Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

二巯基丙磺酸钠解救毒鼠强中毒的疗效分析

目的：探求急性毒鼠强中毒（ＡＴＩ）的临床解毒方法。方法：应用二巯基丙磺酸钠解救ＡＴＩ３４例，进行疗效观察，并与既往常规治疗的２３例进行对照比较。结果：治疗组获得满意疗效，３例死亡，有效率９１．２％；对照组预后欠佳，死亡１３例，有效率４３．５％。结论：二巯基丙磺酸钠（Ｎａ—ＤＭＰＳ）对ＡＴＩ具有良好的止痉作用，可明显提高治疗效果。     

Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolmic rats

This study was conducted to investigate the hypocholesterolemic effect of simvastatin (30 mg/kg BW) and antioxidant effect of coenzyme Q10 (CoQ10, 15 mg/kg BW) or green tea (5%) on erythrocyte Na leak, platelet aggregation and TBARS production in hypercholesterolemic rats treated with statin. Food efficiency ratio (FER, ADG/ADFI) was decreased in statin group and increased in green tea group, and the difference between these two groups was significant (p<0.05). Plasma total cholesterol was somewhat increased in all groups with statin compared with control. Plasma triglyceride was decreased in statin group and increased in groups of CoQ10 and green tea, and the difference between groups of statin and green tea was significant (p<0.05). Liver total cholesterol was not different between the control and statin group, but was significantly decreased in the group with green tea compared with other groups (p<0.05). Liver triglyceride was decreased in groups of statin and green tea compared with the control, and the difference between groups of the control and green tea was significant (p<0.05). Platelet aggregation of both the initial slope and the maximum was not significantly different, but the group with green tea tended to be higher in initial slope and lower in the maximum. Intracellular Na of group with green tea was significantly higher than the control or statin group (p<0.05). Na leak in intact cells was significantly decreased in the statin group compared with the control (p<0.05). Na leak in AAPH treated cells was also significantly reduced in the statin group compared with groups of the control and CoQ10 (p<0.05). TBARS production in platelet rich plasma was significantly decreased in the groups with CoQ10 and green tea compared with the control and statin groups (p<0.05). TBARS of liver was significantly decreased in the group with green tea compared with the statin group (p<0.05). In the present study, even a high dose of statin did not show a cholesterol lowering effect, therefore depletion of CoQ10 following statin treatment in rats is not clear. More clinical studies are needed for therapeutic use of CoQ10 as an antioxidant in prevention of degenerative diseases independent of statin therapy.     

初次献血对红细胞膜Na+-K+-ATP酶活性的影响

目的探讨初次献血对红细胞膜Na+-K+-ATP酶活性的影响.方法应用比色法分别检测50例符合献血条件的健康初次献血者献血前后的红细胞膜Na+-K+-ATP酶活性,并对结果进行分析.结果初次献血者献血前后红细胞膜Na+-K+-ATP酶活性分别为3.121±0.441和2.907±0.397 μmol.Pi/107 RBC.h,两者比较无明显差异(P＞0.05).结论初次献血对红细胞膜Na+-K+-ATP酶活性无影响,献血不会造成红细胞功能损伤.     

补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca2+-Mg2+- ATP酶活性影响的实验研究

本实验研究切除卵巢造成肾虚骨质疏松症大鼠模型。通过观测红细胞膜蛋白激酶Ｃ（ＰＫＣ）和Ｃａ２＋－Ｍｇ２＿－ＡＴＰ酶的活性，探讨肾虎骨质疏松症病理机制中肌醇脂质系统的变化，并结合全身和脊柱骨密度（ＢＭＤ）指标观察了补肾中药（密骨灵）的疗效，与正常对照组、模型空白组和阳性药（骨疏康颗粒剂）对照组进行对照，探讨补肾法的防治机理。结果表明；模型空白组大鼠红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶的活性明显低于正常组（ｐ均＜０．０５）；密骨灵组与骨疏康组大鼠全身、脊柱ＢＭＤ和红细胞膜ＰＫＣ、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶的活性均明显高于模型空白组（ｐ均＜０．０５），并且与正常组大鼠无明显差别（ｐ均＞０．０５）；密骨灵组大鼠红细胞膜Ｍｇ２＋－ＡＴＰ酶活性高于模型空白组和骨疏康组（ｐ＜０．０５），并且与正常组无显著性差异（ｐ＞０．０５）；密骨灵组大鼠红细胞膜ＰＫＣ活性高于骨疏康组（Ｐ＜０．０５）。结论：肾虎骨质疏松症具有红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶活性的改变；密骨灵可以恢复肾虎骨质疏松症大鼠全身骨量，达到防治目的；补肾中药可以恢复红细胞膜ＰＫＣ活性和钙镁泵的活性，是补     

The effects of changes to action potential duration on the calcium content of the sarcoplasmic reticulum in isolated guinea-pig ventricular myocytes

. We have estimated sarcoplasmic reticulum calcium content using rapid application of caffeine on voltage clamped, isolated guinea-pig ventricular myocytes. Caffeine induces the release of calcium from the sarcoplasmic reticulum and this calcium is extruded from the cells by the sarcolemmal Na/Ca exchange. Integrating the inward Na/Ca exchange current thus allows estimations of sarcoplasmic reticulum calcium content. Ventricular myocytes were stimulated to reach new steady-states by action potential voltage clamps of varying duration. Once contractile steady-state had been reached caffeine was rapidly applied in place of the next action potential and sarcoplasmic reticulum calcium content measured. Prolonging the action potential duration increased sarcoplasmic reticulum calcium content and vice-versa. This calcium loading may underlie the positive inotropic effect of increased action potential duration. Received: 11 July 1996 / Received after revision: 15 October 1996 / Accepted: 26 November 1996     

The resistance of cutaneous feline polymodal C-fiber units to tetrodotoxin as revealed by mechanical and thermal stimulation

Mechanical and thermal excitability of cutaneous feline polymodal C-fiber units is maintained under the action of subcutaneous tetrodotoxin injected in concentrations suppressing the mechanosensitivy of A_β-units. A number of features of inhibition and excitation of C-fiber polymodal sensory units can be explained by existence of tetrodotoxinresistant Na channels in their termination. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 369–371, October, 1997     

Down-regulation of Na channel expression by A23187 in NlE-115 neuroblastoma cells

Growth of cultured NlE-115 neuroblastoma cells in 1 μM A23187 for 2 days to elevate internal Ca reduced both membrane Na current and the transient, but not steady state, component of outward K current. Na channel mRNA abundance was reduced by an average value of 45% without effect on Kv3.1. Increases in internal Ca may therefore control excitability by independent regulation of Na and K channel mRNA abundance in neurons.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.