scholarly journals In Vitro and In Vivo Activities of Moxifloxacin and Clinafloxacin against Mycobacterium tuberculosis

1998 ◽  
Vol 42 (8) ◽  
pp. 2066-2069 ◽  
Author(s):  
Baohong Ji ◽  
Nacer Lounis ◽  
Caroline Maslo ◽  
Chantal Truffot-Pernot ◽  
Pascale Bonnafous ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Positive Control ◽  
Lung Lesion ◽  
Spleen Weight ◽  
Tuberculosis Model ◽  
H37rv Strain ◽  
Effective Administration ◽  
Bactericidal Effects

ABSTRACT On 10% oleic acid–albumin–dextrose–catalase-enriched 7H11 agar medium, the MIC at which 90% of the isolates are inhibited for 20 strains of Mycobacterium tuberculosis was 0.5 μg of sparfloxacin (SPFX) or moxifloxacin (MXFX) per ml and 1.0 μg of clinafloxacin (CNFX) per ml, indicating that the in vitro activities of SPFX and MXFX were virtually identical and were slightly greater than that of CNFX. However, the in vivo activities of these drugs in a murine tuberculosis model differed considerably. Female Swiss mice were infected intravenously with 6.2 × 106 CFU of the H37Rv strain and treated for 4 weeks, beginning the next day after infection, with isoniazid (INH) serving as the positive control. By the criteria of 30-day survival rate, spleen weight, gross lung lesion, and mean number of CFU in the spleen, treatment with CNFX at up to 100 mg/kg of body weight six times weekly displayed no measurable effect against M. tuberculosis, whereas both SPFX and MXFX were effective; administration six times weekly of either of the latter two drugs demonstrated dosage-dependent bactericidal effects, as measured by enumeration of CFU in the spleens, and MXFX appeared more bactericidal than the same dosage of SPFX. Of the three fluoroquinolones, only MXFX at 100 mg/kg six times weekly appeared as bactericidal as INH at 25 mg/kg six times weekly. Thus, MXFX may be an important component of the newer combined regimens for treatment of tuberculosis.

scholarly journals Ambroxol Induces Autophagy and Potentiates Rifampin Antimycobacterial Activity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Seong Won Choi ◽  
Yuexi Gu ◽  
Ryan Scott Peters ◽  
Padmini Salgame ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Lead Compound ◽  
Content Type ◽  
Tuberculosis Model

ABSTRACT Host-directed therapy in tuberculosis is a potential adjunct to antibiotic chemotherapy directed at Mycobacterium tuberculosis. Ambroxol, a lead compound, emerged from a screen for autophagy-inducing drugs. At clinically relevant doses, ambroxol induced autophagy in vitro and in vivo and promoted mycobacterial killing in macrophages. Ambroxol also potentiated rifampin activity in a murine tuberculosis model.

scholarly journals In Vitro and In Vivo Activities of Gatifloxacin against Mycobacterium tuberculosis

2002 ◽  
Vol 46 (4) ◽  
pp. 1022-1025 ◽  
Author(s):  
Enrique J. Alvirez-Freites ◽  
Janna L. Carter ◽  
Michael H. Cynamon
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dose Range ◽  
Tuberculosis Model ◽  
Range Study

ABSTRACT Gatifloxacin (GAT) and moxifloxacin (MXF) were evaluated in vitro to determine their activities against Mycobacterium tuberculosis. GAT was subsequently compared in a dose range study to isoniazid (INH) in a murine tuberculosis model. GAT was somewhat less active than INH. GAT and MXF were evaluated in mice infected with M. tuberculosis and were found to have similar activities. GAT was studied alone and in combination with ethambutol, ethionamide (ETA), and pyrazinamide (PZA) and compared to INH and rifampin (RIF). GAT appears to have sufficient activity alone and in combination with ETA with or without PZA to merit evaluation for treatment of tuberculosis.

SILA-421 activity in vitro against rifampicin-susceptible and rifampicin-resistant Mycobacterium tuberculosis, and in vivo in a murine tuberculosis model

2015 ◽  
Vol 46 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Gerjo J. de Knegt ◽  
Irma A.J.M. Bakker-Woudenberg ◽  
Dick van Soolingen ◽  
Rob Aarnoutse ◽  
Martin J. Boeree ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculosis Model

RESULTS OF INVESTIGATION OF THE EFFECTS OF BOVINE PLACENTAL PREPARATION ON IMMUNE FUNCTION

2018 ◽  
Vol 21 (02) ◽  
pp. 22-28
Author(s):  
Dolgorsuren Ts ◽  
Lkhagvasuren N ◽  
Batsaikhan D ◽  
Erdenechimeg D ◽  
Oyunnomin N ◽  
...  
Keyword(s):  
Cell Division ◽  
Stimulation Index ◽  
In Vitro Study ◽  
Positive Control ◽  
Negative Control ◽  
Vitro Study ◽  
Spleen Weight ◽  
Spleen Index

