BACKGROUND & AIMS: OBJECTIVE:To determine the possibility that T cells represent a potential target for therapy in AA amyloidosis. METHODS:AA amyloidosis was induced in C3H/HeN mice by concomitant administration of AgNO3 and amyloid-enhancing factor (AEF). Mice injected with AgNO3 and AEF received intraperitoneal injections of FK506 (2-200 microg/day). The degree of splenic amyloid deposition was determined by Congo red staining. Serum amyloid A (SAA), interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-a concentrations were measured by ELISA. AA amyloidosis was also induced in ICR mice by injection of Freund's complete adjuvant (FCA) and Mycobacterium butyricum without AEF. ICR mice injected with FCA and M. butyricum also received intraperitoneal injections of FK506 (200 microg/day) to eliminate the possibility that FK506 action might depend upon AEF activity in the amyloid formation. Amyloid deposition was also induced with and without AEF in severe combined immunodeficient (SCID) mice and nude mice to clarify the role of T cells in the mechanism of amyloid formation in AA amyloidosis. RESULTS:FK506 treatment significantly reduced the amount of amyloid deposition and incidence of amyloidosis without reducing serum SAA and proinflammatory cytokine levels in the murine AA amyloidosis models with and without AEF. SCID mice and nude mice showed resistance to development of AA amyloidosis. CONCLUSION:Our findings may provide a new therapeutic strategy for amyloidosis. The results suggested that T cells may play an important role in the mechanism of amyloid formation in AA amyloidosis.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Rhinosporidiosis, a fungal infection due to Rhinosporidium seeberi, frequently produces polypoidal lesions in the nose. Sites like the conjunctiva, larynx, trachea, nasopharynx, skin and genitourinary tract are less frequently involved. Generalized rhinosporidiosis with skin and visceral involvement is extremely rare. This report describes the fine needle aspiration cytology (FNAC) of rhinosporidiosis occurring as a solitary lesion with erosion of cortical bone.

CASE REPORT:FNAC of a soft tissue swelling overlying a lytic lesion on the anterior aspect of the tibia was performed in a 40-year-old male. Smears revealed numerous sporangia and spores of R seeberi. There were no mucocutaneous lesions. Histologic examination confirmed the bony involvement.

CONCLUSION:The FNAC diagnosis of rhinosporidiosis is specific. Preoperative diagnosis is possible even in cases with unusual clinical presentations.

背景与目标： 背景 : 鼻孢子虫病是由seeberi鼻孢子虫引起的真菌感染，经常在鼻子中产生息肉样病变。结膜，喉，气管，鼻咽部，皮肤和泌尿生殖道等部位较少受累。皮肤和内脏受累的全身性鼻孢子虫病极为罕见。本报告描述了鼻孢子虫病的细针穿刺细胞学检查 (FNAC)，该检查是孤立的皮质骨侵蚀病变。
病例报告 : 在40岁的男性中，对胫骨前部的溶解性病变进行了软组织肿胀的FNAC。涂片显示出许多孢子囊和R seeberi的孢子。没有皮肤粘膜病变。组织学检查证实了骨受累。
结论 : 鼻孢子虫病的FNAC诊断是特异性的。即使在临床表现异常的情况下，也可以进行术前诊断。

BACKGROUND & AIMS: OBJECTIVE:To compare magnetic resonance imaging-derived right ventricular (RV) dimensions and function between men with type 2 diabetes and healthy subjects, and to relate these parameters to left ventricular (LV) dimensions and function. RESEARCH DESIGN AND METHODS:RV and LV volumes and functions were assessed in 78 men with uncomplicated type 2 diabetes and 28 healthy men within the same range of age using magnetic resonance imaging. Steady-state free precession sequences were used to assess ventricular dimensions. Flow velocity mapping across the pulmonary valve and tricuspid valve was used to assess RV outflow and diastolic filling patterns, respectively. Univariate general linear models were used for statistical analyses. RESULTS:RV end-diastolic volume was significantly decreased in patients compared with healthy subjects after adjustment for BMI and pulse pressure (177 ± 28 mL vs. 197 ± 47 mL, P < 0.01). RV systolic function was impaired: peak ejection rate across the pulmonary valve was decreased (433 ± 54 mL/s vs. 463 ± 71 mL/s, P < 0.01) and pulmonary flow acceleration time was longer (124 ± 17 ms vs. 115 ± 25 ms, P < 0.05). Indexes of RV diastolic function were impaired: peak filling rate and peak deceleration gradient of the early filling phase were 315 ± 63 mL/s vs. 356 ± 90 mL/s (P < 0.01) and 2.3 ± 0.8 mL/s(2) × 10(-3) vs. 2.8 ± 0.8 mL/s(2) × 10(-3) (P < 0.01), respectively. All RV parameters were strongly associated with its corresponding LV parameter (P < 0.001). CONCLUSIONS:Diabetic cardiomyopathy affects the right ventricle, as demonstrated by RV remodeling and impaired systolic and diastolic functions in men with type 2 diabetes, in a similar manner as changes in LV dimensions and functions. These observations suggest that RV impairment might be a component of the diabetic cardiomyopathy phenotype.

