Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man.

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the 'indirect' pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the 'direct' pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7-74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.     

Evidence for capillary leakage during chemotherapy in man

The influence of intensive chemotherapy with high dose VP 16-213, cyclophosphamide and autologous bone marrow transplantation on transcapillary escape rate of albumin was evaluated. Transcapillary escape rate and plasma volume were measured with 131I-labelled albumin. Measurements were performed 1 day before (T0), 1 week after (T1) and 2 weeks after (T2) start of chemotherapy. Before therapy TER (n = 7, means = 7.1% h-1) was already raised in patients compared to controls (n = 5, means = 3.8% h-1, P less than 0.025). No difference was found for transcapillary escape rate on T1 (n = 9, means = 7.6% h-1) compared to T0. There was an increase of transcapillary escape rate from T0 to T2 (n = 8, means = 9.5% h-1, P less than 0.05). Plasma volume did not change during therapy. Serum albumin concentrations were reduced before chemotherapy (means = 38 g 1(-1] compared to controls (means = 44 g l(-1]. After 1 (means = 34 g 1(-1] and 2 weeks (means = 31 g 1(-1] these concentrations decreased further. The same was found for intravascular mass of albumin related to body weight. The intravascular mass of albumin/bodyweight and the transcapillary escape rate are related in the patients (r = -0.477, P less than 0.01) and the patients plus controls (r = -0.585, P less than 0.001). This means the higher the transcapillary escape rate the lower the intravascular mass of albumin. No correlation between transcapillary escape rate and presence of fever was found. It can be concluded that intensive chemotherapy leads to further increase of an already elevated transcapillary escape rate for albumin.     

Evidence for cardiac beta 2-adrenoceptors in man

We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +/- 4(SEM) after placebo to 146 +/- 7 bpm after atenolol and 138 +/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +/- 0.3 micrograms after placebo to 38.9 +/- 8.3 micrograms after propranolol and 8.3 +/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +/- 2.1 and 10.1 +/- 2.5 ml/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.     

心肌梗死后心肌纤维化的研究进展

心肌纤维化是心肌梗死后主要的病理过程,特征是细胞外基质合成和降解失衡,而成纤维细胞和肌纤维母细胞在此过程中起重要作用。心肌梗死后,梗死区域替代性纤维化可以减少梗死区域进一步的扩张,维持心室结构完整性,防止心室壁破裂;而非梗死区域的反应性纤维化,则会改变心室顺应性,增加心室壁的硬度,影响心脏的收缩和舒张功能。因此,心肌梗死后理想的治疗是抑制非梗死区域反应性纤维化、诱导梗死区域心肌再生,从而改善心功能。     

Evidence for concerted effects of aldosterone on a target sodium-transporting epithelium.

The sodium-transporting activity of toad skin is stimulated in vitro with aldosterone in the absence of energy-providing substrate; it can be stimulated further upon addition of glucose after prolonged (overnight) incubation. The magnifying effect exerted by glucose in these conditions could be blocked by inhibitors of ribonucleic acid and protein biosynthesis. In addition, exposure to cycloheximide prevented the increase in thermodynamic affinity resulting from aldosterone treatment. A synthetic 19-nor steroid, (RU 24411), dimethyl-2,2-hydroxy-21-nor-19-pregnene-4-dione-3,20, also stimulated sodium transport by toad skin incubated in the absence of glucose, but there was no magnifying effect of this substrate. Furthermore, there was no change in thermodynamic affinity with RU 24411. Therefore, the magnifying effect seen with glucose and the increase in thermodynamic affinity are not necessarily integral parts of the response of sodium-transporting epithelial to "mineralocorticoids."     

Increased type I collagen synthesis in victims of sudden cardiac death due to idiopathic myocardial fibrosis

Abstract

Aims. Idiopathic myocardial fibrosis (IMF) was observed to be the most prevalent autopsy finding in the victims of sudden cardiac death (SCD) under the age of 40 years in the FinGesture cohort. To elucidate further the mechanisms of IMF, we examined the collagen composition from the myocardial samples taken from the victims of IMF-associated SCD.

