7%) in the first trimester [44% (15/34) versus 80% (16/20); P = 0.01]. Of the 18 successful pregnancies with sequential Treg results, 85% (11/13) showed a T-regulatory-cell-level increase (mean Treg change 0.33 ± 0.32), while only 40% (2/5) of the failed pregnancies showed a Treg increase (mean Treg change −0.08 ± 0.28; P = 0.02). Conclusions  From these data, we propose that CD4+ CD25+ Foxp3+ T regulatory cells may serve as a superior pregnancy marker for assessing miscarriage risk in newly pregnant women. Larger follow-up studies are needed

for confirmation. “
“Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts Selleckchem Napabucasin obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated

DCs have impaired maturation selleck chemicals llc and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated

with P. berghei extracts are able to control autoimmune PAK6 neuroinflammation. “
“It has previously been reported by these authors that cluster of differentiation (CD) 93 is co-expressed on naive T-lymphocytes (CD4+CD45RA+ cells) in neonatal umbilical cord blood cells (UCBCs) but not on normal adult peripheral blood cells (PBCs). In this study, expression of CD93 on other lymphocyte subsets and the concentration of soluble formed CD93 (sCD93) in serum or culture supernatants from neonatal umbilical cord blood (UCB) was examined. It was found that CD93 is also co-expressed on CD2+, CD16+, CD56+ or CD25+ cells in the lymphocyte population of neonatal UCBCs, but not on normal adult PBCs. The concentrations of sCD93 in serum and culture supernatants from neonatal UCB were significantly greater than those from normal adult peripheral blood.

Similar to STAT6–/– mice, IL-5-deficient mice are protected from allergic asthma [35], while monoclonal anti-IL-5 therapy attenuates airway disease successfully [36]. Therefore, it is likely that in crescentic GN, STAT6 activation results in IL-5 production which attenuates renal injury, possibly through the inhibition of Th1 and Th17 responses. Assessing renal injury early in the disease process at day 6 demonstrated no difference between WT and STAT6–/– mice. These results confirmed that the injury seen on day 21 was a result of the heightened systemic immunity which developed between days 6 and 21, and not a reflection of an existing predisposition to renal injury

in STAT6–/– mice. Interestingly, mRNA expression of both T-bet and Rorγt was increased in STAT6–/– mice, with a trend towards increased production of IFN-γ and IL-I7A on day 6. On day 21 differences PD-0332991 mw in production of these cytokines by WT and STAT6–/– mice had reached statistical significance. Previous studies

in STAT6–/– mice in experimental lymphoproliferative disease demonstrated that STAT6 deficiency resulted in a shift from a predominant Th2 phenotype towards production of Th1-associated cytokines. In these experiments no difference was observed in the production of Th17-associated cytokines [37]. Consistent with these results, Th1 differentiation ALK mutation occurred without the provision of extrinsic IFN-γ or IL-12 in conditional GATA3-deficient mice [38]. The ability of other key regulators to influence the associated and reciprocal Th cell lineages is well described. T-bet, the key regulator of Th1 responses, can influence the Th17 phenotype. In experimental allergic encephalomyelitis, inhibition of T-bet by small interfering RNA inhibited the production of both Th1 and Th17 pathogenic responses [39]. Conversely, it has been suggested that T-bet negatively Amrubicin regulates the production of Th17 associated cytokines in vitro[40]; this was demonstrated in vivo in experimental Chagas’ disease [41]. Taken together, these reports demonstrate that key Th1 transcription factors can influence the production of Th17 responses. We propose

that STAT6 influences pathogenic Th1 and Th17 inflammatory responses in experimental crescentic GN. This novel finding suggests a greater role for Th2 cells in experimental crescentic GN than was previously appreciated. In addition to IL-4 and IL-10, it would seem that STAT6 with IL-5 production is required for control of nephritogenic immunity. Production of the regulatory Th2-related cytokines is required not only for regulation of inflammatory Th1 responses but also for regulation of Th17 systemic immunity. In conclusion, we found that STAT6–/– mice developed increased expression of key Th1 and Th17 transcription factors early in the disease. This resulted in increased Th1 and Th17 nephritogenic immunity on day 21. Production of a key Th2-related cytokine, IL-5, was decreased consistently during the disease state.

