• 【注意缺陷多动障碍可能与中枢脑源性神经营养因子活性降低有关: 临床和治疗意义。】 复制标题 收藏 收藏
    DOI:10.1016/j.mehy.2006.06.025 复制DOI
    作者列表:Tsai SJ
    BACKGROUND & AIMS: :Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Despite intensive research efforts, the aetiology of ADHD remains unknown. Current evidence suggests that the aetiology of ADHD is heterogeneous, comprising of multiple factors. Recently, it has been proposed that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be implicated in the pathogenesis of ADHD. This hypothesis is supported by recent genetic studies in ADHD. Drawing on findings from studies into the drugs for ADHD relating to central BDNF expression, hyperactivity in BDNF knockout mice, BDNF effects in midbrain dopaminergic function and the close association between BDNF and the dopamine transporter (an important molecule for ADHD pathogenesis), it is proposed here that decreased central BDNF, particularly in the midbrain region, may play an important role in the pathogenesis ADHD. This hypothesis may have some implications for clinical findings in ADHD (for example, the co-morbidity between ADHD and major depression), and provide a new direction for the development of medication for ADHD treatment.
    背景与目标: : 注意力缺陷多动障碍 (ADHD) 是一种常见的儿童精神疾病。尽管进行了大量研究,但ADHD的病因仍然未知。目前的证据表明,ADHD的病因是异质的,由多种因素组成。最近,有人提出,神经营养因子家族的成员脑源性神经营养因子 (BDNF) 可能与ADHD的发病机理有关。该假设得到了ADHD最近的遗传研究的支持。根据对ADHD药物的研究结果,该药物与中枢BDNF表达,BDNF基因敲除小鼠的活动过度,BDNF在中脑多巴胺能功能中的作用以及BDNF与多巴胺转运蛋白 (ADHD发病机理的重要分子) 之间的密切联系有关,在这里提出降低中枢BDNF,特别是在中脑区域,可能在ADHD的发病机理中起重要作用。该假设可能对ADHD的临床发现 (例如,ADHD与重度抑郁症之间的合并症) 具有一定的意义,并为ADHD治疗药物的发展提供了新的方向。
  • 【RcdA的结构草图,RcdA是控制生物膜形成的主要调节剂的转录因子。】 复制标题 收藏 收藏
    DOI:10.1002/1873-3468.12713 复制DOI
    作者列表:Sugino H,Usui T,Shimada T,Nakano M,Ogasawara H,Ishihama A,Hirata A
    BACKGROUND & AIMS: :RcdA is a regulator of curlin subunit gene D, the master regulator of biofilm formation in Escherichia coli. Here, we determined the X-ray structure of RcdA at 2.55 Å resolution. RcdA consists of an N-terminal DNA-binding domain (DBD) containing a helix-turn-helix (HTH) motif and a C-terminal dimerization domain, and forms a homodimer in crystals. A computational docking model of the RcdA-DNA complex allowed prediction of the candidate residues responsible for DNA binding. Our structure-guided mutagenesis, in combination with gel shift assay, atomic force microscopic observation, and reporter assay, indicate that R32 in α2 of the HTH motif plays an essential role in the recognition and binding of target DNA while T46 in α3 influences the mode of oligomerization. These results provide insights into the DNA-binding mode of RcdA.
