The therapeutic potential of renin angiotensin aldosterone system (RAAS) in chronic pain: from preclinical studies to clinical trials

2016 ◽  
Vol 16 (3) ◽  
pp. 331-339 ◽  
Author(s):  
Flavien Bessaguet ◽  
Laurent Magy ◽  
Alexis Desmoulière ◽  
Claire Demiot
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Therapeutic Potential ◽  
Preclinical Studies ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin

The therapeutic potential of Nrf2 inducers in chronic pain: Evidence from preclinical studies

2021 ◽  
pp. 107846
Author(s):  
Ya-Qun Zhou ◽  
Wei Mei ◽  
Xue-Bi Tian ◽  
Yu-Ke Tian ◽  
Dai-Qiang Liu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Therapeutic Potential ◽  
Preclinical Studies

scholarly journals Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies

2017 ◽  
Vol 126 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Arman Jahangiri ◽  
Aaron T. Chin ◽  
Patrick M. Flanigan ◽  
Rebecca Chen ◽  
Krystof Bankiewicz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Tumor ◽  
Poor Prognosis ◽  
Therapeutic Potential ◽  
Alternative Methods ◽  
Preclinical Studies ◽  
Convection Enhanced Delivery ◽  
Therapeutic Measure ◽  
Toxicity Of Drugs ◽  
Preclinical And Clinical Studies

Glioblastoma is the most common malignant brain tumor, and it carries an extremely poor prognosis. Attempts to develop targeted therapies have been hindered because the blood-brain barrier prevents many drugs from reaching tumors cells. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. A number of alternative methods of delivery have been developed, one of which is convection-enhanced delivery (CED), the focus of this review. The authors describe CED as a therapeutic measure and review preclinical studies and the most prominent clinical trials of CED in the treatment of glioblastoma. The utilization of this technique for the delivery of a variety of agents is covered, and its shortcomings and challenges are discussed in detail.

scholarly journals Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials

2021 ◽  
Vol 8 ◽  
Author(s):  
Frank Lizaraso-Soto ◽  
Eduardo Gutiérrez-Abejón ◽  
Juan Bustamante-Munguira ◽  
Débora Martín-García ◽  
María Montserrat Chimeno ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Serum Potassium ◽  
Resistant Hypertension ◽  
Normal Serum ◽  
Sodium Polystyrene Sulfonate ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Optimal Dosing ◽  
Meta Analyses

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5–5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8–25.2 g/day (SUCRA = 0.94) and patiromer 8.4–16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

scholarly journals HGF/c-MET: A Promising Therapeutic Target in the Digestive System Cancers

2018 ◽  
Vol 19 (11) ◽  
pp. 3295 ◽  
Author(s):  
Hongli Zhang ◽  
Qingqing Feng ◽  
Wei-Dong Chen ◽  
Yan-Dong Wang
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Digestive System ◽  
Therapeutic Potential ◽  
Signaling Networks ◽  
Preclinical Studies ◽  
Current Review ◽  
Promising Therapeutic Target ◽  
Signaling Inhibitors ◽  
Mirna Therapeutics

The HGF/c-MET pathway is active in the development of digestive system cancers, indicating that inhibition of HGF/c-MET signaling may have therapeutic potential. Various HGF/c-MET signaling inhibitors, mainly c-MET inhibitors, have been tested in clinical trials. The observed efficacy and adverse events of some c-MET inhibitors were not very suitable for treating digestive system cancers. The development of new HGF/c-MET inhibitors in preclinical studies may bring promising treatments and synergistic combination (traditional anticancer drugs and c-MET inhibitors) strategies provided anacceptable safety and tolerability. Insights into miRNA biology and miRNA therapeutics have made miRNAs attractive tools to inhibit HGF/c-MET signaling. Recent reports show that several microRNAs participate in inhibiting HGF/c-MET signaling networks through antagonizing c-MET or HGF in digestive system cancers, and the miRNAs-HGF/c-MET axis plays crucial and novel roles for cancer treatment. In the current review, we will discuss recent findings about inhibitors of HGF/c-MET signaling in treating digestive system cancers, and how miRNAs regulate digestive system cancers via mediating HGF/c-MET pathway.

scholarly journals Use of Renin–Angiotensin–Aldosterone System Inhibitors in Older Patients with Heart Failure and Reduced Ejection Fraction

2019 ◽  
Vol 5 (2) ◽  
pp. 70-73 ◽  
Author(s):  
Davide Stolfo ◽  
Gianluigi Savarese
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Ejection Fraction ◽  
Older Patients ◽  
Randomised Clinical Trials ◽  
World Population ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction ◽  
Raas Inhibitors

Patients enrolled in randomised clinical trials may not be representative of the real-world population of people with heart failure (HF). Older patients are frequently excluded and this limits the strength of evidence which supports the use of specific HF treatments in this patient group. Lack of evidence together with fear of adverse effects, drug interactions and lower tolerance may lead to the undertreatment of older patients and a less favourable outcome. Renin–angiotensin–aldosterone system (RAAS) inhibitors are the cornerstone of treatment for patients with HF with reduced ejection fraction (HFrEF), but despite the class I recommendation for all patients regardless of age in the guidelines, there are signs that RAAS inhibitors are underused among older patients. Large registry- based studies suggest that RAAS inhibitors may be at least as effective in older patients as younger ones, but these findings need to be confirmed by randomised clinical trials.

scholarly journals Therapeutic Potential of Human Stem Cell Implantation in Alzheimer’s Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 10151
Author(s):  
Hau Jun Chan ◽  
Yanshree ◽  
Jaydeep Roy ◽  
George Lim Tipoe ◽  
Man-Lung Fung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Morris Water Maze Test ◽  
Preclinical Studies

Alzheimer’s disease (AD) is a progressive debilitating neurodegenerative disease and the most common form of dementia in the older population. At present, there is no definitive effective treatment for AD. Therefore, researchers are now looking at stem cell therapy as a possible treatment for AD, but whether stem cells are safe and effective in humans is still not clear. In this narrative review, we discuss both preclinical studies and clinical trials on the therapeutic potential of human stem cells in AD. Preclinical studies have successfully differentiated stem cells into neurons in vitro, indicating the potential viability of stem cell therapy in neurodegenerative diseases. Preclinical studies have also shown that stem cell therapy is safe and effective in improving cognitive performance in animal models, as demonstrated in the Morris water maze test and novel object recognition test. Although few clinical trials have been completed and many trials are still in phase I and II, the initial results confirm the outcomes of the preclinical studies. However, limitations like rejection, tumorigenicity, and ethical issues are still barriers to the advancement of stem cell therapy. In conclusion, the use of stem cells in the treatment of AD shows promise in terms of effectiveness and safety.

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