64 Subsequent studies demonstrated that renal injury was prevented in fH knockout mice that were also C5-deficient or when given an inhibitory anti-C5 antibody, suggesting that terminal complement activation contributes to the pathology.59 Interestingly,

when fI KO mice were generated they also showed low plasma C3 levels, indicating complement consumption, but unlike fH knockout mice they did not develop MPGN.81 Furthermore, fH/fI double deficient mice also failed to develop MPGN.81 Because fI converts C3b into iC3b and C3d, these data suggest that the development of MPGN may depend more on the forms of activated C3 generated by the AP. Thrombotic microangiopathies are a group of diseases characterized by thrombocytopenia, microangiopathic haemolytic anaemia, and either impaired renal or neurologic BTK inhibitor supplier function.82 Thrombotic Temsirolimus mouse thrombocytopenic pupura has varying degrees of renal impairment, but many other organs can be affected, particularly the nervous system. Contrastingly, haemolytic uraemic syndrome (HUS) is another disease in this category, but symptoms are largely restricted

to the kidney. There are two types of HUS, distinguished by the presence or absence of diarrhoea caused by Shiga toxin-producing bacteria.82 Diarrhoea-positive, or D+ HUS, is the most common form of HUS and can usually be cured with antibiotics and symptomatic treatment.82 On the other hand, diarrhoea-negative HUS, often referred to as atypical HUS (aHUS), only makes up 5–10% of HUS cases but has a much poorer prognosis.83 Approximately 50% of aHUS patients progress to end-stage renal failure and at least 25% of cases are fatal.84 It is still unclear what triggers aHUS episodes although it is believed to be initiated by endothelial Selleck Erastin cell injury caused by

infection or other exogenous injury.35 While mutations in procoagulant proteins such as thrombomodulin have been found in some aHUS cases,85 the majority of mutations found in aHUS patients have been with AP complement proteins. A multitude of clinical studies over the last decade have demonstrated that at least half of the familial cases of aHUS are caused by mutations in the complement system that lead to uncontrolled AP activation.25,35,86 While a few cases have reported mutations in C3 or fB that tend to produce aberrant C3bBb convertases more resistant to inactivation,87–89 most mutations affect the function of regulatory proteins fH, fI and MCP.35,90,91 In fact, the genes for these proteins are all located on the same region of chromosome 1 (1q32), called the regulators of complement activation gene cluster,92,93 making the latter a ‘hot’ chromosomal spot for aHUS-related mutations. A few cases of dysfunctional C4bp have also been reported,94 but interestingly DAF, another regulators of complement activation gene, has not been linked to any aHUS patients to date.

Interestingly, in

IgA nephropathy, glomerular deposition of ficolin-2 with local lectin pathway activation was associated with more severe renal disease [37]. According to our findings, pregnant women with low circulating levels of ficolin-2 or ficolin-3 have an increased risk for pre-eclampsia. Low ficolin-2 and ficolin-3 levels have already been linked to various pathological conditions, such as combined allergic and infectious respiratory disease in children [38,39], bronchiectasis [40], prematurity, low birth weight and perinatal infections [41], sarcoidosis [42], susceptibility to fever and neutropenia in pediatric cancer patients [43] and to neonatal sepsis [44]. Moreover, our research group has demonstrated recently that low ficolin-3 levels in early follow-up serum samples Crizotinib ic50 are related to the severity and unfavourable outcome of acute ischaemic stroke [45]. Genetic variations were shown to affect ligand binding or circulating levels of ficolins [46–48] and to associate with several disorders, including rheumatic fever and chronic rheumatic heart disease [49], bacterial and cytomegalovirus infections after orthotopic liver transplantation [50,51], and even immunodeficiency [52]. As pre-eclampsia is a multi-factorial disease with genetic components, the role of ficolin gene polymorphisms should be examined in buy BMN 673 the

future in the risk of this pregnancy-specific disorder. In our study, the similar plasma ficolin-2 and ficolin-3 levels of pre-eclamptic patients regardless of the severity, the time of onset of the disease or the presence click here of fetal growth restriction might be explained by the complex aetiology of pre-eclampsia. Several genetic, behavioural and environmental factors need to interact to produce the complete picture of this pregnancy-specific disorder. We reported various genetic and soluble factors that were associated with the severity

or complications of pre-eclampsia, including HELLP syndrome and fetal growth restriction [53–56]. Nevertheless, it is also possible that the relatively small sample size of this study prevented the detection of an effect in the subgroup analyses. Although pre-eclampsia is predominantly a disease of primiparas, multiparous women, especially with advanced age or over weight, can also be affected, as in our cases. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta. We thank Veronika Makó, László Cervenak and Levente Lázár for measuring plasma von Willebrand factor antigen and cell-free fetal DNA concentrations.

