scholarly journals Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

1999 ◽  
Vol 43 (7) ◽  
pp. 1638-1643 ◽  
Author(s):  
Linda B. Adams ◽  
Indu Sinha ◽  
Scott G. Franzblau ◽  
James L. Krahenbuhl ◽  
Reeta T. Mehta
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Effective Treatment ◽  
Dose Response ◽  
Therapeutic Efficacy ◽  
Chronic Infection ◽  
Maximum Tolerated Dose ◽  
Toxic Effects ◽  
Unit Reduction ◽  
Higher Doses

ABSTRACT The therapeutic efficacy of liposomal clofazimine (L-CLF) was studied in mice infected with Mycobacterium tuberculosisErdman. Groups of mice were treated with either free clofazimine (F-CLF), L-CLF, or empty liposomes twice a week for five treatments beginning on day 1 (acute), day 21 (established), or day 90 (chronic) postinfection. One day after the last treatment, the numbers of CFU ofM. tuberculosis in the spleen, liver, and lungs were determined. F-CLF at the maximum tolerated dose of 5 mg/kg of body weight was ineffective; however, 10-fold-higher doses of L-CLF demonstrated a dose response with significant CFU reduction in all tissues without any toxic effects. In acutely infected mice, 50 mg of L-CLF/kg reduced CFU 2 to 3 log units in all three organs. In established or chronic infection, treated mice showed no detectable CFU in the spleen or liver and 1- to 2-log-unit reduction in the lungs. A second series of L-CLF treatments cleared M. tuberculosisin all three tissues. L-CLF appears to be bactericidal in the liver and spleen, which remained negative for M. tuberculosis growth for 2 months. Thus, L-CLF could be useful in the treatment of tuberculosis.

scholarly journals Therapeutic Efficacy of SQ641-NE against Mycobacterium tuberculosis

2013 ◽  
Vol 58 (1) ◽  
pp. 587-589 ◽  
Author(s):  
Boris Nikonenko ◽  
Venkata M. Reddy ◽  
Elena Bogatcheva ◽  
Marina Protopopova ◽  
Leo Einck ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Therapeutic Efficacy ◽  
Content Type ◽  
Mouse Macrophages

ABSTRACTA phospholipid-based nanoemulsion formulation of SQ641 (SQ641-NE) was active against intracellularMycobacterium tuberculosisin J774A.1 mouse macrophages, although SQ641 by itself was not. Intravenous (i.v.) SQ641-NE was cleared from circulation and reached peak concentrations in lung and spleen in 1 h. In a murine tuberculosis (TB) model, 8 i.v. doses of SQ641-NE at 100 mg/kg of body weight over 4 weeks caused a 1.73 log10CFU reduction ofM. tuberculosisin spleen and were generally bacteriostatic in lungs.

scholarly journals Activities of Several Novel Oxazolidinones againstMycobacterium tuberculosis in a Murine Model

1999 ◽  
Vol 43 (5) ◽  
pp. 1189-1191 ◽  
Author(s):  
M. H. Cynamon ◽  
S. P. Klemens ◽  
C. A. Sharpe ◽  
S. Chase
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Dose Response ◽  
Murine Model ◽  
Clinical Studies ◽  
Viable Cell ◽  
Test System ◽  
Cell Counts ◽  
Dose Response Study

ABSTRACT The activities of linezolid, eperezolid, and PNU-100480 were evaluated in a murine model of tuberculosis. Approximately 107 viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old outbred CD-1 mice. In the first study, treatment was started 1 day postinfection and was given by gavage for 4 weeks. Viable cell counts were determined from homogenates of spleens and lungs. PNU-100480 was as active as isoniazid. Linezolid was somewhat less active than PNU-100480 and isoniazid. Eperezolid had little activity in this model. In the next two studies, treatment was started 1 week postinfection. A dose-response study was performed with PNU-100480 and linezolid (both at 25, 50, and 100 mg/kg of body weight). PNU-100480 was more active than linezolid, and its efficacy increased with an escalation of the dose. Subsequently, the activity of PNU-100480 alone and in combination with rifampin or isoniazid was evaluated and was compared to that of isoniazid-rifampin. The activity of PNU-100480 was similar to that of isoniazid and/or rifampin in the various combinations tested. Further evaluation of these oxazolidinones in the murine test system would be useful prior to the development of clinical studies with humans.

