BACKGROUND & AIMS: Cardiac troponin T (cTnT) and troponin I (cTnI) have been suggested as new, more specific markers of myocardial cellular damage. The objective of this study was to examine how the distributions of cTnI and cTnT were affected in postinfarction left ventricular remodeled (LVR) myocardium. At 2 months postinfarct in a porcine heart failure model, both Western blot and biochemical assay analyses were performed on left ventricular myocardium remote from the infarct zone in ligation animals (n = 8). Results were compared with data from the left ventricular myocardium from similar sized healthy (control) pigs (n = 7). Autoradiograms from Western blot analysis showed that the protein mass for cTnI and cTnT in LVR hearts decreased 80% (P < 0.001) and 40% (P < 0.02), respectively, when compared with nondiseased tissue. Similarly, the concentrations for cTnI and cTnT in LVR hearts decreased 42% (P < 0.05) and 70% (P < 0.001), respectively, compared with nondiseased normal tissue. The clinical assumption is that the appearance of cTnI and cTnT in the blood is proportional to chronic loss of cTnI and cTnT from injured myocardium associated with left ventricular remodeling.

背景与目标： 心肌肌钙蛋白T（cTnT）和肌钙蛋白I（cTnI）被认为是心肌细胞损伤的新的，更具体的标志物。这项研究的目的是检查梗死后左心室重构（LVR）心肌中cTnI和cTnT的分布如何受到影响。在猪心力衰竭模型中，梗死后2个月，在结扎动物中，对远离梗死区的左心室心肌进行了Western blot和生化分析（n = 8）。将结果与来自类似大小的健康（对照）猪（n = 7）的左心室心肌的数据进行比较。 Western blot分析的放射自显影照片显示，与未患病的组织相比，LVR心脏中cTnI和cTnT的蛋白质质量分别降低了80％（P <0.001）和40％（P <0.02）。同样，与未患病的正常组织相比，LVR心脏中cTnI和cTnT的浓度分别降低了42％（P <0.05）和70％（P <0.001）。临床假设是血液中cTnI和cTnT的出现与左心室重构相关的心肌损伤导致cTnI和cTnT的慢性丧失成比例。

BACKGROUND & AIMS: :Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor.

背景与目标： ：胶质瘤是高度致死性的肿瘤，目前尚无法治愈。替莫唑胺是最近引入的烷基化剂，已在治疗高级神经胶质瘤中产生了显着的益处。然而，从头发生或获得性抗药性经常发生，并且归因于O6-甲基鸟嘌呤-DNA甲基转移酶水平的增加或错配修复能力的丧失。但是，极少的神经胶质瘤过表达O6-甲基鸟嘌呤-DNA甲基转移酶或错配修复缺陷，提示其他机制可能与对替莫唑胺的抗性有关。本研究的目的是从人类神经胶质瘤细胞系（SNB-19）产生抗替莫唑胺的变体，并使用大规模的基因组和转录分析来研究获得的替莫唑胺抗性的分子基础。两个独立获得的替莫唑胺抗性变体对其他烷基化剂[1,3-双（2-氯乙基）-1-亚硝基脲和卡铂]无交叉抗性，并且共有遗传变异，例如2p区域丢失和扩增丢失染色体4和16q区域。核型改变与亲本SNB-19细胞系中先前存在的抗性细胞的克隆选择相容。基因芯片分析显示，在17,000个基因中，有78个在亲代细胞和两种替莫唑胺耐药变体之间差异表达。没有人参与已知的抗性机制，例如DNA修复，而有趣的是，参与分化的几个基因被下调。数据表明，在该模型中获得对替莫唑胺的抗药性是由于在亲本肿瘤中选择了分化程度较低的抗药性细胞而引起的。

