scholarly journals COVID-19 and Cannabidiol: Results from a Rapid Review

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Holst M ◽  
◽  
Nowak D ◽  
Hoch E ◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Animal Studies ◽  
Human Study ◽  
Rapid Review ◽  
Trial Outcomes ◽  
Potential Benefits ◽  
Clinical Trials Registry

Background: SARS-CoV2 has caused over 57 million infections and over 1.3 million deaths within 11 months globally (WHO). Internationally, there is an emerging debate about potential benefits of Cannabidiol (CBD) as treatment of COVID-19. Objective: To assess the beneficial and adverse effects of CBD in the treatment of inflammation from the literature. Methods: We systematically searched Cochrane rCOVID-19 study register, CENTRAL (PubMed, Embase, CINAHL, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform) for studies testing CBD as inflammation intervention. All types of studies and populations were considered. All pre-clinical, clinical, and pharmacological outcomes were of interest. Results: Of 18 papers found, 9 were included: Five in vivo animal studies, 3 in vitro studies on human tissues and 1 ongoing randomized clinical trial. Outcomes in 4 in vivo animal studies and 3 human tissue studies were immune response markers, which decreased. In 1 in vivo study the outcome of monocytes was enhanced. One human study is ongoing. There was no information on adverse effects or drug-interaction. Conclusion: There is not enough evidence to support or refute CBD as a repurpose drug to treat inflammation and other symptoms of COVID-19. Clinical trials are needed to test its efficacy and adverse effects.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

Rifabutin: A Review with Emphasis on its Role in the Prevention of Disseminated Mycobacterium Avium Complex Infection

1994 ◽  
Vol 28 (11) ◽  
pp. 1250-1254 ◽  
Author(s):  
Daniel S. Maddix ◽  
Kimberly B. Tallian ◽  
Paul S. Mead
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Aids Patients ◽  
Double Blind ◽  
Medline Search ◽  
Cd4 Lymphocyte

OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75–50/mm3.

scholarly journals A cautionary perspective regarding the isolation and serial propagation of SARS-CoV-2 in Vero cells

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Simon G. P. Funnell ◽  
Babak Afrough ◽  
John James Baczenas ◽  
Neil Berry ◽  
Kevin R. Bewley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Genetic Variants ◽  
Animal Studies ◽  
Vero Cells ◽  
In Vitro Assays ◽  
Critical Research ◽  
Furin Cleavage ◽  
Furin Cleavage Site

AbstractAn array of SARS-CoV-2 virus variants have been isolated, propagated and used in in vitro assays, in vivo animal studies and human clinical trials. Observations of working stocks of SARS-CoV-2 suggest that sequential propagation in Vero cells leads to critical changes in the region of the furin cleavage site, which significantly reduce the value of the working stock for critical research studies. Serially propagating SARS-CoV-2 in Vero E6 cells leads to rapid increases in genetic variants while propagation in other cell lines (e.g. Vero/hSLAM) appears to mitigate this risk thereby improving the overall genetic stability of working stocks. From these observations, investigators are urged to monitor genetic variants carefully when propagating SARS-CoV-2 in Vero cells.

Atovaquone: A Review with Emphasis on its Role in the Treatment of Pneumocystis Carinii Pneumonia

1994 ◽  
Vol 10 (4) ◽  
pp. 151-155
Author(s):  
Daniel S. Maddix
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mechanism Of Action ◽  
Pneumocystis Carinii Pneumonia ◽  
Pneumocystis Carinii ◽  
Plasmodium Species ◽  
Double Blind ◽  
Medline Search

Objective: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of atovaquone. Data Sources: Pertinent literature published since 1988 was identified via a MEDLINE search. Published proceedings of selected conferences were also used. Study Selection: All basic science, microbiologic, and pharmacokinetic articles were evaluated. Since only limited data regarding atovaquone are available in the literature, all clinical trials involving the use of atovaquone in the treatment of Pneumocystis carinii pneumonia were reviewed. Data Synthesis: Atovaquone is an antiprotozoal agent that was recently approved for the treatment of mild to moderate P. carinii pneumonia (PCP) in patients who are intolerant of trimethoprim/sulfamethoxazole (TMP/SMX). The exact mechanism of action of atovaquone against P. carinii has not been determined. The drug has in vitro and in vivo activity against P. carinii, Toxoplasma gondii, and Plasmodium species. The bioavailability of oral atovaquone is highly variable. The drug must be administered with food to enhance absorption. In a double-blind comparative trial in AIDS patients with mild to moderate PCP, those who were treated with atovaquone had a significantly higher mortality rate than those treated with TMP/SMX. More patients who received TMP/SMX experienced adverse effects that resulted in discontinuation of therapy. Conclusions: Because of concerns of increased mortality in atovaquone recipients, the drug should be reserved for the treatment of mild to moderate PCP in patients who are unable to tolerate TMP/SMX and trimethoprim-dapsone.

