Observational study of the bisphosphonate-related osteonecrosis of jaws.

Introduction: The bisphosphonate-related osteonecrosis of the jaw was first referred to in 2003. Bisphosphonates action is focused on the osteoclasts. The drastic inhibition of the osteoclastic function is harmful for the jaws which are the only bones of the human skeleton in relative contact with the external environment.

Elevated Serum Levels of Sclerostin are Associated with High Disease Activity and Functional Impairment in Patients with Axial Spondyloarthritis.

Background: Recent research suggests that biomarkers may be useful in assessing disease activity, structural damage, and response to therapy in axial spondyloarthritis (axSpA). Our study aims at evaluating the relationship between inflammation and bone remodeling markers and variables assessing disease activity and functional disability in patients with axSpA.

Methods: Serum levels of sclerostin, matrix metalloproteinase-3 (MMP-3), interleukin-17 (IL-17), and IL-23 were measured in 60 patients with axSpA and 20 healthy controls.

Bone mineral content in patients with congenital generalized lipodystrophy is unaffected by metreleptin replacement therapy.

Context: Leptin alters bone and mineral metabolism in rodents, but this has not been verified in humans. PATIENTS with congenital generalized lipodystrophy (CGL) have low leptin due to deficient adipose mass and serve as models of leptin deficiency and replacement.

Objective: To study the effects of recombinant human methionyl leptin (metreleptin) on bone mineral content (BMC) and mineral metabolism.

The role of proinsulin and insulin in the diagnosis of insulinoma: a critical evaluation of the Endocrine Society clinical practice guideline.

Context: An end of fast insulin ≥ 3 μIU/mL and a proinsulin concentration ≥ 5 pmol/L have been suggested as useful cutoffs for the diagnosis of insulinoma.

Objective: The main objective was to evaluate the diagnostic performance of an end of fast insulin concentration ≥ 3 μIU/mL and an end of fast proinsulin concentration ≥ 5 pmol/L.

Design: The design was a case-control series.

Ultrasonography of the non-traumatic lesions of the fingers. Pictorial essay.

The purpose of this pictorial essay is to illustrate the ultrasonographic aspects of the non-traumatic lesions of the fingers. Diffuse (especially dactylitis) and localized (tumors, tophi, calcinosis, etc) lesions of the digits are discussed and illustrated. For a better understanding, the US images are compared with the clinical aspect of the pathological fingers.

The liver diseases of lipodystrophy: the long-term effect of leptin treatment.

Background & Aims: Lipodystrophies are hypoleptinemic conditions characterized by fat loss, severe insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are also features of this condition. We studied the spectrum of liver disease in lipodystrophy and the effects of leptin replacement.

Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome.

Context: The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features.

Objective: The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment.

Cardiomyopathy in congenital and acquired generalized lipodystrophy: a clinical assessment.

Lipodystrophy is a rare disorder characterized by loss of adipose tissue and low leptin levels. This condition is characterized by severe dyslipidemia, insulin resistance, diabetes mellitus, and steatohepatitis. Another phenotypic feature that occurs with considerable frequency in generalized lipodystrophy is cardiomyopathy.

Cyclosporin A inhibits flow-mediated activation of endothelial nitric-oxide synthase by altering cholesterol content in caveolae.

Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an essential role in regulation of vascular function and structure by blood flow. Although cyclosporin A (CsA), an inhibitory ligand of cyclophilin A, is a widely used immunosuppressive drug, it causes arterial hypertension in part by impairing eNOS-dependent vasodilation.

Cyclophilin A is a proinflammatory cytokine that activates endothelial cells.

Objective: Cyclophilin A (CyPA) is an abundant intracellular protein that is considered to be the main target of the immunosuppressive drug cyclosporine A. We and others showed that CyPA is secreted from smooth muscle cells and macrophages in response to oxidative stress and lipopolysaccharide, suggesting a role for CyPA in inflammation. We therefore studied the proinflammatory effects of CyPA on vascular endothelium.

Sphingosine 1-phosphate transactivates the platelet-derived growth factor beta receptor and epidermal growth factor receptor in vascular smooth muscle cells.

Sphingosine 1-phosphate (S1P) is a bioactive lipid generated during vascular injury that regulates cell growth, differentiation, survival, and motility via endothelial differentiation gene (EDG) family G protein-coupled receptors. Although several G protein-coupled receptor ligands transactivate receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), S1P-stimulated receptor tyrosine kinase transactivation has not been well studied. We show that platelet-derived growth factor beta receptor (PDGFbetaR) and EGFR are tyrosine phosphorylated in response to S1P in rat aortic vascular smooth muscle cells (VSMCs).

Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase.

Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an essential role in regulation of vascular function and structure by blood flow, but the molecular mechanisms that transduce mechanical force to eNOS activation are not well understood. In this study, we found that laminar flow (shear stress=12 dyne/cm2) rapidly activates vascular endothelial growth factor receptor 2 (VEGFR2) in a ligand-independent manner and leads to eNOS activation in cultured endothelial cells.