背景与目标：

BACKGROUND & AIMS: :Epidemiologic studies have reported the association between fine particles (aerodynamic diameter ≤ 2.5 μm; PM2.5) and health effects, but the immunological mechanisms are not clear. To investigate the dose and time-dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and systemic inflammation induced by PM2.5, mice were subjected to intratracheal instillation of 2.5, 5, or 10 mg/kg PM2.5 in this study. After 24 h, 72 h, 7 days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral blood. Histopathological changes in lung were also examined. Inflammatory infiltration and macrophages with engulfed particles were found by lung histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but increased in blood at 24 h after the exposure. The low percentage of TLR4 positive cells continued to day 14 in BALF, but recovered at day 7 and decreased further to lower than the control value at day 14 in blood. TLR2 positive cell changed similar to TLR4 in BALF on the dose effects. In BALF at 24 h after the exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently; and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased. These results suggest that acute exposure of PM2.5 leads to acute inflammatory responses locally and systemically in mice. TLR2 and TLR4 are involved in this process and PM2.5 can drive a Th2-biased immune response.

背景与目标： 流行病学研究报道了细颗粒 (空气动力学直径 ≤ 2.5微米; PM2.5) 与健康影响之间的关联，但免疫学机制尚不清楚。为了研究toll样受体 (TLR) 和Th1/Th2转移在PM2.5诱导的局部和全身炎症中的剂量和时间依赖性作用，本研究对小鼠进行气管内滴注2.5、5或10  mg/kg PM2.5。分别于24  h、72  h、7 d、14 d处死小鼠，检测支气管肺泡灌洗液 (BALF) 和外周血中TLR2、TLR4的表达及Th1/Th2相关细胞因子。还检查了肺的组织病理学变化。PM2.5暴露后，通过肺组织病理学发现炎症浸润和巨噬细胞被吞噬的颗粒。暴露后24小时，BALF中TLR4阳性细胞减少，但血液中TLR4阳性细胞增加。BALF中TLR4阳性细胞的低百分比持续到第14天，但在第7天恢复，并进一步下降至低于血液中第14天的对照值。TLR2阳性细胞改变与TLR4在BALF上的剂量效应相似。在暴露后24小时的BALF中，Th2相关细胞因子的IL-5和IL-10呈剂量依赖性增加; 在血液中，Th2相关细胞因子的IL-4，IL-5和IL-10也增加。这些结果表明，PM2.5的急性暴露会导致小鼠局部和全身急性炎症反应。TLR2和TLR4参与了这一过程，PM2.5可以驱动Th2-biased的免疫反应。

BACKGROUND & AIMS: :Intensive agricultural practices and current western consumption patterns are associated with increased ecological pressure. One way to reduce the ecological impact could be a shift to more sustainable food choices. This study investigates consumer opinions towards a series of food choices with a lower ecological impact. The investigated food choices range from well-known meat substitutes to alternatives which are more radical or innovative and that require an adaptation of food habits and cultural patterns. Results are obtained through a survey among 221 Flemish respondents in Spring 2011. Many consumers underestimate the ecological impact of animal production. Well-known alternatives such as organic meat, moderation of meat consumption and sustainable fish are accepted, although willingness to pay is clearly lower than willingness to consume. Consumers are more reluctant to alternatives that (partly) ban or replace meat in the meal. Opportunities of introducing insects currently appear to be non-existent. Five consumer segments were identified based on self-evaluated ecological footprint and personal relevance of the ecological footprint. The segments were termed Conscious, Active, Unwilling, Ignorant and Uncertain. A profile in terms of demographics, attitudinal and behavioral characteristics is developed for each segments, and conclusions with respect to opportunities for sustainable food choices are discussed.

