Dosage sensitivity

BACKGROUND: TAS-102 (Lonsurf® ) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity. METHODS: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m2 , twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12)...

BACKGROUND: Estimation of the drug and development of the method is a critical aspect of formulation development and a critical factor for analytical scientists. Gefitinib is a poorly soluble anticancer drug. OBJECTIVE: The present research enlightens the topic of the development of innovative quality by design methods for the estimation of Gefitinib (GF) from bulk, pharmaceutical tablet formulation and complex nanoformulations. METHODS: To simplify the estimation of poorly soluble drugs like GF, Response Surface Methodology (RSM) was adopted with effective leverages to obtain precise computation design space using the Box-Behnken Design (BBD) model...

Excipients are ubiquitous in pharmaceutical products, and often, they can also play a critical role in maintaining product quality. For a product containing a moisture-sensitive drug, moisture can be deleterious to the product stability during storage. Therefore, using excipients that interact with moisture in situ can potentially alleviate product stability issues. In this study, the interactive behavior of starch with moisture was augmented by coprocessing maize starch with sodium chloride (NaCl) or magnesium nitrate hexahydrate [Mg(NO3 )2 ·6H2 O] at different concentrations (5 and 10%, w/w)...

Ochratoxin A (OTA) is a mycotoxin that can contaminate a variety of agricultural commodities, including fruit juices and wines. The capability of a magnetic solid-phase extraction (MSPE) method with a magnetic metal-organic framework (MOF) material having a three-layer core-shell structure to improve the detection of OTA in food matrices using high performance liquid chromatography is described. Analysis of the material through X-ray diffraction (XRD) indicated the successful synthesis of the magnetic nanomaterial Fe3 O4 @SiO2 @UiO66 -NH2 ...

Differential expression (DE) analysis is a widely used method for identifying genes that are functionally relevant for an observed phenotype or biological response. However, typical DE analysis includes selection of genes based on a threshold of fold change in expression under the implicit assumption that all genes are equally sensitive to dosage changes of their transcripts. This tends to favor highly variable genes over more constrained genes where even small changes in expression may be biologically relevant...

Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients)...

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated...

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions...

A previous study discovered that two speakers with moderate apraxia of speech increased their sequential motion rates after unilateral forced-nostril breathing (UFNB) practiced as an adjunct to speech-language therapy in an AB repeated-measures design. The current study sought to: (1) delineate possible UFNB plus practice effects from practice effects alone in motor speech skills; (2) examine the relationships between UFNB integrity, participant-reported stress levels, and motor speech performance; and (3) sample a participant-led UFNB training schedule to contribute to the literature's growing understanding of UFNB dosage...

There is a need to establish consensus for harmonization in antiretroviral (ARV) therapy (ART) switch treatment strategy and address the dilemma that exists in terms of subpar immune response to therapy or an immunologic deterioration while on therapy. The purpose of this review is to identify the factors that contribute to ARV treatment failure, such as insufficient dosage, drug interactions, poor adherence, drug resistance, and poor medication absorption. It is crucial to adopt a more efficient strategy to address this challenging dilemma...

The use of direct alcohol biomarkers (ethylglucuronide and phosphatidylethanol) has recently been implemented in a clinical setting. Due to their low alcohol detection threshold, high sensitivity, and specificity, these tools are very useful in the pre- and post-liver transplantation setting, where the history and physical signs are not always reliable. However, the interpretation of the results can sometimes be misleading and must be integrated into a global clinical evaluation and, more importantly, in the clinical context of each patient...

Proper insulin management is vital for maintaining stable blood sugar levels and preventing complications associated with diabetes. However, the soaring costs of insulin present significant challenges to ensuring affordable management. This paper conducts a comprehensive review of current literature on the application of machine learning (ML) in insulin management for diabetes patients, particularly focusing on enhancing affordability and accessibility within the United States. The review encompasses various facets of insulin management, including dosage calculation and response, prediction of blood glucose and insulin sensitivity, initial insulin estimation, resistance prediction, treatment adherence, complications, hypoglycemia prediction, and lifestyle modifications...

Varroa destructor is one of the most destructive enemies of the honey bee, Apis mellifera all around the world. Several control methods are known to control V. destructor, but the efficacy of several alternative control methods remains unexplored. Irradiation can be one of these unknown solutions but before practical application, the effectiveness, and the physiological effects of ionizing radiation on the host and the parasite are waiting to be tested. Therefore, the objective of our study was to investigate the effects of different doses (15, 50, 100, and 150 Gy) of high-energy X-ray irradiation through mortality rates and hemocyte composition changes in A...

AIM OF THE STUDY: To evaluate the therapeutic effect of SYNC in diarrhea irritable bowel syndrome (IBS-D) and explore its underlying mechanism through transcriptomic sequencing (RNA-Seq). MATERIALS AND METHODS: A rat model of IBS-D was constructed to elucidate the effects of SYNC. Abdominal withdrawal reflex (AWR), fecal water content (FWC), and recording body weight were calculated to assess visceral sensitivity in rats. Histopathological changes in the colon and alterations in mast cell (MC) count were determined...

For the first time, clemastine was estimated in this work utilizing two validated resonance Rayleigh scattering (RRS) and fluorimetric methods. The methods relied on forming an association complex in an acidic medium between eosin Y reagent and clemastine. In the spectrofluorimetric approach, the investigated drug was quantified by quenching the fluorescence-emission intensity of eosin Y at 543.5 nm. The RRS method relied on enhancing the RRS spectrum at 331.8 nm, which is produced when eosin Y interacts with clemastine...

Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated...

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances ( e.g. , ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies...

A green method based on magnetic micro-solid phase extraction (MNP-TW-μ-SPE) of tea waste impregnated with magnetic nanoparticles (MNP-TW) was developed for the extraction of ibuprofen (IBP) in water samples prior to UV-Vis spectrophotometric analysis. Experimenting parameters that affect the extraction efficiency of IBP, such as pH of the sample solution, sorbent dosage, extraction time, ionic strength, volume of the sample, type of desorption solvent, desorption time, and desorption volume, were studied and optimized in detail...

This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators...

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances...