toxic drugs
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Micromachines ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 45
Author(s):  
Mingyan Guo ◽  
Lukas Marek ◽  
Yixia Liang ◽  
Phei Er Saw

Chemotherapy has led to many undesirable side effects, as these are toxic drugs that are unable to differentiate between cancer and normal cells. Polyphenols (tea catechins) are an ideal option as alternative chemotherapeutics owing to their inherent anticancer properties, antioxidant properties and being naturally occurring compounds, are deemed safe for consumption. However, without proper administration, the bioavailability of these compounds is low and inefficient. Therefore, proper delivery of these phenolic compounds is vital for cancer therapy. Herein, we analyzed three potential solutions to creating nanoparticle drugs using naturally occurring phenolic compounds (piceatannol (PIC), epigallocatechin gallate hydrophilic (EGCG) and l-epicatechin (EPI)). By using a simple pi-pi stacking mechanism, we utilized boronated PEG (PEG-Br) as an anchor to efficiently load EPI, PIC and EGCG, respectively, to produce three effective phenolic compound-based nanoparticles, which could be delivered safely in systemic circulation, yet detach from its cargo intracellularly to exert its anticancer effect for effective cancer therapy.


Author(s):  
Юрий Александрович Губарев ◽  
Наталья Шамильевна Лебедева ◽  
Маргарита Олеговна Тонкушина ◽  
Илья Дмитриевич Гагарин ◽  
Алексей Яковлевич Голуб ◽  
...  

Актуальной проблемой в области адресной доставки лекарственных веществ являются аспекты, относящиеся к транспорту высокотоксичных препаратов, обладающих нежелательными побочными эффектами, в частности противоопухолевых. Были рассчитаны термодинамические параметры комплексообразования нанокластерного полиоксометаллата {MoFe}, перспективного в качестве средства адресной доставки лекарств, и широко применяемого в клинической практике цитостатика - доксорубицина. Взаимодействие доксорубицина с {Mo Fe} сопровождалось экзотермическим эффектом, что говорит об энергетически выгодном образовании комплекса. Кинетика процесса высвобождения доксорубицина из комплекса в буферном растворе с pH , соответствующим значению pH крови, была изучена методом люминесцентной спектроскопии. Были определены константы скорости процессов деструкции {Mo Fe} в комплексе, сопровождающейся высвобождением доксорубицина, и дальнейшего комплексообразования высвободившегося доксорубицина с продуктами распада {MoFe}. В будущем возможно управление скоростью высвобождения доксорубицина путем дополнительной стабилизации {Mo Fe}, например, путем его ассоциации с альбумином. Actual problem in the field of targeted drug delivery is transport of highly toxic drugs, with undesirable side effects, in particular antitumor medicine. The thermodynamic parameters of complexation between nanocluster polyoxometalate {MoFe}, promising as a means of targeted drug delivery, and a cytostatic agent - doxorubicin, widely used in clinical practice, were studied. The interaction of doxorubicin with {MoFe} was accompanied by an exothermic effect, which indicates an energetically favorable formation of the complex. The kinetics of the release of doxorubicin from the complex in a buffer solution with a pH corresponding to the pH value of blood was studied by fluorescence spectroscopy. The rate constants of destruction processes in the complex, accompanied by the release of doxorubicin, and further complexation of the released doxorubicin with decay products were determined. In the future, it is possible to slow down the release of doxorubicin by stabilizing the {MoFe}, for example, when it is associated with albumin.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4972-4972
Author(s):  
Claudia Monteiro ◽  
Cecília Gomes ◽  
Leticia Marani ◽  
Leandro Colli ◽  
Rodrigo T. Calado ◽  
...  