    背景与目标: : RcdA是curlin亚基基因D的调节剂,curlin亚基基因D是大肠杆菌中生物膜形成的主要调节剂。在这里,我们以2.55的分辨率确定了RcdA的x射线结构。RcdA由N端DNA结合结构域 (DBD) 组成,该结构域包含螺旋-螺旋 (HTH) 基序和C端二聚化结构域,并在晶体中形成同二聚体。Rcda-dna复合物的计算对接模型允许预测负责DNA结合的候选残基。我们的结构引导的诱变与凝胶位移分析,原子力显微镜观察和报告分子分析相结合,表明HTH基序 α2中的R32在靶DNA的识别和结合中起着至关重要的作用,而 α3中的T46影响了低聚方式。这些结果为RcdA的DNA结合模式提供了见解。
  • 【加纳人群中普通和中心性肥胖与2型糖尿病风险的测量。】 复制标题 收藏 收藏
    DOI:10.1111/tmi.12024 复制DOI
    作者列表:Frank LK,Heraclides A,Danquah I,Bedu-Addo G,Mockenhaupt FP,Schulze MB
    BACKGROUND & AIMS: OBJECTIVE:The epidemic of obesity and type 2 diabetes is evident in sub-Saharan Africa (SSA). However, their associations have hardly been examined in this region. METHODS:A hospital-based case-control study in urban Ghana consisting of 1221 adults (542 cases and 679 controls) investigated the role of anthropometric parameters for diabetes. Logistic regression was used for analysis. The discriminative power and population-specific cut-off points for diabetes were identified by receiver operating characteristic curves. RESULTS:The strongest association with diabetes was observed for waist-to-hip ratio: age-adjusted odds ratios per 1 standard deviation difference were 1.95 (95% confidence interval [CI]: 1.64-2.31) in women and 1.40 [1.01-1.94] in men. Also, among women, the odds of diabetes increased with higher waist circumference (1.35 [1.17-1.57]) and waist-to-height ratio (1.29 [1.12-1.50]). Among men, this was not discernible. Rather, hip circumference was inversely related (0.69 [0.50-0.95]). Body mass index was neither associated with diabetes in women (1.01 [0.88-1.15]) nor in men (0.74 [0.52-1.04]). Among both genders, waist-to-hip ratio showed the best discriminative ability for diabetes in this population and the optimal cut-off points were ≥ 0.88 in women and ≥ 0.90 in men. Recommended cut-off points for body mass index and waist circumference had a poor predictive ability. CONCLUSION:Our findings suggest that measures of central rather than general obesity relate to type 2 diabetes in SSA. It remains to be verified from larger population-based epidemiological studies whether anthropometric targets of obesity prevention in SSA differ from those in developed countries.
    背景与目标:
  • 【模拟印度中部喉癌的播散组织胞浆菌病-一例报告。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Phatak AM,Bhattacharya I,Misra V,Prabhu AM,Natraj U
    BACKGROUND & AIMS: :A 58 year old male, chronic smoker, with diabetes mellitus (Type II), residing in Madhya Pradesh presented with dysphagia, hoarseness, odynophagia and significant weight loss. Microlaryngoscopy showed reddish ulcerated area involving valleculae, and pharyngo-epiglottic fold. Histopathological examination showed foamy macrophages containing Histoplasma capsulatum. Patient initially responded to Azoles, relapsed three months after stopping the treatment and presented with oral lesions. Biopsy showed H. capsulatum, histologically as well as on culture. The mycelial phase converted to yeast phase on B.H.I.A. at 37 degrees C confirming the isolate as H. capsulatum. The patient responded well to amphotericin B.
    背景与目标: : 一名58岁的男性,慢性吸烟者,患有糖尿病 (II型),居住在中央邦的吞咽困难,声音嘶哑,吞咽困难和体重减轻明显。显微喉镜检查显示带红色的溃疡区域累及山谷和咽-会厌褶皱。组织病理学检查显示泡沫巨噬细胞含有荚膜组织胞浆。患者最初对唑类药物有反应,停止治疗后三个月复发,并出现口腔病变。活检显示H.荚膜,组织学和培养。在37 ℃ 的B.H.I.A. 菌丝体相转化为酵母相,证实分离物为荚膜H.患者对两性霉素b反应良好。
  • 【p21 (CDKN1A) 是p53稳定性的负调节剂。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Broude EV,Demidenko ZN,Vivo C,Swift ME,Davis BM,Blagosklonny MV,Roninson IB
    BACKGROUND & AIMS: :Cell cycle arrest in response to DNA damage involves protein stabilization and consequent upregulation of p53, which induces transcription of cyclin-dependent kinase inhibitor p21 (CDKN1A). We now show that p21 acts as a negative regulator of the cellular levels of p53. p21 knockdown by short hairpin RNA strongly increased p53 upregulation by a DNA-damaging drug doxorubicin in HT1080 fibrosarcoma cells. A protease inhibitor N-Ac-Leu-Leu-norleucinal (ALLN) drastically increased the amount of p53 in HCT116 colon carcinoma cells, but it had no effect on the already high p53 level in a p21(-/-) derivative of this cell line. Inhibition of transcription, which increases p53 levels in different cell lines due to the degradation of p53-destabilizing proteins such as Mdm2, failed to increase but instead decreased the amount of p53 in p21(-/-) cells, despite a drastic decrease in the level of Mdm2. These results indicate that p21 acts as a negative regulator of p53 stability in different cell types. p53 regulation by p21 may provide a negative regulatory loop that limits p53 induction.
