Assay for the quantification of abemaciclib, its metabolites, and olaparib in human plasma by liquid chromatography-tandem mass spectrometry.

An isotope-dilution bioanalytical assay for abemaciclib and its metabolites in combination with olaparib was developed and validated in human plasma K2 EDTA. For the quantitative assay, human plasma samples (or human plasma QC samples) were spiked with internal standard solution before a simple protein precipitation with methanol. The extract was injected onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument where it was chromatographically separated by a polar end-capped reversed phase column and guard using gradient elution with water and methanol both modified with 0.

The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

Purpose: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain.

Methods: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months.

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia.

Selinexor, an oral inhibitor of the nuclear transport protein Exportin-1, shows promising single-agent activity in clinical trials of relapsed/refractory (R/R) acute myeloid leukemia (AML) and preclinical synergy with topoisomerase (topo) IIα inhibitors. We conducted a phase 1, dose-escalation study of selinexor with mitoxantrone, etoposide, and cytarabine (MEC) in 23 patients aged < 60 years with R/R AML. Due to dose-limiting hyponatremia in 2 patients on dose level 2 (selinexor 40 mg/m), the maximum tolerated dose was 30 mg/m.

Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.

Background: Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses.

Hypothesis/objectives: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen.

Exploration of Verticillins in High-Grade Serous Ovarian Cancer and Evaluation of Multiple Formulations in Preclinical In Vitro and In Vivo Models.

Verticillins are epipolythiodioxopiperazine alkaloids isolated from a fungus with nanomolar anti-tumor activity in high-grade serous ovarian cancer (HGSOC). HGSOC is the fifth leading cause of death in women, and natural products continue to be an inspiration for new drug entities to help tackle chemoresistance. Verticillin D was recently found in a new fungal strain and compared to verticillin A.

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares.

Background: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed.

Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.

Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal Cancer.

Objectives: To estimate the maximally tolerated dose (MTD) and describe toxicities associated with lenvatinib and weekly paclitaxel in patients with recurrent endometrial and platinum resistant epithelial ovarian cancer.

Methods: Using a 3 + 3 design patients were given weekly paclitaxel 80 mg/m2 IV day 1, 8, 15 and oral levantinib daily on a 28-day cycle. Lenvatinib dose levels were 8 mg, 12 mg, 16 mg, 20 mg.

Pharmacological Prevention of Neonatal Opioid Withdrawal in a Pregnant Guinea Pig Model.

Newborns exposed to prenatal opioids often experience intense postnatal withdrawal after cessation of the opioid, called neonatal opioid withdrawal syndrome (NOWS), with limited pre- and postnatal therapeutic options available. In a prior study in pregnant mice we demonstrated that the peripherally selective opioid antagonist, 6β-naltrexol (6BN), is a promising drug candidate for preventive prenatal treatment of NOWS, and a therapeutic mechanism was proposed based on preferential delivery of 6BN to fetal brain with relative exclusion from maternal brain. Here, we have developed methadone (MTD) treated pregnant guinea pigs as a physiologically more suitable model, enabling detection of robust spontaneous neonatal withdrawal.

Quantification of Microcystin-LR in Human Urine by Immunocapture Liquid Chromatography Tandem Mass Spectrometry.

Microcystins are toxins produced by many cyanobacteria species, which are often released into waterways during blue-green algal blooms in freshwater and marine habitats. The consumption of microcystin-contaminated water is a public health concern as these toxins are recognized tumor promoters and are hepatotoxic to humans and animals. A method to confirm human exposures to microcystins is needed; therefore, our laboratory has developed an immunocapture liquid chromatography tandem mass spectrometry (LC-MS/MS) method targeting the conserved adda portion of microcystins for the quantitation of a prevalent and highly toxic congener of microcystin, microcystin-LR (MC-LR).

Detection of α-, β-, and γ-amanitin in urine by LC-MS/MS using N-α-amanitin as the internal standard.

The majority of fatalities from poisonous mushroom ingestion are caused by amatoxins. To prevent liver failure or death, it is critical to accurately and rapidly diagnose amatoxin exposure. We have developed a liquid chromatography tandem mass spectrometry method to detect α-, β-, and γ-amanitin in urine to meet this need.

Avanti lipid tools: connecting lipids, technology, and cell biology.

Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed.

Sphingosine induces the aggregation of imine-containing peroxidized vesicles.

Lipid peroxidation plays a central role in the pathogenesis of many diseases like atherosclerosis and multiple sclerosis. We have analyzed the interaction of sphingosine with peroxidized bilayers in model membranes. Cu(2+) induced peroxidation was checked following UV absorbance at 245nm, and also using the novel Avanti snoopers®.

Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome.

Objective: In preclinical reports, restriction of dietary methionine intake was shown to enhance metabolic flexibility, improve lipid profiles, and reduce fat deposition. The present report is the outcome of a "proof of concept" study to evaluate the efficacy of dietary methionine restriction (MR) in humans with metabolic syndrome.

Methods: Twenty-six obese subjects (six male and 20 female) meeting criteria for metabolic syndrome were randomized to a diet restricted to 2 mg methionine/kg body weight per day and were provided capsules containing either placebo (n = 12) or 33 mg methionine/kg body weight per day (n = 14).

Role of beta-adrenergic receptors in the hyperphagic and hypermetabolic responses to dietary methionine restriction.

Dietary methionine restriction (MR) limits fat deposition and decreases plasma leptin, while increasing food consumption, total energy expenditure (EE), plasma adiponectin, and expression of uncoupling protein 1 (UCP1) in brown and white adipose tissue (BAT and WAT). beta-adrenergic receptors (beta-AR) serve as conduits for sympathetic input to adipose tissue, but their role in mediating the effects of MR on energy homeostasis is unclear. Energy intake, weight, and adiposity were modestly higher in beta(3)-AR(-/-) mice on the Control diet compared with wild-type (WT) mice, but the hyperphagic response to the MR diet and the reduction in fat deposition did not differ between the genotypes.

Aluminum oxide nanostructured microcantilever arrays for nanomechanical-based sensing.

Novel nanostructured microcantilever (MC) surfaces were developed by modifying the active side of the MCs with aluminum oxide nanoparticles (AONP) for purposes of enhancing sensitivity in nanomechanical-based sensing. Uniform layers of AONP were spin coated and chemically immobilized on the surfaces of MCs with tetramethoxysilane (TMOS) as a cross-linker. Optimization studies on MC modification were performed for better surface uniformity and higher surface area, based on scanning electron microscope (SEM) images.

Morphological and chemical optimization of microcantilever surfaces for thyroid system biosensing and beyond.

The development of biosensors is vital in many areas of biotechnology and biomedical research. A prominent new class of label-free biosensors are those based on ligand-induced nanomechanical responses of microcantilevers (MCs). The interaction between biologically significant ligands with bioreceptors (e.

Development of a nanomechanical biosensor for analysis of endocrine disrupting chemicals.

A nanomechanical transducer is developed to detect and screen endocrine disrupting chemicals (EDCs) combining fluidic sample injection and delivery with bioreceptor protein functionalized microcantilevers (MCs). The adverse affects of EDCs on the endocrine system of humans, livestock, and wildlife provides strong motivation for advances in analytical detection and monitoring techniques. The combination of protein receptors, which include estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta), as well as monoclonal antibodies (Ab), with MC systems employing modified nanostructured surfaces provides for excellent nanomechanical response sensitivity and the inherent selectivity of biospecific receptor-EDC interactions.