scholarly journals Should azithromycin be used to treat COVID-19? A rapid review

BJGP Open ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. bjgpopen20X101094 ◽  
Author(s):  
Kome Gbinigie ◽  
Kerstin Frie
Keyword(s):  
Clinical Trials ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Rapid Review ◽  
Limited Evidence ◽  
Comparator Group ◽  
Novel Drugs ◽  
Super Infection

BackgroundThere are no established effective treatments for COVID-19. While novel drugs are being developed, azithromycin has been identified as a candidate treatment in the interim.AimTo review the evidence for the effectiveness and safety of azithromycin in treating COVID-19.Design & settingA rapid review of the literature was conducted.MethodElectronic searches were conducted on 16 April 2020 of PubMed, TRIP, EPPI COVID Living Map, MedRxiv, GoogleScholar, and Google. In vivo and in vitro studies were included assessing the safety and effectiveness of azithromycin for treatment of COVID-19, and/or the activity of azithromycin against SARS-CoV-2. In vivo studies needed to include a comparator group.ResultsThree studies were identified, two in vitro and one in vivo, which were suitable for inclusion. All three were published as pre-prints. The in vitro studies revealed conflicting results, with one finding anti-SARS-CoV-2 activity for azithromycin alone, while the other found activity against SARS-CoV-2 only when azithromycin was combined with hydroxychloroquine. A small trial of 36 patients, with high risk of bias, found superior viral clearance in patients with COVID-19 treated with azithromycin and hydroxychloroquine combined, compared with hydroxychloroquine alone.ConclusionThere is no evidence to support the use of azithromycin for the treatment of COVID-19 outside of the context of clinical trials, unless it is used to treat bacterial super-infection. There is extremely limited evidence of a possible synergy between azithromycin and hydroxychloroquine. The adverse events profile of azithromycin in the context of COVID-19 has not yet been established. Well-conducted clinical trials are urgently needed in this area.

scholarly journals Efficacy of riluzole in the treatment of spinal cord injury: a systematic review of the literature

2019 ◽  
Vol 46 (3) ◽  
pp. E6 ◽  
Author(s):  
Shanmukha Srinivas ◽  
Arvin R. Wali ◽  
Martin H. Pham
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Animal Studies ◽  
Pharmacological Intervention ◽  
Average Dose ◽  
Pubmed Database ◽  
Cord Injury

OBJECTIVERiluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.METHODSThe PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.RESULTSA total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.CONCLUSIONSSCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

scholarly journals Hydroxychloroquine for COVID-19: A review and a debate based on available clinical trials/case studies

2020 ◽  
Vol 10 (3) ◽  
pp. 304-311 ◽  
Author(s):  
Kirtikumar Chandulal Badgujar ◽  
Ashish B. Badgujar ◽  
Vikrant P. Patil ◽  
Dipak V. Dhangar
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Outcome ◽  
Case Studies ◽  
In Vitro Study ◽  
Present Review ◽  
Ongoing Research ◽  
The Public

Hydroxychloroquine (HCQ) as a drug grabbed serious attention of whole world in dealing with COVID-19 pandemic. Recently some in-vitro and in-vivo study showing possible inhibition of SARS-CoV-2 by use of HCQ. However at the same time, some case studies showing NO clinical benefit/ poor clinical outcome with substantial detrimental adverse effects by use of HCQ in treatment of coronavirus disease-2019. Thus, the HCQ use (in COVID-19 treatment) is of current international interest, although a consensus has not yet been reached. More evidences are still required to prove efficacy of HCQ against COVID-19. In view of this, the present review highlights the current ongoing research related to use of HCQ in treatment coronavirus disease-2019. The present review will discuss the possible anti-viral mechanism of HCQ, prophylaxis strategy and effect of HCQ against SARS-CoV-2 virus in-vitro study. Further this review also summarizes and debates all available clinical trials/ case studies of HCQ use against COVID-19 (with clinical outcome). Finally possible detrimental adverse effects are also discussed considering the public health and pharmacovigilance concern. Keywords: Potency of hydroxychloroquine; COVID-19; Coronavirus disease-2019; Clinical trials; SARS-CoV-2; Adverse effects of hydroxychloroquine; Pharmacovigilance concern

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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