scholarly journals In vitro long-term treatment with MAPK inhibitors induces melanoma cells with resistance plasticity to inhibitors while retaining sensitivity to CD8 T cells

2017 ◽  
Vol 37 (3) ◽  
pp. 1367-1378 ◽  
Author(s):  
Florencia Paula Madorsky Rowdo ◽  
Antonela Barón ◽  
Erika María Von Euw ◽  
José Mordoh
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Melanoma Cells ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Mapk Inhibitors

scholarly journals Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2607
Author(s):  
Yuzhen Gao ◽  
Jingjing Cao ◽  
Pan Xing ◽  
Ralf Altmeyer ◽  
Youming Zhang
Keyword(s):  
Respiratory Syncytial Virus ◽  
Confidence Interval ◽  
The Elderly ◽  
Term Treatment ◽  
Fusion Inhibitors ◽  
Long Term Treatment ◽  
Statistical Program ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from −50 µM2 % to −176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.

Long-Term Treatment with Pivmecillinam in Patients with Recurrent Bacteriuria

1982 ◽  
Vol 10 (3) ◽  
pp. 179-182
Author(s):  
B Bresky ◽  
K Lincoln
Keyword(s):  
Escherichia Coli ◽  
Adverse Effect ◽  
Renal Function ◽  
Term Treatment ◽  
The Body ◽  
End Of Treatment ◽  
Long Term Treatment ◽  
Tract Infections

Thirty out-patients with chronic recurrent urinary tract infections, who had failed to respond to 10 days treatment with either pivmecillinam and/or amoxycillin, received a 3-month course of pivmecillinam at a dose of 200 mg, three times daily. Twenty-seven patients had bacteriuria due to Enterobacteriaceae, mainly Escherichia coli, sensitive to mecillinam in vitro. Pivmecillinam eradicated all the initial urinary pathogens. Reinfections occurred during treatment in three patients, who remained asymptomatic. Four subjects complained of gastro-intestinal side-effects, and therapy was withdrawn in three instances. Another three patients described unusual adverse events towards the end of the course of treatment, described as an odd sensation in the body and a desire for salt. The sensation disappeared a few days after the end of treatment. Treatment with pivmecillinam had no adverse effect on haematopoietic, hepatic or renal function.

scholarly journals The In Vitro Antiplasmodial Activities of Aqueous Extracts of Selected Ghanaian Herbal Plants

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Elizabeth Cudjoe ◽  
Dickson Donu ◽  
Ruth E. Okonu ◽  
Jones A. Amponsah ◽  
Linda E. Amoah
Keyword(s):  
Moringa Oleifera ◽  
Mangifera Indica ◽  
Term Treatment ◽  
Sybr Green ◽  
Aqueous Extracts ◽  
Herbal Extracts ◽  
Long Term Treatment ◽  
Polyalthia Longifolia

Background. The asexual and sexual stages (gametocytes) of Plasmodium falciparum parasites are known to respond differently to antimalarial drugs. Herbal products with extended treatment regimens and inadequate dosing information are widely used to treat malaria in Ghana. This study set out to determine the in vitro activity of selected herbal extracts on the development of asexual and sexual stage malaria parasites. Methods. The 72-hour SYBR Green 1-based in vitro drug assay was used to determine the asexual parasite growth inhibitory effects exhibited by aqueous extracts of Alchornea cordifolia, Polyalthia longifolia, Moringa oleifera, and Mangifera indica on the NF54, CamWT_C580Y, and IPC 4912 strains of Plasmodium falciparum. The effects of exposure of asexual and early-stage NF54 gametocytes to varying concentrations of the aqueous herbal extracts were assessed by microscopy after 7 days of continuous culturing in the presence of the herbal extract. Qualitative and quantitative phytochemical screening were also performed on the herbal extracts. Results. In the SYBR Green 1 assay, aqueous extracts of Alchornea cordifolia exhibited moderate (IC50 of 5.8, 17.4, and 15.8 μg/ml) and Mangifera indica exhibited low (IC50 of 65.4, 96.7, and 81.7 μg/ml) activities against the NF54, Cam WT_C580Y, and IPC 4912 parasites, respectively, whilst Polyalthia longifolia and Moringa oleifera were inactive. Long-term treatment of NF54 parasites with 1 mg/ml of Polyalthia longifolia produced the highest densities of gametocytes and the least (56%) inhibition of asexual parasites on Day 7. Long-term treatment of NF54 parasites with 10 μg/ml Alchornea cordifolia resulted in complete parasite (asexual and gametocyte) clearance on Day 7. Conclusions. Alchornea cordifolia exhibited a ‘moderate’ activity against the three parasites tested in the 72-hour SYBR Green 1 assay and also effectively cleared both asexual parasites and gametocytes. Long-term treatment of malaria parasites with herbal extracts mimics a treatment regimen and should be used to determine the antimalarial properties of herbal extracts.

