Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control) and second (probucol) groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day), respectively, for two weeks. Animals in the third (CP) and fourth (probucol plus CP) groups were injected with the same doses of corn oil and probucol (61 mg/kg/day), respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.). The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) (117%), lactate dehydrogenase (LDH) (64%), free (69%) and esterified cholesterol (42%) and triglyceride (69%) compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP) (40%) and ATP/ADP (44%) in cardiac tissues. Probucol pretreatment not only counteracted significantly the CP-induced increase in cardiac enzymes and apoptosis but also induced a significant increase in mRNA expression of antioxidant enzymes and improved ATP, ATP/ADP, glutathione (GSH) in cardiac tissues. In conclusion, data from the present study suggest that probucol prevents the development of CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to increase mRNA expression of antioxidant genes and to decrease apoptosis in cardiac tissues with the consequent improvement in mitochondrial oxidative phosphorylation and energy production

Effects of Green Tea Extracts on the Pharmacokinetics of Quetiapine in Rats

Quetiapine is an atypical antipsychotic, used clinically in the treatment of schizophrenia, acute mania in bipolar disorders, and bipolar depression in adults. In this study, the effect of green tea extracts (GTE) on the pharmacokinetics of quetiapine (substrate of CYP3A4) was investigated in rats. Male Wistar albino rats received GTE (175 mg/kg) or saline (control) by oral gavage for 7 days before a single intragastric administration of 25 mg/kg quetiapine. Plasma concentrations of quetiapine were measured up to 12 h after its administration by a validated ultraperformance liquid chromatography-tandem mass spectroscopy. Pretreatment with GTE produced significant reductions in the maximum plasma concentration and area under the curve of quetiapine by 45% and 35%, respectively, compared to quetiapine alone. However, GTE did not produce significant change in elimination half-life and oral clearance of quetiapine. This study concluded that GTE may decrease the bioavailability of quetiapine when coadministered

Eco-Friendly UPLC–MS/MS Method for Determination of a Fostamatinib Metabolite, Tamatinib, in Plasma: Pharmacokinetic Application in Rats

Fostamatinib is a prodrug of the active metabolite tamatinib, which is a spleen tyrosine kinase (Syk) inhibitor used in the treatment of primary chronic adult immune thrombocytopenia and rheumatoid arthritis. A highly sensitive, rapid, reliable, and green method was developed and validated using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC–MS/MS) for quantification of tamatinib in rat plasma. Ibrutinib was used as internal standard and liquid–liquid extraction was applied using tert-butyl methyl ether. The analyte was separated on an AcquityTM CSH C18 (2.1 mm × 100 mm, 1.7 µm) column using mobile phase consisting of 10 mM ammonium acetate and acetonitrile (10:90) and the flow rate was 0.25 mL/min. Electrospray ionization (ESI) was carried out in positive mode. Quantitation of tamatinib and the IS was performed using multiple reaction monitoring mode with precursor-to-product transitions of m/z 471.1 > 122.0 and m/z 441.1 > 84.0, respectively. The calibration range was 0.1–1000.0 ng/mL and the linearity of the method was ≥0.997. The developed method greenness was investigated. All principal parameters for the method, including linearity, accuracy, precision, recovery, and stability, were within acceptable ranges. Tamatinib pharmacokinetic study in rats was successfully carried out using the developed method

Can language influence health decisions? The role of foreign language and grammatical structure

The language used to present an argument has long been argued to influence people’s reaction to that argument. This study examined how language and grammatical structure influenced response to health-related dilemmas. We investigated whether medical students’ willingness to receive a medical treatment or to take an action (regarding advancing one’s own health or other people’s health) was influenced by the language (first versus foreign) and the grammatical structures (modifiers and quantifiers) used. Saudi medical students (N = 368) read health-related dilemmas using different adverbial modifiers and quantifiers in Arabic or in English. The participants were randomly assigned to one of four conditions: Arabic with high certainty (i.e., very-modifier and all-quantifier), Arabic with low certainty (no very-modifier and some-quantifier), English with high certainty, and English with low certainty. The results showed that the participants were susceptible to a foreign language effect, but not to a grammatical structure effect. We discuss the implications of these results in relation to how different health-scenarios may affect decision making for health professionals