背景与目标： : 集约化农业实践和当前的西方消费模式与生态压力增加有关。减少生态影响的一种方法可能是转向更可持续的食物选择。这项研究调查了消费者对一系列生态影响较低的食物选择的看法。所调查的食物选择范围从著名的肉类替代品到更激进或创新的替代品，需要适应饮食习惯和文化模式。结果是通过对2011年春季的221名佛兰德受访者的调查获得的。许多消费者低估了动物生产对生态的影响。众所周知的替代品，例如有机肉，适度的肉类消费和可持续的鱼类被接受，尽管支付意愿明显低于消费意愿。消费者更不愿选择 (部分) 禁止或替换餐食中的肉类的替代品。目前似乎不存在引入昆虫的机会。根据自我评估的生态足迹和生态足迹的个人相关性，确定了五个消费者细分市场。这些部分被称为有意识的，积极的，不愿意的，无知的和不确定的。针对每个细分市场制定了人口统计，态度和行为特征的概况，并讨论了有关可持续食物选择机会的结论。

BACKGROUND & AIMS: :Chronic stress in rats has been shown to impair learning and memory, and precipitate several affective disorders like depression and anxiety. The mechanisms involved in these stress-induced disorders and the possible reversal are poorly understood, thus limiting the number of drugs available for their treatment. Our earlier studies suggest cholinergic dysfunction as the underlying cause in the behavioral deficits following stress. Muscarinic cholinergic agonist, oxotremorine is demonstrated to have a beneficial effect in reversing brain injury-induced behavioral dysfunction. In this study, we have evaluated the effect of oxotremorine treatment on chronic restraint stress-induced cognitive deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed by oxotremorine treatment for 10 days. Spatial learning and memory was assessed in a partially baited eight-arm radial maze task. Stressed rats exhibited impairment in performance, with decreased percentage of correct choices and an increase in the number of reference memory errors (RMEs). Oxotremorine treatment (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in the percent correct choices and a decrease in the number of RMEs compared with stress as well as the stress+vehicle-treated groups. In the retention test, oxotremorine treated rats committed less RMEs compared with the stress group. Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the hippocampus, frontal cortex and septum, which was reversed by both the doses of oxotremorine. Further, oxotremorine treatment also restored the norepinephrine levels in the hippocampus and frontal cortex. Thus, this study demonstrates the potential of cholinergic muscarinic agonists and the involvement of both cholinergic and noradrenergic systems in the reversal of stress-induced learning and memory deficits.

背景与目标： : 大鼠的慢性压力已被证明会损害学习和记忆，并引发几种情感障碍，如抑郁和焦虑。对这些应激引起的疾病的机制和可能的逆转知之甚少，因此限制了可用于治疗的药物数量。我们早期的研究表明，胆碱能功能障碍是压力后行为缺陷的根本原因。毒蕈碱胆碱能激动剂氧代吗啡被证明在逆转脑损伤引起的行为功能障碍方面具有有益作用。在这项研究中，我们评估了氧代吗啡治疗对慢性束缚应激引起的认知缺陷的影响。对大鼠进行约束应激 (6 h/天) 21天，然后进行氧代雷丁治疗10天。在部分诱饵的八臂径向迷宫任务中评估了空间学习和记忆。应激大鼠的表现受损，正确选择的百分比降低，参考记忆错误 (rme) 的数量增加。与应激以及应激 + 媒介物处理组相比，对应激大鼠进行氧代雷丁处理 (0.1或0.2 mg/kg，i.p.) 导致正确选择百分比显着增加，rme数量减少。在保留试验中，与应激组相比，氧代雷莫林处理的大鼠产生的RMEs较少。慢性束缚应激降低了海马，额叶皮层和隔膜中的乙酰胆碱酯酶 (AChE) 活性，这两种剂量的氧代雷莫林都可以逆转。此外，氧代吗啡治疗还恢复了海马和额叶皮层中的去甲肾上腺素水平。因此，这项研究证明了胆碱能毒蕈碱激动剂的潜力，以及胆碱能和去甲肾上腺素能系统参与逆转应激诱导的学习和记忆缺陷。

