BACKGROUND & AIMS: :Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

背景与目标： ：口腔癌是一种具有某些已知原因的肿瘤。增生基因在其少数致病和预后因素中很重要。钙环蛋白是与细胞周期相关的基因，其功能尚不清楚。为了评估它们在鳞状细胞癌中的致病作用，已经研究了它的表达以及Haras和组蛋白H3的表达。从鳞状细胞癌（SCC）和良性病变的病理和正常粘膜中提取的RNA通过聚合酶链反应（PCR）进行逆转录和扩增。仅在SCC中，病理黏膜中所有三个基因的表达均得到增强。这表明它们可能参与其发病机理，并为区分恶性和良性病变提供了另一个参数。

BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

背景与目标： 将含有茶碱，乙酸钙和微晶纤维素的球形小球挤出并滚圆，然后通过界面复合将六种不同的果胶或藻酸盐包被。这项研究的目的是发现包衣对物理机械性能的影响，这对于确定微丸作为缓释系统的用途至关重要。在核心药丸周围形成了不溶的，光滑且均匀厚的钙多糖涂层。设计了析因实验，以研究颗粒大小，多糖类型和浓度对包封效率，机械性能和其他物理特性的影响。通过扫描电子显微镜观察包衣的小丸，并且根据所使用的特定多糖，发现干衣的厚度为30-80微米。药丸的大小，多糖的类型和浓度影响了包衣药丸中茶碱的产量。尽管通过施加任何凝胶包衣可以改善粒料的机械性能，但是使用具有高含量古洛糖醛酸的藻酸盐或酰胺化果胶包衣的效果最佳。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。

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），这一发现以前未见报道。 。
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: :Immunocompromise after a major injury is presumed to be a predisposing factor for sepsis. Mice subjected to sublethal cecal ligation and puncture (CLP) and challenged 5 days later with Pseudomonas aeruginosa had more bacterial growth in lung tissue, lower serum interferon gamma (IFN-gamma) and interleukin (IL) 12,and higher serum IL-10 when compared with sham CLP mice challenged with Pseudomonas. To test the functional significance of these alterations in cytokine production in the immune response to bacteria, we administered IFN-gamma and anti-IL-10 to post-CLP mice before the Pseudomonas challenge. Administration of IFN-gamma and anti-IL-10 did not improve bacterial clearance or mortality in post-CLP mice. In further studies, we administered IFN-gamma to IL-10 knockout mice before a challenge with P. aeruginosa. Our results showed no significant differences in bacterial clearance or mortality in IL-10 knockout mice with or without IFN-gamma treatment compared with wild-type controls. Finally, because most mortality occurred within 2 to 3 days of the Pseudomonas challenge in the aforementioned studies and was likely associated with a marked proinflammatory response, we investigated the effect of IFN-gamma and anti-IL-10 on clearance of Pseudomonas in C3H/HeJ mice, which do not mount an exaggerated proinflammatory response to endotoxin or Gram-negative bacteria. Neither clearance of the Pseudomonas bacteria nor mortality was improved in C3H/HeJ mice receiving anti-IL-10 and IFN-gamma. These results suggest that the suppressed IFN-gamma and IL-12 responses, in combination with an exaggerated IL-10 response to P. aeruginosa challenge after injury, do not correlate with bacterial clearance or survival.

背景与目标： ：大伤后的免疫功能低下被认为是败血症的诱因。进行半致死盲肠结扎和穿刺（CLP）并在5天后用铜绿假单胞菌攻击的小鼠的肺组织中细菌生长更多，血清干扰素-γ（IFN-γ）和白介素（IL）12更低，而血清IL-10更高与假单胞菌攻击的假CLP小鼠相比。为了测试这些变化对细菌免疫反应中细胞因子产生的功能意义，我们在假单胞菌攻击之前向CLP后小鼠施用了IFN-γ和抗IL-10。在CLP后小鼠中，IFN-γ和抗IL-10的使用不能改善细菌清除率或死亡率。在进一步的研究中，我们在铜绿假单胞菌攻击之前向IL-10敲除小鼠施用了IFN-γ。我们的结果表明，与野生型对照相比，接受或未接受IFN-γ治疗的IL-10基因敲除小鼠的细菌清除率或死亡率无显着差异。最后，由于在上述研究中大多数死亡发生在假单胞菌攻击后的2至3天内，并且可能与明显的促炎反应有关，因此我们研究了IFN-γ和抗IL-10对C3H / P3中假单胞菌清除的影响HeJ小鼠，对内毒素或革兰氏阴性细菌没有过度的促炎反应。接受抗IL-10和IFN-γ的C3H / HeJ小鼠的假单胞菌细菌清除率和死亡率均未提高。这些结果表明，损伤后抑制的IFN-γ和IL-12反应，加上对损伤后铜绿假单胞菌攻击的过大IL-10反应，与细菌清除率或存活率无关。

