• 【大鼠角膜缘和中央角膜上皮中基因表达(SAGE)的系列分析。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0216 复制DOI
    作者列表:Adachi W,Ulanovsky H,Li Y,Norman B,Davis J,Piatigorsky J
    BACKGROUND & AIMS: PURPOSE:To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS:The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression (SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS:The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein (similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin (a cancer marker), marapsin (a trypsin-like serine protease that may control cell growth and migration), K4 and K15 (both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS:The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration.
    背景与目标: 目的:鉴定在大鼠角膜的富含干细胞的角膜缘上皮细胞中优先表达的基因。
    方法:采用显微解剖技术分离6周龄大鼠角膜缘和角膜上皮细胞。构建并分析基因表达(SAGE)库的序列分析,并通过常规方法进行原位杂交,逆转录-聚合酶链反应(RT-PCR)和cDNA克隆。
    结果:大鼠角膜缘和角膜上皮SAGE文库分别由41,894和40,691个标签组成。注释后,该数目减少为角膜缘文库特异的759个转录物和中央角膜文库特异的844个转录物。 2292个成绩单重叠。编码具有代谢功能的蛋白质的转录本在两个文库中均属于主要功能类别。角膜缘上皮细胞中12种最丰富,高度富集的转录本的原位杂交和/或RT-PCR结果与SAGE数据基本一致,表明这些蛋白质也在结膜上皮细胞中表达。有趣的角膜缘丰富的转录本编码WDNM1样蛋白(类似于WDNM1 / Expi,一种推测的分泌蛋白酶和转移抑制剂),间皮素(一种癌症标志物),marapsin(一种胰蛋白酶样丝氨酸蛋白酶,可以控制细胞的生长和迁移)。 ,K4和K15(均为细胞角蛋白)和跨膜四结构域亚家族A成员8B。克隆了类似WDNM1的蛋白质,并确认其为四-二硫键核心家族的成员。
    结论:SAGE结果扩展了在啮齿动物角膜中表达的基因数据库,并暗示了在角膜缘上皮中优先表达的几个基因与细胞增殖和迁移之间的关联。
  • 【阴道和子宫颈的透明细胞腺癌。荷兰中部注册表的更新显示双胞胎年龄发病高峰。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0142(19970601)79:11<2229::aid-c 复制DOI
    作者列表:Hanselaar A,van Loosbroek M,Schuurbiers O,Helmerhorst T,Bulten J,Bernhelm J
    BACKGROUND & AIMS: BACKGROUND:The objective of this study was to update the registry of women in the Netherlands with clear cell adenocarcinoma (CCAC) of the cervix or vagina with or without intrauterine exposure to diethylstilbestrol (DES). METHODS:From a nationwide search in PALGA, the automated pathology registry in the Netherlands, data were gathered on women with CCAC born after 1947. Information obtained from the clinical files of the patients included reported exposure to DES, patterns of complaints previous to diagnosis, the current status of the patients, and the results of cytopathologic examinations previous to histopathologic diagnosis. After review of the histopathologic slides, the specific pathologic characteristics of CCAC were determined. The age distribution of women born after 1947 was compared with that of women born before 1947. RESULTS:Information about possible exposure to DES during pregnancy was available for 73 of 88 women with CCAC born after 1947. Exposure to DES was reported for 47 (64%) of these women. The DES medication was most often reported as having started before the 18th week of pregnancy. Cytopathologic examination was informative in 81% of the cases of CCAC of the cervix, but only in 41% of the cases of CCAC of the vagina. Most patients had Stage I or II tumors at diagnosis. Tumor Stage III and IV and a high grade of nuclear atypia were related to unfavorable outcome. The age distribution of all patients with CCAC showed two distinct peaks; one at young age, (a mean age of 26 years), and one at older age (a mean age of 71 years). This bimodal age distribution still applied when the cases in which DES exposure was reported had been excluded. CONCLUSIONS:Despite the fact that DES has not been prescribed to pregnant women in the Netherlands in the last 20 years, CCAC is still relevant in our times. It is important to stay alert and periodically to update and evaluate the data of this registry, including data on women born outside the DES exposure period. The bimodal age distribution in this study of women without intrauterine exposure to DES suggests a carcinogenesis-promoting role of menarche and menopause and/ or the existence of a subpopulation with genetic risk factors or exogenous risk factors other than exposure to DES. Postmenopausal observation of women exposed to DES must be encouraged for clinical reasons and may help facilitate differentiation between these two hypotheses. If these risk factors of CCAC were better documented and their interrelationships better defined, CCAC could become an important model of multistep carcinogenesis in tissues sensitive to sex hormones.