Coadministration of citric acid allows oxytetracycline dose reduction in yellowtail Seriola quinqueradiata infected with Vibrio anguillarum

2020 ◽  
Vol 140 ◽  
pp. 25-29
Author(s):  
K Akiyama ◽  
N Hirazawa ◽  
A Hatanaka
Keyword(s):  
Body Weight ◽  
Citric Acid ◽  
Effective Treatment ◽  
Dose Reduction ◽  
Vibrio Anguillarum ◽  
Enhancing Effect ◽  
Bacterial Diseases ◽  
Seriola Quinqueradiata ◽  
Poor Efficacy

Oxytetracycline (OTC) has been commonly used as an effective antibiotic against various fish bacterial diseases, including vibriosis. In this study, the absorption-enhancing effect of citric acid on oral OTC pharmacokinetics and treatment of artificial Vibrio anguillarum infection was evaluated in juvenile yellowtail Seriola quinqueradiata followed by serum OTC concentration analysis. When 25 mg kg-1 body weight (BW) OTC was administered in combination with 1250 mg kg-1 BW citric acid, the serum OTC concentration reached almost the same concentration as that of the group treated with 50 mg kg-1 BW OTC. This coadministration successfully suppressed mortality due to vibriosis similar to the group treated with 50 mg kg-1 BW OTC. Conversely, poor efficacy was observed when only 25 mg kg-1 BW OTC was administered. These results suggest that coadministration of citric acid can be beneficial in reducing the dose of OTC needed for effective treatment, and thus contributes to the goal of reduced use of this antibiotic in aquaculture.

scholarly journals Rifampicin-Resistant Disseminated Tuberculosis in an Immunocompetent Adolescent Male Presenting with Retropharyngeal Abscess and Spinal Involvement

2021 ◽  
Author(s):  
Arghya Das ◽  
Vineeta Gupta ◽  
Shampa Anupurba
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Effective Treatment ◽  
Spinal Tuberculosis ◽  
Clinical Specimen ◽  
Retropharyngeal Abscess ◽  
Adolescent Male ◽  
Irreversible Damage ◽  
Disseminated Tuberculosis ◽  
Rare Manifestation ◽  
Microbiological Confirmation

AbstractRetropharyngeal abscess is a rare manifestation in spinal tuberculosis. Early clinical diagnosis followed by microbiological confirmation and effective treatment is crucial to avoid irreversible damage to the spine. Here, we report a case of disseminated tuberculosis in an immunocompetent adolescent male who presented with retropharyngeal abscess, multifocal involvement of the spine, and skin tuberculids. Xpert MTB/RIF assay in this patient facilitated early lifesaving treatment by detecting rifampicin-resistant Mycobacterium tuberculosis (MTB) in the clinical specimen.

scholarly journals Dosimetric Properties of the Newly Developed LiF:Mg,Cu,Si TL Material

2012 ◽  
Vol 5 (1) ◽  
pp. 25-31 ◽  
Author(s):  
M. S. Rahman ◽  
J. I. Lee ◽  
J. L. Kim ◽  
G. Cho
Keyword(s):  
Dose Response ◽  
Linear Response ◽  
Detection Threshold ◽  
Atomic Energy ◽  
Energy Response ◽  
Energy Research ◽  
Higher Doses ◽  
Research Institute

The dosimetric properties of the newly developed thermoluminescence (TL) material (LiF:Mg,Cu,Si) at Korea Atomic Energy Research Institute (KAERI) were investigated. The energy response of the detector was performed for photon energies from 20 to 662 keV. The dose response for this TL material (LiF:Mg,Cu,Si) was linear up to 10 Gy and a sub-linear response was observed for higher doses. The reusability of this newly developed TL detector sufficiently satisfied IEC standards. Detection threshold of LiF:Mg,Cu,Si TL material was investigated and found to be 930 nGy by Harshaw 4500 TLD reader. © 2013 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v5i1.11935        J. Sci. Res. 5 (1), 25-31  (2013) 

scholarly journals Failure To Recruit Anti-Inflammatory CD103+Dendritic Cells and a Diminished CD4+Foxp3+Regulatory T Cell Pool in Mice That Display Excessive Lung Inflammation and Increased Susceptibility to Mycobacterium tuberculosis

2012 ◽  
Vol 80 (3) ◽  
pp. 1128-1139 ◽  
Author(s):  
Chaniya Leepiyasakulchai ◽  
Lech Ignatowicz ◽  
Andrzej Pawlowski ◽  
Gunilla Källenius ◽  
Markus Sköld
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Bacterial Growth ◽  
Lung Inflammation ◽  
Chronic Infection ◽  
Host Immune Response ◽  
Content Type ◽  
Tnf Α

Susceptibility toMycobacterium tuberculosisis characterized by excessive lung inflammation, tissue damage, and failure to control bacterial growth. To increase our understanding of mechanisms that may regulate the host immune response in the lungs, we characterized dendritic cells expressing CD103 (αEintegrin) (αE-DCs) and CD4+Foxp3+regulatory T (Treg) cells duringM. tuberculosisinfection. In resistant C57BL/6 and BALB/c mice, the number of lung αE-DCs increased dramatically duringM. tuberculosisinfection. In contrast, highly susceptible DBA/2 mice failed to recruit αE-DCs even during chronic infection. Even though tumor necrosis factor alpha (TNF-α) is produced by multiple DCs and macrophage subsets and is required for control of bacterial growth, αE-DCs remained TNF-α negative. Instead, αE-DCs contained a high number of transforming growth factor beta-producing cells in infected mice. Further, we show that Tregcells in C57BL/6 and DBA/2 mice induce gamma interferon during pulmonary tuberculosis. In contrast to resistant mice, the Tregcell population was diminished in the lungs, but not in the draining pulmonary lymph nodes (PLN), of highly susceptible mice during chronic infection. Tregcells have been reported to inhibitM. tuberculosis-specific T cell immunity, leading to increased bacterial growth. Still, despite the reduced number of lung Tregcells in DBA/2 mice, the bacterial load in the lungs was increased compared to resistant animals. Our results show that αE-DCs and Tregcells that may regulate the host immune response are increased inM. tuberculosis-infected lungs of resistant mice but diminished in infected lungs of susceptible mice.