6A). However, the percentage of LMP7−/−-derived CD4+ T cells (3.89±0.21%) was clearly decreased in VV-WR-infected WT mice, compared with immunoproteasome expressing CD4+ T cells (7.62±0.4%), LMP2−/−

or MECL-1−/− CD4+ T cells (Supporting Information Fig. 6B). So far, we had mainly used Selleckchem beta-catenin inhibitor CD8+ T cells to study a requirement of immunoproteasomes during antiviral immune responses. To investigate other leukocyte populations, we investigated the development of adoptively transferred LMP7−/− CD4+ T cells (CD4+), B cells (CD19+), DC (CD11c+) and NK cells (NK1.1+) in naïve and LCMV-WE infected WT hosts compared with the corresponding endogenous cell types. Six days after transferring total splenocytes of LMP7−/− (CD45.2+) or C57BL/6 mice (CD45.2+), the numbers of donor-derived CD4+, CD8+, CD19+, CD11c+ and NK1.1+ cells in CD45.1 recipient mice were determined.

In the absence of LCMV infection, the numbers of cells lacking or expressing LMP7 were equal for all cell types analyzed (Fig. 3A). On the contrary, in LCMV-WE-infected host mice, the percentage of LMP7−/− cells was markedly reduced compared with C57BL/6 cells with CD4+, CD8+ and CD11c+ cells being hardly detectable (Fig. 3B). The loss of CD11c+ cells does most likely not represent a loss of DC but rather T cells which have been shown to upregulate CD11c expression during LCMV infection 17. Almost all remaining donor LMP7−/−-derived cells were B cells and also these were significantly reduced compared with WT DAPT clinical trial mafosfamide donor B cells. The almost complete loss of LMP7-deficient CD4+ and CD8+ T cells in the infected mice in face of a relative persistence of B cells argues by itself against an MHC class I-dependent rejection phenomenon being the cause of the loss of LMP7−/−

T cells because flow cytometric analysis of transferred B cells and CD8+ T cells showed a similar cell surface expression of H-2Kb and a slightly higher expression of H-2Db on B cells. To better document this finding, we simultaneously transferred sorted B220+ B cells and CD8+ T cells from CD45.2+ WT or LMP7−/− donor mice into CD45.1+ WT recipient mice and monitored the survival of B cells and T cells up to day 8 post-transfer. Although the LMP7−/−CD8+ T cells had almost completely disappeared by day 8, LMP7−/− B cells survived in the same mouse (Fig. 3C) which is inconsistent with a rejection based on different peptide/MHC I complexes displayed on the surface of LMP7−/− T cells. Instead, this finding points at a function of immunoproteasomes for the expansion and/or survival in the virus-infected host which is particularly crucial for T cells. As immunoproteasome-compromised T cells fail to expand in response to LCMV-WE infections, we crossed LMP7−/− and MECL-1−/− mice with P14 mice, which are TCRtg for the LCMV-WE MHC class I epitope GP33 (glycoprotein derived, aa 33–41). With these mice, we were able to track the in vivo expansion of virus-specific CD8+ T cells that lack LMP7 or MECL-1, respectively.

1b, and data not shown). The D values of EHEC O26 and O111 were comparable to the D value of EHEC O157 that was already proven to be useful in epidemiological analyses (14); the findings of this study suggest a sufficient discriminating power of the MLVA system. In the present study, the new MLVA system was also useful for detecting outbreak-related isolates, and this H 89 is one of the most prioritized objectives of genotyping (Fig. 3; Table 2). Most of the outbreak-related isolates did not exhibit any, or exhibited only single-locus, variations within each outbreak (Table 2). The cluster analysis based on the MLVA profiles revealed that each outbreak could

form a unique cluster. This was also true for the cluster analysis based on the PFGE profiles. Further, consistent results were obtained selleck inhibitor by both these methods (Figs 3, 4). However, the relationships between the clusters observed in one method differed from those observed in the other method because of the differences in the two methods with regard to the targets; MLVA discriminates isolates by repeat copy numbers of specific loci, whereas PFGE differentiates them by restriction fragment length polymorphisms of the entire DNA. Moreover, either PFGE or MLVA can be superior to the other method for discriminating isolates in some outbreaks. These results indicate that MLVA can complement

