胃肠外营养添加精氨酸对胃癌术后患者淋巴细胞免疫功能的作用

为探讨胃肠外营养（ＴＰＮ）添加精氨酸（Ａｒｇ）对胃癌术后患者淋巴细胞免疫功能的影响及意义,对３６例胃癌术后患者进行了ＴＰＮ支持的前瞻性研究,检测常规ＴＰＮ和ＴＰＮ添加Ａｒｇ支持前后患者的Ｔ淋巴细胞亚群、ＮＫ细胞活性、ＩＬ２和ＣＤ２５水平变化。结果：常规ＴＰＮ支持前后患者的Ｔ淋巴细胞亚群、ＮＫ细胞活性、ＩＬ２和ＣＤ２５水平变化无明显差异,而ＴＰＮ添加Ａｒｇ支持后患者的ＣＤ４、ＣＤ４／ＣＤ８比值、ＮＫ细胞活性和ＩＬ２水平均明显增加（Ｐ＜０．０５）。本研究结果显示：常规ＴＰＮ不能纠正胃癌术后患者的淋巴细胞免疫功能抑制,但ＴＰＮ添加Ａｒｇ则可促进ＩＬ２生成增加,ＮＫ细胞活性增强,改善了胃癌术后患者的淋巴细胞免疫功能,提示ＴＰＮ添加Ａｒｇ有免疫促进作用     

Inborn errors of creatine metabolism and epilepsy

Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CT1‐encoded by SLC6A8 gene) deficiency. Epilepsy is one of the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile convulsions in infancy is a relatively common presenting symptom in all the three above‐mentioned diseases. GAMT deficiency results in a severe early onset epileptic encephalopathy with development arrest, neurologic deterioration, drug‐resistant seizures, movement disorders, mental disability, and autistic‐like behavior. In this disorder, epilepsy and associated abnormalities on electroencephalography (EEG) are more responsive to substitutive treatment with creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is mainly characterized by mental retardation and severe language disorder without epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT deficiency. All creatine disorders can be investigated through measurement of creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy (¹H‐MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA) assessment and brain H‐MRS examination should be part of diagnostic workup for all patients presenting with epileptic encephalopathy of unknown origin. In girls with learning and/or intellectual disabilities with or without epilepsy, SLC6A8 gene assessment should be part of the diagnostic procedures. The aims of this review are the following: (1) to describe the electroclinical features of epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the role of a substitutive therapeutic approach on their clinical and electroencephalographic epileptic patterns.     

Raised intracranial pressure,the syndrome of inappropriate antidiuretic hormone secretion,and arginine vasopressin in tuberculous meningitis

Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mm Hg, range 8.4–50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8–42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.     

Release of hypothalamic corticotropin-releasing hormone and arginine-vasopressin by interleukin 1β and αMSH: studies in rats with different susceptibility to inflammatory disease

The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary-adrenal (HPA) axis responsiveness to a variety of inflammatory and neuroendocrine stimuli. In contrast resistance to inflammatory disease of histocompatible Fischer rats is associated with their intact HPA axis responses to the same stimuli. We have examined the contribution of IL-1β to in vitro corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic explants derived from LEW/N and F344/N rats. The same animal model has been used to investigate the regulatory effect of αMSH, an immunosuppressive neurohormone, on IL-1β stimulated CRH and AVP secretion. CRH basal release in both strains was similar. However, LEW/N hypothalamic AVP basal secretion was significantly elevated. CRH relative response of LEW/N hypothalamic explants to IL-1β stimulation was lower compared to Fischer, which is consistent with their hyporesponsiveness to inflammatory mediators. AVP secretion however, was significantly decreased in hypothalamic explants from both strains after 40 min exposure to IL-1β. αMSH suppressed basal CRH and AVP release in both LEW/N and F344/N rats and prevented IL-1β stimulated CRH secretion in these strains. AVP was further diminished in F344/N explants following incubation with αMSH+IL-1β, while LEW/N level was significantly elevated. However, AVP levels remained significantly below baseline in explants from both strains after final incubation with IL-1β. Although our findings indicate a modulatory action of αMSH in HPA axis regulation in vitro, the physiological importance of this phenomenon in Lewis and Fischer rats requires further investigation.     