BACKGROUND & AIMS: Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

背景与目标： 依托泊苷产生对拓扑异构酶II的可逆抑制，导致DNA裂解，因此具有抗肿瘤作用。该机制表明持续的治疗时间越长，抗肿瘤作用越大。在本研究中，对29岁年龄≥65岁的非霍奇金淋巴瘤（NHL）患者进行了长期低剂量口服依托泊苷的治疗，并对其不良反应进行了研究，这些患者对于标准化疗均无效或难治。这些患者尽可能长时间接受依托泊苷50 mg / d的剂量。继续治疗直至白细胞计数降低至<或= 2,000 / microL或血小板计数降低至<或= 5 x 10（4）/ microL。根据世界卫生组织（WHO）的疗效标准，在29例患者中有6例（20.7％）完全缓解，13例（44.8％）部分缓解，缓解率为65.5％。 ≥3级的不良反应包括24例白细胞减少症（82.8％）和7例贫血（24.1％）。由于白细胞减少症（粒细胞计数<或= 1,000 / microL），与依托泊苷联合给予了粒细胞集落刺激因子（G-CSF）与依托泊苷。鉴于出色的主观耐受性，严重不良反应的发生率低和良好的活动性，长时间连续给予单剂口服依托泊苷代表了对老年NHL患者的一种有效治疗方法。

BACKGROUND & AIMS: High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion, but drugs with extramedullary dose-limiting toxicity may be administered in the high-dose range by simple growth factor support. In this study, we evaluated the feasibility and toxicity of a three-drug high-dose regimen supported by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients with histologically proven malignancy were enrolled. Eight had breast cancer, one non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG-CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of chemotherapy). The cycle was repeated as clinically needed up to three times. After the first course, hematologic recovery was rapid and complete without documented infections, and no relevant extramyeloid toxicities were observed. Eight of 10 patients received a second course with comparably low toxicity, and three of them received a third course. We concluded that CEP therapy can be administered safely and even repeatedly, by simple growth factor support, in good performance status cancer patients.

背景与目标： 大剂量化学疗法通常需要重新注入造血祖细胞，但是可以通过简单的生长因子支持在大剂量范围内使用具有髓外剂量限制性毒性的药物。在这项研究中，我们评估了重组人粒细胞集落刺激因子（rhG-CSF）支持的三药大剂量方案的可行性和毒性。十名经组织学证实为恶性肿瘤的患者入选。 8例患有乳腺癌，1例非霍奇金淋巴瘤，1例起源不明的纵隔肿瘤。该方案包括环磷酰胺（C）5 g / m2，依托泊苷（E）1.5 g / m2和顺铂（P）150 mg / m2（CEP），分3天给药，随后用rhG-CSF给药，每次300微克从第5天（化疗结束后36小时）开始的一天。根据临床需要重复该循环多达三次。第一次疗程结束后，血液学恢复迅速且完全，没有记录的感染，也未观察到相关的髓外毒性。 10名患者中有8名接受了第二疗程，毒性较低，其中三名接受了第三疗程。我们得出的结论是，通过简单的生长因子支持，可以对处于良好状态的癌症患者安全，甚至重复使用CEP治疗。

BACKGROUND & AIMS: Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front.

