Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.

We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.     

Differential control of mesangial cell proliferation by interferon-gamma.

Rat mesangial cells were shown to be sensitive to recombinant interferon-gamma (IFN-gamma). IFN-gamma reduced thymidine uptake by these cells and inhibited cell proliferation. Incubation of the cells with 1000 U/ml IFN-gamma decreased thymidine uptake by up to 64% and cell numbers were decreased by 17%. The effects of IFN-gamma were dose and time dependent and were partially reversible by the anti-IFN-gamma monoclonal antibody DB-1. This lymphokine did not reduce incorporation of RNA and protein precursors however. Measurements of 3H-uridine and 3H-leucine incorporation indicated significant increases in RNA and protein synthesis (37% and 45%, respectively) on a per cell basis. The mitogenic effects of IL-1 and platelet-derived growth factor (PDGF) were also susceptible to IFN-gamma-mediated inhibition but the mitogenic response to epidermal growth factor (EGF) was much less sensitive. We conclude that while IFN-gamma may act to modulate the mitogenic signals provided by some factors such as IL-1 and PDGF, the response to EGF appears to be unaffected.     

缬沙坦与苯那普利拉对SHR肾小球系膜细胞的保护作用

目的：观察ARB－valsartan及ACEI－benazeprilat能否抑制由AngⅡ、PDGF引起的SHR肾小球系膜细胞的增殖与肥大。且比较单用时作用孰强孰弱，联合应用后有无协同效应。方法；采用经典SHR系膜细胞培养技术，细胞中加入各种因子和（或）药物，以^3H-leucine或^3H-thymidine掺入后的cpm值反映蛋白或DNA合成。采用t test检验差异的显著性。结果：1、系膜细胞在AngⅡ、PDGF刺激后引起的增殖与肥大，均可被valsartan及benazeprilat抑制。2、比较发现单一用药在同一浓度下，valsartan较benazeprilat能更有效地抑制细胞的增殖与肥大。3、联合用药在同一浓度valsartan benazeprilat均比单用valsartan或benazeprilat效果明显。结论：1、valsartan与benazeprilat均能抑制SHR系膜细胞的增殖与肥大。2、valsartan在抗系膜细胞增殖与肥大作用稍强于benazeprilat。3、在一定浓度条件下联合用药对抗系膜细胞的增殖与肥大作用，较单一用药效果明显。     

无毒棉籽液抗腹泻作用研究

通过对正常小鼠、生大黄致泻小鼠及脾虚小鼠的作用研究表明，无毒棉籽液有较好的抑制排便频度、治疗腹泻的作用．无毒棉籽液６ｇ／ｋｇ可极其显著地抑制正常小鼠的排便频度，无毒棉籽液６ｇ／ｋｇ和３ｇ／ｋｇ可极其显著地抑制生大黄致泻小鼠及脾虚小鼠的排便频度．６ｇ／ｋｇ无毒棉籽液且可极其显著地抑制正常小鼠及脾虚小鼠的小肠推进运动．     

Morphometric insights into nephrotic syndrome in children: Are we any wiser?

Summary: The present study was undertaken in the hope that conflicting opinions concerning interrelationships among minimal change disease (MCD), mesangial proliferative glomerulonephritis (MPG) and focal segmental glomeruloscierosis (FSGS) might be elucidated by morphometric methods performed by image analysis, as well as to study whether serum creatinine and changes in quantitatively analysed glomeruli could correlate with the interstitial fibrosis in these glomerulopathies. Fifteen renal biopsy specimens from children with MCD, 10 with primary MPG and 12 with FSGS for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available, were examined quantitatively. As a control five biopsy and 10 autopsy specimens of the normal kidneys were used. Our quantitative study showed that in MCD, MPG and FSGS glomerular and interstitial values differed from normal. Morphometric differences between MPG and both MCD and FSGS groups were also shown. Although the mean values of total glomerular area and relative interstitial volume were increased in FSGS patients, in total glomerular cells per unit of glomerular area and mesangium (% of total glomerular area) were similar in both MCD and FSGS groups. In MPG strong positive correlations existed between interstitial volume and serum creatinine, interstitial volume and total glomerular cells per unit of glomerular area as well as between interstitial volume and glomerular mesangium (% of total glomerular area). In FSGS there was significant positive correlation between interstitial volume and serum creatinine. In the MCD group all correlations were weak and not significant. In conclusion, our morphometric studies suggest a close relationship between MCD and FSGS, and indicate that MPG is a separate morphologic entity in children.     

Leukocytosis and low serum IgA in workers exposed to the epoxy compound,t-methyl-3-phenylglycidate

Summary Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varing degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.     

微创治疗迟发性脑内血肿(附78例报告)

目的：评价微创治疗迟发性脑内血肿的疗效。方法：采取锥颅穿刺置管 尿激酶灌注引流方法，回顾分析78例迟发脑内血肿的临床资料。结果：78例迟发脑内血肿经微创治疗后存活71例，死亡5例，总死亡率6％。格拉斯哥昏迷指数(GCS)、年龄、瞳孔变化、血肿大小、脑挫伤程度及并发症等6项指标可影响治疗效果。结论：迟发性脑内血肿采取微创治疗具有安全性、少创、经济、恢复时间短、并发症少、死亡率低等优点。是一种有效可靠的方法。     

P_(27)、PCNA与IgA肾病中医证型及病理类型的关系

目的 :运用免疫组化方法研究原发性IgA肾病患者肾组织中细胞周期调控蛋白P2 7(P2 7)、增殖细胞核抗原PCNA(PCNA)的表达 ,探讨两者与IgA肾病病理分级及其与中医证型之间的关系。 方法 :选择行肾穿刺活检的IgA肾病住院患者 5 2例 ,并按照中医辨证分型标准将其分为肺肾气虚证、脾肾阳虚证、肝肾阴虚证、气阴两虚证、血瘀证、湿热证六型。系膜增生的病理组织学分为 4级。运用免疫组化方法检测P2 7、PCNA的表达。结果 :(1)IgA肾病各个病理分级P2 7、PCNA的表达两两比较有统计学意义。显示随着系膜细胞增生的病理分级程度增高 ,PCNA的表达增高 ,而P2 7的表达则按相反方向进行。病理分级和P2 7、PCNA表达的等级相关性检验 (Spearman法 )显示 :P2 7的表达与病理类型呈非常显著负相关 ,而PCNA的表达与病理类型呈显著正相关。 (2 )IgA肾病三个中医证型的病理分级之间有统计学意义 ,其中气阴两虚证的病理分级比湿热证、肝肾阴虚证高 ,湿热证与肝肾阴虚证的病理分级之间无统计学意义。 (3)随着湿热→肝肾阴虚→气阴两虚的进展 ,P2 7的表达呈现出逐渐减少的趋势 ,而PCNA的表达呈现出逐渐增加的趋势。结论 :(1)P2 7、PCNA作为判断IgA肾病肾脏组织学损伤程度和预后的指标值得深入研究。 (2 )IgA肾病中医证型之间病理分