Increased Synapse Elimination by Inflammatory Cells Contributes to Long-lasting Post-Stroke Memory Dysfunction in Old Mice.

Old patients are more likely to experience memory dysfunction than young patients after a stroke. It has been reported that brain astrocytes and microglia cause excessive removal of synapses at the acute and subacute stages of stroke, and inhibition of their phagocytosis improved neurobehavioral outcomes. We hypothesized that memory dysfunction in old subjects is associated with increased synapse removal by inflammatory cells.

Distinct Interactions of Cannabinol and Its Cytochrome P450-Generated Metabolites with Receptors and Sensory Neurons.

Interest in nonpsychotropic cannabinoids like cannabinol (CBN) is increasing for pain therapy. This study delivers critical insights into CBN's metabolism and pharmacological effects, uncovering its therapeutic potential for pain reduction. Using metabolomics, we identify CBN-11-OH as the dominant metabolite, with lower levels of CBN-1'-OH and CBN-quinone.

Association of Endothelial Dysfunction With Chronic Marijuana Smoking and THC-Edible Use.

Importance: Recreational and medicinal cannabis legalization has led to increased cannabis use. To understand the consequences for vascular health, we initiated the CANnabis: Does It Damage Endothelium (CANDIDE) study.

Objective: To investigate whether cannabis use is associated with vascular endothelial dysfunction.

CRISPR: fundamental principles and implications for anaesthesia.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based medical therapies are increasingly gaining regulatory approval worldwide. Consequently, patients receiving CRISPR therapy will come under the care of anaesthesiologists. An understanding of CRISPR, its technological implementations, and the characteristics of patients likely to receive this therapy will be essential to caring for this patient population.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats.

Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cells .

Introduction: Patients with cirrhosis undergoing liver transplantation frequently exhibit systemic inflammation, coagulation derangements, and edema, indicating endothelial dysfunction. This syndrome may worsen after ischemia-reperfusion injury of the liver graft, coincident with organ dysfunction that worsens patient outcomes. Little is known about changes in endothelial permeability during liver transplantation.

Elucidating the Mechanism of Metabolism of Cannabichromene by Human Cytochrome P450s.

Cannabichromene (CBC) is a nonpsychoactive phytocannabinoid well-known for its wide-ranging health advantages. However, there is limited knowledge regarding its human metabolism following CBC consumption. This research aimed to explore the metabolic pathways of CBC by various human liver cytochrome P450 (CYP) enzymes and support the outcomes using data from mice.

Surviving Sepsis Campaign Research Priorities 2023.

Objectives: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock.

Design: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities.

Methods: Each task force member submitted five research questions on any sepsis-related subject.

Multi-Omic blood analysis reveals differences in innate inflammatory sensitivity between species.

Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

The Effect of Route of Administration and Vehicle on the Pharmacokinetics of THC and CBD in Adult, Neonate, and Breastfed Sprague-Dawley Rats.

Basic pharmacokinetic (PK) and pharmacodynamic models of the phytocannabinoids Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are critical for developing translational models of exposure and toxicity. The neonatal period is a particularly important time to study the effects of cannabinoids, yet there are few studies of cannabinoid PKs by different routes such as direct injection or breast milk ingestion. To study this question, we have developed a translationally relevant rodent model of perinatal cannabinoid administration by measuring plasma levels of THC and CBD after different routes and preparations of these drugs.

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels.

Background: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.

Methods: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers.

Metabolites of Cannabigerol Generated by Human Cytochrome P450s Are Bioactive.

The phytocannabinoid cannabigerol (CBG) is the central biosynthetic precursor to many cannabinoids, including Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD). Though the use of CBG has recently witnessed a widespread surge because of its beneficial health effects and lack of psychoactivity, its metabolism by human cytochrome P450s is largely unknown. Herein, we describe comprehensive and cytochrome P450 (CYP)-mediated metabolic studies of CBG, ranging from liquid chromatography tandem mass spectrometry-based primary metabolic site determination, synthetic validation, and kinetic behavior using targeted mass spectrometry.

A Mouse Model of Orotracheal Intubation and Ventilated Lung Ischemia Reperfusion Surgery.

Ischemia reperfusion (IR) injury frequently results from processes that involve a transient period of interrupted blood flow. In the lung, isolated IR permits the experimental study of this specific process with continued alveolar ventilation, thereby avoiding the compounding injurious processes of hypoxia and atelectasis. In the clinical context, lung ischemia reperfusion injury (also known as lung IRI or LIRI) is caused by numerous processes, including but not limited to pulmonary embolism, resuscitated hemorrhagic trauma, and lung transplantation.

A novel approach for the detection of cognitive impairment and delirium risk in older patients undergoing spine surgery.

Background: Postoperative delirium is a common postsurgical complication in older patients and is associated with high morbidity and mortality. The objective of this study was to determine whether a digital cognitive assessment and patient characteristics could identify those at-risk.

Methods: Patients 65 years and older undergoing spine surgeries ≥3 h were evaluated as part of a single-center prospective observational cohort study at an academic medical center, from January 1, 2019, to December 31, 2020.

COVID-19-associated Lung Microvascular Endotheliopathy: A "From the Bench" Perspective.

Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes.

Background: The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic. N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis.

Isolation of Primary Mouse Lung Endothelial Cells.

Endothelial cells play critical roles in the regulation of vascular tone, immunity, coagulation, and permeability. Endothelial dysfunction occurs in medical conditions including diabetes, atherosclerosis, sepsis, and acute lung injury. A reliable and reproducible method to isolate pure endothelial cells from mice is needed to investigate the role of endothelial cells in the pathogenesis of these and other conditions.

Surviving Sepsis Campaign: Research Opportunities for Infection and Blood Purification Therapies.

Unlabelled: Patients with infection can develop sepsis, and their mortality can be high. An important aspect in the treatment of sepsis is adequate management of the infection.

Data Sources: Using a modified Delphi approach, the Surviving Sepsis Campaign research committee recently published a series of 26 priorities for sepsis and septic shock.

ACVR1 extends inflammatory responses in human induced pluripotent stem cell-derived macrophages.

Macrophages play crucial roles in many human disease processes. However, obtaining large numbers of primary cells for study is often difficult. We describe 2D and 3D methods for directing human induced pluripotent stem cells (hiPSCs) into macrophages (iMACs).

Oxidative Stress and Endothelial Dysfunction in Sepsis and Acute Inflammation.

Under homeostatic conditions, the endothelium dynamically regulates vascular barrier function, coagulation pathways, leukocyte adhesion, and vasomotor tone. During sepsis and acute inflammation, endothelial cells (ECs) undergo multiple phenotypic and functional modifications that are initially adaptive but eventually become harmful, leading to microvascular dysfunction and multiorgan failure. Sepsis unbalances the redox homeostasis toward a pro-oxidant state, characterized by an excess production of reactive oxygen species and reactive nitrogen species, mitochondrial dysfunction, and a breakdown of antioxidant systems.

The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

Objectives: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients.

Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document.

Catecholaminergic Vasopressors Reduce Toll-Like Receptor Agonist-Induced Microvascular Endothelial Cell Permeability But Not Cytokine Production.

Objectives: Catecholaminergic vasopressors are the cornerstone of circulatory shock management. Nevertheless, catecholamines have problematic side effects, arousing a growing interest in noncatecholaminergic agents such as vasopressin or angiotensin-II. However, their respective effects on sepsis-associated microvascular endothelial dysfunction such as permeability or inflammation remain elusive.