Adipositas und Typ-2-Diabetes sind häufige Erkrankungen des Stoffwechsels. Zur Basistherapie der Adipositas und des Typ-2-Diabetes gehören eine gesunde Ernährungs- weise und die Erhöhung der körperlichen Aktivität unter anderem mit dem Ziel der Gewichtsreduktion. Vermehrte Bewegung führt neben der Verbesserung der körperlichen Leistungsfähigkeit zur Fettmassenreduktion, Verbesserungen der Hyperglykämie, Lipo- proteinstoffwechsels und des Adipokinprofils. Bone morphogenetic proteins (BMPs) werden im Fettgewebe produziert und spielen eine wichtige Rolle in der Adipogenese und Transdifferenzierung von Adipozyten. Während ein Zusammenhang zwischen der BMP-7-Serumkonzentration und Adipositas vor kurzem belegt wurde, ist bisher nicht bekannt, ob weitere BMPs wie BMP-2 und -4 mit Adipositas und Typ-2-Diabetes assoziiert sind. Ziel dieser Arbeit war es deshalb zu untersuchen, ob die BMP-2 und -4 Serumkonzentrationen im Zusammenhang mit Körpergewicht, Fett- verteilung und Parametern des Glukosestoffwechsels bei Patienten mit Adipositas und Typ-2-Diabetes (n=213) stehen. Im Rahmen von drei Interventionsstudien wurde der Einfluss einer hypokalorischen Ernährungsweise über sechs Monate (n=19), eines 45,3 ± 7,4 kg Gewichtsverlustes ein Jahr nach bariatrischer Chirurgie (n=32) sowie eines zwölf- wöchigen Trainingsprogramms (n=60) auf die BMP-2- und -4-Serumkonzentrationen untersucht. Zusätzlich wurde die BMP-2-und -4-mRNA-Expression in humanen omentalen und subkutanen Fettgewebsproben von 161 Patienten charakterisiert. Die BMP-2- und -4-Serumkonzentrationen und die BMP-2- und -4-mRNA-Expression im viszeralen Fettgewebe korrelieren signifikant mit dem BMI und dem Körperfettgehalt. Zirkulierende BMP-4-Spiegel sind geschlechtsabhängig und bei Patienten mit T2D signifikant niedriger als bei gesunden Kontrollpatienten. Sowohl eine moderate Gewichts- reduktion durch kalorienreduzierte Ernährung als auch ein Gewichtsverlust von 45,3 ± 7,4 kg nach bariatrischer Chirurgie führen zu einer signifikanten Reduktion der zirkulierenden BMP-2- und -4-Spiegel. Das zwölfwöchige Trainingsprogramm führte lediglich zu einer signifikanten Reduktion der BMP-2-Serumkonzentration und zu signifikanten Ver- besserung der Leistungsfähigkeit, von Parametern des Glukosestoffwechsels und der Serumkonzentrationen von Adiponektin und Interleukin-6. Zusammengefasst zeigen die Daten, dass erhöhte Serumkonzentrationen von BMP-2 und 4 mit Adipositas assoziiert sind und durch Gewichtsreduktion und Erhöhung der körperlichen Aktivität verringert werden können. Die BMP-2- und -4-mRNA-Expression im viszeralen Fettgewebe kann zu erhöhten Serumkonzentrationen dieser Adipokine bei viszeraler Fettverteilung beitragen.

