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

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study

BackgroundSpinal muscular atrophy (SMA) is a rare debilitating condition with a significant burden for patients and society. However, little is known about how it affects Saudi Arabia's population. The socioeconomic and medical characteristics of affected SMA patients and their caregivers are lacking.PurposeThis study aimed to describe the socioeconomic and medical characteristics of SMA patients and caregivers in Saudi Arabia.Patients and methodsA cross-sectional questionnaire-based study was conducted using snowball sampling. Assessment tools including EuroQol (EQ-5D-5L) and visual analog scale (EQ-VAS), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Costs for Patients Questionnaire (CoPaQ) were used to assess the quality of life (QoL), anxiety, depression, and out-of-pocket expenditures.ResultsSixty-four caregivers of SMA patients participated. Type I patients had higher sibling concordance, ICU hospitalization, and mechanical support needs. Type III patients had better QoL. Type I patients' caregivers had higher depression scores. Type III patients' caregivers had higher out-of-pocket expenditures. Forty-eight percent received supportive care, while others received SMA approved therapies.ConclusionSMA imposes a significant socioeconomic burden on patients and caregivers, requiring more attention from the healthcare system. Access to innovative therapies varied across SMA types. Pre-marital screening and early detection are crucial to reduce disease incidence and ensure timely treatment

Pharmacokinetic modeling of vancomycin in children, pre-adolescent, and adolescent patients : development, assessment, and application

The development and evaluation of a vancomycin population pharmacokinetic model in children, pre-adolescent, and adolescent patients was performed via non linear mixed effects modeling (NONMEM) in 2 phases. In phase I, a vancomycin population pharmacokinetic model was developed based on data from 200 children (aged 2-17 years) using a two-compartment model. Variables tested for inclusion in the model were serum creatinine (SCR), age (AGE), weight (WT), height (HT), sex (SEX), and body surface area (BSA). Variables were included at the p $In phase II, the performance of the derived model was evaluated in a naive tested population and then compared to the Schaad, et al. model via prediction error techniques (PE). The predictability of 159 measured concentrations was assessed in 68 new patients. In predicting all concentrations types, the mean prediction error (MPE) with a 95$-$1.42 ($-$3.38, 0.54), and 6.01 (4.46, 7.56) mg/L, respectively. When considering only peaks, a MPE with 95$-$0.94, 4.38), and 7.61 (5.13, 10.09) mg/L, respectively. Finally, MPE with 95$-$1.45 ($-$3.42, 0.52), and 3.84 (2.98, 4.70) mg/L, respectively. Maintenance dose (MD) tables were designed, based on the relationship of height and serum creatinine to clearance. In addition, a loading dose (LD) was also recommended, which was 5 mg/cm. It is recommended that the current study model be used for dosing the pediatric population while setting an initial target peak of 30 mg/L and a trough of 5-10 mg/L. This should frequently result in optimal serum vancomycin concentrations within the therapeutic window. Individualization of therapy should then be done, once the measured concentrations are available

Pharmacokinetic modeling of vancomycin in children, pre-adolescent, and adolescent patients : development, assessment, and application

The development and evaluation of a vancomycin population pharmacokinetic model in children, pre-adolescent, and adolescent patients was performed via non linear mixed effects modeling (NONMEM) in 2 phases. In phase I, a vancomycin population pharmacokinetic model was developed based on data from 200 children (aged 2-17 years) using a two-compartment model. Variables tested for inclusion in the model were serum creatinine (SCR), age (AGE), weight (WT), height (HT), sex (SEX), and body surface area (BSA). Variables were included at the p $In phase II, the performance of the derived model was evaluated in a naive tested population and then compared to the Schaad, et al. model via prediction error techniques (PE). The predictability of 159 measured concentrations was assessed in 68 new patients. In predicting all concentrations types, the mean prediction error (MPE) with a 95$-$1.42 ($-$3.38, 0.54), and 6.01 (4.46, 7.56) mg/L, respectively. When considering only peaks, a MPE with 95$-$0.94, 4.38), and 7.61 (5.13, 10.09) mg/L, respectively. Finally, MPE with 95$-$1.45 ($-$3.42, 0.52), and 3.84 (2.98, 4.70) mg/L, respectively. Maintenance dose (MD) tables were designed, based on the relationship of height and serum creatinine to clearance. In addition, a loading dose (LD) was also recommended, which was 5 mg/cm. It is recommended that the current study model be used for dosing the pediatric population while setting an initial target peak of 30 mg/L and a trough of 5-10 mg/L. This should frequently result in optimal serum vancomycin concentrations within the therapeutic window. Individualization of therapy should then be done, once the measured concentrations are available