    背景与目标: 摘要背景:这项研究的目的是更新荷兰妇女宫颈或阴道透明细胞腺癌(CCAC)宫腔内或不暴露于己烯雌酚(DES)的女性登记资料。
    方法:通过在荷兰的自动病理注册机构PALGA进行的全国性搜索,收集了1947年以后出生的CCAC妇女的数据。从患者的临床档案中获得的信息包括报告的DES暴露,诊断前的投诉模式,患者的当前状况以及组织病理学诊断之前的细胞病理学检查结果。在回顾了组织病理学切片之后,确定了CCAC的具体病理学特征。比较了1947年以后出生的妇女和1947年之前出生的妇女的年龄分布。
    结果:1947年后出生的88例CCAC妇女中有73例可获得有关怀孕期间可能接触DES的信息。据报道,这些女性中有47例(64%)接触DES。据报道,DES药物是在怀孕第18周之前开始服用的。在81%的子宫颈CCAC病例中,细胞病理学检查是有益的,但在阴道的CCAC病例中仅41%。大多数患者在诊断时患有I期或II期肿瘤。肿瘤的第三和第四阶段以及高度的核非典型性与不良预后有关。所有CCAC患者的年龄分布均出现两个明显的高峰。一位年龄较小(平均年龄26岁),一位年龄较大(平均年龄71岁)。当排除了报道有DES暴露的病例时,这种双峰年龄分布仍然适用。
    结论:尽管在过去的20年中荷兰没有为孕妇开具DES,但CCAC在我们这个时代仍然具有现实意义。重要的是要保持警惕,并定期更新和评估该注册表的数据,包括有关DES暴露期以外出生的妇女的数据。在这项研究中,没有宫内暴露于DES的妇女的双峰年龄分布表明,月经初潮和更年期的致癌作用和/或除了暴露于DES之外,还存在具有遗传危险因素或外源危险因素的亚群。出于临床原因,必须鼓励对接受DES的妇女进行绝经后观察,这可能有助于促进这两种假说之间的区分。如果更好地记录CCAC的这些危险因素并更好地定义它们之间的相互关系,CCAC可能会成为对性激素敏感的组织中多步骤癌变的重要模型。
  • 【人类前脑神经母细胞对成年大鼠中枢神经系统长轴突通路的改造。】 复制标题 收藏 收藏
    DOI:10.1038/347556a0 复制DOI
    作者列表:Wictorin K,Brundin P,Gustavii B,Lindvall O,Björklund A
    BACKGROUND & AIMS: :The failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to approximately 20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.
    背景与目标: :损伤的轴突在哺乳动物中枢神经系统(CNS)中无法长距离再生的原因不是由于中枢神经元无法再生,而是由于CNS组织环境的非许可性质。例如,在周围神经中生长良好的再生中枢神经轴突不能穿透成熟的中枢神经系统组织超过约1毫米。最近的证据表明,这可能是由于与CNS少突胶质细胞和髓磷脂相关的抑制性膜蛋白所致。我们在这里报告说,植入成年大鼠兴奋毒性损伤的纹状体的人端脑神经母细胞可以逃避或中和成年中枢神经系统环境的这种抑制作用,并沿着主要有髓纤维束延伸轴突的距离可达约20 mm。看到轴突沿着纹状体-黑色和皮质-脊髓束的路径伸长,到达黑质,桥脑核和颈脊髓,这是可能存在的纹状体和皮质投射神经元的正常靶标在这些植入物中。
  • 【注意缺陷多动障碍可能与中枢性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: 注意缺陷多动障碍(ADHD)是儿童期常见的精神病。尽管进行了深入的研究,但多动症的病因仍然未知。当前证据表明,ADHD的病因是异质的,由多种因素组成。最近,已经提出,脑源性神经营养因子(BDNF),神经营养因子家族的成员,可能与ADHD的发病有关。这一假说得到了多动症最近的遗传学研究的支持。根据对ADHD药物的研究发现,该药物与中枢BDNF表达,BDNF基因敲除小鼠的过度活跃,BDNF对中脑多巴胺能功能的影响以及BDNF与多巴胺转运蛋白(ADHD发病机理的重要分子)之间的紧密联系有关,因此提出了这一建议。在这里,中央BDNF的降低,特别是在中脑区域,可能在ADHD的发病中起重要作用。该假设可能对ADHD的临床发现有一定的影响(例如,ADHD与严重抑郁症的合并症),并为ADHD治疗药物的开发提供了新的方向。
