Different astroglial reaction between the vagal dorsal motor nucleus and nucleus ambiguus following vagal-hypoglossal nerve anastomosis in cats

The dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA) were both traced with horseradish peroxidase (HRP) retrograde labelling technique after vagal-hypoglossal nerve anastomosis (VHA). By light microscopy, reinnervation of the new target, viz. tongue skeletal musculature, by DMV and NA was established at 22 days postoperation (dpo) as shown by the neuronal labelling with HRP. Ultrastructurally, signs of retrograde degeneration occurred in some DMV and NA neurons between 3 and 25 days after VHA. The incidence of darkened dendrites, an early sign of dendritic loss, was more common in the DMV compared to the NA. Accompanying the neuronal alteration were drastic astrocytic reactions in the DMV, but not in the NA. Between 3 and 7 dpo, the astrocytes in the DMV showed extensively hypertrophied processes and by 22 dpo, the somata and dendrites of HRP-labelled DMV neurons, but not NA's, appeared to be delineated by the increased lamellar astrocytic processes. Such a feature was sustained throughout the remaining postoperative intervals up to 500 dpo. It is concluded that the DMV motoneurons being autonomic in nature are probably not conducive to the newly acquired target organ. Hence, the insulation of the regenerating DMV motoneurons by the astroglial ensheathment would be vital in the neuronal remodelling and reconstruction of the vagal-hypoglossal pathway.     

Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia

In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.     

皮脂腺细胞体外培养及生长调节的研究进展

皮脂腺是皮肤重要的附属器。皮脂腺体外培养模型的建立为研究相关因子如细胞因子、生长激素及药物等对皮脂腺形态功能、生长发育及病理改变的作用提供了良好的平台。本文对皮脂腺细胞体外培养的实验方法、体外生长特性及影响皮脂腺细胞增殖分化的相关因素作简要综述。     

完全型雄激素不敏感综合征的临床特征与变异

目的　总结中国完全型雄激素不敏感综合征 (CAIS)患者的基本特征和不同变异。方法　回顾性研究了 1976年 3月至 2 0 0 2年 2月北京协和医院收治的 2 8例CAIS患者的临床表现、激素测定和性腺病理结果 ,并与中国正常人群和国外文献报道的CAIS患者进行比较分析。结果　CAIS患者为女性表型 ,成年身高 (16 6 6 7±3 81)cm ,阴毛、腋毛稀少或缺如 ,有乳房发育 ,女性外阴 ,阴道呈盲端 ,深度为 (5 76± 1 6 4 )cm ,无宫颈 ;2 6 1%合并存在睾酮水平下降 ;19 2 %出现睾丸肿瘤 ,11 5 %有较大的睾丸鞘膜积液 ,19 2 %存在有发育不良的子宫。结论　CAIS临床表现较为特异 ,但仍存在异质性 ,包括存在发育不良的子宫、合并存在睾酮水平下降 ;中国CAIS患者肿瘤的发生率高于国外的报道。     

颈前路带锁钢板内固定治疗下颈椎骨折脊髓损伤病人的护理

目的探讨颈前路带锁钢板内固定治疗下颈椎骨折脊髓损伤病人的护理。方法随机选取1999年7月￣2003年7月22例下颈椎骨折脊髓损伤拟行前路带锁钢板内固定手术的病人,进行回顾性分析。结果21例获随访6￣24个月,按Frank分析法评价。4例完全恢复正常(占18.18%),上升1级9例(占40.90%),上升2级6例(占27.27%),无改善2例(占9.09%),死亡1例(占4.55%)。结论加强颈椎骨折脊随损伤病人围手术期护理,可有效预防术后并发症的发生,提高手术成功率。     

微波治疗耳廓假性囊肿的疗效观察

目的 探讨微波治疗耳廓假性囊肿的疗效.方法 对82例耳廓假性囊肿采用微波治疗,观察其疗效.结果 82例总有效率100%,其中痊愈78例,显效4例,随访3～6个月无复发.结论 微波治疗简单易行,术中不易出血,术后反应轻,费用低廉,治疗效果确切,易被患者接受,值得推广使用.     

Target-dependent axonal sprouting following vagal-hypoglossal nerve anastomosis in cats

Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3-315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 +/- 1 myelinated and 74 +/- 4 unmyelinated axons in 727 &mgr;m(2) sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 &mgr;m(2)) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts.     