BACKGROUND & AIMS: :Rat basophilic leukemia (RBL 2H3) cells were passively sensitized by exposure to monoclonal anti-trinitrophenol mouse immunoglobulin E (anti-trinitrophenol IgE) (0.5 microgram/ml) and triggered by exposure to a sub-optimal concentration of trinitrophenol ovalbumin conjugate (5 ng/ml). At this concentration, trinitrophenol-ovalbumin increased histamine release from a basal rate of 4.8 +/- 0.5 to 28.5 +/- 4.6% and peptidoleukotrienes from less than 0.1 to 4.2 +/- 1.3 ng/10(6) cells in the activated cells. Ro 19-3704 and Ro 19-1400, platelet activating factor (PAF) antagonists which are structural analogs of PAF, potently inhibited both the IgE-dependent release of histamine (IC50 values of 3.0 and 3.6 microM, respectively) and LT release (IC50 values of 5.0 microM for both compounds) from the cells. These effects appeared to be independent to the ability of the compounds to act as PAF antagonists since PAF on its own had no effect on mediator release, and WEB 2086 and BN 52021, structurally distinct PAF antagonists, were relatively ineffective as inhibitors of mediator release. Ro 19-3704 and Ro 19-1400 were observed to be potent inhibitors of the soluble phospholipase A2 activity in synovial fluid from rheumatoid arthritic patients (IC50 values of 6.5 and 8.4 microM, respectively). In contrast, WEB 2086 and BN 52021 had no effect on this phospholipase A2. Ro 19-3704 significantly inhibited the IgE-dependent formation of inositol phosphates in RBL 2H3 cells (IC50 value of 7.0 microM). These data suggest that the mediator release inhibitory action of these compounds may be related to the ability of these compounds to inhibit phospholipase A2 and/or phospholipase C.

背景与目标： ：暴露于单克隆抗三硝基苯酚小鼠免疫球蛋白E（抗三硝基苯酚IgE）（0.5微克/毫升）可以被动致敏大鼠嗜碱性粒细胞白血病（RBL 2H3）细胞，并通过暴露于次适量浓度的三硝基苯酚卵白蛋白缀合物（5 ng / ml）。在此浓度下，三硝基苯酚-卵清蛋白将组胺释放从基础速率的4.8 /-0.5增加到28.5 /-4.6％，而肽白三烯从少于0.1到4.2 /-1.3 ng / 10（6）细胞增加。 Ro 19-3704和Ro 19-1400，血小板活化因子（PAF）拮抗剂，是PAF的结构类似物，可有效抑制IgE依赖的组胺释放（IC50分别为3.0和3.6 microM）和LT释放（IC50）。两种化合物的浓度值均为5.0 microM）。这些作用似乎与化合物充当PAF拮抗剂的能力无关，因为PAF本身对介质释放没有影响，并且结构不同的PAF拮抗剂WEB 2086和BN 52021作为介质释放抑制剂相对无效。观察到Ro 19-3704和Ro 19-1400是类风湿关节炎患者滑液中可溶性磷脂酶A2活性的有效抑制剂（IC50值分别为6.5和8.4 microM）。相反，WEB 2086和BN 52021对这种磷脂酶A2没有影响。 Ro 19-3704显着抑制RBL 2H3细胞中IgE依赖性肌醇磷酸的形成（IC50值为7.0 microM）。这些数据表明这些化合物的介质释放抑制作用可能与这些化合物抑制磷脂酶A2和/或磷脂酶C的能力有关。

BACKGROUND & AIMS: OBJECTIVE:The aim of the present investigation was to characterize the effects of supraphysiological doses of the anabolic androgenic steroid nandrolone decanoate (ND) on the fertility of female rats, as well as on the morphology of their uterus. STUDY DESIGN:Female Wistar rats (n=15) received a subcutaneous injection of ND (15 mg/kg) once daily during a 2-week period, while the control animals (n=10) were administered vehicle alone (arachidis oleum) in the same manner. Estrus behavior was evaluated 4 weeks after termination of this treatment and in cases where signs of receptivity were present, the female rat was given the opportunity to copulate with a male. After breeding, the female animals were sacrificed and their uteri examined histomorphologically. RESULTS:All ND-treated animals exhibited abnormal vaginal smears, whereas all of the control smears were normal. Most (73%) of the treated females demonstrated normal estrus behavior (i.e., willingness) on the day of mating, but none got pregnant; whereas all of the control rats became pregnant. The female rats receiving the ND showed an enhanced rate of weight gain and the myometrium thickness of their uteri was significantly increased, while the endometrium was significantly thinner. Furthermore, ND caused a significant proportion of the treated animals to display tortuous and irregularly branching endometrial glands, as well as a lack of the physiologically normal infiltration of eosinophilic leukocytes into the endometrium (endometrial eosinophilic homing), a finding that has not been reported previously. CONCLUSION:The present findings indicate that high doses of ND cause morphological and physiological alterations in the uterus of female rats that are associated with a suppression of their reproductive capacity.