We believe that prolonged ischemia time and hypothermia precipitated erythrocyte sickling within the flap, causing intra-flap thrombosis that propagated to the pedicle. While sickle cell diseases are not a contraindication to free tissue transfer, we believe that flap cooling should be utilized with

caution in this circumstance. © 2012 Wiley Periodicals, Inc. “
“Surgical procedure of great toe wrap-around flap combined with second toe medial flap free transfer cAMP inhibitor for reconstructing completely degloved fingers was introduced. The treatment outcomes were evaluated. 10 fingers in 7 cases were involved in this series. The great toe wrap-around flap with dorsalis pedis skin covered the dorsal and most palmar side of the injured finger. The second toe medial flap covered the proximal palmar portion of the finger. The combined flap was revascularized

with nerve repair. Rehabilitation started Kinase Inhibitor Library cost two weeks postoperatively. All flaps survived except one was partial failure due to distal phalange necrosis. Recipient areas achieved primary wound healing in 9 fingers. Skin graft at donor site achieved primary survival except delayed healing in one case. All patients were followed-up from 34 to 76 months. The appearance of reconstructed fingers was satisfactory. Nail growth well except that one nail was the atrophic and another was defect. Range of active motion in the metacarpophalangeal joint was from 60° to 80° and the proximal interphalange joint was 40° to 70°. Two-point discrimination was between 8 mm and 12 mm. All patients walked with no interference. There was no pain and no swelling at donor site. According to the results, this procedure is recommended to reconstruct total degolving finger which has intact phalanges and tendons. © 2010 Wiley-Liss, Inc. Microsurgery 30:449–456, 2010. “
“Complete circumferential degloving injury of the digits usually results in a large cutaneous defect with tendinous structure and bone and joint exposure. When revascularization is not possible, a thin and adequately sized flap is required to resurface the defect, restore finger function,

and prevent amputation. In this report, we present our experience either with reconstruction of the entire circumferential degloving injury of the digits using free fasciocutaneous flaps. Between February 2006 and January 2011, 9 male patients with circumferential degloving injury of 9 digits underwent reconstruction using free fasciocutaneous flap transfer with the posterior interosseous artery flap, medial sural artery flap, anteromedial thigh flap, or radial forearm flap. The average flap size was 14.2 × 6.9 cm. Donor sites were closed primarily or covered with split-thickness skin graft. All flaps survived completely and the donor sites healed without complications. The mean follow-up period was 34.8 months. A maximum Kapandji score (10/10) was seen in 2 cases with crushed thumbs.

As described above, one remarkable result

of the analysis of the GM polymorphism is the observation of abrupt frequency changes between different continental areas worldwide. By subdividing the world into 10 continental or sub-continental regions (sub-Saharan Africa, North Africa, Europe, West Asia, Northeast Asia, Southeast Asia, Oceania, Circum-Arctic, North and Central America, and South America), we found a proportion of genetic diversity due to differences among regions of about 39%.12 This is much higher Ibrutinib than generally found (albeit based on a different subdivision of the world and different numbers of groups) for allozymes and DNA markers, of the order of 10–15%,22–24 and 3–7% for most HLA loci.25 Extreme values (up to 88%) of human genetic diversity among the main geographic regions have only been found for strongly selected biological traits like skin pigmentation, whereas craniometric

traits also fall within the range of neutrally evolving genetic markers.26,27 We may ask ourselves whether, because of the immunological function of IgG molecules expressing GM allotypes, the GM polymorphism is subject to some kind of (directional) selection. Indeed, some studies have suggested that GM haplotypes were involved in susceptibilities to autoimmune diseases (see ref. 28,29 buy R428 for a review) and infectious diseases like malaria30–32 or filariasis.33 However, conclusive evidence