  • 【加纳人口的一般和中枢肥胖和2型糖尿病风险的度量。】 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: 目的:肥胖症和2型糖尿病的流行在撒哈拉以南非洲(SSA)中很明显。但是,在该地区几乎没有检查过它们的关联。
    方法:一项基于医院病例对照研究,由加纳市区的1221名成年人(542例和679名对照)组成,研究了人体测量学参数在糖尿病中的作用。使用逻辑回归进行分析。糖尿病的鉴别力和特定人群的临界点通过接受者的操作特征曲线来确定。
    结果:腰臀比与糖尿病的关系最大:女性每1个标准差的年龄校正比值比为1.95(95%置信区间[CI]:1.64-2.31),而女性为1.40 [1.01-1.94] ]的男人。另外,在女性中,糖尿病的几率随着腰围(1.35 [1.17-1.57])和腰高比(1.29 [1.12-1.50])的增加而增加。在男人中,这是不明显的。相反,髋围呈负相关(0.69 [0.50-0.95])。体重指数与女性(1.01 [0.88-1.15])和男性(0.74 [0.52-1.04])均与糖尿病无关。在这两个性别中,腰臀比在该人群中表现出对糖尿病的最佳判别能力,并且最佳的临界点是女性≥0.88,男性≥0.90。推荐的体重指数和腰围临界点的预测能力较差。
    结论:我们的研究结果表明,中枢性肥胖而非一般性肥胖的测量与SSA中的2型糖尿病有关。撒哈拉以南非洲地区预防肥胖症的人体测量指标是否与发达国家不同,尚需从更大的基于人群的流行病学研究中得到验证。
  • 【印度中部模仿喉癌的播散性组织胞浆菌病-病例报告。】 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: :一位58岁的男性,慢性吸烟者,患有糖尿病(II型),居住在中央邦,患有吞咽困难,声音嘶哑,吞咽困难和体重减轻。微喉镜检查显示溃疡区带红色的溃疡区域,并有咽咽部褶皱。组织病理学检查显示泡沫状巨噬细胞含有荚膜组织胞浆。患者最初对Azoles有反应,在停止治疗后三个月复发,并出现口腔损伤。活检组织学和培养均显示荚膜H.。菌丝体相在B.H.I.A.上转化为酵母相。在37℃下确认该分离物为荚膜H.。该患者对两性霉素B反应良好。
  • 【关于中美洲和南美洲本土文化中的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: 目的:描述来自几种本土文化的萨满祭司对偏头痛的礼仪和民族植物疗法。
    方法:对Tzeltal Maya(墨西哥),Kamayurá(巴西)和Uru-Chipaya(玻利维亚)的美洲印第安人进行了人类学现场研究。
    结果:偏头痛被特泽塔尔萨满(Tzeltal Shamans)称为yaxti-wanjol chawaj。他们用草药溶液冲洗患者的头部,以治疗头痛。称为paytéwamal(Tagetes nelsonii)的灌木的煮沸的叶子用于缓解偏头痛。偏头痛被卡马尤拉人称为猴子病。该病源于被杀死的猴子的精神报复,袭击了卡马尤拉(Kamayurá)猎人的头部。通过在患者眼睛中使用草药输液进行治疗。奇帕亚人将偏头痛称为eskeclamix,并通过喝水煮沸的卡纳瓦植物(Chenopodium palludicale)进行治疗。病人的头部也可以用萨满发酵的尿液清洗。
    结论:偏头痛的文化等同物存在于孤立的美国文化的康复系统中。
  • 【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,可作为许多亲脂性化合物的外排泵。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。 C3435T多态性的等位基因频率差异已在不同种族之间得到证明。在我们的研究中,我们检查了433位健康个体中的这些多态性。其中,来自尼加拉瓜(n = 117)和萨尔瓦多(n = 112)的229名中美洲混血儿与一组204个北西班牙人进行了比较,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人(0.53)和西班牙人(0.52)之间非常相似,这与中美洲人(美洲印第安人和欧洲高加索人)的种族起源是一致的。与其他先前研究的人群相比,中美洲人的C等位基因频率显着低于非洲人群中的C等位基因频率,并且高于印度和西南亚人群中的C等位基因频率。这些数据可能与P-gp底物药物的剂量推荐以及中美洲人群等位基因疾病关联的研究有关。
