高转换型肾性骨病中骨保护素及其配体的表达和形态计量学观察

目的 观察高转换型肾性骨病中骨保护素及其配体 (OPG，RANKL)的表达，并与骨形态计量学指标进行相关分析。 方法 选择10例慢性肾衰尿毒症患者和3例正常人进行髂骨活检术，获得骨组织标本。采用免疫组化方法检测OPG和RANKL蛋白质的表达。采用全自动图像分析系统进行骨组织形态计量学测定。结果 10例慢性肾衰尿毒症患者经骨病理学检查证实均为高转换型骨病，以破骨细胞活化形成骨吸收陷窝伴或不伴骨矿化不全为特点。免疫组化显示尿毒症患者骨组织中以RANKL阳性表达为主。与正常对照相比，RANKL阳性表达细胞数目显著增加，OPG阳性表达细胞数目显著减少。尿毒症患者RANKL的阳性表达细胞数目与骨吸收面积和破骨细胞数目呈显著正相关。结论 高转换型肾性骨病中，PTH的溶骨作用可能是通过OPG/RANKL/RANK系统介导的。     

尿毒症患者的性激素变化及其临床意义探讨

目的 :探讨女性尿毒症患者卵巢功能障碍的发病情况及其临床意义。方法 :应用酶免疫法 (EIA)测定了2 3例更年期前女性尿毒症非透析患者、15例透析患者及 2 9例健康献血者中促卵泡素 (FSH)、泌乳素 (PRL)、促黄体素 (LH)、雌二醇 (E2 )及孕酮 (P)的水平。结果 :尿毒症女患者PRL、FSH及LH均较健康对照组升高 ,而孕酮值显著降低 ,对此均有显著差异 ;且尿毒症女患者PRL升高、孕酮值降低与肾小球滤过率 (GFR)呈明显相关。透析患者较非透析患者PRL升高更为明显 ,孕酮值亦较非透析患者有所升高 ,但无显著意义。结论 :尿毒症女患者的排卵障碍及月经紊乱等都与尿毒症的严重程度相平行。透析并不能改善尿毒症女患者的卵巢功能障碍 ,只有纠正与改善肾功能 ,才能使尿毒症女患者的卵巢功能得以改善     

Cell volume regulation: a review of cerebral adaptive mechanisms and implications for clinical treatment of osmolal disturbances: II

Cerebral cell volume regulatory mechanisms are activated by sustained disturbances in plasma osmolality. Acute hypernatremia causes a predictable shrinkage of brain cells due to the sudden imposition of a plasma-to-cell osmolal gradient. However, during chronic hypernatremia cerebral cell volume is maintained close to the normal range as a result of the accumulation of electrolytes and organic osmolytes including myo-inositol, taurine, glutamine, glycerophosphorylcholine, and betaine. The increased cytosolic level of these molecules is generally accomplished via increased activity of sodium (Na⁺)-dependent cotransport systems. The slow dissipation of these additional osmotically active solutes from the cell during treatment of hypernatremia necessitates gradual correction of this electrolyte abnormality. Acute hyponatremia leads to cerebral cell swelling and severe neurological dysfunction. However, prolonged hyponatremia is associated with significant reductions in brain cell electrolyte and organic osmolyte content so that cerebral cell volume is restored to normal. While acute hyponatremia can be treated with the administration of moderate doses of hypertonic saline in order to control seizure activity, chronic hyponatremia should be corrected slowly in order to prevent subsequent neurological deterioration. If the rate of correction exceeds 0.5 mmol/l per hour, or if the total increment in serum [Na⁺] exceeds 25 mmol/l in the first 48 h of therapy, then there is an increased risk of the development of cerebral demyelinating lesions. Chronic hyperglycemia activates the brain cell volume regulatory adaptations in the same manner as hypernatremia. Therefore, during the treatment of diabetic ketoacidosis, it is imperative to restore normoglycemia gradually in order to prevent the occurrence of cerebral edema. It is possible that excessive administration of electrolyte-free solutions and high doses of insulin may increase the risk of this complication. While there are some data to suggest that brain cell size is disturbed during acute uremia, additional work is necessary to clarify the role of cerebral cell volume regulation during acute and chronic uremia.     

通调督脉化瘀排毒法治疗尿毒症晚期患者92例临床研究

目的观察应用通调督脉化瘀排毒法治疗尿毒症晚期的临床疗效。方法将92例尿毒症晚期患者随机分为两组,治疗组48例,除一般治疗外,加用海洋生命平衡超导治疗仪,将中药干粉剂作用于督脉、足太阳膀胱经的五脏六腑之俞穴,每日3次,每次1小时;对照组44例,给予一般治疗。结果治疗组总有效率及生化指标与对照组比较均有显著改善(P<0.05)。结论应用调督通脉化瘀排毒法,能提高尿毒症晚期患者的临床疗效。     

