微电极导向同期双侧腹后苍白球 毁损术治疗帕金森病

目的介绍微电极导向同期双侧腹后苍白球毁损术治疗帕金森病的方法与效果。方法应用微电极电生理记录技术术对毁损靶点进行确认定位,对３１例难治性帕金森病患者行同期双侧腹后内侧苍白球毁损治疗,术前及术后于开状态、关状态分别行改良Ｗｅｂｓｔｅｒ记分,计算改善率,评价其疗效。结果经微电极确认后的电生理靶点与ＣＴ定位靶点存在明显差异,靶点调整率８０６％。３１例手术均有效,其中治愈７例,明显进步２４例。Ｗｅｂｓｔｅｒ计分术后１周开状态改善率为７４２％±９５％,关状态改善率为８９１％±８９％。无永久性并发症。结论微电极导向同期双侧腹后苍白球毁损术安全、有效,具有明显临床治疗优势,微电极记录技术可使术中定位精确度大大提高。     

Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation

Cortical metabolites and regional cerebral intracellular pH (pHi) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose approximately 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pHi was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.     

Cholecystokinin/opioid interactions

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK-opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nociception in normal and axotomized rats was examined. The CCK2 receptor antagonist CI-988 did not reduce spinal hyperexcitability following repetitive C-fiber stimulation in normal or axotomized rats, suggesting that CCK is probably not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellular level of CCK in the dorsal horn in a naloxone reversible manner. Morphine also released CCK after axotomy, but not during carrageenan-induced inflammation. In contrast, K(+)-stimulation failed to increase extracellular levels of CCK in axotomized rats, but did so in inflamed rats. Double-coloured immunofluorescence technique revealed partial co-localization between CCK-like immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dorsal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axotomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR-LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK release, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal horn induced by nerve injury.     

Gamma-aminobutyric acid-induced responses in acutely dissociated neurons from the rat sacral dorsal commissural nucleus

The electrophysiological and pharmacological properties of GABA-activated Cl- currents (IGABA) were investigated in enzymatically dissociated rat sacral dorsal commissural nucleus (SDCN) neurons using the nystatin perforated patch recording configuration under voltage-clamp conditions. Exogenous application of GABA to SDCN neurons induced Cl- currents which increased in a concentration-dependent manner. Bicuculline (BIC) and strychnine (STR) antagonized the IGABA in a concentration-dependent manner. Zn2+ suppressed the IGABA with an IC50 of 2.8 X 10(-5) M. Muscimol mimicked the IGABA, while baclofen evoked no response. Pentobarbital (PB) and 5beta-pregnan-3alpha-ol-20-one (pregnanolone, PGN) also induced GABAA-mimic Cl- currents. Diazepam (DZP), PB and PGN all enhanced the IGABA by increasing the apparent affinity of the GABAA receptors to GABA. Moreover, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) were observed in mechanically dissociated SDCN neurons attached with synaptic boutons, so called 'synaptic bouton preparation'. These results indicate that SDCN neurons express GABAA receptors with relatively low sensitivity to Zn2+ inhibition, and that GABA may have a functional role as an inhibitory transmitter in the SDCN regulating nociceptive, analgesic, and autonomic functions.     

Opioid peptide receptor studies, 11: involvement of Tyr148, Trp318 and His319 of the rat mu-opioid receptor in binding of mu-selective ligands

Previous data obtained with the cloned rat mu opioid receptor demonstrated that the "super-potent" opiates, ohmefentanyl (RTI-4614-4) and its four enantiomers, differ in binding affinity, potency, efficacy, and intrinsic efficacy. Molecular modeling (Tang et al., 1996) of fentanyl derivatives binding to the mu receptor suggests that Asp147, Tyr148, Trp318, and His319 are important residues for binding. According to this model, Asp147 interacts with the positively charged opiate agonist to form potent electrostatic and hydrogen-bonding interactions. In this study, the role of weak electrostatic and hydrogen-bonding "pi-pi" interactions of the O atom of the carbonyl group and the phenyl ring structures of RTI-4614-4 and its four enantiomers with residues Tyr148, Trp318, and His319 were explored via site-directed mutagenesis. Tyr148 (in transmembrane helix 3 {TMH3}), Trp318 (TMH7), and His319 (TMH7) were individually replaced with phenylalanine or alanine. Receptors transiently expressed in COS-7 cells were labeled with [125I]IOXY according to published procedures. Mutation of Tyr148 to phenylalanine reduced the binding affinities of some mu-selective agonists (2-7 fold) but did not alter the affinities of DAMGO, naloxone, and the non-selective opiates etorphine and buprenorphine. In contrast, this mutation significantly increased the binding affinities (decreased the Kd values) of [D-Ala2,D-Leu5]enkephalin, IOXY, and dermorphin. Mutation of Trp318 decreased opioid receptor binding to almost undetectable levels. Substitution of alanine for His319 significantly reduced binding affinities for the opioid ligands tested (1.3- to 48-fold), but did not alter the affinities of naloxone and bremazocine. These results indicate the importance of Tyrl48 and His319 for the binding of fentanyl derivatives to the mu receptor. Functional studies using the mutant receptors will provide additional insight into the mechanism of action of RTI-4614-4 and its four enantiomers.     

Intrathecal adenosine does not relieve allodynia-like behavior in spinally injured rats

The intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) reduced pain-related behaviors after peripheral nerve or spinal cord injury in rats. The endogenous ligand adenosine is clinically available and has been tested i.t. as an analgesic. Thus, we set out to investigate whether i.t. adenosine could reduce allodynia in a model of central pain in spinally injured rats. I.t. adenosine did not reduce mechanical and cold allodynia-like behaviors at doses of 10, 100 and 187 nmol, whereas i.t. R-PIA at 10 nmol markedly alleviated allodynia in the same animals. The lack of effect by exogenous adenosine may be due to pharmacokinetic or pharmacodynamic reasons. Alternatively, adenosine may have reduced affinity and selectivity towards the A1-receptors which may be important for the antiallodynic effect.     

Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors

BACKGROUND: Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. METHODS: To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM). Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. RESULTS: Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. CONCLUSION: To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient.     

精氨酸对烧伤创面愈合的影响

目的 探讨精氨酸对烧伤创面愈合的影响和量效关系。方法 通过大鼠深Ⅱ度烫伤模型,伤后肠道站充不同剂量精氨酸,观察烧伤创面愈合时间,测定烧伤创面愈合面积百分比,创面Ｉ型／Ⅲ型胶原比例,羟脯氨酸（ＯＨＰ）含量和真皮细胞增殖周期,结果 每天补充１００－４００ｍｇ／ｋｇ精氨酸可缩短烧伤创面愈合时间,增加烧伤创面中ＯＨＰ含量,降低烧伤创面Ｉ／Ⅲ型胶原比例,加速真皮细胞ＤＮＡ复制。比较喂不同剂量精氨酸各组,发现     

窥镜下激光治疗前列腺增生症

目的 评价经尿道激光前列腺切除术（ＴＵＬＰ）的疗效及其与前列腺大小的关系。方法 回顾分析了１９８８年至１９９８年１０年,采用ＴＵＬＰ治疗的４６９例前列腺增生症患者对手术技术、手术前后的症关改善情况进行比较,并对２３３例符合条件的患者ＴＵＬＰ手术效果与前列腺大小的相关性进行了研究。结果 ４６９例患者前列腺症状评分（ＩＰＳＳ）平均值由术前的２６．７降到术后的１４．２;最大尿流率平均值由６．２ｍｌ／ｓ上