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.     

Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice

The objective of this study was to determine whether the development of tolerance to CP 55,940, a potent cannabinoid agonist, was due to changes in the receptor or second messenger system. ICR mice treated with CP 55,940 (2 mg/kg) twice a day for 6 and one-half days developed a high degree of tolerance to the pharmacological effects of CP 55,940. The ability of CP 55,940 to produce motor hypoactivity, hypothermia and immobility was reduced 163-, 97- and 19-fold, respectively. Evaluation of 3H-CP 55,940 binding to rat brain membranes indicated no difference in receptor affinity between the vehicle- and CP 55,940-treated animals. However, these binding studies revealed a 50% decrease in receptor number in the cerebellum of the CP 55,940-tolerant mice. Although cAMP is generally considered to be the second messenger for cannabinoid receptors, little difference was observed in the inhibitory effects of CP 55,940 on adenylyl cyclase activity in cerebellum between vehicle and drug-treated mice. However, there was an increase in receptor mRNA which suggests a compensation for receptor loss. There are several possible explanations for these results. There may be sufficient spare receptors such that CP 55,940-tolerant mice are capable of producing a maximal effect on the second messenger system. On the other hand, one could conclude that cannabinoid receptor down-regulation does not account for the development of tolerance to all of the effects of CP 55,940 in mice.     

胎盘组织液氨基酸的含量测定及层析鉴别

本文采用层析法进行鉴定,用氨基酸分析仪测氨基酸的含量,为胎盘组织液的质量标准提供可靠依据。本法准确率为99%。     

Unusual Delayed Manifestation of a Penetrating Chest Trauma

Abstract Pericardial tamponade remains a diagnostic challenge to the clinician especially when the patient is well compensated hemodynamically. We report an unusual case who sought medical help 1 month after having been stabbed in his chest. An investigation revealed a perforation of the myocardium and a pericardial tamponade. The patient survived thanks to a large organized clot that plugged the perforation. The patient was exposed to increased risk due to delayed onset, recognition, and therapy of the tamponade. Most reports on this subject deal with acute pericardial tamponade. Only few cases of delayed pericardial tamponade have been reported. A review of the relevant literature and the therapeutic approaches are discussed.     

Similar motion of a hand-held object may trigger nonsimilar grip force adjustments.

The tight coupling between load (L) and grip (G) forces during voluntary manipulation of a hand-held object is well established. The current study is to examine grip-load force coupling when motion of the hand with an object was either self-generated (voluntary) or externally generated. Subjects performed similar cyclic movements of different loads at various frequencies with three types of manipulations: 1) voluntary oscillation, 2) oscillating the right arm via the pulley system by the left leg (self-driven oscillation), and 3) oscillating the arm via the pulley system by another person (other-driven oscillation). During the self-generated movements: 1) the grip forces were larger and 2) grip-load force modulation was more pronounced than in the externally generated movements. The G-L adjustments are not completely determined by the mechanics of object motion; nonmechanical factors related to movement performance, for instance perceptual factors, may affect the G-L coupling.     

Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.

Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. INTRODUCTION: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. MATERIALS AND METHODS: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3alpha,17beta-diol-3glucuronide (3G) and androstane-3alpha,17beta-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. RESULTS: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. CONCLUSIONS: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.     

红花注射液治疗老年慢性肾功能衰竭32例临床观察

老年人肾功能随着年龄增长有“自然减退”现象，加上既往存在的高血压、糖尿病、慢性肾炎等疾病，更易出现慢性肾功能衰竭（CRF）。目前老年慢性肾衰的治疗目标是延缓肾功能减退的进程，主要的手段有控制血压、低蛋白饮食、纠正贫血、增加肠道排毒等。笔者采用中医活血化瘀的方法，通过静脉滴注红花注射液改善肾脏的供血，增加肾小球的滤过率，临床取得一定效果，现报道如下，供同道参考。[第一段]     

Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

肱骨干骨折--髓内钉与钢板固定的比较

总体而言，这些报道提示：采用髓内钉治疗肱骨干骨折较采用钢板带来更多的并发症，尤其是采用顺行人路。同时，这些报道没有提供确切的证据证明何种方法在骨折愈合、减少感染或上肢总体功能上优于另一种。