Pharmacokinetics and Pharmacodynamics of Intravenous Magnesium Sulfate in Pediatric Acute Asthma Exacerbations.

Pediatric asthma exacerbations represent a significant cause of emergency department use and hospitalizations. Despite available treatment options, many children's exacerbations are refractory to standard therapies and require adjunct treatments. The Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department study investigated the pharmacology of intravenous magnesium sulfate (IVMg) in treating pediatric asthma exacerbations.

CYP6B6 mediated adaptation to capsaicinoids in the generalist Helicoverpa armigera and specialist H. assulta: Transcriptional response and metabolic detoxification.

Capsaicin and dihydrocapsaicin are the principal pungent compounds in hot peppers. The generalist Helicoverpa armigera and the specialist H. assulta are two of the few insects that can feed on hot pepper fruits.

Interaction of azithromycin and methylprednisolone with ex-vivo extracorporeal membrane oxygenation circuits (ECMO).

Background: Azithromycin and methylprednisolone are two medications that are commonly used in patients who require ECMO support. Unfortunately, ECMO support can decrease drug concentrations through adsorption to circuit components. Such interactions have not been well described for either azithromycin or methylprednisolone.

Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.

Sensitivity to the subjective reinforcing properties of opioids has a genetic component and can predict addiction liability of opioid compounds. We previously identified as a candidate gene underlying increased brain concentration of the oxycodone () metabolite oxymorphone () in BALB/cJ () versus BALB/cByJ () females that could increase OXY state-dependent reward. A large structural intronic variant is associated with a robust reduction of Zhx2 expression in J mice, which we hypothesized enhances OMOR levels and OXY addiction-like behaviors.

Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes.

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes.

The Cytochrome P450 2C8*3 Variant (rs11572080) Is Associated with Improved Asthma Symptom Control in Children and Altered Lipid Mediator Production and Inflammatory Response in Human Bronchial Epithelial Cells.

This study investigated an association between the cytochrome P450 (CYP) 2C8*3 polymorphism with asthma symptom control in children and changes in lipid metabolism and pro-inflammatory signaling by human bronchial epithelial cells (HBECs) treated with cigarette smoke condensate (CSC). CYP genes are inherently variable in sequence, and while such variations are known to produce clinically relevant effects on drug pharmacokinetics and pharmacodynamics, the effects on endogenous substrate metabolism and associated physiologic processes are less understood. In this study, CYP2C8*3 was associated with improved asthma symptom control among children: Mean asthma control scores were 3.

A Ropivacaine-Eluting Poly(Lactide-Co-Caprolactone) Wound Dressing Provided Enhanced Analgesia in Partial-Thickness Porcine Injuries.

Background: Partial-thickness skin wounds are some of the most painful injuries because of large areas of exposed nerve endings. These injuries often require systemic opioid treatment to manage pain adequately. However, the Centers for Disease Control and Prevention reported nearly 17,000 prescription opioid-related deaths in the United States in 2021 alone, highlighting the ongoing need for nonopioid treatment strategies.

Clinical pharmacokinetics of atropine oral gel formulation in healthy volunteers.

Sialorrhea or drooling is a common problem in children and adults with neurodevelopmental disorders. It can negatively impact the quality of life due to its physical and psychological manifestations. Providers commonly prescribe atropine eye drops for topical administration to the oral mucosa, as an off-label treatment to manage sialorrhea.

Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.

Objectives: Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown.

Capsaicin binds the N-terminus of Hsp90, induces lysosomal degradation of Hsp70, and enhances the anti-tumor effects of 17-AAG (Tanespimycin).

Heat shock protein 90 (Hsp90) and its co-chaperones promote cancer, and targeting Hsp90 holds promise for cancer treatment. Most of the efforts to harness this potential have focused on targeting the Hsp90 N-terminus ATP binding site. Although newer-generation inhibitors have shown improved efficacy in aggressive cancers, induction of the cellular heat shock response (HSR) by these inhibitors is thought to limit their clinical efficacy.

Evaluation and comparison of pharmacokinetic profiles and safety of two extended-release buprenorphine formulations in common marmosets (Callithrix jacchus).

While sustained-release buprenorphine (BSR) is used as a long-lasting opioid analgesic in common marmosets (Callithrix jacchus), there are no published studies on pharmaceutical-grade extended-release buprenorphine options such as Ethiqa XR (EXR) for this species. However, BSR is a compounded product and has been reported to cause injection site reactions in multiple species, including marmosets. Additionally, now with the availability of EXR, a pharmaceutical-grade veterinary product, the use of BSR in laboratory animals is not compliant with the Guide for the Care and Use of Laboratory Animals (Guide) unless scientifically justified and approved by the IACUC.

