Cholangiocytes are the epithelial cells that line the bile ducts. Along the biliary tree, two different kinds of cholangiocytes exist: small and large cholangiocytes. Each type has important differences in their biological role in physiologic and pathologic conditions. In response to injury, cholangiocytes become reactive and acquire a neuroendocrine-like phenotype with the secretion of a number of peptides. These molecules act in an autocrine/paracrine fashion to modulate cholangiocyte biology and determine the evolution of biliary damage. The failure of such mechanisms is believed to influence the progression of cholangiopathies, a group of diseases that selectively target biliary cells. Therefore, the understanding of mechanisms regulating cholangiocyte response to injury is expected to foster the development of new therapeutic options to treat biliary diseases. In this review, we discuss the most recent findings in the mechanisms driving cholangiocyte adaptation to damage, with particular emphasis on molecular pathways that are susceptible of therapeutic intervention. Morphogenic pathways (Hippo, Notch, Hedgehog), which have been recently shown to regulate biliary ontogenesis and response to injury, are also reviewed as well as the results of ongoing clinical trials evaluating new drugs for the treatment of cholangiopathies.

Our aim was to correlate the health status with objective and radiological outcomes in patients treated by open reduction and internal fixation for fractures of both bones of the forearm.We assessed 23 patients (24 fractures) subjectively, objectively and radiologically at a mean of 34 months (11 to 72). Subjective assessment used the disability of the arm, shoulder and hand (DASH) and musculoskeletal functional attachment (MFA) questionnaires. The range of movement of the forearm and wrist, grip and pinch strength were measured objectively and standardised radiographs were evaluated.In general, patients reported good overall function based on the DASH (mean 12; range 0 to 42) and MFA (mean 19; range 0 to 51) scores. However, pronation and grip and pinch strength were significantly decreased (p < 0.005). These deficiencies correlated with poorer subjective outcomes.Operative stabilisation of fractures of the radius and ulna led to a reliably acceptable functional outcome. However, despite these generally satisfactory results, the outcome scores worsened with reduction in the range of movement of the forearm and wrist.Fractures of both bones of the forearm are relatively common injuries which can challenge the treating physician. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Healing occurs reliably after closed treatment but malunion, with resultant decreased rotation of the forearm, is common and has been associated with poor results. 17,18 Rotation of the forearm is a complex interaction between the radius and ulna and the restoration of this movement depends on both an accurate reduction of the fractures and early initiation of post-operative movement.

Unilateral and bilateral DRS show considerable differences in gender distribution, associated ocular deviation, overshoots, and ocular and systemic associations.

Biliary hyperplasia and liver fibrosis are common features in cholestatic liver disease. Melatonin is synthesized by the pineal gland as well as the liver. Melatonin inhibits biliary hyperplasia of bile duct-ligated (BDL) rats. Since melatonin synthesis (by the enzyme serotonin N-acetyltransferase, AANAT) from the pineal gland increases after dark exposure, we hypothesized that biliary hyperplasia and liver fibrosis are diminished by continuous darkness via increased melatonin synthesis from the pineal gland. Normal or BDL rats (immediately after surgery) were housed with light-dark cycles or complete dark for 1 wk before evaluation of 1) the expression of AANAT in the pineal gland and melatonin levels in pineal gland tissue supernatants and serum; 2) biliary proliferation and intrahepatic bile duct mass, liver histology, and serum chemistry; 3) secretin-stimulated ductal secretion (functional index of biliary growth); 4) collagen deposition, liver fibrosis markers in liver sections, total liver, and cholangiocytes; and 5) expression of clock genes in cholangiocytes. In BDL rats exposed to dark there was 1) enhanced AANAT expression/melatonin secretion in pineal gland and melatonin serum levels; 2) improved liver morphology, serum chemistry and decreased biliary proliferation and secretin-stimulated choleresis; and 4) decreased fibrosis and expression of fibrosis markers in liver sections, total liver and cholangiocytes and reduced biliary expression of the clock genes PER1, BMAL1, CLOCK, and Cry1. Thus prolonged dark exposure may be a beneficial noninvasive therapeutic approach for the management of biliary disorders.