Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model.

Tivozanib is a triple vascular endothelial growth factor receptor inhibitor, recently approved for the treatment of refractory advanced renal cell carcinoma. Clinical studies showed that around 46% of patients who received tivozanib suffer from hypertension in all grades. Thus, the present study was conducted to identify the role of angiotensin-II (AngII) in the mechanism underlying tivozanib-induced vascular toxicity and hypertension. C57BL/6 male mice received tivozanib (1 mg/kg) with or without losartan (10 or 30 mg/kg) for 3 weeks. Blood pressure was recorded every 3 days, and proteinuria was measured every week. On day 21, all mice were euthanized, and samples were harvested for further analysis. Tivozanib elevated blood pressure until systolic blood pressure reached 163 ± 6.6 mmHg on day 21 of treatment with low urination and high proteinuria. AngII and its receptors, endothelin-1, and oxidative stress markers were significantly increased. While nitric oxide (NO) levels were reduced in plasma and aortic tissues. AngII type 1 receptor blockade by losartan prevented these consequences caused by tivozanib and kept blood pressure within normal range. The results showed that AngII and ET-1 might be potential targets in the clinical studies and management of hypertension induced by tivozanib.

Prevalence and Determinants of Road Traffic Accidents in Saudi Arabia: A Systematic Review.

Globally, the frequency of road traffic accidents (RTAs) is sharply rising. It is concerning that the number of RTAs in the Kingdom of Saudi Arabia (KSA) has risen within the past ten years. As a result, laws governing things like speeding and seat belt use must be implemented to ensure driving safety. This study aims to determine the prevalence and determinants of road traffic accidents in Saudi Arabia. A thorough search was carried out in November 2023, mostly using PubMed, in compliance with PRISMA criteria. The search was limited to English-language research examining the causes of road traffic accidents and their prevalence. Certain inclusion and exclusion criteria were developed to guarantee the quality and applicability of the evaluated research. A wide spectrum of research from Saudi Arabia was included in the study without focusing on a specific gender. A discernible pattern indicated a high proportion of individuals affected by road traffic accidents. According to the findings of our investigation, there is growing evidence that Despite recent improvements in the incidence of road accidents, there is still significant variation in the incidence of accidents in Saudi Arabia. These results indicate that further study is needed to understand road accident prevention better.

Angiotensin II type 1 receptor blockade attenuates gefitinib-induced cardiac hypertrophy via adjusting angiotensin II-mediated oxidative stress and JNK/P38 MAPK pathway in a rat model.

Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR), used for the treatment of advanced or metastatic non-small cell lung cancer. Recently, studies proved that Gefitinib-induced cardiotoxicity through induction of oxidative stress leads to cardiac hypertrophy. The current study was conducted to understand the mechanisms underlying gefitinib-induced cardiac hypertrophy through studying the roles of angiotensin II (AngII), oxidative stress, and mitogen-activated protein kinase (MAPK) pathway. Male Wistar albino rats were treated with valsartan, gefitinib, or both for four weeks. Blood samples were collected for AngII and cardiac markers measurement, and hearts were harvested for histological study and biochemical analysis. Gefitinib caused histological changes in the cardiac tissues and increased levels of cardiac hypertrophy markers, AngII and its receptors. Blocking of AngII type 1 receptor (AT1R) via valsartan protected hearts and normalized cardiac markers, AngII levels, and the expression of its receptors during gefitinib treatment. valsartan attenuated gefitinib-induced NADPH oxidase and oxidative stress leading to down-regulation of JNK/p38-MAPK pathway. Collectively, AT1R blockade adjusted AngII-induced NADPH oxidase and JNK/p38-MAPK leading to attenuation of gefitinib-induced cardiac hypertrophy. This study found a pivotal role of AngII/AT1R signaling in gefitinib-induced cardiac hypertrophy, which may provide novel approaches in the management of EGFRIs-induced cardiotoxicity.

