IgA antibody response to both antigens did differ in Mtb-infected and non-infected subjects. Moreover, there was a positive correlation between the level of IFN-γ induced by the specific antigens and the level of serum IgA against ESAT-6/CFP-10 and Rv2031 in healthy Mtb-infected U0126 mouse subjects. These results encourage further follow-up studies on the specific roles of IgA antibody and its subclasses in the progression of Mtb infection and of the immunodiagnostic test using additional antigens in population under various epidemiological settings of the disease. ML designed the study, participated in data collection, data analysis and drafted the manuscript. GA participated in designing the study, data

collection, analysis and write-up. GMD participated in designing the study, data analysis and interpretation and write-up. GM participated in designing the study and write-up. KF produced the recombinant antigens for the study and write-up. TO participated in selleck chemicals llc designing of the study, the writing up of the manuscript, and supervised antigen production and its QC. GB involved in designing of the study and critically revised the manuscript. FA involved in designing the study and write-up of the manuscript and critically revised the manuscript. All authors read and approved the final manuscript. ML is the guarantor of the manuscript. We are grateful to study participants, Afar Regional and Amibara District Health

Bureau, Dubti hospital, Meleka Werer Health Centres. We would like to thank nurse Gezahegn Getachew, staff of Melka Werer Health Centre, for his assistances in physical and clinical examinations. We would like to thank Mr. Sisay Dessie, Mr. Girma Kebede and Ms

Kokobe Gebre-Michael for their technical assistance. We would like to thank staff of Dubti hospital for their technical and clinical examinations of patients suspected of PTB. We would also like to thank staff of Armauer Hansen Research Institute for their cooperation during selleck chemicals laboratory work. The study was financially supported by Norwegian Programme for Development, Research and Education, NUFU (NUFU PRO-2007/10198) as well as the Research Council of Norway. “
“The pathogenesis of vitiligo is still controversial. The purpose of this study was to gain insight into the nature of lymphoid cells infiltrating depigmented areas of skin in vitiligo. Immunochemical procedures were carried out in biopsies from 20 patients with active lesions to search for cells expressing CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD25, CD30, CD56, CD68 and CD79a. Results indicate that early lesions are infiltrated mainly by dendritic cells, whereas older lesions display significantly lower proportions of these cells and increased percentages of mature T cells. This finding might suggest that the autoimmune reactivity towards melanocyte antigens might be T cell-dependent and antigen-driven.

01 (95% CI 0.70–1.44; P=0.97), respectively, compared with the 1513 A and −762 T alleles. Polymorphisms at the 1513 locus had a statistically significant association with P2X7 variants

and tuberculosis susceptibility, while the −762 locus allele variants were not significantly associated with P2X7 variants and tuberculosis susceptibility. Tuberculosis is a major cause of morbidity and mortality worldwide, especially in Asia and Africa. Genetic variability, combined with environmental factors, are expected to contribute to the risk of developing active tuberculosis (Cooke & Hill, 2001). Human P2X7, which encodes the P2X7 receptor, has been cloned and mapped to human chromosome 12q24 and linked to tuberculosis susceptibility (Buell et al., 1998). The MEK inhibitor P2X7 receptor is a ligand-gated cation channel that is highly expressed on human and murine macrophages (Nicke

et al., 1998; Gu et al., 2001). The activation of P2X7 by adenosine Compound Library chemical structure triphosphate (ATP) causes the immediate opening of a cation-selective channel, allowing the influx of Ca2+ and Na+ and the efflux of K+. This initiates a number of downstream signaling events, including caspase activation, resulting in apoptosis and phospholipase D (PLD) activation, which promotes phagosome–lysosome fusion, resulting in mycobacteria death (Humphreys et al., 2000; Kusner & Barton, 2001; Coutinho-Silva et al., 2003). P2X7 is highly polymorphic and several single nucleotide polymorphisms (SNPs) that

