激光治疗瘢痕的特征

目的:介绍国内近20年来激光治疗瘢痕的临床研究概况,以期进一步了解激光治疗瘢痕的新进展。资料来源:应用计算机检索Pubmed和中国生物医学文献数据库1983/2006的相关文章,限定文章语言种类为英文和中文,检索词为“cicatrices(瘢痕),laser(激光)”。资料选择:对资料进行初审,选择临床试验研究文献查找全文。纳入标准:①有明确诊断标准。②随机对照实验或对照试验。有无随访,是否采用盲法不限制。③治疗组干预措施为激光或激光联合药物;对照组干预措施为曲安奈德、冷冻联合曲安奈德或不采用药物措施。排除标准:①非对照研究。②治疗组或对照组的干预措施不符合纳入标准。③机制研究。④重复研究。资料提炼:共收集到相关文献120篇,按上述标准纳入31篇,其余文献均被排除。资料综合:31篇文章中11篇为随机对照研究,10篇为对照研究,各研究的研究期为1～6个月。各研究所纳入的病例数量为10～50例。其中6个研究对比了激光与传统药物治疗瘢痕的疗效及安全性,2个研究进行了激光治疗瘢痕基础研究机制比较,10个研究观察了激光结合与单纯药物或单纯激光对瘢痕的疗效,4个研究比较了激光联合西药治疗瘢痕的疗效,2个研究观察了激光治疗瘢痕的副作用。7篇介绍国内或国外瘢痕治疗的研究情况。结论:激光治疗瘢痕的疗效可靠,具有副作用少,方法简单,安全性高,易被患者接受等优势。但由于激光治疗瘢痕还存在着一定的局限性,今后还需要在激光的穿透深度方面研究。     

Valerenic acid derivatives as novel subunit-selective GABAA receptor ligands �Cin vitro and in vivo characterization

BACKGROUND AND PURPOSE

Subunit-specific modulators of γ-aminobutyric acid (GABA) type A (GABA_A) receptors can help to assess the physiological function of receptors with different subunit composition and also provide the basis for the development of new drugs. Valerenic acid (VA) was recently identified as a β_2/3 subunit-specific modulator of GABA_A receptors with anxiolytic potential. The aim of the present study was to generate VA derivatives as novel GABA_A receptor modulators and to gain insight into the structure–activity relation of this molecule.

EXPERIMENTAL APPROACH

The carboxyl group of VA was substituted by an uncharged amide or amides with different chain length. Modulation of GABA_A receptors composed of different subunit compositions by the VA derivatives was studied in Xenopus oocytes by means of the two-microelectrode voltage-clamp technique. Half-maximal stimulation of GABA-induced chloride currents (I_GABA) through GABA_A receptors (EC₅₀) and efficacies (maximal stimulation of I_GABA) were estimated. Anxiolytic activity of the VA derivatives was studied in mice, applying the elevated plus maze test.

KEY RESULTS

Valerenic acid amide (VA-A) displayed the highest efficacy (more than twofold greater I_GABA enhancement than VA) and highest potency (EC₅₀= 13.7 ± 2.3 µM) on α₁β₃ receptors. Higher efficacy and potency of VA-A were also observed on α₁β₂γ_2s and α₃β₃γ_2s receptors. Anxiolytic effects were most pronounced for VA-A.

CONCLUSIONS AND IMPLICATIONS

Valerenic acid derivatives with higher efficacy and affinity can be generated. Greater in vitro action of the amide derivative correlated with a more pronounced anxiolytic effect in vivo. The data give further confidence in targeting β₃ subunit containing GABA_A receptors for development of anxiolytics.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

Production of genetically stable high-titer retroviral vectors that carry a human gamma-globin gene under the control of the alpha-globin locus control region

