Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous infusion

Based on the tail-flick response to noxious thermal stimuli, we determined in the present study that effective antinociception could be achieved in adult male Sprague-Dawley rats 15 min after intravenous infusion of propofol at 60 mg/kg/h. Simultaneous power spectral analysis of the electroencephalographic (EEG) and systemic arterial pressure signals further revealed a concomitant depression of the activity of all EEG frequency bands (δ, θ, , β), alongside hypotension, negative inotropic and chronotropic actions, and attenuated baroreceptor reflex and vasomotor activity. These effects were congruent with a plasma concentration of propofol in the arterial blood of 1.70 ± 0.13 μg/ml, as determined by high-performance liquid chromatography.     

实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。     

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.     

Profile of autoantibody to basement membrane zone proteins in patients with mucous membrane pemphigoid: long-term follow up and influence of therapy

Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy.     

Intermediate-term toxicity of repeated orally administered doses of the anti-malarial β-artemether in dogs

The artemisinin derivative beta-artemether, an anti-malarial, was evaluated for its toxicity and tolerability in a 2-week, multiple-dose study in dogs. Eight beagle dogs (4 females, 4 males) were given beta-artemether by oral gavage 3 times daily at 45 mg/kg/dosing (a total daily dose-level of 135 mg/kg) for 2 weeks. This beta-artemether dose regime was well tolerated. Body weight changes were normal although feed consumption during the treatment period reduced compared to that of the pre-trial period. Clinical signs were transient spells of soft to liquid feces. On completion of the treatment period, the animals were sacrificed and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and a complete light microscopic examination was performed on 43 selected tissues from 1 animal per sex, and on the liver, kidneys, thymus, mandibular lymph nodes and lungs of the three other animals per sex. Major findings were high liver weight and histopathologic findings of slight diffuse hepatocellular hypertrophy and distal tubular dilatation, together with flattened epithelium, in the kidneys. With the dose regime used in this trial beta-artemether produced no clinical or apparent histopathological signs of neurotoxicity in dogs.     

Effect of rectal administration of rebamipide on dextran sulfate sodium-induced colitis: Role of hepatocyte growth factor

Objective and design: Since rebamipide is effective for the treatment of ulcerative colitis (UC), we examined the involvement of hepatocyte growth factor (HGF) in the action of rebamipide. Materials: Fifty-five and forty female Balb/c mice, respectively, were used in Exp. 1 and 2. Treatment: 50 mg/kg/day rebamipide (Exp. 1) and 1 × 10⁷ pfu pAxCAHGF (the CAG promoter-driving HGF gene in adenovirus vector) (Exp. 2) were intrarectally introduced after induction of colitis by 4 % dextran sulfate sodium (DSS). Methods: Therapeutic effects were assessed by cell proliferation and apoptosis. Results: Rebamipide caused proliferation of epithelial cells at 10 days after treatment, and decreased apoptosis at 10, 14 and 21 days, compared with controls. Expression of HGF was greatly increased in rebamipide-treated mice. pAxCAHGF caused cell proliferation and apoptosis, which showed the same pattern as with rebamipide treatment. Conclusions: Rectal administration of rebamipide is effective for DSS-induced colitis in association with induction of HGF. Received 17 June 2006; returned for revision 23 August 2006; returned for final revision 29 October 2006; accepted by I. Ahnfelt-R?nne 14 December 2006     

Insulin Minimal Model Indexes and Secretion: Proper Handling of Uncertainty by a Bayesian Approach

The identification of the insulin minimal model (MM) for the estimation of insulin secretion rate (ISR) and physiological indexes (e.g. beta-cell sensitivity) requires the knowledge of C-peptide (CP) kinetics. The four parameters of the two-compartment model of CP kinetics in a given individual can be derived either from an additional bolus experiment or, more frequently, from a population model. However, in both situations, the CP kinetics is uncertain and, in MM identification, it should be treated as such. This paper shows how to handle CP kinetics uncertainty by using a Bayesian methodology. In seven subjects, MM indexes and ISR were estimated together with their confidence intervals, using either the bolus data or the population model to assess CP kinetics. The two main results that arise from the application of the new methodology are: (i) the use of the population model in place of the bolus data to determine CP kinetics does not affect, on average, the point estimates of ISR profile and MM parameters but only the confidence intervals which becomes wider (less than 50%); (ii) in both the bolus and population situation neglecting the uncertainty of CP kinetics, as done in MM literature so far, introduces no bias, on average, on point estimates of MM indexes but only an underestimation of confidence intervals.     

mPEG表面修饰的PLGA嵌段共聚物的血液相容性评价

本实验室设计合成了三种不同LA／GA比例的mPEG修饰PLGA（PELGA，含15％mPEG），为了评价它们的血液相容性，我们以硅化玻璃试管为阴性对照，未硅化的试管为阳性对照，参照国际标准（ISO10993）和《中华人民共和国国家标准GB／T16886医疗器械生物学评价》方法进行了体外评价实验。试验包括溶血率实验，血小板黏附实验，动态凝血时间实验，凝血时间实验，血浆复钙时间实验和凝血酶原时间实验等综合评价指标。结果表明，合成材料具有优良的血液相容性，材料制成的纳米粒有望应用于静脉注射。     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Desensitization protocols improving access and outcome in transplantation

Sensitization to antigens of the HLA and ABO system has been the biggest barrier to access in renal transplantation and, increasingly, in transplantation of other organs. Additionally, antibody to donor antigens has been shown to result in injury to the graft ranging from catastrophic, irreversible hyperacute rejection to the slower, more insidious, chronic form of rejection. The problem of access has been recognized globally and has been the incentive for measures to overcome the disadvantage experienced by the sensitized patient. However, early attempts to reduce sensitization achieved only transient success. Newer immunosuppressive agents that affect B-cell function or viability have permitted the development of treatment protocols to eliminate and, potentially, downregulate donor-specific antibodies. The use of these protocols has achieved successful transplants that were HLA and/or ABO incompatible prior to treatment and, as such, has provided some patients with their only opportunity for transplantation.