BACKGROUND & AIMS: :The soya-derived phytoestrogen genistein has been suggested to be protective in cardiovascular diseases. In the present study, we have analysed whether chronic oral genistein might influence endothelial function in male SHRs (spontaneously hypertensive rats) via ERs (oestrogen receptors), changes in eNOS (endothelial NO synthase) activity and vascular O(2)(-) (superoxide) production. Rats (23-weeks old) were divided into the following groups: WKY (Wistar-Kyoto)-vehicle, SHR-vehicle, WKY-genistein (10 mg.kg(-1) of body weight.day(-1)); SHR-genistein; SHR-genistein-faslodex (ICI 182780; 2.5 mg.kg(-1) of body weight.day(-1)). Vascular expression of eNOS, caveolin-1 and calmodulin-1 were analysed by Western blotting, eNOS activity by conversion of [(3)H]arginine into L-[(3)H]citrulline and O(2)(-) production by chemoluminescence of lucigenin. In SHRs, after 5 weeks of treatment, genistein reduced systolic blood pressure and enhanced endothelium-dependent aortic relaxation to acetylcholine, but had no effect on the vasodilator responses to sodium nitroprusside. Compared with WKY rats, SHRs had up-regulated eNOS and down-regulated caveolin-1 and calmodulin-1 expression, increased NADPH-induced O(2)(-) production, but reduced eNOS activity. Genistein increased aortic calmodulin-1 protein abundance and eNOS activity, and reduced NADPH-induced O(2)(-) production in SHRs. The pure ERalpha and ERbeta antagonist faslodex did not modify any of the changes induced by genistein in SHRs, suggesting that these effects are unrelated to ER stimulation. In conclusion, genistein reduced the elevated blood pressure and endothelial dysfunction in SHRs. This latter effect appears to be related to increased eNOS activity associated with increased calmodulin-1 expression and decreased O(2)(-) generation.

背景与目标： : 大豆衍生的植物雌激素染料木黄酮被认为对心血管疾病具有保护作用。在本研究中，我们分析了慢性口服染料木黄酮是否可能通过ERs (雌激素受体)，eNOS (内皮NO合酶) 活性的变化和血管O(2)(-) 影响雄性shr (自发性高血压大鼠) 的内皮功能 (超氧化物) 产生。将大鼠 (23周龄) 分为以下组: WKY (Wistar-Kyoto)-载体，SHR-载体，WKY-染料木黄酮 (10 mg.kg(-1) 体重)。天 (-1)); SHR-染料木黄酮; SHR-genistein-faslodex (ICI 182780; 体重2.5 mg.kg(-1) 天 (-1))。通过蛋白质印迹法分析eNOS，caveolin-1和calmodulin-1的血管表达，通过将 [(3)H] 精氨酸转化为L-[(3)H] 瓜氨酸和通过荧光素的化学发光产生O(2)(-) 的eNOS活性。在shr中，治疗5周后，金雀异黄素降低了收缩压，增强了内皮依赖性主动脉对乙酰胆碱的舒张作用，但对硝普钠的血管舒张反应没有影响。与WKY大鼠相比，SHRs上调了eNOS，下调了caveolin-1和calmodulin-1表达，增加了NADPH诱导的O(2)(-) 产生，但降低了eNOS活性。染料木黄酮增加了主动脉calmodulin-1蛋白丰度和eNOS活性，并降低了NADPH诱导的shr中O(2)(-) 的产生。纯的ERalpha和ERbeta拮抗剂faslodex没有改变由染料木黄酮在shr中诱导的任何变化，提示这些作用与ER刺激无关。总之，染料木黄酮降低了shr的血压升高和内皮功能障碍。后一种作用似乎与与calmodulin-1表达增加和O(2)(-) 生成减少相关的eNOS活性增加有关。

