Intracellular complement activation in podocytes aggravates immune kidney injury in trichloroethylene-sensitized mice.

Trichloroethylene (TCE) as a common organic solvent in industrial production can cause occupational medicamentosa-like dermatitis (OMDT) in some exposed workers. In addition to systemic skin damage, OMDT is also accompanied by severe kidney injury. Our previous studies show that complement (C) plays an important role in immune kidney injury caused by TCE. Specifically, C3 is mainly deposited on glomeruli. Recent studies have found that intracellular complement can be activated by cathepsin L (CTSL) and exert a series of biological effects. The purpose of this study was to explore where C3 on glomeruli comes from and what role it plays. A BALB/c mouse model of skin sensitization induced by TCE in the presence or absence of CTSL inhibitor (CTSLi,10 mg/kg). In TCE sensitization-positive mice, C3 was mainly expressed on podocytes and the expression of CTSL significantly increased in podocytes. Kidney function test and related indicators showed abnormal glomerular filtration and transmission electron microscopy revealed ultrastructure damage to podocytes. These lesions were alleviated in TCE/CTSLi positive mice. These results provide the first evidence that in TCE-induced immune kidney injury, intracellular complement in podocytes can be over-activated by CTSL and aggravates podocytes injury, thereby damaging glomerular filtration function. Intracellular complement activation and cathepsin L in podocytes may be a potential target for treating immune kidney injury induced by TCE.

Oxidative stress mediates renal endothelial cell damage in trichloroethylene-sensitized mice.

The purpose of this study was to explore whether renal endothelial cell injury is associated with oxidative stress in trichloroethylene (TCE)-induced immune kidney damage by detecting adhesion molecules and oxidative stress indexes. In this study, a mouse model of skin sensitization with the antioxidant Tempol was used to explore the mechanism. Blood urea nitrogen (BUN), creatinine (Cre), and histological examination were used for kidney function evaluation. Kidney homogenates were used for detecting renal nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA). Renal endothelial nitric oxide synthase (eNOS), E-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) protein levels were measured by immunohistochemical and Western blot. We found that BUN and Cre levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. In the TCE sensitization positive group, a partial area of vacuolar degeneration and lysed epithelial cells were observed in renal tubules. In TCE+Tempol sensitization positive group, small areas were also found to be vacuolar degenerated and renal tubules were dissolved. Renal NO, NOS, SOD and eNOS levels decreased and MDA levels increased, renal E-selectin, VCAM-1and ICAM-1 protein levels increased in the TCE sensitization positive group and the TCE+Tempol sensitization positive group. Tempol attenuated TCE induced up-regulation of MDA, E-selectin, VCAM-1and ICAM-1 and down-regulation of NO, NOS, SOD and eNOS. In conclusion, trichloroethylene-sensitized mice renal immune injury is associated with the renal endothelial cells' oxidative stress state.

NF-κB signaling pathway-enhanced complement activation mediates renal injury in trichloroethylene-sensitized mice.

Both NF-κB pathway and complement activation appear to be involved in kidney damage induced by trichloroethylene (TCE). However, any relationship between these two systems has not yet been established. The present study aimed to clarify the role of NF-κB in complement activation and renal injury in TCE-sensitized BALB/c mice. Mice were sensitized by an initial subcutaneous injection and repeated focal applications of TCE to dorsal skin at specified timepoints. NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was injected (intraperitoneal) before the final two focal TCE challenges. In the experiments, mice had their blood and kidneys collected. Kidney function was evaluated via blood urea nitrogen (BUN) and creatinine (Cr) content; renal histology was examined using transmission electron microscopy (TEM). Kidney levels of phospho-p65 were assessed by Western blot and kidney mRNA levels of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor (TNF)-α, and p65 by real-time quantitative PCR. Presence of C3 and C5b-9 membrane attack complexes in the kidneys was evaluated via immunohistochemistry. The results showed there was significant swelling, vacuolar degeneration in mitochondria, shrinkage of microvilli, disappearance of brush borders, segmental foot process fusion, and glomerular basement membrane thickening (or disrobing) in kidneys from TCE-sensitized mice. In conjunction with these changes, serum BUN and Cr levels were increased and IL-1ß, IL-6, IL-17, and TNFα mRNA levels were elevated. Levels of p65 and phospho-p65 protein were also up-regulated, and there was significant C3 and C5b-9 deposition. PDTC pretreatment attenuated TCE-induced up-regulation of p65 and its phosphorylation, complement deposition, cytokine release, and renal damage. These results provide the first evidence that NF-κB pathway has an important role in TCE-induced renal damage mediated by enhanced complement activation in situ.

Viral mimic polyinosine-polycytidylic acid potentiates liver injury in trichloroethylene-sensitized mice - Viral-chemical interaction as a novel mechanism.