背景与目标： 目的：本研究的目的是表征同化雄性类固醇癸酸nandrolone癸酸酯的超生理剂量对雌性大鼠生育能力以及子宫形态的影响。
研究设计：Wistar雌性大鼠（n = 15）在2周内每天一次皮下注射ND（15 mg / kg），而对照组（n = 10）单独给予媒介物（花生油）。同样的方式。终止该治疗4周后评估发情行为，并且在出现接受迹象的情况下，给予雌性大鼠与雄性交配的机会。繁殖后，将雌性动物处死并对其子宫进行组织形态学检查。
结果：所有接受ND治疗的动物均表现出异常的阴道涂片，而所有对照涂片均正常。接受治疗的大多数女性（73％）在交配当天表现出正常的发情行为（即意愿），但没有人怀孕；而所有对照大鼠都怀孕了。接受ND的雌性大鼠体重增加率增加，子宫肌层厚度明显增加，而子宫内膜明显变薄。此外，ND导致相当一部分被治疗的动物表现出曲折和不规则分支的子宫内膜腺体，并且缺乏正常的嗜酸性白细胞进入子宫内膜的生理正常浸润（子宫内膜嗜酸性归巢），这一发现此前尚未见报道。 。
结论：本研究结果表明，高剂量的ND可导致雌性大鼠子宫形态和生理改变，从而抑制其生殖能力。

BACKGROUND & AIMS: Previous work has shown that the type strain of Streptococcus sanguis, NCTC 7863, induces aggregation of normal platelets by a complement-dependent mechanism. We investigated the roles of IgG and fibrinogen in the aggregation process. Plasma depleted of IgG by passage through protein A-sepharose failed to support platelet aggregation, as did plasma absorbed at 0 degrees C with whole bacteria. However, absorption of plasma with a non-aggregating strain of S. sanguis, SK96, did not remove aggregating activity for NCTC 7863. Supplementing 0 degrees C-absorbed plasma with purified IgG restored the aggregation supporting activity. A monoclonal antibody to the Fc gammaRII receptor inhibited platelet aggregation by the bacteria, indicating a requirement for bacteria-IgG complexes interacting with the Fc receptor in platelet aggregation. There was a lag time to the onset of platelet aggregation of 7-19 min depending upon the platelet donor, but the length of this lag did not correlate with either total IgG concentration recognizing NCTC 7863 in subjects' plasma, or the concentration any of the four IgG subclasses or with IgG avidity levels. Fibrinogen was shown to bind rapidly to the bacterial cell surface. Monoclonal antibody to GPIIb/IIIa, RGDS peptide, and a specific antagonist for the platelet fibrinogen receptor, GPIIb/IIIa, FK633, inhibited platelet aggregation by NCTC 7863, indicating that platelet aggregation is fibrinogen dependent. These data suggest that platelet aggregation by some strains of S. sanguis requires multiple stimuli/agonists, including IgG-Fc receptor interaction, complement and fibrinogen.

背景与目标： 先前的研究表明，血链球菌型菌株NCTC 7863通过补体依赖性机制诱导正常血小板聚集。我们调查了IgG和纤维蛋白原在聚集过程中的作用。通过蛋白A-sepharose清除IgG的血浆不能支持血小板聚集，全细菌在0摄氏度下吸收的血浆也不能支持血小板聚集。但是，用无聚集链球菌SK96的非聚集菌株吸收血浆并不能消除NCTC 7863的聚集活性。在0°C吸收的血浆中添加纯化的IgG可以恢复聚集支持活性。 FcγRII受体的单克隆抗体抑制细菌的血小板聚集，表明在血小板聚集中需要细菌-IgG复合物与Fc受体相互作用。根据血小板供体的不同，血小板凝集的发生会有7-19分钟的滞后时间，但是该滞后的时间与受试者血浆中识别NCTC 7863的总IgG浓度或任何血浆中的浓度无关。四个IgG亚类或具有IgG亲和力水平。纤维蛋白原被证明与细菌细胞表面迅速结合。抗GPIIb / IIIa的单克隆抗体RGDS肽，以及血小板纤维蛋白原受体的特异性拮抗剂GPIIb / IIIa的FK633被NCTC 7863抑制血小板聚集，表明血小板聚集是纤维蛋白原依赖性的。这些数据表明某些血链球菌菌株的血小板聚集需要多种刺激/激动剂，包括IgG-Fc受体相互作用，补体和纤维蛋白原。

