Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Download Full-text

Activity of ketoconazole against Mycobacterium tuberculosis in vitro and in the mouse model

Journal of Medical Microbiology ◽

10.1099/jmm.0.47058-0 ◽

2007 ◽

Vol 56 (8) ◽

pp. 1047-1051 ◽

Cited By ~ 24

Author(s):

Sean T. Byrne ◽

Steven M. Denkin ◽

Peihua Gu ◽

Eric Nuermberger ◽

Ying Zhang

Keyword(s):

Mycobacterium Tuberculosis ◽

Term Treatment ◽

New Drugs ◽

Bacteriostatic Effect ◽

Short Term ◽

Short Term Treatment ◽

Neutral Conditions

There is an urgent need for the development of new drugs that are active against drug-resistant Mycobacterium tuberculosis strains and can shorten tuberculosis (TB) therapy. It has previously been reported that the azole class of antifungals has anti-TB activity in vitro. This study evaluated ketoconazole (KTC) for activity against M. tuberculosis. The MIC of KTC for different M. tuberculosis strains ranged from 8 to 16 μg ml−1 under both acidic and neutral conditions, with the minimum bactericidal concentration being about twofold higher than the MIC. KTC had enhanced activity against old, non-growing bacilli in vitro when combined with pyrazinamide (PZA) and rifampicin (RIF). A single oral dose of KTC at 75 mg kg−1 led to an inhibitory serum concentration 2 h after administration. The in vivo activity of KTC was evaluated in established pulmonary TB in the murine model, compared alone and in combination with isoniazid (INH), PZA and RIF. KTC alone exhibited little effect after short-term treatment, with a borderline bacteriostatic effect on spleen colony counts but not on lung counts. KTC, when added in combination with INH, PZA and RIF, significantly improved the treatment outcome in the lungs (compared with treatment with INH, PZA and RIF). The lowest numbers of bacilli in lungs were found in mice treated with KTC, PZA and RIF. Further investigation is necessary to determine the role of KTC in the treatment of TB.

Download Full-text

Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies

Journal of Endocrinology ◽

10.1677/joe.1.06122 ◽

2005 ◽

Vol 186 (1) ◽

pp. 213-220

Author(s):

M Asfari ◽

S Berta ◽

S Coffy ◽

M Kergoat ◽

C Charon ◽

...

Keyword(s):

Mycophenolic Acid ◽

Cell Clone ◽

Day Treatment ◽

Immunosuppressive Drugs ◽

Term Treatment ◽

Β Cell ◽

Short Term ◽

Short Term Treatment

One of the major requirements for a successful and life-lasting organ transplant is the access to safe, least toxic and permanent tolerance-inducing drugs. In this study we wished to evaluate the effects of tolerogenic doses of the immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal β-cell lines, both in vivo and in vitro. Here we demonstrate that combined administration of low-dose MPA and Tac for 23 days induced permanent tolerance in an allogeneic β-cell line transplant in Wistar rat liver through the portal vein. This short-term treatment of tolerogenic doses of the two drugs was deleterious to the survival of the transplanted cells but a small percentage of the cells could resist the effect and become fully active when the drugs were removed. The surviving cells, retrieved from growth in vivo, did not exhibit increased resistance in comparison to the original cells when tested in vitro at two glucose concentrations, 10 and 20 mM. The presence of a small percentage of resistant cells at the two glucose concentrations was also detected in the in vitro study after a continuous 8-day treatment demonstrating that the in vivo resistance was not related to micro-environmental protection but possibly to a phenotypic cell state that is yet to be determined.

Download Full-text

Lymphocyte Immunoglobulin Secretion during Short-term Treatment with Cephalosporins in Vivo and in Vitro: Effects on Plaque-forming Cell Response of Human Peripheral Blood Lymphocytes

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365548609032311 ◽

1986 ◽

Vol 18 (1) ◽

pp. 83-84

Author(s):

Palle Tauris ◽

Finn T. Black

Keyword(s):

Cell Response ◽

Human Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

Human Peripheral Blood Lymphocytes ◽

In Vitro Effects

Download Full-text

DER TSH-RESERVE-TEST AN DER RATTE

Acta Endocrinologica ◽

10.1530/acta.0.0440570 ◽

1963 ◽

Vol 44 (4) ◽

pp. 570-580 ◽

Cited By ~ 2

Author(s):

H. W. Iff ◽

H. Studer ◽

F. Wyss

Keyword(s):

Time Course ◽

Term Treatment ◽

Short Term ◽

Iodide Uptake ◽

Short Term Treatment ◽

Similar Time ◽

Clinical Method ◽

Tsh Secretion

ABSTRACT A rebound of 131I-uptake by the thyroid gland after a thyrostatic treatment may be taken as evidence of an unimpaired pituitary TSH-secretion. The iodide uptake in vivo and the iodide accumulation in vitro were studied in rat thyroids following a short-term treatment of the animals with carbimazole. The experiments served as models for the clinical method of assaying the pituitary TSH-reserve. The total iodide uptake reaches a peak 36 hours after the end of a carbimazole treatment and returns to normal after 96 hours. The rebound of the iodide accumulation has a similar time course. Extending the carbimazole treatment from 6 to 12 days leads to a definite increase in the peak iodide accumulation while the peak of the total iodide uptake was not significantly increased. The duration of the rebound-phase is not changed by prolonged carbimazole treatment.