PFGE analysis. Considering that the procedure of MLVA is simpler and more rapid than that of PFGE, MLVA can be applied for the first screening of isolates in outbreak investigations before the results can be confirmed by PFGE. PFGE analysis is currently the golden method for subtyping bacterial pathogens. (13). Other researchers reported that subtyping methods, such as AFLP, rep-PCR and MLST, could be useful

for analyzing EHEC O157, but PFGE was the best method to discriminate isolates, for example, in outbreak investigations (17, 18). In this study, the results of MLVA were similar to those of PFGE analysis in outbreak investigations; this suggests that CYTH4 the discriminating power of MLVA is greater than that of the above-mentioned methods, although it might be necessary to evaluate the discriminating power of them for EHEC non-O157 strains, as described below. Furthermore, other methods are more time-consuming than MLVA. The results of the other methods, except MLST, are deduced from anonymous banding patterns, which can lead to ambiguous typing, whereas the results of MLVA are deduced from known loci and can be controlled by direct sequencing of the amplified products (19). Recently, infection with EHEC serogroups other than O157 has raised concerns not only in Japan but also in other countries: EHEC O26:[H11], O103:H2, O111:[H8], and O145:[H28] are frequently associated with HC and HUS (20). Although PFGE is the first line of choice for subtyping, most of the methods mentioned above have not yet been evaluated for analyzing EHEC non-O157 strains.

Moreover, morphological alterations of fungal cells were investigated using scanning electron microscopy. All disinfectant solutions killed all remaining fungal cells on the specimens. Interestingly, 4% chlorhexidine did not remove these cells from the acrylic resin surface whereas sodium hypochlorite solutions (1% and 2%) provided almost complete biofilm removal. Furthermore, treating the specimens with sodium hypochlorite induced cell morphology

alterations, as seen in the residual fungal cells. Finally, according to our findings, it can be suggested that sodium hypochlorite solutions are the first choice as denture cleanser when compared with 4% chlorhexidine because those solutions not only killed C. albicans biofilms but also removed them from the this website heat-polymerised acrylic resin. “
“AMG-148, an oxathiolone-fused

chalcone derivative, exhibited in vitro antifungal activity against several strains of human pathogenic yeast, with minimum inhibitory concentration values within the range of 1–16 μg ml−1 and a fungicidal effect was observed at higher concentrations. Presence of major drug-effluxing membrane proteins Cdr1p, Cdr2p or Mdr1p, did not affect substantially the fungistatic activity of this compound against clinical Candida albicans strains. Studies on the mode of action revealed that AMG-148 inhibited chitin and β(13)glucan biosynthesis and was in vitro an inhibitor of β(13)glucan synthase. Inhibition of chitin biosynthesis was responsible for fungistatic activity, while the fungicidal effect was a consequence isothipendyl of disturbance of β(13)glucan Selleckchem AZD2014 synthase function. The chalcone derivative may be a useful lead compound for the development of novel antifungal agents. “
“Due to the increased number of immunocompromised patients, the infections associated with the pathogen of the genus Candida have significantly

increased in recent years. To grow, Candida albicans may form a germ tube extension from the cells, which is essential for virulence. In this work, we studied the effect of crude glycolic extract of Aloe vera fresh leaves (20% w/v) on growth and germ tube formation by C. albicans. The C. albicans growth was determined in the presence of different concentrations of A. vera extracts in Sabouraud dextrose broth medium. In the presence of A. vera extract (10% v/v), the pronounced inhibition in the C. albicans growth (90–100%) was observed. This inhibition occurred parallel to the decrease in the germ tube formation induced by goat serum. Our results demonstrated that A. vera fresh leaves plant extract can inhibit both the growth and the germ tube formation by C. albicans. Our results suggest the possibility that A. vera extract may be used as a promising novel antifungal treatment. “
“Colonisation may be the first step for the development of Candida infection.

