Moderate sodium restriction in hypertensive subjects: renal effects of ACE-inhibition

It has been suggested that AII-mediated renal mechanisms limit the efficacy of moderate sodium restriction in the lowering of blood pressure (BP) in hypertension. We therefore studied renal hemodynamics and sodium handling in nine essential hypertensives in balance on 200 and on a 50 mmol sodium diet, before and during ACE-inhibition (enalapril 10 mg bid for 8 days) in a cross-over fashion. BP was similar on 50 and 200 mmol Na before enalapril, the fall in BP during enalapril was significantly more pronounced on 50 mmol Na. On 50 mmol Na, GFR and filtered Na were significantly lower, and tubular reabsorption was significantly higher than on 200 mmol Na. GFR increased during enalapril in 50 but not on 200 mmol Na. Consequently, the differences in GFR and filtered load elicited by sodium restriction were no longer present during ACE-inhibition. In contrast, the differences in tubular reabsorption between 50 and 200 mmol Na persisted during enalapril. In conclusion, moderate sodium restriction, not affecting BP, can elicit a renal hemodynamic response. As this response is blunted by ACE-inhibition it is probably mediated by AII. This blunting may contribute to the increased sodium sensitivity of BP during ACE-inhibition. The adaptation of tubular sodium reabsorption is not affected by ACE-inhibition.     

Effect of intravenous infusion of low-dose dopamine on renal function in normal individuals and in patients with renal disease

A low dose of dopamine was infused in 28 normal volunteers and in 137 patients with varying degrees of renal insufficiency during a routine measurement of the glomerular filtration (GFR) and the effective renal plasma flow (ERPF). Dopamine infusion led to an increase in ERPF and GFR and to fall in the filtration fraction. The effect of dopamine on renal function was most pronounced if the baseline GFR was normal. However, healthy individuals showed greater increases in both ERPF and GFR than renal patients with a comparable baseline GFR. In renal patients no effect was observed if the baseline GFR was below 50 ml/min/1.73 m2. Firstly, it is concluded that already early in renal disease there exists a diminished reserve filtration capacity. Secondly, if the GFR is less than 50 ml/min/1.73 m2, the renal reserve filtration capacity seems to be exhausted.     

INFLUENCE OF EXPERIMENTAL DIABETES ON THE MICROCIRCULATION OF INJURED PERIPHERAL NERVE - FUNCTIONAL AND MORPHOLOGICAL ASPECTS

Regeneration of diabetic axons has delays in onset, rate and maturation. It is possible that microangiopathy of vasa nervorum, the vascular supply of the peripheral nerve, may render an unfavorable local environment for nerve regeneration. We examined local nerve blood flow proximal and distal to sciatic nerve transection in rats with long-term (8 month) experimental streptozotocin diabetes using laser Doppler flowmetry and microelectrode hydrogen clearance polarography. We then correlated these findings, using in vivo perfusion of an India ink preparation, by outlining the lumens of microvessels from unfixed nerve sections. There were no differences in baseline nerve blood flow between diabetic and nondiabetic uninjured nerves, and vessel number, density, and area were unaltered. After transection, there were greater rises in blood flow in proximal stumps of nondiabetic nerves than in diabetic animals associated with a higher number, density, and caliber of epineurial vessels. Hyperemia also developed in distal stumps of nondiabetic nerves but did not develop in diabetic nerves. In these stumps, diabetic rats had reduced vessel numbers and smaller mean endoneurial vessel areas. Failed or delayed upregulation of nerve blood flow after peripheral nerve injury in diabetes may create a relatively ischemic regenerative microenvironment.     

Circulating anti-neutrophil cytoplasmic autoantibodies in subglottic stenosis: a useful aid in diagnosing vasculitis in this condition?