BACKGROUND & AIMS: Since loss of heterozygosity on 8p22-p21.3 has been found frequently in prostate cancer, the status of a candidate tumor suppressor gene named PRLTS gene, recently cloned from the same region in some human malignancies, was examined in the present study. DNAs were isolated from 69 Japanese prostate cancer patients (37 localized and 32 cancer-death cases). Loss of heterozygosity at this gene locus was observed in 15 of 36 (42%) localized prostate cancer patients and 22 of 32 (69%) cancer-death patients. One cancer-death patient had a missense mutation, ACG-->ATG (Thr-->Met) at codon 64 in metastatic tumor tissues of pelvic lymph node and liver, and these tissues showed loss of the homologous allele, indicating that "two-hit" mutation of the PRLTS gene had occurred in this case. The others did not show any mutation, regardless of the presence or absence of loss of heterozygosity. Although loss of heterozygosity at the PRLTS gene locus is a relatively common abnormality, mutation of this gene is rare in prostate cancer.

背景与目标： 由于在前列腺癌中经常发现8p22-p21.3杂合性丧失，因此本研究研究了一种候选的抑癌基因PRLTS基因的状态，该基因最近在某些人类恶性肿瘤中从同一区域克隆。从69位日本前列腺癌患者（37位局部和32位癌症死亡病例）中分离出DNA。在36位局部前列腺癌患者中有15位（42％）和32位癌症死亡患者（22％）中有22位在该基因位点观察到杂合性缺失。一名癌症死亡患者的盆腔淋巴结和肝转移性肿瘤组织中第64位密码子有错义突变，ACG-> ATG（Thr-> Met），这些组织显示出同源等位基因缺失，表明“两个在这种情况下发生了PRLTS基因的“ -hit”突变。其余的没有显示任何突变，无论是否存在杂合性缺失。尽管PRLTS基因位点的杂合性丧失是一个相对普遍的异常现象，但该基因的突变在前列腺癌中很少见。

BACKGROUND & AIMS: :Benzodiazepines have been used for decades as first-line treatment for status epilepticus (SE). For reasons that are not fully understood, the efficacy of benzodiazepines decreases with increasing duration of seizure activity. This often forces clinicians to resort to more drastic second- and third-line treatments that are not always successful. The antiseizure properties of benzodiazepines are mediated by γ-aminobutyric acid type A (GABA(A) ) receptors. Decades of research have focused on the failure of GABAergic inhibition after seizure onset as the likely cause of the development benzodiazepine resistance during SE. However, the details of the deficits in GABA(A) signaling are still largely unknown. Therefore, it is necessary to improve our understanding of the mechanisms of benzodiazepine resistance so that more effective strategies can be formulated. In this review we discuss evidence supporting the role of altered GABA(A) receptor function as the major underlying cause of benzodiazepine-resistant SE in both humans and animal models. We specifically address the prevailing hypothesis, which is based on changes in the number and subtypes of GABA(A) receptors, as well as the potential influence of perturbed chloride homeostasis in the mature brain.