lead to loss of receptor function have been described (Fernando et al., 2005; Shemon et al., 2006). The most common is the 1513AC polymorphism, resulting in a glutamic acid to alanine substitution at position 496. This substitution results in the expression of a nonfunctional P2X7 receptor in macrophages from subjects homozygous for the 1513 C allele and patients heterozygous at this locus have impaired P2X7 receptor function. Additionally, the −762TC SNP Adenosine triphosphate in the P2X7 promoter region has been shown to be protective against tuberculosis in a Gambian population (Li et al., 2002). However, there is no evidence that the −762 C allele has functional consequences for gene expression. Several studies have looked at associations between the P2X7 gene 1513 and −762 loci allele variants and susceptibility to tuberculosis; however, these analyses have yielded mixed results depending on the population studied, in part due to the lack of adequate statistical power, selection bias or population diversity. Because a metaanalysis may overcome some of these methodological difficulties, a systematic review of the literature using metaanalysis was carried out as a means of providing a quantitative estimate on the association between P2X7 polymorphisms and susceptibility tuberculosis. To the best of our knowledge, no metaanalysis of the literature exploring the relationship between P2X7 gene polymorphisms and susceptibility to tuberculosis has been carried out to date.

pneumoniae is the use of LAB as carriers of different pneumococcal antigens. In previous studies we have demonstrated that immunization with PppA, expressed learn more as a wall-anchored protein on the surface of L. lactis, was able to induce cross-protective immunity against different pneumococcal serotypes, afforded protection against both systemic and respiratory pneumoccocal challenges, and induced

protective immunity in adult and infant mice [16]. Additionally, on the basis of previous studies, we have demonstrated that the nasal route is the best alternative for protection against a pneumococcal infection using L. lactis as adjuvant [14,15] and as antigen delivery vehicle [16,31]. This agrees with the findings of other researchers HDAC inhibitor who demonstrated the convenience of the nasal route for the immunization of mucosae against respiratory pathogens [32,33]. In this work we have assessed new immunization strategies using an inactivated recombinant bacterium by itself and in association with a probiotic strain. Analysis of the immunostimulatory properties of non-viable LAB strains showed that they depend upon the strain used, although

there is evidence indicating that viable bacteria are more effective for mucosal immunostimulation. In most cases, heat-killed strains were assessed in which differences in immunostimulation might be associated with heat-induced alteration of epitopes [34]. In order to conserve the structure of the PppA expressed in the surface of L. lactis, death was carried out by chemical inactivation. The inactivated strain proved to be effective for the induction of high levels of specific IgA and IgG antibodies in BAL and of IgG in the serum of the vaccinated young mice, which

were higher than those obtained with the live vaccine. The association of the live and dead vaccines with the probiotic increased specific anti-PppA antibodies, reaching maximum values in the D-LL + Lc (N) group. The increase in IgA and IgG anti-PppA is of fundamental importance at the lung level, because while IgA prevents pathogen attachment to epithelial cells, during thus reducing colonization, IgG would exert protection at the alveolar level, promoting phagocytosis and preventing local dissemination of the pneumococcus and its passage into blood [35]. We demonstrated that the vaccine-induced humoral immune response was increased in all assessed groups at both the lung and systemic compartments, although the highest levels of specific antibodies were obtained when the vaccine, dead or live, was associated with the probiotic. This was coincident with the increase in IL-4 in the lung compartment, indicating activation of the Th2 cell population, which enhanced the humoral immune response. Recent reports have shown that certain lactobacilli improved the specific antibody response after vaccination against some viral and bacterial pathogens [21,36]. In addition, L.

We conclude that cellular differentiation of pre-BI cells to a pre-BII-like stage, induced by the removal of IL-7, is delayed, but not inhibited by the doxycycline-induced overexpression

of Myc and Pim1, as judged by the retarded loss of c-kit expression, the retarded loss of clonability on stromal cells in the presence of IL-7 and by the slower gain of CD25. Furthermore, CH5424802 cell line acquisition of IgM on the surface or intracellularly is blocked. It appears that the Myc-single and the Pim1/Myc-double-transduced cells are arrested in differentiation before sIgM+ immature B cells. Transplantation of Pim1/Myc-double-overexpressing pre-BI cells in doxycycline-fed Rag1−/− recipient mice (Fig. 3) led to a marked expansion of CD19+ B-lineage cells in selleck chemicals vivo. In two separate experiments, the transplanted pre-B cells were kept either for 4 weeks (Fig. 3A–C) or for 8 weeks (Fig. 3D) in doxycycline-fed mice, followed each by a 4-week period without doxycycline in the drinking water. At 4 weeks, high numbers of transplanted cells overexpressing Pim1 and Myc were detected in BM, spleen and