背景与目标： 已经发现，在多种人类癌症中，处于癌症侵袭性前沿的肿瘤细胞与其余肿瘤细胞有很大的不同。目前对94例口腔鳞状细胞癌（OSCC）的多因素生存分析表明，侵袭性肿瘤细胞的嗜银性核仁组织者区域相关蛋白（AgNOR）含量和多参数组织病理学肿瘤前沿均与肿瘤相关死亡显着且独立相关，与常规Broders的肿瘤分级和临床分期无关。因此，在侵袭性OSCC前沿，较高的肿瘤前沿评分和AgNOR含量似乎反映出恶性潜能的增加。通过标准化AgNOR分析评估的增殖活性很可能代表了评估侵袭性肿瘤前沿有用性的生物学特征之一。

BACKGROUND & AIMS: OBJECTIVES:To describe the prevalence of oral diseases and their impact on oral-health-related quality of life in people with severe mental illness undertaking community-based psychiatric care. METHODS:A survey was conducted at eight outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and twelve consecutive patients with mental illness were invited to participate in this study. They were clinically examined and asked to complete the oral health impact profile (OHIP) questionnaire. RESULTS:The response rate was 79% (n = 89); 57 (64%) males and 58 persons over 45 years of age (65%) participated in this survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%) respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and 14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%) of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:Overall, this survey found that oral health has a great impact on patients with severe mental illness being treated in the community setting and their oral health is poorer than the national adult general population. Future research should consider the causes that relate to the poorer oral health in this population and potential health promotion mechanisms in this population to encourage an upstream approach to health.

背景与目标： 目的：描述在进行基于社区的精神病治疗的重度精神疾病患者中口腔疾病的流行及其对口腔健康相关生活质量的影响。
方法：在英国伦敦塔哈姆雷特市的八家门诊精神病诊所进行了一项调查。连续邀请112名精神疾病患者参加这项研究。对他们进行了临床检查，并要求他们填写口腔健康影响资料（OHIP）调查表。
结果：回应率为79％（n = 89）；男性（57％）（64％）和58岁以上的58人（65％）参加了这项调查。 OHIP总体得分为25.4（95％CI 23.3、27.4），吸烟者70（78％）和最近两年去牙医的45（51％）。 47名（53％）的被调查者的至少一颗牙齿上有龋齿； 60（67％）的人有21颗及以上的牙齿，以及14颗（16％）的假牙。 42名（55％）患者表示进行了牙周治疗，目前有疼痛的患者占52.8％（n = 47）。
结论：总体而言，该调查发现，口腔健康对在社区环境中接受治疗的严重精神疾病患者有很大影响，并且其口腔健康状况比全国成年人口人群差。未来的研究应考虑与该人群口腔健康较差的原因以及该人群中潜在的健康促进机制，以鼓励采用上游健康方法。

BACKGROUND & AIMS: :Melatonin improves survival and functional impairment including hemolysis, thrombocytopenia, and hypotension when administered in a prophylactic manner or early after initiation of sepsis or endotoxemia. In the present study, melatonin was given not before first symptoms of systemic inflammation became manifest. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose 3 mg/kg × 15 min) was intravenously administered 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic and vital parameters (e.g., systemic blood pressure and breathing rate) as well as blood and plasma parameters (acid-base parameters; electrolytes; parameters of tissue injury such as glucose concentration, lactate concentration, hemolysis, and aminotransferase activities; parameters of thromboelastometry; and platelet count) were determined in regular intervals. Infusion of lipopolysaccharide led to characteristic symptoms of severe systemic inflammation including hypotension, metabolic acidosis and hypoglycemia, electrolyte and hemostatic disturbances, thrombocytopenia, and hemolysis. Melatonin neither decreased mortality nor reduced lipopolysaccharide-dependent changes to vital, blood, and plasma parameters. Even though melatonin may have a beneficial effect in early stages of systemic inflammation, it can hardly be an option in therapy of manifest sepsis or endotoxemia in an intensive care unit.

