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We compared the toxicokinetics of methylmercury (MeHg) in KK‐Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12‐week‐old KK‐Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK‐Ay mice, while the terminal elimination half‐life was lower in almost all samples of KK‐Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK‐Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK‐Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK‐Ay mice under the experimental conditions. Different patterns of tissue‐to‐plasma and tissue‐to‐whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states. Toxicokinetics of methylmercury measured in KK‐Ay diabetic mice and C57BL/6J mice indicate that methylmercury is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK‐Ay mice. Notable differences in the tissue‐to‐plasma partition coefficients of blood cells between the two mouse strains suggest that MeHg transfer between plasma and blood cells affects its distribution in tissues. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL)-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNγ upregulated IL-32 expression and that oxidative stress augmented IFNγ-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNγ induced IL-32 expression in human airway epithelial cells. Methods Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFNγ, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNγ, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. Results There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNγ for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNγ induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNγ + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its transcriptional activity. Further, knocking down CREB expression by siRNA resulted in significant suppression of IL-32 induction by IFNγ and H2O2 in HBE cells. Conclusion IL-32 expression in airway epithelium may be augmented by inflammation and oxidative stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key transcriptional factors in IFNγ and H2O2 induced IL-32 expression.

A study reports an alternative method for generating metal-mediated base pairs in deoxyribonucleic acid (DNA) duplexes using only naturally occurring pyrimidine bases. Thymine-thymine (T--T) mispairs in DNA duplexes selectively capture Hg(super II) ions, and the metal-meidated thymine-Hg(super II)-thymine base pairs form in DNA duplexes.

Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities. Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function. COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids. Some of these factors have been shown to deteriorate with COPD exacerbations. We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations. Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated. Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited. During follow-up, exacerbations had been prospectively recorded. Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated. The change was compared between patients with and without a history of exacerbations. Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ΔBMD mg/ml⋅year: -3.78 versus -0.30, p = 0.02). Moreover, multivariate regression analysis showed that exacerbations and baseline PaO2 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation. Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression. Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. [ABSTRACT FROM AUTHOR]

Vascular cell adhesion molecule-1 (VCAM-1, CD106) is important in leukocyte trafficking and its increased expression is associated with a number of chronic inflammatory diseases, including rheumatoid arthritis (RA). A soluble form of VCAM-1 (sVCAM-1) is generated by shedding of the membrane-bound molecule. The concentration of sVCAM-1 is increased in the sera of RA patients, but its pathological role has not been elucidated. The effect of sVCAM-1 relative to protection or aggravation of disease on the development of spontaneous arthritis was examined in an animal model of RA, namely MRL- Fas lpr mice (which display a disease resembling human RA), by generation of sVCAM-1 transgenic MRL- Fas lpr mice. Transgenic MRL- Fas lpr mice that expressed sVCAM-1 had higher incidence and increased severity of arthritis associated with higher levels of serum IgG rheumatoid factor compared with non-transgenic MRL- Fas lpr mice. These results suggest that sVCAM-1 plays an arthritogenic role in the development of inflammatory arthritis in MRL- Fas lpr mice and may present an important target for therapeutic strategy of RA. [ABSTRACT FROM AUTHOR]

The article provides information on a study that describes the stabilization of DNA duplexes via the formation of a Hg2mediated base pair. The study basically investigated the interactions of metal ions with nucleic acids, nucleosides and nucleobases. The article also presents the figure of thermally induced transition profiles of DNA duplex. According to the study, the transition profiles shifted to higher temperatures in the presence of Hg2 ions. The study also informed about some of the metals that are known to bind to nucleic acids.

Microsporidia can cause infection in various animals and humans. To determine the recent prevalence of Encephalitozoon in companion birds in Japan, 364 bird feces and 16 conjunctival exudates, as well as 28 exhibition bird feces, were examined using polymerase chain reaction (PCR). Thirty-five (9.6%) feces and 2 (12.5%) conjunctival exudates from companion birds were PCR positive, and sequence analysis revealed that all detected organisms were Encephalitozoon hellem genotype 1A. The prevalence by region varied from 4.5% in the Shikoku region to 14.3% in the Chugoku region. By age, the prevalence in birds younger than 6 months of age was 13.3%. We also discuss the threat of human infection as a zoonotic disease.

A 49-year-old female was admitted to our hospital because of worsening of congestive heart failure on November 2000 in a state after insertion of permanent pacemaker for complete atrioventricular block in 1986, followed by a clinical history of chronic heart failure due to dilated cardiomyopathy. After admission, her general condition had been improved, but, she had massive hemoptysis suddenly and died on February 2001. At autopsy, noncaseating granulomas were observed scattering in lungs, liver and spleen, not associated with any infectious lesions, therefore indicating systemic sarcoidosis. In lungs, granulomatous arteritis in small- and medium-sized muscular arteries associated with disputation of the media and elastic laminae were observed, suggesting the direct cause of hemoptysis. This is the extremely rare case of pulmonary arteritis with systemic sarcoidosis resulting the death from massive hemoptysis.