Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty.

Purpose: To evaluate the association between endothelial cell density (ECD) after Descemet's stripping automated endothelial keratoplasty (DSAEK) and preoperative cytokine levels in the aqueous humor (AqH). Methods: This prospective consecutive case series included 97 consecutive patients who underwent DSAEK (64 eyes) or cataract surgery (33 eyes). AqH samples were collected at the beginning of each surgery. The levels of cytokines (IL-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured by multiplex beads immunoassay. The correlations between preoperative aqueous cytokine levels and the ECD at 12 months after DSAEK were analyzed. Results: The ECD decreased from 2747 ± 259 cells/mm2 in the donor graft to 1235 ± 607 cells/mm2 at 12 months after DSAEK. In all subjects undergoing DSAEK, the postoperative ECD at 12 months was significantly correlated with the preoperative levels of MCP-1 (r = -0.467, 95% confidence interval [CI]: -0.650 to -0.222, P = 0.0003). In an analysis excluding Fuchs endothelial corneal dystrophy (11 eyes), the ECD at 12 months after DSAEK was significantly correlated with preoperative levels of IL-17A (r = -0.635, 95% CI: -0.819 to -0.319, P = 0.0004), MCP-1 (r = -0.605, 95% CI: -0.779 to -0.345, P < 0.0001), IFN-γ (r = -0.633, 95% CI: -0.796 to -0.385, P < 0.0001), E-selectin (r = -0.516, 95% CI: -0.756 to -0.276, P = 0.0004), and sICAM-1 (r = -0.537, 95% CI: -0.735 to -0.253, P = 0.0005). Conclusions: Higher preoperative levels of IL-17A, MCP-1, IFN-γ, E-selectin, and sICAM-1 in the AqH were associated with lower ECD after DSAEK for bullous keratopathy.

Elevated Aqueous Cytokine Levels in Eyes With Ocular Surface Diseases.

PURPOSE: To evaluate cytokine and protein levels in the aqueous humor (AqH) of eyes with ocular surface diseases. DESIGN: Prospective consecutive case series. METHODS: This study includes 14 patients (aged 62.4 ± 13.7 years) with chronic-phase ocular surface diseases (4 with ocular cicatricial pemphigoid, 5 with chemical burns, 2 with a thermal burn, 2 with Stevens-Johnson syndrome, and 1 with exposure keratitis), 14 matched patients without ocular surface disease (controls with corneal scar), and 30 patients who underwent cataract surgery (healthy controls). AqH samples were collected at the beginning of surgery. AqH levels of cytokines (interleukin [IL]-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, monocyte chemotactic protein [MCP]-1, interferon [IFN]-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1ß, P-selectin, E-selectin, soluble-intercellular adhesion molecule [s-ICAM]-1, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], IFN-γ-induced protein [IP]-10) were measured using multiplex beads immunoassays. RESULTS: The levels of IL-6, IL-10, IL-17A, GM-CSF, E-selectin, P-selectin, and s-ICAM in AqH were significantly elevated in eyes with ocular surface diseases (in pg/mL: 1696 ± 804, 4.0 ± 1.0, 24.3 ± 9.8, 26.0 ± 18.3, 5150 ± 1232, 13122 ± 7219, and 7914 ± 2813, respectively), compared to healthy controls (IL-6: 6.36 ± 0.94, P = .001; IL-10: 1.68 ± 0.04, P = .0006; IL-17A: 3.7 ± 0.2, P = .008; GM-CSF: 2.7 ± 0.3, P = .007; E-selectin: 2093 ± 37, P = .0001; P-selectin: 3658 ± 137, P = .0001; sICAM-1: 1397 ± 119, P = .008). The levels of IL-6, IL-17A, E-selectin, and P-selectin in AqH were significantly higher in eyes with ocular surface diseases compared to those with corneal scar (IL-6: 44.1 ± 15.0, P = .0077; IL-17A: 4.1 ± 0.7, P = .034; E-selectin: 2439 ± 302, P = .039; and P-selectin: 5673 ± 1553, P = .017). CONCLUSIONS: Multiple AqH cytokine levels were elevated in chronic ocular surface diseases.

Association between corneal endothelial cell densities and elevated cytokine levels in the aqueous humor.

