Protective and therapeutic effects of the resuscitation-promoting factor domain and its mutants against Mycobacterium tuberculosis in mice

2015 ◽  
Vol 73 (3) ◽  
Author(s):  
Shanmin Zhao ◽  
Xiaoqin Song ◽  
Yong Zhao ◽  
Yi Qiu ◽  
Fengfeng Mao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Therapeutic Effects

scholarly journals Calcium and 1,25‒dihydoxyvitamin D3 levels are useful for diagnosing Mycobacterium tuberculosis and evaluating the therapeutic effects of anti‒tuberculosis drugs

2021 ◽  
Vol 54 (4) ◽  
pp. 183-187
Author(s):  
Takashi Araki ◽  
Naoto Minematsu ◽  
Kaori Kanbe ◽  
Rihiro Shigehara ◽  
Muneaki Kouda ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Therapeutic Effects

Therapeutic Effects of Citric and Succinic Acids in Rats Exposed to Inactivated M. tuberculosis

2021 ◽  
pp. 69-75
Author(s):  
SV Skupnevskiy ◽  
GM Trukhina ◽  
EG Pukhaeva ◽  
AK Badtiev ◽  
FK Rurua ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Succinate Dehydrogenase ◽  
Blood Cells ◽  
Morphological Changes ◽  
White Blood Cells ◽  
Therapeutic Effects ◽  
X Rays ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Introduction. The search for methods of correcting pathogenetic disorders related to Mycobacterium tuberculosis, the causative agent of tuberculosis, a highly hazardous communicable and socially significant disease, determines the relevance of the research and its objective to study the role of citric and succinic acids in protective and adaptive processes in warm-blooded animals with connective tissue disorders induced by inactivated mycobacteria. Materials and methods. The study was conducted on male Wistar rats with diseases induced by complete Freund’s adjuvant (a mineral oil emulsion containing heat-killed Mycobacterium tuberculosis). The animals were given a feed-added mixture of organic acids at 17 mg/kg body weight (minimum) and 88 mg/kg body weight (maximum) for 4 weeks. Hematology and bio�chemistry tests were performed using standard methods. The activity of succinate dehydrogenase in blood lymphocytes was determined by the cytobiochemical method. X-rays were obtained using stationary veterinary imaging equipment. Results. The protective effect of carboxylic acids in the exposed animals with Freund’s adjuvant-induced leukocytosis (expressed by a 28 % increase in white blood cells compared to the negative control, p < 0.05), oxidative stress (expressed by an increase in the concentration of malondialdehyde (MDA) by 40 %, p < 0.001, and in inhibition of catalase by 4 %), and subchondral bone sclerosis was characterized by a dose-dependent reduction in immunotoxic manifestations of the disease such as normalization of the number of white blood cells (p < 0.05 compared to model animals); a 27 % reduction in MDA, p < 0.001, a 10 % catalase activation, p < 0.01; succinate dehydrogenase normalization, and a decrease in dystrophic changes in the articular system of animals. Conclusion. The results of hematological, biochemical and radiological tests prove that pathological biochemical and morphological changes related to administration of inactivated M. tuberculosis to warm-blooded animals can be modified by a mixture of citric and succinic acids added to feed, which allows a better understanding of the pathogenesis and an increased therapy effectiveness.

Immunogenicity and Therapeutic Effects of Latency-Associated Genes in a Mycobacterium Tuberculosis Reactivation Mouse Model

2019 ◽  
Vol 30 (2) ◽  
pp. 60-69 ◽  
Author(s):  
Yan Liang ◽  
Xiaoyan Zhang ◽  
Xuejuan Bai ◽  
Yourong Yang ◽  
Wenping Gong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mouse Model ◽  
Therapeutic Effects ◽  
Tuberculosis Reactivation

Immunogenicity and Therapeutic Effects of pVAX1-rv1419 DNA from Mycobacterium tuberculosis

2016 ◽  
Vol 16 (4) ◽  
pp. 249-255 ◽  
Author(s):  
Yan Liang ◽  
Xiaoyan Zhang ◽  
Li Xiao ◽  
Xuejuan Bai ◽  
Xiaomei Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Therapeutic Effects

scholarly journals Moxifloxacin Replacement in Contemporary Tuberculosis Drug Regimens Is Ineffective against Persistent Mycobacterium tuberculosis in the Cornell Mouse Model

2018 ◽  
Vol 62 (7) ◽  
pp. e00190-18 ◽  
Author(s):  
Yingjun Liu ◽  
Henry Pertinez ◽  
Geraint R. Davies ◽  
Stephen H. Gillespie ◽  
Anthony R. Coates ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Animal Studies ◽  
Drug Regimen ◽  
Therapeutic Effects ◽  
Standard Regimen ◽  
Standard Drug ◽  
Content Type ◽  
Persistent Infections ◽  
Future Drug ◽  
Relapse Rates

