scholarly journals In Vitro and In Vivo Effects of Quinupristin-Dalfopristin against Pneumocystis carinii

2001 ◽  
Vol 45 (11) ◽  
pp. 3234-3237 ◽  
Author(s):  
Peter D. Walzer ◽  
Alan Ashbaugh ◽  
Margaret Collins ◽  
Melanie T. Cushion
Keyword(s):  
Body Weight ◽  
Toxoplasma Gondii ◽  
Inhibitory Concentration ◽  
Pneumocystis Carinii ◽  
High Dose ◽  
Dose Administration ◽  
In Vivo Effects ◽  
Immunosuppressed Mice

ABSTRACT Quinupristin-dalfopristin (Q-D), which is active against bacteria and Toxoplasma gondii, was examined for its activity against Pneumocystis carinii. After 72 h of incubation with rat P. carinii in an ATP cytotoxicity assay, the 50% inhibitory concentration of Q-D was 10.6 μg/ml, a level that can be achieved in serum with high-dose administration. Q-D administered intraperitoneally at doses of 50 to 200 mg per kg of body weight per day in the treatment and 100 mg/kg/day three times per week in the prophylaxis of pneumocystosis in immunosuppressed mice reduced the organism burden up to 15- and 302-fold, respectively. We conclude that Q-D has activity against P. carinii in vitro and in vivo.

scholarly journals Spiroindolone That Inhibits PfATPase4 Is a Potent, Cidal Inhibitor of Toxoplasma gondii TachyzoitesIn VitroandIn Vivo

2013 ◽  
Vol 58 (3) ◽  
pp. 1789-1792 ◽  
Author(s):  
Ying Zhou ◽  
Alina Fomovska ◽  
Stephen Muench ◽  
Bo-Shiun Lai ◽  
Ernest Mui ◽  
...  
Keyword(s):  
Body Weight ◽  
Toxoplasma Gondii ◽  
Inhibitory Concentration ◽  
Parasite Burden ◽  
Content Type ◽  
Medicine Development ◽  
Lead Candidate ◽  
Oral Doses

ABSTRACTHere, we show that spiroindolone, an effective treatment for plasmodia, is also active againstToxoplasma gondiitachyzoites.In vitro, spiroindolone NITD609 is cidal for tachyzoites (50% inhibitory concentration [IC50], 1μM) and not toxic to human cells at ≥10μM. Two daily oral doses of 100 mg/kg of body weight reduced the parasite burden in mice by 90% (P= 0.002), measured 3 days after the last dose. This inhibition ofT. gondiitachyzoitesin vitroandin vivoindicates that spiroindolone is a promising lead candidate for further medicine development.

scholarly journals Use of Terbinafine in Mouse and Rat Models of Pneumocystis carinii Pneumonia

2002 ◽  
Vol 46 (2) ◽  
pp. 514-516 ◽  
Author(s):  
Peter D. Walzer ◽  
Alan Ashbaugh
Keyword(s):  
Pneumocystis Carinii Pneumonia ◽  
Drug Testing ◽  
Inhibitory Concentration ◽  
Pneumocystis Carinii ◽  
Rat Models ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT Terbinafine, an allylamine used to treat onychomycosis, has been reported to be active against rat Pneumocystis carinii in vitro and in vivo. By contrast, our in vitro data showed that the 50% inhibitory concentration of terbinafine against rat P. carinii is 3.7 μg/ml, a level that cannot be clinically achieved in serum. In the present study, terbinafine administered orally at doses of 20 to 400 mg/kg/day and 50 to 250 mg/kg/day was ineffective therapy for mouse and rat models of pneumocystosis, respectively. These results emphasize the complexities of P. carinii drug testing and the need for caution before considering studies in humans.

scholarly journals Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

Parasitology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Dawei Wang ◽  
Mengen Xing ◽  
Saeed El-Ashram ◽  
Yingying Ding ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Parasite Burden ◽  
Vero Cells ◽  
Negative Control ◽  
Protective Mechanism ◽  
High Dose ◽  
Mouse Tissues

Abstract Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

scholarly journals In vitro (anti-alpha-glucosidase) activity and in vivo anti-diabetic activity of Androsace foliosa (common rock jasmine) in alloxan-induced diabetic BALB/c mice

2019 ◽  
Vol 17 ◽  
pp. 205873921985742
Author(s):  
Jawad Zaheer ◽  
Qazi Najam-Us-Saqib ◽  
Misba Qamar ◽  
Muhammad Akram
Keyword(s):  
Body Weight ◽  
Inhibitory Concentration ◽  
Methanolic Extract ◽  
Type Ii ◽  
Standard Drug ◽  
Diabetes Mellitus Type Ii ◽  
Reduce Body Weight ◽  
Alpha Glucosidase

