Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist.

MDP-SPECT Versus Hybrid MDP-SPECT/CT in the Evaluation of Suspected Pars Interarticularis Fracture in Young Athletes.

Background And Purpose: To assess benefits of hybrid (single photon emission computerized tomography [SPECT]/computed tomography [CT]) imaging over SPECT imaging only in the management of young athletes with low back pain (LBP) due to suspected pars interarticularis fracture.

Methods: Retrospectively reviewed medical records of 163 consecutive patients who had radionuclide SPECT imaging for evaluation of LBP between January 1, 2010 and December 30, 2015. All enrolled patients were divided into two groups (group 1: patients with radionuclide SPECT imaging only and group 2: patients with radionuclide hybrid imaging).

Cost-effective teaching of radiology with preclinical anatomy.

Graduating physicians in all subspecialties have an increased need for competency in radiology, particularly since the use of diagnostic imaging continues to grow. To integrate the teaching of radiology with anatomy during the first year of medical school at Howard University, a novel approach was developed to overcome the limitations of resources including funding, faculty, and curricular time. The resulting program relies on self-study and peer-to-peer interactions to develop proficiency at manipulating free versions of medical image viewer software (using the DICOM standard), identifying normal anatomy in medical images, and applying critical thinking skills to understand common clinical conditions.

Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis.

Class IIa histone deacetylases (HDACs) are signal-dependent modulators of transcription with established roles in muscle differentiation and neuronal survival. We show here that in liver, class IIa HDACs (HDAC4, 5, and 7) are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, class IIa HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase.

AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation.

Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands of genes. Whereas the master clock in the brain is set by light, pacemakers in peripheral organs, such as the liver, are reset by food availability, although the setting, or "entrainment," mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1).

Benefit of farnesoid X receptor inhibition in obstructive cholestasis.

The nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor have been implicated in regulating bile acid, lipid, carbohydrate, and xenobiotic metabolism. Bile duct ligation was used to increase endogenous bile acids and evaluate the roles of these receptors in modulating cholestatic liver injury. FXR knockout (KO) mice were found to be protected from obstructive cholestasis.

Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury.

Cholestasis is associated with accumulation of bile acids and lipids, and liver injury. The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic nuclear receptors that coordinate protective hepatic responses to potentially toxic stimuli, including bile acids. We investigated the role of these receptors in the regulation of bile acid and lipid metabolism in a bile duct ligation (BDL) model of cholestasis applied to receptor knockout mice.

A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR.

The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds.