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The anti-histamine activity of diethylaminoethyldihydroanthracine-carboxylate and other substances
Allergic
Manifestations
of the Newborn
Period.
(hlr~phli,
c-i.
A.
:
~‘allad.
Jr.
A. J. 52: 280,194F.i. A variety of signs which should make one suspicious OCpotential allergy may occur in the newborn period. The results of questionnaires sent to sis hundred obstet,ricians, allergists, and pediatricians suggested that, any one of many signs may indicate that the infant is potent,ially allergic. The reports included anaphylactic shock from human milk, retro-aurieular intertrigo, infantile eczema, cough, vomiting, \vheezillg, seborrhea, intestinal bleeding after feeding cow’s milk, geographical tongue, excessive rubbing of the nose, urticaria, asthma in a breast-fed baby, esccssivc sneezing, &ma of the hands and feet, etc. An analysis of the histories of t\vo huutlretl cases observed by the author of allergy in late infancay a11t1childhootl ~~~vealeclthat 25 per cent of them had shown allergic symptoms clurin, 0’ their nrwbot~ period which might, have l)een easily recognized. Twenty-four case historit>s are cited. Two C~SCSof extrenlr sensitivity to human milk iu newl~~rn infants are ~~mt~lcd. A .
Anaphylaxis Sensitization to Ragweed Extract and the Production of Antibodies by Means of Adjuvants. Kulka, A. M., and Hirsch, Ljorothy : .J. Immunol. 50: 127, 1945. Rabbits and guinea pigs sensitized with a mixture of ragweed pollen estract, killed tubercle bacilli, paraffin oil, and Aquaphor developed sensitivity to ragweed more rapidly and to a more marked degree than control animals sensitized with ragweed extract alone. h’urthermore, the antibody level was more sustained in the group sensitized with the aid of adjuvants. A cutaneous test with ragweed extract resulted in an erythematous reaction when read at one hour and at twenty-four hours. l’hc intensity of the cutaneous response paralleled the precipitin titer. The sera sensitized smooth muscle and passive sensitization was demonstrable by the Dale technique. When a cutaneous site of a normal guinea pig was sensitized \vith rabbit antiserum, an injection of ragweed antigen elsewhere after a twenty-four-hour interval produced an erythema and edema at the sensitized site within fifteen to thirty minutes. In four cases, rabbit antiragweed serum was injected into human skin and the sites were tested twenty-four hours later with ragweed pollen extract. Two of these tests gave positive reactions within fifteen minutes and one gave a faintly positive response after forty-eight hours. A high percentage of sensitized rabbits reacted with dyspnea, wheezing! and jumping to the inhalation of ragweed antigen administered by a spray. Such reactlons could not be correlated with the precipitin titers or cutaneous sensitivities. The question of whether reagins were formed in atltlition to th(I 1)recipitin antibodies is discussed. %:. Kailin.
The Action of Histaminase Ciochem.
in Vivo.
Lemley,
J. Al., ant1 Laskowski,
I\I. : Arch.
6: 115, 1945.
In order to demonstrate the activity of histaminase in living animals the amount used must be great enough to destroy at least half of the active dose of histamine in the interval of time between introduction of histamine and the onset of symptoms. The contradictory reports in the literature concerning the action of histanlinase in viva are of little value since the amounts of histaminase employed were much too small to be effective. Guinea pigs were injected intraperitoneally, intracardially, or intravenously with one and a half times the lethal (experimentally determined) dose of Histaminase in variable large closes was injected histamine dihydrochloride. either intracardially or int)ravenously immediately preceding the administra111 a control group of ten animals that received on1.y histion of histamine. tamine, no animal survived longer than thirty minutes. In a group of thirteen
animals that received histaminase immediately before the histamine injection, six animals survived longer than thirt,y minutes and four of these six survived indefinitely. The remaining animals died within three days, and all but, one showed massive intrapericmdial hemorrhage. Of four animals that received histaminase alone, only one survived longer than three days. The others showed symptoms similar to those seen in the unsuccessfully protected animals of the histamine-histaminase group. On autopsy, they also showed massive pericardial damage. It was concluded tha,t histaminase in its present state of development is highly toxic when injected into animals. Adequate protection would require doses of histaminase which could not be attained with the present preparation. A.