Silicon substituted hydroxyapatite (SiHA) has been reported to produce faster bone in- growth in vitro compared to hydroxyapatite (HA). The mechanism by which silicate ions in these materials trigger bone growth and differentiation remains unclear. In vitro models were used in this thesis to investigate human osteoblast cell responses on exposure to silicon containing materials and silicate ion solutions. The amounts of serum protein bound to SiHA was significantly higher than that in HA (p<O.OOl). Culture of both primary human osteoblast (HOB) cells and an osteosarcoma cell line (MG-63 cells) showed that SiHA discs were biocompatible to the cells; flat cell morphologies, higher degree of cellular processes, and a covering with minuscule bone mineral-like crystals were observed. To elucidate the effects of silicate ions alone on osteoblast functions, a 1000 ppm standard silicon solution was supplemented into cell culture medium to produce silicate ion concentration of 20 and 500 ~M; it was found that the former had little effect on both cell types. Significant increases in levels of total DNA (p<0.001), protein (p<0.001), and collagen (p<0.001) were observed in HOB cells, but not in MG-63 cells, in cultures with 500 ~M silicate ions. Likewise, expression of COL-J al (p<0.001), BMP-2 (p<0.05), PHOSPHO-J (p<0.001) genes were up-regulated in both cells types cultured with 500 ~M silicate ions. Further studies proposed that the activation of cell proliferation by this silicate ion-containing medium, observed as increases in total DNA, involved TGF~1 and/or IGF-I receptors. In trying to understand this, it was latterly identified that the pH changes of the serum- supplemented culture medium that occurred during supplementation with the alkali silicate ion solution and subsequent neutralisation with HCI were the actual cause of the marked enhancement in HOB cell proliferation. Silicate ions did still appear to have a direct effect on some HOB cell responses, due to observing comparable effects of 20 and 500 ~M silicate ions on e.g. TNAP and PHOSPHO-J gene expression, compared to silicate ion-free controls.

No description available.

No description available.

Bisphosphonates (BPs) are stable analogues of pyrophosphate widely used for the treatment of bone diseases characterised by increased bone resorption. Studies over the years have shown that the pharmacological potencies of BPs are dependent both on their binding affinities for bone mineral and on their inhibitory actions on osteoclasts. In addition, potential effects on other cell types present locally in the environment of skeletal tissues have been reported. The present study systematically evaluated the relative mineral-binding affinities of individual BPs of clinically relevance in mixtures of these compounds and the changes with elution pH by using column chromatography with ceramic hydroxyapatite and fluoroapatite combined with mass spectrometric identification and quantitation of the individual BPs. The results indicate that pH has a profound effect on the ionisation of the phosphonate and R2 functional groups, with BPs having greater affinities at lower pH as shown by increased retention times. Moreover, two other approaches, namely using Langmuir adsorption isotherms and competition assays based on fluorescent BP, have been developed to assess the mineral-binding capacities and dissociation constants of BPs. These results suggest that there are substantial differences among BPs in their binding to hydroxyapatite. From the cellular aspect of my study, I present evidence for the anti-apoptotic effects of BPs in osteocytes and osteoblasts. However, the study of prosurvival signalling pathways involved in these cells needs to be optimised. The work described in this thesis provides novel insights into the physiological and biological mechanisms of BP action. My project has provided a better knowledge of the physicochemical properties of BPs, which are highly relevant to their differential distributions within bone, their biological potencies, and their durations of action. Additionally, the cell culture studies may provide new information on the cellular effects of BPs on osteocytes and osteoblasts.

The effect of excess gravity on bone-forming elements of the growing perichondrial shaft of embryonic chicks was investigated through the use of the transmission electron microscope and various cytochemical techniques.

Purpose: In oncological orthopedics, navigation systems are limited to use in specialized centers, because specific, expensive, software is necessary. To resolve this problem, we present a technique using general spine navigation software to resect tumors located in different segments. Materials and Methods: This technique requires a primary surgery during which screws are inserted in the segment where the bone tumor is; next, a CT scan of the entire segment is used as a guide in a second surgery where a resection is performed under navigation control. We applied this technique in four selected cases. To evaluate the procedure, we considered resolution obtained, quality of the margin and its control. Results: In all cases, 1 mm resolution was obtained; navigation allowed perfect control of the osteotomies, reaching the minimum wide margin when desired. No complications were reported and all patients were free of disease at follow-up (average 25.5 months). Conclusions: This technique allows any bone segment to be recognized by the navigation system thanks to the introduction of screws as landmarks. The minimum number of screws required is four, but the higher the number of screws, the greater the accuracy and resolution. In our experience, five landmarks, placed distant from one another, is a good compromise. Possible disadvantages include the necessity to perform two surgeries and the need of a major surgical exposure; nevertheless, in our opinion, the advantages of better margin control justify the application of this technique in centers where an intraoperative CT scanner, synchronized with a navigation system or a dedicated software for bone tumor removal were not available.

