Relation of cumulative low-level lead exposure to depressive and phobic anxiety symptom scores in middle-age and elderly women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation.Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women.Methods: Participants were 617 Nurses’ Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations.Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead.Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.     

Eosinophil peroxidase mediates protein nitration in allergic airway inflammation in mice.

The eosinophilic inflammatory response in asthma is associated with protein nitration, detected as immunostaining for 3-nitrotyrosine (3NT). As the presence of 3NT is strongly correlated with upregulation of the inducible form of nitric oxide synthase (NOS II), it has been hypothesized that 3NT formation results from the action of peroxynitrite (ONOO-), a highly reactive NO derivative produced from the reaction of molecular NO and O2-. However, recent observations have suggested that the action of peroxidases, including eosinophil peroxidase (EPO), may be responsible for protein nitration. In this study, we used murine models of allergic asthma to address the relative contribution of EPO and NOS II to protein nitration. We studied EPO-deficient New Zealand White (NZW) mice, which were sensitized and challenged intranasally with ovalbumin (OVA). Despite comparable levels of eosinophilia, NO, and superoxide production, NZW mice exhibited markedly decreased 3NT staining around the airways after OVA challenge when compared with two other strains (A/J and C57BL/6J). Immunocytochemical analysis of bronchoalveolar lavage (BAL) cells and lung sections suggested that 3NT staining was largely confined to eosinophils. This was confirmed by Western Blot analysis of proteins from different subsets of BAL cells that demonstrated a marked decrease in 3NT formation in eosinophils from NZW mice. These results contrast with those obtained in OVA-sensitized and -challenged NOS II deficient mice, which despite decreased NO production, exhibited similar 3NT staining in the airways after OVA challenge as in wild-type control mice. In this model, protein nitration was thus not a function of NO production by NOS II. We conclude that in the mouse, 3NT formation after specific allergen challenge is dependent on EPO activity, particularly in eosinophils themselves. In contrast, 3NT formation is not driven by upregulation of NOS II expression in this model and does not appear to depend on increases in the level of NO production.     

Establishment of a human acute promyelocytic leukemia-ascites model in SCID mice

Acute promyelocytic leukemia (APL) is an interesting model for cancer research because of the presence of the specific PML-RARalpha fusion gene associated with the clinical response to retinoic acid differentiation therapy. To better understand and improve differentiation induction with retinoic acid, we have established a human APL-ascites model in SCID mice using the NB4 human APL cell line. NB4 (1 x 10(6) cells) were transplanted into the peritoneum (IP) of SCID mice for 1 month. NB4 ascites cells (A-NB4) appeared, which were then engrafted in SCID mice periodically for 18 passages at an interval of 3 to 4 weeks with a 100% success rate of tumor induction. The mean survival times of SCID mice transplanted with 1 x 10(6) A-NB4 cells was 21.6 +/- 2.3 days. Analysis of the biologic characteristics of ninth passage NB4 ascitic cells was performed and they were found to have the morphologic, immunologic, cytogenetic, and molecular features of cultured NB4 cells. Furthermore, A-NB4 cells were capable of differentiating when treated with all-trans retinoic acid (ATRA), as manifested by enhanced NBT reduction and CD11b expression. In vivo treatment with ATRA in SCID mice for 4 days also increased NBT reduction by A-NB4 cells. ATRA treatment significantly prolonged survival time in the group after transplantation (28.1 +/- 6.8 to 29.1 +/- 8.4 days) compared with the control (P < .001). Furthermore, treatment with adriamycin, an effective chemotherapeutic drug in APL, had a strong growth suppressive effect on A-NB4 cells. These results demonstrate that this SCID-APL (NB4 ascites cells) model is a useful preclinical system for evaluating new or known drugs in the treatment of APL.     