The Anti-Histamine Activity of Diethylaminoethyldihydroanthracine-Carboxylate and Other Substances. Lehmann, G., and Young, J. MT. : J. Pharmacol. & Exper. Therap. 83: 90, 1945. One hundred one guinea pigs, sensitized with egg white, were given shocking doses of various strengths of the antigen thirty minutes following t,he intravenous injection of Diethylaminoethyldihydroanthracine-, Xanthin-, or Fluorene-, Carboxylate. One hundred per cent of the animals were protected by the Dihydroanthracine compound against a dose of antigen which was lethal for 90 per cent of the control group and 27 per cent were protected against doses twice and one hundred times as strong. The other substances studied afforded less protection. The protective action is presumed to be due to an antihistamine effect on smooth muscle rat,her than to interference with the antigen-antibody reaction. D. a.lso reduced the volume but not the acid concentration of histamine-induced gastric secretion and diminished the cutaneous reaction of histamine. Resistance of the pulmonary circulation of the isolat.ed perfused guinea pig lung is reduced by aminophylline and D. D. was found to be a less potent bronchial dilator than aminophylline. li’ .
The Inhibition
of Histamine Release by a Pituitary-Adrenal
Mechanism.
Ungar,
G. : J. Physiol. 103: 333, 1944. The bloods of normal rabbits, guinea pigs, and ra,ts, when mixed in vitro with peptone, release amounts of histamine which are constant for the species. In guinea pigs treated with peptone? the release of histamine in vitro is less than in controls. In the blood of gumea pigs which are anesthetized and subjected to trauma, histamine release in vitro by peptone was diminished for a period of time beginning four hours after the trauma a,nd lasting up to ninet,een days, depending on the amount of trauma and the time needed for healing of the wound. In ether-anesthetized animals the histamine release was small but became normal after one hour. The factor inhibiting histamine release by peptone was present in the The injection int,o normal animals of sera serum of traumatized animals. taken from sensitized animals three to twenty-four hours after anaphylactic shock inhibited the histamine release. The amount, of inhibiting factor in the postanaphylactic serum was less than 1 per cent of tha.t in the serum of a substance appeared in animals four to twentytraumatized animal. Inhibiting four hours after an injection of peptone. Histamine release was also inhibited by adrenalin, local anesthetics, and ascorbic acid. In rats the adrenal glands are not essential for the production of t.he inhibiting factor. However, hypophysectomized rats lack the inhibiting factor. Crude adrenal and pituitary extracts added to normal blood are strong inPurified hibitors of histamine release. Liver extract lacks this property. adrenal and pituitary extracts are less effective hhan crude extracts. Desoxycorticosterone is inactive. Crude adrenal extract is about 100 times as active The most active product tested so far is a corticotrophic as cortic,al extract. The evidence suggests that the inhibitory substance is produced hormone. bv the pituitary gland and.acts through the adrenals which then affect the I,iood cells so as to inhibit histanline release.
Manifestations
of the Newborn
Period.
(hlr~phli,
c-i.
A.
:
~‘allad.
Jr.
A. J. 52: 280,194F.i. A variety of signs which should make one suspicious OCpotential allergy may occur in the newborn period. The results of questionnaires sent to sis hundred obstet,ricians, allergists, and pediatricians suggested that, any one of many signs may indicate that the infant is potent,ially allergic. The reports included anaphylactic shock from human milk, retro-aurieular intertrigo, infantile eczema, cough, vomiting, \vheezillg, seborrhea, intestinal bleeding after feeding cow’s milk, geographical tongue, excessive rubbing of the nose, urticaria, asthma in a breast-fed baby, esccssivc sneezing, &ma of the hands and feet, etc. An analysis of the histories of t\vo huutlretl cases observed by the author of allergy in late infancay a11t1childhootl ~~~vealeclthat 25 per cent of them had shown allergic symptoms clurin, 0’ their nrwbot~ period which might, have l)een easily recognized. Twenty-four case historit>s are cited. Two C~SCSof extrenlr sensitivity to human milk iu newl~~rn infants are ~~mt~lcd. A .
Anaphylaxis Sensitization to Ragweed Extract and the Production of Antibodies by Means of Adjuvants. Kulka, A. M., and Hirsch, Ljorothy : .J. Immunol. 50: 127, 1945. Rabbits and guinea pigs sensitized with a mixture of ragweed pollen estract, killed tubercle bacilli, paraffin oil, and Aquaphor developed sensitivity to ragweed more rapidly and to a more marked degree than control animals sensitized with ragweed extract alone. h’urthermore, the antibody level was more sustained in the group sensitized with the aid of adjuvants. A cutaneous test with ragweed extract resulted in an erythematous reaction when read at one hour and at twenty-four hours. l’hc intensity of the cutaneous response paralleled the precipitin titer. The sera sensitized smooth muscle and passive sensitization was demonstrable by the Dale technique. When a cutaneous site of a normal guinea pig was sensitized \vith rabbit antiserum, an injection of ragweed antigen elsewhere after a twenty-four-hour interval produced an erythema and edema at the sensitized site within fifteen to thirty minutes. In four cases, rabbit antiragweed serum was injected into human skin and the sites were tested twenty-four hours later with ragweed pollen extract. Two of these tests gave positive reactions within fifteen minutes and one gave a faintly positive response after forty-eight hours. A high percentage of sensitized rabbits reacted with dyspnea, wheezing! and jumping to the inhalation of ragweed antigen administered by a spray. Such reactlons could not be correlated with the precipitin titers or cutaneous sensitivities. The question of whether reagins were formed in atltlition to th(I 1)recipitin antibodies is discussed. %:. Kailin.
