Metallothionein as an Anti-Inflammatory Mediator

The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT) is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions

On-line Identification of Electro-Conductivity in Electrolytic Solutions

An on-line method is proposed to identify electro-conductivity in electrolytic solutions. The method uses a model of a cell of electrolytic solutions in a micro reactor modeled by an electronic circuit. The circuit consists of a cell part with a resister and a capacitor connected in series and a measurement part having a resister. Then the resistance and the capacitance of the cell part are identified to calculate the electro-conductivity. The identification scheme is the least-square method with a forgetting factor calculated on-line. To avoid the effect of differentiation of measured signals, a filter is added to the identification method. The effectiveness of the proposed control scheme is shown by numerical simulation.</p

Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions

Introduction. Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mor­tality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD. Material and methods. A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase. Results. A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions. Conclusions. These findings suggest that collagen deposition resulting from the altered regulation of extracel­lular matrix is associated with granuloma formation in the lungs of mice treated with ASD

Effects of scattering and dust grain size on the temperature structure of protoplanetary discs: A three-layer approach

The temperature in the optically thick interior of protoplanetary discs is essential for the interpretation of millimeter observations of the discs, for the vertical structure of the discs, for models of the disc evolution and the planet formation, and for the chemistry in the discs. Since large icy grains have a large albedo even in the infrared, the effect of scattering of the diffuse radiation in the discs on the interior temperature should be examined. We have performed a series of numerical radiation transfer simulations including isotropic scattering by grains with various typical sizes for the diffuse radiation as well as for the incident stellar radiation. We also have developed an analytic model including isotropic scattering to understand the physics concealed in the numerical results. With the analytic model, we have shown that the standard two-layer approach is valid only for grey opacity (i.e. grain size \ga10 \micron) even without scattering. A three-layer interpretation is required for grain size \la10 \micron. When the grain size is 0.1--10 \micron, the numerical simulations show that isotropic scattering reduces the temperature of the disc interior. This reduction is nicely explained by the analytic three-layer model as a result of the energy loss by scatterings of the incident stellar radiation and of the warm diffuse radiation in the disc atmosphere. For grain size \ga10 \micron (i.e. grey scattering), the numerical simulations show that isotropic scattering does not affect the interior temperature. This is nicely explained by the analytic two-layer model; the energy loss by scattering in the disc atmosphere is exactly offset by the "green-house effect" due to scattering of the cold diffuse radiation in the interior.Comment: MNRAS accepte

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): effects of lowered serum zinc level on the toxicity

Introduction. We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. Material and methods. Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1β as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. Results. Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1β, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1β-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. Conclusions. These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD

Utility of Contrast-Enhanced FDG-PET/CT in the Clinical Management of Pancreatic Cancer Impact on Diagnosis, Staging, Evaluation of Treatment Response, and Detection of Recurrence

Objectives: Fluorodeoxyglucose (FDG)-positron emission tomography/contrast-enhanced computed tomography (PET/CE-CT) involving whole-body scanning first by non-CE-CT and FDG-PET followed by CE-CT has been used for detailed examination of pancreatic lesions. We evaluated PET/CE-CT images with regard to differential diagnosis, staging, treatment response, and postoperative recurrence in pancreatic cancer. Methods: Positron emission tomography/CE-CT was conducted in 108 patients with pancreatic cancer and in 41 patients with other pancreatic tumor diseases. Results: The maximum standardized uptake value (SUVmax) overlapped in benign and malignant cases, suggesting that differential diagnosis of pancreatic tumors based on the SUVmax is difficult. In the evaluation of staging in 31 resectable pancreatic cancer by PET/CE-CT, the diagnostic accuracy rate was more than 80% for most factors concerning local invasion and 94% for distant metastasis but only 42% for lymph node metastasis. Significant positive correlations were found between the SUVmax and tumor size/markers, suggesting that SUVmax may be a useful indicator for the treatment response. Regarding the diagnosis of the postoperative recurrence, PET/CE-CT correctly detected local recurrence in all the 11 cases of recurrence, whereas abdominal CE-CT detected only 7 of 11 cases, suggesting that PET/CE-CT is superior in this context. Conclusions: Positron emission tomography/CE-CT is useful for the clinical management of pancreatic cancer