Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo

AbstractChondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors

In vivo safety evaluation of the Clostridium butyricum MIYAIRI 588 strain in broilers, piglets, and turkeys

Clostridium butyricum MIYAIRI 588 (CBM 588) is a nonpathogenic, anaerobic, gram-positive bacillus characterized by the production of short-chain fatty acids, including butyrate. The safety and tolerance of CBM 588 was investigated as a feed additive for broiler chickens, weaned piglets, and turkeys. CBM 588 administered to broilers at doses up to 5 × 107 CFU/g feed for 42 days produced no detrimental effects on zootechnical performance, natural mortality, hematology, or biochemical parameters. Piglets receiving CBM 588 at doses up to 5 × 107 CFU/g feed for 42 days showed no significant differences from controls in zootechnical performance, mortality, or morbidity. Finally, CBM 588 administered to turkeys at doses up to 2.5 × 107 CFU/g feed for 84 days produced no detrimental effects on zootechnical performance, hematology, or biochemical parameters. Some improvements in zootechnical performance were seen with CBM 588, including improved average daily gain (ADG) and feed conversion for broilers from days 1 to 21 as well as final body weight and overall ADG for turkeys. Overall, CBM 588 administered in feed at dose up to 5 × 107 CFU/g (broilers and piglets) or 2.5 × 107 CFU/g (turkeys) was shown to be safe and well-tolerated in all tested animals and may provide some nutritional benefit when added to standard commercial feedinfo:eu-repo/semantics/publishedVersio

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a debilitating, progressive joint disease.</p> <p>Methods</p> <p>Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone.</p> <p>Results</p> <p>Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery.</p> <p>Conclusions</p> <p>In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.</p

Studies on Behavior of Fluorine for Animal Organs Part 1. Determination of Small smounts of fluorine in plant and animal tissue

Fundamental studies of this subject were carried out in the following method. A new reagent "Nen-Thorin" (2-(1, 8-dihydroxy-3, 6-disulfo-2-naphthylazo)-benzene arsonic acid) (max. absorption, 500 mμ in an aq. solution of pH 2.3) was synthesised and complex of this reagent with thorium (max. absorption, 570 mμ at pH 2.3) was studied for the determination of F (<50 γ in 50 ml). The extinctions of both Neo-Thorin and its complex with Th are sensitive towards change in pH, but remain constant between pH 2.1 and 2.4, the extinction of the complex decreasing in proportion to the amount of F(-). Common ions, including Cl(-), SO(4)(2-), PO(4)(3-), Al(3+), Fe(3+), Ca(2+), and Mg(2+), interefere. Any F in the sample is distilled from an H(2)SO(4) soln. in the presence of SiO(2). (1) By using the Thorium-Neo-Thorin method, small amounts of fluorine may be easily determined. Color of this reagent changes from red to purple with small amounts of fluorine ion. So that the visual qualitative test for flurorine possible. Realisable limit of fluorine is 1/100 p. p. m. (2) After the plant tissue was mixed with CaO (3% by weight of dry sample) and a small amount of water, it was evaporated to dryness and the volatile matter was expelled at 250 to 300°C and then ignited at 650°C. Maximum recovery of fluorine was 98.5%. (3) A small amount of fluorine in animal tissue was satisfactory determined by the same procedure as in plant tissue. Namely, the sample was calcinated with CaO in proportion of 15 to 20% by weight of dry sample, charred at 350 to 400°C and ignited at 750°C. Maximum recovery of fluorine was 98.93%

Studies on Behavior of Fluorine for Animal Organs Part 3. Effect of administration of NaF to rabbit on total calcium in serum

Rabbits were used as experimental animals. Total calcium contents in serum and weights of rabbits were determined. When 1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg and 40 mg/kg of NaF were administered for 10 weeks. (1) Total Calcium contents in serum (a) When small amounts of fluorine (1 mg/kg and 10 mg/kg of NaF) was administred, total calcium contents in serum increased. (b) When 20 mg/kg, 30 mg/kg and 40 mg/kg of NaF were administered, amounts of calcium in serum decreased remakably. (2) Weights of rabbits It was found that rabbits administered with 1 mg/kg, 5 mg/kgand 10 mg/kg of NaF tend to gain weight and to loss when 20 mg/kg, 30 mg/kg and 40 mg/kg of NaF was given

Studies on Behavior of Fluorine for Animal Organs part 2. Effect of administration of NaF+CaCO(3) and NaF+AlK(SO(4))(2) to rabbit on fluorine contents in bone and organs

Rabbits were used as experimental animals. It was investigated how much fluorine was accumulated in their bones and organs, when NaF, CaCO(3)+NaF, and AlK(SO(4))(2)+NaF were respectively administered to them. (1) Amounts of fluorine contained in organs of non administered rabbits were considered to be the physiological required amounts which was taken as food from natural source. (2) When 1 mg/kg, and 10 mg/kg of NaF were respectively administered. amounts of fluorine in bones and organs did not increase so remarkably, but when 20 mg/kg of NaF, fluorine contents increased suddenly in all bones and organs. (3) When both CaCO(3) and NaF were administered in the same amount of fluorine, fluorine was much more accumulated in bones and less in all organs than when NaF alone was administered. (4) When both AlK(SO(4))(2) and NaF were administered, it showed a reverse result as that of CaCO3 and NaF namely, fluorine was more or less accumulated in bones, but much more in organs than amounts of fluorine which was accumulated when the same amount of fluorine alone was administred