背景与目标： 褪黑素以预防性方式或在脓毒症或内毒素血症开始后的早期给药，可改善生存和功能障碍，包括溶血，血小板减少和低血压。在本研究中，褪黑激素未在系统性炎症的最初症状显现之前就给予。以0.5 mg / kg×h的速度注入脂多糖以诱导雄性Wistar大鼠全身性炎症。开始注入脂多糖后180和270分钟静脉注射褪黑激素（单次剂量3 mg / kg×15分钟）。全身和生命参数（例如全身血压和呼吸频率）以及血液和血浆参数（酸碱参数；电解质；组织损伤参数，例如葡萄糖浓度，乳酸浓度，溶血和转氨酶活性；血栓弹力测定法参数；以及血小板计数）是定期确定的。输注脂多糖会导致严重的全身性炎症，包括低血压，代谢性酸中毒和低血糖，电解质和止血失调，血小板减少和溶血。褪黑激素既不能降低死亡率，也不能降低脂多糖依赖性的生命，血液和血浆参数变化。即使褪黑激素在全身性炎症的早期阶段可能具有有益的作用，但在重症监护病房治疗明显的败血症或内毒素血症时，它几乎不是一种选择。

BACKGROUND & AIMS: :Two-hundred and ninety-three patients without a previous vaginal delivery were randomized to intracervical/extra-amniotic application of 0.5 mg prostaglandin E2 (PGE2) or to gel only. Of the patients who received PGE2, 18.7% were admitted before the next morning due to spontaneous abortion, bleeding or pains. No other side-effect was observed. A statistically significant dilatation of the cervical canal was found in the prostaglandin group. Thirty percent of the treated patients did not need further dilatation of the cervix 25.4% were non-responders to PGE2 and 7.7% were hyper-responders. The number of uterine perforations, pelvic inflammatory disease (PID) or retained pregnancy products were not influenced by the pretreatment with PGE2.

背景与目标： ：293例以前没有阴道分娩的患者被随机分配至0.5 mg前列腺素E2（PGE2）的脑内/羊膜外给药或仅凝胶化。在接受PGE2的患者中，由于自然流产，出血或疼痛，第二天早上入院的患者为18.7％。没有观察到其他副作用。在前列腺素组中发现了颈管的统计学上显着的扩张。接受治疗的患者中有30％不需要进一步扩张子宫颈，PGE2无反应者为25.4％，高反应者为7.7％。子宫穿孔，盆腔炎（PID）或保留的妊娠产物的数量不受PGE2预处理的影响。

BACKGROUND & AIMS: :The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

背景与目标： ：已对50例与癌症相关的严重疼痛的患者评估了使用皮下植入的门禁系统连接传统的16号硬膜外导管的可行性。该技术允许以8-12小时的间隔经皮硬膜外给予吗啡以控制疼痛。平均植入时间为12周，而门户留在原位的最长时间为36周。由于各种原因，必须删除五个门户。由于导管阻塞（六次）和门静脉阻塞（两次），注射系统已发生八次阻塞。当更换导管或门静脉时，这些患者继续获得出色的镇痛效果。在尸体中，使用22号Huber点针或一次性针头（25号针头）模拟了300次注射，并通过光学和扫描电子显微镜对注射进行了检查。两种类型的针都导致微粒污染，建议的Huber点式针污染更大。

BACKGROUND & AIMS: :Oral squamous cell carcinoma (OSCC) is a growing global public health problem for which standard therapeutic strategies have failed to contribute significantly to improve the survival rates that have remained around 50% over the past three decades. Therefore, there is a pressing need for new therapeutic strategies. Curcumin is a natural dietary compound with known anti-neoplastic activities, hence its classification as a nutraceutical agent. This review presents the current in vitro and in vivo studies in which curcumin has been examined for its anti-cancer potential in treating OSCC. Its mechanisms of action are also beginning to become unveiled. The available studies have been focusing on the impact of curcumin on epithelial malignant cells, but overlooking the components of the tumor microenvironment. Curcumin has been emerging as a promising therapeutic agent in oral cancer, either alone or in combination with standard therapeutic agents, and will probably become of practical use once its route of administration has overcome its poor bioavailability.