Annual reduction rate of corneal endothelial cell density (ECD) varies among etiologies, however, the cause of chronic endothelial cell loss is still unknown. We recently reported the elevation of inflammatory cytokines in the aqueous humor (AqH) in eyes with bullous keratopathy and low ECD. To evaluate the association between ECD and aqueous cytokine levels, we collected a total of 157 AqH samples prospectively. The AqH levels of cytokines were measured and multivariate analyses were conducted to find the correlation between ECD, aqueous cytokine levels and clinical factors, such as number of previous intraocular surgeries and protein concentration in AqH. As a result, ECD was negatively correlated with specific cytokine levels, including IL-1α, IL-4, IL-13, MIP-1ß, TNF-α and E-selectin (all P < 0.05). The aqueous cytokine levels showed different correlations with these clinical factors; the number of previous intraocular surgeries was associated with all cytokines except MIP-1α. The AqH protein concentration and the status of intraocular lens showed similar patterns of elevation of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, MIP-1ß, MCP-1, E-selectin, P-selectin and sICAM-1. In conclusion, elevation of AqH cytokine levels was associated with reduced ECDs. AqH cytokine levels showed significant correlations with clinical factors associated with low ECDs.

Preoperative Aqueous Cytokine Levels Are Associated With a Rapid Reduction in Endothelial Cells After Penetrating Keratoplasty.

PURPOSE: To evaluate the influence of preoperative inflammatory cytokine levels in the aqueous humor (AqH) on the endothelial cell density (ECD) after penetrating keratoplasty (PKP). DESIGN: Prospective, interventional, consecutive case series. METHODS: This study includes 70 consecutive patients (mean age 73.7 ± 10.6 years) who underwent PKP (37 eyes) or cataract surgery (controls, 33 eyes). A total of 70 AqH samples were collected at the beginning of each surgery. The levels of cytokines (interleukin [IL]-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon [IFN]-α, IFN-γ, monocyte chemotactic protein [MCP]-1, E-selectin and P-selectin) in AqH were measured by multiplex bead immunoassay. The subjects who underwent PKP were classified into 2 groups: ECD ≥ 1200 cells/mm2 at 6 months (24 eyes), and ECD < 1200 cells/mm2 at 6 months (13 eyes). RESULTS: The ECD at 3 months significantly correlated with the preoperative levels of IL-10 (r = -0.428, P = .02) and IFN-γ (r = -0.412, P = .029). The ECD at 6 months significantly correlated with the preoperative levels of IL-10 (r = -0.399, P = .024), MCP-1 (r = -0.444, P = .011), and IFN-γ (r = -0.474, P = .006). The preoperative levels of IL-6, IL-10, MCP-1, IFN-γ, and P-selectin in AqH were significantly higher in eyes with ECD < 1200 cells/mm2 compared with those with ECD ≥ 1200 cells/mm2 at 6 months (P < .05). CONCLUSIONS: Higher preoperative levels of IL-10, MCP-1, and IFN-γ in the AqH were associated with low ECD after PKP.

Iris Damage Is Associated With Elevated Cytokine Levels in Aqueous Humor.

Purpose: To evaluate the association between iris damage and cytokine levels in the aqueous humor (AqH). Methods: A total of 201 AqH samples from 201 consecutive patients (mean age 73.7 ± 10.6) were collected at the beginning of corneal transplantation or cataract surgery. Iris damage of each case was assessed from preoperative slit-lamp findings based on its severity. The subjects were classified into three groups: eyes without iris damage (126 eyes), eyes with mild iris damage (51 eyes), and eyes with severe iris damage (24 eyes). The levels of cytokines (IL-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17a, interferon gamma-induced protein [IP]-10, monocyte chemotactic protein [MCP]-1, IFN-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1ß, P-selectin, E-selectin, soluble intercellular adhesion molecule [sICAM]-1, TNF-α, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in AqH were measured by multiplex beads immunoassay. Results: The levels of aqueous protein, IL-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17A, MCP-1, TNF-α, E-selectin, P-selectin, and sICAM-1 in eyes with mild and severe iris damage were higher than in those without iris damage (P < 0.033). Multivariate analyses of clinical factors revealed that iris damage was associated with the history of complicated glaucoma, and the number of previous intraocular surgeries. The levels of AqH IL-6, IL-8, IL-13, MIP-1α, TNF-α, and sICAM-1 were significantly elevated in eyes with mild and severe iris damage in phakic eyes, and the levels of AqH IL-8 and sICAM-1 were significantly elevated in eyes with severe iris damage in pseudophakic eyes, compared with the eyes without iris damage (P < 0.045). Conclusions: Iris damage was associated with the elevation in the levels of aqueous protein and cytokines.

