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  • 1
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The objective of this study was to evaluate the use of cultured porcine chondrocyte xenotransplantation for the repair of human chondral defects. Two-millimeter-diameter defects were drilled into explants of femoral cartilage from healthy adult donors. No cells were implanted in the chondral defects of the control group, while pig chondrocytes from normal femoral cartilage were deposited into the treated chondral defects. Cartilage explants were cultured for 4, 8, and 12 weeks. Tissue sections were processed for standard histologic staining and immunostaining with monoclonal antibodies against types I and II collagen, chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and integrin subunit β1. The porcine origin of chondrocytes was confirmed using a specific pig monoclonal anti-CD46. Repair was only observed in the cell-treated defects. Mono- or bilayers of cells were detected after 4 culture weeks on the bottom of the defects, while after 8–12 weeks a repair tissue filled near 30–40 percent of the defect. At 8 weeks, the newly synthesized tissue was composed of a fibrous mesh including some cells. However, at 12 weeks it showed a hypercellular hyaline-like region. This hypercellular region showed excellent bonding with the native cartilage, cells were located in numerous lacunae, and a high content of proteoglycans as indicated by an intense toluidine blue stain was observed. The repaired tissue showed positive immunostaining for both type I and II collagen, as well as chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and integrin subunit β1. Positive staining for porcine anti-CD46 was localized exclusively in the neo-synthesized tissue. We conclude that xenotransplantation of pig chondrocytes can repair, in an in vitro model, defects in human articular cartilage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Articular cartilage has only a limited ability to regenerate. The transplantation of autologous chondrocytes is currently used to treat focal defects in human articular cartilage, although use of organs, tissues, or cells from different species is being investigated as an alternative treatment. The object of this study was to use xeno-transplantation of cultured pig chondrocytes for the repair of rabbit chondral defects, and to analyze the significance of tissue rejection in this animal model. Partial chondral defects, including removal of cartilage tissue and a part of the subchondral bone, were created in the lateral femoral condyles of 30 adult New Zealand White rabbits. A periosteal flap was sutured to the native cartilage with the cambium layer facing the defect. As a control, culture medium was injected into the defect void of one group of rabbits while in a treatment group, chondrocytes, isolated from normal femoral pig cartilage, were injected into the defect void. All rabbits were killed by 24 weeks. Macroscopic changes of the cartilage were analyzed using Mankin's score. The distal femoral portion was studied histologically using hematoxylin and eosin, alcian blue, toluidine blue, and Mason's trichrome. Pig cells and pig genetic material were detected in the neo-synthesized tissue by immunohistochemical detection of SLA-II-DQ and polymerase chain reaction analysis of the gene SLA-II-DQB. The synovial membrane was studied histologically by hematoxylin and eosin staining. In the control group, on average, less than 25 percent of the chondral defect was filled. The repair tissue had an irregular surface with few cells similar to chondrocytes or fibroblasts and a minimal formation of extracellular matrix. In the treatment group, the chondral defect was approximately 90 percent filled with good integration between the neo-synthesized cartilage and the native cartilage. The repair tissue had a smooth surface with cells similar to chondrocytes and a hyaline-like extracellular matrix. The neo-synthesized cartilage was morphologically similar to hyaline cartilage. Importantly, there were no signs of graft-vs.-host rejections or infiltration by immune cells. In the neo-synthesized tissue, pig genetic material was detected in 27 ± 5 percent of all cells. These cells containing pig genetic material were distributed throughout the neo-synthesized cartilage. We conclude that the xeno-transplantation of chondrocytes could be an alternative method for the repair of articular cartilage defects.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 34 (1995), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Liver cirrhosis is a critical stage of chronic liver diseases that can produce liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative stress plays a key role in cell damage and fibrosis induced during liver cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on the development of parenchymal destruction and stellate cell activation in experimental liver cirrhosis. Melatonin was administered to rats with liver cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was assessed by serological analysis, as well as hematoxylin-eosin staining and the in situ apoptosis detection assay in liver sections. Oxidative stress was evaluated by lipoperoxide and reduced glutathione levels, and by the measurement of catalase and superoxide dismutase activities in liver and serum respectively. The activation of stellate cells was evaluated by α-smooth muscle actin expression in liver sections. Our results showed that TAA induced oxidative stress with extensive tissue damage and enhanced α-smooth muscle actin expression in liver. Melatonin prevented the oxidative stress-related changes associated with TAA toxicity. In conclusion, the study showed that melatonin prevents the tissue damage and fibrosis associated with TAA-induced liver cirrhosis in rats.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Clusters of galaxies are visible as concentrations of physically associated galaxies and as regions of extended X-ray emission. But optical surveys for distant clusters are hampered by the likely superposition of physically separate systems along the line of sight. This makes it difficult to use ...