MA failed to decrease at 24 hours in the subgroup,

which went on to develop muti- organ dysfunction, necessitating organ support. Appropriate interventions viz. quicker administration of right antibiotic and fluid resuscitation was associated with a decrease in MA. MA also decreased in the subgroup, who received steroids. Higher doses of insulin, rather than actual glucose level was seen to decrease MA in non-diabetics. A higher ratio of VEGF/ sFLT level on admission was associated with gretaer MA (p = 0.0079). However, it was a rising level of sFlt at 24 hours, which correlated with mortality. Conclusions: Microalbuminuria, a manifestation of endothelial dysfunction, was more in patients with SIRS due to sepsis and those Z-VAD-FMK price who developed multi organ dysfunction.

Interventions like right antibiotic, fluid resuscitation, insulin, steroids, where indicated, helped to decrease MA. A high VEGF/sFLT ratio correlated with higher MA but a rising sFlt portended a poor outcome. BUNANI EUNICE, DUMDUM Cagayan de Oro Medical Center Background: Renal nurses develop their expertise over time and in the exercise of their professional skills deliver the essence of safe, competent, and compassionate care. The knowledge, attitude and skills of a nurse develop progressively where complexities of clinical procedures and experiences are intertwined. Objective: This study identifies whether Quality Patient Dialysis Outcomes (QPDO) were directly affected by eleven key areas of nurse responsibility used when evaluating renal staff competency Ixazomib (SC). Methods: 59 Staff Nurses were appraised evaluating SC while 525 hemodialysis patients were evaluated using the QPDO parameters. Univariate linear regression and Pearson rho moment correlation were used to build PLEK2 relationships. Results: Data indicated both increase and decrease trends in relation to staff competency. Competencies related to Health Education (172.6), Communication (147.5), Records

Management (141.6), Safe and Quality Nursing Care (135.0), and Management of Resources (133.5) demonstrated increase trends. Competencies related to Research ( −35.2), Quality Improvement ( −12.3), and Legal Responsibility ( −6.68) were relatively decreased as the period of competency evaluation progressed. It was notable that QPDO related to Kt/V, Albumin, Hemoglobin, and Hematocrit Levels were directly proportional to increasing extent of SC ρ = (+0.61) while calcium and phosphorus levels were directly associated to areas where staff were demonstrated an decreasing trend ρ = (+0.66). Conclusion & Application to Practice: The eleven key areas of responsibility used to measure SC in a periodic evaluation demonstrated a strong correlation to the increasing extent of QPDO. Additionally, as the nurses progressed to becoming expert a direct correlation to the QPDO was notable.

Given the major differences observed in parasite epigenetic features compared with all other eukaryotic organisms, inhibitors developed against Plasmodium-specific epigenetic enzymes have a strong potential for new therapeutic strategies against P. falciparum. Many of the current drug therapies are based on chemically engineered variants of already known antimalarial compounds (e.g. aminoquinolines and/or peroxides). Intensive exploration of the P. falciparum genome

has lead to the identification Staurosporine datasheet of parasite-specific essential genes or metabolic pathways that could be targeted for rational drug designs (18,23,60,62,91–93). For example, a fosmidomycin-sensitive mevalonate-independent pathway of isoprenoid biosynthesis, absent from higher eukaryotes and located in the plant plastid-like parasite organelle namely the

apicoplast, was identified in P. falciparum (94). Along with the discovery of new drug targets, the discovery of mechanisms of drug resistance has been significantly refined using genome-wide analysis. Typically, mechanisms of drug resistance are determined by examining the genetic differences between sensitive and resistant strains. The best-studied case of drug resistance in P. falciparum is chloroquine resistance (CQR). Chloroquine resistance is mediated by a transporter ACP-196 datasheet gene (Pfcrt) and by the multidrug resistance gene (Pfmdr1). The discovery of the genes associated with CQR took years of heavy molecular, epidemiology and genetic studies. Research is still ongoing to fully comprehend CQR in the parasite. Today, whole-genome analytic tools provide the capability of analysing rapidly the genetic changes that occur in the genome of a resistant strain. Whole-genome not scanning using tiling microarrays has already been used for this purpose. For example, initial analyses found relatively abundant copy number variations in P. falciparum -resistant strains (5). Point mutations in the apicoplast were recently associated with resistance to clindamycin, a drug used in combination with quinine for the treatment

of malaria in pregnant women and infants (95). Another striking example of the power of genomics in drug discovery is the identification of a potent drug by cell proliferation–based compound screening (96) followed by the discovery of one of its targets using high-density microarrays and sequencing (97). Without the advent of genomics, such a process would have required many years. All together, it is likely that these genome-wide approaches will soon uncover mechanism of drug resistance including emerging resistance of artemisinin. To further highlight the power of genomic studies for the discovery of new effective antimalarial strategies, a recent genome-wide SNP analysis identified regions of high and low recombination frequencies (hot spots and cold spots).