    背景与目标: : 响应DNA损伤的细胞周期停滞涉及蛋白质稳定和随后的p53上调,p53诱导细胞周期蛋白依赖性激酶抑制剂p21 (CDKN1A) 的转录。现在,我们显示p21充当p53细胞水平的负调节剂。短发夹RNA的p21敲除强烈增加了HT1080纤维肉瘤细胞中DNA损伤药物阿霉素的p53上调。蛋白酶抑制剂N-Ac-Leu-norleucinal (ALLN) 大大增加了HCT116结肠癌细胞中p53的含量,但对p21(-/-) 衍生物中已经很高的p53水平没有影响该细胞系。由于p53-destabilizing蛋白 (例如Mdm2) 的降解而增加了不同细胞系中p53水平的转录抑制,尽管其水平急剧下降,但未能增加,而是减少了p21(-/-) 细胞中p53的量。Mdm2。这些结果表明,p21在不同细胞类型中充当p53稳定性的负调节剂。p21对p53的调节可能会提供限制p53诱导的负调节环。
  • 【关于中美洲和南美洲本土文化中头痛和偏头痛的人类学研究。】 复制标题 收藏 收藏
    DOI:10.1111/j.1526-4610.2007.00778.x 复制DOI
    作者列表:Carod-Artal FJ,Vázquez-Cabrera C
    BACKGROUND & AIMS: OBJECTIVE:To describe the ritual and ethnobotanical treatments about migraine performed by shamans from several native cultures. METHODS:Anthropological field study conducted with Tzeltal Maya (Mexico), Kamayurá (Brazil), and Uru-Chipaya (Bolivia) American Indians. RESULTS:Migraine is called yaxti-wanjol chawaj by Tzeltal shamans. They wash the head of the patient with an herbal solution to treat headache. The boiled leaves of a shrub called payté wamal (Tagetes nelsonii) are used to relieve migraine. Migraine is called monkey's disease by Kamayurá natives. The disease is originated by the revenge of the killed monkey's spirit, striking to Kamayurá hunter on his head. It is treated with an herbal infusion applied in the eyes of the patient. Migraine is called eskeclamix by Chipaya people, and is treated by drinking the cañahua plant (Chenopodium palludicale) boiled with water. The patient's head may also be washed with shaman's fermented urine. CONCLUSIONS:Cultural equivalents of migraine exist in the healing system of isolated American cultures.
    背景与目标:
  • 【中美洲和西班牙人MDR1基因的多态性C3435T。】 复制标题 收藏 收藏
    DOI:10.1007/s11033-007-9109-z 复制DOI
    作者列表:Vicente J,Sinues B,Fanlo A,Vasquez P,Medina JC,Martinez-Jarreta B
    BACKGROUND & AIMS: :The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.
