In Vivo Studies of Pulsatile Implantable Impeller Assist and Total Hearts

Abstract: A pulsatile impeller assist heart and a total heart were tested as a chronic left ventricular assist device in 5 calves and an acute biventricular assist device in 4 pigs respectively, to evaluate their blood compatibility. During the left ventricular assist experiments, the indicators for hemolysis, thrombogenesis, renal dysfunction, and hepatic dysfunction were measured preoperatively, at the beginning of the pumping, 6 h postoperatively, and every following day. The results demonstrated that the impeller assist heart causes no severe blood damage nor organ dysfunction in the experiments lasting up to 11 days. In biventricular assist experiments, the number of red blood cells, white blood cells, platelets, and the he-matocrit, hemoglobin, free hemoglobin, and lactate dehy-drogenase levels were tested preoperatively at the beginning of the pumping and every 2 h postoperatively. The data remained in acceptable ranges during experiments lasting 6 h. It is confirmed that the authors' impeller assist heart and total heart have the advantages of simplicity, implantability, and pulsatility with good blood compatibility.     

Serial peritoneal macrophage function studies in new and established continuous ambulatory peritoneal dialysis patients

Peritoneal macrophages (PM) perform first-line defense activity against peritonitis, the most important complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Our longitudinal study has compared the PM function in 20 uremic patients during periods free of peritonitis since they started CAPD therapy in January 1987. The results showed that at the initiation of CAPD, there was a higher bactericidal activity, phagocytosis index, H2O2 production and interleukin-1 (IL-1), gamma-interferon (IFN-gamma) and tumor necrosis factor (TNF) production ability and MHC expression. As time went on, these progressively decreased, and by 9 months after CAPD therapy had started they were significantly lower than at the beginning. During the 1.5-year follow-up period, there was a significantly increased peritonitis rate in the period 6 months after the beginning of CAPD than in the period before the 6th month (88.3 vs. 11.7% respectively; p less than 0.001). These results indicate that PM of new CAPD patients have a more active function than those of established patients. The established patients had a greater risk of peritonitis. A comparison of the immunological profiles of PM from patients who had a peritonitis history shows that phagocytosis index, bactericidal activity and IL-1 and TNF production of PM were significantly decreased during the period free of peritonitis. This result suggests that these parameters may serve as an indicator in developing peritonitis.     

Brain natriuretic peptide enhances the endothelium-independent cAMP and vasorelaxant responses of calcitonin gene-related peptide in rat aorta

Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and cGMP levels. When endothelium is removed, preincubation with exogenous NO uncovers and potentiates direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves elevation of cGMP and inhibition of Type III (cGMPinhibitable) phosphodiesterase, causing accumulation of cAMP. However, NO may have other actions. The aim of the present study was to determine if brain natriuretic peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM) significantly elevated cAMP levels (from control of 0.95 ± 0.08 to 1.53 ± 0.09 pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and this response was not altered by co-administration of CGRP (100 nM).Pretreatment with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control of 0% to 57.6 ± 6.8% relaxation of phenylephrineprecontractions). Our findings indicate that BNP enhances direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic smooth muscle cells.     

Behavioral, biochemical and neurotoxicological actions of the alpha-ethyl homologue of p-chloroamphetamine

The present set of experiments was designed to examine the effects of extension of the alpha-methyl of p-chloroamphetamine (PCA) to an alpha-ethyl. Therefore, the alpha-ethyl homologue of PCA, 1-(4-chlorophenyl)-2-aminobutane (CAB), was compared to PCA in a number of pharmacological assays. CAB was 2-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and 5-fold less potent at inhibiting uptake of [3H]dopamine ([3H]DA). In drug discrimination assays, CAB was approximately 3-fold less potent than PCA in animals trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or its alpha-ethyl homologue, S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-(+)-MBDB), from saline. Monitoring with in vivo microdialysis, 10 mg/kg of PCA caused a large increase in extracellular DA and a significant decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. In contrast, 11 mg/kg CAB caused no increase and 22 mg/kg CAB caused only a slight increase in extracellular DA. Both doses of CAB caused a decrease in extracellular DOPAC. The potential 5-HT neurotoxicity of CAB was examined by measuring monoamine and metabolite levels and [3H]paroxetine binding at one week following acute doses. A 10 mg/kg dose of PCA caused an 80% decrease in cortical and hippocampal serotonergic markers, while an equimolar dose of CAB decreased only hippocampal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels. However, 22 mg/kg of CAB produced a 20-40% decrease in all serotonergic markers. Thus, extension of the alpha-alkyl significantly decreases the dopaminergic effects of PCA. The similar decrease in relative 5-HT neurotoxicity and the decreased ability to alter dopaminergic systems in vivo and in vitro supports the involvement of DA in the neurotoxicity of PCA.     

钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高

用AR CM MIC阳离子测定系统,测量单个细胞内游离钙浓度([Ca²⁺]i),研究8-(N,N-二乙胺)-n-辛基 3,4,5-三甲氧基苯甲酸酯(TMB-8)对培养乳牛基底动脉平滑肌[Ca²⁺]i的作用。在细胞外钙浓度为1.3mmol·L^-1时,TMB-8(30μmol·L^-1)可明显抑制BHQ,NE及KCl引起[Ca²⁺]i的升高。在细胞外钙为零+EGTA 0.1mmol·L^-1时,TMB-8(10,30及100μmol·L^-1)可浓度依赖性地降低静息[Ca²⁺]i,TMB-8(30μmol·L^-1)可几乎完全阻断BHQ及NE引起[Ca²⁺]i的增加。研究表明TMB-8降低培养乳牛基底动脉平滑肌[Ca²⁺]i的机制,主要是抑制肌浆网Ca²⁺的释放,或增加肌浆网对Ca²⁺的摄入,并由此间接地抑制细胞外钙的内流。     

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.     

单波长荧光分光光度计测定细胞内Ca^2＋浓度的方法探索

在使用单波长荧光分光光度计测定细胞内游离钙浓度时，通过快速（４～６ｓ）手动转换激发波长（ＥＸ），分别测定ＥＸ３４０和３８０ｎｍ时的荧光强度变化，并计算出３４０ｎｍ与３８０ｎｍ时的荧光强度比率（Ｒ），然后也采用双波长荧光分光光度计测定细胞内Ｃａ２＋浓度的计算公式计算细胞内游离钙浓度。结果显示单波长荧光分光光度计按比例法测得的细胞内游离Ｃａ２＋浓度与使用双波长荧光分光光度计测得的结果相似。