For example,

in normal human placentas, VEGFxxx protein occupies the majority of the total VEGF protein expressed and VEGFxxxb occupies only less than 2% of the total VEGF protein; however, their concentrations are positively correlated (r = 0.69, p < 0.02). In contrast, VEGFxxx isoforms are upregulated and VEGFxxxb isoforms are significantly downregulated in preeclamptic placentas, resulting in a significant negative correlation between VEGFxxxb and VEGFxxx protein expression (r = −0.8, p < 0.02) [7]. These data indicate that preeclampsia uncouples VEGF splicing in human placenta, which further adds to the soluble Flt1/VEGF complex in the deranged angiogenesis during preeclampsia [72]. These data also implicate that the discovery of VEGFxxxb has greatly devalued total VEGF as an index of angiogenic activity in preeclampsia and most likely under other disease-related conditions as well. Contrasting Daporinad ic50 to the conventional VEGFxxx, the expression and function of VEGFxxxb in normal and abnormal placental development and angiogenesis awaits further investigation. The Slit/Robo signaling systems are members of a conserved neuronal guidance cue family selleck chemicals that also includes netrin/DCC/Unc5

[43], ephrin/Eph [20], and semaphorin/plexin/neuropilin [91]. In these systems, the former ones (i.e., Slit, netrin, epherin, and semaphorin) are secreted proteins that function as ligands, whereas the latter ones (i.e., Robo, DCC/Unc5, Eph, and plexin/neuropilin) are their corresponding receptors. Mammals

have at least three slit genes (slit 1, slit 2, and slit 3) [10, 52] that encode three Slit proteins with ~1500 amino acids, and four Robo proteins, Robo1, 2, 3, and 4 [10, 62, 61, 51, 93]. Robo4 seems to be a vascular-specific Slit receptor [51, 93] that is important for the maintenance of vascular integrity by inhibiting abnormal angiogenesis and endothelial hyperpermeability [55]. Slit2, upon binding to Robo1, functions as an attractant to promote the directional migration and vascular network formation in vitro. Moreover, Amisulpride these cellular effects are inhibited by an anti-Robo1 antibody and are blocked by a soluble Robo1 extracellular fragment (RoboN) [117]. Slit2 is also able to promote endothelial cell migration and tube formation in vitro, possibly mediated by Robo1/Robo4 [109]. Secreted soluble Robo4 is able to inhibit in vivo angiogenesis and the VEGF- and FGF2-stimulated endothelial cell proliferation and migration [110]. Knockdown or overexpression of Robo4 leads to either lack of or misdirected intersomitic vessels [8]. In human placenta, Slit2 and Robo1 proteins are expressed in the syncytiotrophoblast, while Slit3 and Robo1 and Robo4 are detected in capillary endothelium of the placental villi [77, 78].

None of the non-transplanted rats were excluded. The body weights of the animals were similar in controls and hyaluronidase-treated rats, and they showed a similar decrease in weight after transplantation (Table 1). In contrast, in non-transplanted BAY 57-1293 nmr rats, there was a decrease in body weight

in hyaluronidase-treated rats only (Table 1). Wet weights of the endogenous or transplanted pancreases were similar in all groups studied (Table 1). Haematocrit values were lower in transplanted rats, but they were not affected by hyaluronidase treatment (Table 1). Blood glucose and serum insulin concentrations were similar in all groups studied, as was mean arterial blood pressure (Table 1). In the transplanted animals, hyaluronidase treatment induced a decrease in the total blood