背景与目标： ：苯二氮卓类药物已被用作癫痫持续状态（SE）的一线治疗。由于尚未完全理解的原因，苯二氮卓类药物的功效会随着癫痫发作持续时间的增加而降低。这通常迫使临床医生诉诸于并非总是成功的更激烈的二线和三线治疗。苯二氮卓类药物的抗癫痫作用是由γ-氨基丁酸A型（GABA（A））受体介导的。数十年的研究集中在癫痫发作后GABA能抑制的失败，这可能是SE期间对苯二氮卓类药物产生耐药性的可能原因。但是，GABA（A）信号转导的赤字的细节仍然很大程度上未知。因此，有必要增进我们对苯二氮卓类药物耐药性机制的了解，以便制定更有效的策略。在这篇综述中，我们讨论了在人和动物模型中支持改变的GABA（A）受体功能作为苯二氮卓类抗药性SE的主要原因的作用的证据。我们专门针对流行的假说，该假说基于GABA（A）受体的数量和亚型的变化，以及成熟脑中摄动氯稳态的潜在影响。

BACKGROUND & AIMS: :In this review the authors discuss persistent and cumulative alterations in both cognitive and motor function after sports concussions detected with some of the newest, most sophisticated brain investigation techniques. Ranging from subclinical neurophysiological alterations in young concussed athletes to quantifiable cognitive and motor function declines in former athletes in late adulthood with concussions sustained decades earlier, this review is also intended to provide new insights into the neuropathophysiology of sports concussion.

背景与目标： ：在这篇综述中，作者讨论了使用一些最新，最先进的脑部检查技术发现运动性脑震荡后认知和运动功能的持续和累积性变化。从年轻的脑震荡患者的亚临床神经生理学变化到成年后期持续数十年的脑震荡的前运动员在可量化的认知和运动功能下降方面，本综述还旨在为运动脑震荡的神经病理生理学提供新的见解。

BACKGROUND & AIMS: :Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

背景与目标： ：数据表明，通过与铁螯合剂去铁胺（DFO）和免疫球蛋白G（IgG）单克隆抗转铁蛋白受体抗体联合治疗，可以在体外以协同方式抑制5种鼠类淋巴瘤中5种的生长。 ATRA）。双向剂量/响应分析表明，随着DFO剂量的增加，ATRA作为抑制剂的效率更高。流式细胞术研究进一步支持这样一种观点，即即使存在DFO时，IgG ATRAS也会通过引起TR下调和降解而损害运铁蛋白受体（TR）的功能，即使DFO的存在会促进细胞表面TR表达的增加。还显示了当与DFO组合使用时，IgG ATRA在抑制肿瘤细胞生长方面几乎与IgM ATRA一样有效。最后，对铁螯合剂吡啶甲酸的研究表明，当与ATRA结合使用时，它仅产生加成或极轻微的超加成作用。因此，这些研究不仅继续表明，螯合剂/ ATRA组合疗法作为造血系统恶性肿瘤治疗的工具值得进一步研究，而且还提出了以下新观点：（1）临床上熟悉的铁螯合剂去铁胺，但并非所有铁螯合剂，在体外与ATRAS产生协同抑制肿瘤生长的作用； （2）IgG ATRAS在临床上可能比IgA或IgM ATRAS具有更强的吸引力，因为它可以更好地进入多余的血管组织空间，与DFO组合使用时，出乎意料地起到了强大的生长抑制剂的作用。

BACKGROUND & AIMS: :We investigated immunoglobulin G (IgG) subclass antibody responses to Plasmodium falciparum merozoite surface protein 1 (MSP-1) and MSP-2 in 112 malaria-exposed subjects in Brazil. IgG3 polarization was primarily epitope driven, being little affected by cumulative or current exposure to malaria and not affected by a subject's age and Fcgamma receptor IIA genotype.

背景与目标： ：我们调查了巴西112名疟疾暴露者对恶性疟原虫裂殖子表面蛋白1（MSP-1）和MSP-2的免疫球蛋白G（IgG）亚类抗体反应。 IgG3极化主要是由表位驱动的，几乎不受累积或当前暴露于疟疾的影响，并且不受受试者的年龄和Fcgamma受体IIA基因型的影响。

BACKGROUND & AIMS: :An automated microparticle enzyme immunoassay (IMx Rubella IgG Antibody Assay; Abbott Laboratories, North Chicago, Ill.) was compared with a conventional enzyme-linked immunosorbent assay (ELISA) for detection of rubella-specific immunoglobulin G (IgG) in 400 consecutive antenatal patients. There was complete agreement between the two tests in this population, which had a positivity rate of 99% for rubella-specific IgG antibodies. The performance of the IMx was also evaluated at the cutoff zone by assaying 64 selected antenatal serum samples with low or negative rubella antibody titers as determined by ELISA. Overall, the IMx was found to be a specific, sensitive assay for the detection of rubella-specific IgG and is virtually fully automated for easy performance.

