Abstract. We aimed to investigate whether a supplementary diet containing chicken comb extract (ccE) rich in hyaluronic acid (ha) has an effect on pain and other symptoms, as well as cartilage type ii collagen (cii) metabolism in patients with knee osteoarthritis (Oa). a randomized double-blind placebo-controlled study was conducted in 43 subjects with knee Oa (Kellgren/lawrence grade, mainly 1-2) comprising 22 patients receiving concurrent exercise therapy (Et) and 21 without Et (referred as Et-receivers and Et-unreceivers, respectively). Subjects were randomized to a ccE-containing diet (active diet) group administered a dose of 1,800 mg/day (containing 630 mg of ccE and approximately 60 mg of ha) and a placebo group, and the intervention was continued for 16 weeks. Symptomatic efficacy was evaluated based on the Japanese Orthopaedic association clinical trials response criteria (JOa response criteria) and visual analog scales (vaS) before (baseline) and during the intervention. to further examine its effect on cii metabolism, the levels of two degradation biomarkers (ctx-ii and c2c) and one synthesis biomarker (cpii) were measured using urine or serum samples. nineteen subjects (10 Et-receivers and 9 Et-unreceivers) in the active diet group and 21 subjects (10 Et-receivers and 11 ET-unreceivers) in the placebo group were finally included in the study. compared to the baseline, subscale scores of the JOa response criteria, i.e., 'pain/walking function', 'pain/step-up and -down function' and 'aggregate total symptoms' were more intensely improved in the active diet group than in the placebo group. moreover, subgroup analyses of ET-receivers and ET-unreceivers indicated that significant improvements were restricted to Et-receivers of the active diet group. Furthermore, vaS assessment indicated that the 'pain on pressing' subscale was significantly improved in Et-receivers of the active diet group. in addition, analysis of cii biomarkers revealed that serum c2c and cpii levels, but not the urinary ctx-ii level, were increased in the active diet group. notably, both urinary ctx-ii/serum cpii and serum c2c/serum cpii ratios were reduced in the active diet group (particularly Et-unreceivers), suggesting that cii synthesis was relatively increased compared to cii degradation in the active diet group. Finally, no diet-related side effects were observed. the ccE-containing diet is likely to be effective in relieving symptoms in patients with knee Oa. in addition, it has the potential to improve the balance of cii degradation/ synthesis in knee Oa.
Six cases of primary glomeruionephritis with predominant IgG deposits in the mesangium are described on the basis of a review of renal-biopsy-proven 1,116 cases with primary glomeruionephritis between 1977 and 1990. All patients were female (6-52 years old). Six patients appeared with microscopic hematuria: 3 with episodes of gross hematuria and 3 with mild proteinuria, but none with the nephrotic syndrome. Renal function was normal except for 1 case (52 years old) complicated with hypertension. Serum levels of immunoglobulins and complements were almost normal. Morphologically minor or focal/segmental glomerular alterations were observed. Immunofluorescence showed that pure mesangial IgG deposition was characterized in all cases, whereas no IgA nor IgM was found in any of them. Mesangial deposition of C3 and C1q was observed in 4 and 3 cases, respectively. Electron microscopy revealed dense deposits within the mesangial area in all cases. The clinical course was benign, and the complication with systemic diseases like a rheumatic disease was not observed. This primary glomeruionephritis is an entity characterized by low incidence in Japan, mild abnormalities in urinalysis, minor glomerular alterations with predominant mesangial IgG deposits and a relative benign course.
The direct effects of recombinant human erythropoietin(rHuEPO) on coagulation and fibrinolysis factors were evaluated in a cultured endothelial cell (EC) system. Confluent quiescent ECs were incubated with or without 5.0 U/ml rHuEPO for 1, 6, and 18 hours, and supernatant concentrations of plasminogen activator inhibitor-1 (PAI-1): antigen (Ag), tissue plasminogen activator and thrombomodulin, and supernatant activities of tissue factor pathway inhibitor and von Willebrand factor were measured. The results showed that only PAI-1 levels were increased by the presence of rHuEPO. In order to assess the effect of rHuEPO on PAI-1 production by EC more precisely, confluent ECs were incubated with various doses of rHuEPO (0, 1.0, 2.5, 5.0, 10.0 U/ml) for 1, 6, 12, and 18 hours, and PAI-1:Ag concentrations in the supernatants of media were measured. PAI-1:Ag in the supernatants were increased by the presence of rHuEPO at all incubation times (P < 0.01) and the increase in PAI-1:Ag was dependent on rHuEPO concentration. The increases in PAI-1:Ag by 5.0 U/ml rHuEPO were comparable to those by 0.1 U/ml tumor necrosis factor-alpha, 1.0 microgram/ml lipopolysaccharide, and 0.5 U/ml thrombin. The increase in PAI-1:Ag by rHuEPO was suppressed by pre-incubation with 10 micrograms/ml cycloheximide (P < 0.01) or 0.2 microgram/ml actinomycin D (P < 0.01). These results indicate that rHuEPO directly stimulates PAI-1 production in cultured EC via de novo protein and RNA syntheses.
The authors analysed CD4+ subset populations and particularly subset killing in order to evaluate the presence of antilymphocyte antibody against CD4 + subsets in patients with IgA nephropathy (IgA N). This study was performed in 45 patients with IgA N, 30 patients with other forms of glomerulonephritis and 30 healthy controls. CD4 + CD4 + CD45R- and CD4 + CD45R+ cells in the peripheral blood were counted by a flow cytometric analysis, and those cell killings were analysed by microcytotoxic assays. The percentage of circulating CD4 + CD45R + cells was significantly decreased in IgA N, and the percentage of CD4 + CD45R+ cell killing was significantly elevated in IgA N compared with other groups. There was a significant negative correlation between the percentage of CD4 + CD45R + cells present in IgA N patients’ peripheral blood lymphocytes and the killing CD4 + CD45R + cells by the same patients’ serum. Both a depletion of CD4 + CD45R+ cells in peripheral blood lymphocytes and an elevation of CD4 + CD45R+ cell killing correlated with the grade of mesangial proliferation in patients with IgA N. However, there were no correlations in other clinicopathological indices. These results suggest that low levels of antilymphocyte antibodies against CD4 + CD45R+ cells were present in patients with IgA N, who showed a depletion of CD4 + CD45R+ cells in the peripheral blood. These antibodies were strongly associated with the elimination of CD4 + CD45R+ cells and the proliferation of glomerular mesangial cells in patients with IgA N.
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