Five patients with subglottic stenosis, occurring either as a presenting symptom or as a manifestation in the course of a systemic disease, are described. Indirect immunofluorescence revealed the presence of circulating autoantibodies against both cytoplasmic and perinuclear constituents of neutrophils in all five. Antibodies directed against a 29 kDa antigen of the azurophilic granules (two patients), against myeloperoxidase (one patient), and against both the 29 kDa antigen and myeloperoxidase (one patient) were found by enzyme-linked immunosorbent assay. These autoantibodies have previously been found in patients with Wegener's granulomatosis, microscopic polyarteritis, (idiopathic) glomerulonephritis and Churg-Strauss syndrome. However, only one of these five patients fulfilled the criteria for these conditions. Since these autoantibodies are seldom observed in other conditions, and other diseases had been excluded by careful evaluation, we suggest that their presence places subglottic stenosis within the spectrum of necrotizing (granulomatous) vasculitis. Whether immunosuppressive therapy is always warranted in patients with subglottic stenosis and circulating anti-neutrophil cytoplasmic antibodies is a matter of debate.     

关节部位Ⅲ度烧伤削痂植皮与切痂植皮的效果比较

目的:Ⅲ度烧伤创面的处理临床上仍然以切痂植皮术治疗为主,由于切痂时切除了并未损伤的皮下脂肪组织,使其愈后外观变化明显。实验拟观察关节部位Ⅲ度烧伤削痂后于脂肪层移植大张自体中厚皮的疗效,并与切痂植皮进行比较。方法:①于2001-01/2007-06南昌大学第一附属医院烧伤科收治的关节Ⅲ度烧伤患者中抽取39例(45个关节)作为削痂组,同时抽取45例(共60个关节)作为切痂组。所有患者对治疗及实验方案均知情同意,且得到医院伦理道德委员会批准。②削痂组削痂植皮,保留正常皮下脂肪等组织。切痂组切痂植皮,切痂平面包括全层皮肤和皮下脂肪组织一并切除直至深筋膜层。削痂或切痂后植大张自体中厚皮。③创面修复后4￣6周观察两组患者的关节外观和关节活动功能;比较两组患者术后2周的植皮成活率和创面修复时间。结果:两组患者均进入结果分析。①两组患者烧伤关节创面修复后与对称的正常关节比较,削痂组外观变化不明显,周径缩小3.6%(P>0.05),功能好,关节活动度减少5.3%(P>0.05);切痂组外观变化明显,周径缩小23.4%(P<0.05),功能较差,关节活动度减少21.9%(P<0.05)。②两组患者术后2周植皮成活率和创面修复时间差异均无显著性意义(P>0.05)。结论:脂肪层移植大张自体中厚皮于Ⅲ度烧伤削痂后关节部位,能够维护肢体的美观,保护关节功能,疗效优于切痂植皮。     

预防治疗2型糖尿病药物分子作用靶点的相关研究与进展

目的:综合分析2型糖尿病新药研究的分子靶点。资料来源:应用计算机检索Springer1990-01/2005-02和Pubmed2000-01/2005-08有关预防和治疗2型糖尿病药物的文献,检索词“diabetes,drug,target”,并限定文献语言种类为English。资料选择:对检索到的有关预防和治疗2型糖尿病药物的相关信息进行整理,筛选针对性强、影响因子较大、最近几年发表的论文。资料提炼:共检索到相关文献49篇,其中15篇符合要求,排除34篇。排除的文章中6篇是关于2型糖尿病的病理生理及生化方面的基础研究,其余为2型糖尿病预防和治疗效果方面的文献。资料综合:综合文献资料发现,以往研制的治疗糖尿病的药物或者因缺乏明确的分子靶点,或者因对疾病本身的病理反应不清楚,因而存在各种弊端。有关预防和治疗2型糖尿病和代谢综合征的分子靶点为抗糖尿病药物的研发展示了光明的前景,涉及的药物包括经典受体的小分子调节剂、酶作用靶点、蛋白质制剂和反义寡核苷酸等。结论:根据2型糖尿病和代谢综合征特异的病理反应机制作为筛选药物的分子基础是未来抗糖尿病药物研发的主攻方向。     

Renal function and metabolism during endotoxemia in rats: role of hypoperfusion.