scholarly journals Investigation on the possibility of spontaneous cure of mice infected with different strains of Trypanosoma cruzi

1994 ◽  
Vol 36 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Juracy B. Magalhães ◽  
Sonia G. Andrade
Keyword(s):  
Body Weight ◽  
Trypanosoma Cruzi ◽  
Chronic Infection ◽  
Initial Phase ◽  
Newborn Mice ◽  
Blood Examination ◽  
Spontaneous Cure ◽  
Single Exception ◽  
Duration Of Infection ◽  
Different Strains

Seventy Swiss mice chronically infected with different strains of Trypanosoma cruzi, with persistently negative parasitemia on routine blood examination were parasitologically investigated to find out whether spontaneous cure occurred. Duration of infection varied from 90 to 250 days in the initial phase of this investigation. Parasitological tests consisted of daily direct blood examination performed during at least 25 days, followed by xenodiagnosis and subinoculation of blood into newborn mice. Mice that persisted negative were treated with Cyclophosphamide with one dose of 250 mg/kg of body weight and then investigated by direct blood examination, xenodiagnosis and subinoculation. A second dose of 250 mg/kg b. w. was given to the persistently negative mice. With one single exception, all mice showed positive parasitological tests in the different stages of the present investigation and we conclude that spontaneous cure did not occur in this group, which is representative of the chronic infection with different strains of T cruzi.

scholarly journals Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

2014 ◽  
Vol 59 (1) ◽  
pp. 475-481 ◽  
Author(s):  
Michael J. Schlosser ◽  
Hiromi Hosako ◽  
Ann Radovsky ◽  
Mark T. Butt ◽  
Dragomir Draganov ◽  
...  
Keyword(s):  
Body Weight ◽  
Optic Nerve ◽  
Body Weight Gain ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Once Daily ◽  
Clinical Observations ◽  
Activity Measures ◽  
Dose Levels ◽  
Neurobehavioral Effects

ABSTRACTTedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (−6.7%) and females (−5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

A Study of the Acid Dose-Response Curve to Small Doses of Pentagastrin in Duodenal Ulcer Patients

1972 ◽  
Vol 43 (2) ◽  
pp. 181-191
Author(s):  
J. B. Elder ◽  
G. Gillespie ◽  
E. H. G. Campbell ◽  
I. E. Gillespie ◽  
G. P. Crean ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Body Weight ◽  
Dose Response ◽  
Response Curve ◽  
Acid Output ◽  
Twilight Zone ◽  
Response Curves ◽  
Small Doses ◽  
Threshold Doses ◽  
Body Weight Dose

1. The acid secretory responses to a range of small doses of pentagastrin in 0·15 m-NaCl have been studied in thirty-one preoperative duodenal ulcer subjects. Acid output increased significantly above basal values when a dose of 0·064 μg h−1 kg−1 was given. 2. Control observations in sixteen duodenal ulcer patients using the saline solvent alone at identical rates of infusion showed no significant increase in acid output. 3. From the dose-response curves sub-threshold and threshold doses of pentapeptide are suggested for duodenal ulcer patients before truncal vagotomy. 4. Considerable variation in acid response was noted between patients given the same body-weight dose of pentapeptide. The results suggest that a ‘twilight zone’ of stimulation exists between the dose of pentagastrin by which few patients are stimulated and the dose by which the majority are stimulated. This may reflect some variation in the sensitivity to stimulation by pentagastrin from one patient to another.

Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers

2002 ◽  
Vol 20 (9) ◽  
pp. 2251-2266 ◽  
Author(s):  
Andrew L. Pecora ◽  
Naiyer Rizvi ◽  
Gary I. Cohen ◽  
Neal J. Meropol ◽  
Daniel Sterman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Intravenous Administration ◽  
Single Agent ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Repeat Dose ◽  
Tumor Cell Membrane ◽  
Dosing Regimens ◽  
Higher Doses

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 × 109 plaque-forming units (PFU)/m2 was established for outpatient dosing. After an initial dose of 12 × 109 PFU/m2, patients tolerated an MTD for subsequent doses of 120 × 109 PFU/m2. The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site–specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.

Sign in / Sign up

Export Citation Format

Share Document