High-density lipoprotein protects normotensive and hypertensive rats against ischemia-reperfusion injury through differential regulation of mTORC1 and mTORC2 signaling.

Background: High-density lipoprotein (HDL) protects against myocardial ischemia-reperfusion (I/R) injury. Mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) play opposing roles in protecting against I/R injury, whereby mTORC1 appears to be detrimental while mTORC2 is protective. However, the role of HDL and mTORC signaling in protecting against I/R in hypertensive rodents is not clearly understood.

The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin.

Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin.

Methods: Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days.

High-Density Lipoprotein Signaling via Sphingosine-1-Phosphate Receptors Safeguards Spontaneously Hypertensive Rats against Myocardial Ischemia/Reperfusion Injury.

Background: High-density lipoprotein (HDL) protects against ischemia/reperfusion (I/R) injury via signaling through scavenger-receptor class B type-I (SR-BI) and sphingosine-1-phosphate receptors (S1PRs). We recently reported that HDL protects the hearts of spontaneously hypertensive rats (SHRs) against I/R injury in an SR-BI-dependent manner.

Objective: In this study, we examined the role of S1PRs in HDL-induced protection against myocardial I/R injury in hypertensive rats.

Upregulation of NADPH-oxidase, inducible nitric oxide synthase and apoptosis in the hippocampus following impaired insulin signaling in the rats: Development of sporadic Alzheimer's disease.

NADPH-oxidase (NOX) is a multi-subunit enzyme complex. The upregulation of NOX causes massive production of superoxide (O), which avidly reacts with nitric oxide (NO) and increases cellular reactive oxygen/nitrogen species (ROS/RNS). Increased ROS/RNS plays pivotal role in the sporadic Alzheimer's disease (sAD) development and brain damage following impaired insulin signaling.

Insights into early pathogenesis of sporadic Alzheimer's disease: role of oxidative stress and loss of synaptic proteins.

Oxidative stress, induced by impaired insulin signaling in the brain contributes to cognitive loss in sporadic Alzheimer's disease (sAD). This study evaluated early hippocampal oxidative stress, pre- and post-synaptic proteins in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) models of impaired insulin signaling. Adult male Wistar rats were injected with STZ, IP, or ICV, and sacrificed 1-, 3-, or 6-weeks post injection.

Impaired Insulin Signaling Alters Mediators of Hippocampal Synaptic Dynamics/Plasticity: A Possible Mechanism of Hyperglycemia-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurological condition that affects the elderly and is characterized by progressive and irreversible neurodegeneration in the cerebral cortex [...

Early time course of oxidative stress in hippocampal synaptosomes and cognitive loss following impaired insulin signaling in rats: Development of sporadic Alzheimer's disease.

Oxidative stress, caused by impaired insulin signaling, plays a pivotal role in the pathogenesis of sporadic Alzheimer's disease (sAD). We investigated the oxidative stress parameters in the synaptosomes prepared from the hippocampus tissue in order to identify their potential role in sAD development in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) injections models of insulin signaling impairment. Rats were harvested 1, 3, or 6 weeks post treatment.

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner.

Background: Hypertension is a key risk factor in the development of cardiovascular diseases. Elevation in blood pressure alters high density lipoprotein (HDL) function and composition. The exact role of HDL in cardiovascular complications observed in hypertension is however not clearly understood.

Exome Sequencing Reveals Novel Variants in Saudi Patients with Congenital Titinopathies.

Our goal was to determine the genetic basis of early-onset myopathy in patients from two unrelated families. Whole-exome sequencing, autozygosity mapping, and confirmatory targeted Sanger sequencing were performed using genomic DNA extracted from blood samples from three myopathic patients of two unrelated families. Variant filtering and pathogenicity analyses were evaluated according to standard protocols and up-to-date pipelines applied at the King Faisal Specialist Hospital and Research Center.

Case Report: Neonatal Multi-System Inflammatory Syndrome Associated With SARS-CoV-2 Exposure in Two Cases From Saudi Arabia.

Vertical transmission of SARS-CoV-2 is under investigation. A few reports suggest the possibility of SARS-CoV-2 transmission from mothers to their neonates. Most neonates have mild symptoms, but some develop multisystem involvement and shock.

Role of Extracellular Calcium and Calcium Sensitization in the Anti-Contractile Effect of Perivascular Adipose Tissue in Pregnant Rat Aorta.

Previous studies have shown that the anti-contractile effect of the perivascular adipose tissue (PVAT) is attenuated in pregnancy. In the present investigation, we have examined the possibility that this loss of anti-contractile effect could be due to changes in calcium mobilization. PVAT exerted anti-contractile effect against 5-hydroxytryptamine (5-HT)-induced contractions of aorta segments from pregnant and non-pregnant rats and this anti-contractile effect was attenuated in segments from pregnant rats.

