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

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

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

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini
Keyword(s):  
Rattus Norvegicus ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Term Treatment ◽  
Genotoxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
Chromosomal Aberration Test

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.

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

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.

scholarly journals Protein kinases influence bovine oocyte competence during short-term treatment with recombinant human follicle stimulating hormone

Reproduction ◽  
2005 ◽  
Vol 130 (3) ◽  
pp. 303-310 ◽  
Author(s):  
Atef Ali ◽  
Marc-André Sirard
Keyword(s):  
Protein Kinase ◽  
Follicle Stimulating Hormone ◽  
Term Treatment ◽  
Developmental Competence ◽  
Blastocyst Formation ◽  
Short Term ◽  
Short Term Treatment ◽  
Developmental Capacity ◽  
Bovine Oocytes

The aim of this study was to investigate the effect of short-term treatment (first 2 or 6 h) with recombinant human follicle-stimulating hormone (r-hFSH) during in vitro maturation (IVM) on the developmental competence of bovine oocytes. The roles of protein kinase A (PKA) and protein kinase C (PKC) (possibly involved in FSH response), were investigated using activators (Sp-cAMPS, PMA) or inhibitors (Rp-cAMPS, sphingosine) of these two protein kinases, respectively. The developmental competence of bovine oocytes was measured by the rate of blastocyst formation after in vitro fertilization (IVF). Our results showed that when cumulus–oocyte complexes (COCs) were cultured with r-hFSH for the first 6 h, a highly significant (P < 0.0001) improvement is seen in blastocyst development rate as a proportion of oocytes in culture compared with those matured with r-hFSH for the first 2 or 24 h. A transient exposure (6 h) to the highest dose (100 μM) of forskolin (an activator of adenylate cyclase) increased (P < 0.05) the rate of blastocyst formation. But the PKA inhibitors (Rp-cAMPS) did not affect the stimulatory effects of r-hFSH on the blastocyst yield. However, stimulation of PKC by low doses of PMA (0.1–0.5 μM) during short-term treatment, enhanced (P < 0.0001) the developmental capacity of oocytes, while sphingosine (a specific inhibitor of PKC) inhibited (P < 0.05) the stimulatory effects of r-hFSH on the rate of blastocyst formation. Our results indicate that although the developmental capacity of bovine oocytes in vitro can be modulated by both the PKA, and the PKC pathways, the activation of PKC during short-term treatment can mimic the effect of r-hFSH on the cytoplasmic maturation in bovine oocytes in vitro.

scholarly journals Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma

2019 ◽  
Vol 21 (7) ◽  
pp. 890-900 ◽  
Author(s):  
Jubayer A Hossain ◽  
Md A Latif ◽  
Lars A R Ystaas ◽  
Sandra Ninzima ◽  
Kristoffer Riecken ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tumor Cells ◽  
Suicide Gene ◽  
Term Treatment ◽  
Suicide Gene Therapy ◽  
Short Term ◽  
Short Term Treatment ◽  
Long Term Treatment

Abstract Background Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.

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

2007 ◽  
Vol 56 (8) ◽  
pp. 1047-1051 ◽  
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.

Toxicity, Clastogenicity and Genotoxicity of Theophylline and Pentoxifylline in Mammalian Cells Cultured In Vitro

1995 ◽  
Vol 23 (4) ◽  
pp. 504-512
Author(s):  
Darina Slameňová ◽  
Ivan Chalupa ◽  
Alena Gábelová ◽  
Eva Bozsakyová ◽  
Eva Horváthová ◽  
...  
Keyword(s):  
Human Lymphocytes ◽  
Term Treatment ◽  
Single Strand ◽  
Toxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
V79 Cells ◽  
Strand Breaks ◽  
Single Strand Breaks

— As part of a developmental study on theophylline and pentoxifylline, these drugs were tested for possible cytotoxic, mutagenic and clastogenic effects on V79 hamster cells and human lymphocytes cultured in vitro. After the short-term treatment of V79 cells with theophylline and pentoxifylline, the cells were relatively resistant to the toxic effects of these methylxanthines. Generally, only high concentrations of theophylline or pentoxifylline had toxic effects on exposed V79 cells. Short-term treatment of V79 cells with theophylline or pentoxifylline did not induce 6-thioguanine resistant mutations in either the presence or absence of S9 fractions. However, in the absence of an S9 fraction, elevated levels of single-strand breaks in DNA were induced. Both methylxanthines caused clastogenic effects in human lymphocytes and hamster V79 cells after long-term exposure. We suggest that theophylline and pentoxifylline are clastogenic but not genotoxic, and that the molecular mechanism for the induction of single-strand breaks in DNA and the induction of chromosomal aberrations in cells treated with theophylline and pentoxifylline is not the induction of lesions in the DNA but the inhibition of DNA chain elongation.

scholarly journals A retrospective, observational, single center study of gonadotropin-releasing hormone agonist protocols at the Reproductive Center of Farah Hospital in Jordan

2019 ◽  
Vol 7 (8) ◽  
pp. 3103
Author(s):  
Zaid Kilani ◽  
Mohammad Shaban
Keyword(s):  
Term Treatment ◽  
Gonadotropin Releasing Hormone ◽  
Clinical Pregnancy ◽  
Short Term ◽  
Short Term Treatment ◽  
Releasing Hormone ◽  
Long Term Treatment ◽  
Group A

Background: Data on infertility and in vitro fertilization (IVF) are incomplete and uncertain in Jordan and worldwide because of difficulties in evaluating infertility in the general population. This study aimed at comparing the effectiveness of the gonadotropin-releasing hormone agonists (GnRH-a) long and short protocols as part of IVF or intracytoplasmic sperm injection.Methods: This observational, retrospective, comparative, longitudinal study was conducted in a reproductive center in Jordan. It reviewed data charts from women who took GnRH-a for IVF, from 2010 to 2013. These were categorized in Group A (long-term GnRH-a: single 3.75 mg-monthly injection) or Group B (short-term GnRH-a: multiple daily 0.1 mg injections). The primary endpoint was the rate of ongoing clinical pregnancy (number of pregnancies/number of women) and live birth rate in fresh cycle/protocols.Results: Out of 1,946 eligible women, 471 underwent the long-term treatment of GnRH-a administration and 1,523 the short-term treatment. The women’s mean age was 29.61±3.80 years old. Out of the 471 women in Group A, 216 (45.9%) women had ongoing clinical pregnancy, of whom 69 (31.9%) had live births. In the short-protocol group, 485 (31.8%) women had ongoing clinical pregnancy, of whom 133 (27.4%) had live births.Conclusions: GnRH-a long protocol is more effective than the short protocol regardless of the agonist formulation used in subfertile women/men who underwent IVF/ intracytoplasmic sperm injection.

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