Gender-specific association between iron status and the history of attempted suicide: implications for gender paradox of suicide behaviors

PURPOSE: Iron deficiency (ID) has been linked with high impulsivity, and an increased risk of ID was reported among suicide attempters. We hypothesized that poor iron status might be prevalent among suicide attempters, who have high impulsivity. METHODS: As a part of the third National Health and Nutrition Examination Survey (1988-1994), a set of iron indices were measured in 2598 men and 2975 women aged 17-39 years, who completed a mental disorder diagnostic interview. RESULTS: Using non-attempters as reference within each gender, we observed a gender-dependent association between poor iron status and the history of attempted suicide. For male attempters (n=74), the prevalence ratios (PR) of abnormal serum ferritin, serum iron and protoporphyrin were 18.3 (95%CI=3.3-101.7), 3.2 (1.1-9.4) and 5.4(1.8-15.6). In contrast, the PR of abnormal serum ferritin for female attempters (n=217) was 0.3 (0.1-0.6). The hematological indices did not differ significantly between attempters and non-attempters among either men or women. Compared with non-attempters, male attempters were prone to a higher odds [17.5 (4.2-72.4)] while female attempters to a lower odds [0.6 (0.3-1.1)] of ID. CONCLUSION: These data suggest new opportunities for exploring biological bases of gender paradox of suicidal behaviors and a novel way to enhance therapeutic and preventive interventions against suicide.     

α1D-Adrenergic receptor insensitivity is associated with alterations in its expression and distribution in cultured vascular myocytes

Aim:

It is unclear why α_1D-adrenergic receptors (α_1D-ARs) play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native α₁-adrenergic functional performance between the vascular smooth muscle and myocytes.

Methods:

The α₁-adrenergic mediated contraction, Ca²⁺ signaling and the subcellular receptor distribution were evaluated using the Fluo-4, BODIPY-FL prazosin and subtype-specific antibodies.

Results:

Rat aortic rings and freshly dissociated myocytes displayed contractile and increased intracellular Ca²⁺ responses to stimulation with phenylephrine (PE, 10 μmol), respectively. However, the PE-induced responses disappeared completely in cultured aortic myocytes, whereas PE-enhanced Ca²⁺ transients were seen in cultured rat cardiac myocytes. Further studies indicated that α_1D-ARs, the major receptor subtype responsible for the α₁-adrenergic regulation of aortic contraction, were distributed both intracellularly and at the cell membrane in freshly dispersed aortic myocytes, similar to the α_1A-AR subcellular localization in the cultured cardiomyocytes. In the cultured aortic myocytes, however, in addition to a marked decrease in their protein expression relative to the aorta, most labeling signals for α_1D-ARs were found in the cytoplasm. Importantly, treating the culture medium with charcoal/dextran caused the reappearance of α_1D-ARs at the cell surface and a partial restoration of the Ca²⁺ signal response to PE in approximately 30% of the cultured cells.

Conclusion:

Reduction in α_1D-AR total protein expression and disappearance from the cell surface contribute to the insensitivity of cultured vascular smooth muscle cells to α₁-adrenergic receptor activation.     

Levofloxacin pharmacokinetics in adult cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. METHODS: Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. RESULTS: When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC(24)), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 microg x h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 microg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC(24)/MIC ratio. CONCLUSION: CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (>/= 750 mg); and establish PK/PD targets for managing PA pulmonary infections.     

Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases

Haptoglobin (Hp) is a plasma alpha(2)-glycoprotein which binds free haemoglobin, thus preventing oxidative damage. The complex is rapidly removed from the circulation by a specific receptor (CD163) found on macrophages. Three major subtypes, Hp1-1, Hp2-1 and Hp2-2 are the product of two closely related genes HP(1) and HP(2). The frequency of the HP(1) and HP(2) genes varies worldwide depending on racial origin: the HP(1)frequency varying from about 0.07 in parts of India to over 0.7 in parts of West Africa and South America. Both HP(1) and HP(2) have been linked to susceptibility to various diseases. Such associations may be explained by functional differences between the subtypes in the binding of Hb and its rate of clearance from the plasma. However, there are also corresponding negative reports for disease associations. The conflicting evidence on disease association and the lack of association between disease and particular populations, despite the wide range of HP(1) and HP(2) gene frequencies across the world, may indicate that any associations are marginal.     