Effects of Cardiac Hypertrophy, Diabetes, Aging, and Pregnancy on the Cardioprotective Effects of Postconditioning in Male and Female Rats.

Background: Aging, left ventricular hypertrophy (LVH), diabetes mellitus, and pregnancy are well-recognized risk factors that increase the prevalence of cardio-ischemic events and are linked to poor clinical recovery following acute myocardial infarction. The coexistence of these risk factors with ischemic heart disease (IHD) deteriorates disease prognosis and could potentially lead to fatal arrhythmias and heart failure. The objective of this study was to investigate the vulnerability of hearts with aging, LVH, diabetes, and pregnancy to ischemic insult and their response to pacing postconditioning- (PPC-) induced heart protection.

Medical and pharmacy students' attitudes towards physician-pharmacist collaboration in Kuwait.

Objective: To assess and compare the attitudes of medical and pharmacy students towards physician-pharmacist collaboration and explore their opinions about the barriers to collaborative practice in Kuwait.

Methods: A cross-sectional survey of pharmacy and medical students (n=467) was conducted in Faculties of Medicine and Pharmacy, Kuwait University. Data were collected via self-administered questionnaire from first-year pharmacy and medical students and students in the last two professional years of the pharmacy and medical programs.

The effect of sphingosine-1-phosphate on colonic smooth muscle contractility: Modulation by TNBS-induced colitis.

Aim: Increased levels of circulating sphingosine-1-phosphate (S1P) have been reported in ulcerative colitis. The objective of this study was to examine the effect of S1P on colonic smooth muscle contractility and how is it affected by colitis.

Methods: Colonic inflammation was induced by intrarectal administration of trinitrobenzene sulfonic acid.

Understanding pacing postconditioning-mediated cardiac protection: a role of oxidative stress and a synergistic effect of adenosine.

We and others have demonstrated a protective role for pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury in the heart; however, the underlying mechanisms behind these protective effects are not completely understood. In this study, we wanted to further characterize PPC-mediated cardiac protection, specifically identify optimal pacing sites; examine the role of oxidative stress; and test the existence of a potential synergistic effect between PPC and adenosine. Isolated rat hearts were subjected to coronary occlusion followed by reperfusion.

The Interplay between the Renin Angiotensin System and Pacing Postconditioning Induced Cardiac Protection.

Background: Accumulating evidence suggests a cardioprotective role of pacing postconditioning (PPC) maneuvers in animal models and more recently in humans. The procedure however remains to be optimized and its interaction with physiological systems remains to be further explored. The renin angiotensin system (RAS) plays a dual role in ischemia/reperfusion (I/R) injury.

Loss of Anticontractile Effect of Perivascular Adipose Tissue on Pregnant Rats: A Potential Role of Tumor Necrosis Factor-α.

The present investigation examined the effect of pregnancy on the anticontractile effect of perivascular adipose tissue (PVAT) on the rat. Ring segments of the aorta, with and without PVAT, were set up in organ baths for isometric tension recording. In both groups, concentration-response curves to 5-hydroxytryptamine (5-HT) were displaced to the right with a reduction of the maximum response in aorta segments with PVAT.

High density lipoprotein stimulated migration of macrophages depends on the scavenger receptor class B, type I, PDZK1 and Akt1 and is blocked by sphingosine 1 phosphate receptor antagonists.

HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P) and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer.

Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy.

Background: Tyrosinemia type 1 (TT1) is an autosomal recessive disorder caused by deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). TT1 usually presents in infancy with features suggestive of liver disease or with sepsis-like symptoms.

Case Presentation: We report two Saudi siblings with TT1.

The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice.

Objectives: To examine the effects of pomegranate extract on inflammation and oxidative stress and the development of spontaneous occlusive coronary artery atherosclerosis in the SR-BI/apoE double knockout mouse model of coronary heart disease.

Methods And Results: SR-BI/apoE double KO mice were treated for two weeks with pomegranate extract via drinking water, beginning at three weeks of age. Treatment with pomegranate extract increased cholesterol ester content and reduced the abnormally high unesterified/esterified cholesterol ratio of VLDL-sized lipoproteins.

Ototoxicity of baby oil in a chinchilla animal model.

Objective: Baby oil is commonly used to soften ear wax in order to aid its removal. The aim of this study was to determine the potential ototoxicity of baby oil.

Method: A prospective controlled animal study was conducted using ten chinchillas with normal hearing function.

Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms.

Insulin-like growth factor binding proteins (IGFBPs) play important physiological functions through the modulation of IGF signaling as well as IGF-independent mechanisms. Despite the established role of IGFs in development, a similar role for the seven known IGFBPs has not been established in humans. Here, we show that an autosomal-recessive syndrome that consists of progressive retinal arterial macroaneurysms and supravalvular pulmonic stenosis is caused by mutation of IGFBP7.