peritoneum. At 8 weeks, the transplanted pre-B cells could also be detected in the swollen lymph nodes of the animals (data not shown). FACS analysis of the phenotypes of B lineage cells showed that spleens of doxycycline-induced mice, which harbored Pim1/Myc overexpressing B cells contained 100-fold higher numbers of pre-B cells, up to 6-fold higher numbers of immature IgM+ B cells, and up to twice the numbers of mature B cells than spleens of doxycycline-uninduced mice (Fig. 3B and C). The expanded number of cells detected after 8 weeks in BM, spleen, peritoneum and lymph nodes in the presence of doxycycline were, in majority, CD93+IgM− pre-B

cells (data not shown). Removal of doxycycline from the drinking water from transplanted mice 4 or 8 weeks after transplantation resulted in the disappearance of the previously expanded numbers of pre-B-, immature, and the slightly increased numbers of mature B cells from the spleen to normal numbers seen in uninduced mice (Fig. 3A, B and D). In a separate experiment, the capacities of Pim1/Myc-overexpressing pre-B cells to proliferate ex MycoClean Mycoplasma Removal Kit vivo after expansion in vivo were tested (Fig. 3E and F). These Pim1/Myc-overexpressing IgM− pre-B cells isolated from spleen and LNs of mice fed for 8 weeks with doxycycline could be propagated in vitro without IL-7 and OP9 cells in the presence, but not in the absence of doxycycline. Upon removal of doxycycline from these ex vivo cultures, the cells terminated proliferation and acquired IgM on their surface (Fig. 3F). The reasons for this oncogene-dependent inhibition of IgM expression are presently under detailed investigation.

3b-2, b-3) (17). We also found that clustering of RILP in the perinuclear regions was disrupted and diffused by the expression

of Rab7T22N. Collectively, our data demonstrate that Rab7 is vital for recruiting RILP to phagosomes during the maturation process, but not for recruiting CD63. How M.tb escapes the effects of the bactericidal components within the phagosome while still acquiring nutrients for growth is very important question. It has been suggested that mycobacterial phagosomes arrest their maturation at an early stage and completely avoid fusion with lysosomes (18, 19). However, we have shown the localization of CD63 (Fig. 2) and LAMP-2 (4) on M.tb phagosomes in macrophages. It Selleck Doxorubicin has been proposed that phagolysosome biogenesis is achieved by a series of fusions with heterogeneous lysosomes (20). This model is supported by a report demonstrating the existence of sub-populations of lysosomes in macrophages (6). Our previous and current studies demonstrating the alternative localization of lysosomal markers on M.tb phagosomes further support this model. From these observations, it seems that dissociation

of Rab7 from M.tb phagosomes selectively inhibits fusion with harmful lysosomes despite continued fusion with non-microbicidal lysosomes. In conclusion, based on our findings we propose the following model for M.tb-induced inhibition of phagolysosome biogenesis: Early M.tb phagosomes are capable of recruiting Rab7 and can potentially fuse with lysosomes. RILP is also recruited to M.tb phagosomes, which form the Rab7-RILP-dynein/dynactin protein complex followed by promotion of selleck chemicals llc phagolysosome biogenesis. However, viable M.tb is able to release Rab7 from phagosomes, resulting in inhibition of further fusion with lysosomal vesicles and disassembly of the RILP-phagosome complex. This causes the blocking of subsequent phagolysosome biogenesis. over On the other hand, non-microbicidal vesicles expressing CD63 and/or LAMP-2 continuously fuse with M.tb phagosomes

despite Rab7 dissociation, and this fusion would support the acquisition of nutrients for mycobacterial proliferation within the phagosome. We thank Drs. Toshi Nagata and Masato Uchijima (Hamamatsu University School of Medicine, Hamamatsu, Japan) for their helpful discussion. M.tb strain H37Rv was kindly provided by Dr. Isamu Sugawara (Research Institute of Tuberculosis, Tokyo, Japan). This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, COE Research and Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health and Labor Science Research Grants for Research into Emerging and Reemerging Infectious Diseases from the Ministry of Health, Labor and Welfare of Japan, and the United States-Japan Cooperative Medical Science Committee.

