Multiplexed quantification of venlafaxine and metabolites in human plasma by liquid chromatography-tandem mass spectrometry.

Background: Venlafaxine (VEN) and its O-demethylated metabolite, O-desmethylvenlafaxine (ODV), are commonly prescribed serotonin-norepinephrine reuptake inhibitors, approved for the treatment of depression and anxiety. Both are metabolized to inactive metabolites via cytochrome P450 enzymes. While previous studies have focused on quantifying VEN and ODV, bioanalytical methods for the simultaneous measurement of all metabolites are needed to fully characterize the pharmacology of VEN and ODV.

Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults.

Objectives: We investigated the utility of urine phosphoethanolamine (PEA) as a marker to aid in diagnosing and/or confirming hypophosphatasia (HPP) in adults and for monitoring patients on enzyme replacement therapy (ERT).

Methods: Data was collected from seventy-eight adults who were referred to the Vanderbilt Program for Metabolic Bone Disease for evaluation of a possible or confirmatory HPP diagnosis between July 2014 through December 2019. Fifty-nine patients were diagnosed with HPP and nineteen were excluded from a diagnosis of HPP.

Using data to make the case for program resources and sustainability: the BEST action inventory case study.

Career development programs are a valuable part of any student's experience, and increasingly is an expected part of graduate school training. While such programs are commonly available to undergraduates, there is a growing need for career support to be offered to graduate students. Making the case for resources can be a challenge in this domain, however.

Physiology and Pharmacology of Neurotransmitter Transporters.

Regulation of the ability of a neurotransmitter [our focus: serotonin, norepinephrine, dopamine, acetylcholine, glycine, and gamma-aminobutyric acid (GABA)] to reach its receptor targets is regulated in part by controlling the access the neurotransmitter has to receptors. Transporters, located at both the cellular plasma membrane and in subcellular vesicles, carry a myriad of responsibilities that include enabling neurotransmitter release and controlling uptake of neurotransmitter back into a cell or vesicle. Driven largely by electrochemical gradients, these transporters move neurotransmitters.

Comparative evaluation of blood collection tubes for clinical chemistry analysis.

Background: Routine chemistry testing is typically performed using serum or plasma to assess a patient's clinical status. At our institution, serum is the specimen type used. To reduce processing times, evaluation of plasma-based and rapid serum gel separator tubes was performed.

Procalcitonin Correlates With but Is Not Superior to Other Diagnostic Markers of Bacterial Pneumonia.

Objectives: Despite extensive research on procalcitonin (PCT)-guided therapy in lower respiratory tract infections, the association between PCT and bacterial pneumonia remains unclear.

Methods: We evaluated retrospectively the performance of PCT in patients presenting with lower respiratory tract infection symptoms and grouped by seven diagnoses. All patients had microbial testing, chest imaging, and CBC counts within 1 day of PCT testing.

Benefits and Risks of Direct-to-Consumer Testing.

Context.—: Convenience, avoidance of doctor's appointments, curiosity, and the desire to take control of one's health are driving interest toward direct-to-consumer (DTC) testing. DTC is laboratory testing that is initiated by the consumer without a physician order.

A Computational Approach to Identify Interfering Medications on Urine Drug Screening Assays without Data from Confirmatory Testing.

Urine drug screening (UDS) assays can rapidly and sensitively detect drugs of abuse but can also produce spurious results due to interfering substances. We previously developed an approach to identify interfering medications using electronic health record (EHR) data, but the approach was limited to UDS assays for which presumptive positives were confirmed using more specific methods. Here we adapted the approach to search for medications that cause false positives on UDS assays lacking confirmation data.

NCOA4 is regulated by HIF and mediates mobilization of murine hepatic iron stores after blood loss.

The mechanisms by which phlebotomy promotes the mobilization of hepatic iron stores are not well understood. NCOA4 (nuclear receptor coactivator 4) is a widely expressed intracellular protein previously shown to mediate the autophagic degradation of ferritin. Here, we investigate a local requirement for NCOA4 in the regulation of hepatic iron stores and examine mechanisms of NCOA4 regulation.

Interpreting Anion Gap Values in Adult and Pediatric Patients: Examining the Reference Interval.

Background: The anion gap is primarily used in the diagnosis of acid-base disorders. We conducted a study to determine the anion gap reference interval in our patient population, investigated the workup of abnormal vs normal anion gaps, and examined the anion gap variation upon repeated testing.

Methods: A retrospective review was performed on 17137 adult and pediatric patients who presented to Yale-New Haven Hospital outpatient clinics, emergency department, or intensive care units between 2012 and 2017.

Perivascular Adipocytes Store Norepinephrine by Vesicular Transport.

Objective- Perivascular adipose tissue (PVAT) contains an independent adrenergic system that can take up, metabolize, release, and potentially synthesize the vasoactive catecholamine norepinephrine. Norepinephrine has been detected in PVAT, but the mechanism of its protection within this tissue is unknown. Here, we investigate whether PVAT adipocytes can store norepinephrine using VMAT (vesicular monoamine transporter).

Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting.

Expansion of Perivascular Adipose Tissue (PVAT), a major regulator of vascular function through paracrine signaling, is directly related to the development of hypertension during obesity. The extent of hypertrophy and hyperplasia depends on depot location, sex, and the type of Adipocyte Progenitor Cell (APC) phenotypes present. Techniques used for APC and preadipocytes isolation in the last 10 years have drastically improved the accuracy at which individual cells can be identified based on specific cell surface markers.

Perivascular Adipose Tissue's Impact on Norepinephrine-Induced Contraction of Mesenteric Resistance Arteries.

Perivascular adipose tissue (PVAT) can decrease vascular contraction to NE. We tested the hypothesis that metabolism and/or uptake of vasoactive amines by mesenteric PVAT (MPVAT) could affect NE-induced contraction of the mesenteric resistance arteries. Mesenteric resistance vessels (MRV) and MPVAT from male Sprague-Dawley rats were used.

3T3-L1 cells and perivascular adipocytes are not equivalent in amine transporter expression.

Rat perivascular adipose tissue (PVAT) stores, takes up, and releases norepinephrine (NE; Ayala-Lopez et al. (2014) Pharmacol Res Perspect 2, e00041). We hypothesized that 3T3-L1 adipocytes would exhibit similar behaviors and, thus, could serve as a model for PVAT adipocytes.

New actions of an old friend: perivascular adipose tissue's adrenergic mechanisms.

Unlabelled: The revolutionary discovery in 1991 by Soltis and Cassis that perivascular adipose tissue (PVAT) has an anti-contractile effect changed how we think about the vasculature. Most experiments on vascular pharmacology begin by removing the fat surrounding vessels. Thus, PVAT was thought to have a minor role in vascular function and its presence was just for structural support.

The distribution and adipogenic potential of perivascular adipose tissue adipocyte progenitors is dependent on sexual dimorphism and vessel location.

There are sex associated differences in the risk for cardiovascular comorbidities in obesity and metabolic syndrome. A common clinical finding in these diseases is the expansion of perivascular adipose tissues (PVAT) which is associated with alterations in their role as regulators of vessel function. PVAT hyperplasia and hypertrophy are dependent on the biology of populations of adipocyte progenitor cells (APC).

Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.

Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism.