QUANTITATIVE AIR-BORNE TUBERCULOSIS IN THE RABBIT

1. Pulmonary tuberculosis in unselected rabbits, induced by primary quantitative air-borne infection with human type tubercle bacilli, may retrogress or progress. Some animals whose disease was in a stationary condition might have fallen into one of the above groups had the experiments been prolonged. 2. Within the limits of the observations natural resistance or susceptibility appears to be the chief factor in determining the course of the disease. 3. Following the development of the primary lesions the tuberculin reaction became positive but thereafter proved to be an unreliable indicator of the course of the disease. 4. Tubercle bacilli can be recovered from macroscopically normal lung tissue of rabbits several weeks after primary infection. 5. Reinfection did not induce the formation of new lesions nor alter the course of the disease caused by the primary infection.

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Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22137064 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7064

Author(s):

Christine Hansel ◽

Samantha Barr ◽

Alina V. Schemann ◽

Kirsten Lauber ◽

Julia Hess ◽

...

Keyword(s):

Epithelial Cells ◽

Lung Tissue ◽

Cellular Stress ◽

Lung Epithelial Cells ◽

Normal Lung Tissue ◽

Normal Lung ◽

Metformin Treatment ◽

Acute Effects ◽

Lung Epithelial ◽

Radiation Induced

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.

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