The basis of its stimulatory function is not well understood but is thought to occur through an as yet unidentified receptor.43 In contrast, many of the studies published to date have focused on its inhibitory function, which occurs by signaling through programmed death-1 (PD-1). B7-H1 shares this receptor with the related B7 family member B7-DC. B7-DC appears to have higher affinity for PD-1 than B7-H1,47 but its expression is much more limited than B7-H1, and is found predominantly on macrophages and DCs following cytokine

induction.48 Like B7-H1, Compound Library ic50 B7-DC exhibits dual inhibitory and stimulatory functions, but its restricted expression to APCs suggests that it primarily affects the priming stage of immune responses.49,50 PD-1 is expressed on activated T cells, B cells, and cells of the myeloid lineage and contains two cytoplasmic signaling domains consisting of an intracellular tyrosine inhibitory motif (ITIM) and an intracellular tyrosine switch motif (ITSM).51In vitro studies have suggested that the ITSM on PD-1 is critical for its inhibitory activity

and acts by recruiting SHP-1 and/or SHP-2 phosphatases which then interfere with CD28 signaling by preventing activation of phosphoinositide 3-kinase (PI3K) activation – a critical enzyme in CD28 signaling.52–54 The ultimate effect of PD-1 ligation on self-reactive T cells can be apoptosis or anergy. This regulatory pathway appears essential, as peripheral tolerance to some MHC class I-restricted self-antigens requires PD-1.55,56 In addition, genetic deletion of PD-1 results in severe autoimmunity buy Roxadustat because of the loss of peripheral tolerance of self-reactive T cells.57,58 Blocking PD-1 accelerated the onset and worsened the severity of both spontaneous and induced autoimmune disease.59,60 Similarly, accumulation of self-reactive T cells occurs when B7-H1 and B7-DC are depleted, resulting in increased susceptibility to induced autoimmune disease.46,61 T-cell exhaustion, a state of gradually acquired unresponsiveness to antigen,

can also occur when PD-1 is chronically ligated by B7-H1, although this phenomenon has only been implicated in the failure to clear infection, and it is not certain whether this occurs in tolerance to self-antigen.62 Finally, B7-H1 has also Methisazone recently been recognized to have a novel role in inducing differentiation of Tregs from naïve CD4+ T cells.63,64 There is also evidence that binding of PD-1 to B7-H1 or B7-DC can induce signaling through their intracellular domains, back into the APC; although the biological roles of this reverse signaling are less clear. Tumor cells receiving this signal become resistant to CTL-induced cytolysis, without the requirement for PD-1 signaling into the T cell.65 The signaling mechanism for this remains enigmatic but does require the approximately 30 amino acid, evolutionarily conserved cytoplasmic domain of B7-H1. Reverse signaling appears to occur through B7-DC as well.

Descriptive statistics, frequency analysis, chi-squared test, and Student’s t-test were performed to evaluate types of causative organisms and associated patient characteristics. One hundred and eighty-nine charts of patients with a positive scalp culture for tinea capitis were located.

Trichophyton tonsurans (88.9%) was the foremost causative agent followed by Trichophyton violaceum (4.2%). Tinea capitis was more prevalent among African Americans and was more common in urban areas (P < 0.05). Children of African descent inhabiting urban settings were most vulnerable to tinea capitis. The most common organism isolated in this retrospective study was T. tonsurans. Trichophyton violaceum and Trichophyton soudanense were also isolated, which are not commonly reported causes HDAC inhibitor of tinea capitis in the US. “
“Posaconazole is the newest triazole antifungal agent available as an oral suspension with an extended spectrum of activity against Candida species, Aspergillus species, Cryptococcus neoformans, Zygomycetes and endemic fungi. Among posaconazole advantages are the relatively low potential of cross-resistance with other azoles, few drug interactions compared with other azoles and its activity against Zygomycetes. Randomised, double-blind trials have shown that posaconazole is effective for prophylaxis against invasive fungal infections (IFI), especially aspergillosis, see more in high-risk

patients. Results of Phase III Thalidomide clinical trials and case/series reports indicate that posaconazole is effective in treating oesophageal candidiasis, including azole-refractory disease, and other IFI refractory to standard antifungal therapies. To date, posaconazole has appeared to be well tolerated even in long-term courses; it has an excellent safety profile with gastrointestinal disturbances being the most common adverse events reported. The dose of posaconazole is 200 mg three times daily for prophylaxis, 800 mg daily in

two or four divided doses for the treatment of IFI and 100 mg daily (200 mg loading dose) for the treatment of oropharyngeal candidiasis. On the basis of early clinical experience, it appears that posaconazole will be a valuable aid in the management of life-threatening fungal infections. “
“The increasing incidence of fungal infections together with the emergence of strains resistant to currently available antifungal drugs calls for the development of new classes of antimycotics. Naturally occurring antifungal proteins and peptides are of interest because of low toxicity, immunomodulatory potential and mechanisms of action distinct from those of currently available drugs. In this study, the potent antifungal activity of cystatin, affinity-purified from chicken egg white (CEWC), against the most frequent human fungal pathogens of the genus Candida was identified and characterised.