Download Full-text

Unsuccessful intravenous D-mannose treatment in PMM2-CDG

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1213-3 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Sarah C. Grünert ◽

Thorsten Marquardt ◽

Ekkehart Lausch ◽

Hans Fuchs ◽

Christian Thiel ◽

...

Keyword(s):

Term Treatment ◽

First Year ◽

Short Term ◽

Multisystem Disorder ◽

Short Term Treatment ◽

Congenital Disorder Of Glycosylation ◽

First Year Of Life ◽

Glycosylation Defect

Abstract Background PMM2-CDG (Phosphomannomutase 2 - Congenital disorder of glycosylation-Ia; CDG-Ia) is the most common glycosylation defect, often presenting as a severe multisystem disorder that can be fatal within the first years of life. While mannose treatment has been shown to correct glycosylation in vitro and in vivo in mice, no convincing effects have been observed in short-term treatment trials in single patients so far. Results We report on a boy with a severe PMM2-CDG who received a continuous intravenous mannose infusion over a period of 5 months during the first year of life in a dose of 0.8 g/kg/day. N-glycosylation of serum glycoproteins and mannose concentrations in serum were studied regularly. Unfortunately, no biochemical or clinical improvement was observed, and the therapy was terminated at age 9 months. Conclusion Postnatal intravenous D-mannose treatment seems to be ineffective in PMM2-CDG.

Download Full-text

In vitro effects of methadone on lymphocyte proliferation following a short-term treatment with methotrexate-loaded liposomes in a murine model of arthritis

Toxicology Letters ◽

10.1016/j.toxlet.2006.06.233 ◽

2006 ◽

Vol 164 ◽

pp. S110-S111

Author(s):

Maria Barca ◽

Anne Marie Ciobanu ◽

Dan Balalau ◽

Daniela Luiza Baconi ◽

Mihaela Ilie ◽

...

Keyword(s):

Murine Model ◽

Lymphocyte Proliferation ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

In Vitro Effects

Download Full-text

Investigation of soy sauce treated with nitrite in the chromosomal aberration test in vitro and the micronucleus test in vivo

Mutation Research Letters ◽

10.1016/0165-7992(91)90018-y ◽

1991 ◽

Vol 262 (3) ◽

pp. 171-176 ◽

Cited By ~ 2

Author(s):

A. Nagahara ◽

K. Ohshita ◽

S. Nasuno

Keyword(s):

Chromosomal Aberration ◽

Micronucleus Test ◽

Soy Sauce ◽

Chromosomal Aberration Test

Download Full-text

Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 in Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02680-20 ◽

2021 ◽

Author(s):

Karen A. Gammeltoft ◽

Yuyong Zhou ◽

Carlos R. Duarte Hernandez ◽

Andrea Galli ◽

Anna Offersgaard ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Protease Inhibitors ◽

Viral Suppression ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

Direct Acting Antiviral ◽

Human Lung Carcinoma

Antivirals targeting SARS-CoV-2 could improve treatment of COVID-19. We evaluated efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PI) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment. HCV PI showed differential potency in short-term treatment assays based on detection of SARS-CoV-2 Spike protein in VeroE6 cells. Linear PI boceprevir, telaprevir and narlaprevir had 50% effective concentrations (EC50) of ∼40 μM. Among macrocyclic PI, simeprevir had the highest (EC50 15 μM) and glecaprevir the lowest (EC50 >178 μM) potency, with paritaprevir, grazoprevir, voxilaprevir, vaniprevir, danoprevir and deldeprevir in between. Acyclic PI asunaprevir and faldaprevir had EC50 of 72 and 23 μM, respectively. ACH-806, inhibiting the HCV NS4A protease cofactor, had EC50 of 46 μM. Similar and slightly increased PI potencies were found in human hepatoma Huh7.5 cells and human lung carcinoma A549-hACE2 cells, respectively. Selectivity indexes based on antiviral and cell viability assays were highest for linear PI. In short-term treatments, combination of macrocyclic but not linear PI with remdesivir showed synergism in VeroE6 and A549-hACE2 cells. Longer-term treatment of infected VeroE6 and A549-hACE2 cells with 1-fold EC50 PI revealed minor differences in barrier to SARS-CoV-2 escape. Viral suppression was achieved with 3- to 8-fold EC50 boceprevir or 1-fold EC50 simeprevir or grazoprevir, but not boceprevir, in combination with 0.4- to 0.8-fold EC50 remdesivir; these concentrations did not lead to viral suppression in single treatments. This study could inform development and application of protease inhibitors for optimized antiviral treatments of COVID-19.

Download Full-text