Elevated Cytokine Levels in the Aqueous Humor of Eyes With Bullous Keratopathy and Low Endothelial Cell Density.

PURPOSE: To evaluate cytokine levels in the aqueous humor (AqH) of eyes with bullous keratopathy (BK) and low endothelial cell density (ECD). METHODS: A total of 145 AqH samples (60 BK, 16 low ECD, 35 corneal diseases with normal ECD, and 34 normal controls) were collected from consecutive patients who underwent corneal transplantation or cataract surgery. None of the patients had any clinically apparent inflammation at the time of AqH collection. The AqH levels of cytokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-α, IFN-γ, monocyte chemotactic protein [MCP]-1, TNF-α, E-selectin, P-selectin, soluble intercellular adhesion molecule [sICAM]-1, granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage inflammatory protein [MIP] -1α and MIP-1ß) were compared among the groups. RESULTS: The levels of IL-1α, IL-8, IL-17A, TNF-α, GM-CSF, MIP-1α, IFN-γ, and E-selectin in the AqH were significantly elevated in BK and low ECD eyes, compared with healthy controls (all P < 0.03). The levels of IL-4, IL-6, IL-10, IL-12p70, IL-13, MCP-1, MIP-1ß, P-selectin, and sICAM-1 were significantly elevated only in BK eyes, compared with healthy control (all P < 0.001). There were no significant differences in AqH cytokine levels between corneal diseases with normal ECD and normal control eyes. Among BK eyes, the IL-6 and IFN-γ levels were elevated in eyes with pseudophakic BK (PBK), Fuchs' endothelial corneal dystrophy (FECD), postkeratoplasty, posttrabeculectomy, and postlaser iridotomy (LI) (all, P < 0.04), whereas IL-1α, IL-10, IL-17A, MIP-1ß, and sICAM-1 levels were elevated only in PBK, postkeratoplasty, posttrabeculectomy, and post-LI eyes (all, P < 0.05). CONCLUSIONS: Subclinical elevation of AqH cytokine levels may cause endothelial cell loss.

Molecular epidemiology of Newcastle disease virus isolates from vaccinated commercial poultry farms in non-epidemic areas of Japan.

BACKGROUND: Newcastle Disease (ND) is a highly contagious and economically devastating disease of poultry. At present, limited molecular epidemiological data are available regarding the causes of ND outbreaks in vaccinated commercial poultry farms. Knowing the genomic characteristics of Newcastle disease virus (NDV) infecting commercial poultry operations in spite of vaccination might give important insights on the infection dynamics of these viruses. In addition, molecular analyses at the subgenotype level and studies on the relationship of Japanese NDVs with other isolates from around the world are lacking. Therefore, in the present study, a molecular epidemiological investigation was conducted to characterize nine NDVs isolated from vaccinated commercial poultry flocks in five different Prefectures in non-epidemic areas of Japan between 1969 and 2002. METHODS: Nucleotide sequencing and phylogenetic studies were performed to characterize the complete fusion (F)-protein gene, 3-prime end of the nucleoprotein (NP)-gene and 5-prime end of the RNA dependent RNA polymerase (L)-gene. Sequence data were compared with 180 NDV strains from GenBank representing different NDV genotypes and subgenotypes from different regions of the world at different time periods. Deduced amino acids were analyzed for homologies, recombination and mutation. Recombination events were estimated using Recombination Detection Program (RDP) version 3.44. Phylogenetic trees were constructed to determine evolutionary relationships among strains. RESULTS: Mean death time (MDT: 48-56 hr), Intracerebral Pathogenicity Index (ICPI: 1.7-1.9) and deduced amino acid sequences of the F0 proteolytic cleavage site (112RRQKR116) revealed that all nine field isolates were velogenic. Phylogenetic analysis showed that these isolates could be classified into two genetic lineages and three sublineages namely genotypes VIa (lineage 4a), VId (lineage 4d) and VIId (lineage 5d). No recombination events were observed but a point mutation in one of the neutralizing epitope of the F-protein was identified in the field isolates from Japan. CONCLUSIONS: All field isolates from vaccinated commercial poultry in non-epidemic areas of Japan were part of much bigger outbreaks in provinces and regions and, in some cases, continents. In general, four ND panzootics occurred in Japan and that these outbreaks were mostly characterized by co-circulation of genetically distinct virus lineages due to involvements of infected wild birds. The point mutation identified in the field isolates from Japan may be due to escape from vaccine pressure. The identification of such mutation may be useful for future site-directed mutagenesis to understand the dynamics of NDV infection in vaccinated chickens.