贺普丁、卡提素、复方益肝灵联合治疗慢性乙肝36例观察

目的 探讨贺普丁、卡提素、复方益肝灵联合应用治疗慢性乙肝的疗效。方法 对确诊为慢性乙肝的患者随机分 为治疗组和对照组,治疗组采用贺普丁、卡提素、复方益肝灵联合用药。贺普丁50mg,口服,每日1次;卡提素0．5mg,穴位注 射,每半月1次;复方益肝灵2片,每日3次,口服。疗程半年。而对照组采用聚肌胞4mg,穴位注射,每周1次;乙肝疫苗 30μg,肌肉注射,每半月1次;护肝片2片,每日3次,口服。疗程半年。结果 治疗组各项指标明显优于对照组。结论 贺普 丁、卡提素及复方益肝灵合用治疗慢性乙肝疗效确切。     

Insights into oxazaphosphorine resistance and possible approaches to its circumvention.

The oxazaphosphorines cyclophosphamide, ifosfamide and trofosfamide remain a clinically useful class of anticancer drugs with substantial antitumour activity against a variety of solid tumors and hematological malignancies. A major limitation to their use is tumour resistance, which is due to multiple mechanisms that include increased DNA repair, increased cellular thiol levels, glutathione S-transferase and aldehyde dehydrogenase activities, and altered cell-death response to DNA damage. These mechanisms have been recently re-examined with the aid of sensitive analytical techniques, high-throughput proteomic and genomic approaches, and powerful pharmacogenetic tools. Oxazaphosphorine resistance, together with dose-limiting toxicity (mainly neutropenia and neurotoxicity), significantly hinders chemotherapy in patients, and hence, there is compelling need to find ways to overcome it. Four major approaches are currently being explored in preclinical models, some also in patients: combination with agents that modulate cellular response and disposition of oxazaphosphorines; antisense oligonucleotides directed against specific target genes; introduction of an activating gene (CYP3A4) into tumor tissue; and modification of dosing regimens. Of these approaches, antisense oligonucleotides and gene therapy are perhaps more speculative, requiring detailed safety and efficacy studies in preclinical models and in patients. A fifth approach is the design of novel oxazaphosphorines that have favourable pharmacokinetic and pharmacodynamic properties and are less vulnerable to resistance. Oxazaphosphorines not requiring hepatic CYP-mediated activation (for example, NSC 613060 and mafosfamide) or having additional targets (for example, glufosfamide that also targets glucose transport) have been synthesized and are being evaluated for safety and efficacy. Characterization of the molecular targets associated with oxazaphosphorine resistance may lead to a deeper understanding of the factors critical to the optimal use of these agents in chemotherapy and may allow the development of strategies to overcome resistance.     

Pharmacokinetics of tacrolimus and mycophenolic acid are altered, but recover at different times during hepatic regeneration in rats.

Hepatic regeneration is very critical to the success of living donor liver transplantation, which allows a reduced size liver to grow in size to accommodate the requirements of both the donor and the recipient. The objectives of this study were to evaluate 1) the hepatic metabolism of the two immunosuppressive drugs, tacrolimus and mycophenolic acid (MPA), and 2) the pharmacokinetics of tacrolimus and mycophenolic acid at various time points after initiation of hepatic regeneration by partial hepatectomy in rats. The hepatic intrinsic clearance of tacrolimus was decreased to 70% and 51% of the control level at the 24th h and the 6th day, respectively, but returned to normal level by day 14. The total body clearance of tacrolimus was reduced transiently but recovered completely by day 18. The hepatic intrinsic clearance of MPA was decreased to 52% and 51% of that in control rats at the 24th h and the 6th day, respectively, but recovered to normal level by day 14. The total body clearance of MPA was reduced at the 24th h but recovered by day 6. The magnitude of reduction in the clearance of tacrolimus and MPA was much smaller than what was predicted from in vitro data. The elimination clearance of MPA glucuronide was also impaired during hepatic regeneration but recovered to normal level with time. In conclusion, the pharmacokinetics of tacrolimus and mycophenolic acid were altered during hepatic regeneration but recovered completely at different rates over time. Caution must be exercised in extrapolating in vitro data to in vivo conditions during hepatic regeneration.