  • 【舌下触觉传入神经的外周和中央末端,支配了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)结合的霍乱毒素B亚基注射到四种雀科的舌下神经的舌状分支中,以鉴定舌头真皮乳头的机械感受器的神经支配,并同时确定舌下传入神经的中央投影的模式。结果表明,舌下纤维支配着舌头背部精心组织的乳头的所有Herbst小体和终末细胞受体,腹侧舌头的较短乳突以及在乳头下区域松散的Herbst小体集合。在舌内腺,固有的舌头肌肉和后嗅上皮中也观察到标记的纤维,在那里它们形成了芽状结构。逆行标记的细胞体位于颈神经节中,其中央过程在三叉神经下降道(TTD)内的整个脑干内上升和下降。在TTD尾状核的背外侧部分,主要在同侧,以及在双侧头4-6个颈段的背角内侧部分,观察到了终场。在TTD内插核的背外侧亚核上和主要三叉神经感觉核的两个区域内有密集的终止斑块:一个大的外侧和一个小内侧。在尾状孤立复合体的前外侧腹核内和相邻核内也观察到终末场,这可能与其他禽类的面部和舌咽神经的背感觉核相同。根据舌头在雀类中特定物种的喂养方式中的作用以及对触摸和味觉的集中整合的可能要求,来解释结果。
  • 【静脉溶栓在视网膜中央动脉阻塞中是否安全有效?极受好评的主题。】 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: 背景:视网膜中央动脉阻塞(CRAO)是一种神经和眼科急症,伴有视力恢复不良。由于缺乏正式的指导方针,因此在适当的治疗上存在两难选择。尽管被认为是脑梗死的等效眼药,静脉溶栓治疗在CRAO中获得最大疗效和安全性的时间窗口仍然不确定。
    目的:严格评估有关IV溶栓治疗CRAO患者的安全性和有效性的现有证据。
    方法:通过制定一个严格评估的主题来解决该目标,该主题包括临床方案,结构化问题,文献检索策略,严格评估,结果评估,证据总结,评论和底线结论。参加者包括血管神经病学和眼科领域的顾问和住院神经病学家,医学馆员以及内容专家。
    结果:选择了近期的患者水平荟萃分析进行严格评估。这项研究比较了CRAO静脉溶栓后的视力恢复率与该疾病的自然病史和保守治疗方法(眼部按摩,前房穿刺和/或血液稀释)。溶栓治疗的时间对CRAO的视力恢复有显着影响(P <0.001)。在症状发作后的最初4.5小时内进行静脉溶栓治疗可导致50.0%的患者恢复视力[95%置信区间(CI),32.4%-67.6%]。视觉恢复率比自然史队列高出近3倍[赔率,比率4.7(95%CI,2.3-9.6); P <0.001],绝对危险度降低32.3%,需要治疗的数字为4.0(95%CI,2.6-6.6)。对于4.5小时后接受治疗的患者,溶栓后的恢复率与自然史队列相比无显着差异。在这项荟萃分析中,服用阿替普酶后未发生大出血。
    结论:CRAO中的IV溶栓似乎在症状发作的最初4.5小时内是安全有效的。由于一些限制,不能仅基于这种荟萃分析做出临床决定。在CRAO中早期静脉给予阿替普酶的随机对照临床试验对于提供循证治疗指导是必要的。
  • 【感染Acanthamoeba sp。的AIDS患者的生存。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: 病例描述:一名38岁的男性出现头痛和全身无力。他被发现患有艾滋病;在大脑成像中发现了增强环的中枢神经系统病变,他的血清弓形虫IgG水平升高。诊断为推定性弓形虫脑炎,他接受了抗逆转录病毒药物和抗弓形虫疗法治疗了4年。间歇性头痛和神经影像学上疾病进展的证据值得进一步评估,脑脊液分析显示苏木精和曙红染色中的阿米巴形式以及棘阿米巴属菌种的阳性聚合酶链反应测试。他被放置在miltefosine,fluconazole,trimethoprim-sulfamethoxazole和flucytosine上7个月。停药五个月后,他无症状,仅接受抗逆转录病毒疗法。
