Experimental Tuberculosis In Guinea Pigs Research Articles

Acción terapéutica de la estreptomicina e isoniacida en la tuberculosis experimental del cobayo

Se ha estudiado la acción terapéutica de la estreptomicina y de la isoniacida en la tuberculosis experimental del cobayo. Un grupo fue tratado desde el día siguiente de ser inoculado con isoniacida, y sacrificado a los 30 días. Otros dos grupos fueron tratados 30 días después de ser infectados con estreptomicina o isoniacida. y sacrificados a los 60 días de ser infectados. Cobayos inoculados sirvieron de control a estas experiencias. Los hechos de mayor significación son los siguientes: ausencia de nódulo en el lugar de la inoculación, y ausencia de lesiones de generalización en los órganos receptivos del grupo tratado al día siguiente de ser inoculado. En los animales tratados tardíamente, las lesiones caseosas en el nódulo de inoculación y ganglios satélites, no experimentaron modificaciones de consideración, pero las lesiones de generalización en los órganos receptivos fueron discretas, y en proporción menor que lo observado en los controles. En todos los animales tratados. la sensibilidad tuberculínica decreció apreciablemente, llegando a desaparecer en algunos, en mayor proporción en los tratados con isoniacida. La sensibilidad tuberculínica no se hizo presente en los animales tratados al día siguiente de ser inoculados. Las pruebas de inoculación animal, efectuadas con bazos aparentemente normales de los cobayos tratados, demostraron la presencia de gérmenes virulentos en un elevado porcentaje. No se observó en los animales tratados, fenómenos tóxicos locales o generales, imputables a estos quimioterápicos.

Evidence for Oxidative Stress and Defective Antioxidant Response in Guinea Pigs with Tuberculosis

The development of granulomatous inflammation with caseous necrosis is an important but poorly understood manifestation of tuberculosis in humans and some animal models. In this study we measured the byproducts of oxidative stress in granulomatous lesions as well as the systemic antioxidant capacity of BCG vaccinated and non-vaccinated guinea pigs experimentally infected with Mycobacterium tuberculosis. In non-vaccinated guinea pigs, oxidative stress was evident within 2 weeks of infection as measured by a decrease in the serum total antioxidant capacity and blood glutathione levels accompanied by an increase in malondialdehyde, a byproduct of lipid peroxidation, within lesions. Despite a decrease in total and reduced blood glutathione concentrations, there was an increase in lesion glutathione by immunohistochemistry in response to localized oxidative stress. In addition there was an increase in the expression of the host transcription factor nuclear erythroid 2 p45-related factor 2 (Nrf2), which regulates several protein and non-proteins antioxidants, including glutathione. Despite the increase in cytoplasmic expression of Nrf2, immunohistochemical staining revealed a defect in Nrf2 nuclear translocation within granulomatous lesions as well as a decrease in the expression of the Nrf2-regulated antioxidant protein NQO1. Treating M. tuberculosis–infected guinea pigs with the antioxidant drug N-acetyl cysteine (NAC) partially restored blood glutathione concentrations and the serum total antioxidant capacity. Treatment with NAC also decreased spleen bacterial counts, as well as decreased the lung and spleen lesion burden and the severity of lesion necrosis. These data suggest that the progressive oxidative stress during experimental tuberculosis in guinea pigs is due in part to a defect in host antioxidant defenses, which, we show here, can be partially restored with antioxidant treatment. These data suggest that the therapeutic strategies that reduce oxidant-mediated tissue damage may be beneficial as an adjunct therapy in the treatment and prevention of tuberculosis in humans.

Influence of dietary (n-3)-polyunsaturated fatty acids on leukotriene B4 and prostaglandin E2 synthesis and course of experimental tuberculosis in guinea pigs.

In the present study eicosanoid synthesis was studied in macrophages of guinea pigs fed different amounts of (n-6)- and (n-3)-polyunsaturated fatty acids (PUFA). Three groups of weanling guinea pigs were fed by isocaloric diets differing only in their contents of PUFA: controls with 2.8 Cal% of linoleic acid (LA; 18:2(n-6)); (n-6)-rich fed animals with 15.4 Cal% of LA; and (n-3)-rich fed animals with 10.1 Cal% of LA, 1.4 Cal% of eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)). After 13 weeks half the number of animals from each group was infected i.m. by 180 colony forming units of Mycobacterium tuberculosis strain H37Rv. Seven weeks after infection the release of leukotriene (LT)B4 and prostaglandin (PG)E2 was quantified in calcium ionophore stimulated whole blood, peritoneal macrophage cultures and alveolar macrophages by immunoassays after high performance liquid chromatography. Synthesis of LTB4 and PGE2 was found to be reduced in (n-3)-rich fed guinea pigs (p < 0.05), and equivalent between controls and (n-6)-rich fed animals. Controls and (n-6)-rich fed animals showed the same mycobacterial counts in the spleen whereas (n-3)-rich fed guinea pigs demonstrated an increased number of mycobacteria (p < 0.05). Our results demonstrate that an increased dietary intake of (n-3)-PUFA suppress LTB4 and PGE2 synthesis. The increased number of M. tuberculosis found in the spleens of (n-3)-rich fed animals could represent persistence of the experimental infection. It may be speculated that a functional relationship exists between the two findings.

Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine

The antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro. 1. 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 μg/ml in liquid media, showing no cross-resistance. However, loss of potency occured in Ogawa's egg media, and 50 μg/ml of RP were required for inhibition of growth. 2. 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect. In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required. When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy. 3. 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs. Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage. 4. 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M. intracellulare appeared to be extremely low.

Evaluation of subdermal biodegradable implants incorporating rifampicin as a method of drug delivery in experimental tuberculosis of guinea pigs.

Conventional chemotherapy of tuberculosis and leprosy requires rifampicin to be administered orally. The long period of treatment and adverse side effects of the drug lead to poor compliance. To overcome this, subdermal implants incorporating rifampicin in pure and micro-encapsulated forms with biodegradable material were used as a new drug delivery system in experimental tuberculosis of guinea pigs. Two experiments were performed with 45-mg and 100-mg drug implants. Progress of infection was followed at intervals by studying necropsy scores and weights of the organs of predilection and levels of the drug in the blood were determined. There was a constant and sustained release of the drug in therapeutic concentrations for 30 and 50 days until the implants were completely assimilated without causing any damage to the implant site. The importance of multiple implants at long intervals is discussed.

Antituberculous activity of rifampicin for the experimental tuberculosis of guinea pigs

Antituberculous activity of rifampicin for the experimental tuberculosis of guinea pigs

The immuno-suppressive effect of thalidomide in experimental tuberculosis in guinea-pigs

Two groups of guinea-pigs were given thalidomide orally in doses of 500 mg./kg. daily and infected with Myco. tuberculosis var. hominis , H37Rv strain. In one group thalidomide was begun on the day of infection; and in the other group 14 days before infection. The response to intradermal injection of 1000 TU of PPD was similar in both groups and also in a control group that received no thalidomide. Histological examination of the lungs and spleen showed that there was less caseation in the lesions from animals that had received thalidomide compared with those that had not. No antimycobacterial action of thalidomide was demonstrated in Löwenstein's medium. Deux groupes de cobayes ont reçu de la thalidomide par voie orale à la dose journalière de 500 mg./kg. et ont été infecté avec la souche H37Rv de Myco. tuberculosis var. hominis . Pour un groupe, la thalidomide fut commencé le jour de l'infection, et pour l'autre groupe, 14 jours avant l'infection. La réaction à une injection intra dermique de 1000 TU de PPD fut identique dans les deux groupes, et également dans un groupe controle qui n'avait pas reçu de thalidomide. L'examen histologique des poumons et des rates révéla qu'il y avait moins de formations caséeuses dans les lesions provenant d'animaux qui avaient reçu de la thalidomide, comparés à ceux qui n'en avaient pas reçu. Aucune action antimycobactérienne de la thalidomide ne fut retrouvée en milieu de Löwenstein. Dos grupos de cobayos que recibieron thalidomida por vía oral en dosis de 500 mg. diarios fueron infectados con cepas de Mycobacterium tuberculosis var. hominis. En un grupo la thalidomida se inició el mismo dia de la infección; en el otro grupo, 14 dias antes. La respuesta a una inyección intradermica de 1000 TU de PPD fué similar en ambos grupos así como en otro grupo control que no recibió thalidomida. El examen histológico de los pulmones y el bazo mostró que había menos caseosis en las lesiones de los animales que habían recibido thalidomida que en aquellos que no habían recibido. La thalidomida no mostró acción antibacteriana en el medio de Löwenstein.

Cellular Transfer of Immunological Reactions in Experimental Tuberculosis of Guinea pigs

Cellular Transfer of Immunological Reactions in Experimental Tuberculosis of Guinea pigs

THE IMMUNOGENICITY OF BCG (PHIPPS) AND ITS ISONIAZID-RESISTANT MUTANT IN GUINEA PIGS SIMULTANEOUSLY VACCINATED, INFECTED, AND TREATED.

Studies (5-11) have proved that experimental tuberculosis in guinea pigs can be suppressed or prevented during the period of isoniazid pro­ phylaxis, but, when treatment is discontinued, a varying number of animals develop progres­ sive tuberculosis. It has been demonstrated (8) that a percentage of the animals which do not develop allergy (immunity) or show any ap­ preciable sign of tuberculous disease during an observation period of two years varies inversely with the size of the challenge, and directly with the duration of the treatment. This experiment was designed primarily to determine the degree of protection against tuberculosis in guinea pigs which were vacci

A Study on the Effect of Maruyama Vaccine on Experimental Tuberculosis of Guinea Pigs.

