ABSTRACT
Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro.
Subject(s)
Cartilage, Articular/metabolism , Methylene Blue , Nitric Oxide Synthase/metabolism , Nitric Oxide/metabolism , Osteoarthritis, Hip/metabolism , Osteoarthritis, Knee/metabolism , Humans , Nitric Oxide Synthase Type I , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Receptors, Transforming Growth Factor beta/metabolismABSTRACT
The genetic polymorphism of red cell delta aminolevulinate dehydrase (ALADH) has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from North Africa, Egypt, Turkey, Iraq, Iran, Yemen and the Balkans, and Arabs. The distribution of the ALADH genes was not homogeneous (chi 2 = 36.83; d.f. = 8; p less than 0.0005). A significantly higher frequency of the ALADH2 gene was observed among the Ashkenazi Jews (0.2021) than among the non-Ashkenazi Jews and Arabs (gene frequencies 0.0825-0.1290) or all the other population samples so far studied (Liberia, Japan, Italy, Germany and Spain).
Subject(s)
Polymorphism, Genetic , Porphobilinogen Synthase/genetics , Erythrocytes/enzymology , Ethnicity , Gene Frequency , Humans , Israel , Phenotype , Porphobilinogen Synthase/bloodABSTRACT
Previous studies demonstrated a significantly lower mean activity of glutathione peroxidase (GSH-Px) in erythrocytes of patients with multiple sclerosis than in control groups of normal subjects or patients with various neurological disorders. The present investigation has demonstrated that, in contradistinction to erythrocytes, a normal activity of GSH-Px is found in lymphocytes, granulocytes and platelets of multiple sclerosis patients. These results were obtained both with hydrogen peroxide, which serves as a specific substrate for selenium dependent GSH-Px, and t-butyl hydroperoxide which reacts both with selenium dependent and independent GSH-Px.
Subject(s)
Blood Cells/enzymology , Glutathione Peroxidase/blood , Multiple Sclerosis/enzymology , Peroxidases/blood , Glutathione Peroxidase/genetics , Humans , Multiple Sclerosis/blood , Polymorphism, Genetic , Selenium/deficiencyABSTRACT
The genetic polymorphism of phosphoglycolate phosphatase (PGP) found in red blood cells has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from Iraq, Yemen, Turkey, Iran, Balkan, North Africa and Arabs. The distribution of the PGP genes was not homogeneous (chi 2 = 40.545; d.f. = 20; p less than 0.005). The PGP2 gene frequency varied between 0.0185 in the Yemenite and 0.0688 in the Iranian Jews. PGP3 gene frequency ranged between 0.0062 in the Iranian and 0.0547 in the Moroccan Jews. Depsite this heterogeneity all the Israeli population groups showed some unifying characteristics which differentiated them from a random European population sample, namely higher frequencies of PGP1 gene (92-97% as opposed to 82% in th European sample) and lower frequencies of PGP2 gene (1.8-6.8% compared to 12.9% among Europeans).
Subject(s)
Jews , Phosphoric Monoester Hydrolases/genetics , Polymorphism, Genetic , Erythrocytes/enzymology , Gene Frequency , HumansABSTRACT
The mean activity of glutathione peroxidase (GSH-PX) in erythrocytes of 22 Israel-Jewish patients with multiple sclerosis (19.3 +/- 4.5 U/gHb) was significantly lower than in a control group of 30 Jewish patients with various neurological disorders (24.3 +/- 5.1 U/gHb). This observation confirms a similar finding of a decreased activity of GSH-Px in erythrocytes of multiple sclerosis patients in Denmark (Shukla et al. 1977). These results are discussed in relation to the possibility of selenium deficiency and to the recently described genetic polymorphism and ethnic variation of GSH-Px activity in human red cells. It is concluded that additional investigations are required in order to elucidate the cause of the decreased activity of this enzyme in red cells of patients with multiple sclerosis.
Subject(s)
Erythrocytes/enzymology , Glutathione Peroxidase/blood , Multiple Sclerosis/enzymology , Peroxidases/blood , Genotype , Humans , Jews , Multiple Sclerosis/genetics , Spectrophotometry, UltravioletABSTRACT
The genetic polymorphism of red blood cell glyoxalase I (GLO) has been investigated in 9 population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from Iran, Iraq, Balkan, North Africa, Yemen, Turkey and Egypt as well as Arabs living in Israel. The distribution of GL01 and GLO2 genes in the 9 communities was not homogeneous (x2 = 14.48; d.f. = 8; p less than 0.0005). Jews from Iran were found to have the lowest GLO1 frequency (0.2294), while those from Egypt had the highest gene frequency (0.3968). The other investigated communities were shown to have intermediate values for this gene frequency. No significant difference has been found between Ashkenazi and non-Ashkenazi Jews (with the exception of those from Egypt) or Arabs living in Israel.
Subject(s)
Erythrocytes/enzymology , Gene Frequency , Jews , Lactoylglutathione Lyase/genetics , Lyases/genetics , Polymorphism, Genetic , Ethnicity , Humans , Israel , Lactoylglutathione Lyase/bloodABSTRACT
The genetic polymorphism of red blood cells esterase D (EsD) has been investigated in 9 population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from North Africa, Iran, Turkey, Egypt, Balkan, Iraq, Yemen as well as Arabs living in Israel. The distribution of EsD1 and EsD2 genes among the 9 communities was not homogenous chi2 = 42.3; d.f. = 8; p less than 0.0005). The Ashkenazi and North African Jews had significantly lower frequencies of EsD2 (0.100 and 0.102 respectively) than did Yemenite Jews and Arabs (0.212 and 0.206 respectively). The other communities investigated showed intermediate values. A Jewish family from Greece carrying the rare allele EsD2 has been detected.