Ecofriendly, Simple, Fast and Sensitive UPLC-MS/MS Method for Determination of Erdafitinib, a Novel Tyrosine Kinase Inhibitor, in Plasma and Its Application to Metabolic Stability

Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor and has a potent antitumor activity against FGFR-aberrant malignancies. Erdafitinib has a narrow therapeutic index, and its pharmacokinetics are influenced by genetic variability and interacting medication. Routine therapeutic drug monitoring and dose adjustment are recommended. This study aims at developing a new UPLC-MS/MS method for determination and quantitation of erdafitinib in human plasma using ibrutinib as an internal standard. The sample ionization was performed by using electrospray ionization in positive mode, and multiple reaction monitoring was used for the quantification of target analytes. The chromatographic separation of erdafitinib and IS was achieved by an UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm). Erdafitinib metabolic stability was studied using intrinsic clearance and in vitro half-life. The greenness of the developed method was evaluated using appropriate, analytical Eco-Scale and AGREE software. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.99 with a limit of quantitation of 0.5 ng/mL. The accuracy and precision were within acceptable limits and the average recovery and matrix effects were 86.11% and 90.51%, respectively. Erdafitinib metabolic stability was studied and its in vitro half-life was 7.28 min and intrinsic clearance was 95.11 µL/min/mg. The assessment of the greenness profile of the method indicated that the method is eco-friendly. The proposed method can be utilized for therapeutic drug monitoring and pharmacokinetic studies

Eco-Friendly, Simple, Fast, and Sensitive UPLC-MS/MS Method for Determination of Pexidartinib in Plasma and Its Application to Metabolic Stability

Pexidartinib is the first drug approved by the U.S. Food and Drug Administration specifically to treat the rare joint tumor tenosynovial giant cell tumor. In the current study, a validated, selective, and sensitive UPLC-MS/MS assay was developed for the quantitative determination of pexidartinib in plasma samples using gifitinib as an internal standard (IS). Pexidartinib and IS were extracted by liquid-liquid extraction using methyl tert-butyl ether and separated on an acquity BEH C18 column kept at 40 °C using a mobile phase of 0.1% formic acid in acetonitrile: 0.1% formic acid in de-ionized water (70:30). The flow rate was 0.25 mL/min. Multiple reaction monitoring (MRM) was operated in electrospray (ESI)-positive mode at the ion transition of 418.06 > 165.0 for the analyte and 447.09 > 128.0 for the IS. FDA guidance for bioanalytical method validation was followed in method validation. The linearity of the established UPLC-MS/MS assay ranged from 0.5 to 1000 ng/mL with r > 0.999 with a limit of quantitation of 0.5 ng/mL. Moreover, the metabolic stability of pexidartinib in liver microsomes was estimated

Orthopedic Surgeons’ Views of Hyaluronic Acid Formulations in the Management of Knee Osteoarthritis: A Questionnaire-Based Cross-Sectional Study

Background and Objectives: Multiple hyaluronic acid (HA) products were approved and marketed to manage osteoarthritis (OA). Although these products are widely prescribed by orthopedic surgeons to manage OA, especially knee OA, the therapeutic value of these products is highly uncertain. Few studies with significant limitations in their designs have indicated positive outcomes among OA patients treated with HA; however, their results were inconclusive. Thus, we aimed to explore the therapeutic value of different HA products in alleviating knee OA pain and improving patients’ physical function from the orthopedic surgeons’ perspective. Materials and Methods: This was a questionnaire-based cross-sectional study in which practicing orthopedic surgeons in two countries (e.g., Saudi Arabia and Jordan) were invited to participate. The 10-item, newly developed questionnaire inquired about the respondents’ sociodemographic characteristics (e.g., age, gender, country, years of experience), and their opinions regarding the efficacy of HA products in the management of OA (e.g., efficacy in improving mobility and alleviating pain). Results: Out of the 200 orthopedic surgeons who were invited to participate, 122 (61%) filled out the questionnaire. Most of the respondents were from Saudi Arabia (58%), aged 35 to 55 years (68%), had at least 10 years of experience (69%), and male (98%). About 80% of the respondents reported prescribing HA, such as Hyalgan®, Orthovisc®, Hyalubrix®, and Crespine Gel®. About 66% of the respondents believed that HA was moderately to highly effective in managing knee OA, and 34% believed that HA was either ineffective or mildly effective. Pain at the site of injection (44.3%) and rash or local skin reactions (22.1%) were the most commonly reported adverse events. Conclusions: The variations in the formulation of different HA brands (e.g., molecular weight and cross-linking) did not seem to offer any therapeutic advantage. HA might have value in the management of knee OA; however, its value is highly uncertain and necessitates more well-designed studies to further examine its therapeutic value

