Studies on the Effects of Phagocytic Stimulation on Microbial Disease: I. Action of Some Derivatives of the BICYCLO[0.3.5]DECAPENTAENE Skeleton on Endothelial Cells of Skin Vessels

Gözsy, B.; Kátó, L

doi:10.1139/m55-057

Cited by 7 publications

(6 citation statements)

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“…Modern chemotherapeutics are playing an increasingly important role in the treatment of leprosy, but there is an increasing body of opinion that greater therapeutic effectiveness could be attained by simultaneous action on the host with a RES-stimulating agent and on the parasite with an antibacterial drug. Similar studies conducted by us in experimental tuberculosis have been described elsewhere (3,4,6,7).…”

supporting

confidence: 77%

“…In every case the antihistamine inhibited the induced phagocytic activity of the endothelial cells. The inhibiting effect of the antihistamine on the endothelial phagocytosis induced by histamine has been described elsewhere (3,5,6).…”

Section: Resultsmentioning

confidence: 99%

“…He demonstrated that the endothelial cells of the vessels of the skin undergo a functional metamorphosis under the influence of histamine, and that these cells become active phagocytes. Gozsy and K:it6 (3,6) showed that the same cells could be stimulated to phagocytic activity by the administration of certain derivatives of bicyclo-(O, 3,5)decapentane. In both cases this activity was inhibited by antihistamine.…”

Section: Working Hypothesismentioning

confidence: 99%

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Studies on the Effects of Phagocytic Stimulation on Microbial Disease: Iii. The Influence of Antihistamines and 1,4-Dimethyl-7-Isopropylazulene on Experimental Tuberculosis—preliminary Experiments

Gözsy¹,

Kátó²

1955

Can. J. Microbiol.

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Albino mice were infected intravenously with Mycobacterium tuberculosis var. bovis (Ravenel strain). The animals treated with the given antihistaminic substance died significantly sooner than the non-treated control animals. In a similar experiment, the deteriorating effect of antihistamine drug on experimental tuberculosis in guinea pigs was demonstrated. On the basis of previous experiments, it is supposed that the physiological stimulation of the defense mechanism by histamine has been hampered in its function. The administration of 1,4-dimethyl-7-isopropylazulene, which is believed to be a non-toxic agent simulating histamine production, prolonged the life of infected animals. When antihistamine was given in addition to 1,4-dimethyl-7-isopropylazulene, the deteriorating effect of the antihistamine was inhibited. Results are discussed in terms of whether the host–parasite relationship can be favorably influenced by means of a stimulant of the reticulo-endothelial system.

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supporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Working Hypothesismentioning

confidence: 99%

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Studies on the Effects of Phagocytic Stimulation on Microbial Disease: Iii. The Influence of Antihistamines and 1,4-Dimethyl-7-Isopropylazulene on Experimental Tuberculosis—preliminary Experiments

Gözsy¹,

Kátó²

1955

Can. J. Microbiol.

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“…This resulted in the speculation that these compounds interfered with bacterial cell wall synthesis or function, by a decrease of surface tension or by the adsorption of a monomolecular film onto the surface of the organisms (5,6,8,11). More recent work has attributed the action of chaulmoogra oil to an effect on host defense mechanisms rather than to a direct effect on the organisms (3,4).…”

mentioning

confidence: 99%

Mechanism by Which Hydnocarpic Acid Inhibits Mycobacterial Multiplication

Jacobsen

Levy

1973

Antimicrob Agents Chemother

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Recent work in this laboratory has shown that hydnocarpic acid (HA), a principal constituent of chaulmoogra oil, inhibits multiplication in vitro of a number of mycobacterial species. This activity of HA was not shared by several straight-chain fatty acids and by dihydrochaulmoogric acid. A study of the interaction of HA with biotin has been undertaken, based on a structural analogy between biotin and the cyclopentenyl fatty acid. The multiplication of a strain of Mycobacterium intracellulare susceptible to 2 Mug of HA/ml was measured turbidimetrically in Dubos medium, in the presence and absence of biotin and several other compounds. Biotin and, to a lesser extent, adenine plus guanine, palmitic acid, and linoleic acid antagonized growth inhibition by HA. Desthiobiotin, thioctic acid, and succinic acid did not block inhibition of bacterial multiplication by HA. HA may act by blocking the coenzymatic activity of biotin, or it may inhibit microbial biotin synthesis. Resumption of multiplication of M. intracellulare after a period of inhibition by HA in broth culture was found to be accompanied by reduction of the effective concentration of the drug; this could have resulted from metabolism of HA or production of an antagonist to HA by the organisms. Also, those organisms that multiplied in the presence of HA were found to represent HA-resistant mutants of M. intracellulare. Chaulmoogra oil and its major components, chaulmoogric [chemical name 13-(2-cyclopenten-1-yl)tridecanoic] and hydnocarpic [chemical name 1l-(2-cyclopenten-1-yl)undecanoic] acids, were used in the treatment of leprosy for many years, apparently with some effect. However, the mechanism of action of these substances was never elucidated. Early work focused on the fatty acid character of these compounds and the important lipid content of mycobacteria. This resulted in the speculation that these compounds interfered with bacterial cell wall synthesis or function, by a decrease of surface tension or by the adsorption of a monomolecular film onto the surface of the organisms (5,6,8,11). More recent work has attributed the action of chaulmoogra oil to an effect on host defense mechanisms rather than to a direct effect on the organisms (3, 4).Recent work in this laboratory has shown that hydnocarpic acid inhibits both multiplication of Mycobacterium leprae in the mouse foot pad (unpublished data) and also multiplication of a number of cultivable mycobacterial strains in vitro (P. L. Jacobsen, H. Ng, and L. Levy, Amer. Rev. Resp. Dis., in press). Although an effect on host defense mechanisms cannot be excluded, there can be no doubt that hydnocarpic acid exerts a direct antimicrobial action. Adams and his co-workers (10) demonstrated that saturation of chaulmoogric acid reduced antimicrobial activity measured in vitro; the studies in this laboratory confirmed those of Adams, showing that dihydrochaulmoogric acid in a concentration of 2O0Ag/ml failed to inhibit multiplication of several mycobacterial strains susceptible to 2 ,ug of chaulmoogric acid per ...

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“…Protein factors which increase phagocytosis have been isolated from normal plasma. Histamine also stimulates phagocytes, and antihistaminic factors neutralize this property (14–16). Chlorine stimulates the reticulum‐endothelial system in relation to phagocytosis (17).…”

mentioning

confidence: 99%