Occupational trichloroethylene (TCE) exposure can induce hypersensitivity dermatitis and severe liver injury. Recently, several clinical investigations indicate that viral infection, such as human herpesvirus-6, is associated with hepatic dysfunction in patients with TCE-related generalized skin disorders. However, whether viral infection potentiates TCE-induced liver injury remains unknown. This study aimed to explore the contribution of viral infection to the development of TCE-sensitization-induced liver injury in BALB/c mice. Female BALB/c mice were randomly assigned into four groups: solvent control group (n = 20), TCE group (n = 80), poly(I:C) group (n = 20) and combination of TCE and poly(I:C) (poly(I:C)+TCE) group (n = 80). Poly(I:C) (50 µg) was i.p. administrated. TCE and poly(I:C)+TCE groups were further divided into sensitization and non-sensitization subgroup. Complement 3 and C3a protein levels, and complement factors were measured. Combination treatment significantly enhanced TCE-induced liver injury, decreased complement 3, but increased C3a in serum and liver tissues in sensitization group. These changes were not correlated with the hepatic complement 3 transcription. Moreover, combination treatment specifically promoted complement factor B, but not factor D and factor H expressions. These data provide first evidence that poly(I:C) potentiates liver injury in BALB/c mouse model of TCE-sensitization. Upregulated C3a and factor B contributes to the poly(I:C) action in TCE-induced liver injury. This new mode of action may explain increased risk of chemical-sensitization induced tissue damage by viral infection.

Downhole Applications of Magnetic Sensors.

In this paper we present a review of the application of two types of magnetic sensors-fluxgate magnetometers and nuclear magnetic resonance (NMR) sensors-in the oil/gas industry. These magnetic sensors play a critical role in drilling wells safely, accurately and efficiently into a target reservoir zone by providing directional data of the well and acquiring information about the surrounding geological formations. Research into magnetic sensors for oil/gas drilling has not been explored by researchers to the same extent as other applications, such as biomedical, magnetic storage and automotive/aerospace applications. Therefore, this paper aims to serve as an opportunity for researchers to truly understand how magnetic sensors can be used in a downhole environment and to provide fertile ground for research and development in this area. A look ahead, discussing other magnetic sensor technologies that can potentially be used in the oil/gas industry is presented, and what is still needed in order deploy them in the field is also addressed.

Lattice structure for generalized-support multidimensional linear phase perfect reconstruction filter bank.

Multidimensional linear phase perfect reconstruction filter bank (MDLPPRFB) can be designed and implemented via lattice structure. The lattice structure for the MDLPPRFB with filter support N(MΞ) has been published by Muramatsu , where M is the decimation matrix, Ξ is a positive integer diagonal matrix, and N(N) denotes the set of integer vectors in the fundamental parallelepiped of the matrix N. Obviously, if Ξ is chosen to be other positive diagonal matrices instead of only positive integer ones, the corresponding lattice structure would provide more choices of filter banks, offering better trade-off between filter support and filter performance. We call such resulted filter bank as generalized-support MDLPPRFB (GSMDLPPRFB). The lattice structure for GSMDLPPRFB, however, cannot be designed by simply generalizing the process that Muramatsu employed. Furthermore, the related theories to assist the design also become different from those used by Muramatsu . Such issues will be addressed in this paper. To guide the design of GSMDLPPRFB, the necessary and sufficient conditions are established for a generalized-support multidimensional filter bank to be linear-phase. To determine the cases we can find a GSMDLPPRFB, the necessary conditions about the existence of it are proposed to be related with filter support and symmetry polarity (i.e., the number of symmetric filters ns and antisymmetric filters na). Based on a process (different from the one Muramatsu used) that combines several polyphase matrices to construct the starting block, one of the core building blocks of lattice structure, the lattice structure for GSMDLPPRFB is developed and shown to be minimal. Additionally, the result in this paper includes Muramatsu's as a special case.

Construction of arbitrary dimensional biorthogonal multiwavelet using lifting scheme.

This paper focuses on the construction of multidimensional biorthogonal multiwavelets and the perfect reconstruction multifilter banks. Based on the Hermite-Neville filter, two lifting structures have been proposed and systematically investigated, and a general design framework has been developed for building biorthogonal multiwavelets and Hermite interpolation filter banks with any multiplicity for any lattice in any dimension with any number of primal and dual vanishing moments. The construction is an important generalization of the Neville-based lifting scheme and inherits all of the advantages of lifting schemes such as fast transform, in-place computation and integer-to-integer transforms. Our multiwavelet systems preserve most of the desirable properties for applications, such as interpolating, short support, symmetry, and high vanishing moments.