Immunohistochemical localization of RANK, RANKL and OPG in healthy and arthritic canine elbow joints

OBJECTIVE: To determine if the receptor activator of nuclear factor-kappaB-receptor activator of nuclear factor-kappaB ligand-osteoprotegerin (RANK-RANKL-OPG) system is active in bone remodeling in dogs and, if so, whether differences in expression of these mediators occur in healthy and arthritic joints. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Fragmented processus coronoidei (n=20) were surgically removed from dogs with elbow arthritis and 5 corresponding healthy samples from dogs euthanatized for reasons other than elbow joint disease. METHODS: Bright-field immunohistochemistry and high-resolution fluorescence microscopy were used to investigate the distribution of RANK, RANKL, and OPG in healthy and arthritic joints. RESULTS: All 3 molecules were identified by immunostaining of canine bone tissue. In elbow dysplasia, the number of RANK-positive osteoclasts was increased. In their vicinity, cells expressing RANKL, a mediator of osteoclast activation, were abundant whereas the number of osteoblasts having the potential to limit osteoclastogenesis and bone resorption via OPG was few. CONCLUSIONS: The RANK-RANKL-OPG system is active in bone remodeling in dogs. In elbow dysplasia, a surplus of molecules promoting osteoclastogenesis was evident and is indicative of an imbalance between the mediators regulating bone resorption and bone formation. Both OPG and neutralizing antibodies against RANKL have the potential to counterbalance bone resorption. CLINICAL RELEVANCE: Therapeutic use of neutralizing antibodies against RANKL to inhibit osteoclast activation warrants further investigation.

Albrecht von Haller. Leben - Werk- Epoche

Zum 300. Geburtstag des Dichters, Sammlers, Professors und Experimentalforschers am 16. Oktober 2008.Der Universalgelehrte Albrecht von Haller (1708-1777) ist eine der zentralen Gestalten des Jahrhunderts der Aufklärung. Als Dichter und Gelehrter, Sammler und Enzyklopädist, Universitätsprofessor und Experimentalforscher, Gesellschaftspräsident und Korrespondent, profilierter Autor und mächtiger Rezensent, Magistrat und orthodoxer Christ spiegelt er zahlreiche Strömungen, Ereignisse und Verhältnisse seiner Zeit.Der Band führt in die einzelnen Wirkungsgebiete Hallers ein. In drei Abschnitten Leben und Umfeld, Werk und Wirkung und Haller in seiner Zeit liefern die Beiträge vielfältige und überraschende Einblicke in die Problemlagen und Entwicklungen seiner Epoche.

High protein intake reduces intrahepatocellular lipid deposition in humans

BACKGROUND: High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown. OBJECTIVE: The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men. DESIGN: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens. RESULTS: The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14). CONCLUSIONS: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.

Berns goldene Zeit. Das 18. Jahrhundert neu entdeckt

Wie bereits die drei ersten Bände der Arbeitsgemeinschaft Berner Zeiten, behandelt nun auch Band vier "Berns goldene Zeit" die Geschichte von Stadt und Landschaft Bern. Er berücksichtigt das Kantonsgebiet in den Grenzen vor 1798 und somit auch den bernischen Aargau und die Waadt. Er öffnet zudem den Blick über die Epochenzäsur von 1798 hinaus auf die Umbruchsphase der Helvetischen Republik und der Mediation. Der Anspruch, eine Gesamtschau zu vermitteln, schliesst konzeptionell alle Schichten und Gruppen der Bevölkerung - Eliten ebenso wie die breite Bevölkerung - mit ein. Dies gilt ebenso für sämtliche geschichtlichen Felder - Verfassung, Politik und Verwaltung, Wirtschaft, Umwelt und Gesellschaft, das geistige und kulturelle Leben in Kirche, Wissenschaften und Künsten.