Hearing Following Prolonged and Delayed Ganciclovir Treatment in a Murine Cytomegalovirus Model.

Objective: Compare hearing outcomes utilizing standard, prolonged and delayed ganciclovir (GCV) therapy in a murine model of cytomegalovirus (CMV).

Methods: BALB/c mice were inoculated with mouse cytomegalovirus (mCMV) or saline via intracerebral injection on postnatal day 3 (p3). Intraperitoneal GCV or saline was administered at 12 h intervals for the duration of the standard (p3-p17), delayed (p30-p44), or prolonged treatment windows (p3-p31).

Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic Expression by Vasaka (; Malabar Nut) Tea.

This study tested whether a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus production. Wood/biomass smoke is a pneumotoxic air pollutant. Mucus normally protects the airways, but excessive production can obstruct airflow and cause respiratory distress.

External assessment and refinement of a population pharmacokinetic model to guide tacrolimus dosing in pediatric heart transplant.

Study Objective: The immunosuppressant tacrolimus is a first-line agent to prevent graft rejection following pediatric heart transplant; however, it suffers from extensive inter-patient variability and a narrow therapeutic window. Personalized tacrolimus dosing may improve transplant outcomes by more efficiently achieving and maintaining therapeutic tacrolimus concentrations. We sought to externally validate a previously published population pharmacokinetic (PK) model that was constructed with data from a single site.

Pharmacokinetics of intranasal amiloride in healthy volunteers.

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models.

Mechanisms and Consequences of Variable TRPA1 Expression by Airway Epithelial Cells: Effects of Genotype and Environmental Agonists on Cellular Responses to Pollutants and Asthma.

Background: Transient receptor potential ankyrin-1 [transient receptor potential cation channel subfamily A member 1 (TRPA1)] and vanilloid-1 [transient receptor potential cation channel subfamily V member 1 (TRPV1)] detect inhaled irritants, including air pollutants and have roles in the development and exacerbation of asthma.

Objectives: This study tested the hypothesis that increased expression of TRPA1, stemming from expression of the loss-of-function (I585V; rs8065080) polymorphic variant by airway epithelial cells may explain prior observations of worse asthma symptom control among children with the I585I/V genotype, by virtue of sensitizing epithelial cells to particulate materials and other TRPA1 agonists.

Methods: TRP agonists, antagonists, small interfering RNA (siRNA), a nuclear factor kappa light chain enhancer of activated B cells (NF-) pathway inhibitor, and kinase activators and inhibitors were used to modulate TRPA1 and TRPV1 expression and function.

CYP1B1-derived epoxides modulate the TRPA1 channel in chronic pain.

Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury.

Cannabis Use Is Associated With Decreased Antiretroviral Therapy Adherence Among Older Adults With HIV.

Background: Conflicting evidence exists on the impact of cannabis use on antiretroviral therapy (ART) adherence among people with human immunodeficiency virus (PWH). We leveraged data collected among older PWH to characterize longitudinal associations between cannabis use and ART adherence.

Methods: AIDS Clinical Trials Group (ACTG) A5322 study participants were categorized as <100% (≥1 missed dose in past 7 days) or 100% (no missed doses) ART adherent.

Evaluating the efficacy of prototype antiseizure drugs using a preclinical pharmacokinetic approach.

Objective: Pharmacokinetics (PK) of a drug drive its exposure, efficacy, and tolerability. A thorough preclinical PK assessment of antiseizure medications (ASMs) is therefore essential to evaluate the clinical potential. We tested protection against evoked seizures of prototype ASMs in conjunction with analysis of plasma and brain PK as a proof-of-principle study to enhance our understanding of drug efficacy and duration of action using rodent seizure models.

Effect of combustion particle morphology on biological responses in a Co-culture of human lung and macrophage cells.

Atmospheric aging of combustion particles alters their chemical composition and morphology. Previous studies have reported differences in toxicological responses after exposure to fresh versus aged particles, with chemical composition being the prime suspect behind the differences. However, less is known about the contribution of morphological differences in atmospherically aged particles to toxicological responses, possibly due to the difficulty in resolving the two properties (composition and morphology) that change simultaneously.