Renal failure often complicates endotoxin shock. This might be due to renal hypoperfusion, but endotoxemia could also have additional effects. We studied in anesthetized rats renal plasma flow (RPF), glomerular filtration rate (GFR), and metabolism (ATP, CrP = creatine phosphate, energy charge = [ATP + 0.5 ADP]/[ATP + ADP + AMP], lactate, glucose) during endotoxin shock (Escherichia coli endotoxin, 10 mg/kg for 60 min; n = 10) and "balloon shock" (balloon inflated in vena cava below renal vein to cause comparable decreases in cardiac output and RPF as in endotoxin-treated rats; n = 10). A third group of rats served as controls (n = 10). At t = 0 infusion of endotoxin was started. At t = 90 min, when cardiac output was low and serum lactate was high (indicating shock), GFR and RPF were obtained from plasma disappearance rates (from t = 90 to t = 135 min) of 125I-thalamate and 131I-hippurate, respectively. Experiments ended at t = 135 min. In both shock groups RPF decreased (by ca. - 75% compared with control rats), but filtration fraction only increased (by 72%) in the "balloon shock" rats. In renal biopsies lactate concentration increased more (by 407 vs. 167%) and ATP decreased more (by -63 vs. - 35%) during endotoxin shock than during "balloon shock"; the endotoxin-treated rats also showed a significant decrease in CrP (by - 58%), energy charge (by - 31%), and glucose concentration (by - 34%), and an increase in the number of leukocytes in the glomeruli (by 730%). Renal function and metabolism thus was more affected in this hypodynamic form of endotoxin shock than in "balloon shock." This may be caused by the effects of endotoxin on sticking of leukocytes and renal metabolism.     

Recognising patients who will die in the near future: a nationwide study via the Dutch Sentinel Network of GPs

Background

Recognising patients who will die in the near future is important for adequate planning and provision of end-of-life care. GPs can play a key role in this.

Aim

To explore the following questions: How long before death do GPs recognise patients likely to die in the near future? Which patient, illness, and care-related characteristics are related to such recognition? How does recognising death in the near future, before the last week of life, relate to care in during this period?

Design and setting

One-year follow-back study via a surveillance GP network in the Netherlands.

Method

Registration of demographic and care-related characteristics.

Results

Of 252 non-sudden deaths, 70% occurred in the home or care home and 30% in hospital. GP recognition of death in the near future was absent in 30%, and occurred prior to the last month in 15%, within the last month in 19%, and in the last week in 34%. Logistic regression analyses showed cancer and low functional status were positively associated with death in the near future; cancer and discussing palliative care options were positively associated with recognising death in the near future before the last week of life. Recognising death in the near future before patients’ last week of life was associated with fewer hospital deaths, more GP–patient contacts in the last week, more deaths in a preferred place, and more-frequent GP–patient discussions about specific topics in the last 7 days of life.

Conclusion

Recognising death in the near future precedes several aspects of end-of-life care. The proportion in whom death in the near future is never recognised is large, suggesting GPs could be assisted in this process through training and implementation of care protocols that promote timely recognition of the dying phase.     

Negligible radiation protection of endothelial cells by vascular endothelial growth factor

Glioblastoma multiforme (GBM) is a radioresistant tumor. Tumor neoangiogenesis is an important mechanism for tumor sustenance. Angiogenesis is primarily mediated by vascular endothelial growth factor (VEGF), and earlier studies have suggested that VEGF protects human umbilical vein endothelial cells (HUVECs) against high doses of radiation. We tried to extend these findings to other endothelial cell lines and clinically relevant irradiation doses. Therefore, four different endothelial cell lines (HUVEC-C, primary HUVEC-P, an immortalized HUVEC cell line: EC-RF24, and bovine retina endothelial cells: BREC) were cultured without or with recombinant human VEGF165 (rhVEGF165). Cells were irradiated with gamma-rays from a 137Cs-source. Radiosensitivity was determined by proliferation or clonogenic assay. Apoptosis was assayed by flow cytometric determination of the sub-G1 population or by counting nuclear fragmentation. We found that the biologically active rhVEGF165 was able to improve clonogenic survival of HUVEC-C after 2 and 5 Gy. However, rhVEGF165 could not significantly alter the radiosensitivity of all cell lines studied in proliferation assays. rhVEGF165 only slightly reduced apoptosis in HUVEC-C after 3 Gy. In conclusion, the radioprotective effect from rhVEGF165 was found on different endothelial cell lines after clinically relevant radiation doses was negligible. We therefore hypothesize that the high VEGF-levels found in GBM in vivo do not reduce the radiosensitivity of endothelial cells, which is thought to contribute to the strong radioresistance of the tumor vasculature.