ACE2 and RAAS: Therapeutic intervention point for COVID-19

COVID-19 has caused widespread mortality and morbidity and significant economic disruption. Several potential therapeutic and/ or preventive approaches to address the pandemic are being worked out, a few effective vaccines are under clinical trials and few vaccines has been approved but still the expected result has not been achieved. Some Spiritual Leader claims it to be natural process and can be protected by chant of Mantra 'Pujya Anakarananta Nirakar niranjan shivajyoti mahamanav pita'. Renin-Angiotensin-Aldosterone System (RAAS) is no more a mere research area in cardio-pulmonary and renal physiology alone but has gained focus as an infection and therapeutic point for COVID-19. This article discusses about ACE2 receptor as a centre point of infection of SARS-CoV-2 and also suggests it as the therapeutic intervention point for COVID-19.

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The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine

Molecules ◽

10.3390/molecules26113081 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3081

Author(s):

Mohammad Amin Atazadegan ◽

Mohammad Bagherniya ◽

Gholamreza Askari ◽

Aida Tasbandi ◽

Amirhossein Sahebkar

Keyword(s):

Clinical Trials ◽

Medicinal Plants ◽

Vascular Endothelium ◽

Animal Studies ◽

Natural Compounds ◽

Herbal Products ◽

Mortality And Morbidity ◽

Beneficial Effects ◽

Serum Homocysteine ◽

Prevention And Treatment

Background: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. Results: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.

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CHAPTER 9. IKKβ as a Therapeutic Intervention Point for Diseases Related to Inflammation

RSC Drug Discovery - Anti-Inflammatory Drug Discovery ◽

10.1039/9781849735346-00255 ◽

2012 ◽

pp. 255-296 ◽

Cited By ~ 6

Author(s):

ERICK R. R. YOUNG

Keyword(s):

Therapeutic Intervention ◽

Intervention Point

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Individual Meaning-Centered Psychotherapy for Advanced Cancer Patients

10.1093/med/9780199837229.003.0003 ◽

2017 ◽

Author(s):

William Breitbart ◽

Wendy G. Lichtenthal ◽

Allison J. Applebaum ◽

Melissa Masterson

Keyword(s):

Clinical Trials ◽

End Of Life ◽

Cancer Patients ◽

Advanced Cancer ◽

Therapeutic Intervention ◽

Well Being ◽

Existential Psychology ◽

Advanced Cancer Patients ◽

Spiritual Well Being ◽

Existential Concerns

Among the advanced cancer population, existential concerns are major issues that promote significant distress. For patients who are facing death, meaning and the preservation of meaning are not only clinically and existentially important but also central concepts to a therapeutic intervention. Based on Viktor Frankl’s logotherapy and the principles of existential psychology and philosophy, “meaning-centered psychotherapy” was developed to help patients with advanced cancer sustain or enhance a sense of meaning, peace, and purpose in their lives. This chapter provides an overview of work developing and testing individual meaning-centered psychotherapy (IMCP). It provides an overview of the session content in the IMCP intervention. It also presents findings from clinical trials, which support the efficacy of IMCP as an intervention to increase a sense of meaning, spiritual well-being, and hope while decreasing end-of-life despair. Furthermore, it presents difficult scenarios that may arise when delivering IMCP for clinicians interested in this work.

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Renin-angiotensin-aldosterone system blockers and cardiovascular outcomes: A meta-analysis of randomized clinical trials

Turk Kardiyoloji Dernegi Arsivi-Archives of the Turkish Society of Cardiology ◽

10.5543/tkda.2016.78006 ◽

2016 ◽

Cited By ~ 1

Author(s):

Pınar Kızılırmak

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin

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

Frontiers in Medicine ◽

10.3389/fmed.2021.686729 ◽

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.

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The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense

Military Medicine ◽

10.1093/milmed/usz174 ◽

2019 ◽

Vol 184 (Supplement_2) ◽

pp. 44-50 ◽

Cited By ~ 2

Author(s):

Christian Coles ◽

Eugene V Millar ◽

Timothy Burgess ◽

Martin G Ottolini

Keyword(s):

Clinical Trials ◽

Influenza Vaccine ◽

Clinical Research ◽

Military Personnel ◽

Pandemic Influenza ◽

Respiratory Infections ◽

Respiratory Viruses ◽

Research Area ◽

Acute Respiratory Infections ◽

Live Attenuated Influenza Vaccine

Abstract Introduction Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. Methods The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. Results The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. Conclusions The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.

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Nanomedicinal Strategies as Emerging Therapeutic Avenues for the Management Cerebral Ischemia

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666201102100330 ◽

2020 ◽

Vol 19 ◽

Author(s):

Saman Fatima ◽

Syed Naved Quadri ◽

Shaheda Parveen ◽

Sarwar Beg ◽

Md Abul Barkat ◽

...

Keyword(s):

Clinical Trials ◽

Ischemic Stroke ◽

Cerebral Ischemia ◽

Health Risks ◽

Global Scale ◽

Preclinical Studies ◽

Neuronal Regeneration ◽

Stroke Patients ◽

Mortality And Morbidity ◽

The Brain

: Amongst the various diseases on global scale, the second leading cause of mortality and morbidity is ischemic stroke due to the unavailability of an effective therapy. With the growing occurrence and its related health risks along with the absence of effective therapeutics, the ischemic stroke demands the continued and intensive research to explore the effective and safe therapeutics. These therapies may positively affect the numerous pathways associated with neuroprotection thus, extending the advantages to a larger population of stroke patients. Several preclinical studies employing neuroprotectants have shown promising outcomes, but failed in clinical trials either because of the lack of safety or efficacy. The blood brain barrier (BBB) restricts delivery of various potent neuroprotectants to the specific areas of the brain. The application of nanovehicles for delivery of drugs in the brain however, could revolutionize the treatment of ischemic stroke. These nanovehicles loaded with the drug could readily traverse the BBB via carrier, receptor and adsorptive-mediated endocytosis into the brain without compromising the integrity of BBB. Recent advances in neuronanotherapeutics have resulted in the improved neuronal regeneration and recovery after the ischemic stroke. In this review, we have attempted to discuss unexploited neuronanotherapeutics potentials to treat and manage ischemic stroke.

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