The Action of Histaminase Ciochem.
in Vivo.
Lemley,
J. Al., ant1 Laskowski,
I\I. : Arch.
6: 115, 1945.
In order to demonstrate the activity of histaminase in living animals the amount used must be great enough to destroy at least half of the active dose of histamine in the interval of time between introduction of histamine and the onset of symptoms. The contradictory reports in the literature concerning the action of histanlinase in viva are of little value since the amounts of histaminase employed were much too small to be effective. Guinea pigs were injected intraperitoneally, intracardially, or intravenously with one and a half times the lethal (experimentally determined) dose of Histaminase in variable large closes was injected histamine dihydrochloride. either intracardially or int)ravenously immediately preceding the administra111 a control group of ten animals that received on1.y histion of histamine. tamine, no animal survived longer than thirty minutes. In a group of thirteen
animals that received histaminase immediately before the histamine injection, six animals survived longer than thirt,y minutes and four of these six survived indefinitely. The remaining animals died within three days, and all but, one showed massive intrapericmdial hemorrhage. Of four animals that received histaminase alone, only one survived longer than three days. The others showed symptoms similar to those seen in the unsuccessfully protected animals of the histamine-histaminase group. On autopsy, they also showed massive pericardial damage. It was concluded tha,t histaminase in its present state of development is highly toxic when injected into animals. Adequate protection would require doses of histaminase which could not be attained with the present preparation. A.
The Anti-Histamine Activity of Diethylaminoethyldihydroanthracine-Carboxylate and Other Substances. Lehmann, G., and Young, J. MT. : J. Pharmacol. & Exper. Therap. 83: 90, 1945. One hundred one guinea pigs, sensitized with egg white, were given shocking doses of various strengths of the antigen thirty minutes following t,he intravenous injection of Diethylaminoethyldihydroanthracine-, Xanthin-, or Fluorene-, Carboxylate. One hundred per cent of the animals were protected by the Dihydroanthracine compound against a dose of antigen which was lethal for 90 per cent of the control group and 27 per cent were protected against doses twice and one hundred times as strong. The other substances studied afforded less protection. The protective action is presumed to be due to an antihistamine effect on smooth muscle rat,her than to interference with the antigen-antibody reaction. D. a.lso reduced the volume but not the acid concentration of histamine-induced gastric secretion and diminished the cutaneous reaction of histamine. Resistance of the pulmonary circulation of the isolat.ed perfused guinea pig lung is reduced by aminophylline and D. D. was found to be a less potent bronchial dilator than aminophylline. li’ .
The Inhibition
of Histamine Release by a Pituitary-Adrenal
Mechanism.
Ungar,
G. : J. Physiol. 103: 333, 1944. The bloods of normal rabbits, guinea pigs, and ra,ts, when mixed in vitro with peptone, release amounts of histamine which are constant for the species. In guinea pigs treated with peptone? the release of histamine in vitro is less than in controls. In the blood of gumea pigs which are anesthetized and subjected to trauma, histamine release in vitro by peptone was diminished for a period of time beginning four hours after the trauma a,nd lasting up to ninet,een days, depending on the amount of trauma and the time needed for healing of the wound. In ether-anesthetized animals the histamine release was small but became normal after one hour. The factor inhibiting histamine release by peptone was present in the The injection int,o normal animals of sera serum of traumatized animals. taken from sensitized animals three to twenty-four hours after anaphylactic shock inhibited the histamine release. The amount, of inhibiting factor in the postanaphylactic serum was less than 1 per cent of tha.t in the serum of a substance appeared in animals four to twentytraumatized animal. Inhibiting four hours after an injection of peptone. Histamine release was also inhibited by adrenalin, local anesthetics, and ascorbic acid. In rats the adrenal glands are not essential for the production of t.he inhibiting factor. However, hypophysectomized rats lack the inhibiting factor. Crude adrenal and pituitary extracts added to normal blood are strong inPurified hibitors of histamine release. Liver extract lacks this property. adrenal and pituitary extracts are less effective hhan crude extracts. Desoxycorticosterone is inactive. Crude adrenal extract is about 100 times as active The most active product tested so far is a corticotrophic as cortic,al extract. The evidence suggests that the inhibitory substance is produced hormone. bv the pituitary gland and.acts through the adrenals which then affect the I,iood cells so as to inhibit histanline release.