BACKGROUND & AIMS: :7-hydroxymitragynine, a constituent of the Thai herbal medicine Mitragyna speciosa, has been found to have a potent opioid antinociceptive effect. In the present study, we investigated the mechanism of antinociception and the inhibitory effect on gastrointestinal transit of 7-hydroxymitragynine, and compared its effects with those of morphine. When administered subcutaneously to mice, 7-hydroxymitragynine produced antinociceptive effects about 5.7 and 4.4 times more potent than those of morphine in the tail-flick (ED50=0.80 mg/kg) and hot-plate (ED50=0.93 mg/kg) tests, respectively. The antinociceptive effect of 7-hydroxymitragynine was significantly blocked by the mu1/mu2-opioid receptor antagonist beta-funaltrexamine hydrochloride (beta-FNA) and the mu1-opioid receptor-selective antagonist naloxonazine in both tests. Thus, 7-hydroxymitragynine acts predominantly on mu-opioid receptors, especially on mu1-opioid receptors. Isolated tissue studies further supported its specificity for the mu-opioid receptors. Further, 7-hydroxymintragynine dose-dependently (ED50=1.19 mg/kg, s.c.) and significantly inhibited gastrointestinal transit in mice, as morphine does. The inhibitory effect was significantly antagonized by beta-FNA pretreatment, but slightly antagonized by naloxonazine. The ED50 value of 7-hydroxymitragynine on gastrointestinal transit was larger than its antinociceptive ED50 value. On the other hand, morphine significantly inhibits gastrointestinal transit at a much smaller dose than its antinociceptive dose. These results suggest that mu-opioid receptor mechanisms mediate the antinociceptive effect and inhibition of gastrointestinal transit. This compound induced more potent antinociceptive effects and was less constipating than morphine.

背景与目标： : 7-hydroxyymyramynine，泰国草药mitramyna speciosa的一种成分，已被发现具有有效的阿片类药物抗伤害作用。在本研究中，我们研究了7-羟基雌米雌酮的抗伤害感受机制和对胃肠道转运的抑制作用，并将其与吗啡的作用进行了比较。当皮下给药小鼠时，在甩尾 (ED50 = 0.80 mg/kg) 和热板 (ED50 = 0.93 mg/kg) 测试中，7-羟基肌酸产生的抗伤害感受作用比吗啡的作用强约5.7和4.4倍。在两次测试中，mu1/mu2-opioid受体拮抗剂 β-氟曲胺盐酸盐 (β-FNA) 和mu1-opioid受体选择性拮抗剂纳洛酮嗪均显着阻断了7-羟基酪氨酸的抗伤害感受作用。因此，7-羟甲基主要作用于 μ-阿片受体，尤其是mu1-opioid受体。孤立的组织研究进一步支持了其对 μ 阿片受体的特异性。此外，7-羟基喹啉呈剂量依赖性 (ED50 = 1.19 mg/kg，s.C.)，并显著抑制小鼠的胃肠转运，如吗啡。Β-FNA预处理可显着拮抗抑制作用，但纳洛酮嗪可轻微拮抗。7-羟基雌杆菌在胃肠道运输中的ED50值大于其抗伤害感受ED50值。另一方面，吗啡以比其抗伤害感受剂量小得多的剂量显着抑制胃肠道转运。这些结果表明，μ 阿片受体机制介导了抗伤害感受作用和抑制胃肠道转运。与吗啡相比，该化合物可产生更有效的抗伤害感受作用，并且便秘更少。

BACKGROUND & AIMS: BACKGROUND:The reasons for low adherence to cereal dietary guidelines are not well understood but may be related to knowledge, attitudes, beliefs and perceived barriers. This study aims to assess trends in cereal foods consumption, intention to change and factors associated with intake among Western Australian (WA) adults 18 to 64 years. METHOD:Cross-sectional data from the 1995, 1998, 2001, 2004, 2009, and 2012 Nutrition Monitoring Survey Series involving 7044 adults were pooled. OUTCOME VARIABLES:types and amount of cereals (bread, rice, pasta, and breakfast cereal) eaten the day prior. Attitudes, knowledge, intentions, weight status and sociodemographic characteristics were measured. Descriptive statistics, multiple binary logistic and multinomial logistic regressions assess factors associated with consumption. RESULTS:Bread (78%) was the most commonly consumed cereal food. The proportion eating bread decreased across survey years (Odds Ratio OR = 0.31; 95% Confidence Interval; 0.24-0.40 in 2012 versus 1995), as did the amount (4.1 slices of bread in 1995 to 2.4 in 2012). The odds of consuming whole-grain cereal foods increased since 2009 (OR = 1.27; 1.02-1.58 versus 1995 p < 0.05). The likelihood of trying to eat less cereal food in the past year was greater in 2012 compared to 1995 (Relative Risk Ratio RRR 10.88; 6.81-17.4). Knowledge of cereal recommendations decreased over time (OR = 0.20; 0.15-0.27 in 2012 versus 1995 p < 0.001). Overweight and obese respondents were more likely than healthy weight respondents to have tried to eat less cereals (RRR 1.65; 1.22-2.24 and 1.88; 1.35-2.63 respectively). 'I already eat enough' was the main barrier (75% in 1995 to 84% in 2012 (p < 0.001)). CONCLUSIONS:WA adults are actively reducing the amount of cereal foods they eat and intake is associated with a misperception of adequacy of intake. Nutrition intervention is needed to increase awareness of the health benefits of cereal foods, particularly whole-grains, and to address barriers to incorporating them daily. TRIAL REGISTRATION:Not applicable.

