Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes

Haemoglobin (Hgb) levels are known to be associated with numerousadverse outcomes in both chronic kidney disease (CKD) and non-CKDpatients. This analysis evaluates the association of baseline haemoglobinlevels on survival in CKD patients, who are followed by nephrologists,irrespective of glomerular filtration rate (GFR), prior to initiationof renal replacement therapy (RRT) and erythropoietin hormonereplacement therapy. Analysis of data from the provincial database (PROMIS, PatientRegistration and Outcome Management Information System) in BritishColumbia, Canada, was undertaken. Records used for the analysisincluded all CKD patients at first registration: GFR <60ml/min/1.73 m², not yet on dialysis, starting from May 1998to October 2002, and who had complete data (defined as age andgender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the associationof Hgb and survival controlling for eGFR at first registrationvalue, age, gender and diabetic status. Multivariate Cox proportionalhazards analysis with time to death as outcome variable wasperformed. The cohort included 3028 patients: the mean age was 65 years,28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73m². The cohort is representative of the BC CKD and dialysispopulation regarding ethnicity: 64% Caucasian, 32% Asian. Medianfollow-up was 27 months, 1 year survival was 0.92, 2 year survivalwas 0.85. Hgb at initial registration is a statistically independentpredictor of survival (RR = 0.875 for every 10 g/l, 95% CI:0.835–0.917, P = 0.0001), after adjusting for age, gender,diabetic status and baseline eGFR. Further analysis, controllingfor RRT, demonstrated a similar association between Hgb andsurvival (RR = 0.853 for every 10 g/l, 95% CI: 0.799–0.910,P = 0.0001), after adjusting for above variables. Substantialvariation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb atall GFR levels, and the need to study the impact of modificationof Hgb at different GFR levels on survival.     

Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.     

氧化亚氮联合利多卡因行无痛人工流产术280例临床分析

目的: 探讨吸入 50%氧化亚氮 (N2O) 与 50%氧气 (O2 ) 的混合气体联合宫颈注射 2%利多卡因进行无痛人工流产术 (人流术) 的有效性和安全性。方法: 将人流术 580例分为A、B两组。其中A组 280例吸入 50%氧化亚氮 (N2O)与 50%氧气的混合气体联合宫颈注射 2%利多卡因进行无痛人流术, 称为联合组; B组 300例, 不用任何药物, 为对照组, 分析比较两组手术中镇痛效果, 宫口松弛情况, 手术出血量, 人流综合反应。结果: 联合组镇痛完全, 有效率达 97 5%。宫口完全松弛率 97 9%。两组比较有显著性差异 (P<0 05)。结论: 吸入氧化亚氮联合宫颈注射利多卡因进行无痛人流术, 镇痛效果确定, 人流时受术者意识处于朦胧状态, 安静, 无痛苦, 不良反应少, 苏醒快等。     

肿胀法外超声吸脂术的组织学研究

目的 观察外超声能量作用于活体组织后的组织学变化，以探索其作用机制。方法 对3只家猪腹部两侧进行外超声与非超声比较，作用不同时间后在光镜和电镜下观察其皮肤组织全层的变化。结果 在外超声作用18min内，随着作用时间的延长，猪的皮下脂肪组织和生物大分子结构的破坏程度不断加重，脂肪组织中产生的空泡不断增大而皮肤组织及血管无明显变化。结论 外超声吸脂术可通过稳定的空泡效应选择性地使脂肪细胞结构发生不可逆的坏死性改变，这一改变与作用时间成正比。     

32例腹部开放性损伤的救治体会

目的:探讨开放性腹部损伤的治疗方法。方法:回顾性分析1991年-1994年32例开放性腹部损伤患者的临床资料。结果:开腹探查26例,单纯缝合6例,阴性探查3例,二次手术2例,术后切口感染2例,感染性休克死亡1例,治愈31例,病死率为3.12%。结论:开放性腹部外伤,首先要根据临床表现及辅助检查判定内脏是否损伤,手术时机的掌握是治疗的关键。     

Pathological effects on mice by gambierol, possibly one of the ciguatera toxins

Gambierol was isolated from Gambierdiscus toxicus, which causes ciguatera fish poisoning. The acute toxicological effects induced in mice by synthesized gambierol were studied. The lethal doses were about 80 μg/kg by i.p. and i.v., and 150 μg/kg by p.o. The main injury by this toxin was observed in the lung, and secondary in the heart, resulting in systemic congestion. Another toxic effect was seen in the stomach, inducing hypersecretion and ulceration. With survival from the severe stage during the initial 3 h, recovery was favorable, especially after 4 days. Additional effects were not evident during 1-week post-administration observation.     

高原环境对部队适应人群内分泌系统的急性效应

本文对初入海拔5170米高原5日内未发生急性高山病的46名新战士进行了17项内分泌指标的检测,发现高原环境对适应人群内分泌系统的急性效应主要有:下丘脑一垂体应激反应增强;甲状腺功能增强;皮质醇分泌增多,醛固酮分泌减少,肾素活性降低,血管紧张素Ⅱ增多;性腺功能无明显变化。     

Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323–339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance

BACKGROUND: Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance. OBJECTIVE: To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323-339 (OVAp). METHODS: BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis. RESULTS: Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4(+) T cells in BLN of OVA-treated mice only. CONCLUSION: INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4(+) T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.     

神经导航在颅内肿瘤手术中的应用

目的探讨神经导航在神经外科显微手术中的应用。方法对101例颅内肿瘤患者均采用神经导航辅助的显微神经外科治疗。结果101例病变显微镜下全切89例(88．1%),次全切9例(8．9%),大部分切除3例(3．0%)；注册误差1．2～3．2mm,平均为(2．3±0．48)mm。术后症状改变或无变化92例(91．1%),9例(8．9%)出现不同程度的功能障碍,未出现术中及术后死亡。结论神经导航提供了实时、准确、可靠的定位,有助于提高手术疗效,降低术后神经功能损伤,缩短手术时间,使手术更微侵袭化。