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

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 Remdesivir for COVID-19: A review of pharmacology, mechanism of action, in-vitro activity and clinical use based on available case studies

2020 ◽  
Vol 10 (4-s) ◽  
pp. 264-270
Author(s):  
Kirtikumar Chandulal Badgujar ◽  
Avadheshkumar H. Ram ◽  
Rahoul Zanznay ◽  
Hemant Kadam ◽  
Vivek C. Badgujar
Keyword(s):  
Adverse Events ◽  
Case Studies ◽  
Mechanism Of Action ◽  
Clinical Results ◽  
Clinical Use ◽  
Literature Study ◽  
Ongoing Research ◽  
In Vitro Inhibition

Remdesivir as a drug attracted a very serious consideration of whole Globe in treatment of the pandemic disease COVID-19. More recently published in-vitro inhibition activity and in-vivo case studies were showing promising clinical results and outcome of effective inhibition of SARS-CoV-2 virus by the use of remdesivir. However at the same time, use of the remdesivir showed substantial detrimental adverse events in patients which needs a special attention during treatment course of COVID-19. Thus, the use of remdesivir in treatment of COVID-19 is having current international interest although some more clinical evidences are still necessary in order to understand the actual efficiency and mechanism of remdesivir against COVID-19. In view of this, the present literature study spotlight the current ongoing research related to use of remdesivir which includes (i) pharmacology of remdesivir, (ii) mechanism of action of remdesivir (iii) in-vitro inhibition of remdesivir against SARS-CoV-2 virus, (iv) in-vivo analysis and clinical use of remdesivir against COVID-19. Finally possible adverse events (of use of remdesivir) are also discussed considering the pharmacovigilance concern. Keywords: Remdesivir; COVID-19; Remdesivir side effects, Remdesivir pharmacology; SARS-CoV-2 virus

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 Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2272 ◽  
Author(s):  
Salehi ◽  
Sharopov ◽  
Boyunegmez Tumer ◽  
Ozleyen ◽  
Rodríguez‐Pérez ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Present Review ◽  
Current Evidence ◽  
Over The Counter ◽  
Antimicrobial Spectrum ◽  
Cochrane Database ◽  
Food Applications ◽  
Fatal Adverse Events

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo.

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.

Effects of TSH and calcitriol on bone metabolism: in vivo and in vitro study

2014 ◽  
Author(s):  
Ivo Dumic-Cule ◽  
Dunja Rogic ◽  
Damir Jezek ◽  
Lovorka Grgurevic ◽  
Slobodan Vukicevic
Keyword(s):  
Bone Metabolism ◽  
In Vitro Study ◽  
Vitro Study

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 64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elodie A. Pérès ◽  
Jérôme Toutain ◽  
Louis-Paul Paty ◽  
Didier Divoux ◽  
Méziane Ibazizène ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Vitro Study ◽  
Tumor Location ◽  
Preclinical Study ◽  
Significant Rise ◽  
Lower Oxygen ◽  
Cu Complexes ◽  
Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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