Description of pharmacists\u27 reported interventions to prevent prescribing errors among in hospital inpatients: a cross sectional retrospective study

BACKGROUND: Prescribing errors (PEs) are a common cause of morbidity and mortality, both in community practice and in hospitals. Pharmacists have an essential role in minimizing and preventing PEs, thus, there is a need to document the nature of pharmacists\u27 interventions to prevent PEs. The purpose of this study was to describe reported interventions conducted by pharmacists to prevent or minimize PEs in a tertiary care hospital. METHODS: A retrospective analysis of the electronic medical records data was conducted to identify pharmacists\u27 interventions related to reported PEs. The PE-related data was extracted for a period of six-month (April to September 2017) and comprised of patient demographics, medication-related information, and the different interventions conducted by the pharmacists. The study was carried in a tertiary care hospital in Riyadh region. The study was ethically reviewed and approved by the hospital IRB committee. Descriptive analyses were appropriately conducted using the IBM SPSS Statistics. RESULTS: A total of 2,564 pharmacists\u27 interventions related to PEs were recorded. These interventions were reported in 1,565 patients. Wrong dose (54.3 %) and unauthorized prescription (21.9 %) were the most commonly encountered PEs. Anti-infectives for systemic use (49.2 %) and alimentary tract and metabolism medications (18.2 %) were the most common classes involved with PEs. The most commonly reported pharmacists\u27 interventions were dose adjustments (44.0 %), restricted medication approvals (21.9 %), and therapeutic duplications (11 %). CONCLUSIONS: In this study, PEs occurred commonly and pharmacists\u27 interventions were critical in preventing possible medication related harm to patients. Care coordination and prioritizing patient safety through quality improvement initiatives at all levels of the health care system can play a key role in this quality improvement drive. Future studies should evaluate the impact of pharmacists\u27 interventions on patient outcomes

A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid–liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies

Validation of an Arabic Version of the Adherence to Refills and Medications Scale (ARMS)

Background: Medication non-adherence is a complex multifactorial phenomenon impacting patients with various health conditions worldwide. Therefore, its detection can improve patient outcomes and minimize the risk of adverse consequences. Even though multiple self-reported medication adherence assessment scales are available, very few of them exist in Arabic language. Therefore, the aim of this study was to validate a newly translated Arabic version of the Adherence to Refills and Medications Scale (ARMS) among patients with chronic health conditions. Methods: This is a single-center cross-sectional study that was conducted between October 10th 2018 and March 23rd 2021. ARMS was first translated to Arabic using the forward-backward translation method. The translated scale was then piloted among 21 patients with chronic health conditions (e.g., diabetes, hypertension, etc.…) to examine its reliability and comprehensibility using the test-retest method. Thereafter, the Arabic-translated ARMS was self-administered to adult patients aged ≥18 years with chronic health conditions visiting the primary care clinics of a university-affiliated tertiary care hospital in Riyadh, Saudi Arabia. Construct validity was examined using factor analysis with varimax rotation. Results: Of the 264 patients who were invited to participate, 202 (76.5%) consented and completed the questionnaire. Most of the participants were males (69.9%), married (75.2%), having a college degree or higher (50.9%), retired or unemployed (65.2%), aged ≥ 50 years (65.2%), and are diabetic (95.9%). The 12-item Arabic-translated ARMS mean score was 17.93 ± 4.90, and the scale yielded good internal consistency (Cronbach’s alpha = 0.802) and test-retest reliability (Intraclass correlation coefficient = 0.97). Two factors were extracted explaining 100% of the of the total variance (factor 1 = 52.94% and factor 2 = 47.06%). Conclusions: The 12-item Arabic version of ARMS demonstrated good validity and reliability. Therefore, it should help in the detection of medication non-adherence among Arabic-speaking patient population and minimize the risk of adverse consequences