Transforming growth factor-β (TGF-β) activity in urine of patients with glomerulonephritis is related to their renal functional and structural changes

Transforming growth factor-β (TGF-β) has been considered the principal cytokine involved in the pathogenesis of renal fibrosis. In the present study, we evaluated TGF-β activity in occasional samples from 22 normal individuals and 29 patients (11 with focal glomerulosclerosis, 11 with membranous nephropathy, five with Berger disease, one with type I membranoproliferative glomerulonephritis and one with postinfectious glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay.
A significantly increased urinary TGF-β activity (reported in relation to urine creatinine, Ucreat. and median) was observed in patients with glomerulonephritis compared with normal individuals ( P <0.01). The patients with Berger disease [median (Md)=9.96/10 μg Ucreat.], membranous glomerulonephritis (Md=7.23/10 μg Ucreat.) and focal glomerulosclerosis (Md=16.6/10 μg Ucreat.) showed higher urinary TGF-β than normal individuals (Md=1.09/10 μg Ucreat.) ( P <0.01). We found a positive correlation between the TGF-β activity in the urine of these patients and the incidence of segmental glomerulosclerosis ( r =0.45, P <0.05) and their plasma creatinine levels ( r =0.87, P <0.01). A negative correlation was observed between the TGF-β activity in the urine of these patients and their creatinine clearance ( r =−0.75, P <0.01).
Our data suggest that measurement of urinary TGF-β activity could be a useful non-invasive procedure for the evaluation of renal TGF-β production, permitting the assessment of prognosis and the evaluation of therapeutic efficacy in patients with renal disease.     

Time-dependent alterations in the deformability of human neutrophils in response to chemotactic activation

Transit times of individual human neutrophils through single capillary- sized pores were measured to determine the time-dependent changes in the mechanical behavior of the cells during activation by the chemotactic agent formyl-methionyl-leucyl-phenylalanine (FMLP) and in response to cytochalasin B (CTB) and colchicine. FMLP elicited a two- phase response consisting of a rapid increase in cell stiffness, which peaked between 2 and 3 minutes, followed by a partial recovery of deformability to a level significantly above that of control after 5 minutes. The mechanical changes closely followed changes in F-actin content, although the peak in cell stiffness appeared to lag the F- actin response. Treatment with 3 mumols/L CTB produced a transient decrease in cell rigidity followed by a return to control level in 10 minutes, whereas treatment with 30 mumols/L CTB resulted in a sustained decrease in cell transit times to a level 60% of control. Addition of 3 mumols/L CTB to cells prestimulated with FMLP produced a rapid (1 to 2 minutes) cessation of changes in cellular deformability produced by the FMLP. Colchicine treatment did not decrease cell rigidity, but produced a delayed increase in F-actin content accompanied by increased stiffness of the cells. These results implicate actin as the major determinant of the mechanical behavior of the neutrophil, as measured by whole cell deformability tests. The significant changes in cell deformability that occur in response to fractional changes in F-actin content suggest that changes in the structure of the actin network occur during these processes.     

浙贝母化学成分的研究——Ⅲ.浙贝酮的分离和鉴定

A new C-nor D-homo steroidal alkaloid named zhebeinone was iso-lated from the bulbs of Fritillaria thunbergii Miq..Its structure was determined by spe-tral analyses and chenmical conversion as 5α, 14α-cevanine-3β, 20β-dihydroxy-6-one or C-27 epimer of periminine.