here show that when Calcodur blue dye is injected in amnio in pregnant rats the dye appears predominantly in the digestive tract not in the fetal lungs unless intrauterine hypoxia is experimentally induced. 2. 2. In the latter event, the dye is readily and almost routinely to be found in the fetal lung. 3. 3. Because so many other factors in the experimental framework can predispose the intrauterine environment toward a hypoxic state, which varies in degree of severity as either gestation itself or the time of water bath exposure varies, the question as to whether intrauterine respiration is or is not a normal spontaneous event during certain stages of fetal life may well have to be resolved on a statistical basis in which large population samples are studied. 4. 4. Workers in this area must also be critically cognizant of the factors operant in their particular experimental design which will effect the very phenomenon they are trying to observe.

Sex differences in the response of rats to pentobarbital sodium

Abstract 1.1. Pentobarbital disappears from the blood of pregnant rats relatively more slowly than from the blood of nonpregnant females. From the eighth through the twelfth hour after injection the blood level remains significantly higher in the pregnant animal. 2.2. Brain levels remain significantly higher in the pregnant rat from the sixth hour. Two to 4 hours after injection fetal brain levels are 90 per cent of maternal values and up to 12 hours fetal levels remain approximately 75 per cent of that of the mother. 3.3. Similarly, the drug level remains higher in the liver of the pregnant rat than in the nonpregnant rat. Fetal liver has a slightly higher affinity for barbiturate than does the fetal brain. It is doubtful, however, that the fetal rat liver contains enzymes capable of detoxifying the drug. 4.4. Pentobarbital is also present in small amounts in amniotic fluid, but its disappearance from this site is slower than from the fetal tissues. 5.5. Thus, when the nonpregnant female is given drug, the brunt of detoxification falls upon the liver at once. The respiratory, circulatory, and temperature regulatory mechanisms are severely depressed until detoxification is achieved within a few hours, and the drugged rat awakens relatively early. 6.6. In the pregnant rat, on the other hand, the liver does not receive the full burden of the drug as rapidly. It crosses the placental barrier and pools in fetal tissues and in amniotic fluid, only to be fed back into maternal tissues gradually. The fetal tissues play no role in detoxification, but merely serve to decrease the load thrown upon the mother at one time. Thus, maternal barbiturate levels remain high and sleep is prolonged. 7.7. In light of the higher barbiturate levels in pregnancy, the failure of the pregnant rat to become as severely depressed as the nonpregnant female remains enigmatic. A possible cause could lie in alterations of protein-binding in pregnancy. 8.8. Two unknowns remain to be solved: (1) Is the assumption that fetal rats are incapable of detoxifying barbiturate valid as in neonatal rabbits, guinea pigs, and mice? (2) To what degree is protein-binding of pentobarbital altered in pregnancy?

Studies on nicotine absorption during pregnancy: II. The effects of acute heavy doses on mother and neonates

Abstract When primipara pregnant rats, 140–150 days old, receive a single heavy subcutaneous injection of nicotine on the twenty-first day of pregnancy, one day prior to expected term delivery, they respond differently from nonpregnant females the same age, similarly treated. The pregnant animal tolerates less drug and hyperventilates excessively while body temperature depression is not as marked as in the nonpregnant rat. Many of the treated animals fail to build adequate nests or to take proper care of their young. Delivery is delayed 2 to 4 days beyond term, the young tend to be lighter in weight than normal, and the young survive poorly through the first critical 48 hours of life. Our data does not support the idea of an extremely rapid elimination of nicotine from tissues when it is present in near-lethal amounts.

Sex differences in the response of rats to pentobarbital sodium: IV. Pentobarbital levels in pregnant and nonpregnant rats☆

Abstract 1. 1. Pentobarbital disappears from the blood of pregnant rats relatively more slowly than from the blood of nonpregnant females. From the eighth through the twelfth hour after injection the blood level remains significantly higher in the pregnant animal. 2. 2. Brain levels remain significantly higher in the pregnant rat from the sixth hour. Two to 4 hours after injection fetal brain levels are 90 per cent of maternal values and up to 12 hours fetal levels remain approximately 75 per cent of that of the mother. 3. 3. Similarly, the drug level remains higher in the liver of the pregnant rat than in the nonpregnant rat. Fetal liver has a slightly higher affinity for barbiturate than does the fetal brain. It is doubtful, however, that the fetal rat liver contains enzymes capable of detoxifying the drug. 4. 4. Pentobarbital is also present in small amounts in amniotic fluid, but its disappearance from this site is slower than from the fetal tissues. 5. 5. Thus, when the nonpregnant female is given drug, the brunt of detoxification falls upon the liver at once. The respiratory, circulatory, and temperature regulatory mechanisms are severely depressed until detoxification is achieved within a few hours, and the drugged rat awakens relatively early. 6. 6. In the pregnant rat, on the other hand, the liver does not receive the full burden of the drug as rapidly. It crosses the placental barrier and pools in fetal tissues and in amniotic fluid, only to be fed back into maternal tissues gradually. The fetal tissues play no role in detoxification, but merely serve to decrease the load thrown upon the mother at one time. Thus, maternal barbiturate levels remain high and sleep is prolonged. 7. 7. In light of the higher barbiturate levels in pregnancy, the failure of the pregnant rat to become as severely depressed as the nonpregnant female remains enigmatic. A possible cause could lie in alterations of protein-binding in pregnancy. 8. 8. Two unknowns remain to be solved: (1) Is the assumption that fetal rats are incapable of detoxifying barbiturate valid as in neonatal rabbits, guinea pigs, and mice? (2) To what degree is protein-binding of pentobarbital altered in pregnancy?

Protein dynamics in the amniotic fluid of the rat and guinea pig near term

Abstract 1. 1. The total protein in the amniotic fluid of the rat increases from 18 days, 12 hours, to 21 days, 18 hours, whereas the guinea pig total protein shows an increase, then a decline to term, but this value never becomes much greater than the lowest total protein of the rat. 2. 2. The albumin concentration in the amniotic fluid of the rat increases from 18 days, 12 hours, to 21 days, 18 hours, as does the globulin concentration; but the per cent of albumin also increases throughout this period which implies that the per cent of globulin decreases. 3. 3. The per cent of beta and gamma globulins remains stable throughout the observation period, but the per cent of alpha globulins shows a decline. 4. 4. The albumin/globulin ratio increases throughout the observation period. 5. 5. The changes in protein dynamics are discussed in relation to amniotic fluid viscosity changes, aspiration of fluid during the stress of hypoxia, and the effects upon neonatal survival in these two species.