Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To be used in diagnostic studies, it must be demonstrated that biomarkers can differentiate between diseased and non-diseased patients. Therefore, the purpose of this study was to answer the following questions: (1) Is serum cartilage oligomeric matrix protein (sCOMP) elevated in patients with radiographically diagnosed knee osteoarthritis (OA) compared to controls? (2) Are there differences in sCOMP levels when comparing differing radiographic OA severities to controls? METHODS: Systematic review and meta-analysis. DATA SOURCES: A systematic search of CINAHL, PEDro, Medline, and SportsDiscus was completed in March 2010. KEYWORDS: knee, osteoarthritis, sCOMP, radiography. Study inclusion criteria: Studies were written in English, compared healthy adults with knee OA patients, used the Kellgren Lawrence (K/L) classification, measured sCOMP, and reported means and standard deviations for sCOMP. RESULTS: For question 1, seven studies were included resulting in seven comparisons. A moderate overall effect size (ES) indicated sCOMP was consistently elevated in those with radiographically diagnosed knee OA when compared to controls (ES = 0.60, P < 0.001). For question 2, four studies were included resulting in 13 comparisons between radiographic OA severity levels and controls. Strong ESs were calculated for K/L-1 (ES = 1.43, P = 0.28), K/L-3 (ES = 1.05, P = 0.04), and K/L-4 (ES = 1.40, P = 0.003). A moderate ES was calculated for K/L-2 (ES = 0.60, P = 0.01). CONCLUSIONS: These results indicate sCOMP is elevated in patients with knee OA and is sensitive to OA disease progression. Future research studies with a higher level of evidence should be conducted to investigate the use of this biomarker as an indicator for OA development and progression.

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.

Potential antiradiation drugs containing no nitrogen, and related compounds.

Capabilities are reported of di- and higher sulfides (RSnR') terminated by sulfinate functions [-S(O)O-] for protecting mice against otherwise lethal effects of ionizing radiation. With the use of congeners, structure-activity correlations are developed for the effects of esterification of the sulfinate function, of changing the length of the chain of sulfur atoms, of reduction to a mercapto sulfinate, and of changing the substituents R and R' to chiral and other types of groups. Neither a trisulfide nor a sulfinate by itself was significantly radioprotective. The key requirement for radio-protection in the series appears to be the presence of a sulfur function (-Sn-) from which a thiol can be engendered by a neighboring-group effect of an electron-donating group; sulfoxide functions may afford alternatives to sulfinate functions as such neighboring groups. The relevance of structure-activity relations to the chemical and biological mechanisms involved in the radioprotective activities is discussed.

2-Acetylpyridine thiosemicarbazones XI: 2-(alpha-Hydroxyacetyl)pyridine thiosemicarbazones as antimalarial and antibacterial agents.

A series of 2-(alpha-hydroxyacetyl)pyridine thiosemicarbazones was synthesized as potential antimalarial and antibacterial agents. Their synthesis was achieved by the condensation of N4-mono- or N4,N4-disubstituted thiosemicarbazides with 2-(alpha-hydroxyacetyl)pyridine. The latter was prepared by selective bromine oxidation of (2-pyridinyl)-1,2-ethanediol. The new compounds show potent inhibitory activity against penicillin-sensitive as well as penicillin-resistant Neisseria gonorrhoeae (MIC, 0.5-0.004 micrograms/mL), against Neisseria meningitidis (MIC, 0.5-0.032 micrograms/mL), and Staphylococcus aureus (MIC, 0.5-2 micrograms/mL). Good in vitro antimalarial effects against Plasmodium falciparum (Smith strain; ID50, 6.7-38 ng/mL) were observed in most of these new agents, but only 3 of 12 compounds exhibit moderate in vivo activity against Plasmodium berghei. These new agents appear to be less toxic to the host and more water soluble than the corresponding 2-acetylpyridine thiosemicarbazones.

Synthesis and characterization of 2-(2-hydroxyphenyl)-4-aryl-1,5-benzodiazepines.

Four benzodiazepine derivatives, reported earlier by other authors, were resynthesized and characterized by NMR, IR, GC/MS and elemental analysis. Three of the four compounds have melting points different from those initially reported by 35-70 degrees C. The differences in melting point along with the discrepancies in IR spectra between our samples and those previously reported suggest that at least three of the eight compounds reported to be 1,5-benzodiazepines have incorrect structural assignments.