In vitro activity of multiple antibiotic combinations against Nocardia: relationship with a short-term treatment strategy in heart transplant recipients with pulmonary nocardiosis

2010 ◽  
Vol 13 (4) ◽  
pp. 335-343 ◽  
Author(s):  
M.-F. Tripodi ◽  
E. Durante-Mangoni ◽  
R. Fortunato ◽  
S. Cuccurullo ◽  
Y. Mikami ◽  
...  
2006 ◽  
Vol 164 ◽  
pp. S110-S111
Author(s):  
Maria Barca ◽  
Anne Marie Ciobanu ◽  
Dan Balalau ◽  
Daniela Luiza Baconi ◽  
Mihaela Ilie ◽  
...  

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini

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.


Author(s):  
Karen A. Gammeltoft ◽  
Yuyong Zhou ◽  
Carlos R. Duarte Hernandez ◽  
Andrea Galli ◽  
Anna Offersgaard ◽  
...  

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.


Reproduction ◽  
2005 ◽  
Vol 130 (3) ◽  
pp. 303-310 ◽  
Author(s):  
Atef Ali ◽  
Marc-André Sirard

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.


2019 ◽  
Vol 21 (7) ◽  
pp. 890-900 ◽  
Author(s):  
Jubayer A Hossain ◽  
Md A Latif ◽  
Lars A R Ystaas ◽  
Sandra Ninzima ◽  
Kristoffer Riecken ◽  
...  

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.


1985 ◽  
Vol 71 (6) ◽  
pp. 555-561 ◽  
Author(s):  
Nadia Zafferoni ◽  
Rosella Silvestrini ◽  
Ornella Sanfilippo ◽  
Maria Grazia Daidone ◽  
Giampietro Gasparini

1998 ◽  
Vol 25 (2) ◽  
pp. 197 ◽  
Author(s):  
A. J. Escobar-Gutiérrez ◽  
B. Zipperlin ◽  
F. Carbonne ◽  
A. Moing ◽  
J.P. Gaudillére

Photosynthesis, metabolic carbon partitioning and the contribution of sorbitol to the osmotic potential of mature peach (Prunus persica (L.) Batsch) leaves and phloem sap were examined in plants undergoing two levels of a short term drought stress. The relationship between osmotic potential at full turgor and water potential showed that neither mild nor severe drought stress induced a significant active osmotic adjustment in mature leaves. The osmotic potential of leaves at full turgor was -1.9 MPa; sorbitol was the major organic component (20%). Leaf sucrose and starch contents were significantly reduced by drought. The partitioning of newly-fixed carbon was also affected by stress. These changes appeared to originate from the inhibition of photosynthesis induced by drought stress. At low photosynthetic rates, the turnover of organic ions was low, and sorbitol synthesis was favoured over that of sucrose. Water stress did not affect the in vitro activity of sucrose phosphate synthase (EC 2.4.1.14), the key enzyme in sucrose synthesis. The in vitro activity of aldose-6-phosphate reductase (EC 1.1.1.200), the key enzyme in sorbitol synthesis, tended to increase linearly in response to drought stress. It is concluded that, contrary to some other polyol-synthesising species, peach did not seem to benefit from sorbitol synthesis during short term drought stress for active osmotic adjustment in mature leaves. However, in phloem sap, increases in sucrose and especially sorbitol concentration were observed in stressed plants.


Sign in / Sign up

Export Citation Format

Share Document