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12.
S Khom B Strommer J Ramharter T Schwarz C Schwarzer T Erker GF Ecker J Mulzer S Hering 《British journal of pharmacology》2010,161(1):65-78
BACKGROUND AND PURPOSE
Subunit-specific modulators of γ-aminobutyric acid (GABA) type A (GABAA) 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 β2/3 subunit-specific modulator of GABAA receptors with anxiolytic potential. The aim of the present study was to generate VA derivatives as novel GABAA 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 GABAA 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 (IGABA) through GABAA receptors (EC50) and efficacies (maximal stimulation of IGABA) 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 IGABA 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 α1β2γ2s and α3β3γ2s 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 GABAA receptors for development of anxiolytics. 相似文献13.
Henrik B Mortensen Peter GF Swift Reinhard W Holl P Hougaard Lars Hansen Hilde Bjoerndalen Carine E De Beaufort Michael Knip and Hvidoere Study Group on Childhood Diabetes 《Pediatric diabetes》2010,11(4):218-226
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. 相似文献
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15.
M Perry I Drašković T van Achterberg GF Borm MIJ van Eijken PL Lucassen MJFJ Vernooij-Dassen MGM Olde Rikkert 《BMC health services research》2008,8(1):71
Background
Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses. 相似文献16.
17.
激光治疗瘢痕的特征 总被引:3,自引:0,他引:3
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。 相似文献
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19.
Arizono N; Kasugai T; Yamada M; Okada M; Morimoto M; Tei H; Newlands GF; Miller HR; Kitamura Y 《Blood》1993,81(10):2572-2578
Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c- kit gene and are deficient in both mucosal mast cells (MMC) and connective tissue-type mast cells (CTMC). The role of the c-kit receptor in the development of MMC and CTMC was investigated by infecting Ws/Ws and control +/+ rats with Nippostrongylus brasiliensis (NB), which induces T-cell-dependent mast cell proliferation. Although mast cells did not develop in the skin of Ws/Ws rats, a significant number of mast cells developed in the jejunum after NB infection. These mast cells had the MMC protease phenotype (rat mast cell protease [RMCP] I-/II+) and lacked heparin because they were not stained with berberine sulfate. Globule leukocytes were also detected in the mucosal epithelium of these rats. However, the number of MMC and the serum concentration of RMCP II in NB-infected Ws/Ws rats were only 13% and 7% of those of NB-infected +/+ rats, respectively. A small number of mast cells also developed in the lung, liver, and mesenteric lymph nodes of Ws/Ws rats after NB infection. Although mast cells in these tissues had the MMC phenotype throughout the observation period, the increased mast cells in the lung and liver of +/+ rats acquired a CTMC-like phenotype and were RMCP I+/II+, berberine sulfate+, and formalin resistant. These results indicate that the need for the stimulus through the c-kit receptor appears to be greater in the development of CTMC in the skin as well as for CTMC-like mast cells in the lung and liver than for the development of MMC. 相似文献
20.
射频消融治疗儿童快速性心律失常100例 总被引:3,自引:0,他引:3
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。 相似文献