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ABSTRACT: : Sepsis is the most common cause of acute kidney injury in critically ill patients; however, the mechanisms leading to acute kidney injury in sepsis remain elusive. Although sepsis has been considered an excessive systemic inflammatory response, clinical trials that inhibit inflammation have been shown to have no effect. The purpose of this study was to examine the pathophysiology of septic acute kidney injury focusing on immune responses and renal tubular cell apoptosis by providing an on-site quantitative comparison between septic- and ischemia/reperfusion-induced acute kidney injury.
: Twenty-four hours after cecal ligation and puncture or ischemia/reperfusion injury, biochemical, histologic, and cytokine changes were compared in C57BL/6 mice. Apoptosis was assessed, and the effect of caspase 3 inhibition on renal function was also examined. The percentage of regulatory T cells and the effect of depletion were determined and compared with ischemia/reperfusion-induced acute kidney injury. The effect of interleukin-10 blocking was also compared.
: Despite comparable renal dysfunction, acute tubular necrosis or inflammation was minimal in septic kidneys. However, tubular cell apoptosis was prominent, and caspase 3 activity was positively correlated with renal dysfunction. A decrease in apoptosis by caspase 3 inhibitor resulted in attenuation of renal dysfunction. In assessment of systemic immunity, septic acute kidney injury was associated with an increase in interleukin-10, and also showed massive immune cell apoptosis with increased regulatory T cells. In contrast to ischemia/reperfusion injury in which depletion of regulatory T cells aggravated renal injury, depletion of regulatory T cells before cecal ligation and puncture resulted in renoprotection. In addition, blocking interleukin-10 rescued septic mice from the development of acute kidney injury, whereas it had no effect in ischemia/reperfusion injury.
: Pathogenesis of septic acute kidney injury is thought to be different from that of ischemia/reperfusion-induced acute kidney injury. Our data showed a link between apoptosis, immune suppression, and the development of acute kidney injury during sepsis and suggest that strategies targeting apoptosis or enhancing immunity might be a potential therapeutic strategy for septic acute kidney injury.
Critical care medicine 08/2012; 40(11):2997-3006. · 6.37 Impact Factor
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ABSTRACT: Patients with end-stage renal disease (ESRD) are known to have impaired immune function. Dendritic cells (DCs) are the major antigen-presenting cells that initiate primary immune responses, linking innate and adaptive immunity. Although suboptimal immune responses to vaccination, as frequently observed in ESRD patients, might suggest the presence of impaired DC function, the precise nature of altered DC function is not fully understood.
In the current study, we compared the maturation status, viability, and function of monocyte-derived DCs (moDCs) of patients on hemodialysis (HD) with healthy controls.
Surface expression of major histocompatibility complex class II, CD83, and CD86, and chemokine receptor CCR7 in moDCs was not different between HD patients and healthy controls. No significant difference was detected in the viability of moDCs determined by expression of annexin V and propidium iodide between two groups. However, moDCs from HD patients produced significantly higher amounts of IL-6 when stimulated by cytokine cocktails compared to healthy controls. In addition, mature moDCs from HD patients showed significantly enhanced allogeneic T-cell proliferation compared to healthy controls.
Our data demonstrate aberrant DC function in HD patients and suggest that this might contribute to impaired immune responses.
Clinical and Experimental Nephrology 03/2011; 15(4):546-53. · 1.37 Impact Factor
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ABSTRACT: An increased percentage of pro-inflammatory CD14(+)CD16(+) monocytes might contribute to inflammation in hemodialysis (HD) patients. The purpose of the study was to evaluate the possible contribution of pro-inflammatory monocytes to inflammation in HD patients and also to evaluate the effect of on-line hemodiafiltration (HDF).
Flow cytometric detection of monocytes in patients undergoing HD, on-line HDF and healthy controls as well as plasma cytokines and cytokine mRNA measurement were performed.
Percent pro-inflammatory monocytes, plasma cytokines and cytokine mRNA significantly increased in HD patients. Intracellular cytokine staining showed pro-inflammatory monocytes were the predominant source of tumor necrosis factor-α. Percent pro-inflammatory monocytes positively correlated with plasma inflammatory cytokines. Percent pro-inflammatory monocytes, plasma cytokines and cytokine mRNA significantly decreased in on-line HDF patients.
Increased pro-inflammatory monocytes are likely to contribute to inflammation in HD patients, and beneficial effect of on-line HDF might be partially mediated by modulating the inflammatory response.
Blood Purification 01/2011; 31(4):281-8. · 2.10 Impact Factor
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ABSTRACT: End-stage renal disease patients are known to be in a state of chronic low-grade inflammation and to have high infection-related morbidity and mortality. However, the precise mechanisms are not understood. The purpose of this study was to determine the mechanisms underlying chronic low-grade inflammation and defects in innate immune responses in hemodialysis (HD) patients.
In 33 HD patients, we measured the basal status of toll-like receptor 4 (TLR4) positivity in the CD14-positive monocyte population in the peripheral blood (not strong, i.e., CD14(low)), with plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12p70 compared with 22 healthy controls. After stimulation by lipopolysaccharide (LPS), the plasma cytokine response was also compared.