Only arginine vasopressin, not oxytocin and endogenous opiate peptides, in hypothalamic paraventricular nucleus play a role in acupuncture analgesia in the rat

Our previous study proved that hypothalamic paraventricular nucleus (PVH) plays an important role in acupuncture analgesia. The effect of acupuncture on the concentrations of arginine vasopressin (AVP), oxytocin (OXT), leucine-enkephaline (L-Ek), beta-endorphin (beta-Ep) and dynorphinA(1-13) (DynA(1-13)) was investigated in rat PVH. Electrical acupuncture of "Zusanli" points (St. 36) 30 min increased the AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) concentrations in PVH tissue using micropunch and radioimmunoassay, which showed a negative relationship between the pain threshold and AVP concentrations in PVH tissue. Electrical acupuncture could elevate the AVP concentrations in PVH perfuse liquid during acupuncture, and then reduce the AVP concentrations in PVH perfuse liquid after acupuncture. But no change in OXT, L-Ek, beta-Ep and DynA(1-13) concentrations was detected in PVH perfuse liquid. Electrical acupuncture decreased the number of AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) immunoreactive cells in PVH using immunocytochemistry. The results suggested that only AVP, not OXT and endogenous opiate peptides in PVH involved acupuncture analgesia in the rat.     

补阳还五汤治疗大鼠气虚血瘀型脑缺血的代谢组学研究

目的：探讨补阳还五汤对气虚血瘀型脑缺血大鼠生物代谢途径的影响。方法：将30只大鼠随机分为假手术组、模型组和补阳还五汤组(3.49 g/kg)。模型组和补阳还五汤组采用荧光微球诱导多发性脑梗死合并睡眠剥夺,建立气虚血瘀型脑缺血动物模型,并分别给予蒸馏水或补阳还五汤灌胃。假手术组给予蒸馏水灌胃,不睡眠剥夺和微球注射。记录各组大鼠的体质量。实验结束后,处死大鼠,采血分析。酶联免疫吸附试验法检测大鼠血清中血栓素B₂(TXB₂)和6-酮基-前列环素1α(6-keto-PGF_1α)水平。采用液质联用的代谢组学方法检测血清样品。结果：与假手术组比较,模型组大鼠平均体质量明显降低,TXB₂/6-keto-PGF_1α比值升高(均P<0.05);与模型组比较,补阳还五汤组大鼠平均体质量升高,药物干预可降低TXB₂/6-keto-PGF_1α比值(P<0.05)。代谢组学结果显示,假手术组与模型组比较,差异有统计学意义(P<0.05),补阳...     

Behavior of pancreatic glucagon,insulin, and HGH in liver cirrhosis,after arginine and i.v. glucose

Summary The authors studied the behavior of plasma levels of glucagon, HGH and insulin in a group of cirrhotic patients both in basal conditions and after i.v. arginine and glucose in order to assess their respective importance in the pathogenesis of carbohydrate disorders. After i.v. arginine an increased plasma concentration of pancreatic glucagon was found which reached its highest level at 15 min; i.e. glucose did not suppress the increased plasma glucagon levels. Plasma HGH which is consistently increased is not influenced by i.v. glucose. Plasma insulin was consistently raised during both tests; however, the insulinogenic index after i.v. glucose behaved like that of mild diabetics. The true importance of glucagon in the pathogenesis of carbohydrate intolerance in cirrhotics cannot as yet be determined with certainty; according to the authors, hyperglucagonemia is not the primary factor but only one of the main causes of this intolerance.     