for disease associations has not been found. Moreover, we did not detect any departure from selective neutrality by using Ewens–Watterson’s tests (with Bonferroni’s correction) on 82 populations tested for GM worldwide.12 Therefore, our explanation of the unusual apportionment of genetic diversity observed for the GM polymorphism is, first, that this system has been tested by serological typing, thereby providing only a broad description of its molecular variation, and, second, as explained above, that the frequencies of the most frequent haplotypes Cell press in each geographic region are over-estimated because most GM frequencies were estimated by following a parsimonious approach considering a minimum number of haplotypes deduced ‘by hand’ from the phenotypic distributions. As a consequence, the proportion of genetic variation observed among regions has probably also been over-estimated. On the other hand, the most frequent GM haplotypes defined by serology may be seen as broad GM haplogroups including phylogenetically related haplotypes, an interpretation that is sustained by previous analyses performed at the DNA sequence level34 and that recalls the definition of Y-chromosome (non-recombining region, or NRY) haplogroups.35 The Y-chromosome markers deviate from other DNA markers in being, like GM, highly structured at the global scale: according to Hammer et al.

All of patients except for one regained protective sensation from 3 to 12 months postoperatively. Our experience Fostamatinib chemical structure showed

that the sural flap and saphenous flap could be good options for the coverage of the defects at malleolus, dorsal hindfoot and midfoot. Plantar foot, forefoot and large size defects could be reconstructed with free anterolateral thigh perforator flap. For the infected wounds with dead spce, the free latissimus dorsi musculocutaneous flap remained to be the optimal choice. © 2013 Wiley Periodicals, Inc. Microsurgery 33:600–604, 2013. “
“The aim of this study was to investigate intestinal ischemia-reperfusion and its local and systemic hemorheological relations in the rat. Ten anaesthetized female CD outbred rats were equally divided into 2 experimental groups. (1) Ischemia-reperfusion (I/R): the superior mesenterial artery was clipped for 30 minutes. After removing the clip, 60 minutes of the reperfusion was observed before extermination. Blood samples were taken from the caudal caval vein and from the portal vein before

ischemia, 1 minute before and after clip removal, and at the 15th, 30th, and 60th minutes of the reperfusion. (2) Sham operation: median laparotomy and blood sampling were done according to the timing as in I/R group. Hematological parameters, red blood cell aggregation, and deformability were determined. Leukocyte Talazoparib molecular weight count and mean volume of erythrocytes increased slightly but continuously in portal venous samples during the reperfusion period. Red blood cell aggregation values were higher in portal blood by the end of ischemia, and then became elevated further comparing to the caval venous blood. Both in caval and portal venous samples of I/R group red blood cell deformability significantly worsened during the experimental

period compared to its base and Sham group. In portal blood red blood cell deformability was impaired more than in caval vein samples. Histology showed denuded villi, dilated capillaries, and the inflammatory cells were increased after a 30 minutes ischemia. In conclusion, intestinal ischemia-reperfusion causes changes Rebamipide in erythrocyte deformability and aggregation, showing local versus systemic differences in venous blood during the first hour of reperfusion. © 2009 Wiley-Liss, Inc. Microsurgery, 2010. “
“Closing large skin defects of the upper back is a challenging problem. We have developed an efficient design for a latissimus dorsi musculocutaneous flap for reconstruction in this region. The longitudinal axis of the skin island was designed to be perpendicular to the line of least skin tension at the recipient site so that primary closure of the flap donor site changed the shape of the recipient site to one that was easier to close. We used this method for four patients with skin cancers or soft-tissue sarcomas of the upper back in 2011 and 2012.

Since the uptake of virus–antibody complexes is more efficient than the entry of free virus through host cell receptor,

DENV infection is enhanced.[2, 29] It is not well understood how a greater viral load emerges from ADE-infected cells and how a greater viral load would provoke severe disease, especially because increased viral load alone is not the direct cause of plasma leakage.[1, 16] The final interpretation of ADE in terms of mechanisms and real impact on disease remains to be further explored. There is no perfect Paclitaxel solubility dmso animal model to the study of DENV infection pathogenesis. A great part of these studies was performed using patient samples (plasma or peripheral blood mononuclear cells). These studies were descriptive and a link between systemic and local immune responses in the course of infection is frequently not possible to address. Non-human primates have been extensively used to study ADE and to test the efficacy and safety of pre-clinical vaccines.[39] However, there is an intense debate in terms of cost and accessibility of these models to answer precise questions about disease pathogenesis. In the face see more of those limitations, a genetically appropriate mouse model would be essential

to determine how different immune system components regulate a protective immune response, and to investigate how T cells and other leucocytes, endothelial cells and cytokines contribute to severe disease during primary and secondary heterologous infection. Idoxuridine Initial attempts to develop a mouse model for dengue in immunocompetent mice with high titre viral infection were unable to recapitulate several important aspects of human DENV infection, including replication in peripheral tissues and development of the hallmark symptoms of DENV disease.[19, 40] Immune-competent mouse models have been shown to be resistant to DENV infections, because of the ability of their innate immune system to respond efficiently with total viral clearance, though success has been seen with mouse-adapted viruses