紫外分光光度法测定复方酮康唑软膏中酮康唑和氧氟沙星的含量

目的：建立复方酮康唑软膏的含量测定方法。方法：用双波长分光光度法测定酮康唑的含量，用单波长法测定氧氟沙星的含量。结果：两被测组分的平均回收率和相对标准偏差分别为酮康唑１００．３３％和０．３２％；氧氟沙星１００．８５％和０．２７％。结论：方法简便、准确，可用于复方酮康唑软膏的质量控制。     

High thermal stability and cold-denaturation of an artificial polypeptide

An amphipathic polypeptide, P_n, with a tandemly repeated LKELPEKL sequence including a proline every eight residues, as well as a series of shorter peptides having the same sequence, P₂, P₃, P₄, P₅ and P₆, were synthesized. Their conformation in aqueous solution was mainly studied by CD. At low temperature, these peptides and polypeptide are completely unordered and undergo a reversible transition leading to a partly α-helical structure upon heating. Such behavior has been demonstrated for a few proteins by other authors and has been called cold-denaturation. The transition temperature of the polypeptide is close to 20 ° C. The conformational change does not depend on concentration, indicating a monomolecular process. The high-temperature structure seems to be compact as for globular proteins. A model of folded structure is proposed from experimental data and from molecular modelling studies. © Munksgaard 1996.     

Salt-dependent conformational diversity of alternating poly (Glu-Leu)

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH⁺₄ to a final 0.1 M solution, induces a transition to a water soluble β-structure. The salt effect is quite selective since no transition was observed with Li⁺, Na⁺ or Cs⁺ ions. Addition of 0.5 equiv. of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to β-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu²⁺ or 0.15 equiv. of Fe³⁺ induces a coil to α-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions. © Munksgaard 1997.     

6-取代苯基哒嗪的3位γ-氨基丁酸衍生物的合成及抗惊活性

GABA的合成类似物是开发新型抗惊剂和抗癫痫药物的新领域。由芳香醛与吗啉、氰化钾反应形成的α-芳基-α-(4-吗啉)乙腈,可对α,β-不饱和腈或酯进行1,4-加成,生成1,4-酮酸型化合物。此物与肼缩合,再经芳构化即得6-芳基-3(2H)哒嗪酮。后者再经氯化后。与GABA缩合,制备3-(N-GABA)-6-芳基哒嗪类及其分子内脱水产物3-(N-丁内酰胺)-6-芳基哒嗪类化合物。本文应用此法合成了17个上述苯代哒嗪的GABA衍生物,并初步测验了它们的抗惊(MES)活性。活性最强的是3-(N-GABA)-6-(2′,4′-二氯苯基)哒嗪(ED₅₀=21.05mg/kg)。     

伊贝碱甙B的分离和结构测定

本文报道自吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)中分得一种新的C-去甲-D-异甾体生物碱甙,命名为伊贝碱甙B(yibeinoside B)。根据红外、质谱、氢谱和碳谱确定了结构。     

Optic disc oval ness,refractive error and axial length of Hong Kong Chinese

Myopic crescent, refractive error and axial length were previously investigated in Hong Kong Chinese subjects. The myopic crescent was found to correlate with axial length and myopic refraction. In this study, three groups of Hong Kong Chinese with different degrees of myopia were assessed for optic disc ovalness, refractive error and axial length. The axial length was significantly correlated with the degree of myopia, indicating that the myopia was axial in nature. The regression line shows that 0.44 mm of axial elongation would give about one dioptre of increase in myopia. The elliptical ratio of the optic disc was defined as the maximal disc diameter divided by the minimal disc diameter. All three groups showed an oval disc with vertical axis greater and an increased ovalness for the high myopic group with an elliptical ratio from 1.11 in low myopia to 1.29 in high myopia. There is a small amount (about four degrees) of temporal rotation of this vertical oval orientation, which is independent of the amount of myopia. This result shows an association between axial elongation of the globe and optic disc ovalness, in addition to the previously described temporal myopic crescent. Therefore, in myopic subjects, a vertically oval disc may be associated with a myopic refraction rather than glaucoma.