The Importance of Analytical Chemistry in Therapeutic Drug Monitoring for Personalized Medicine

Personalized therapy (PM) has the potential to adapt treatment with the best response and highest safety to provide better patient care. Key data is drug concentration of biological materials such as plasma and serum.Individual drug therapy means, choice of a drug and its dose regime should fit every individual specifically. Thus efficacy of a drug treatment would improve significantly. When developing an analytical method for (Therapeutic drug monitoring) TDM, it is important to choose a clinically relevant calibration range. This quantitation range should be built around the proposed target concentration, covering majority of samples as seen in the clinic (Ciocan-Cartita et al. 2019).Inter-individual variability in Pharmacokinetic variables may affect the blood concentration of drug so TDM approaches could solve the dosing problem.To achieve individual drug therapy with a reasonably predictive outcome, one must further account for different patterns of drug response among geographically and ethnically distinct populations. Keywords: LC-MS/MS, Therapeutic Drug Monitoring, Lenalidomide, Anastrozole DOI: 10.7176/CMR/12-7-05 Publication date:September 30th 202

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation

The Predictors of Pneumonia in Children with COVID-19

The purpose of this study was to evaluate the relationship between the presence of pneumonia and blood parameters in cases of Coronavirus disease (COVID-19) and to examine their predictive characteristics in terms of pneumonia. We reviewed the file records of 151 pediatric patients with a diagnosis of COVID-19 confirmed by the real time-reverse transcription polymerase chain reaction test in nasopharyngeal swabs. The patients were divided into two groups based on direct chest X-ray and computed tomography results in [Group 1 (n:41), with pneumonia findings, and Group 2 (n:110), with no pneumonia findings]. The groups’ demographic data, clinical and laboratory findings were compared. Pulmonary involvement was determined in 41 (27.1%) of the 151 patients. The [body mass index (BMI) Z-score], red blood cell distribution width (RDW), mean platelet volume (MPV), neutrophil lymphocyte ratio, passive leg raise, and D-dimer levels were significantly higher in patients with pneumonia than those without pneumonia in our study. Based on multivariate logistic regression analysis, BMI Z-score, MPV, and RDW were found to be independent risk factors of pneumonia in patients. The current study showed higher levels of blood parameters in patients with coronavirus disease 2019 (COVID -19) presenting with pneumonia than those without pneumonia. We suggest that BMI-Z score and MPV value may assist in predicting pulmonary involvement in patients with COVID-19