and/or artificial infection routes such as intracranial and intraperitoneal injection. In vivo studies have shown that DENV inhibits type I IFN production and that lack of type I IFN response renders mice susceptible, indicating that this mechanism of immune response subversion is critical for DENV success and so affects transmission.[41, 42] In addition, others have shown that downstream protein expression induced by type I IFN and the Janus kinase/STAT pathway play important roles in DENV infection control.[42, 43] Sabin and Schlesinger showed in 1945 that DENV can be propagated by intracerebral inoculation in mice.[44] Even if the initial adaptation to the mouse seemed to be a tedious and difficult process, 16 consecutive passages have been achieved and the virus propagated in mice produced dengue in human volunteers, but was not pathogenic for cotton rats, hamsters, guinea-pigs or rabbits.

Consequently, upon migrating into the intestinal lymph nodes, CD103+ DCs produce RA, which in turn drives the expression of gut-specific homing receptors (CCR9 and α4β7) by activated T and B cells [16, 17]. However, while RA is now well accepted to condition DCs within the intestine, its contribution to DC development elsewhere in the body is not yet fully resolved. Given this association with intestinal immunity, Beijer et al. [13] set out to examine whether vitamin A influences the splenic DC composition and made the intriguing discovery that, relative to splenic CD8+ DCs (CD11bloCD4−CD8hi), splenic CD4+ DCs (CD11bhiCD4hiCD8−), and splenic DN DCs (CD11bhiCD4−CD8−) have

elevated expression of a number of RA target genes (MMP9, gp91hox, and TG2). It was also observed that CD4+ DCs and DN DCs express gene signatures indicative of preferential RA metabolism and utilization. check details To determine whether these RA responsive elements in CD4+ DCs and DN DCs reflect developmental or functional dependencies on vitamin A, the authors fed newborn mice (day 7.5–10 of gestation) a vitamin A-deficient diet and analyzed the relative proportion of the three DC subsets in the spleen after at least 9 weeks of diet. Strikingly, while the relative proportion of CD8+ DCs remained

unaffected by the absence of RA, there was a significant reduction in the proportion of both CD4+ DCs and DN DCs. Collectively, this suggests that in contrast selleck inhibitor to CD8+ DCs, CD11bhi

DCs are subject to RA signaling and that these signaling events are necessary for their differentiation within the spleen. To further probe the activity of RA in shaping the differentiation of splenic DCs, Beijer et al. [13] performed the reverse experiment, placing mice on a RA-rich diet before examining the relative proportion of the three DC subsets in the spleen. Here, excessive RA resulted in a shift toward DN DCs. Specifically, the frequency of CD11bhi DN DCs increased dramatically in the spleen, while the proportion of CD8+ DCs and, unexpectedly, CD4+ DCs was significantly suppressed in mice fed the vitamin A-rich diet. The lack of an increase in CD4+ DCs in response to RA overexposure and MRIP subtle, but significant differences in the expression patterns of some of the nuclear RA receptors (RXRα, RARα, RXRβ) between CD4+ DCs and DN DCs are likely related to heterogeneity within the CD11bhi DC population. Indeed, when Beijer et al. [13] segregated CD11bhi DCs on the basis of ESAM expression, which has recently been shown to resolve two distinct subsets within the CD11bhi DC population [11], they noted that RA specifically affected ESAMhi CD11bhi DCs with this subset being selectively reduced in the absence of RA and increased upon overexposure to RA.

To this end, we used two human cell lines as targets: (i) the HTLA-230 neuroblastoma cells that display a low basal sensitivity to TCRγδ+ T cell-mediated lysis and (ii) the DAUDI Burkitt lymphoma cells that show high sensitivity to TCRγδ+ T-cell mediated lysis. As shown in Fig. 2A, IL-27 pretreatment rendered

activated Vγ9Vδ2+ T cells more effective in HTLA-230 cell lysis at different Selleck Erismodegib E:T ratios (E:T ratio, percent specific lysis, medium versus IL-27: 50:1, 38.5 versus 55.5, p < 0.001; 25:1, 33.25 versus 46.5, p < 0.01; 12:1, 27 versus 36.5, p < 0.05; 6:1, 18.25 versus 28.5, p < 0.05; 3:1, 13 versus 22.75, p < 0.05). The addition of anti-TCR Vγ9, but not of anti-NKG2D blocking mAb, inhibited target cell lysis, thus