The present study aimed to investigate the effects of bovine placental preparation under in vitro and in vivo conditions. Cell Proliferation Kit I (MTT) was used for in vitro study of placental preparation effect to proliferate lymphocytes. Lymphocytes were isolated from spleen of Balb C mice, 100 μl cell was added to each well of 96 well culture plate, followed by addition of 10 μl placental preparation and mitogen (concanavalin-A) separately and in combination and cell culture only as control was used. Results were obtained by measuring and comparing the absorbance reading of the wells of the samples against the standards with ELISA microplate reader. Effect of placental preparation to proliferate lymphocytes in vivo condition was investigated in mice, which were divided into 4 groups and 4 subgroups. The results were estimtaed with spleen weight, spleen index and splenocyte counts. Results of in vitro study demonstrated that stimulation index increased by 1.19 or 19% for cell division in wells to which no mitogen was added, but the preparation was added as compared to control wells, cell division index increased with 1.38 or 38% for cell division in wells to which mitogen was added as compared to control wells and stimulation index was higher by 1.68 or 68% for cell division in wells with cells to which both mitogen and preparation were added than control wells. For in vivo experiments, spleen index and splenocyte count for animals of positive control subgroup-1 treated once by 0.2 ml sheep red blood cells were greater by 1.38 and 1.5 times respectively than relevant negative control animals, whereas spleen index and splenocyte count for animals of experimental subgroup -1 were greater by 3.09 and 2.2 times respectively. For animals of positive control subgroup -2, both spleen index and splenocyte count decreased by 1.35 and 1.3 times respectively than negative control animals, whereas they dropped by 1.1 and 1.17 times respectively in mice of experimental subgroup -2. Spleen index and splenocyte count in mice treated with the preprartion only increased by 1.2 times or 20% as compared to negative control animals. From above results, it is shown that bovine placental preparation is able to exert immunomodulatory effect regardless of antigen under both in vitro and in vivo conditions.

scholarly journals Rapid and spontaneous loss of phthiocerol dimycocerosate (PDIM) from Mycobacterium tuberculosis grown in vitro: implications for virulence studies

Microbiology ◽  
2009 ◽  
Vol 155 (11) ◽  
pp. 3532-3543 ◽  
Author(s):  
Pilar Domenech ◽  
Michael B. Reed
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Types ◽  
Heterogeneous Population ◽  
Short Length ◽  
Multiple Mutation ◽  
Negative Cell ◽  
H37rv Strain ◽  
Phthiocerol Dimycocerosate

Isolated in vitro more than half a century ago, the H37Rv strain of Mycobacterium tuberculosis still remains the strain of choice for the majority of laboratories conducting in vivo studies of TB pathogenesis. In this report we reveal that H37Rv is highly prone to losing the ability to synthesize the cell wall lipid phthiocerol dimycocerosate (PDIM) during extended periods of in vitro culture. In addition, H37Rv stocks that have been held in vitro for even a short length of time should be thought of as a heterogeneous population of PDIM-positive and PDIM-negative cell types. We demonstrate that after weekly subculture of PDIM-positive isolates over a period of 20 weeks, the proportion of PDIM-negative cells rises above 30 %. That PDIM biosynthesis is negatively selected in vitro is evident from the broad range of mutation types we observe within cultures originating from a single PDIM-positive parental clone. Moreover, the appearance of these multiple mutation types coupled with an enhanced growth rate of PDIM-negative bacteria ensures that ‘PDIM-less’ clones rapidly dominate in vitro cultures. It has been known for almost a decade that strains of M. tuberculosis that lack PDIM are severely attenuated during in vivo infection. Therefore, the loss of PDIM raises a very serious issue in regard to the interpretation of putative virulence factors where heterogeneous parental cultures are potentially being compared in vivo to recombinant clones isolated within a PDIM-negative background. It is essential that researchers undertaking in vivo virulence studies confirm the presence of PDIM within all recombinant clones and the parental strains they are derived from.

scholarly journals Bioluminescence for Assessing Drug Potency against Nonreplicating Mycobacterium tuberculosis

2015 ◽  
Vol 59 (7) ◽  
pp. 4012-4019 ◽  
Author(s):  
Anthony Vocat ◽  
Ruben C. Hartkoorn ◽  
Benoit Lechartier ◽  
Ming Zhang ◽  
Neeraj Dhar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Time Course ◽  
Drug Efficacy ◽  
Luciferase Assay ◽  
Luciferase Expression ◽  
Content Type ◽  
Drug Potency ◽  
Bactericidal Effects