    背景与目标: : 人类多药耐药基因 (MDR1) 编码P-糖蛋白 (P-gp),P-糖蛋白是一种跨膜转运蛋白,可作为许多嗜酸性化合物的外排泵。它对细胞免受DNA损伤起保护作用。外显子26的摆动C3435T多态性与不同的表达水平和活性有关。已在不同种族之间证明了C3435T多态性的等位基因频率差异。在我们的研究中,我们在433健康个体中检查了这些多态性。从这些229中,将尼加拉瓜 (n = 117) 和萨尔瓦多 (n = 112) 的中美洲混血儿与一组204的北西班牙人进行比较,目的是检测这些人群之间的潜在基因型差异。通过pcr-rflp确定基因型。C等位基因的频率在中美洲 (0.53) 和西班牙人 (0.52) 之间非常相似,这与中美洲个体 (美洲印第安人和欧洲高加索人) 的种族起源一致。与其他先前研究的人群相比,中美洲人的C等位基因频率明显低于非洲人群,高于印度和西南亚人群。这些数据可能与P-gp底物药物的剂量推荐有关,也与中美洲人群的等位基因疾病关联研究有关。
  • 【舌下传入神经的周围和中央末端支配着Fringillidae的舌触觉机械感受器复合体。】 复制标题 收藏 收藏
    DOI:10.1002/cne.902980203 复制DOI
    作者列表:Wild JM
    BACKGROUND & AIMS: :Injections of cholera toxin B subunit conjugated to horseradish peroxidase (CTB-HRP) were made into the lingual branch of the hypoglossal nerve in four species of finch in order to identify the innervation of the mechanoreceptors of the dermal papillae of the tongue, and simultaneously to determine the pattern of central projections of lingual hypoglossal afferents. The results showed that hypoglossal fibers innervate all the Herbst corpuscles and terminal cell receptors of the elaborately organized papillae of the dorsum of the tongue, of the shorter papillae in the ventral tongue, and the loose collection of Herbst corpuscles in the subpapillary region. Labelled fibers were also observed in the intralingual glands, in the intrinsic tongue muscles, and in the posterodorsal epithelium where they formed budlike structures. Retrogradely labelled cell bodies were located in the jugular ganglion and their central processes ascended and descended throughout the brainstem within the descending trigeminal tract (TTD). Terminal fields were observed within the dorsolateral part of the nucleus caudalis of TTD, predominantly ipsilaterally, and within the medial part of the dorsal horn of the first 4-6 cervical segments bilaterally. There were dense patches of termination over a dorsolateral subnucleus of the interpolated nucleus of TTD, and within two regions of the principal sensory trigeminal nucleus: a large one laterally and a small one medially. Terminal fields were also observed within the nucleus ventralis lateralis anterior of the rostral solitary complex, and within adjacent nuclei, which are probably equivalent to the dorsal sensory nuclei of the facial and glossopharyngeal nerves of other avian species. The results are interpreted in the light of the role of the tongue in species-specific patterns of feeding in finches, and the possible requirement for the central integration of touch and taste.
    背景与目标: : 将与辣根过氧化物酶 (ctb-hrp) 缀合的霍乱毒素B亚基注射到四种雀科的舌下神经的舌下分支中,以鉴定舌头真皮乳头的机械感受器的神经支配,同时确定舌下舌骨传入的中央投影模式。结果表明,舌下纤维支配了舌背精心组织的乳头,腹侧舌较短的乳头以及乳头下区域松散的Herbst小体的所有Herbst小体和末端细胞受体。在舌内腺,内在舌肌和后背上皮中也观察到标记的纤维,它们形成了芽状结构。逆行标记的细胞体位于颈静脉神经节中,其中央过程在三叉神经降束 (TTD) 内的整个脑干中上升和下降。在TTD尾核的背外侧部分 (主要是同侧) 和双侧前4-6个子宫颈节段的背角内侧部分内观察到末端区域。在TTD内插核的背外侧亚核上以及在主要感觉三叉核的两个区域内有密集的终止斑块: 横向较大,中间较小。在喙状孤立复合体的前腹外侧核以及相邻核内也观察到了末端磁场,这可能相当于其他鸟类的面部和舌咽神经的背感觉核。根据舌头在雀科取食的物种特定模式中的作用以及触觉和味觉集中融合的可能要求来解释结果。
  • 【静脉溶栓治疗视网膜中央动脉阻塞安全有效吗?一个经过严格评估的主题。】 复制标题 收藏 收藏
    DOI:10.1097/NRL.0000000000000129 复制DOI
    作者列表:Dumitrascu OM,Shen JF,Kurli M,Aguilar MI,Marks LA,Demaerschalk BM,Wingerchuk DM,O'Carroll CB
    BACKGROUND & AIMS: BACKGROUND:Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain. OBJECTIVE:To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO. METHODS:The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology. RESULTS:A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis. CONCLUSIONS:IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.
