Citrate and recurrent idiopathic calcium urolithiasis

Summary In male patients with idiopathic recurrent calcium urolithiasis (RCU) the effects of oral potassium sodium citrate (PSC) on acid-base, citrate and mineral metabolism were investigated. There were 17 normocitraturic and 15 hypocitraturic patients. The examination time points in our clinical laboratory were prior to medication and after 3, 6 and over 12 months of medication. Urine collection periods were over 24 h, 2 h — after an overnight fast — 3 h postprandially. Acceptance by the patients was poor, a large number refusing to take PSC for 12 months. Compliance of the patients continuing with the study was adequate as assessed by the urinary excretion of potassium and sodium. No unwanted side effects were observed. After 3 months of PSC medication a compensated metabolic alkalosis developed; in the urine calcium was decreased, while citrate, pH and oxalate were increased, as were hydroxyapatite supersaturation and calcium phosphate particles. After more than 12 months of PSC medication, citrate and pH tended toward the pretreatment baseline values, while hydroxyapatite supersaturation and calcium had already returned to pretreatment values. Despite ongoing PSC intake, patients with pre-existing hypocitraturia had lower urinary citrate than patients with previous normocitraturia, while the concomitant pH and hydroxyapatite supersaturation in the urine of the former remained at levels close to those of the latter. Under the influence of PSC, parathyroid gland function remained unchanged, but serum levels of bone alkaline phosphatase and osteocalcin were low, and urinary hydroxyproline was high. We conclude that (1) PSC shifts the acid-base status toward metabolic alkalosis, and also modulates bone metabolism; (2) over the long term, PSC may be unable to achieve a constantly high urinary citrate, in particular in RCU with pre-existent hypocitraturia — in contrast to its short- and medium-term effects. Long-term interrupted medication with PSC is proposed for the metaphylaxis of RCU. A regimen of this type may also be expected to yield more insight into the mechanism(s) underlying hypocitraturia.     

三氧化二砷联合5-氟尿嘧啶对人大肠癌SW480细胞的抑制作用

目的:比较5-氟尿嘧啶(5-FU)单独以及联合三氧化二砷(As2O3)对人大肠癌SW480的细胞毒作用,为临床联合用药提供实验依据。方法:以MTT法观察不同浓度的As2O3、5-FU以及两者合用对大肠癌SW480细胞的细胞毒作用,比较药物对细胞增值的抑制效应。结果:与单用5-FU相比,As2O3与5-FU联用能显著抑制人大肠癌SW480细胞的增值作用。结论:As2O3与5-FU联合应用具有显著抑制人大肠癌SW480细胞的作用。     

JWA as a functional molecule to regulate via MAPK cascades and F-actin cancer cells migration cytoskeleton

Mitogen activated protein kinase （MAPK） cascades are thought to mediate diverse biological functions such as cell growth, differentiation and migration. Activated MAPK may affect microtubule （MT） which is essential for cellular polarity, differentiation and motility. Data in this study show that JWA, a newly identified novel microtubule-associated protein （MAP） was essential for the rearrangement of F-actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide （As2O3） and phorbol ester （PMA）. Over-expression of JWA alone in HeLa, B16 and HCCLM3 cancer cells effectively inhibited cellular migration, whereas, cellular migration was significantly accelerated when cells were deficient in JWA expression. The mechanism underlying these phenomena might be due to JWA affected F-actin rearrangement. Furthermore, JWA deficiency blocked anti-migratory effect produced by As2O3 but enhanced the migratory effect initiated by PMA in HeLa cells.     

莪术、三氧化二砷对晶状体上皮细胞增殖及信号转导分子的影响

目的：探讨莪术(RC)、三氧化二砷(As₂O₃)对晶状体上皮细胞(LEC)增殖及细胞信号转导的影响,为防治后发性白内障提供实验依据。方法：采用重组人碱性成纤维细胞生长因子(rhbFGF)诱导牛LEC增殖；四甲基偶氮唑蓝法(MTT)检测RC,As₂O₃对LEC增殖的抑制率；流式细胞术(FCM)检测RC,As₂O₃对LEC增殖细胞核抗原(PCNA)蛋白表达的抑制作用；荧光分光光度法检测LEC内［Ca²⁺］i、放射免疫分析法检测cAMP和cGMP。结果：RC,As₂O₃对rhbFGF诱导的LEC增殖的抑制率增加(P＜0.01)；明显下调rhbFGF诱导增殖的LEC内PCNA蛋白表达(P＜0.01)；使增殖的LEC内［Ca²⁺］i和cAMP显著增高(P＜0.01),cGMP显著降低(P＜0.01)。上述指标均呈剂量-效应关系。结论：RC,As₂O₃能显著抑制LEC增殖；Ca²⁺,cAMP和cGMP细胞信号转导是其抑制LEC增殖的重要分子机制；RC,As₂O₃对防治后发性白内障具有广阔的前景。     

27例三氧化二砷严重不良反应病例报告分析

目的了解三氧化二砷严重不良反应的特点，为临床使用提供参考。方法通过检索1994～2007年《中国期刊全文数据库》，对收集到的27例三氧化二砷严重不良反应的文献报道进行统计分析。结果三氧化二砷所致严重不良反应累计多个系统-器官，其中分别导致心、肝、肾功能衰竭的例数分别为13例、6例、3例，占23．2％、10．71％、5．38％；全身严重水肿5例，导致死亡9例。严重不良反应多发生在用药2周内。结论应加强对三氧化二砷所致严重不良反应的研究及再评价。     

