scholarly journals In vitro and in vivo evaluation of the antihypertensive drug atenolol in cultured human lymphocytes: effects of long-term therapy

Mutagenesis ◽  
2000 ◽  
Vol 15 (3) ◽  
pp. 195-202 ◽  
Author(s):  
M. Telez
Keyword(s):  
Antihypertensive Drug ◽  
Human Lymphocytes ◽  
Term Therapy ◽  
In Vivo Evaluation ◽  
Long Term Therapy

Long-term imatinib therapy promotes bone formation in CML patients

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2538-2547 ◽  
Author(s):  
Stephen Fitter ◽  
Andrea L. Dewar ◽  
Panagiota Kostakis ◽  
L. Bik To ◽  
Timothy P. Hughes ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Imatinib Therapy ◽  
Term Therapy ◽  
Bone Homeostasis ◽  
Bone Biopsies ◽  
Long Term Therapy

Imatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting that long-term therapy may alter bone homeostasis. To investigate this question, we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken from chronic myeloid leukemia (CML) patients at diagnosis and again after 2 to 4 years of imatinib therapy. Half the patients (8 of 17) showed a substantive increase in TBV (> 2-fold), after imatinib therapy, with the TBV in the posttreatment biopsy typically surpassing the normal upper limit for the patient's age group. Imatinib-treated patients exhibited reduced serum calcium and phosphate levels with hypophosphatemia evident in 53% (9 of 17) of patients. In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic gene expression and mineralized-matrix production by inhibiting PDGF receptor function. In PDGF-stimulated cultures, imatinib dose-dependently inhibited activation of Akt and Crk-L. Using pharmacologic inhibitors, inhibition of PI3-kinase/Akt activation promoted mineral formation, suggesting a possible molecular mechanism for the imatinib-mediated increase in TBV in vivo. Further investigation is required to determine whether the increase in TBV associated with imatinib therapy may represent a novel therapeutic avenue for the treatment of diseases that are characterized by generalized bone loss.

INFLUENCE OF CHLOROPHENOXYISOBUTYRATE (CPIB) ON THYROID PARAMETERS

1969 ◽  
Vol 60 (2) ◽  
pp. 294-302 ◽  
Author(s):  
J. Mølholm Hansen
Keyword(s):  
Free Thyroxine ◽  
Term Therapy ◽  
Low Doses ◽  
Testosterone Metabolism ◽  
Pre Treatment ◽  
Long Term Therapy ◽  
Higher Doses

ABSTRACT Chlorophenoxyisobutyrate (CPIB) added to serum in vitro increases the quantity of dialysable thyroxine. The same effect can be obtained in vivo following large doses of the preparation. After low doses, increase in serum proteinbound iodine (PBI) is observed and with higher doses this increase is not observed, probably because of the thyroxine-displacing effect. Free thyroxine increases in practically all patients investigated. In long-term treated patients the alterations in dialysable thyroxine, serum proteinbound iodine and free thyroxine are transient; pre-treatment values being regained in the course of ½–4 months. 131I uptake in the thyroid gland is influenced irregularly and transiently possibly via inhibition of the thyrotrophin production in the hypophysis. The effect of CPIB on serum cholesterol appears, in long-term therapy, to be completely independent of the effect on these thyroid parameters. This observation is also supported by the fact that the 14C-testosterone metabolism is normal in patients receiving long-term therapy.

Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells

2001 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Samia Ragheb ◽  
Sarah Abramczyk ◽  
Deena Lisak ◽  
Robert Lisak
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Glatiramer Acetate ◽  
Mechanisms Of Action ◽  
Term Therapy ◽  
In Vitro Proliferation ◽  
Long Term Therapy

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-b therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207

2021 ◽  
Vol 26 (3) ◽  
pp. 349-361
Author(s):  
Napoleon-Nikolaos Vrettos ◽  
Peng Wang ◽  
Yan Zhou ◽  
Clive J. Roberts ◽  
Jinyi Xu ◽  
...  
Keyword(s):  
Sustained Release ◽  
Antihypertensive Drug ◽  
The Novel ◽  
In Vivo Evaluation

Effect of long-term therapy with an oral contraceptive on some aspects of hepatic lipid metabolism in vitro

1975 ◽  
Vol 24 (17) ◽  
pp. 1583-1588 ◽  
Author(s):  
Ira Weinstein ◽  
Richard Belitsky ◽  
Susan Seedman ◽  
Melvin J. Fregly ◽  
Terry N. Thrasher
Keyword(s):  
Lipid Metabolism ◽  
Oral Contraceptive ◽  
Term Therapy ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Long Term Therapy

scholarly journals Long-Term Azithromycin Therapy in Cystic Fibrosis Patients: A Study on Drug Levels and Sputum Properties

2004 ◽  
Vol 11 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Ulrich Baumann ◽  
Malcolm King ◽  
Ernst M App ◽  
Shusheng Tai ◽  
Armin König ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Low Dose ◽  
Term Therapy ◽  
High Dose ◽  
Drug Levels ◽  
Diffuse Panbronchiolitis ◽  
Underlying Mechanisms

BACKGROUND:Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro.OBJECTIVES:Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo.METHODS:In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology.RESULTS:AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 µg/mL (0.6 to 79.3 µg/mL, interquartiles 1.4 to 33.4 µg/mL) and 0.5 µg/mL (range less than 0.1 [below detection level] to 5.2 µg/mL, interquartiles 0.2 to 1.4 µg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one.CONCLUSIONS:The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.

scholarly journals TMOD-32. GL261 LUCIFERASE-EXPRESSING CELLS ELICIT AN ANTI-TUMOR IMMUNE RESPONSE: AN EVALUATION OF MURINE GLIOMA MODELS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi269-vi270
Author(s):  
Victoria Sanchez ◽  
John Lynes ◽  
Stuart Walbridge ◽  
Xiang Wang ◽  
Nancy Edwards ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Tumor Growth ◽  
Median Survival ◽  
In Vivo Evaluation ◽  
Kaplan Meier ◽  
Long Term Survivors

Abstract Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. Intracranially injected GL261 cells are widely used as an immunocompetent animal model of glioma, but it is common practice to transfect these with luciferase to facilitate tumor monitoring during treatment. Our group has previously shown that the luciferase-expressing GL261 Red-FLuc cells create an inflammatory response when implanted intracranially. Now, we additionally explore the inflammatory response of GL261-Luc2 cells and demonstrate a similar host immune response occurs with this model as well. In our in vivo evaluation, C57BL/6 mice underwent stereotaxic, intracranial implantation with GL261, GL261 Red-FLuc or GL261-Luc2 cells at doses of 5x104cells/5mL or 3x105cells/5uL.MRIs were performed to monitor relative tumor growth. To assess intrinsic differences between cell lines, in vitro cytokine profiles were evaluated by proteome microarray. Kaplan-Meier survival analyses demonstrated median survival for mice implanted with GL261 cells at 5x104cells was 18 to 21 days. The GL261-Red FLuc implanted mice cells did not reach median survival at either tumor dose with greater than 60% of mice termed long-term survivors. Finally, mice injected with GL261-Luc2 cells at 3x105cells reached median survival at 23 days, but median survival was significantly prolonged for mice implanted with GL261-Luc2 at a dose of 5x104cells (37 days, with 40% becoming long-term survivors) compared to GL261 implanted mice. MRIs reveal differences in tumor growth that correspond with the differences in median survival between groups. In addition, proteomic analyses revealed significantly elevated inflammatory cytokines such as IFN-gamma, IL-7 and TNF-alpha in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Further immune characterization is ongoing. Our data suggests that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators which stimulate the tumoricidal function of immune cells in the tumor microenvironment.

Sign in / Sign up

Export Citation Format

Share Document