Pharmaceutical Care in the Community Pharmacies of Saudi Arabia: Present Status and Possibilities for Improvement.

Pharmaceutical care can be given in all settings: The community, hospitals, long-term care, and the clinic. However, published literature indicates that there is a substantial barrier to implementing pharmaceutical care programs in community pharmacies. This review was conducted to discover gaps and limitations in pharmaceutical care services in community pharmacies in the Kingdom of Saudi Arabia (KSA). We searched PubMed and other available scientific website databases using the following key words to retrieve the relevant articles: Community Pharmacy, Healthcare System, Pharmaceutical Care, KSA. Two authors independently screened the titles and abstracts of promising articles. They discarded irrelevant studies and retained studies, and reviews that held the promise of relevant data or information. The review revealed that only one out of the four studies conducted in KSA retrieved by the authors reported pharmaceutical care service other than dispensing. The same results were reported in other studies conducted in some developing countries. All pharmaceutical care services were reported in studies conducted in Europe. The authors came to the conclusion that in KSA, dispensing of medicines is the dominant service provided by community pharmacists and that there was very limited if not a total absence of other pharmaceutical care services.

Systematic review and meta-analysis of efficacy and safety of combinational therapy with metformin and dipeptidyl peptidase-4 inhibitors.

Combinational therapies are often required in the management of type 2 diabetes mellitus (T2DM). Among the important candidates, dipeptidyl peptidase-4 inhibitors (DPPIs) and metformin combination (DPPI-MET) have shown promising endeavors. In order to examine the efficacy and safety of such a combination therapy in T2DM patients finding inadequate control with metformin, this systematic review and meta-analysis has been conducted. Literature search was made in multiple electronic databases. Inclusion criteria included; RCTs examining the efficacy and safety of DPPI-MET against placebo-MET or MET-only groups of T2DM patients by observing changes in disease endpoints including HbA1c and FPG, and the length of trial be at least 12 weeks. Mean differences based meta-analyses were performed and heterogeneity assessment was carried out. Nineteen studies were selected and included in the meta-analyses. DPPI-MET significantly improved all disease endpoints and the difference could be noticed up to 2 years in the majority of outcome measures. In comparison with PBO-MET, the DPPI-MET combinational therapy resulted in the percent HbA1c changes from baseline with a mean difference [95% CI] of -0.77 [-0.86, -0.69] in 3-month (P < 0.00001), -0.67 [-0.76, -0.59] in 6-month (P < 0.00001), -0.67 [-0.88, -0.47] in 1-year (P < 0.00001) and -0.36 [-0.53, -0.20] in 2-year trials (P < 0.0003). Reduction in body weight and safety profile in the treated and control groups were not different. A combinational therapy with DPPI and metformin significantly improves diabetes clinical indicators and this effect has been observed for up to 2 years herein. Safety and tolerability of DPPI-MET combination have been found well-manageable with a very similar adverse event profile in both treated and control groups.

The role of nutraceuticals in the management of autism.

Autism and related disorders are increasingly prevalent behavioral syndromes of impaired verbal and nonverbal communication and socialization owing to neurodevelopmental abnormalities. The most recent estimate for the prevalence of autistic disorders is about 1% on a global scale. Etiology of autism is multifactorial and multidimensional that makes therapeutic intervention even harder. Heterogeneity of genetic factors, oxidative stress, autoimmune mechanism, and epigenetic mechanisms complicate the nature of pathogenesis of the disease. Nutraceutical approach to treat this disease is a promising strategy, especially in some areas, it is more attractive than others. This review critically analyzes the roles of vitamins and cofactors, dietary modifications and gut abnormalities, probiotics and prebiotics, phytochemicals, and environmental factors in order to determine the state of evidence in nutraceutical-based autism management practices. This article presents a systematic review of randomized- and placebocontrolled trials to examine the evidence supports the use of autism nutraceu10.1016/j.jsps.2012.10.001ticals. The results will be discussed in the light of all relevant evidence generated from other clinical and exploratory studies.