Androsace foliosa syn. Androsace sarmentosa (botanical name of common rock jasmine) ( Primulaceae) is used in the treatment various disorders. The aim of this study is to evaluate in vitro anti-diabetic activity of crude methanolic extract of leaves and roots of A. foliosa by anti -alpha-glucosidase (α-Glc) and in vivo anti-diabetic activity of n-hexane fraction on alloxan-induced diabetic mice. Results of in vitro anti-diabetic (α-Glc) activity showed that n-hexane leaves fraction was most potent among all the fractions and showed IC50 (half maximal inhibitory concentration) value of 64.91 ± 0.16 µg and % inhibition of 89.35 ± 0.45, comparable to that of standard acarbose. In vivo n-hexane leaves fraction decreases blood glucose level and reduces body weight similar to that of standard drug glibenclamide. Based on the conclusion of both in vitro and in vivo activities, it can be accomplished that the plant A. foliosa acquires noteworthy anti-diabetic action and can be used to treat diabetes mellitus type II and to reduce body weight.

scholarly journals In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii

2012 ◽  
Vol 45 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Thaís Cobellis Gomes ◽  
Heitor Franco de Andrade Júnior ◽  
Susana Angélica Zevallos Lescano ◽  
Vicente Amato-Neto
Keyword(s):  
Toxoplasma Gondii ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Congenital Disease ◽  
Nonlinear Regression Analysis ◽  
Antiparasitic Drugs ◽  
Effective Drugs ◽  
Disposable Plastic

INTRODUCTION: Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS), or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. METHODS: LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. RESULTS: Artesunate showed a mean tachyzoite inhibitory concentration (IC50) of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. CONCLUSIONS: Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

scholarly journals Isavuconazole Therapy Protects Immunosuppressed Mice from Mucormycosis

2014 ◽  
Vol 58 (4) ◽  
pp. 2450-2453 ◽  
Author(s):  
Guanpingsheng Luo ◽  
Teclegiorgis Gebremariam ◽  
Hongkyu Lee ◽  
John E. Edwards ◽  
Laura Kovanda ◽  
...  
Keyword(s):  
Liposomal Amphotericin ◽  
High Dose ◽  
Investigational Drug ◽  
Rhizopus Delemar ◽  
Content Type ◽  
Fungal Burden ◽  
Further Development ◽  
Immunosuppressed Mice

ABSTRACTWe studied thein vitroandin vivoefficacies of the investigational drug isavuconazole against mucormycosis due toRhizopus delemar. Isavuconazole was effective, with MIC and minimal fungicidal concentration (MFC) values ranging between 0.125 and 1.00 μg/ml. A high dose of isavuconazole prolonged the survival time and lowered the tissue fungal burden of cyclophosphamide/cortisone acetate-treated mice infected withR. delemarand was as effective as a high-dose liposomal amphotericin B treatment. These results support the further development of this azole against mucormycosis.

scholarly journals In vitro and in vivo effects of doxycycline on Toxoplasma gondii.

1990 ◽  
Vol 34 (5) ◽  
pp. 775-780 ◽  
Author(s):  
H R Chang ◽  
R Comte ◽  
J C Pechere
Keyword(s):  
Toxoplasma Gondii ◽  
In Vivo Effects

scholarly journals Anti- Toxoplasma gondii effect of Lumefantrine in vitro and in vivo

2020 ◽  
Author(s):  
Dawei Wang ◽  
Mengen Xing ◽  
Saeed El-Ashram ◽  
Yingying Ding ◽  
Xiaoyu Sang ◽  
...  
Keyword(s):  
Side Effects ◽  
Toxoplasma Gondii ◽  
Mtt Assay ◽  
Vero Cells ◽  
Protective Mechanism ◽  
High Dose ◽  
Mouse Tissues ◽  
Ifn Γ

Abstract Background: Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulfadiazine and pyrimethamine. However, both drugs have serious side effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-Toxoplasma drugs with high potency and less or no side-effects. Methods: The cytotoxicity of sulfadiazine and lumefantrine to Vero cells was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. And MTT assay was also used to detect the inhibitory effects of lumefantrine on parasites invasion and proliferation. Flow cytometry was conducted to further verify parasites proliferation. qPCR was performed to evaluate the parasite load in the mice after lumefantrine treatment. In order to determine whether lumefantrine treatment enhances Th1 or Th2 cytokine response, IFN-γ, IL-4, and IL-10 levels in the serum of mice were determined. Results: Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its replication and invasion of Vero cells in vitro without being toxic to the cells. Furthermore, lumefantrine protected mice with acute toxoplasmosis from death to a certain extent and reduced the parasite burden in mouse tissues in vivo. In addition, a significant increase in IFN-γ production was observed in high dose lumefantrine-treated mice while IL-10 and IL-4 levels increased in low dose lumefantrine-treated mice. Conclusions: The results of this study demonstrated that lumefantrine may be a promising agent to treat toxoplamosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.Key words: Toxoplasma gondii, Lumefantrine, anti-Toxoplasma gondii, Invasion, Proliferation

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