scholarly journals In Vitro and In Vivo Efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae

2001 ◽  
Vol 45 (1) ◽  
pp. 312-315 ◽  
Author(s):  
Masahiro Takahata ◽  
Masako Shimakura ◽  
Ritsuko Hori ◽  
Kazuo Kizawa ◽  
Yozo Todo ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycoplasma Pneumoniae ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
In Vitro Activity ◽  
Free Base ◽  
Once Daily ◽  
Viable Cells

ABSTRACT T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.0313 μg/ml) against Mycoplasma pneumoniae. The MIC90 of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).

scholarly journals Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

2006 ◽  
Vol 50 (6) ◽  
pp. 1989-1992 ◽  
Author(s):  
James E. Moon ◽  
Michael C. Ellis ◽  
Matthew E. Griffith ◽  
Joshua S. Hawley ◽  
Robert G. Rivard ◽  
...  
Keyword(s):  
Body Weight ◽  
Untreated Control ◽  
Antimicrobial Agents ◽  
Leptospira Interrogans ◽  
In Vitro Activity ◽  
Hamster Model ◽  
In Vivo Efficacy ◽  
Daily Dose

ABSTRACT Human studies support the use of β-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Ninety to 100% of doxycycline controls, treated for 5 days with 5 mg/kg of body weight of drug, survived to 21 days. Treatment with azithromycin (daily dose: 6.25, 12.5, 25, 50, 100, or 200 mg/kg) resulted in 100% survival at all evaluated doses. Animals receiving 20 mg/kg or more of clarithromycin (daily dose: 1, 5, 10, 15, 20, 40, 60, or 100 mg/kg) had improved survival. Ninety-eight percent of animals treated with telithromycin (daily dose: 1, 5, 10, 15, 20, or 40 mg/kg) survived. We conclude that all agents tested have demonstrated in vivo efficacy in treating acute leptospirosis. These results provide support for further evaluation of macrolide and ketolide antimicrobial agents in human trials.

scholarly journals Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic

Pharmacology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Huda R. Taha ◽  
Nour Keewan ◽  
Farah Slati ◽  
Nour A. Al-Sawalha
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Clinical Evidence ◽  
High Selectivity ◽  
Lavage Fluid ◽  
In Vivo Studies ◽  
Nucleotide Analog ◽  
Positive Results ◽  
Adenosine Nucleotide

<b><i>Background:</i></b> The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide. <b><i>Summary:</i></b> Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. <b><i>Key Messages:</i></b> Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.

scholarly journals Effects of Roflumilast, Selective PDE4 Inhibitor, on Airway Reactivity in Ovalbumin-Sensitized Guinea Pigs

2015 ◽  
Vol 5 (1) ◽  
pp. 12-19
Author(s):  
Nirmathan Tharmalingam ◽  
I. Medvedova ◽  
A. Eichlerova ◽  
M. Prso ◽  
D. Mokra ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Whole Body ◽  
Pde4 Inhibitor ◽  
Airway Reactivity

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.

scholarly journals In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum

2002 ◽  
Vol 46 (5) ◽  
pp. 1388-1393 ◽  
Author(s):  
Noboru Tsuchimori ◽  
Ryogo Hayashi ◽  
Naomi Kitamoto ◽  
Kentaro Asai ◽  
Tomoyuki Kitazaki ◽  
...  
Keyword(s):  
Clinical Isolates ◽  
Sterol Synthesis ◽  
In Vitro Activity ◽  
Promising Candidate ◽  
Once Daily ◽  
Fluconazole Resistant ◽  
Therapeutic Activities ◽  
In Vitro Antifungal Activity

ABSTRACT TAK-456 is a novel oral triazole compound with potent and broad-spectrum in vitro antifungal activity and strong in vivo efficacy against Candida albicans and Aspergillus fumigatus. TAK-456 inhibited sterol synthesis of C. albicans and A. fumigatus by 50% at 3 to 11 ng/ml. TAK-456 showed strong in vitro activity against clinical isolates of Candida spp., Aspergillus spp., and Cryptococcus neoformans, except for Candida glabrata. The MICs at which 90% of the isolates tested were inhibited byTAK-456, fluconazole, itraconazole, voriconazole, and amphotericin B were 0.25, 4, 0.5, 0.13, and 0.5 μg/ml, respectively, for clinical isolates of C. albicans and 1, >64, 0.5, 0.5, and 0.5 μg/ml, respectively, for clinical isolates of A. fumigatus. Therapeutic activities of TAK-456 and reference triazoles against systemic lethal infections caused by C. albicans and A. fumigatus in mice were investigated by orally administering drugs once daily for 5 days, and efficacies of the compounds were evaluated by the prolongation of survival. In normal mice, TAK-456 and fluconazole were effective against infection caused by fluconazole-susceptible C. albicans at a dose of 1 mg/kg. In transiently neutropenic mice, therapeutic activity of TAK-456 at 1 mg/kg of body weight against infection with the same strain was stronger than those at 1 mg/kg of fluconazole. TAK-456 was effective against infections with two strains of fluconazole-resistant C. albicans at a dose of 10 mg/kg. TAK-456 also expressed activities similar to or higher than those of itraconazole against the infections caused by two strains of A. fumigatus in neutropenic mice at a dose of 10 mg/kg. These results suggest that TAK-456 is a promising candidate for development for the treatment of candidiasis and aspergillosis in humans.

scholarly journals In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent

2002 ◽  
Vol 46 (2) ◽  
pp. 367-370 ◽  
Author(s):  
Yasuki Kamai ◽  
Tamako Harasaki ◽  
Takashi Fukuoka ◽  
Satoshi Ohya ◽  
Katsuhisa Uchida ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
The Other ◽  
In Vitro Activity ◽  
Effective Doses ◽  
Low Levels ◽  
Systemic Infections

ABSTRACT The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 μg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.

