The discovery of 12β-methyl-17-epi-18-nor-bile acids as potent and selective TGR5 agonists.

Recent discoveries have demonstrated that the physiological function of bile acids extends to the regulation of diverse signaling processes through interactions with nuclear and G protein-coupled receptors, most notably the Farnesoid-X nuclear receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Targeting such signaling pathways pharmacologically, i.e.

3α,7-Dihydroxy-14(13→12)-5β,12α(H),13β(H)-cholan-24-oic Acids Display Neuroprotective Properties in Common Forms of Parkinson's Disease.

Parkinson's Disease is the most common neurodegenerative movement disorder globally, with prevalence increasing. There is an urgent need for new therapeutics which are disease-modifying rather than symptomatic. Mitochondrial dysfunction is a well-documented mechanism in both sporadic and familial Parkinson's Disease.

Synthesis of 12β-methyl-18--avicholic acid analogues as potential TGR5 agonists.

In the quest for new modulators of the Farnesoid-X (FXR) and Takeda G-protein-coupled (TGR5) receptors, bile acids are a popular candidate for drug development. Recently, bile acids endowed with a C16-hydroxy group emerged as ligands of FXR and TGR5 with remarkable agonistic efficacies. Inspired by these findings, we synthesised a series of C16-hydroxylated 12β-methyl-18--bile acid analogues from a Δ-12β-methyl-18--chenodeoxycholic acid intermediate (16), the synthesis of which we reported previously.

C5-Iminosugar modification of casein kinase 1δ lead 3-(4-fluorophenyl)-5-isopropyl-4-(pyridin-4-yl)isoxazole promotes enhanced inhibitor affinity and selectivity.

The quest for isoform-selective and specific ATP-competitive protein kinase inhibitors is of great interest, as inhibitors with these qualities will come with reduced toxicity and improved efficacy. However, creating such inhibitors is very challenging due to the high molecular similarity of kinases ATP active sites. To achieve selectivity for our casein kinase (CK) 1 inhibitor series, we elected to endow our previous CK1δ-hit, 3-(4-fluorophenyl)-5-isopropyl-4-(pyridin-4-yl)isoxazole (1), with chiral iminosugar scaffolds.

Synthesis of 12β-Methyl-18--bile Acids.

Decoupling the roles of the farnesoid X nuclear receptor and Takeda G-protein-coupled bile acid receptor 5 is essential for the development of novel bile acid therapeutics targeting metabolic and neurodegenerative diseases. Herein, we describe the synthesis of 12β-methyl-18--bile acids which may serve as probes in the search for new bile acid analogues with clinical applicability. A Nametkin-type rearrangement was applied to protected cholic acid derivatives, giving rise to tetra-substituted Δ- and Δ-unsaturated 12β-methyl-18--bile acid intermediates ( and ).

Correlation between optic nerve sheath diameter and Rotterdam computer tomography scoring in pediatric brain injury.

Background: Pediatric head trauma is the most common presentation to emergency departments. Increased intracranial pressure (ICP) may lead to secondary brain damage in head trauma and early diagnosis of increased ICP is very important. Measurement of optic nerve sheath diameter (ONSD) is a method that can be used for determining increased ICP.

The utility of susceptibility-weighted imaging to evaluate the extent of iron accumulation in the choroid plexus of patients with β-thalassaemia major.

Aim: To assess iron accumulation in the choroid plexus of β-thalassaemia patients using fast spin echo (FSE) T2-weighted, gradient echo (GRE) T2*-weighted, susceptibility-weighted imaging (SWI) and compare the results.

Materials And Methods: Eighteen patients with transfusion-dependent β-thalassaemia and the control group underwent magnetic resonance imaging (MRI) examinations. Signal intensities were separately evaluated using a "number of hypointensity in the choroid plexus" (NHICP) grading system on axial FSE T2-weighted, GRE T2*-weighted, and SWI images.

Acoustic radiation force impulse (ARFI) elastography in the evaluation of renal parenchymal stiffness in patients with ureteropelvic junction obstruction.

Purpose: To investigate the role of acoustic radiation force impulse (ARFI) elastography in the detection of renal parenchymal damage in kidneys with and without ureteropelvic junction obstruction (UPJO).

Methods: Twenty-five pediatric patients with a diagnosis of UPJO who underwent surgery and 15 pediatric patients with conservatively managed UPJO were prospectively evaluated with ARFI elastography. Sixteen healthy volunteers constituted the control group.

New radiological clues in the diagnosis of spindle cell oncocytoma of the adenohypophysis.

Aim: To present three new cases of spindle cell oncocytoma (SCO) from a single centre and to identify new radiological clues in the diagnosis of SCO according to the information obtained from the cases presented.

Materials And Methods: Three adults with SCO confirmed at histopathology were retrospectively reviewed. The medical records, imaging findings, operative notes, and histopathology findings for each patient were recorded.