5. Partially folded HLA-B27 molecules, linked by the relatively unique cysteine 67 residue in the peptide-binding groove have been detected both in vitro and in vivo,8,9,33,34 and may be a contributory factor to the development of the arthritic condition ankylosing spondylitis, either by altered NK receptor recognition at the cell surface,35 or by induction of

intracellular unfolded protein cellular stress responses.36 HLA-G molecules form unique dimers by disulphide linkage at position 42 on Y-27632 concentration an external loop of the peptide-binding groove.12 These dimers may be relevant in tolerizing signals in pregnancy and in regulatory T-cell subsets.11,37 Lastly, a population of folded MHC class I dimers can exist on exosomes and redox-altered normal cells, and apoptotic cells, induced by disulphide linkages between cysteines in the cytoplasmic tails.15 The work in this study was funded in part by the Chief Scientist’s Office (CSO) of LDK378 research buy the Scottish Government. No competing financial interests exist. “
“Signals from the T-cell recognition

of antigen program effector functions are necessary to clear infections and tumors. The JNK pathway is critically important in regulating this process. In T lymphocytes, JNK1 and JNK2 have distinct functions depending on their maturation state and cell-type. However, the mechanisms that regulate their isoform-specific activity and function are still unclear. Here, we identify plenty of SH3 (POSH) and JNK-interacting protein 1 (JIP-1) as a multiprotein scaffold network for TCR-mediated JNK1 activation in CD8+ T cells. Disruption of the POSH/JIP-1 complex led to profound defects in the activation of JNK1, as well as deficient activation or induction of the transcription factors c-Jun, T-bet, and Eomesodermin. Furthermore, disruption of the POSH/JIP complex in CD8+ T cells resulted in impaired proliferation, decreased cytokine expression, and the inability to control tumors. Collectively,

these data identify a mechanism for the specific regulation of TCR-dependent JNK1 activation and function that is key for CD8+ T-cell responses. Upon infection, T-cell activation and differentiation are initiated through TCR engagement of peptide-MHC molecules on the surface of Bacterial neuraminidase APCs in the context of co-stimulation and inflammatory cytokines. These cues trigger numerous signal transduction cascades, whose integration is “translated” into changes in gene transcription, protein activity, and expression. This ultimately leads to the development of effector function and T-cell-mediated immunity [1]. The MAPK SAPK/JNK cascade plays a major role in regulating a variety of fate decisions including activation, proliferation, differentiation, and death [2, 3]. Three genes encode the JNK family members. JNK1 and JNK2 are ubiquitously expressed, whereas the expression of JNK3 is restricted to the brain, heart, and testis [2].

Recently, faecal-TB PCR test targeting IS6110 has also been documented by Balamurugan et al. (2010) in differentiating these two diseases. However, clinical utility of this PCR test is not validated in large number of patients. One major drawback of conventional PCR is that it requires tissue destruction and nucleic acid extraction making impossible Venetoclax mw correlation with histological characteristics (Almadi et al., 2009). An in situ PCR has been developed where IS6110 target was amplified within the intact cells and that combined the ability to localize specific DNA within tissues (Pulimood

et al., 2008). This method could also differentiate intestinal TB from Crohn’s disease in archival mucosal biopsy specimens. However, the sensitivity of in situ PCR needs to be improved and studies should be carried out on large number of patients with Crohn’s disease and intestinal TB before its usefulness is confirmed (Pulimood et al., 2008; Almadi et al., 2009). Cutaneous TB constitutes about 1.5% of all EPTB