Epizootiologic role of feeds in the epidemiology of Salmonella Senftenberg contamination in commercial layer farms in eastern Japan.

In total, 40 commercial layer farms and 32 replacement pullet farms with a combined population of 7.5 million adult layers and 6.6 million replacement pullets from six prefectures in eastern Japan were investigated for Salmonella Senftenberg contamination. We randomly collected 17,956 environmental samples, 5816 feed samples, and 218,470 egg samples from commercial layer farms; and 427 feed samples and 2896 environmental samples from replacement pullet farms. We monitored all samples for Salmonella. Samples were primarily enriched in Hajna tetrathinoate broth for 24 hr at 37 C followed by incubation in desoxycholate hydrogen sulfide lactose agar for 18 hr at 37 C. Salmonella colonies were confirmed and identified by biochemical tests and serotyped using Salmonella O and H antigens. We recorded 171 environmental samples (0.95%) and 10 feed samples (0.17%) that were positive for Salmonella spp. in which 36 environmental samples (0.20%) and six feed samples (0.10%) were identified as Salmonella Senftenberg. All Salmonella Senftenberg strains were isolated from nine replacement pullet farms. No Salmonella Senftenberg strains were isolated from adult layer farms and from eggs. Pulse field gel electrophoresis of BlnI-digested chromosomal DNA of 19 Salmonella Senftenberg isolates from feeds and environmental samples yielded a single identical DNA pattern. Traceback information showed that all positive feed samples were from a single feed source. Timeline studies showed that Salmonella Senftenberg contamination occurred first mostly in the feeds and then spread to the environment and other farms. This study demonstrated that the prevalence of Salmonella Senftenberg contamination in commercial layer facilities in eastern Japan is very low. Moreover, feed contamination played a major role in the epizootiology and spread of this pathogen in commercial poultry flocks. Given the resilient and persistent nature of this particular Salmonella serotype, routine monitoring and strict quality control measures at the feed level are recommended to prevent the colonization of poultry facilities with Salmonella Senftenberg that may lead to future outbreaks.

Transmission and shedding patterns of Salmonella in naturally infected captive wild roof rats (Rattus rattus) from a Salmonella-contaminated layer farm.

