scholarly journals Experimental Drugs for Chemotherapy- and Cancer-Related Anemia

2021 ◽  
Vol Volume 13 ◽  
pp. 593-611
Author(s):  
Clelia Madeddu ◽  
Manuela Neri ◽  
Elisabetta Sanna ◽  
Sara Oppi ◽  
Antonio Macciò
Keyword(s):  
Experimental Drugs ◽  
Cancer Related Anemia

Fast and Reproducible Vascular Neointima Formation in the Hamster Carotid Artery: Effects of Trapidil and Captopril

1995 ◽  
Vol 74 (06) ◽  
pp. 1591-1596 ◽  
Author(s):  
H Matsuno ◽  
J M Stassen ◽  
M F Hoylaerts ◽  
J Vermylen ◽  
H Deckmyn
Keyword(s):  
Carotid Artery ◽  
Enzyme Inhibitor ◽  
Neointima Formation ◽  
Proliferating Cells ◽  
Dental Cement ◽  
Proliferation Indices ◽  
Experimental Drugs ◽  
The Media ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryNeointima formation was induced in the hamster carotid artery by mechanical intraluminal injury with a catheter covered with roughened dental cement. Neointimal thickening occurred as early as 7 days after denudation and further increased during the next 1 to 2 weeks. Proliferation indices of smooth muscle cells (SMCs) showed the highest proportion of proliferating cells in the media and neointima respectively 1 and 5 days after the vascular injury. Transmission and scanning electron microscopy of damaged carotid artery sections as well as immuno-histochemical stainings of von Willebrand factor (vWF) confirmed that reendothelialization was progressive and already complete on day 14, at which time the neointima formation was almost complete.In order to pharmacologically characterize this model further, the effects on neointima formation of trapidil (triazolopyrimidine), a platelet-derived growth factor (PDGF) antagonist, and captopril, an angiotensin converting enzyme inhibitor, were investigated. Trapidil administered orally twice daily at total doses of 25, 50 and 100 mg/kg/day, started 3 days prior to infliction of injury and up to 7 or 14 days after the catheterization, significantly reduced neointima formation. Captopril administered orally three times daily at a total dose of 100 mg/kg/day, equally reduced neointima formation, with 100 mg/kg/day trapidil being more effective than 100 mg/kg/day captopril 7 days after injury. When the treatment by either one of these drugs was arrested on day 7, neointima formation resumed quickly.The hamster appears to be a small, reproducible and fast model for the study of SMC proliferation, requiring only relatively small amounts of experimental drugs. The model furthermore is sensitive to substances known to reduce neointima formation in other animal models.

Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

2015 ◽  
Vol 24 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Federica Furfaro ◽  
Cristina Bezzio ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Roberto De Franchis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immunosuppressive Agents ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Proinflammatory Mediators ◽  
Experimental Drugs ◽  
New Treatments ◽  
Aggressive Clinical Course ◽  
Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

scholarly journals Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

2020 ◽  
Vol 75 (12) ◽  
pp. 3417-3424 ◽  
Author(s):  
Catherine Hodge ◽  
Fiona Marra ◽  
Catia Marzolini ◽  
Alison Boyle ◽  
Sara Gibbons ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Herbal Medicines ◽  
Qt Prolongation ◽  
Critically Ill Patient ◽  
Experimental Drugs ◽  
Mesh Terms ◽  
Experimental Therapies ◽  
Clinically Significant ◽  
Novel Coronavirus

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

scholarly journals Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 482
Author(s):  
Valentina Natalucci ◽  
Edy Virgili ◽  
Federica Calcagnoli ◽  
Giacomo Valli ◽  
Deborah Agostini ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Complex Problem ◽  
Low Grade ◽  
Inflammatory Status ◽  
Line Of Therapy ◽  
Cancer Related Anemia ◽  
Low Grade Inflammation

Cancer is often accompanied by worsening of the patient’s iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

scholarly journals Thiazole Ring—A Biologically Active Scaffold

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3166
Author(s):  
Anthi Petrou ◽  
Maria Fesatidou ◽  
Athina Geronikaki
Keyword(s):  
Recent Literature ◽  
Biological Activities ◽  
Literature Survey ◽  
Biologically Active ◽  
Thiazole Ring ◽  
Peer Reviews ◽  
Experimental Drugs ◽  
Wide Range ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.

