Urinary excretion of C5b-9 reflects disease activity in passive Heymann nephritis

Passive Heymann nephritis (PHN) is a model of membranous nephropathy in rats in which glomerular injury is mediated by the terminal C5b-9 membrane attack complex of complement. This model has been shown to be associated with markedly elevated urinary excretion of C5b-9, compared to other experimental models of glomerulonephritis To determine if urinary C5b-9 excretion could serve as an index of disease activity by correlating with the formation and quantity of glomerular subepithelial immune deposits in PHN, we measured urinary excretion of C5b-9 in PHN under several experimental conditions. In the heterologous phase a direct correlation was demonstrated between levels of urinary C5b-9 excretion and the amount of anti-Fx1A IgG deposited in glomeruli (r = 0.85). In the autologous phase, C5b-9 excretion correlated with the amount of deposit forming antibody present in the serum and resolved when antibody disappeared, despite persistence of glomerular deposits of antigen, antibody, C5b-9 and heavy proteinuria. Glomerular C3 deposits paralleled urinary C5b-9 excretion. Re-initiation of active deposit formation by a second injection of anti-Fx1A produced new C3 deposits and a marked rise in C5b-9 excretion. Finally, complete abrogation of deposit formation by transplanting PHN kidneys into normal recipients also halted C5b-9 excretion. Our findings demonstrate that urinary excretion of C5b-9 is a sensitive index of on-going immunologic disease activity in the PHN model of membranous nephropathy.     

Renal vein thrombosis in patients with nephrotic syndrome: CT diagnosis

A retrospective evaluation of the computed tomography (CT) findings in 50 patients with the nephrotic syndrome was undertaken. In four patients with clinical manifestations of acute renal vein thrombosis (RVT) on initial examination, the diagnosis was confirmed by CT findings. Three patients had left RVT, one had right RVT, and all four had thrombus in the inferior vena cava (IVC) at the level of the renal veins. Of the remaining 46, otherwise asymptomatic patients, one had bilateral RVT, two had left RVT, and five had isolated IVC thrombus. The abnormalities noted on CT scans were widened renal vein(s) containing thrombus, thrombus in the IVC, renal enlargement, thickened Gerota fascia and formation of pericapsular venous collaterals, and an abnormal renal parenchymal enhancement pattern consisting of prolonged corticomedullary discrimination, delayed and/or persistent paraenchymal opacification, and delayed or absent pyelocalyceal visualization.     

二羟丙氧甲基乌嘌呤抗单纯疱疹病毒Ⅰ型的实验研究

二羟丙氧甲基鸟嘌岭(DHPG),在组织培养中对单纯疱疹病毒Ⅰ型(HSV-1)KOS株抑制50%空斑形成的浓度(IC_(50))为0.1μg/ml。DHPG与环胞苷联合应用的抗HSV活性呈协同作用;DHPG分别与无环鸟苷、酞丁安合用有相加作用。0.1和0.05%DHPG溶液滴眼对家兔实验性浅层单纯疱疹病毒角膜炎有显著治疗作用,浓度降低至0.025和0.0l%无明显疗效。对实质层型单疱角膜炎,0.1%DHPG溶液滴眼治疗有效。     

Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model.

Expansion of the mesangial extracellular matrix (ECM) with subsequent glomerular sclerosis is a prominent finding in most progressive renal diseases. To investigate the chronology of accumulation of ECM components as it relates to previously described cellular events, biopsies were obtained from rats at various times following 5/6-nephrectomy as well as from sham-operated controls. The biopsies were stained with PAS as well as immunostained for PCNA (a cell proliferation marker), monocytes/macrophages, types I and IV collagen, laminin, s-laminin, fibronectin, heparan sulfate proteoglycan and entactin/nidogen. Immunostaining of biopsies obtained from 5/6 nephrectomized rats demonstrated an early glomerular cell proliferation, peaking at week 2. Expansion of the glomerular tuft area with rare glomeruli demonstrating focal sclerosis were also seen at week 2. Glomerular macrophage influx correlated with later ECM expansion and glomerulosclerosis. A progressive accumulation of all ECM proteins investigated was noted in the pathological mesangial matrix at week 2 and later time points. Northern analysis of total glomerular RNA at weeks 2 and 6 after 5/6 nephrectomy showed de novo expression type I collagen mRNA as well as small increases of glomerular mRNA levels for type IV collagen (1.2- and 1.4-fold over control RNA) and laminin (1.3- and 1.5-fold) but not s-laminin (1.1- and 0.9-fold). We conclude that cellular events including glomerular cell proliferation and macrophage influx are associated with increased gene and protein expression by ECM proteins in the remnant kidney model and may contribute to the development of sclerosis.     

Mediation of immune glomerular injury

This paper reviews current concepts of glomerular immune injury of both inflammatory and noninflammatory types. In noninflammatory lesions induced by antibody alone or C5b-9, the glomerular epithelial cell appears to be the principal target of injury. Similar mechanisms are probably operative in human diseases such as minimal change nephrotic syndrome and membranous nephropathy. In inflammatory lesions, circulating effector cells including neutrophils, macrophages, platelets, and probably lymphocytes as well as resident glomerular mesangial cells may mediate tissue injury. Human equivalents of these inflammatory lesions include most diseases associated with mesangial and/or subendothelial immune deposits and/or mesangial cell proliferation. Neutrophil-mediated injury appears to be consequent to both proteinases and oxidants, particularly the myeloperoxidase-H2O2-halide system. Platelets may be critically involved in neutrophil mediated injury as well. Platelets also mediate mesangial cell proliferation, probably by a release of platelet growth factors and stimulation of mesangial cell platelet-derived growth factor and platelet-derived growth factor receptor expression. Immunologically induced mesangial cell proliferation is associated with increased production of nephritogenic proteinase in vivo.     

Intranasal administration of growth hormone-releasing hormone(1–29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth

The growth-promoting potential of growth hormone-releasing hormone(1— 29)-NH, (GHRH(1–29)- NH,) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 μg/l in two stimulation tests (arginine, insulin), but above 12 (24–90) μg/l after intravenous GHRH, 1 μglkg. GHRH, 50 μg/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRHinsufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 μg/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment ( p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.