Biocompatibility of Charcoal Hemoperfusion. Effects of Long-Term Treatment on Lymphocyte Characteristics and Function

1986 ◽  
Vol 9 (5) ◽  
pp. 301-304 ◽  
Author(s):  
S. Stefoni ◽  
A. Nanni Costa ◽  
G. Liviano D'Arcangelo ◽  
M. Biavati ◽  
S. lannelli ◽  
...  
Keyword(s):  
Antigen Expression ◽  
Term Treatment ◽  
T Cell Subsets ◽  
Long Term Treatment ◽  
Circulating Lymphocytes ◽  
And Function ◽  
Charcoal Hemoperfusion

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.

Effects of long term treatment with corticotropin releasing factor on corticotropic tumor cells in vitro

1998 ◽  
Vol 74 (1) ◽  
pp. 35-40 ◽  
Author(s):  
M.F Melzig ◽  
G Papsdorf ◽  
R Loose ◽  
A Winkler ◽  
M Beyermann ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Term Treatment ◽  
Corticotropin Releasing Factor ◽  
Long Term Treatment

Plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-containing superoxide dismutase in alcoholics treated with disulfiram

1986 ◽  
Vol 70 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Michael Öhman ◽  
Stefan L. Marklund
Keyword(s):  
Superoxide Dismutase ◽  
Chronic Alcoholism ◽  
Term Treatment ◽  
Extracellular Superoxide Dismutase ◽  
Healthy Controls ◽  
Efficient Inhibitor ◽  
Long Term Treatment

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase. 2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls. 3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

2009 ◽  
Vol 296 (3) ◽  
pp. F605-F613 ◽  
Author(s):  
Francisco J. Mendoza ◽  
Ignacio Lopez ◽  
Rocio Canalejo ◽  
Yolanda Almaden ◽  
David Martin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Term Treatment ◽  
Parathyroid Cell ◽  
Calcium Sensing Receptor ◽  
Short Term ◽  
Calcium Sensing ◽  
Long Term Treatment ◽  
Acute Increase

To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR mRNA, whereas the combination (1.81 ± 0.20) produced no additional benefit. AMG 641 also increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 ± 0.14) and calcitriol (0.99 ± 0.12) increased VDR mRNA ( P < 0.05 vs. 5/6 Nx+vehicle, 0.49 ± 0.10), and the increase was more accentuated when the drugs were combined (1.49 ± 0.45). In the short-term protocol, only treatment with AMG 641, alone (1.52 ± 0.41) or combined with calcitriol (1.86 ± 0.24), increased VDR mRNA. In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell proliferation was uncontrolled, thus supporting a direct effect of calcimimetics on CaSR and VDR expression by hyperplastic parathyroid cells.

scholarly journals Comparative evaluation of methods testing in vitro sensitivity to azithromycin in multi-drug resistant Pseudomonas aeruginosa isolated from cystic fibrosis patients

2020 ◽  
Author(s):  
Michael Soerensen ◽  
Dennis Nurjadi ◽  
Bakhodur Khakimov ◽  
Sébastien Boutin ◽  
Alexander H. Dalpke ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Therapeutic Option ◽  
Calf Serum ◽  
Multidrug Resistant ◽  
Term Treatment ◽  
In Vitro Sensitivity ◽  
Mueller Hinton ◽  
Long Term Treatment

Abstract Long-term treatment with azithromycin is a therapeutic option in Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa . It was recently shown that azithromycin has direct antimicrobial activity when P. aeruginosa isolates are tested in Roswell Park Memorial Institute medium supplemented with fetal calf serum (RPMI 1640/FCS) by broth microdilution. We now investigated whether (i) azithromycin might also be active against multidrug resistant (MDR) P. aeruginosa isolated from CF patients and (ii) how in vitro sensitivity assays perform in synthetic cystic fibrosis sputum medium (SCFM), a medium that mimics the particular CF airway environment. In 17 (59%) out of 29 MDR P. aeruginosa CF isolates MICs for azithromycin ranged between 0.25 and 8 µg/ml and 12 isolates (41%) showed a MIC ≥512 µg/ml when measured in RPMI/FCS. In contrast, MICs were ≥256 µg/ml for all P. aeruginosa MDR isolates when tested in either SCFM or in conventional cation-adjusted Mueller Hinton Broth. High MIC values observed in CF adapted medium SCFM for both PAO1 and MDR P. aeruginosa CF isolates, as opposed to findings in RPMI, argue against routine azithromycin MIC testing of CF isolates.

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