Anatomical distribution of 3He apparent diffusion coefficients in severe chronic obstructive pulmonary disease

PURPOSE: To evaluate the anatomical distribution of apparent diffusion coefficients (ADC) using hyperpolarized helium-3 (3He) MRI in chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Hyperpolarized 3He MRI was performed in eight healthy and seven COPD subjects under breathhold conditions in the supine position to determine ADC values from diffusion-weighted images and evaluate anterior-posterior (AP) and superior-inferior (SI) differences. RESULTS: ADC differences between anterior and posterior slices, DeltaAP, was 0.06 +/-0.01 cm2/second for healthy volunteers and 0.04 +/-0.02 cm2/second for COPD subjects and was significant for each subject (P < 0.01). The AP ADC gradient was -3.98 x 10(-3) +/-0.59 cm2/second/cm for healthy volunteers and -2.04 x 10(-3) +/-0.89 cm2/second/cm for COPD subjects. The difference in ADC between superior and inferior regions of interest (ROIs), DeltaSI, was 0.02 +/-0.02 cm2/second for healthy volunteers and 0.10 +/-0.09 cm2/second for COPD subjects, which was significant for each subject (P < 0.05). The SI ADC gradient was -0.63 x 10(-3) +/-2.23 cm2/second/cm for healthy volunteers and -6.61 x 10(-3) +/-6.68 cm2/second/cm for COPD subjects. DeltaAP, AP-gradient, and SI-gradient were significantly different between healthy volunteers and COPD subjects (P < 0.05). CONCLUSION: In all subjects, ADC anatomical differences were significant and mean ADC was dependent on anatomic location and disease status.     

基于分段Prony建模的脑电相位同步分析方法

本研究提出采用一种分段的Prony方法(PPM),将非平稳EEG信号分解为幅度为指数上升或下降的正弦波,从而获得各频率成分的幅度、频率和初始相位,并计算两通道相位差;用香侬熵来衡量两路信号的相位同步程度.首先对该方法的频率、相位分辨率和检测同步程度的效果等进行仿真研究,结果显示了该方法具有高的频率和相位分辨率.最后将该方法用于实际的三组脑电信号,得到的结果与经典方法一致.将该方法与希尔伯特变换方法进行了比较,说明该方法具有较好的抗噪性能,可作为非平稳信号的相位同步检测的有效工具.     

天然关节软骨的液体质量分布特征

目的采用切片称重的方法,研究关节软骨的液体分布特征。方法通过Leica冷冻切片机把软骨样品切成31块均匀厚度的薄片,采用真空恒温箱和高精度电子天平,得到液体的质量分数随深度变化的关系曲线。结果软骨质量随距表面的深度呈动态变化,距表面的49％区域内,软骨薄片的质量最大。软骨液体的质量分数随深度呈波动式下降趋势,从最表层的94．2％到最底层的78．1％。结论液体的质量分布与关节软骨的生理结构有关,胶原纤维网架阻止了蛋白多糖的充分伸展,使得液体的质量分数与距表面的深度呈递减趋势。     

Efficient Calculation of Empirical <Emphasis Type="Italic">P</Emphasis>-values for Genome-Wide Linkage Analysis Through Weighted Permutation

Linkage analysis in multivariate or longitudinal context presents both statistical and computational challenges. The permutation test can be used to avoid some of the statistical challenges, but it substantially adds to the computational burden. Utilizing the distributional dependencies between (defined as the proportion of alleles at a locus that are identical by descent (IBD) for a pairs of relatives, at a given locus) and the permutation test we report a new method of efficient permutation. In summary, the distribution of for a sample of relatives at locus x is estimated as a weighted mixture of drawn from a pool of ‘representative’ distributions observed at other loci. This weighting scheme is then used to sample from the distribution of the permutation tests at the representative loci to obtain an empirical P-value at locus x (which is asymptotically distributed as the permutation test at loci x). This weighted mixture approach greatly reduces the number of permutation tests required for genome-wide scanning, making it suitable for use in multivariate and other computationally intensive linkage analyses. In addition, because the distribution of is a property of the genotypic data for a given sample and is independent of the phenotypic data, the weighting scheme can be applied to any phenotype (or combination of phenotypes) collected from that sample. We demonstrate the validity of this approach through simulation. Edited by David Allison.