    背景与目标:
  • 【感染棘阿米巴后AIDS患者的存活率。中枢神经系统。】 复制标题 收藏 收藏
    DOI:10.1007/s15010-017-1037-9 复制DOI
    作者列表:El Sahly H,Udayamurthy M,Parkerson G,Hasbun R
    BACKGROUND & AIMS: CASE DESCRIPTION:A 38-year-old man presented with headaches and generalized weakness. He was found to have AIDS; a ring-enhancing central nervous system lesion was found on brain imaging and he had elevated serum Toxoplasma gondii IgG levels. A diagnosis of presumptive toxoplasma encephalitis was made and he received antiretrovirals and antitoxoplasma therapy for 4 years. Intermittent headaches and evidence of disease progression on neuroimaging warranted further evaluation and cerebrospinal fluid analysis revealed amebic forms on hematoxylin and eosin staining and positive polymerase chain reaction testing for Acanthamoeba spp. He was placed on miltefosine, fluconazole, trimethoprim-sulfamethoxazole and flucytosine for 7 months. Five months after therapy discontinuation he remains asymptomatic and is taking only antiretroviral therapy. CONCLUSION:This is the first report of a patient with AIDS and granulomatous amebic encephalitis who survived with medical therapy only.
    背景与目标:
  • 【中枢或外周瘦素给药对确定的脂肪库中去甲肾上腺素周转的影响。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00368.2006 复制DOI
    作者列表:Penn DM,Jordan LC,Kelso EW,Davenport JE,Harris RB
    BACKGROUND & AIMS: :Leptin preserves lean tissue but decreases adipose tissue by increasing lipolysis and/or inhibiting lipogenesis. The sympathetic nervous system (SNS) is a primary regulator of lipolysis, but it is not known if leptin increases norepinephrine turnover (NETO) in white adipose tissue. In this study, we examined the effect of leptin administered either as a chronic physiological dose (40 microg/day for 4 days from ip miniosmotic pumps) or as an acute injection in the third ventricle (1.5 microg injected two times daily for 2 days) on NETO and the size of brown and white fat depots in male Sprague Dawley rats. NETO was determined from the decline in tissue norepinephrine (NE) during 4 h following administration of the NE synthesis inhibitor alpha-methyl-para-tryrosine. The centrally injected leptin-treated animals demonstrated more dramatic reductions in food intake, body weight, and fat pad size and an increase in NETO compared with the peripherally infused animals. Neither route of leptin administration caused a uniform increase in NETO across all fat pads tested, and in both treatment conditions leptin decreased the size of certain fat pads independent of an increase in NETO. Similar discrepancies in white fat NETO were found for rats pair fed to leptin-treated animals. These results demonstrate that leptin acting either centrally or peripherally selectively increases sympathetic outflow to white fat depots and that a leptin-induced change in fat pad weight does not require an increase in NETO.
    背景与目标: : 瘦素保留瘦组织,但通过增加脂肪分解和/或抑制脂肪生成来减少脂肪组织。交感神经系统 (SNS) 是脂肪分解的主要调节剂,但尚不清楚瘦素是否会增加白色脂肪组织中的去甲肾上腺素更新 (neo)。在这项研究中,我们检查了瘦素作为慢性生理剂量 (40微克/天,从ip小渗透泵中持续4天) 或在第三脑室中急性注射 (1.5微克,每天两次,持续2天) 对neto和雄性Sprague棕色和白色脂肪库的大小道利老鼠。Neo是根据给予NE合成抑制剂 α-甲基-对三酪氨酸后4小时内组织去甲肾上腺素 (NE) 的下降确定的。与外周注射的动物相比,经中央注射的瘦素处理的动物的食物摄入量,体重和脂肪垫大小的减少幅度更大,neto增加。瘦素给药的任何一种途径都不会在所有测试的脂肪垫中引起neo的均匀增加,并且在两种治疗条件下,瘦素均减小了某些脂肪垫的大小,而与neo的增加无关。对于用瘦素处理的动物喂养的大鼠对,发现白色脂肪内托也有类似的差异。这些结果表明,瘦素在中枢或外周上选择性地增加了对白色脂肪库的交感神经流出,并且瘦素诱导的脂肪垫重量变化不需要增加neo。
  • 【用抗感染剂治疗的中心静脉导管在预防血流感染方面的临床有效性和成本效益: 系统评价和经济评价。】 复制标题 收藏 收藏
    DOI:10.3310/hta12120 复制DOI
    作者列表:Hockenhull JC,Dwan K,Boland A,Smith G,Bagust A,Dündar Y,Gamble C,McLeod C,Walley T,Dickson R