背景与目标： ：口腔鳞状细胞癌（OSCC）是一个日益严重的全球性公共卫生问题，对于该问题，标准的治疗策略未能显着提高其存活率，在过去的三十年中，其存活率一直保持在50％左右。因此，迫切需要新的治疗策略。姜黄素是一种具有已知抗肿瘤活性的天然饮食化合物，因此被归类为营养药物。这篇综述介绍了目前的体外和体内研究，其中姜黄素已被检测出其在治疗OSCC中的抗癌潜力。其作用机制也开始被揭示。现有的研究集中在姜黄素对上皮恶性细胞的影响上，但忽略了肿瘤微环境的组成部分。姜黄素已经单独或与标准治疗剂结合起来成为口腔癌中有希望的治疗剂，一旦其给药途径克服了其不良的生物利用度，姜黄素可能会变得实用。

BACKGROUND & AIMS: UNLABELLED:Endothelial dysfunction drives vascular derangement and organ failure associated with sepsis. However, the consequences of sepsis on liver sinusoidal endothelial function are largely unknown. Statins might improve microvascular dysfunction in sepsis. The present study explores liver vascular abnormalities and the effects of statins in a rat model of endotoxemia. For this purpose, lipopolysaccharide (LPS) or saline was given to: (1) rats treated with placebo; (2) rats treated with simvastatin (25 mg/kg, orally), given at 3 and 23 hours after LPS/saline challenge; (3) rats treated with simvastatin (25 mg/kg/24 h, orally) from 3 days before LPS/saline injection. Livers were isolated and perfused and sinusoidal endothelial function was explored by testing the vasodilation of the liver circulation to increasing concentrations of acetylcholine. The phosphorylated endothelial nitric oxide synthase (PeNOS)/endothelial nitric oxide synthase (eNOS) ratio was measured as a marker of eNOS activation. LPS administration induced an increase in baseline portal perfusion pressure and a decrease in vasodilation to acetylcholine (sinusoidal endothelial dysfunction). This was associated with reduced eNOS phosphorylation and liver inflammation. Simvastatin after LPS challenge did not prevent the increase in baseline portal perfusion pressure, but attenuated the development of sinusoidal endothelial dysfunction. Treatment with simvastatin from 3 days before LPS prevented the increase in baseline perfusion pressure and totally normalized the vasodilating response of the liver vasculature to acetylcholine and reduced liver inflammation. Both protocols of treatment restored a physiologic PeNOS/eNOS ratio. CONCLUSION:LPS administration induces intrahepatic endothelial dysfunction that might be prevented by simvastatin, suggesting that statins might have potential for liver protection during endotoxemia.

背景与目标： 未加标签：内皮功能障碍可导致败血症相关的血管紊乱和器官衰竭。然而，败血症对肝窦窦内皮功能的影响在很大程度上尚不清楚。他汀类药物可能会改善败血症中的微血管功能障碍。本研究探讨了内毒素血症大鼠模型中的肝血管异常和他汀类药物的作用。为此，将脂多糖（LPS）或盐水给予以下动物：（1）用安慰剂治疗的大鼠； （2）在LPS /盐水刺激后3和23小时给予辛伐他汀（25mg / kg，口服）治疗的大鼠； （3）从LPS /盐水注射前3天开始，用辛伐他汀（25 mg / kg / 24 h，口服）治疗的大鼠。分离并灌注肝脏，并通​​过测试肝循环的血管舒张作用以增加乙酰胆碱的浓度来探索正弦内皮功能。测量磷酸化内皮一氧化氮合酶（PeNOS）/内皮一氧化氮合酶（eNOS）的比率作为eNOS活化的标志。 LPS给药引起基线门静脉灌注压力增加，乙酰胆碱（正弦血管内皮功能障碍）的血管舒张减少。这与减少的eNOS磷酸化和肝脏炎症有关。 LPS刺激后的辛伐他汀不能阻止基线门静脉灌注压力的升高，但可以减轻正弦血管内皮功能障碍的发展。 LPS前3天开始用辛伐他汀治疗可防止基线灌注压力增加，并使肝血管对乙酰胆碱的血管舒张反应完全正常化，并减轻肝脏炎症。两种治疗方案均恢复了生理性PeNOS / eNOS比率。
结论：LPS给药可引起辛伐他汀可预防肝内内皮功能障碍，这表明他汀类药物可能在内毒素血症期间具有保护肝脏的潜能。