    结论:这是第一例仅通过药物治疗幸存下来的艾滋病和肉芽肿性阿米巴脑炎患者的报告。
  • 【中央或外周施用瘦素对确定的脂肪库中去甲肾上腺素更新的影响。】 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: 瘦素可通过增加脂肪分解和/或抑制脂肪生成来保留瘦肉组织,但可以减少脂肪组织。交感神经系统(SNS)是脂解作用的主要调节剂,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周转率(NETO)。在这项研究中,我们检查了瘦素作为慢性生理剂量(腹腔镜微渗透泵每天40微克/天,连续4天)或作为急性注射在第三脑室中的作用(1.5微克,每天两次,连续2天)的效果雄性Sprague Dawley大鼠的NETO和棕色和白色脂肪储库的大小。 NETO是根据NE合成抑制剂α-甲基-对-酪氨酸给药后4小时内组织去甲肾上腺素(NE)的下降确定的。与外围注入的动物相比,以瘦素为中心注射的动物表现出食物摄入量,体重和脂肪垫尺寸的显着减少,NETO增加。瘦素的两种给药方式均不会在所有测试的脂肪垫上引起NETO的均匀增加,并且在两种治疗条件下,瘦素均会降低某些脂肪垫的大小,而与NETO的增加无关。在喂给瘦素治疗的动物中,发现白脂肪NETO的相似差异。这些结果表明,瘦素在中央或外周选择性地起作用,增加了向白色脂肪贮库的交感性流出,并且瘦素诱导的脂肪垫重量变化不需要增加NETO。
  • 【用抗感染剂治疗的中心静脉导管在预防血液感染方面的临床效果和成本效益: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: 目的:评估用抗感染药治疗的中心静脉导管(CVC)在预防导管相关的血流感染(CRBSI)方面的临床效果和成本效益。
    数据来源:从1985年到2005年8月,检索了主要的电子数据库。
    审查方法:根据公认的程序进行系统的临床和经济审查。只有将将抗感染中心静脉导管(AI-CVC)与未经治疗的CVC或其他经过治疗的导管的使用进行比较的全面经济评估(成本和收益的综合)才被选入经济评估。
    结果:总共32项试验符合临床纳入标准。鉴定出七种不同类型的AI-CVC,最常测试的是洗必太和磺胺嘧啶银(CHSS)(外部治疗),CHSS(外部和内部治疗)和米诺环素利福平(内部和外部治疗)。总体而言,就报告的方法学,微生物学相关性和混杂变量的控制而言,这些试验的质量较差。汇总结果表明,与标准导管相比,AI-CVC在降低CRBSI方面具有统计学上的显着优势[比值比(OR)0.45,95%置信区间(CI)0.34至0.60,24个研究,I平方= 0%,固定效果]。导管亚组的分析表明,抗生素治疗过的导管和内外治疗过的导管显着降低了CRBSI率(OR 0.26,95%CI 0.15至0.46,六项研究,I平方= 0%,固定效应,OR 0.43,95 %CI 0.26至0.70,九项研究,I平方= 0%,分别为固定效应)。仅经外部治疗的导管显示出较宽的置信区间,且无显着影响(OR为0.67,95%置信区间为0.43至1.06,九项研究,I平方= 0%,固定效应)。对于平均持续时间为5至12天的试验以及平均持续时间超过20天的一项研究,也发现了治疗效果。股骨和颈静脉插入部位以及报告混合插入部位的研究在统计学上均具有显着的治疗效果。在仅使用锁骨下插入位点的试验中未观察到治疗效果。在比较经治疗的导管的四项试验中,有一项报告指出,与经CHSS外部治疗的导管相比,经抗生素治疗的导管有益处。针对研究设计差异的所有三个敏感性分析测试均报告了统计学上显着的治疗效果。由于包括的试验质量,CRBSI的诊断定义和诊断方法存在明显差异以及危险因素和患者人群因素的报告不一致,因此该审查受到了限制。此外,三分之二的试验是由商业资助的。还审查了使用AI-CVC减少需要CVC的患者中CRBSI数量的经济表现(成本效益和潜在的成本节省)。结果表明,使用AI-CVC代替标准CVC可以减少CRBSI并降低医疗成本。为了补充评论,构建了基本的决策分析模型,以探索英格兰和威尔士的NHS的各种可能方案。结果表明,每位接受AI-CVC的患者估计可节省138.20磅。多元敏感性分析估计,在广泛的成本和临床假设下,取决于人群的规模,可能会节省大量成本。但是,考虑购买AI-CVC的人员应确保其患者人数和当地临床实践的重要特征确实与本经济评估中所述的相似。