Effect of mineral trioxide aggregate on cytokine production by peritoneal macrophages

AIM: To test the effect of two commercial brands of grey mineral trioxide aggregate (ProRoot and MTA-Angelus) on cytokine production by M1 and M2 inflammatory macrophages. METHODOLOGY: M1 (from C57BL/6 mice) and M2 peritoneal inflammatory macrophages (from C57BL/6 IL12p40-/- mice) were obtained and cultured in vitro in the presence of MTA. The cellular viability and the production of tumour necrosis factor-alpha, interleukin (IL)-12 and IL-10 in response to stimulation with interferon-gamma and Fusobacterium nucleatum or Peptostreptococcus anaerobius were evaluated. Data were analysed by Mann-Whitney, Kruskal-Wallis and anova tests. RESULTS: The cements did not interfere with cellular viability or with cytokine production by either type of macrophage. However, M2 macrophages produced higher levels of IL-10 when stimulated with F. nucleatum than M1 macrophages (P < 0.05). CONCLUSIONS: The brands of MTA evaluated did not interfere in the cytokine response by M1 or M2 macrophages to the two bacteria tested. However, a difference in cytokine production between the two types of macrophages was found.     

Evaluation of biocompatibility of mineral trioxide aggregate with an improved rabbit ear chamber

In the present study, the biocompatibility of mineral trioxide aggregate (MTA) to the revascularization of the connective tissues was evaluated by using the improved rabbit ear chamber, in vivo. Twenty improved rabbit ear chamber was prepared from 12 male albino-rabbit by using a well through which a material could be introduced into the living vascular tissue. Ten chambers were provided for MTA, and the remaining 10 chambers were used for a calcium hydroxide-containing root canal sealer (Sealapex), as a comparator. A volume of about 1.5 mm(3) of the materials were inserted into the chamber and the interaction between the vascular tissue and materials was observed by using a biomicroscope immediately after application, at 1, 3, 5.5, 8, 24, 48, 72 h, and once a week up to 4 weeks. The results revealed that revascularization of connective tissue took place with complete recovery of microcirculation within 4 weeks in both MTA and Sealapex. However, the precipitate-barrier and brown zone around periphery of Sealapex was not observed in MTA treated samples. It can be concluded that MTA is biocompatible and does not produce any adverse site effect on microcirculation of the connective tissue.     

Proteomic analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in leukemia K562 cells

Background Arsenic trioxide (As2O3 ) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3 -target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics. Methods K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. Results As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells. Conclusions: As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.     

Improving ecological inference using individual-level data

In typical small-area studies of health and environment we wish to make inference on the relationship between individual-level quantities using aggregate, or ecological, data. Such ecological inference is often subject to bias and imprecision, due to the lack of individual-level information in the data. Conversely, individual-level survey data often have insufficient power to study small-area variations in health. Such problems can be reduced by supplementing the aggregate-level data with small samples of data from individuals within the areas, which directly link exposures and outcomes. We outline a hierarchical model framework for estimating individual-level associations using a combination of aggregate and individual data. We perform a comprehensive simulation study, under a variety of realistic conditions, to determine when aggregate data are sufficient for accurate inference, and when we also require individual-level information. Finally, we illustrate the methods in a case study investigating the relationship between limiting long-term illness, ethnicity and income in London.     

Studies in the basic mineralizing system,CaO-P2O5-H2O

Equilibrium phase diagrams have been determined for the system CaO-P₂O₅-H₂ using hydrothermal synthesis techniques in the temperature range 300–600° and 2 Kb H₂O pressure. Well-crystallized hydroxyapatite has been produced and characterized. Small variations in unit cell parameters dependent on temperature of synthesis and bulk composition of the starting materials have been determined. Precise chemical conditions were required to obtain apatite as the only solid phase in equilibrium with solution. Equilibrium phase diagram results are compared with previous synthetic investigations.

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Zusammenfassung Es wurden Gleichgewichts-Phasendiagramme für das System CaO-P₂O₅-H₂O bestimmt, indem hydrothermale Synthese-Techniken im Temperaturbereich von 300–600° und bei einem Druck von 2 Kb H₂O verwendet wurden. Es wurde gut-kristallisiertes Hydroxyapatit erzeugt und charakterisiert. Es wurden geringe Unterschiede in den Parametern der Zelleinheiten festgestellt, welche von der angewandten Temperatur und der Zusammensetzung des Startmaterials abhingen. Es waren genaue chemische Bedingungen nötig, um Apatit als die einzige feste Phase im Gleichgewicht mit der Lösung zu erhalten. Die Resultate der Gleichgewichts-Phasendiagramme werden mit früheren Untersuchungen mit der Synthesetechnik verglichen.

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Résumé Des diagrammes de phase d'équilibre ont été déterminés pour le système CaO-P₂O₅-H₂O en utilisant des techniques de synthèse hydrothermique au cours de variatio nsde température allant de 300–600° et 2 Kb H₂O de pression. De l'hydroxyapatite bien cristallisé a été synthétisé et caractérisé. De faibles variations de paramètres de la maille cristalline, liées à la température de synthèse et composition globale du matériel initial, ont été déterminées. Des conditions chimiques précises sont nécessaires pour obtenir de l'apatite, en tant que seule phase solide en équilibre dans la solution. Les résultats de diagramme de phase d'équilibre sont comparés avec ceux obtenus dans des milieux synthétiques.