背景与目标：

BACKGROUND & AIMS: :HSP90 is a molecular chaperone that participates in folding, stabilization, activation, and assembly of several proteins, all of which are key regulators in cell signaling. In dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, the adaptation to a higher temperature, acid pH and oxidative stress, is an essential event for fungal survival and also for the establishing of the infectious process. To further understand the role of this protein, we used antisense RNA technology to generate a P. brasiliensis isolate with reduced PbHSP90 gene expression (PbHSP90-aRNA). Reduced expression of HSP90 decreased yeast cell viability during batch culture growth and increased susceptibility to acid pH environments and imposed oxidative stress. Also, PbHSP90-aRNA yeast cells presented reduced viability upon interaction with macrophages. The findings presented here suggest a protective role for HSP90 during adaptation to hostile environments, one that promotes survival of the fungus during host-pathogen interactions.

背景与目标： : HSP90是一种分子伴侣，参与多种蛋白质的折叠，稳定，激活和组装，所有这些蛋白质都是细胞信号传导的关键调节剂。在双态致病性真菌 (例如巴西Paracoccidioides brasiliensis) 中，适应较高的温度，酸性pH和氧化应激是真菌存活以及建立感染过程的重要事件。为了进一步了解该蛋白的作用，我们使用反义RNA技术生成了具有降低PbHSP90基因表达 (PbHSP90-aRNA) 的巴西假单胞菌分离株。HSP90的表达降低了分批培养过程中酵母细胞的活力，并增加了对酸性pH环境的敏感性并施加了氧化应激。此外，PbHSP90-aRNA酵母细胞在与巨噬细胞相互作用时表现出降低的活力。此处提出的发现表明，HSP90在适应敌对环境期间具有保护作用，在宿主-病原体相互作用期间可促进真菌的存活。

BACKGROUND & AIMS: :Coenzyme A (CoA) biosynthesis in bacteria and eukaryotes is regulated primarily by feedback inhibition towards pantothenate kinase (PanK). As most archaea utilize a modified route for CoA biosynthesis and do not harbour PanK, the mechanisms governing regulation of CoA biosynthesis are unknown. Here we performed genetic and biochemical studies on the ketopantoate reductase (KPR) from the hyperthermophilic archaeon Thermococcus kodakarensis. KPR catalyses the second step in CoA biosynthesis, the reduction of 2-oxopantoate to pantoate. Gene disruption of TK1968, whose product was 20-29% identical to previously characterized KPRs from bacteria/eukaryotes, resulted in a strain with growth defects that were complemented by addition of pantoate. The TK1968 protein (Tk-KPR) displayed reductase activity specific for 2-oxopantoate and preferred NADH as the electron donor, distinct to the bacterial/eukaryotic NADPH-dependent enzymes. Tk-KPR activity decreased dramatically in the presence of CoA and KPR activity in cell-free extracts was also inhibited by CoA. Kinetic studies indicated that CoA inhibits KPR by competing with NADH. Inhibition of ketopantoate hydroxymethyltransferase, the first enzyme of the pathway, by CoA was not observed. Our results suggest that CoA biosynthesis in T. kodakarensis is regulated by feedback inhibition of KPR, providing a feasible regulation mechanism of CoA biosynthesis in archaea.