indicating that HTLA-230 cell line recognition was mediated by TCR (Fig. 2A, inset). Furthermore, IL-27 pretreatment rendered both resting and activated Vγ9Vδ2+ T cells more effectively against DAUDI target cells (Fig. 2B, E:T ratio, percent specific lysis, medium versus IL-27: activated: 25:1, 80 versus 96, p < 0.001; 12.5:1, 80 versus 96, p < 0.001; 6:1, 69 versus 92, p < 0001; 3:1, 60 versus 91, p < 0.001; 1.5:1, 55 versus 82, p < 0.001; resting: 25:1, 21.5 versus 33.5, p < 0.01; 12.5:1, 16 versus 28, p < 0.01; 6:1, 11 versus 21.5, p < 0.01; 3:1, 6.5 versus 9.5, ns; 1.5:1, 3 versus 3.5, ns). As shown in Fig. 2C and D, IL-27-mediated increase of TCRγδ+ T cell cytotoxicity was closely related to the stimulation of cytotoxic granules production, as demonstrated by significant

increase of Granzyme B (MRFI mean ± SD: activated Vγ9Vδ2+ T cells treated MK-8669 in vitro with medium versus IL-27 = 84.61 ± 2.29 versus 124.6 ± 12.87, p = 0.04; resting Vγ9Vδ2+ T cells treated with medium versus IL-27 = 63.01 ± 7.57 versus 94.29 ± 16.28, p = 0.04) and perforin (MRFI mean ± SD: activated Vγ9Vδ2+ T cells second treated with medium versus IL-27 = 1.29 ± 0.02 versus 3.08 ± 0.09, p = 0.0003; resting Vγ9Vδ2+ T cells treated with medium versus IL-27 = 10.28 ± 0.69 versus 16.14 ± 0.53, p = 0.003). Finally, IL-27 significantly increased Granzyme A in resting Vγ9Vδ2+ T cells (MRFI mean ± SD: medium versus IL-27-treated cells = 12.76 ± 1.05, versus 16.77 ± 2.01, p = 0.04) but not in activated Vγ9Vδ2+ T cells (MRFI mean ± SD: medium versus IL-27-treated cells = 9,43 ± 1.49 versus 10.45 ± 1.19) (Fig. 2C and D). Finally, the IL-27 role on TCRγδ+ T-cell function was investigated in terms of modulation of (i) cytokine release and (ii) expression of chemokine receptors (CXCR3, CCR5, and CCR6), activating/inhibitory receptors (CD16, TCRγδ, NKG2A), and of the adhesion molecule CD62L. These experiments revealed that IL-27 significantly downregulated Th2-type cytokine secretion in activated Vγ9Vδ2+ T cells, as demonstrated by the inhibition of IL-5 (pg/mL ± SD: medium 177.6 ± 34.22, IL-27 108.5 ± 41.02, p = 0.04) and IL-13 (pg/mL ± SD: medium 1969 ± 313.

Macrophages are thought to promote renal fibrosis and tubular damage in the obstructed kidney. Furthermore, upregulation of MMP-12 expression by infiltrating Tyrosine Kinase Inhibitor Library nmr macrophages in the obstructed kidney has been described, but the potential role of MMP-12 in renal injury induced by this non-immune insult is unknown. Methods:  Groups of eight MMP-12 gene deficient (MMP-12−/−) and wild type (WT) C57BL/6J mice were killed 3, 7 or 14 days after UUO. Results:  Analysis of three different lineage markers found no difference in the degree of interstitial macrophage accumulation between MMP-12−/− and WT UUO groups at any time point. Examination of renal fibrosis by total collagen staining,

α-SMA + myofibroblast accumulation, and TGF-β1, PAI-1 and collagen IV mRNA levels showed no difference between MMP-12−/− and WT UUO groups. Finally, tubular damage (KIM-1 levels) and tubular

apoptosis (cleaved caspase-3) in the obstructed kidney was not affected by MMP-12 gene deletion. Conclusion:  In contrast to lung injury and antibody-dependent glomerular injury, MMP-12 is not required for renal interstitial macrophage accumulation, interstitial fibrosis or tubular damage in the obstructed kidney. “
“Aim:  The development of lupus nephritis (LN) is associated with increased morbidity and mortality. In view of scarce data from South Africa on factors affecting renal outcome in LN, the authors’ experience was reviewed to identify predictors of poor renal outcome. Methods:  This is a retrospective