精氨酸加压素对星形胶质细胞水孔蛋白-4表达的调节及脑水肿形成影响的研究

目的研究精氨酸加压素(AVP)对星形胶质细胞水孔蛋白-4(AQP4)表达的调节,以及p38 MAPK信号通路在AQP4表达过程的作用,明确AVP及AQP4在脑水肿发生过程中的作用。方法大鼠大脑皮质分离星形胶质细胞,星形胶质细胞经分别用AVP、V1a受体(V1aR)拮抗剂和SB 203580进行处理,采用免疫组织化学技术及RT-PCR对AQP4 mRNA进行检测,Western blot检测p38 MAPK信号通路在AVP诱导AQP4表达中的活化程度。结果500nmol/L的AVP处理6h后,AQP4 mRNA表达开始升高(P<0.01),到12h达高峰(P<0.01),24h后仍维持在较高的水平(P<0.05)。加入p38 MAPK抑制剂SB 203580干预后,AQP4 mRNA表达水平与对照组比较差异不显著(P>0.05);AVP处理15min后p38 MAPK磷酸化水平开始增加,30min达高峰,持续到60min开始下降。V1aR拮抗剂处理后p38 MAPK磷酸化水平整个时间段均未出现明显变化。结论AVP通过激活V1aR引起p38MAPK信号通路活化从而诱导AQP4 mRNA高表达,从基因水平对AQP4进行调节,可能在脑水肿发生中,尤其是在星形胶质细胞水肿形成中起重要作用。V1aR拮抗剂及p38 MAPK抑制剂能抑制AQP4 mRNA的表达,避免星形胶质细胞肿胀。     

Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction

PURPOSE: The goal of this double-blind, placebo-controlled, three-way crossover, randomized clinical trial was to compare the efficacy and safety of the combination of 6g of L-arginine glutamate and 6 mg of yohimbine hydrochloride (AY) with that of 6 mg of yohimbine hydrochloride (YP) alone and that of placebo (PP) alone, for the treatment of erectile dysfunction (ED). MATERIALS AND METHODS: Forty-five patients were included in this study. During each of the 2-week, crossover periods, drug was administered orally, one to two hours before intended sexual intercourse. The primary endpoint was change in the Erectile Function Domain score of the International Index of Erectile Function (IIEF). The secondary endpoints were patient and investigator assessments of treatment success. RESULTS: At the end of each treatment period, the Erectile Function Domain scores for AY, YP and PP were 17.2+/-7.17, 15.4+/-6.49 and 14.1+/-6.56, respectively. The difference between AY and PP was statistically significant (p=0.006). When stratified according to baseline scores over 14, those patients with mild to moderate MED had a better Erectile Function Domain response to treatment (AY=22.2+/-4.99, YP=18.2+/-5.59, PP=16.9+/-6.91, respectively) than those with scores 14 and below (AY=12.4+/-5.48, YP=12.7+/-6.25, PP=11.4+/-5.02, respectively). Investigators' and patients' assessment of efficacy was significantly improved by YP over PP. CONCLUSIONS: This pilot study shows that the on-demand oral administration of the L-arginine glutamate 6g and 6 mg yohimbine combination is effective in improving erectile function in patients with mild to moderate ED. It appears to be a promising addition to first-line therapy for ED.     

Quantitative in vivo assessment of arginine utilization and nitric oxide production in endotoxemia

BACKGROUND: Until recently no methods were available to quantitate nitric oxide (NO) production in vivo. The advent of stable isotope techniques has allowed quantitation of NO production in different animal models and human disease states. METHODS: In vivo NO production was assessed with the use of stable isotope labeled arginine. Enrichments of metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Knock-out mice were used to assess the influence of knocking out inducible NOS (iNOS) or constitutively expressed NOS (cNOS) on arginine-NO metabolism. Pig models were used to assess the role of individual organs on arginine-NO fluxes. RESULTS: In mice under basal conditions cNOS mediates half of the NO production. After endotoxin challenge NO production doubles as a result of iNOS induction and cNOS-mediated NO production is downregulated. In larger animal models (pig) whole body NO production is augmented after endotoxin challenge, largely resulting from NO production in liver, intestine and kidney. Arginine supplementation increases NO production in pigs in liver, intestine and kidney both in the basal state and after endotoxin challenge. CONCLUSIONS: Stable isotope techniques employing LC-MS allow in vivo assessment of NO production in small and large animal models and in patients. This allows definition of the role that iNOS and cNOS-mediated NO production play in several disease states.