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-8744
    Keywords: tolmetin, pharmacokinetic–pharmacodynamic modeling ; mechanism-based analysis ; population approach ; analgesia ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The relationship between the pharmacokinetics and the antinociceptive effect of tolmetin was characterized by an indirect model using a population approach. Animals received an intra-articular injection of uric acid in the right hindlimb to induce its dysfunction. Once dysfunction was complete, rats received an oral tolmetin dose of 1, 3.2, 10, 31.6, 56.2, or 100mg/kg and antinociceptive effect and blood tolmetin concentration were simultaneously evaluated. Tolmetin produced a dose-dependent recovery of functionality, which was not directly related to blood concentration. An inhibitory indirect response model was used based on these response patterns and the fact that tolmetin reduced nociception by inhibiting prostaglandin synthesis. Pharmacokinetic (PK) and pharmacodynamic (PD) data were simultaneously fitted using nonlinear mixed effects modeling (NONMEM) to the one-compartment model and indirect response model. The individual time courses of the response were described using Bayesian analysis with population parameters as a priori estimates. There was good agreement between the predicted and observed data. Population analysis yielded a maximal inhibition of the nociceptive response of 76% and an IC50 of 9.22 μg/ml. This IC50 is similar to that for tolmetin-induced prostaglandin synthesis inhibition in vitro (3.0 μg/ml). The present results demonstrate that mechanism-based PK-PD analysis using a population approach is useful for quantitating individual responses as well as reflecting the actual mechanism of action of a given drug in vivo.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-6903
    Keywords: Oxygen toxicity ; glutathione ; nervous tissue ; free radicals ; 4-hydroxy-nonenal ; sciatic nerve ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nervous tissue, central and peripheral, is, as any other, subject to variations in oxygen tension, and to the attack of different xenobiotics; these situations may promote the generation of activated oxygen species of free radical character. Results are presented showing that the content of total glutathione (GSH) in brain is 10-fold that found in the sciatic nerve of the rat (2620 vs. 261 nmol/g wet weight, respectively). The existence of a relatively high superoxide dismutase activity in peripheral nervous tissue, when compared with brain or liver, in combination with the DT-diaphorase activity detected in the sciatic nerve might represent an effective defense mechanism against quinone toxicity, as is also discussed. Nervous tissue, both central and peripheral lack Se-independent GSH peroxidase activity. Finally, the activities of other glutathione-related enzymes studied in the sciatic nerve are very low, when compared with the central nervous tissue, thus suggesting a higher susceptibility of peripheral tissue to oxidative stress damage, since GSH concentration and/or any GSH-related enzymatic activities, e.g. GSH peroxidase or glutathione disulfide reductase, might become limiting.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-2622
    Keywords: Acute retinal necrosis ; AIDS ; Cytomegalovirus ; Ganciclovir ; Liposomes ; Retinitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 μg/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of organic chemistry 53 (1988), S. 5960-5963 
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 85 (1981), S. 1961-1963 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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