Testing Meldonium: Assessing Soviet pragmatic alternatives to the randomized controlled trial

2021 ◽  
pp. 174077452110085
Author(s):  
Anastasiya Chirkova ◽  
Alexander Petrenko ◽  
Pavel Vasilyev
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trial ◽  
Soviet Union ◽  
Drug Testing ◽  
Controlled Trial ◽  
Randomized Controlled ◽  
Experimental Drugs ◽  
The Soviet Union ◽  
Experimental Drug ◽  
Second World

Background/aims Current research largely tends to ignore the drug-testing model that was developed in the “Second World” as an explicit alternative to the randomized controlled trial. This system can be described as “socialist pharmapolitics,” accounting for the specific features of state socialism that influenced the development and testing of experimental drugs. The clinical trials model employed in the “Second World” was heavily influenced by the Soviet Union, which was by far the most influential player in the socialist bloc during the Cold War. Based on extensive archival research, this article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It accounts for the divergences between the official model prescribed by the Soviet authorities and the messy realities of healthcare practice. It further outlines different factors that ultimately shaped how clinical trials were organized in Soviet institutions “on the ground.” Accordingly, this article presents a “real-life” history of “socialist pharmapolitics” and outlines the problems that this system faced in practice. Methods Archival research was conducted at the Russian State Archive of Scientific and Technical Documentation in Moscow. Archival files include scientific, technical, and registration documentation such as biochemical, pharmacological, and clinical descriptions of the experimental drug Meldonium, letters between various hospitals, research institutes and the Soviet regulatory body, as well as 26 reports of completed clinical trials. Manual content analysis was used for the interpretation of results. Results This article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It demonstrates some key differences from the randomized controlled trial model. This article also highlights some of the discrepancies between the model that was officially prescribed by the Soviet authorities and the realities of experimental drug testing in the Soviet Union in the late 1980s and early 1990s. In particular, it notes some elements of randomization, double-blinding, and the use of placebo that were present in Meldonium trials despite being formally denounced by Soviet bioethics. Conclusion The Soviet model for testing experimental drugs differed from the Western one substantially in a number of respects. This difference was not only proclaimed officially by the Soviet authorities, but was for the most part enforced in clinical trials in practice. At the same time, our research demonstrates that there were important differences between the official model and the clinical realities on the ground.

scholarly journals Polypharmacologicalin SilicoBioactivity Profiling and Experimental Validation Uncovers Sedative-Hypnotic Effects of Approved and Experimental Drugs in Rat

2017 ◽  
Vol 12 (6) ◽  
pp. 1593-1602 ◽  
Author(s):  
Georgios Drakakis ◽  
Keith A. Wafford ◽  
Suzanne C. Brewerton ◽  
Michael J. Bodkin ◽  
David A. Evans ◽  
...  
Keyword(s):  
Experimental Validation ◽  
Experimental Drugs

COVID-19: Are Experimental Drugs Cure or Ill?

2021 ◽  
Vol 16 ◽  
Author(s):  
Bensu Karahalil ◽  
Aylin Elkama
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Adverse Effects ◽  
Antiviral Treatment ◽  
Herd Immunity ◽  
Mortality Rates ◽  
Death Rates ◽  
Experimental Drugs ◽  
Combined Use ◽  
The World

Background: Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or “are there any contributions of the frequently used drugs in this period to these deaths?” Surely herd immunity plays a major role and has the contribution in the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made to the dosage and combined use of frequently used drugs. Objective: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in both Turkey and all over the world will be summarized. Conclusion: Among these drugs favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

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