Rodents play a major role in the transmission and maintenance of Salmonella contamination cycles in poultry facilities. However, very limited field data are available regarding the transmission routes, infection cycle, and shedding patterns of Salmonella by naturally infected wild rodents from commercial layer farms. In this study, a total of 128 resident wild roof rats (Rattus ratus) were captured from a Salmonella-contaminated layer facility. All roof rats were divided into 51 laboratory cages, and weekly monitoring of Salmonella fecal shedding patterns was conducted for 53 wk. Seven roof rats from cages that were observed to frequently shed Salmonella were isolated in individual cages, and daily Salmonella monitoring was performed for 35 days. At the end of monitoring, each roof rat was euthanatized, and isolation of Salmonella from different organs was performed. Results of weekly monitoring of Salmonella showed that 21 of 51 cages (41.2%) were positive for Salmonella Infantis, while two cages (3.92%) were positive for Salmonella Enteritidis. Moreover, 11 cages were positive for Salmonella for at least two sampling weeks. Isolation of Salmonella from fecal droppings was mainly observed during the first 12 wk of captivity. The longest interval between two Salmonella-positive fecal dropping was 24 wk. In the daily Salmonella monitoring, only Salmonella Infantis was isolated from fecal droppings, in which the highest number of Salmonella Infantis organisms per fecal dropping was at 1 x 10(8) colony-forming units (cfu), while the lowest measured quantity was 1 x 10(3) cfu. It was noted that the frequency of Salmonella shedding in fecal droppings appeared to have a linear correlation (r = 0.85) with the number of Salmonella organisms (cfu) per fecal pellet (P < 0.05). Moreover, pulsed-field gel electrophoresis analysis of Salmonella Infantis isolates revealed a single identical pulsed-field pattern. Salmonella Enteritidis isolates from fecal droppings and internal organs also generated a single identical pulsed-field pattern. Interestingly, Salmonella Infantis was not isolated from any of the organs examined, while Salmonella Enteritidis was isolated from the spleen and liver of one roof rat. These results may indicate that wild roof rats could persistently carry Salmonella and contaminate commercial poultry facilities through intermittent fecal shedding. Moreover, Salmonella Enteritidis in wild roof rats appears to be more of a systemic infection, in which isolation is most likely to occur in internal organs, whereas Salmonella Infantis is more likely an enteric type of infection, in which isolation is most likely to occur in the intestinal contents. It is very plausible that layer chickens could become infected with Salmonella through ingestion of Salmonella-positive fecal droppings or feeds contaminated with these fecal droppings from infected resident roof rats. This is likely one of the major reasons why layer houses can be persistently infected by Salmonella even if the facilities are thoroughly cleaned and disinfected and if replacement stocks are obtained from Salmonella-free breeders and rearing units. It is therefore a noteworthy suggestion that rodent control programs inside poultry premises comprise an essential and effective tool in the management and control of Salmonella contamination in layer flocks.

Comparison of the prevalence of Salmonella infection in layer hens from commercial layer farms with high and low rodent densities.

A comparison on the prevalence of Salmonella infection in layer hens from commercial layer farms with high and low rodent densities was investigated. Out of 280 laying hens sampled from three commercial layer farms with high rodent densities, Salmonella enterica subsp. enterica serovar Enteritidis (Salmonella Enteritidis) was isolated from 20 (7.14%) hens and Salmonella enterica subsp. enterica serovar Infantis (Salmonella Infantis) from three (1.07%) hens. In contrast, layer hens sampled from four commercial layer farms with low rodent densities were negative for any salmonellae. Significant differences (P < 0.05) in the isolation rates of Salmonella from various organs of infected layer hens were also noted. For Salmonella Enteritidis, liver (55.0%) and the oviduct (55.0%) had the highest isolation rates while all Salmonella Infantis isolates were from the oviduct. Pulsed field gel electrophoresis (PFGE) analysis of BlnI-digested chromosomal DNA of Salmonella Enteritidis isolated from layer hens and rodents showed similar patterns. PFGE analysis of Salmonella Infantis isolated from layer hens, rodents, eggs, and the environment yielded identical patterns. In this study, the significantly higher prevalence rate (P < 0.05) of Salmonella Enteritidis and Salmonella Infantis in layer hens from high rodent density farms could be attributed to the high rodent population density. The persistent Salmonella Enteritidis and Salmonella Infantis infection inside layer houses may have been amplified by the increasing numbers in the rodent population over the years, which increased the opportunity for environment-rodent-chicken interaction and the transmission of salmonellae to chickens. Monitoring of salmonellae from rodents inside poultry premises is recommended to be an effective additional tool in the assessment of the Salmonella status of layer flocks.

Evaluation of in vivo genotoxic potential of fenofibrate in rats subjected to two-week repeated oral administration.