A Study on the Effect of Maruyama Vaccine on Experimental Tuberculosis of Guinea Pigs.

モルモットの実験的結核症に対して4,4'-Diisoamyloxythiocarbanihde(Isoxyl®)を用いた治療実験

モルモットの実験的結核症に対して4,4'-Diisoamyloxythiocarbanihde(Isoxyl®)を用いた治療実験

Effects of U. V. Irradiation by a Fluorescent Sunlamp (280-390mμ) on Experimental Guinea Pig Tuberculosis and Human Pulmonary Tubercurosis

Effects of U. V. Irradiation by a Fluorescent Sunlamp (280-390mμ) on Experimental Guinea Pig Tuberculosis and Human Pulmonary Tubercurosis

正誤表

正誤表

結核動物の脱感染に関する実験

結核動物の脱感染に関する実験

Effects of kanamycin in experimental tuberculosis of guinea pigs.

Effects of kanamycin in experimental tuberculosis of guinea pigs.

Comparison of 4,4′-Diaminodiphenylsulfone and Its Thymolated Derivative in Experimental Tuberculosis in Guinea Pigs

SUMMARY AND CONCLUSIONS Each of 36 guinea pigs was infected intraperitoneally with virulent tubercle bacilli. After 16 days, six were killed and found to have tuberculous lesions. On the same day, the remaining animals were divided into three groups of 10 animals each, namely controls, those treated with 4,4′-diaminodiphenylsulfone (DDS), and those treated with DDS-thymol. Treatment continued for 116 days, at which time all survivors were killed. Six controls had died by this time. All controls, including four survivors, had extensive tuberculosis. Of those animals treated with DDS-thymol, two died prematurely; two others died after 53 and 81 days of treatment, respectively, and had extensive lesions. Of the surviving six animals, one had a few residual foci in the liver and lungs and two others had microscopically evident lesions in the lungs only. All had caseous lesions in lymph nodes. None of these animals showed any toxic effect from the drug. None of the animals given DDS died; four had evidence of pulmonary tuberculous lesions. All had caseous foci in the lymph nodes and enlarged cyanotic spleens with dilated sinusoids and many pigment-laden macrophages. The administration of DDS-thymol to tuberculous guinea pigs resulted in regression of the disease, but the beneficial effect was less than that of DDS. The hematotoxic effects of DDS, as determined by splenic changes, were not seen in animals given DDS-thymol. It was not determined whether DDS-thymol has a direct action or if it is active because of DDS liberated in vivo.

Therapeutic effect of kanamycin upon advanced experimental tuberculosis of guinea pigs.

Therapeutic effect of kanamycin upon advanced experimental tuberculosis of guinea pigs.

Kanamycinに関する研究

Kanamycinに関する研究

Kanamycinに関する研究

Kanamycinに関する研究

Plasma Glycoproteins in Pulmonary Tuberculosis

The glycoproteins of plasma are a heterogeneous group of conjugated proteins consisting of polysaccharides in firm union with peptides or proteins.’ Increased interest has been shown in this group of proteins in the past few years due to the demonstration that their concentration is markedly increased in a number of pathologic and physiologic states.2 With respect to infectious diseases, the carbohydrate-containing proteins of serum have been studied most extensively in relation to tuberculosis. Marked increases in the total serum glycoprotein have been reported in clinical tuberculosis38 and in experimental tuberculosis of guinea pigs#{176} and of rabbits.1#{176} Elevated levels of the seromucoid (mucoprotein) fraction have been observed in clinical tuberculosis8 and in the experimental disease in guinea pigs.#{176} Recently, Method 10 developed by Cohn and associates” has been adapted by Lever and co-workers for the fractionation of 5 ml. amounts of human plasma into four primary fractions.12 It seemed possible that such a method might provide more information on the response of the carbohydrate-containing proteins to pulmonary tuberculosis than could be obtained from total plasma glycoprotein and seromucoid determinations. In the present investigation, 5 ml. of plasma samples from normal individuals and from patients with minimal, moderately advanced and far advanced tuberculosis have been separated by the low temperature-low salt-ethanol procedure of Lever1’ into four primary fractions, proteinbound carbohydrate (hexose) and protein have been measured in the fractions and the results have been correlated with total glycoprotein, seromucoid, and total protein determinations on whole plasma. Materials and Methods Plasma: Seventeen ml. of blood were obtained by venipuncture. The blood was immediately added to 3 ml. of A.C.D. solution.12 Following sep-. aration by centrifugation from the blood cells, the A.C.D. plasma was stored at minus 20#{176} C. until the fractionations and the chemical determinations could be conducted.