    BACKGROUND & AIMS: OBJECTIVES:To assess the clinical effectiveness and cost-effectiveness of central venous catheters (CVCs) treated with anti-infective agents in preventing catheter-related bloodstream infection (CRBSI). DATA SOURCES:Major electronic databases were searched from 1985 to August 2005. REVIEW METHODS:The systematic clinical and economic reviews were conducted according to accepted procedures. Only full economic evaluations (synthesis of costs and benefits) comparing the use of anti-infective central venous catheters (AI-CVCs) with untreated CVCs or other treated catheters were selected for inclusion in the economic review. RESULTS:A total of 32 trials met the clinical inclusion criteria. Seven different types of AI-CVC were identified, with the most frequently tested being chlorhexidine and silver sulfadiazine (CHSS) (externally treated), CHSS (externally and internally treated) and minocycline rifampicin (internally and externally treated). In general, the trials were of a poor quality in terms of reported methodology, microbiological relevance and control of confounding variables. The pooled result suggests a statistically significant advantage for AI-CVCs in comparison to standard catheters in reducing CRBSI [odds ratio (OR) 0.45, 95% confidence interval (CI) 0.34 to 0.60, 24 studies, I-squared = 0%, fixed effects]. Analysis by subgroups of catheters demonstrates that antibiotic-treated catheters and catheters treated internally and externally decrease CRBSI rates significantly (OR 0.26, 95% CI 0.15 to 0.46, six studies, I-squared = 0%, fixed effects, and OR 0.43, 95% CI 0.26 to 0.70, nine studies, I-squared = 0%, fixed effects, respectively). Catheters treated only externally demonstrate a wider CI and non-significant effect (OR 0.67, 95% CI 0.43 to 1.06, nine studies, I-squared = 0%, fixed effects). A treatment effect was also found for trials with an average duration of between 5 and 12 days, and for the one study with a mean duration of over 20 days. There was a statistically significant treatment effect for both femoral and jugular insertion sites and for those studies reporting a mix of insertion sites. The treatment effect was not observed in trials using exclusively subclavian insertion sites. Of the four trials that compared treated catheters, one reported a benefit of antibiotic-treated catheters over catheters treated externally with CHSS. All three sensitivity analyses testing for study design differences reported a statistically significant treatment effect. The review was limited owing to the quality of the trials included, marked differences in the definitions and methods of diagnosis of CRBSI, and inconsistent reporting of risk factors and patient population factors. Furthermore, two-thirds of trials were commercially funded. The economic performance (cost-effectiveness and potential cost-savings) of using AI-CVCs to reduce the number of CRBSIs in patients requiring a CVC was also reviewed. Results show that the use of AI-CVCs instead of standard CVCs can lead to a reduction in CRBSIs and decreased medical costs. To complement the reviews, a basic decision-analytic model was constructed to explore a range of possible scenarios for the NHS in England and Wales. Results show that for every patient who receives an AI-CVC there is an estimated cost-saving of 138.20 pounds. The multivariate sensitivity analyses estimate potentially large cost-savings, depending on the size of the population, under a wide range of cost and clinical assumptions. However, those considering the purchase of AI-CVCs should ensure that their patient populations and the important characteristics of local clinical practice are indeed similar to those described in this economic evaluation. CONCLUSIONS:Overall, AI-CVCs are clinically effective and relatively inexpensive and therefore their integration into clinical practice can be justified. However, the use of these anti-infective catheters without the appropriate use of other practical care initiatives will have only a limited success on the prevention of CRBSIs. Comparative trials are required to determine which, if any, of the treated catheters is the most effective. Pragmatic research related to the effectiveness of bundles of care that may reduce rates of CRBSI is also warranted.