Methods. Eighteen cases with IMF as a cause of death, confirmed by autopsy, were selected for the analysis. Controls (n = 27) included were cases in whom no cardiac or non-cardiac disease could be found as a cause of unexpected death at autopsy. In addition to conventional histological examination, immunohistochemical staining of procollagens I and III (PINP and PIINP), mature collagen III (IIINTP), and the cross-linked collagen I degradation product (ICTP) were performed.

Results. Increased accumulation of PINP was observed in the fibrotic tissue of the IMF cases in comparison with control samples. In contrast, type III collagen was not as frequently expressed in the fibrotic areas.

Conclusion. Myocardial accumulation of PINP in the victims of IMF-associated SCD indicates increased type I collagen synthesis. Future studies on the role of circulating type I collagen biomarkers are needed to study further the implications of the described association.     

两种体位激发试验对醛固酮瘤的诊断价值

目的：比较单纯体位激发试验及体位联合呋塞米双重激发试验对临床确诊的醛固酮瘤（APA）患者肾素活性（PRA）、醛固酮（ALD）、醛固酮/肾素比值（ARR）的影响。方法：对112例经我院手术切除并行病理检查确诊为醛固酮瘤（APA）的患者进行统计分析,其中60例术前行单纯体位激发试验（单纯激发组）,52例行体位联合呋塞米双重激发试验（双重激发组）,比较两组患者的一般情况、PRA、ALD数值,并计算ARR。结果：行体位联合呋塞米双重激发试验与单纯体位激发试验患者的一般情况、PRA、ALD、ARR均无显著性差异,双重激发组不良反应更多见,与单纯体位激发组相比差异有统计学意义（P〈0.05）。结论：在体位激发试验中是否加用呋塞米对APA患者的ARR影响不大,反而增加了不良反应的发生率。     

原醛性肾上腺腺瘤的螺旋CT诊断(附68例报告)

目的 :探讨螺旋CT对原发性醛固酮增多症性肾上腺腺瘤的诊断价值。方法 :对 68例原发性醛固酮增多症性肾上腺腺瘤的螺旋CT征象进行回顾性分析。观察肿瘤的大小、边界、内部结构及其与同侧肾上腺的关系 ,测量肿瘤平扫和增强后CT值及强化程度。结果 :肿瘤呈类圆形或椭圆形 ,最大直径 0 .8～ 3 .2cm ,密度均匀 ,未见坏死、出血及钙化 ,肿瘤均与同侧肾上腺相连或相邻层面可见相对正常的肾上腺 ,平扫CT值 -5 3～ 2 0 .9HU ,增强后CT值 12 .8～ 5 6.8HU ,增强程度 15 .5～ 40 .7HU ,2 0个病灶边缘呈薄纸样环形强化。螺旋CT诊断正确率 97.1%。结论 :螺旋CT结合临床及化验资料 ,可以对原发性醛固酮增多症性肾上腺腺瘤做出正确的定性及定位诊断。     

Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man

We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean +/- SEM increment 352 +/- 23 pmol/l, n = 7, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P less than 0.001). Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 +/- 0.9 mmHg, P less than 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 +/- 0.7 mmHg, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P less than 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.     

Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man

Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40 000 i.u. of cholecalciferol. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.     

Stimulation and suppression of aldosterone in plasma of normal man and in primary aldosteronism

The effect of stimulating and suppressive influences on plasma aldosterone in normal man and in patients with primary aldosteronism were studied using a sensitive double-isotope derivative assay for aldosterone.     

血浆醛固酮、血管紧张素-Ⅱ含量与肾间质纤维化相关性研究

目的 探讨慢性肾脏疾病间质纤维化发生过程中血浆醛固酮（ALD）、血管紧张素．Ⅱ（Ang-Ⅱ）含量的变化。方法 应用放射免疫分析法检测各种慢性肾脏间质纤维化患者血浆中ALD和Arg-Ⅱ含量表达。结果 肾间质纤维化患者血浆中ALD和Arg-Ⅱ含量均升高，与对照组相比差异非常显著P0．01，而ALD和Arg-Ⅱ呈正相关，r=0．842。结论 慢性肾脏间质纤维化与血浆ALD和Arg-Ⅱ含量有关。临床治疗慢性肾脏疾病应给予ALD和Arg-Ⅱ拮抗剂，防止肾间质纤维化的形成。