In the basal state, the percentage of peripheral blood TLR4(+)CD14(low) monocytes and plasma cytokines were significantly higher in HD patients (p < 0.05), suggesting that preactivated primed monocytes might be responsible for the chronic inflammatory state in HD patients. However, upon LPS challenge, the fold increase in plasma cytokine response was significantly reduced in HD patients (p < 0.05) compared with controls. More importantly, the fold increase of these cytokines showed a positive correlation with plasma albumin (p < 0.05) and a negative correlation with C-reactive protein (CRP) (p < 0.05), suggesting the presence of a possible link between chronic low-grade inflammation and suboptimal innate immune response.
Chronic low-grade inflammation due to preactivated peripheral blood CD14(+) leukocyte subset might be a mechanism for impaired innate immune responses, thus resulting in the high rates of infection-related morbidity and mortality observed in HD patients.
Clinical and Experimental Nephrology 12/2010; 15(2):258-63. · 1.37 Impact Factor
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ABSTRACT: Dendritic cells have the potential to induce tolerance and here we attempted to identify their role in the tolerance seen in ischemic pre-conditioning. We induced bilateral renal ischemic preconditioning in mice and then challenged them with an ischemic insult 7 days later. Compared to sham-operated controls, preconditioned mice were found to have reduced injury with less inflammation, but had an increased number of regulatory T cells (Tregs) in their kidneys after the delayed insult. Splenocytes from these mice had more Tregs and mature CD11c(+) cells, but reduced proliferative and cytokine-secretory responses, suggesting a state of immunosuppression compared to control mice. Anti-CD25 depletion followed by adoptive transfer of Tregs partially mitigated and then restored the protective effect of preconditioning. Depletion of CD11c(+) cells with liposomes containing clodronate was associated with partial loss of preconditioning benefits. The increased numbers of Tregs or impaired immune response found in splenocytes from preconditioned mice were partially reversed in splenocytes from liposome clodronate-treated animals, suggesting that CD11c(+) cells contribute to immune cell-mediated ischemic preconditioning. Hence, our results show that ischemic preconditioning of the kidney provides a negative signal to the peripheral immune system, partially mediating the tissue-protective and anti-inflammatory effects of this maneuver.
Kidney International 11/2010; 78(10):981-92. · 6.61 Impact Factor
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ABSTRACT: Continuous catalytic hydrodechlorination of polychlorinated biphenyls (PCBs) in the presence of transformer oils was carried out in a fixed bed reactor using a 57.6 wt% Ni on silicon oxide-aluminum oxide (SiO(2)-Al(2)O(3)) catalyst. Reaction temperatures ranging 150-300 degrees C, PCBs concentrations ranging 50-200 ppm, and reaction times ranging 1-8 h were tested. At a higher reaction temperature or at a lower PCBs concentration, catalytic activity was higher and complete dechlorination of PCBs resulted even at long reaction time. Catalyst regeneration using hexane and 0.1 M sodium hydroxide (NaOH) was effective to restore the catalytic activity. Fresh, spent and regenerated catalysts were characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis. XRD analysis revealed growth of Ni crystallite size of the spent and the regenerated catalysts. XPS analysis showed that a considerable amount of chlorine and carbon species were deposited on the surface of the spent catalyst, which may play a role in the catalysts deactivation.
Journal of Environmental Science and Health Part A Toxic/Hazardous Substances & Environmental Engineering 12/2009; 44(14):1538-44.
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ABSTRACT: Catalytic hydrodechlorination of polychlorinated biphenyls (PCBs) in the presence of transformer oil was carried out in a batch mode to detoxify PCBs and to recycle the treated oil. Various metal supported catalysts, including 0.98 wt% Pt, 0.79 wt% Pd and 12.8 wt% Ni on gamma -alumina (gamma -Al(2)O(3)) support, and 57.6 wt% Ni on silicon oxide-aluminum oxide (SiO(2)-Al(2)O(3)) support were used for the hydrodechlorination. Metal particle size of the Pt catalyst was 2.0 nm and metal particle sizes of the Pd and Ni catalysts were in the range of 6.4-6.9 nm. Various supercritical fluids, supercritical carbon dioxide (scCO(2)), supercritical propane (scPropane), supercritical dimethyl ether (scDME) and supercritical isobutane (scIsobutane) were used as reaction media. PCBs conversion, dechlorination degree of PCBs, was measured using gas chromatograph (GC) with an electron capture detector (ECD). The hydrodechorination degree increased in the order Ni > Pd > Pt, possibly due to higher metal loading and larger metal size of the Ni catalysts. At temperatures below 175 degrees C, scCO(2) was effective as the reaction media for the catalytic hydrodechlorination of PCBs in the presence of the transformer oil. However, PCBs conversion decreased significantly when the hydrodechlorination was carried out in a homogeneous phase with using scPropane, scDME or scIsobutane as a reaction medium. This was attributed to dilution effect of the supercritical fluids. Molecular weights of the transformer oils before and after the catalytic hydrodechlorination were analyzed using high-performance size exclusion chromatography (HPSEC). The molecular weight of the treated oil with 100 % PCBs conversion did not change after the catalytic hydrodechlorination at 200 degrees C. This process has proven to be effective to detoxify PCBs containing transformer oil and to recycle the treated oil.
Journal of Environmental Science and Health Part A 05/2009; 44(5):494-501. · 1.19 Impact Factor