背景与目标： : 细菌和真核生物中的辅酶a (CoA) 生物合成主要通过对泛酸激酶 (PanK) 的反馈抑制来调节。由于大多数古细菌利用改良的CoA生物合成途径并且不携带PanK，因此控制CoA生物合成的机制尚不清楚。在这里，我们对来自嗜热古细菌热球菌kodakarensis的酮托酸酯还原酶 (KPR) 进行了遗传和生化研究。KPR催化CoA生物合成的第二步，即2-氧尿囊酸酯还原为泛酸酯。TK1968的基因破坏 (其产物与先前来自细菌/真核生物的KPRs 20-29% 相同) 导致了具有生长缺陷的菌株，该菌株通过添加泛酸补充。TK1968蛋白 (Tk-KPR) 显示出对2-氧尿囊酸酯具有特异性的还原酶活性，并且首选NADH作为电子供体，与细菌/真核NADPH依赖性酶不同。在CoA存在下，tk-kpr活性显着降低，无细胞提取物中的KPR活性也受到CoA的抑制。动力学研究表明，CoA通过与NADH竞争来抑制KPR。未观察到CoA对该途径的第一个酶-酮体羟甲基转移酶的抑制作用。我们的研究结果表明，科达卡氏菌CoA的生物合成受KPR的反馈抑制调节，为古菌CoA的生物合成提供了可行的调控机制。

BACKGROUND & AIMS: :The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

背景与目标： : 发作期后不动综合症之后，动物和男性的伤害性阈值显着增加。在这种有趣的发作期后行为反应中，已经提出了内源性阿片肽介导的机制以及胆碱能介导的抗伤害感受过程。然而，考虑到许多血清素能下降途径与抗伤害感受反应有关，因此本工作的目的是研究5-HT(2)-血清素能受体亚家族在发作期抗伤害感受中的参与。每组7或8只Wistar大鼠通过甩尾试验测量镇痛效果。抽搐后，至少在发作后的120分钟内，甩尾潜伏期 (TFL) 具有统计学上的显着增加。雄性Wistar大鼠接受立体定向手术，以在菱形脑中引入引导套管，以瞄准中缝大核 (NRM) 或千兆体复合体。在独立的动物组中，这些核通过单侧微量注射ibotenic酸 (1.0 microg/0.2 microL) 被神经化学损伤。NRM或网状核巨囊细胞/旁囊细胞复合物的神经元损伤降低了发作后的镇痛作用。同样，在其他独立组中，在研究的所有发作期后，与对照组相比，将利坦色林 (5.0 microg/0.2 microL) 或生理盐水集中施用到每个研究的网状形成核中，引起抓住动物的TFL在统计学上显着降低。这些结果表明，脑桥和延髓网状核的5-羟色胺输入连接的神经元可能参与了发作期后的镇痛。

BACKGROUND & AIMS: :To elucidate the mechanism of palytoxin (PTX)-induced Na+ influx, we examined the effect of amiloride, an inhibitor of Na+/H(+)-antiporter, on PTX-induced Na+ influx into cultured bovine adrenal chromaffin cells in relation to its effects on Ca2+ influx and catecholamine secretion. Amiloride dose-dependently inhibited PTX-induced 22Na+ influx, whereas tetrodotoxin (TTX) had no effect. Amiloride also inhibited PTX-induced Na(+)-dependent 45Ca2+ influx and catecholamine secretion. PTX alone did not significantly affect the intracellular pH, but it decreased in the presence of PTX and amiloride. These results indicate that an amiloride-sensitive Na+/H+ exchange mechanism is probably involved in PTX-induced, TTX-insensitive Na+ influx that triggers Ca2+ influx and catecholamine secretion from the cells.

背景与目标： : 为了阐明palytoxin (PTX) 诱导的Na内流的机制，我们研究了Na/H ()-反转运蛋白抑制剂阿米洛利的作用，关于PTX诱导的Na流入培养的牛肾上腺嗜铬细胞及其对Ca2流入和儿茶酚胺分泌的影响。阿米洛利剂量依赖性地抑制PTX诱导的22Na内流，而河豚毒素 (TTX) 没有作用。阿米洛利还抑制PTX诱导的Na () 依赖性45Ca2内流和儿茶酚胺分泌。单独的PTX不会显着影响细胞内pH，但在PTX和阿米洛利存在下会降低。这些结果表明，对阿米洛利敏感的Na/H交换机制可能参与PTX诱导的，对TTX不敏感的Na内流，从而触发细胞中Ca2内流和儿茶酚胺分泌。