cases (Singal & Sonthalia, 2010). However, this disease has re-emerged during the last two decades together with high incidence of PTB and multiple-drug resistant TB (MDR-TB; Abdalla et al., 2009). Differentiation of cutaneous TB from other infectious granulomas of the skin (sarcoidosis, leprosy, fungal AUY-922 or NTM infections) is difficult because of insufficient AFB in the tissue biopsies (Bravo & Gotuzzo, 2007). Of all the clinical types, scrofuloderma is the most commonly encountered variant followed by lupus vulgaris, TB verrucosa cutis and lichen scrofulosorum (Singal & Sonthalia, 2010). Sucrase These clinical types

of cutaneous TB have been confirmed by PCR, while smear microscopy and culture test completely failed (Padmavathy et al., 2003). Interestingly, Okazaki et al. (2005) reported first case of M. bovis BCG-derived cutaneous TB (localized at different area from the vaccination site) without immune deficiency by multiplex PCR assay based on region of difference (RD)1, complement sequence of RD1, RD2, RD8, RD14 and SenX3-RegX3 regions originating from M. bovis BCG Tokyo 172. TB cutis orificialis, a rare manifestation of cutaneous TB (caused by auto-inoculation of M. tuberculosis in patients with advanced internal TB), has been confirmed by PCR (Choi et al., 2009). Using culture/histopathology as the gold standard, IS6110-based conventional PCR/nested PCR has been well documented in diagnosing cutaneous TB and that showed superiority over 16S rRNA gene-based PCR (Ogusku et al., 2003; Obieta et al., 2010). A highly sensitive and specific PCR assay targeting 65 kDa protein gene has also been developed for the diagnosis of cutaneous TB, considering culture/response to ATT as the gold standard (Negi et al., 2005a; Abdalla et al., 2009). Ocular TB represents a rare form of EPTB, which accounts for 0.

We explore the lingering questions regarding pericyte phenotypic identity and lineage. The expression of different pericyte markers (e.g., SMA, Desmin, NG2, and PDGFR-β) varies for different subpopulations and tissues. Previous use of these markers to identify pericytes has suggested potential phenotypic overlaps and plasticity toward other

cell phenotypes. Our review chronicles the state of the literature, identifies critical unanswered questions, and motivates future research aimed at understanding this intriguing cell type and harnessing its therapeutic potential. “
“This chapter Linsitinib in vivo contains sections titled: Introduction What Are Speckles? Basic Properties Significance of Speckles in LDPI Further Analysis of the Consequence of Speckle in LDPI Consequences and Concluding Remarks References “
“Hypoxia-inducible factor is a hypoxia-responsive transcriptional factor that controls the expression of proteins contributing to homeostatic responses to hypoxia. Spatial heterogeneity of tissue oxygenation

has been postulated as a determinant of structure and function of hepatic lobules, although its molecular mechanisms remain unknown. This study aimed to examine the role of HIF-1 expressed in hepatocytes in regulation of hepatic microcirculation. We have generated mice harboring a floxed HIF-1α allele, and employed the albumin-Cre transgenic line to inactivate the gene site-specifically in hepatocytes. Intravital observation IWR-1 in vivo of the hepatic microcirculation revealed extension of hepatic lobules in HIF-1α-deficient mice. Measurement of microvascular diameter, velocity, and local oxygen tension by laser-assisted phosphorimetry showed that the oxygen consumption in the lobules of HIF-1α-deficient mice was greater than that in those of control mice. Isolated hepatocytes from HIF-1α-deficient mice also stimulated oxygen consumptions with increased contents of mtDNA.

Overexpression of HIF-1α decreased the expression of PGC-1α mRNA, whereas the knockdown of the HIF-1α gene increased it, suggesting that HIF-1 regulates cellular respiration through mitochondrial biogenesis. Our results suggest that constitutive expression of HIF-1α in hepatocytes acts as a determinant of hepatic Sclareol lobular structure and oxygen consumption by changing mitochondrial contents. “
“NADPH oxidase activation results in ROS overproduction that is the pathological basis of I/R injury. This study aimed to investigate potential effects of ORG on I/R-induced ROS production in rat mesenteric microvasculature and underlying mechanisms. Mesenteric I/R in Male Wistar rats (200~250 g) was induced by ligation of the mesenteric artery and vein for 10 minutes followed by reperfusion for 60 minutes by releasing of the occlusion. The rats were infused intravenously with or without ORG (5 mg/kg per hour) 10 minutes before ischemia (pretreatment) or 20 minutes after reperfusion (posttreatment).