Abstract COVID-19 is an infectious disease caused by the virus SARS-CoV-2, which was first described at the end of 2019. Since then, it has affected a growing portion of the world's population because of its high transmissibility. Most patients are asymptomatic or present with mild symptoms, but approximately 5-10% of cases can develop more serious manifestations, such as severe acute respiratory syndrome, acute kidney injury, shock, myocardial injury and even death. These features seem to occur more commonly in patients with essential hypertension, diabetes mellitus, obesity and chronic pulmonary disease. However, there are few studies that clarify the natural history of the disease and its broad clinical spectrum owing to the fact that it is a new entity. Since individuals with malignancies tend to present some degree of immunological deficiency and are more prone to opportunistic infections, especially those being treated with immunosuppressive drugs, it is possible that this group has a higher incidence of COVID-19. The current recommendations of oncology specialists advise to postpone treatments and to use less toxic drugs when possible. However, we still do not know how much these measures will affect in cancer mortality. Also, the incidence of COVID-19 in this population remains undetermined. We do not know if infectious symptoms are a good parameter to motivate these therapeutic changes or if there is benefit to test asymptomatic patients. In this context, this research submitted 100 patients with hematological malignancies or solid tumors on chemotherapy at the Ribeirão Preto Medical School of the University of São Paulo's Hospital, asymptomatic for COVID-19, to RT PCR to determine the SARS-CoV-2 infection incidence in this population. Only two patients were diagnosed with COVID-19. Both had gastrointestinal cancer. One of them developed symptoms, but none presented severe manifestations. Both had their treatment postponed initially and reinitiated after the appropriate period of isolation. Hence, we believe that it's reasonable not to test every asymptomatic patient when the resource for that is scarce, prioritizing those at greater risk of infection and those more prone to severe outcomes as long as the appropriate preventive measures are being taken. Disclosures Calado: Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Instituto Butantan: Consultancy; Alexion Brasil: Consultancy; AA&MDS International Foundation: Research Funding; Novartis Brasil: Honoraria.


Author(s):  
Denise Lessa Aleixo ◽  
Mateus Joacir Benvenutti ◽  
Katiucha Rebeca Jennifer Lopes Lera ◽  
Larissa Ciupa ◽  
Fabiana Nabarro Ferraz ◽  
...  

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment.


2021 ◽  
Vol 9 (8) ◽  
pp. 1856-1860
Author(s):  
Mahtab Alam ◽  
Ajay Kumar ◽  
Santosh Kr. Vishvakarma

According to Ayurveda, prevention of disease and maintenance of health are more important than the treatment of disease. As given in Ayurvedic Samhitas, a poison is a substance that vitiates the normal functioning of dosha, dhatu, mala. Thousands of harmful toxins are present in our atmosphere (Air, water and earth) that are ingested by human beings on daily basis. As described in our Ayurvedic Samhitas, Dushi Visha is an intake of toxic drugs which is less potent (Denatured) and remains in a dormant state within the body for years together without causing any major harm to the body. As we see in today's era workers working in the lead industry like enamel workers, glass blowers, printing works have typical chronic lead poisoning symptoms such as constipation, tremors, menstrual disarrangements etc. Due to chronic exposure to lead which accumulates in the body and produces its ill effect like Dushi Visha. Arsenic, copper, mercury chronic occupational poisoning also happened due to long exposure of poi- son working in the respective industry. In agriculture, chronic exposure to OPP, OCP, weed killers like parquet, chlorophenoxy acetates, chlorates used to prevent infection in plants, being sprayed by farmers on daily basis, leads to symptoms like dysphasia, oropharyngeal ulcers, coughing, pain in the abdomen, etc. These symptoms resemble Dushi Visha like symptoms. From this article, we may correlate the symptoms of Dushi Visha with the dermatolog- ical manifestation of chronic occupational poisoning and agricultural field exposure to weed killers, which may behelpful to understand the concept of Dushi Visha. We need to realize the health hazardous effects of cumulative poison and its proper time to time prevention as well as its proper treatment. Keywords: Dushi Visha, Skin manifestation, Slow acting poison


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3946
Author(s):  
Laura De Lellis ◽  
Serena Veschi ◽  
Nicola Tinari ◽  
Zhirajr Mokini ◽  
Simone Carradori ◽  
...  

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1362
Author(s):  
Richard Thomas Meehan ◽  
Isabelle Anne Amigues ◽  
Vijaya Knight

Despite the growing number of biologic and JAK inhibitor therapeutic agents available to treat various systemic autoimmune illnesses, the lack of a validated companion diagnostic (CDx) to accurately predict drug responsiveness for an individual results in many patients being treated for years with expensive, ineffective, or toxic drugs. This review will focus primarily on rheumatoid arthritis (RA) therapeutics where the need is greatest due to poor patient outcomes if the optimum drug is delayed. We will review current FDA-approved biologic and small molecule drugs and why RA patients switch these medications. We will discuss the sampling of various tissues for potential CDx and review early results from studies investigating drug responsiveness utilizing advanced technologies including; multiplex testing of cytokines and proteins, autoantibody profiling, genomic analysis, proteomics, miRNA analysis, and metabolomics. By using these new technologies for CDx the goal is to improve RA patient outcomes and achieve similar successes like those seen in oncology using precision medicine guided therapeutics.


2021 ◽  
Author(s):  
Haiyang Jin ◽  
Peng Gao ◽  
Jijun Cao ◽  
Yucheng He ◽  
Ying Hu ◽  
...  
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