ABSTRACT Tuberculosis (TB), which is caused by Mycobacterium tuberculosis, remains a leading killer worldwide, and disease control is hampered by the ineffective control of persistent infections. Substitution of moxifloxacin for isoniazid or ethambutol in standard anti-TB regimens reduces the treatment duration and relapse rates in animal studies, and 4-month regimens were not noninferior in clinical trials. Resuscitation-promoting factor (RPF)-dependent bacilli have recently been implicated in M. tuberculosis persistence. We aimed to investigate the therapeutic effects of the substitution of moxifloxacin for a drug used in the standard drug regimen in eradicating CFU count-positive and RPF-dependent persistent M. tuberculosis using the Cornell murine model. M. tuberculosis-infected mice were treated with regimens in which either isoniazid or ethambutol was replaced by moxifloxacin in the standard regimen. The efficacy of the regimens for bacterial CFU count elimination and removal of persistent tubercle bacilli, evaluated using culture filtrate (CF) derived from M. tuberculosis strain H37Rv, was compared to that of the standard regimen. We also measured disease relapse rates. The regimen in which moxifloxacin replaced isoniazid achieved total organ CFU count clearance at 11 weeks posttreatment, which was faster than that by the standard regimen (14 weeks), and showed a 34% lower relapse rate. The regimen in which moxifloxacin replaced ethambutol was similar to standard regimens in these regards. Importantly, neither the regimen in which moxifloxacin replaced isoniazid or ethambutol nor the standard regimen could remove CF-dependent persistent bacilli. The finding of CF-dependent persistent M. tuberculosis in TB treatment requires confirmation in human studies and has implications for future drug design, testing, and clinical applications.

Immunogenicity and therapeutic effects of recombinant Ag85AB fusion protein vaccines in mice infected with Mycobacterium tuberculosis

Vaccine ◽  
2017 ◽  
Vol 35 (32) ◽  
pp. 3995-4001 ◽  
Author(s):  
Yan Liang ◽  
Junxian Zhang ◽  
Yourong Yang ◽  
Xuejuan Bai ◽  
Qi Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fusion Protein ◽  
Therapeutic Effects ◽  
Protein Vaccines

scholarly journals Investigation of Elimination Rate, Persistent Subpopulation Removal, and Relapse Rates of Mycobacterium tuberculosis by Using Combinations of First-Line Drugs in a Modified Cornell Mouse Model

2016 ◽  
Vol 60 (8) ◽  
pp. 4778-4785 ◽  
Author(s):  
Yanmin Hu ◽  
Henry Pertinez ◽  
Fatima Ortega-Muro ◽  
Laura Alameda-Martin ◽  
Yingjun Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mouse Model ◽  
Culture Filtrate ◽  
Control Method ◽  
Elimination Rate ◽  
Therapeutic Effects ◽  
Content Type ◽  
Solid Agar ◽  
Main Components ◽  
Relapse Rates

ABSTRACTCurrently, the most effective tuberculosis control method involves case finding and 6 months of chemotherapy. There is a need to improve our understanding about drug interactions, combination activities, and the ability to remove persistent bacteria using the current regimens, particularly in relation to relapse. We aimed to investigate the therapeutic effects of three main components, rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA), in current drug regimens using a modified version of the Cornell mouse model. We evaluated the posttreatment levels of persistentMycobacterium tuberculosisin the organs of mice using culture filtrate derived fromM. tuberculosisstrain H37Rv. When RMP was combined with INH, PZA, or INH-PZA, significant additive activities were observed compared to each of the single-drug treatments. However, the combination of INH and PZA showed a less significant additive effect than either of the drugs used on their own. Apparent culture negativity of mouse organs was achieved at 14 weeks of treatment with RMP-INH, RMP-PZA, and RMP-INH-PZA, but not with INH-PZA, when conventional tests, namely, culture on solid agar and in liquid broth, indicated that the organs were negative for bacteria. The relapse rates for RMP-containing regimens were not significantly different from a 100% relapse rate at the numbers of mice examined in this study. In parallel, we examined the organs for the presence of culture filtrate-dependent persistent bacilli after 14 weeks of treatment. Culture filtrate treatment of the organs revealed persistentM. tuberculosis. Modeling of mycobacterial elimination rates and evaluation of culture filtrate-dependent organisms showed promise as surrogate methods for efficient factorial evaluation of drug combinations in tuberculosis in mouse models and should be further evaluated against relapse. The presence of culture filtrate-dependent persistentM. tuberculosisis the likely cause of disease relapse in this modified Cornell mouse model.

In vitro bactericidal and in vivo therapeutic activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis.

1996 ◽  
Vol 40 (2) ◽  
pp. 426-428 ◽  
Author(s):  
T Yamamoto ◽  
R Amitani ◽  
K Suzuki ◽  
E Tanaka ◽  
T Murayama ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Culture Method ◽  
Therapeutic Effects ◽  
Survival Times ◽  
Promising Candidate ◽  
Mycobacterium Tuberculosis H37rv ◽  
Therapeutic Activities ◽  
Coated Slide

The in vitro and in vivo activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis H37Rv were compared with those of rifampin. Bactericidal activity was evaluated by using a silicone-coated slide culture method. The MBC of KRM-1648 was 0.15 to 0.3 microgram/ml for 24 h of exposure, while that of rifampin was > 160 microgram/ml under the same conditions. Against experimental murine tuberculosis, KRM-1648 exhibited significant therapeutic effects, in terms of prolonged survival times for mice compared with those with rifampin treatment, even at lower doses, such as 1 and 3 mg/kg. At a dose of 3 mg/kg, KRM-1648 was at least as effective as rifampin at 10 mg/kg. The combination of KRM-1648 (3 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg) exhibited much more activity than did rifampin (10 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg). These findings suggest that KRM-1648 is a promising candidate for the treatment of tuberculosis.

scholarly journals Immunogenicity and therapeutic effects of a Mycobacterium tuberculosis rv2190c DNA vaccine in mice

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Yan Liang ◽  
Xiaoyan Zhang ◽  
Xuejuan Bai ◽  
Li Xiao ◽  
Xiaomei Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Vaccine ◽  
Therapeutic Effects
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