背景与目标： ：将自动微粒酶免疫测定（IMx风疹IgG抗体测定；伊利诺伊州北芝加哥的雅培实验室）与常规酶联免疫吸附测定（ELISA）相结合，以检测400例连续的产前风疹特异性免疫球蛋白G（IgG）耐心。在该人群中的两次测试之间完全一致，风疹特异性IgG抗体的阳性率为99％。 IMx的性能也可以通过在64个选择的产前血清样本中通过ELISA测定的低或阴性风疹抗体滴度来评估，在临界区进行评估。总体而言，IMx被发现是一种用于检测风疹特异性IgG的特异性，灵敏的检测方法，并且实际上是全自动的，操作简便。

BACKGROUND & AIMS: PURPOSE:Tear film can be altered by chronic medications that may disrupt the equilibrium responsible for the functioning of the lacrimal gland and ocular surface. The purpose of this study was to determine if antiglaucomatous chronic treatment induced alterations in the tear film and ocular surface. METHODS:After informed consent, 21 patients using antiglaucomatous eye drops for more than 8 months and 20 age- and sex-matched volunteers without eye and systemic medications (control group) were enrolled. The data of ocular discomfort, fluorescein and lisamine green staining, tear film break-up time and Schirmer test were collected and compared by Student's t test. The impression cytology data were graded and compared by chi-square test. RESULTS:Patients chronically using antiglaucomatous medications presented with significant higher fluorescein staining (p=0.003), lisamine green staining (p=0.02) and lower TFBUT (p=0.001). The other compared parameters, including impression cytology were similar between the treated and control group (p>0.05). CONCLUSIONS:The present study shows that the tear film and the ocular surface are altered in patients under antiglaucomatous medications. In common, all medications were preserved with benzalkonium chloride. Efforts to minimize the adverse effects of chronic use of antiglaucomatous drugs must be addressed.

背景与目标： 目的：长期用药可能会改变泪膜，这可能会破坏负责泪腺和眼表功能的平衡。这项研究的目的是确定抗青光眼的慢性治疗是否引起泪膜和眼表的改变。
方法：征得知情同意后，招募了21例使用抗青光眼滴眼液超过8个月的患者和20名年龄和性别相匹配的无眼和全身药物的志愿者（对照组）。收集眼部不适，荧光素和赖氨酰胺绿染色，泪膜破裂时间和Schirmer试验的数据，并通过Student's t检验进行比较。对印象细胞学数据进行分级并通过卡方检验进行比较。
结果：长期使用抗青光眼药物的患者表现出较高的荧光素染色（p = 0.003），赖氨胺绿染色（p = 0.02）和较低的TFBUT（p = 0.001）。在治疗组和对照组之间，其他比较参数（包括印象细胞学）相似（p> 0.05）。
结论：本研究表明，在接受抗青光眼药物治疗的患者中，泪膜和眼表发生了改变。通常，所有药物均使用苯扎氯铵保存。必须努力减少长期使用抗青光眼药物的不良影响。