perfusion in both the pancreatic grafts and the native pancreas (Fig. 6), and in a similar way in islet blood flow (Fig. 7). Pancreatic and islet blood flow in the non-transplanted rats were not affected by the hyaluronidase treatment (Figs. 6 and 7). The fraction of total pancreatic blood flow diverted through the islets was similar in all groups (Table 2). Likewise, both graft and endogenous duodenal blood flow was similar when comparing control and hyaluronidase-treated rats (Table 2). Neither did hyaluronidase treatment affect islet nor duodenal blood Pictilisib manufacturer flows in non-transplanted control rats (Table 2). However, the duodenal blood flow values were higher in transplanted rats, when compared to non-transplanted control rats (Table 2). Whenever an organ, including the pancreas, is transplanted and re-connected to the vascular system of the recipient, Non-specific serine/threonine protein kinase an ischaemia/reperfusion injury occurs [18–20]. When pancreases

are transplanted, this injury often manifests itself as an acute pancreatitis in the early postoperative period [9, 10]. In the present study, the presence of an acute pancreatitis was confirmed in microscopy slides and by the macroscopical appearance of the graft, including oedema, haemorrhages and calcified infiltrates. This accumulation of HA constitutes a part of the graft pancreatitis, which probably targets the inflamed gland to leucocytes to combat the post-transplant inflammation [1, 5, 7]. The increased pancreatic graft HA content is actually similar to that seen during caerulein-induced acute pancreatitis in rats [8], and in accordance with that study, there was no clear correlation between HA and water content. This suggests that, in contrast to the conditions during rejection [6], oedema associated with pancreatitis is not HA dependent. It should be noted that the rats used in the present study retained their endogenous pancreas, i.e. they had two glands with functional endocrine cells. When examining these glands 2 days after transplantation, we, as mentioned earlier, clearly saw an acute pancreatitis in the grafted pancreas.

infantum antigens at 8 weeks after challenge (Figure 1e). However, the amount of nitric oxide in G2 vaccinated with DNA/DNA in cSLN formulation remained significantly higher than the control groups. Similar levels of cytokines were produced with ConA in all groups (data not shown). As shown in Figure 2(a), rA2–rCPA–rCPB-specific IgG1 and IgG2a were higher in G1 compared with the other groups (P < 0·001) before challenge. Also, G2 showed a higher amount of rA2–rCPA–rCPB-specific IgG1 than control groups, although much lower than G1. This is consistent with previously reported data that both Th1 and Th2 responses

were needed for protection against visceral leishmaniasis [12, 27-29]. No significant differences in the levels of IgG1 and IgG2 were seen among groups with L. infantum F/T antigen stimulation Y-27632 mw (Figure 2b). As shown in Figure 3, immunization with pcDNA–A2–CPA–CPB−CTE

via DNA/DNA vaccination with chemical or physical delivery drastically (P < 0·01) reduced the infection levels in both liver (Figure 3a) and spleen (Figure 3b) at 4–6 weeks after L. infantum infection in contrast to the control groups. The liver parasite load (Figure 3a) of both control groups selleck products started increasing early following infection, reaching its maximum at 4 weeks after challenge to rapidly decline. Control of the hepatic infection did not result into complete clearance of the parasite, as at week 12 there were still few detectable parasites in the liver that were dependent on the inoculum size [30]. In contrast, the parasite burden in the vaccinated group peaked with a 4-week delay. In the spleen (Figure 3b), the highest parasite burden was observed 12 weeks after challenge and the organ stayed chronically infected. Interestingly, it was observed that between weeks 8 and 12 the parasite burden has intense slope towards growing in control groups, while in vaccinated groups, parasites were controlled (Figure 3b). Therefore, it can be concluded that these designed vaccines have a partial protection against L. infantum infection. In liver, all groups showed

variable degree of portal inflammation, but the most severe inflammation and interface hepatitis were observed only in control groups (G3 and G4). The severity of lobular inflammation at 4th week was significantly higher in G3 and G4 [13-16/10 4-Aminobutyrate aminotransferase hpf (high-power field)] compared with vaccinated groups (0–2/10 hpf) (P < 0·05) (Figure 4a). No significant difference in this inflammatory response was seen among groups at 8 weeks after challenge, whereas the degree of lobular inflammation had a peak of increase in all groups and decreased in week 14. All groups had Kupffer cell hyperplasia which was especially prominent at 8th week (data not shown). Hepatic hydropic change and clearing of the cytoplasm were a significant finding at weeks 4 and 8 and disappeared in the 14th week.