Immunoregulatory effects of regulated, lung-targeted expression of IL-10 in vivo

2005 ◽  
Vol 288 (2) ◽  
pp. L251-L265 ◽  
Author(s):  
Donn Spight ◽  
Bin Zhao ◽  
Michael Haas ◽  
Susan Wert ◽  
Alvin Denenberg ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Targeted Expression ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Regulation of pulmonary inflammation involves an intricate balance of both pro- and anti-inflammatory mediators. Acute lung injury can result from direct pulmonary insults that activate alveolar macrophages to respond with increased cytokine expression. Such cytokine gene expression is mediated in part via NF-κB. IL-10 has been previously identified as an important endogenous anti-inflammatory cytokine in vivo on the basis of inhibiting NF-κB activation; however, the mechanism of this inhibition remains incompletely defined. We hypothesized that IL-10 regulated NF-κB activation in vivo via IκK inhibition. A bitransgenic mouse that allowed for externally regulated, lung-specific human IL-10 overexpression was generated. In the bitransgenic mice, introduction of doxycycline induced lung-specific, human IL-10 overexpression. Acute induction of IL-10 resulted in significant decreases in bronchoalveolar lavage fluid neutrophils (48%, P = 0.03) and TNF (62%, P < 0.01) following intratracheal LPS compared with bitransgenic negative mice. In vitro kinase assays showed this decrease to correlate to diminished lung IκK activity. Furthermore, we also examined the effect of chronic IL-10 overexpression in these transgenic mice. Results show that IL-10 overexpression in lungs of mature mice increased the number of intrapulmonary cells the phenotype of which was skewed toward increased B220+/CD45+ B cells and CD4+ T cells and was associated with increased CC chemokine expression. Thus regulated, lung-specific IL-10 overexpression may have a variety of complex immunologic effects depending on the timing and duration of expression.

Effect of Hematoporphyrin « in Vivo » and « in Vitro » on ATPC+ Tumor Cells

1968 ◽  
Vol 54 (5) ◽  
pp. 361-368
Author(s):  
Giorgio Cittadini ◽  
Tommaso De Cata ◽  
Carlo Gubinelli
Keyword(s):  
Growth Rate ◽  
Weight Loss ◽  
Body Weight ◽  
Drug Toxicity ◽  
Body Weight Loss ◽  
Ascites Tumor ◽  
Once Daily ◽  
Fluid Interaction

ATPC+ ascites tumor transplants of different size were performed in NMRI mice. Hematoporphyrin chlorhydrate (Hp) was administered i.p. once daily during the seven days following transplantation. In the first series « in vivo » (1.9 x 106 cells; 0.1, 0.3, 0.9 mg of Hp), body weight, ascitogenic time (Tasc) and total ascitic volume (TV) were determined. Hematoporphyrin-treated animals showed, after the apprearance of the ascites, a body weight loss superior to controls, due to the drug toxicity caused by Hp vs. ascitic fluid interaction. Neither Tasc nor TV were significantly modified. In the second series « in vivo » (2.3 x 104 or 2.3 x 102 cells; 0.3 mg Hp), body weight loss was lower, Tasc was significantly increased and also the survival varied. In a third experiment ATPC+ cells were incubated « in vitro » with Hp in a range from 102 to 108 molecules/cell). No effect was observed on growth rate when the cells were transplanted into the host.

Long-Lasting Production of TGF-β1 by Alveolar Macrophages Exposed to Low Doses of Asbestos without Apoptosis

2007 ◽  
Vol 20 (4) ◽  
pp. 661-671 ◽  
Author(s):  
Y. Nishimura ◽  
T. Nishiike-Wada ◽  
Y. Wada ◽  
Y. Miura ◽  
T. Otsuki ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Tnf Α ◽  
Pulmonary Cells ◽  
Low Exposure ◽  
The Relationship ◽  
Tgf Β1

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2 of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2 of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.

scholarly journals Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

2005 ◽  
Vol 49 (8) ◽  
pp. 3311-3316 ◽  
Author(s):  
Cristina Pichardo ◽  
José Manuel Rodríguez-Martínez ◽  
María E. Pachón-Ibañez ◽  
Carmen Conejo ◽  
José Ibáñez-Martínez ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Klebsiella Pneumoniae ◽  
Untreated Control ◽  
In Vitro Activity ◽  
Postantibiotic Effect ◽  
Bacterial Concentration ◽  
Inoculum Effect

ABSTRACT Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type β-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1×, 2×, 4×, 6×, and 8× MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 μg/ml, respectively. ΔT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

scholarly journals Activities of Dalbavancin In Vitro and in a Rabbit Model of Experimental Endocarditis Due to Staphylococcus aureus with or without Reduced Susceptibility to Vancomycin and Teicoplanin

2004 ◽  
Vol 48 (3) ◽  
pp. 1061-1064 ◽  
Author(s):  
Agnès Lefort ◽  
Juliette Pavie ◽  
Louis Garry ◽  
Françoise Chau ◽  
Bruno Fantin
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Half Life ◽  
Rabbit Model ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Once Daily ◽  
Elimination Half Life ◽  
Elimination Half

ABSTRACT For the treatment of rabbit endocarditis, dalbavancin given once daily (10 mg/kg of body weight for 4 days) or as a single 40-mg/kg dose was active against Staphylococcus aureus with or without reduced susceptibility to glycopeptides, as expected from its good in vitro activity, even in broth supplemented with 90% serum and given its prolonged elimination half-life.

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