BACKGROUND & AIMS: AIMS:To identify the causative agent of the mortality in the fish, Mugil cephalus, in Muttukadu lagoon. METHODS AND RESULTS:An enteric bacterium from the kidneys of moribund fish M. cephalus, was isolated and identified as Enterobacter cloacae (MK). Mugil cephalus was experimentally infected by this isolate and was re-isolated from the kidneys of the moribund fish. Enterobacter cloacae isolates from the lagoon water (MW1, MW2 and reference strain ATCC 13047) and the reference strain were not able to induce similar pathogenesis. The putative factor imparting pathogenicity to the MK isolate was identified as a cationic molecule, which migrated towards the cathode on agarose gel electrophoresis. CONCLUSIONS:The Ent. cloacae (MK) isolate harbouring a cationic factor was the causative agent for the mortality of M. cephalus, found in Muttukadu lagoon. SIGNIFICANCE AND IMPACT OF THE STUDY:This study reveals that human enteric bacteria MK which is considered as nonpathogenic to fish, may become pathogenic to fish when it harbours this cationic factor. This cationic factor is found to be pathogenic to the fish M. cephalus leading to mortality. It was also found to be pathogenic to mice. Therefore, the shuttling of Ent. cloacae, harbouring cationic factor, between human and fish may be of human health importance.

背景与目标：

BACKGROUND & AIMS: STUDY QUESTION:What was the impact on access to assisted reproductive technology (ART) treatment by different socioeconomic status (SES) groups after the introduction of a policy that increased patient out-of-pocket costs? SUMMARY ANSWER:After the introduction of a policy that increased out-of-pocket costs in Australia, all SES groups experienced a similar percentage reduction in fresh ART cycles per 1000 women of reproductive age. Higher SES groups experienced a progressively greater reduction in absolute numbers of fresh ART cycles due to existing higher levels of utilization. WHAT IS KNOWN ALREADY:Australia has supportive public funding arrangements for ARTs. Policies that substantially increase out-of-pocket costs for ART treatment create financial barriers to access and an overall reduction in utilization. Data from the USA suggests that disparities exist in access to ART treatment based on ethnicity, education level and income. STUDY DESIGN, SIZE, DURATION:Time series analysis of utilization of ART, intrauterine insemination (IUI) and clomiphene citrate by women from varying SES groups before and after the introduction of a change in the level of public funding for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS:Women undertaking fertility treatment in Australia between 2007 and 2010. MAIN RESULTS AND THE ROLE OF CHANCE:Women from higher SES quintiles use more ART treatment than those in lower SES quintiles, which likely reflects a greater ability to pay for treatment and a greater need for ART treatment as indicated by the trend to later childbearing. In 2009, 10.13 and 5.17 fresh ART cycles per 1000 women of reproductive age were performed in women in the highest and lowest SES quintiles respectively. In the 12 months after the introduction of a policy that increased out-of-pocket costs from ∼$1500 Australian dollars (€1000) to ∼$2500 (€1670) for a fresh IVF cycle, there was a 21-25% reduction in fresh ART cycles across all SES quintiles. The absolute reduction in fresh ART cycles in the highest SES quintile was double that in the lowest SES quintile. LIMITATIONS, REASONS FOR CAUTION:In this study, SES was based on the average relative socioeconomic advantage and disadvantage of small geographic areas, and therefore may not reflect the SES of an individual. Additionally, the policy impact was limited to the 12 months following its introduction, and may not reflect longer term trends in ART treatment. WIDER IMPLICATIONS OF THE FINDINGS:While financial barriers are an important obstacle to equitable access to ARTs, socioeconomic differences in utilization are likely to persist in countries with supportive public funding, due in part to differences in childbearing patterns and treatment seeking behaviour. Policy makers should be informed of the impact that changes in the level of cost subsidization have on access to ART treatment by different socioeconomic groups. STUDY FUNDING/COMPETING INTEREST(S):G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. P.J.I. is Medical Director of the IVF Clinic, IVFAustralia and has a financial interest in the parent group, Virtus. TRIAL REGISTRATION NUMBER:N/A.

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