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythroid cells. The regulatory element known as the beta-globin locus control region (BetaLCR) can provide a linked Beta-globin gene with these properties. However, addition of BetaLCR sequences to a retrovirus carrying a beta-globin gene increases its genetic instability. We have developed a new generation of retroviral vectors in which a human gamma- globin gene is placed under the control of the alphaLCR, the major regulatory element of the alpha-globin gene cluster. We demonstrate that these retroviruses are genetically stable in producer cell lines and can be produced at high titers that exceed 5 x 10(6) colony-forming units (CFU)/mL. In addition, we show that the transduced gamma-globin gene can be expressed in the adult erythroid environment of mouse erythroleukemia (MEL) cells at a level comparable to that of a single endogenous Betamaj-globin gene. These retroviruses can also transduce primary murine bone marrow progenitor cells as efficiently as retroviruses that carry the neomycin resistance (neor) gene. This new generation of globin retroviral vectors may prove useful for gene therapy of human beta-globin gene disorders such as sickle cell disease and beta-thalassemia.     

射频消融治疗儿童快速性心律失常100例

探讨射频导管消融（ＲＦＣＡ）在治疗儿童快速性心律失常中的临床价值，采用ＲＦＣＡ治疗儿童室上性心动过速（ＳＶＴ）９３例、特发性室性心动过速（ＩＶＴ）７例。结果：ＳＶＴ消融成功率为９１．４％，右侧旁道消融成功率低于左侧旁道及房室结慢径路消融的成功率（８１．８％ｖｓ９６．８％及９６．６％；Ｐ均＜０．０５）。随访３７．３±２０．７个月，８例复发，其中２例发作次数较术前减少，口服普罗帕酮可预防发作，另６例再次消融成功。ＩＶＴ首次消融均成功，随访１９．５±１０．３个月，２例复发，均再次消融成功。全组无并发症发生。结果提示ＲＦＣＡ治疗儿童快速性心律失常是有效的、安全的。     

Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age,ketoacidosis, HLA status,and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis

HB Mortensen, PGF Swift, RW Holl, P Hougaard, L Hansen, H Bjoerndalen, CE de Beaufort, M Knip. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis. Objective: To identify predictors of residual beta‐cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D). Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal‐stimulated C‐peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally. Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta‐cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C‐peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C‐peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C‐peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non‐white Caucasian ethnicity (p = 0.002). Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta‐cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.     

鼠尾静脉流体力学转染技术对绿色荧光蛋白表达质粒器官靶向分布的影响

目的:观察流体力学尾静脉注射对绿色荧光蛋白基因器官靶向性的影响,为今后质粒载体的基因治疗和功能研究寻找潜在的靶器官。方法:实验于2005-12/2006-04在江西省分子医学重点实验室完成。选用健康雄性昆明鼠40只,将32只小鼠按随机数字表法分为流体力学注射和常规注射两大组,每大组再分为转染组和对照组两个小组(n=8),并设正常对照组(n=8)。①流体力学转染组将100μg/只绿色荧光蛋白表达质粒溶液2mL在5s内快速注入尾静脉;对照组仅在5s内注入林格氏液2mL。②常规注射组则将2mL林格氏液或绿色荧光蛋白表达质粒溶液在30s左右注入尾静脉。注射结束后24h采集各组小鼠血清检测转氨酶,并采集肝、脾、心、肾、肺和脑组织进行冰冻切片,部分肝组织采用多聚甲醛固定后切片,荧光显微镜下观察。结果:40只小鼠全部进入结果分析,无脱失。①流体力学注射组和常规注射组小鼠血清转氨酶与正常对照组比较差异均无显著性意义(P>0.05)。②常规尾静脉注射引起少数肾小球细胞表达绿色荧光蛋白,而肝、脾、心、肺及脑等组织未见明显绿色荧光蛋白表达。③流体力学注射引起肝内绿色荧光蛋白高水平表达,肝细胞表达率接近45%,其他组织则无绿色荧光蛋白表达。结论:流体力学方法是肝靶向性的活体基因转染方法,绿色荧光蛋白可作为该方法进行目的基因研究的一个可靠和方便的示踪剂。     

Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.