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.     

大鼠脑缺血时脑细胞膜磷脂含量变化

采用SD大鼠一侧大脑中动脉阻断致局限性脑缺血模型。脑缺血后迅速断头置于液氮中,HPLC外标定量法测定各磷脂组分。观察脑缺血1、5、15、60、360min时脑细胞膜磷脂含量变化。结果显示,PI在缺血早期显著低于对照组(P<0.01～0.05);PE、PC早期仅呈下降趋势,PE在缺血60min组、PC缺血360min组显著低于对照组(P<0.01～0.05)。PS在缺血全过程中变化轻微(P>0.05)。提示磷脂降解与脑缺血存在一定关系,缺血早期首先出现脑细胞膜功能磷脂降解,膜结构磷脂则在缺血后期出现显著变化,且PE较PC优先降解。     

胫骨延长术后的功能康复程序初探

胫骨延长术是矫治小儿麻痹后遗症下肢短缩最常见的术式，但如何恢复或改善术后的功能，目前尚无一套系统的程序。本文作者根据自行设计的胫骨延长休后功能康复的临床观察，作较系统地介绍，并就该程序的合理性，进行了讨论与论证。     

Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

Apolipoprotein E—associated risk for Alzheimer's disease in the African-American population is genotype dependent

As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites.     

慢性肾血管性高血压大鼠脑细胞膜游离脂肪酸水平变化

采用SD大鼠慢性肾血管性高血压模型,气-液色谱法测定高血压组(n=8)、对照组(n=9)脑细胞膜游离脂肪酸(Free Fatty Acid,FFA)单组分水平。结果显示高血压组脑细胞膜FFA组份中C20:4、C22:6水平显著高于对照组(PO.05)。提示继发性高血压大鼠存在脑细胞膜FFA代谢障碍。     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

ACTIVIT OF HUMAN PLACENTAL GAMMA GLOBULININ BLOCKING IMMUNE FUNCTIONS IN VITRO AND IN ABROGATING THE XENOGENEIC, LOCAL GRAFT-VERSUS-HOST-REEACTEON

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft – versus –host disease (GCHD) following bone marrow transplantation (BMT) ,we have examined the effect of PGG in vitro and in a model of the xenogeneic , local graft –ver- sus – host reaction (LGVHR) .PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P<0.005) and depressed interleukin -2 (IL-2) levels in such cultures at 72 hours (P<0.01) . In contrast phytohemagglutinin (PHA) –and pokeweed mitogen (PWM) –induced T and B lymphocyte blastogenesis was not affected by such PGG treatment .PGG treatment .PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability .Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation . An immunosuppressive effect of PGG on the LGCHR was tested in a model of intracutaneous transplantation of PGG –treat human lymphocytes into cyclophosphamide – immunosuppressed rats. Lymphoprep – separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing：（1）PGG,4mg/ml,(2) human plasma albumin,4mg/ml,(3)mitomycin-C,25ug/ml, or (4) no additive. Cell of each preparation (3x107cells in 0.1ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells ,each rat received [125 I]IUdR (10uCi) intraperitoneally and was killed after 5 hours. For each site of injection, the diameters of induration were measured and 125 I was counted . There was no difference between buffer – treated and a ibumin – treated groups either in the diameter of the area of induration (t=0.66;P>0.5)or in radioactive counts(t=0.22;P>0.05).In the PGG –treated group, the induration and radioactivity measurements were significantly less than in control groups (t=3.72 and P<0.1;t=2.62 and P<0.02,respectively ) Cytophilic antibodies in PGG were thought to inhibit an early phase of T cell activation, and not to be cytotoxicity .In the LGVHR, the immune response might be abrogated either by immuno- regulatory suppression of T cell function or by toxicity to the infused lymphoid cells. For some clinical purposes, immuno- modulating, human antibodies might be preferred to murine, monoclonal antibodies.     

纸质病案保存期限的思考

本文作者比较了不同时期的纸质病案的使用率,讨论了旧病案的缺点,如难于保存,占用空间及实用价值不大.作者提出了改进保存病案的办法.