No description available.

The skeletal system is a dynamic organ that provides support, protection, aids in the production of all blood cells, and serves as a calcium ion reservoir. It is constantly undergoing a process called ‘remodeling’, which occurs through the actions of osteoclast and osteoblast cells. The former is responsible for breaking down bone whereas the latter secretes an organic matrix for bone synthesis. Two experiments were conducted to analyze the effects of physiological perturbations on the bone remodeling process. Specifically, the impact of aging and selective serotonin re-uptake inhibitor administration coupled with lactation on bone morphology and composition were observed. The bony skeleton is not a stagnant organ, rather it undergoes functional, mechanical, and compositional changes throughout life. Thus, we wanted to determine the consequences age had on various bone parameters and found a decrease in bone volume fraction (BV/TV), trabecular number (Tb.N), cortical thickness (C.Th), and an increase in periosteal area, endosteal area, and cortical porosity (C.Po). In regards to pregnancy, post-partum depression is a common condition. As a result, many women utilize selective serotonin re-uptake inhibitors (SSRIs) to combat the negative symptoms associated with it. Serotonin is an important hormone involved in mood regulation and the mammary-derived form has a role in lactation. It induces the production of parathyroid hormone-related protein, which is essential for regulating maternal calcium. Because the calcium source for milk production is derived from the maternal bone, we were interested in the impact peri-partum usage of SSRIs had on maternal bone mineral density. Additionally, we sought to understand the effect that circulating SSRIs had on the bone formation of pups. Analysis revealed age-related decreases in BV/TV, Tb.N, trabecular thickness (Tb.Th), C.Th and increases in trabecular spacing (Tb.Sp) and C.Po, with the effects being exacerbated in cohorts treated with a SSRI during lactation. We did not observe, however, any change in trabecular bone mineral density (Tb.BMD) or cortical bone mineral density (C.BMD) over time. In regards to the pups, we observed similar results to those of the dams in addition to a significant reduction in femur length. With the data obtained from the two projects, we hope that they bring awareness to potential consequences that physiological perturbations may have on the bone remodeling process. Both experiments have clinical correlations to humans. Further understanding the relationship between aging and bone may aid in developing methodologies to prevent age-related changes. On the other hand, analyzing the effects that SSRI usage has on maternal and child bone density may result in alternative methods to combat post-partum depression.

INTRODUCTION: Bone marrow examination (BME) is performed in Human Immunodeficiency Virus-infected (HIV+) children with haematologic abnormalities to exclude specific disease (SD). AIMS: To describe the: (1) indications for BME , (2) utility of BME to diagnose SD, (3) patient characteristics associated with SD or non-specific disease (NSD). METHODS: Design: Retrospective review. Definitions: SD: BME positive for opportunistic infection (OI) or HIV-related malignancy. NSD: HIV-related changes only. RESULTS: Eighty six BME’s were done. Suspected SD in 56/86(65.1%) was the most common clinical indication. Bicytopaenia(n=32) and isolated cytopaenia(n=31) were the most common haematologic indications. NSD 48/86 (55.8%) was a more common finding than SD 32/86 (37.2%). Granulomas, pure red cell aplasia and malignancy were the SD identified. Pre- highly active antiretroviral therapy (HAART), advanced stage, and not being virally suppressed were significantly associated with NSD. CONCLUSION: The yield of SD (37.2%) on BME is comparable to adult studies. HAART should be instituted before BME as NSD will be the most likely finding.