Insulin, branched-chain amino acids, and growth failure in uremia

Insulin and branched-chain amino acid (BCAA) metabolism was studied in 14 adolescents with uremia on hemodialysis. Glucose tolerance was measured by intravenous glucose tolerance tests. Insulin sensitivity was measured by the euglycemia clamp technique. Insulin secretion during constant hyperglycemia was measured by the hyperglycemic clamp technique. Fasting plasma BCAA concentrations were compared with data from 8 adolescent controls, whereas insulin indices were compared with 8 young adults controls and with published normal data in adolescents. The patients could be further sub-divided into two groups with respect to their growth velocity standard deviation score (GVSDS). Group 1 consisted of 7 patients with GVSDS less than −2. This group demonstrated insulin resistance, glucose intolerance, and low insulin secretion. This group also had low plasma valine, leucine, and isoleucine concentrations compared with control values. Group 2 consisted of 7 patients with GVSDS more than −2. This group demonstrated insulin resistance, but normal glucose tolerance and normal insulin secretion. Plasma valine, leucine, and isoleucine concentrations in group 2 were not different from control values. Total plasma BCAA correlated with glucose tolerance index and with insulin secretion, but not with insulin sensitivity. Growth failure in uremia is associated with glucose intolerance, hypoinsulinemia, and low plasma BCAA concentrations. Impaired utilization of conventional energy sources leading to preferential oxidation of BCAA may contribute to reduced anabolism and growth failure in uremia. Received October 8, 1997; received in revised form February 3, 1998; accepted February 6, 1998     

不同分子量尿毒血清组分对人肾小管上皮细胞CTGF基因和蛋白表达的影响

目的：探讨不同分子量尿毒血清组分对人肾小管上皮细胞结缔组织生长因子（CTGF）基因和蛋白表达的影响。方法:无菌条件下收集40份尿毒症病人血清和20例正常人血清，应用Centricon Plus 20 Centrifugal Filter Devices将尿毒血清分离成分子量 >10 000 D，5 000-10 000 D，<5 000 D 3个组分。应用Western blotting方法检测CTGF的蛋白表达，RT-PCR方法检测CTGF mRNA表达。结果:2.5%-20%浓度尿毒血清组CTGF基因表达均明显高于正常对照组，以10%尿毒血清组最高；分子量 <5 000 D尿毒血清组CTGF基因表达与正常对照组差异无显著，而分子量 5 000-10 000 D和 >10 000 D尿毒血清组CTGF基因表达均高于正常对照组，以分子量 >10 000 D尿毒血清组最高。不同浓度尿毒血清组CTGF蛋白表达均高于正常对照组，且有随着尿毒血清浓度的升高而增高，在不同分子量尿毒血清组中，以分子量 >10 000 D组增高最为显著。结论：尿毒症毒素通过影响人肾小管上皮细胞致纤维化细胞因子CTGF基因和蛋白表达从而在人肾小管-间质纤维化中起重要作用，而以分子量大于 10 000 D的尿毒症毒素在其中起主要作用。     

Fetal development in experimental uremia

Summary Uremic women on hemodialysis with metabolic bone disease (hyperparathyroidism, osteomalacia resulting from defective vitamin D metabolism) and anemia (erythropoietin deficiency) are known to give birth to infants without bone disease or anemia. Therefore, skeletal development (enchondral and desmal bone formation) and hepatic erythropoiesis were evaluated in fetuses of uremic rats. These fetuses failed to show defective mineralisation or evidence of bone disease. Bolus injection of high doses of exogenous PTH into the maternal or fetal organism did not affect fetal bone histology. In addition, no apparent defect of bone mineralisation or bone formation was found in fetuses of ricketic rats. Normal mineralisation in the offspring of uremic rats may be explained by fetal hyperphosphatemia and/or insensitivity of fetal (woven) bone mineralisation to vitamin D.Absence of fetal anemia (normal hematocrits, normal density of hematopoietic cells in the liver) in the presence of maternal anemia is presumably due to the insensitivity of fetal erythropoiesis to erythropoietin.With the support of Deutsche Forschungsgemeinschaft     

活体亲属供肾肾移植的临床分析

目的　总结分析活体亲属供肾肾移植的手术和治疗经验 ,探讨其临床效果 .方法　回顾性分析 33例活体亲属供肾肾移植的临床资料 ,包括手术方法和创新、免疫抑制药物的用药方案及临床效果 .结果　本组全部切取左肾 ,经腹手术 ,手术顺利 ,移植肾在开放血液循环后 1～ 10分钟内分泌尿液 .供体肾功能在 1周内恢复正常 ,未出现严重并发症 .受者仅 2例出现急性排斥反应 .全部受者至今存活 ,肾功能良好 .结论　活体亲属供肾 ,移植效果明显优于尸体供肾肾移植 .排斥反应发生率低 ,恢复顺利     

METABOLIC AND CNS CORRELATES OF COGNITIVE DYSFUNCTION WITH RENAL FAILURE

Experimental uremia in primates has been demonstrated to produce severe decrements in psychological functions which are related to the accumulation of toxic metabolites in blood. More recent neurophysiological research has referred uremic encephalopathy to disrupted sodium-potassium exchange in uremic brain. The present clinical investigations have found decrements in cognitive functioning with repeated testing in patients maintained on intermittent hemodialysis, which were correlated with plasma concentrations of potassium and creatinine. Power Spectral Density analyses of EEG indicated a shift to lower frequencies in these patients as compared to control subjects. No significant departure from normal functioning has been determined in patients receiving renal transplant tested within 60 days post-surgically.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.