ABSTRACTTargeting dormantMycobacterium tuberculosisrepresents a challenge to antituberculosis drug discovery programs. We previously reported and validated the use of the streptomycin (STR)-dependentM. tuberculosis18b strain as a tool for assessing drug potency against nonreplicating bacteria bothin vitroandin vivo. In this study, we generated a luminescent 18b strain, named 18b-Lux, by transforming the bacteria with a vector expressing theluxCDABEoperon fromPhotorhabdus luminescens. Luciferase expression was demonstrated under replicating conditions, and, more importantly, luminescence levels significantly above background were detected following STR removal. The sensitivity of STR-starved 18b-Lux to approved and candidate antituberculosis therapeutic agents was evaluated by means of a luciferase assay in a 96-well format. Results mirrored the data obtained with the standard resazurin reduction microplate assay, and the luminescence readout allowed time course assessments of drug efficacyin vitro. Specifically, we proved that bedaquiline, the rifamycins, and sutezolid displayed time-dependent activity against dormant bacteria, while pyrazinamide and SQ109 showed bactericidal effects at the highest concentrations tested. Overall, we established the optimal conditions for an inexpensive, simple, and very sensitive assay with great potential for future applications.

Tuberkulose - Screening

2011 ◽  
Vol 68 (7) ◽  
pp. 381-387
Author(s):  
Otto Schoch
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Interferon Gamma ◽  
Wird Eine ◽  
Interferon Gamma Release Assays

Das primäre Ziel der Aktivitäten zur bevölkerungsbezogenen Tuberkulosekontrolle ist die Identifizierung von Patienten mit sputummikroskopisch positiver Lungentuberkulose. Wenn diese Patienten umgehend therapiert werden, haben sie nicht nur eine optimale Heilungschance, sondern übertragen auch den Krankheitserreger nicht weiter auf andere Personen. Das Screening, die systematische Suche nach Tuberkulose, erfolgt in der Regel radiologisch bei der Suche nach Erkrankten, während immunologische Teste bei der Suche nach einer Infektion mit Mycobacterium tuberculosis zur Anwendung kommen. Diese Infektion, die ein erhöhtes Risiko für die Entwicklung einer Tuberkulose-Erkrankung mit sich bringt, wird im Rahmen der Umgebungsuntersuchungen oder bei Hochrisikogruppen gesucht. Neben dem traditionellen in vivo Mantoux Hauttest stehen heute die neueren in vitro Blutteste, die sogenannten Interferon Gamma Release Assays (IGRA) zur Verfügung, die unter anderem den Vorteil einer höheren Spezifität mit sich bringen, weil die verwendeten Antigene der Mykobakterien-Wand beim Impfstamm Bacille Calmitte Guerin (BCG) und bei den meisten atypischen Mykobakterien nicht vorhanden sind. Zudem kann bei Immunsupprimierten dank einer mitgeführten Positivkontrolle eine Aussage über die Wahrscheinlichkeit eines falsch negativen Testresultates gemacht werden. Bei neu diagnostizierter Infektion mit Mycobacterium tuberculosis wird eine präventive Chemotherapie mit Isoniazid während 9 Monaten durchgeführt.

In Vitro and In Vivo Neutralizing Activity of Uvaria chamae Leaves Fractions on the Venom of Naja nigricollis in Albino Rat and Bovine Blood

2020 ◽  
Vol 14 (4) ◽  
pp. 295-311
Author(s):  
Ada Gabriel ◽  
Mamman Mohammed ◽  
Mohammed G. Magaji ◽  
Yusuf P. Ofemile ◽  
Ameh P. Matthew ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Neglected Tropical Diseases ◽  
Lethal Dose ◽  
Positive Control ◽  
Haemolytic Activity ◽  
Cytotoxic Activities ◽  
Albino Rat ◽  
Aqueous Residue

Background: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. Objective: This study aimed to investigate U. chamae’s potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. Methods: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. Results: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. Conclusion: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.

Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

2019 ◽  
Vol 12 (1) ◽  
pp. 27-49 ◽  
Author(s):  
Shahinda S.R. Alsayed ◽  
Chau C. Beh ◽  
Neil R. Foster ◽  
Alan D. Payne ◽  
Yu Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Enzymatic Activity ◽  
Bacterial Pathogen ◽  
Building Blocks ◽  
Mycolic Acid ◽  
Adaptive Responses ◽  
Mycolic Acids ◽  
Hydroxylated Fatty Acids

Background:Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.Objective:Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.Conclusion:Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.

scholarly journals Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee
Keyword(s):  
Nk Cell ◽  
Neoplastic Cell ◽  
Positive Control ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Therapeutic Effects ◽  
Control Drug ◽  
Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

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