BACKGROUND & AIMS: :The recruitment process induced by acclimation of mammals to cold includes a marked alteration in the acyl composition of the phospholipids of mitochondria from brown adipose tissue: increases in 18:0, 18:2(n-6), and 20:4(n-6) and decreases in 16:0, 16:1, 18:1, and 22:6(n-3). A basic question is whether these alterations are caused by changes in the concentration of uncoupling protein-1 (UCP1) or the thermogenesis it mediates-implying that they are secondary effects-or whether they are an integrated, independent part of the recruitment process. This question was addressed here using wild-type and UCP1-ablated C57BL/6 mice acclimated to 24 degrees C or 4 degrees C. In wild-type mice, the phospholipid fatty acyl composition of mitochondria from brown adipose tissue showed the changes in response to cold that were expected from observations in other species and strains. The changes were specific, as different changes occurred in skeletal muscle mitochondria. In UCP1-ablated mice, cold acclimation induced acyl alterations in brown adipose tissue that were qualitatively identical and quantitatively similar to those in wild-type mice. Therefore, neither the increased content of UCP1 nor mitochondrial uncoupling altered the effect of cold on acyl composition. Cold acclimation in wild-type mice had little effect on phospholipid acyl composition in muscle mitochondria, but cold-acclimation in UCP1-ablated mice caused significant alterations, probably due to sustained shivering. Thus, the alterations in brown adipose tissue phospholipid acyl composition are revealed to be an independent part of the recruitment process, and their functional significance for thermogenesis should be elucidated.

背景与目标： ：哺乳动物适应寒冷引起的募集过程包括棕色脂肪组织线粒体磷脂的酰基组成显着改变：增加18：0、18：2（n-6）和20：4（n -6）并以16：0、16：1、18：1和22：6（n-3）递减。一个基本问题是这些变化是否是由解偶联蛋白1（UCP1）的浓度变化或其介导的生热作用引起的，这暗示它们是次要作用，或者它们是否是募集过程中不可或缺的独立部分。使用野生型和UCP1消融的C57BL / 6小鼠适应24°C或4°C时可以解决此问题。在野生型小鼠中，棕色脂肪组织线粒体的磷脂脂肪酰基组成显示出响应其他物种和品系的观测所预期的寒冷。这些变化是特定的，因为骨骼肌线粒体发生了不同的变化。在UCP1消融的小鼠中，冷驯化在棕色脂肪组织中诱导了酰基改变，其在质上与野生型小鼠的酰基改变相同且在数量上相似。因此，UCP1含量的增加和线粒体的解偶联都不会改变寒冷对酰基组成的影响。野生型小鼠的冷驯化对肌肉线粒体中磷脂酰基组成的影响很小，但是UCP1消融小鼠的冷驯化引起了显着的变化，这可能是由于持续的发抖。因此，揭示棕色脂肪组织磷脂酰基组成的改变是募集过程的独立部分，并且应阐明它们对生热的功能意义。

BACKGROUND & AIMS: :This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in people developing post-traumatic stress disorder (PTSD) following recent trauma. Sixty-two participants who had experienced recent acute traumatic events underwent a 7.3 min resting fMRI scan within 2 days post accident. Of these, 22 participants were diagnosed with PTSD within 1 to 6 months. Nineteen age- and sex-matched subjects without PTSD were selected as the trauma-exposed control group. Posterior cingulate cortex connectivity was determined from 17 PTSD patients and 15 control subjects by investigating synchronic low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between PTSD symptom severity and PCC connectivity, the contrast image representing areas correlated with the PCC was correlated with the 17 PTSD subjects' Clinician Administered PTSD Scale (CAPS) scores at diagnosis. Compared with the control group, PTSD patients exhibited decreased functional connectivity in the right lingual and right middle temporal gyri, and left lingual/posterior cingulate cortex. The left inferior temporal gyrus, right middle temporal gyrus, left middle temporal gyrus/insula, left medial frontal lobe/anterior cingulate cortex, and right medial frontal gyrus also showed increased connectivity within two days post accident. A negative correlation was found between PCC connectivity and CAPS scores in the left medial prefrontal cortex (mPFC). These results suggest that patients who develop PTSD exhibit different resting-state patterns of neuronal activity following recent trauma. Abnormal FC of mPFC may be a major risk factor predisposing patients to the development of PTSD.