    结论:总体而言,AI-CVC具有临床效果且相对便宜,因此可以证明将其整合到临床实践中是合理的。但是,在没有适当使用其他实践护理措施的情况下使用这些抗感染导管在预防CRBSI方面仅会取得有限的成功。需要进行比较试验来确定哪一种治疗过的导管最有效。还必须进行与可能降低CRBSI发生率的护理捆绑的有效性相关的务实研究。
  • 【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: :由于与三价形式相比,Cr(VI)具有更高的迁移率和毒性,因此对环境中Cr(VI)含量升高的关注日益增加。在蒂瓦盆地(希腊中部)更广阔地区的灌溉地下水中确定了异常的六价铬浓度(高达212μg/ L),经常超过人类允许的摄入限量(总Cr含量为50μg/ L)。根据Cr(VI)值的空间分布,区分了两组地下水样品,可能反映了控制污染水平的不同自然和/或人为因素。第一组在空间上位于Thiva镇以北,其浓度范围为13至212μg/ L(中位数58μg/ L),而第二组位于Mouriki村附近,Cr(VI)值的范围为< 9至14μg/ L。六价铬化学异常代表了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六价铬暴露相关的健康影响。
  • 【奎那普利对慢性ACE的抑制作用可调节中枢血管加压素系统。】 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: 目的:尚不清楚脑作为血管紧张素转化酶(ACE)抑制剂的靶标在治疗心力衰竭和高血压中的作用。为了检验ACE抑制剂可能调节其他中枢神经肽系统(例如中枢加压素系统)的假设,我们研究了用ACE抑制剂奎纳普利进行慢性治疗对大鼠特定大脑区域ACE活性和中枢加压素含量的影响。
    方法:对22只大鼠进行喹那普利慢性治疗(每天每管饲喂6 mg.kg-1 BW,连续6周;未治疗的对照组,n = 14)。使用特定的ACE抑制剂125I-351A,通过体外放射自显影评估大脑各个区域的ACE密度。在已知参与心血管调节的19个脑区(微穿孔技术)中测定了加压素的含量。
    结果:慢性奎纳普利治疗后,丘脑(-38%),下丘脑(-37%),垂体(-35%),小脑(-36%)脉络丛(-20%)和蓝斑ACE的ACE显着降低(-35%)。另外,观察到血清ACE活性显着降低(-97%)。奎尼普利治疗后血浆血管加压素水平显着降低(对照组为0.97 [s.e.m。0.11] vs.对照组的1.63 [0.24] pg.ml-1,P <0.05)。在19个特定脑区中的9个中,加压素含量显着降低。关于下丘脑产生血管加压素的细胞核,室旁旁加压素的含量(对照组为292 [197]对2379 [585] pg.mg-1 crotein; P <0.001)和视上核(13618 [1979] vs.24525 []]降低。 [3894] pg.mg-1蛋白; P <0.05),但不在视交叉上核中。在下丘脑室旁核的血管加压能纤维连接的大脑区域中,血管加压素的含量显着降低:即中央灰色,连合下器官,椎板的末端器官,背ra核和轨迹小核。加压素的含量在中位显着性方面也显着降低(5887 [1834]对28321 [4969] pg.mg-1蛋白,P <0.001),该激素主要集中在下丘脑下垂体。
    结论:体外放射自显影研究表明,口服奎尼普利可抑制慢性治疗后的中枢ACE活性。奎那普利对ACE的抑制作用会强烈影响重要的脑部区域中血管加压素的含量,这些区域涉及中枢性心血管调节。因此,ACE抑制剂的中央调节作用也可能有助于总体治疗功效。

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