Fenofibrate (FF), a peroxisome proliferator-activated receptor-alpha agonist, has been used as one of the hypolipidemic drugs in man and induces oxidative stress and promotes hepatocarcinogenesis in the liver of rodents. This chemical belongs to a class of non-genotoxic carcinogens, but DNA damage secondary to oxidative stress resulting from reactive oxygen species (ROS) generation is suspected in rodents given this chemical. To examine whether FF has genotoxic potential, partially hepatectomized F344 male rats were treated orally with 0, 1,000 or 2,000 mg/kg of FF for 2 weeks, followed by diet containing 0.15% 2 acetyl aminofluorene (2 AAF) for enhancement the tumor-promoting effect for 10 days and a single oral dose of carbon tetrachloride (CCl4) as the first experiment (liver initiation assay). As the second experiment, the in vivo liver comet assay was performed in hepatectomized rats, and the expression of some DNA repair genes was examined. In the liver initiation assay, the number and area of glutathione S-transferase placental form (GST-P)-positive single cells and foci did not increase in the FF treated groups. In the comet assay, positive results were obtained after 3 h of the last treatment of FF, and the expression of some DNA repair genes such as Apex1, Ogg1 and Mlh1 were upregulated in rats given the high dose of FF at 3 h after the treatment but not in 24 h after the treatment. The results of the present study suggest that FF causes some DNA damage in livers of rats, but is not a strong genotoxic substance leading to a DNA mutation since such DNA damage was repaired by the increased activity of some DNA repair genes.

Evaluation of in vivo liver genotoxic potential of Wy-14,643 and piperonyl butoxide in rats subjected to two-week repeated oral administration.

Wy-14,643 (WY), a peroxisome proliferator-activated receptor-alpha agonist, and piperonyl butoxide (PBO), a pesticide synergist, induce oxidative stress and promote hepatocarcinogenesis in the liver of rodents. These chemicals belong to a class of non-genotoxic carcinogens, but DNA damage secondary to the oxidative stress resulting from reactive oxygen species generation is suspected in rodents given these chemicals. To examine whether WY or PBO have DNA-damaging potential in livers of rats subjected to repeated oral administration for 14 days, the in vivo liver comet assay was performed in partially hepatectomized rats, and the expression of some DNA-repair genes was examined. Then, to examine whether they have genotoxic potential, the in vivo liver initiation assay was performed in rats. In the comet assay, positive results were obtained at 3 h after the last treatment of WY, and some DNA-repair genes such as Apex1, Mlh1, Xrcc5, and Gadd45 were up-regulated in the liver. In the liver initiation assay, negative results were obtained for both WY and PBO. The results of the present study suggest that WY, but not PBO, causes some DNA damage in livers of rats, but such DNA damage was repaired by the increased activity of some DNA repair genes and may not lead to a DNA mutation.

Antioxidant enzymatically modified isoquercitrin suppresses the development of liver preneoplastic lesions in rats induced by beta-naphthoflavone.

To investigate the modifying effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by beta-naphthoflavone (BNF) treatment, male rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) and were fed a diet containing BNF (0.5%) for 6 weeks with or without EMIQ (0.2%) in the drinking water after DEN initiation. One week after the commencement of the administration of BNF, rats were subjected to a two-thirds partial hepatectomy. The number and area of GST-P positive foci, the number of COX2-positive cells and the area of elastica-van Gieson (EVG)-positive connective tissue fibers promoted by BNF were significantly suppressed by the administration of the antioxidant EMIQ. Real-time RT-PCR analysis revealed that EMIQ treatment decreased mRNA expression levels of Gstm1, Serpine1, Cox2 and Nfkbia and increased mRNA expression levels of Yc2 compared with those in the DEN-BNF group. These results suggest that co-administration of EMIQ suppresses the hepatocellular tumor-promoting activity of BNF in rats through the anti-inflammatory effects of EMIQ and restores the cellular redox balance altered by BNF.

A case report of an uncommon sex-cord stromal tumor consisted of luteal and sertoli cells in a spayed bitch.

We report a rare case of benign sex cord-stromal tumor consisted largely of luteoma with minor portion of Sertoli cell tumor located at the position of the left ovary excision in an 11-year-old ovariectomized bitch. Granulosa cell component was lacking, and both luteal and Sertoli cell portions were entirely positive for inhibin alpha and neuron-specific enolase, whereas luteoma portion alone was positive for Wilms' tumor-1 (WT1), immunohistochemically. The results suggest that this tumor is a possible complication of incomplete ovarian excision at the time of ovariectomy and consisted of uncommon hybrid of luteal and Sertoli cells to be diagnosed as an unclassified sex cord-stromal tumor if applied in human cases. WT1-expression pattern suggested the signature of the difference in the phenotype of these cell types.