BACKGROUND & AIMS: This multicenter, open-label, third-party-masked trial compared the efficacy and safety of itraconazole oral solution (200 mg once daily) and clotrimazole troches (10 mg five times daily) in a population of immunocompromised subjects composed primarily of patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Patients were treated for 14 days; patients who exhibited a clinical response were followed up for an additional month to document the occurrence of relapse. Efficacy was judged by changes from baseline in symptoms of oropharyngeal candidiasis (erythema, soreness/burning), extent of oral lesions, and the presence/absence of Candida species on fungal culture. A total of 162 patients were randomized, and 149 were evaluated for efficacy. The percentage of patients with negative cultures at the end of treatment was significantly greater in the itraconazole group than in the clotrimazole group (60% vs 32%, respectively). Negative culture plus clinical response was achieved in significantly more itraconazole-treated patients (53%) than clotrimazole-treated patients (30%); results were similar in the subgroup of patients with HIV/AIDS. Both drugs were well tolerated, with the most frequently reported adverse events for both agents involving the gastrointestinal system. In conclusion, systemic therapy with intraconazole oral solution is efficacious and well tolerated in immunocompromised patients, including those with HIV/AIDS, when administered once daily for 14 days for the treatment of oral candidiasis.

背景与目标： 这项多中心，开放标签，第三方掩盖的试验在主要由人类患者组成的免疫功能低下人群中比较了伊曲康唑口服溶液（每天200 mg）和克霉唑锭剂（每天10 mg，五次）的疗效和安全性。免疫缺陷病毒（HIV）/后天免疫缺陷综合症（AIDS）。患者接受了14天的治疗；表现出临床反应的患者需要再随访一个月，以记录复发的发生。通过口咽念珠菌病的症状（红斑，酸痛/灼烧），口腔病变的程度以及真菌培养物中是否存在念珠菌，从基线的变化来判断疗效。总共162例患者被随机分组​​，并评估149例疗效。伊曲康唑组治疗结束时培养阴性的患者百分比显着高于克霉唑组（分别为60％和32％）。伊曲康唑治疗的患者（53％）比克霉唑治疗的患者（30％）获得了阴性培养和临床反应。 HIV / AIDS患者亚组的结果相似。两种药物均具有良好的耐受性，两种药物均涉及胃肠道系统，是最常见的不良事件。综上所述，使用康康唑口服液进行全身治疗对于免疫功能低下的患者（包括艾滋病毒/艾滋病患者）有效，并且耐受性良好，每天口服一次，持续14天，可治疗口腔念珠菌病。

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： 大豆来源的植物雌激素染料木黄酮已被建议在心血管疾病中具有保护作用。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ER（雌激素受体），eNOS（内皮型NO合酶）活性和血管O（2）（-）（超氧化物）生产。将大鼠（23周龄）分为以下几组：WKY（Wistar-Kyoto）车辆，SHR车辆，WKY-染料木黄酮（10 mg.kg（-1）体重.day（-1））； SHR-染料木黄酮; SHR-genistein-faslodex（ICI 182780; 2.5 mg.kg（-1）体重.day（-1））。通过蛋白质印迹分析eNOS，caveolin-1和钙调蛋白-1的血管表达，通过将[（3）H]精氨酸转化为L-[（3H）]瓜氨酸和通过生成O（2）（-）来分析eNOS活性。发光素的化学发光。在SHR中，经过5周的治疗，金雀异黄素降低了收缩压，增强了内皮依赖性的主动脉对乙酰胆碱的舒张作用，但对血管扩张剂对硝普钠的反应没有影响。与WKY大鼠相比，SHRs上调了eNOS，下调了Caveolin-1和calmodulin-1的表达，增加了NADPH诱导的O（2）（-）的产生，但降低了eNOS的活性。金雀异黄素增加主动脉钙调蛋白1蛋白的丰度和eNOS活性，并减少NADPH诱导SHRs中的O（2）（-）生产。单纯的ERalpha和ERbeta拮抗剂faslodex并未改变染料木黄酮在SHRs中诱导的任何变化，表明这些作用与ER刺激无关。总之，金雀异黄素减轻了SHRs的血压升高和内皮功能障碍。后者的作用似乎与增加的钙调蛋白-1表达和减少的O（2）（-）生成有关的eNOS活性有关。