scholarly journals Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Emanuel J. Novais ◽  
Victoria A. Tran ◽  
Shira N. Johnston ◽  
Kayla R. Darris ◽  
Alex J. Roupas ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Chronic Back Pain ◽  
The Elderly ◽  
Term Treatment ◽  
Specific Effects ◽  
Long Term Treatment ◽  
Age Dependent

AbstractIntervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, p19ARF, and SASP molecules IL-6 and MMP13. Treatment also preserves cell viability, phenotype, and matrix content. Although transcriptomic analysis shows disc compartment-specific effects of the treatment, cell death and cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide an attractive strategy to mitigating age-dependent disc degeneration.

scholarly journals Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

2021 ◽  
Author(s):  
Makarand Risbud ◽  
Emanuel Novais ◽  
Victoria Tran ◽  
Kayla Darris ◽  
Alex Roupas ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Chronic Back Pain ◽  
The Elderly ◽  
Term Treatment ◽  
Specific Effects ◽  
Novel Approach ◽  
Long Term Treatment ◽  
Age Dependent

Abstract Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts showed lower incidences of degeneration, and the treatment resulted in a significant decrease in senescent markers p16INK4a, p19ARF, and SASP molecules IL-1β, and IL-6. Treated animals also showed preserved cell viability, phenotype, and matrix content. Although transcriptomic analysis showed disc compartment-specific effects of the treatment, cell death and cytokine response pathways were commonly modulated across tissue types. Results suggest that senolytics may provide a novel approach to mitigating age-dependent disc degeneration.

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.

Effect of long-term treatment with L-deprenyl on the age-dependent microanatomical changes in the rat hippocampus

1995 ◽  
Vol 79 (2-3) ◽  
pp. 169-185 ◽  
Author(s):  
Yong-Chun Zeng ◽  
Stefano Bongrani ◽  
Elena Bronzetti ◽  
Sandro Cadel ◽  
Alberto Ricci ◽  
...  
Keyword(s):  
Term Treatment ◽  
Rat Hippocampus ◽  
Long Term Treatment ◽  
Age Dependent

The Influence of Axial Compression on the Cellular and Mechanical Function of Spinal Tissues; Emphasis on The Nucleus Pulposus and Annulus Fibrosus

2021 ◽  
Author(s):  
John McMorran ◽  
Diane Gregory
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Axial Compression ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Chronic Back Pain ◽  
Physiological State ◽  
Movement Pattern ◽  
Mechanical Function

Abstract In light of the correlation between chronic back pain and intervertebral disc degeneration, this literature review seeks to illustrate the importance of the hydraulic response across the nucleus pulposus- annulus fibrosus interface, by synthesizing current information regarding injurious biomechanics of the spine, stemming from axial compression. Damage to vertebrae, endplates, the nucleus pulposus, and the annulus fibrosus, can all arise from axial compression, depending on the segment's posture, the manner in which it is loaded, and the physiological state of tissue. Therefore, this movement pattern was selected to illustrate the importance of the bracing effect of a pressurized nucleus pulposus on the annulus fibrosus, and how injuries interrupting support to the annulus fibrosus may contribute to intervertebral disc degeneration.

scholarly journals Efficacy of Citalopram in the prevention of recurrent depression in elderly patients: Placebo-controlled study of maintenance therapy

2002 ◽  
Vol 181 (1) ◽  
pp. 29-35 ◽  
Author(s):  
René Klysner ◽  
Jesper Bent-Hansen ◽  
Hanne L. Hansen ◽  
Marianne Lunde ◽  
Elisabeth Pleidrup ◽  
...  
Keyword(s):  
Major Depression ◽  
Elderly Patients ◽  
Rating Scale ◽  
The Elderly ◽  
Term Treatment ◽  
Fixed Dose ◽  
Controlled Study ◽  
Recurrence Time ◽  
Long Term Treatment

BackgroundThe highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment.AimsTo compare the prophylactic efficacy of citalopram and placebo in elderly patients; to evaluate long-term tolerability of citalopram.MethodOut-patients, ⩾65 years, with unipolar major depression (DSM – IV: 296.2 x or 296.3 x) and Montgomery – Åsberg Depression Rating Scale score ⩾22 were treated with citalopram 20–40 mg for 8 weeks. Responders continued on their final fixed dose of citalopram for 16 weeks before randomisation to double-blind treatment with citalopram or placebo for at least 48 weeks.ResultsNineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence. Time to recurrence was significantly different between citalopram— and placebo-patients, in favour of citalopram (log-rank test, P < 0.0001). Long-term treatment was well tolerated.ConclusionsLong-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated.

scholarly journals Newer v. older antidepressants in long-term pharmacotherapy: Revisiting… Prevention of relapse and recurrence of depression

2005 ◽  
Vol 11 (3) ◽  
pp. 184-194 ◽  
Author(s):  
J. Guy Edwards
Keyword(s):  
Drug Acquisition ◽  
Term Treatment ◽  
First Line ◽  
Specific Effects ◽  
Drug Choice ◽  
Long Term Treatment ◽  
Acquisition Costs ◽  
Prevention Of Relapse ◽  
First Line Treatment

There is much evidence from clinical trials that antidepressants help prevent relapse and recurrence of major depression. However, this is unlikely to hold true for all patients with depression, particularly those treated in primary care. Individual antidepressants are equally efficacious, so choice (as first-line treatment in general or for individual patients) is largely determined by differences in side-effects, even though many of these disappear during long-term treatment, owing to adaptation. Specific effects that are considered in choosing a drug include those on cognition, psychomotor performance and sexual function; drug interactions, lethality in overdose and the potential for teratogenicity are also considered. There are insufficient entirely objective and generally accepted data on pharmaco-economics to allow for confident recommendations on drug choice for long-term treatment. Drug acquisition costs must be considered by those with restricted budgets, and especially patients in developing countries where difference in cost between newer and older drugs can be translated into more food for a hungry family.

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