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Dec 2025
Tariku Belay YilkalCorresponding author
Background Research and drug development industries have multiphase drug screening procedures, which can be debated. As a result, harmful products may still reach for public health service delivery due to vulnerabilities in the process. Main body A wide range of test compounds have delayed manifestation of undesired effect on the study subject, with the time to undesired effects after acute exposure being weeks and months. Acute toxicology in a preclinical trial also has limited clinical value as its lethal dose is the endpoint for a conclusion, and death sometimes occurs after a scheduled period of acute toxicology. Countless resources are wasted, and numerous new drugs are introduced into the pharmaceutical market with assumed safety analysis every year due to vulnerable multi-procedures in preclinical trials. The principal use of collected data from a preclinical trial is to support regulatory categorization and harmful labelling decisions. However, the data can also be used to derive safe use threshold levels, which may lead to the use of unsafe material. The criteria for classification and labelling also differ among countries, sometimes among authorities within the same country. The fundamental concept of toxicology states that ‘all chemical substances are potential poisons depending on the amount and duration of exposure. However, the toxic property of a test compound cannot be created or eliminated by simply the amount administered to study animals. Conclusion All xenobiotics are poisons at any amount with different severity that can be calculated using biological parameters.
Oct 2019 DOI 10.14302/issn.2641-7669.ject-19-3040
Kader Mohiuddin AbdulCorresponding author
Secretary & Treasurer, Dr. M. Nasirullah Memorial Trust, Tejgaon, Dhaka 1215
Many lay people along with some so called “key opinion leaders” have a common slogan “There's no answer for cancer”. Again, mistake delays proper treatment and make situation worse, more often. Compliance is crucial to obtain optimal health outcomes, such as cure or improvement in QoL. Patients may delay treatment or fail to seek care because of high out-of- pocket expenditures. Despite phenomenal development, conventional therapy falls short in cancer management. There are two major hurdles in anticancer drug development: dose-limiting toxic side effects that reduce either drug effectiveness or the QoL of patients and complicated drug development processes that are costly and time consuming. Cancer patients are increasingly seeking out alternative medicine and might be reluctant to disclose its use to their oncology treatment physicians. But there is limited available information on patterns of utilization and efficacy of alternative medicine for patients with cancer. As adjuvant therapy, many traditional medicines shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The literature reviews non-pharmacological interventions used against cancer, published trials, systematic reviews and meta-analyses.
May 2019 DOI 10.14302/issn.2324-7339.jcrhap-19-2847
Sharma BechanCorresponding author
Department of Biochemistry, Faculty of Science, University of Allahabad, Allahabad-211002, UP, India.
Background Carissa carandas L. is a well-known wild fruit plant distributed through-out the India and also present in other countries. The fruits are rich in nutrients and minerals. A number of medicinally important phytochemicals such as carrisone, carindone, carandinol, lupeol, scopoletin, stigmasterol, β-sitosterol, myo-inositol, β-amyrin, Des-n-methylnoracronycine etc. have been reported from the extract of this plant. Being safe and cost effective molecules, the activity of phytochemicals against HIV-1 enzymes needs to be screened. Objective The aim of this study was to screen the potent phytocompound of C. carandas against human immunodeficiency virus-1 using docking method. Methods Total nine compounds viz. carandinol, caridone, carrisone, lupeol, p-coumaric acid, gallic acid, rutin, scopoletin and ursolic acid were used for in-silico study towards drug development against human immunodeficiency virus-1 reverse transcriptase (HIV-1RT; PDB ID: 1REV) and human immunodeficiency virus-1 protease (PDB ID:1EBY) using Autodock software. Results The qualitative characterization of the extracts showed the presence of a number of phytochemicals such as phenolics, flavonoids, alkaloids, terepnoids, terpenes, steroids, glycosides etc. Carandinol was observed as most effective anti-HIV-1 molecule having lowest binding energy and small inhibition coefficient. Another compound, p-coumaric acid, showed least effectiveness against human immunodeficiency virus- 1 reverse transcriptase or human immunodeficiency virus-1 protease showing highest binding energy and inhibition coefficients among all the evaluated phytocompounds. Conclusion The in-silico study demonstrated that some phytoconstituents of C. carandas exhibit potential anti-human immunodeficiency virus -1 activity and hence can be optimized to develop as a drug candidate in future.
Jul 2017 DOI 10.14302/issn.2574-4372.jesr-17-1705
Varma VijayalakshmiCorresponding author
Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Studies, Jefferson, AR
Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Pathophysiological alteration prevalent under such conditions can alter or exacerbate cardiotoxic responses. The growing incidence of obesity, diabetes and metabolic syndrome subject a significant percentage of the population to drug treatments, thereby augmenting their risk for drug-induced cardiovascular toxicity. Hence, screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The advent of human pluripotent stem cells (hPSC) and induced pluripotent stem cell (iPSC)-derived cardiomyocytes are revolutionizing safety/toxicity screening in human cells by providing relevant human-specific, renewable model systems to explore human drug toxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, now offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Use of appropriate disease models will not only provide cost savings by decreasing potential drug attrition and withdrawals, seen with many drugs, but will also be a promising option to advance precision medicine