背景与目标： ：这项研究使用静止状态功能磁共振成像（fMRI）来研究在最近的创伤后发展为创伤后应激障碍（PTSD）的人们的功能连接性是否发生了改变。事故发生后两天内，最近经历过急性创伤事件的62名参与者进行了7.3分钟的静息功能磁共振成像扫描。其中，有22名参与者在1-6个月内被诊断为PTSD。选择十九名没有PTSD的年龄和性别匹配的受试者作为暴露于创伤的对照组。通过使用时间相关性方法调查同步低频fMRI信号波动，从17例PTSD患者和15例对照受试者中确定了扣带后部皮层的连通性。为了评估PTSD症状严重程度与PCC连通性之间的关系，将代表与PCC相关的区域的对比图像与17 PTSD受试者在诊断时由临床医生管理的PTSD量表（CAPS）评分相关联。与对照组相比，PTSD患者在右舌和右颞中回以及左舌/后扣带皮层的功能连接性降低。左下颞回，右中颞回，左中颞回/孤立，左内侧额叶/前扣带回皮层以及右内侧额回在事故发生后两天内也显示出增强的连通性。左内侧前额叶皮层（mPFC）中的PCC连接性和CAPS得分之间呈负相关。这些结果表明，在最近的创伤之后，发展为PTSD的患者表现出不同的静止状态神经元活动。 mPFC的FC异常可能是使患者易患PTSD的主要危险因素。

BACKGROUND & AIMS: BACKGROUND:Disturbances of beta2-adrenoceptors are discussed as a pathogenic factor in atopic diseases.

METHODS:In this study the expression and function of beta2-adrenoceptors on peripheral blood leucocytes (PBL) of seven atopic patients with seasonal rhinoconjunctivitis and their seven healthy controls was evaluated in relation to disease activity. Earlier reported data during pollen season were now compared with data obtained from the same subjects after their allergic symptoms had subsided.

RESULTS:The variables that had indicated a beta2-adrenoceptor subsensitivity in the patients during pollen season returned to control values, i.e. the reduced beta2-adrenoceptor affinity, the reduced beta2-adrenoceptor sensitivity, the reduced increase of intracellular cyclic adenosine monophosphate (cAMP) content upon stimulation with isoproterenol, and the reduced cAMP plasma concentration (values no longer significantly different from those of controls). However, the variable that had suggested an increase in activity of the cAMP degrading enzyme phosphodiesterase (PDE), i.e. the reduced basal intracellular cAMP content of the patients, remained reduced after the pollen season (4.9 +/- 1.1 pmol/10(6) cells in patients vs 8.2 +/- 0.9 pmol/10(6) cells in controls: P<0.05). There were no significant differences in beta2-adrenoceptor density between patients and controls at both investigations.

CONCLUSIONS:Atopic seasonal rhinoconjunctivitis is associated with various alterations in the PBL beta2-adrenoceptor/cAMP system that depend on disease activity. The reversible beta2-adrenoceptor subsensitivity is likely to be a consequence of the disease, whereas the irreversibly decreased basal intracellular cAMP content, suggested an elevated PDE activity, might be a basic trait of atopy.

背景与目标： 背景：讨论了β2-肾上腺素受体的紊乱是特应性疾病的致病因素。

方法：本研究中β2-肾上腺素受体的表达和功能对7例季节性鼻结膜炎的特应性患者及其7名健康对照者的外周血白细胞（PBL）进行评估，以评估其与疾病活动的关系。现在将花粉季节中较早报告的数据与相同受试者变态反应症状缓解后获得的数据进行比较。

结果：表明β2肾上腺素受体亚敏性的变量患者在花粉季节恢复到控制值，即降低的β2-肾上腺素受体亲和力，降低的β2-肾上腺素受体敏感性，异丙肾上腺素刺激后细胞内环磷酸腺苷（cAMP）含量的增加减少以及cAMP血浆浓度的降低（与对照组相比有明显的差异）。然而，在花粉季节后，提示cAMP降解酶磷酸二酯酶（PDE）活性增加（即患者基础细胞内cAMP含量降低）的变量仍降低了（4.9 /-1.1 pmol / 10（6）细胞与对照组的8.2 /-0.9 pmol / 10（6）细胞相比（P <0.05）。在两次调查中，患者和对照组之间的β2肾上腺素受体密度没有显着差异。

结论：特应性季节性鼻结膜炎与PBL beta2肾上腺素受体/ cAMP系统的各种改变有关取决于疾病的活动。可逆的β2肾上腺素受体亚敏感性可能是该疾病的结果，而基础细胞内cAMP含量不可逆地降低，提示PDE活性升高，可能是特应性的基本特征。