    背景与目标:
  • 【希腊中部蒂瓦盆地地下水中的六价铬污染。】 复制标题 收藏 收藏
    DOI:10.1007/s00128-012-0831-4 复制DOI
    作者列表:Tziritis E,Kelepertzis E,Korres G,Perivolaris D,Repani S
    BACKGROUND & AIMS: :There is an increasing concern regarding elevated levels of Cr(VI) in the environment due to its higher mobility and toxicity compared to the trivalent form. Anomalous hexavalent chromium concentrations (up to 212 μg/L) were determined in irrigated groundwaters from the wider area of Thiva Basin (central Greece), frequently exceeding the permissible limit for human consumption (50 μg/L for total Cr). Based on the spatial distribution of Cr(VI) values, two groups of groundwater samples were distinguished, possibly reflecting different natural and/or anthropogenic factors that govern the levels of contamination. The first group is spatially located northwards of Thiva town and is consisted of concentrations that range from 13 to 212 μg/L (median 58 μg/L), while the second group is located near Mouriki village and Cr(VI) values range from <9 to 14 μg/L. The Cr(VI) chemical anomalies represent an important social problem because the agricultural products of this region are a major vegetable supply for Greece, bringing up the urgent need to evaluate the health effects associated with Cr(VI) exposure by ingesting the potentially contaminated foods.
    背景与目标: : 与三价形式相比,由于其更高的迁移率和毒性,环境中Cr(VI) 的水平升高引起了越来越多的关注。在来自锡瓦盆地 (希腊中部) 更广阔地区的灌溉地下水中,测定了六价铬的异常浓度 (最高212 μ g/L),经常超过人类食用的允许限值 (总Cr为50 μ g/L)。根据Cr(VI) 值的空间分布,区分了两组地下水样品,这可能反映了控制污染水平的不同自然和/或人为因素。第一组位于Thiva镇的北部,其浓度范围为13至212 μ g/L (中位数为58 μ g/L),而第二组位于Mouriki村附近,Cr(VI) 值范围为 <9至14 μ g/L。Cr(VI) 化学异常是一个重要的社会问题,因为该地区的农产品是希腊的主要蔬菜供应,因此迫切需要通过摄入可能受到污染的食物来评估与Cr(VI) 暴露相关的健康影响。
  • 【喹普利的慢性ACE抑制调节中枢血管加压素能系统。】 复制标题 收藏 收藏
    DOI:10.1016/s0008-6363(97)00084-9 复制DOI
    作者列表:Muders F,Elsner D,Jandeleit K,Bahner U,Kromer EP,Kirst I,Riegger GA,Palkovits M
    BACKGROUND & AIMS: OBJECTIVE:The role of the brain as a target for angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure and hypertension is unclear. To test the hypothesis that ACE inhibitors may modulate other central neuropeptide systems such as the central vasopressin system, we studied the effects of chronic treatment with the ACE inhibitor, quinapril, on ACE activity and on central vasopressin content in specific brain areas in rats. METHODS:22 rats were chronically treated with quinapril (6 mg.kg-1 BW per gavage daily for 6 weeks; untreated controls, n = 14). ACE density in various brain regions was assessed by in vitro autoradiography using the specific ACE inhibitor, 125I-351A. Vasopressin content was determined in 19 brain areas (micropunch technique) known to be involved in cardiovascular regulation. RESULTS:Following chronic quinapril treatment ACE was significantly decreased in the thalamus (-38%), hypothalamus (-37%), hypophysis (-35%), cerebellum (-36%) choroid plexus (-20%), and locus coeruleus (-35%). Additionally, a marked reduction in serum ACE activity (-97%) was observed. Plasma levels of vasopressin were significantly decreased after quinapril treatment (0.97[s.e.m. 0.11] vs. 1.63[0.24] pg.ml-1 in controls, P < 0.05). Vasopressin content was significantly reduced in 9 of 19 specific brain areas. Regarding the hypothalamic vasopressin-producing nuclei, vasopressin was decreased in the paraventricular (292[197] vs. 2379[585] pg.mg-1 crotein in controls; P < 0.001) and supraoptic nuclei (13618[1979] vs. 24525[3894] pg.mg-1 protein; P < 0.05), but not in the suprachiasmatic nucleus. Vasopressin content was significantly reduced in brain areas connected by vasopressinergic fibres originating in the hypothalamic paraventricular nucleus: namely central gray, subcommissural organ, organum vasculosum laminae terminalis, dorsal raphe nucleus, and locus coerules. Vasopressin content was also significantly reduced in the median eminence (5887[1834] vs. 28321[4969] pg.mg-1 protein, P < 0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. CONCLUSIONS:Autoradiographic studies in vitro indicate that orally administered quinapril suppresses central ACE activity after chronic treatment. ACE inhibition by quinapril strongly influences vasopressin content in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitors may also contribute to overall therapeutic efficacy.