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

Quality of life and complementary and alternative medicine use among women with breast cancer

Background: Complementary and Alternative Medication (CAM) is commonly used among women with breast cancer to improve their quality of life (QoL). However, few studies examine the prevalence of CAM and its’ relation to the patients’ QoL among women with breast cancer. Methods: A cross-sectional study was conducted among 95 women with breast cancer at a tertiary hospital in Saudi Arabia. The outcome measure of interest was the QoL. The correlation was used to assess the association between CAM use and QoL. Bivariate and multivariate analyses were used to examine the factors that affect the use of CAM. The data was analysed using Statistical Package for the Social Sciences (SPSS) version 24.0. Results: CAM use was reported by 81.1% of the study participants. The most commonly used CAM therapy was spiritual therapy 70.5%, followed by honey 36.8%, olive oil 24.2% and 23.2% herbal therapy. We found that those who were undergoing cancer treatment had a significantly higher percentage of CAM usage as compared to those not undergoing cancer therapy (72.6% vs. 8.4%, P=0.008). With regards to QoL, there was a statistically significant difference between CAM users and non-CAM users in global health status (73.2% vs. 64.8%, P = 0.049). Conclusions: CAM therapy was commonly used among women in our study sample which was correlated with higher overall global QoL. As CAM is widely used, health care providers may need to discuss the use of CAM with breast cancer women and be up to date on the benefits and risk of CAM use through well-equipped training programs and workshops

The Commonly Utilized Natural Products during the COVID-19 Pandemic in Saudi Arabia: A Cross-Sectional Online Survey

Objectives: The utilization rate of herbal and dietary supplements among the Saudi population is reported to be high. However, the utilization rate and types of herbal and dietary supplements during the COVID-19 pandemic are largely unknown. Methods: This was an online questionnaire-based cross-sectional study that used convenience sampling and social media platforms (Telegram®, Twitter®, and WhatsApp®) to disseminate a 12-item questionnaire across the Saudi general public aged 18 years and above. The questionnaire inquired about the sociodemographic characteristics (e.g., age, gender, education, geographical location), presence of chronic health conditions and the use of prescription medications, awareness of the viral nature of COVID-19 infection and its common symptoms, and the commonly utilized herbal and/or dietary supplements. Results: Sixty-four percent of the 1473 participants reported using herbal and/or dietary supplements for the purpose of boosting their immune system to prevent COVID-19 infection. In addition, 88.2% of the respondents were misinformed about the manifestation of COVID-19 symptoms. Most of the participants were Saudi (91.9%), aged 49 years and younger (83%), female (52%), and healthy (81%). Honey (46%), lemon (45%), ginger (36%), vitamin C (32%), black seed (26%), garlic (26%), and turmeric (19%) were the most commonly used herbal and/or dietary supplements by the participants. Saudi nationals (OR = 1.67, 95% CI: 1.08 to 2.6, p = 0.02), older adults (OR = 1.30, 95% CI:1.10 to 1.55, p = 0.002), and those taking prescription medications had higher odds of using dietary and/or herbal supplements (OR = 3.31, 95% CI: 2.61 to 4.18, p < 0.0001). Conclusion: The utilization rate of herbal and dietary supplements among the Saudi public during the COVID-19 pandemic is high. Future studies should examine the impact of different public awareness campaigns aimed at improving the public knowledge of the risk and benefits associated with the use of different commonly utilized herbal and dietary products identified in this study

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

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

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