review of 105 patients with biopsy-proven LN under our care from January https://www.selleckchem.com/products/Deforolimus.html 1995 to December 2007. Results:  Forty-three (41.0%) patients reached the composite end-point of persistent doubling of the serum creatinine over the Methisazone baseline value, development of end-stage renal disease (ESRD) or death during a mean follow-up period of 51.1 months (range 1–137 months). Baseline factors associated with the composite end-point included presence of systemic hypertension (P = 0.016), mean systolic blood pressure (SBP) (P = 0.004), mean diastolic blood pressure (DBP) (P = 0.001), mean serum creatinine (P = 0.001), estimated glomerular filtration rate (eGFR) (P = 0.003) and diffuse proliferative glomerulonephritis (World Health Organization class IV) (P = 0.024). Interstitial inflammation (P = 0.049), failure of remission in the first year following therapy (P < 0.001), the mean SBP on follow up (P < 0.001) and mean DBP on follow up (P < 0.001) were also associated with composite end-point. On multivariate analysis, baseline serum creatinine, non-remission following therapy (P = 0.038) and mean SBP on follow up (P = 0.016) were predictors of poor renal outcome. Conclusion:  Baseline serum creatinine, failure of remission in the first year and mean SBP were predictors of poor renal outcome.

However, the

role of innate immunity in diabetic nephropathy (DN) has yet to be demonstrated. The aim of this study was to investigate the expression of toll-like receptors (TLR) and its ligands in human kidney tissue of DN. Methods: We studied 12 type 2 DN patients with renal biopsy, and 12 patients with nephrectomy for renal cancer served as controls. Clinical characteristics were recorded, and intrarenal expression of TLRs (TLR2 and TLR4) and its ligands (heat shock protein70, HSP70 and MYD88) was examined by immunohistochemistry. Results: The intrarenal expression of TLR2 was markedly decreased in glomerulus of the DN group (1.30 ± 0.21%/mm2 vs. 28.50 ± 3.45%/mm2, P < 0.01), whereas its expression was increased in the tubulointerstitum (16.55 ± 0.75%/mm2 vs. 8.93 ± 0.62%/mm2, P < 0.05), and this trend was accompanied by MYD88 expression (Glomerulus:

1.76 ± 0.60%/mm2 PF-02341066 cell line EX 527 concentration vs. 90.92 ± 10.69%/mm2; tubulointerstitum: 24.48 ± 2.38%/mm2 vs. 16.15 ± 1.12%/mm2, P < 0.01, respectively). In contrast, TLR4 immunoreactivity was significantly increased in the glomerulus of DN group (45.65 ± 3.08%/mm2 vs. 31.61 ± 1.32%/mm2, P < 0.01) but not in the tubulointerstitum. HSP70 expression, a TLR ligand, was significantly increased in the DN group compared with the Con group (Glomerulus: 91.40 ± 13.88%/mm2 vs. 50.91 ± 4.07%/mm2; tubulointerstitum: 19.27 ± 1.23%/mm2 vs. 9.25 ± 0.74%/mm2, P < 0.01, respectively). Correlation new analysis revealed that TLRs expression was correlated with the proteinuria and the eGFR. Conclusion: These findings suggest that an alteration in TLRs and its ligands expression is closely associated with diabetic renal injury, and that innate immunity may be one of important

players in type 2 DN. FUJITA TAKAYUKI1, WATANABE HIDETSUNA WATANABE2, HEMMI SEIICHIRO1, YABUKI MINAKO1, FUKE YOSHINOBU1, SATOMURA ATAUSHI3, SOMA MASAYOSHI1,4 1Department of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine; 2Department of Internal Medicine, Sakuboukai Tokiwadaigeka Hospital, Tokyo, Japan; 3Department of Laboratory Medicine, Nihon University School of Medicine, Tokyo, Japan; 4Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan Introduction: Glomerular endothelial injury is commonly encountered in diabetic nephropathy, as in type 2 diabetes mellitus (T2DM). Microalbuminuria is associated with endothelial cell dysfunction, and is a significant risk factor for cardiovascular mortality in diabetes. This study was undertaken to study the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, on microalbuminuria as a mechanism of improving glomerular endothelial injury in patients with T2DM. Methods: Sitagliptin, a DPP4 inhibitor, was administered to twenty patients with T2DM, 50 mg/day, for 8 weeks.