    背景与目标:
  • 【奥氮平和利培酮在中央延伸杏仁核中诱导Fos表达。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejphar.2019.172764 复制DOI
    作者列表:Pinna A,Costa G,Contu L,Morelli M
    BACKGROUND & AIMS: :The extended amygdala has been proposed to play an essential role in cognitive and affective processes and in neuropsychiatric disorders. In the present study, we examined the induction of Fos-like nuclei in the central amygdaloid nucleus (CeA), sublenticular extended amygdala (SLEA), interstitial nucleus of the posterior limb of the anterior commissure (IPAC), and bed nucleus of the stria terminalis (BSTL) of rodents to improve the knowledge regarding the pharmacological profile, therapeutic efficacy, and side-effects of olanzapine, an atypical antipsychotic drug and risperidone, a mixed atypical/typical antipsychotic drug in the rat brain. In addition, we evaluated the induction of Fos-like-nuclei in areas connected with these structures such as prefrontal cortex (PFCx), and nucleus accumbens shell, and in other important areas including the lateral septum and caudate-putamen that are involved in the therapeutic efficacy or side-effects of antipsychotic drugs. Fos-like-immunoreactivity induced by olanzapine and risperidone was compared with that by the atypical antipsychotic clozapine and typical antipsychotic haloperidol. Regarding the extended amygdala, and similarly to clozapine, olanzapine (5-10 mg/kg) and, with a lower efficacy, risperidone (1-3 mg/kg), induced Fos-like-nuclei in CeA, IPAC, SLEA, and BSTL. Both these drugs increased the induction of Fos-like-nuclei in PFCx, nucleus accumbens shell, lateral septum, and caudate-putamen. On the contrary, the increase of Fos-like-nuclei in the extended amygdala by haloperidol was restricted to IPAC only. These findings, consistent with the important role of extended amygdala in neuropsychiatric disorders characterized by affective disturbances, showed that olanzapine and risperidone, contrary to haloperidol, preferentially activated Fos-expression in these brain areas.
    背景与目标: : 已提出扩展的杏仁核在认知和情感过程以及神经精神疾病中起重要作用。在本研究中,我们检查了杏仁核中央核 (CeA),扁桃体下扩展杏仁核 (SLEA),前连合后肢间质核 (IPAC) 中Fos样核的诱导,和啮齿动物的纹状体核 (BSTL),以提高对非典型抗精神病药物奥氮平和大鼠大脑中非典型/典型抗精神病药物利培酮的药理作用,治疗功效和副作用的认识。此外,我们评估了与这些结构相关的区域 (例如前额叶皮层 (PFCx) 和伏隔核壳) 以及其他重要区域 (包括外侧隔膜和尾状壳核) 的诱导作用抗精神病药物的治疗功效或副作用。将奥氮平和利培酮诱导的Fos样免疫反应性与非典型抗精神病药氯氮平和典型抗精神病药氟哌啶醇诱导的Fos样免疫反应性进行了比较。关于延长的杏仁核,与氯氮平类似,奥氮平 (5-10毫克/千克) 和效力较低的利培酮 (1-3毫克/千克) 在CeA、IPAC、SLEA和BSTL中诱导Fos样核。这两种药物均增加了PFCx,伏隔核壳,外侧隔膜和尾状壳核中Fos样核的诱导。相反,氟哌啶醇在延长的杏仁核中增加Fos样核仅限于IPAC。这些发现与延长的杏仁核在以情感障碍为特征的神经精神疾病中的重要作用相一致,表明奥氮平和利培酮与氟哌啶醇相反,优先激活了这些大脑区域的Fos表达。

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