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Despite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants' environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated. [ABSTRACT FROM AUTHOR]

Bone replacement and osteosynthesis require materials which can at least temporarily bear high mechanical loads. Ideally, these materials would eventually degrade and would be replaced by bone deposited from the host organism. To date several metals, notably iron and iron-based alloys have been identified as suitable materials because they combine high strength at medium corrosion rates. However, currently, these materials do not degrade within an appropriate amount of time. Therefore, the aim of the present study is the development of an iron-based degradable sponge-like (i.e. cellular) implant for bone replacement with biomechanically tailored properties. We used a metal powder sintering approach to manufacture a cylindrical cellular implant which in addition contains phosphor as an alloying element. No corrosion inhibiting effects of phosphorus have been found, the degradation rate was not altered. Implant prototypes were tested in an animal model. Bone reaction was investigated at the bone-implant-interface and inside the cellular spaces of the implant. Newly formed bone was growing into the cellular spaces of the implant after 12 months. Signs of implant degradation were detected but after 12 months, no complete degradation could be observed. In conclusion, iron-based open-porous cellular biomaterials seem promising candidates for the development of self-degrading and high load bearing bone replacement materials. [ABSTRACT FROM AUTHOR]

The safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction. [ABSTRACT FROM AUTHOR]

To characterize long-term actions and interactions of growth hormone (GH) and insulin-like growth factor-II (IGF-II) on postnatal body and organ growth, hemizygous phosphoenolpyruvate carboxykinase (PEPCK)-human IGF-II transgenic mice were crossed with hemizygous PEPCK-bovine GH transgenic mice. The latter are characterized by two-fold increased serum levels of IGF-I and exhibit markedly increased body, skeletal and organ growth. Four different genetic groups were obtained: mice harbouring the IGF-II transgene (I), the bGH transgene (B), or both transgenes (IB), and non- transgenic controls (C). These groups of mice have previously been studied for circulating IGF-I levels (Wolf et al., 1995a), whereas the present study deals with body and organ growth. Growth curves (week 3 to 12) were estimated by regression with linear and quadratic components of age on body weight and exhibited significantly (p < 0.001) greater linear coefficients in B and IB than in I and C mice. The linear coefficients of male I and C mice were significantly (p < 0.001) greater than those of their female counterparts, whereas this sex-related difference was absent in the bGH transgenic groups. The weights of internal organs as well as the weights of abdominal fat, skin and carcass were recorded from 3.5- to 8- month-old mice. In addition, organ weight-to-body weight-ratios (relative organ weights) were calculated. Except for the weight of abdominal fat, absolute organ weights were as a rule significantly greater in B and IB than in I and C mice. IGF-II overproduction as a tendency increased the weights of kidneys, adrenal glands, pancreas and uterus both in the absence and presence of the bGH transgene. Analysis of relative organ weights demonstrated significant (p < 0.05) effects of elevated IGF- II on the relative growth of kidneys (males and females) and adrenal glands (females), confirming our previous report on organ growth of PEPCK-IGF-II transgenic mice. In females, IGF-II and GH overproduction were additive in stimulating the growth of spleen and uterus, providing evidence for tissue-specific postnatal growth promoting effects by IGF-II in the presence of elevated IGF-I [ABSTRACT FROM AUTHOR]

Canine and feline platelet cytocentrifuge preparations (CCPs), cryostat and paraffin-embedded bone marrow sections were used in this study. We evaluated whether platelets, megakaryocytes and megakaryocyte precursor cells could be labelled by monoclonal antibodies (Y2/51, CLB-thromb/1, HPL1) against human platelet membrane glycoprotein GP IIIa and the GP IIb/IIIa complex or by the following 10 biotinylated lectins: concanavalin A (Con A), Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PsA), wheat germ agglutinin (WGA), peanut agglutinin (PNA), Phaseolus vulgaris lectin (PHA-L), Ricinus communis agglutinin 120 (RCA), Ulex europaeus agglutinin - I(UEA-1), soybean agglutinin (SBA) and Dolichos biflorus agglutinin (DBA). Monoclonal antibodies Y2/51 and HPL1 cross reacted with platelets and megakaryocytic cells from both species, whereas CLB-thromb/1 was unreactive with canine preparations. Only Y2/51 labelled megakaryocytic cells in paraffin-embedded samples. LCA, PSA, WGA and PHA-L labelled feline and canine platelets and different numbers of morphologically identifiable megakaryocytes and numerous other, mostly myeloid, cells. Immunoblots of dog and cat platelet lysates using Y2/51 visualized a single protein of 95 kDa (unreduced), a mol·wt value within the range of those reported for GP IIIa. Some of the platelet (but not necessarily megakaryocyte) glycoproteins reacting with LCA, PSA and WGA could be identified in lectin blots following one- or two (nonreduced/reduced)-dimensional sodium dodecyl sulphatepolyacrylamide gel electrophoresis (SDS-PAGE). Thus in dogs and cats, the immunohistochemical detection of GP IIIa (and eventually GP IIb/IIIa) rather than lectin binding patterns could be important for the diagnosis of megakaryoblastic leukaemias. [ABSTRACT FROM AUTHOR]

Effects of growth hormone (GH) overproduction were studied in transgenic mice expressing murine metallothionein I-GH fusion genes. The most obvious consequence was the acceleration of growth, which led to substantial increases in body weight of up to more than twice that seen in controls. Growth of the internal organs was stimulated, with hepatomegaly and nephromegaly as the most prominent features. GH transgene expression was also reflected in increased skeletal growth which affected various bones to different extents. The mean life-span of human GH transgenic mice with serum levels of hGH ranging from 3×10 to 9×10 ng/ml was drastically reduced at 160 days in both sexes. Severe renal lesions were the primary cause of the decrease in life expectancy and were characterized by marked nephron atrophy, obsolescence of numerous glomeruli, and a massive cystic dilation of the tubules. Initial changes involved the glomeruli, which showed significant enlargement and sclerotic lesions. The liver exhibited a pronounced hepatocellularmegaly and progressive degenerative as well as hyperplastic changes. One-third of the hGH transgenic animals displayed myocardial fibrosis. Hepatocellylar carcinoma was found in bovine GH transgenic mice older than 12 months. Our observations are compared with results of other investigators. [ABSTRACT FROM AUTHOR]