Liver Tissue Specimens Research Articles

Prognostic significance of the combined expression of neutral endopeptidase and dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery resection

AimThe aim of this study was to investigate the relationship between the expression of neutral endopeptidase (NEP) and dipeptidyl peptidase IV (DPP IV) proteins, and the clinical significance of the two proteins in patients with intrahepatic cholangiocarcinomas (IHCC).MethodsExpression patterns and subcellular localizations of NEP and DPP IV proteins in 186 primary IHCC and 60 noncancerous liver tissue specimens were detected by immunohistochemistry.ResultsBoth the expression of NEP and DPP IV proteins in IHCC tissues were significantly higher than those in noncancerous liver tissues (both P<0.001). Of 186 patients with IHCC, 128 (68.82%) highly expressed both NEP and DPP IV proteins. In addition, the coexpression of NEP and DPP IV proteins was significantly associated with advanced tumor stage (P=0.009), positive lymph node metastasis (P=0.016) and distant metastasis (P=0.013), and the presence of recurrence (P=0.027). Moreover, Kaplan–Meier analysis showed that IHCC patients with high NEP expression, high DPP IV expression, and combined overexpression of NEP and DPP IV proteins all had poorer overall survival and early recurrence after surgery. Furthermore, Cox analysis suggested that NEP expression, DPP IV expression, and combined expression of NEP and DPP IV proteins were all independent prognostic markers for overall survival and recurrence-free survival in patients with IHCC.ConclusionOur data suggest, for the first time, that both the expression of NEP and DPP IV proteins may be upregulated in human IHCC tissues and the combined expression of NEP and DPP IV proteins may play important roles in progression and prognosis of patients with IHCC.

Immunohistochemical staining in liver resection margins: evaluation after metastatic colorectal carcinoma surgical treatment

Specimens of liver tissue from 30 patients with CRC macrome-tastases after liver resection were examined, preparing new recut sections (with 1mm interval) from the 5-7 paraffin blocks from each patient, and performing H&E stains and immunostains (using the antibody for cytokeratins 20). Discrete groups of cytokeratins 20 positive atypical cells were diagnosed as micrometastases. The study included 30 patients after combination treatment of CRC including liver resection. The status of resection margins was R0 (tumor cells absent) and R1 (tumor cells found). In group R0 cases the measurement of distance between macrometastasis and resection margins was done. In group R1 cases the distance between macrometastasis and resection margins was 0mm. In all, 182 intrahepatic micrometastases were found. Micrometastases localize in sinusoidal spaces (n=8), in portal tracts (n=12). In group R0 cases (n=13) the distance between macrometastasis and resection margins was ≥10mm in 3 cases, and ≤10mm in 9 cases. In one case micrometastases were not found. The determination of liver micrometastases predicts high risk of recurrence after surgical treatment and correlates with worse prognosis. The distance ≥1cm between macrometastasis and resection margins is associated with minimal amount of micrometastases in liver tissue.

Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

Metabolic profiles are principally different between cancers of the liver, pancreas and breast.

Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin.

Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis

Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on bacterial translocation and the liver status in experimental cirrhosis. Liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at week 12. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (10(9) cfu/daily) or placebo intragastrically. All animals received Escherichia coli (10(7) cfu/single dose) intragastrically 24 hours before laparotomy. A group of naïve non-treated animals was included as control. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected. Liver histology, profibrogenic genes expression, bacterial DNA translocation, serum endotoxaemia and liver cytokine levels were measured. Bifidobacterium pseudocatenulatum CECT7765 showed no significant effect on structural liver damage, as determined by histological evaluation, alpha-smooth muscle actin distribution, profibrogenic gene expression levels, total hydroxyproline levels and malon dialdehyde production compared with mice receiving placebo. Interestingly, bacterial DNA translocation and serum endotoxin levels were significantly decreased in mice receiving the Bifidobacterium strain compared with placebo. Gut barrier integrity markers were up-regulated in mice receiving B. pseudocatenulatum CECT7765 and quantitatively correlated with intestinal gene copy numbers of the bifidobacterial strain. Gene expression levels of several anti-inflammatory mediators were also increased in mice receiving B. pseudocatenulatum CECT7765 compared with placebo. Oral administration of B. pseudocatenulatum CECT7765 is associated with improved gut barrier integrity and shows a beneficial effect against induced bacterial antigen translocation in the CCl4 -model of cirrhosis.

Protective effects of L-carnitine, N-acetylcysteine and genistein in an experimental model of liver fibrosis

Liver fibrosis is a reversible wound-healing response that occurs following liver injury. In this study, we aimed to investigate the possible protective effects of L-carnitine, N-acetylcysteine and genistein in liver fibrosis induced by carbon tetrachloride (CCl4). In addition, the effects of these agents were compared in the same study. In this study, rats were randomly allocated into 8 groups, consisting of 10 rats each, as follows: a control group, CCl4, L-carnitine, N-acetylcysteine, genistein, CCl4 and L-carnitine, CCl4 and N-acetylcysteine, and CCl4 and genistein. At the end of 6 weeks, blood and liver tissue specimens were collected. Alanine aminotransferase (ALT); aspartate aminotransferase (AST); complete blood count, tumor necrosis factor-α (TNF-α); platelet-derived growth factor-BB (PDGF-BB); interleukin-6 (IL-6); liver glutathione level; oxidant/antioxidant status; scores of hepatic steatosis, necrosis, inflammation, and fibrosis; and the expression of α-smooth muscle actin were studied. Although the ALT and AST values in the group administered CCl4 were significantly higher than in all the other groups (P<0.05), there was no significant difference between the control group and the groups administered CCl4 combined with L-carnitine, N-acetylcysteine and genistein (P>0.05). There were significant differences in the levels of TNF-α, PDGF-BB and IL-6 (P<0.05) between the CCl4 group and the groups with L-carnitine, N-acetylcysteine and genistein added to CCl4. N-acetylcysteine and genistein had positive effects on the oxidant/antioxidant status and on liver necrosis and fibrosis scores. In our study, L-carnitine, N-acetylcysteine and genistein showed significant protective effects in liver fibrosis induced by CCl4.

Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer

To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer. Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively. Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05). S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.

Viral Hepatitis Markers in Liver Tissue in Relation to Serostatus in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) incidence is increasing in the United States. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of HCC. Hepatitis infection in patients with HCC is generally diagnosed by serology, which is not always consistent with the presence of HBV and HCV in the liver. The relationship of liver viral status to serostatus in hepatocarcinogenesis is not fully understood. HBV and HCV were evaluated in formalin-fixed, paraffin-embedded liver tissue specimens in a retrospective study of 61 U.S. HCC cases of known serologic status. HBV DNA and HCV RNA were detected by PCR, reverse transcription PCR (RT-PCR), and pyrosequencing, and HBsAg and HBcAg were evaluated by immunohistochemistry. Viral markers were detected in the liver tissue of 25 of 61 (41%) HCC cases. Tissue viral and serologic status were discordant in 27 (44%) cases, including those with apparent "occult" infection. Specifically, HBV DNA was detected in tissue of 4 of 39 (10%) serum HBsAg (-) cases, including 1 anti-HCV(+) case; and HCV RNA was detected in tissue of 3 of 42 (7%) anti-HCV seronegative cases, including two with serologic evidence of HBV. Viral hepatitis, including HBV-HCV coinfection, may be unrecognized in up to 17% of patients with HCC when based on serology alone. Further research is needed to understand the clinical significance of viral makers in liver tissue of patients with HCC in the absence of serologic indices. The contribution of HBV and HCV to the increasing incidence of HCC in the United States may be underestimated.

Effects of Intra- and Post-Operative Ischemia on the Metabolic Profile of Clinical Liver Tissue Specimens Monitored by NMR

Metabolomic profiles of tissues could greatly contribute to advancements in personalized medicine but are influenced by differences in adopted preanalytical procedures; nonhomogeneous pre- and post-excision ischemia times are potential sources of variability. In this study, we monitored the impact of ischemia on the metabolic profiles, acquired with high-resolution magic-angle-spinning (1)H NMR, of 162 human liver samples collected during and up to 6 h after routine surgery. The profiles changed significantly as a function of intraoperative warm ischemia (WI) and postresection cold ischemia (CI) time, with significant variations in the concentration of the same 16 metabolites. Therefore, a tight control of the preanalytical phase is essential for reliable metabolomic analyses of liver diseases. The NMR profiles provide a reliable "fingerprint" of ischemia and have predictive value: the best-performing predictive models are found to discriminate extreme time points of CI (0' vs 360 ') in the training set with cross-validation accuracy of ~90%; samples in the validation cohort can discriminate short (≤60') from long (≥180') CI with an accuracy of ~80%. For WI, the corresponding figures are 95.6 and 92%, respectively. Therefore, ischemia NMR profiles might become a tool for tissue quality control in biobanks.

Transjugular liver biopsy: Indications, technique and results

Transjugular liver biopsy is a safe, effective and well-tolerated technique to obtain liver tissue specimens in patients with diffuse liver disease associated with severe coagulopathies or massive ascites. Transjugular liver biopsy is almost always feasible. The use of ultrasonographic guidance for percutaneous puncture of the right internal jugular vein is recommended to decrease the incidence of local cervical minor complications. Semiautomated biopsy devices are very effective in obtaining optimal tissue samples for a precise and definite histological diagnosis with a very low rate of complication. The relative limitations of transjugular liver biopsy are the cost, the radiation dose given to the patient, the increased procedure time by comparison with the more common percutaneous liver biopsy, and the need of a well-trained interventional radiologist.

Methylation of nucleolar and coiled-body phosphoprotein 1 is associated with the mechanism of tumorigenesis in hepatocellular carcinoma

Nucleolar and coiled-body phosphoprotein1 (NOLC1) plays an essential role in the synthesis of rRNA and the biosynthesis of ribosomes. Previous studies suggest that NOLC1 is crucial for normal cell growth, and plays a role in the regulation of tumorigenesis of nasopharyngeal carcinoma (NPC) and demonstrate that both NOLC1 and tumor protein53 work synergistically to activate the MDM2 promoter in NPC cells. Yet, the functioning of NOLC1 in liver cancer remains unknown. The aim of the present study was to understand how the NOLC1 gene is regulated in liver carcinogenesis. In this study, we showed that NOLC1 was silenced or downregulated in liver tumor tissues when compared with that in the matched non-cancer tissues. In addition, human hepatoma cells weakly expressed NOLC1, whereas cultured human normal liver cell lines expressed abundant levels. The hypermethylation status in the promoter CpG1 start region appeared to be correlated with the NOLC1 expression levels in liver cell lines or liver normal and tissue specimens. We found that four CpG dinucleotides were located at the CpG1 start region. Further molecular analysis of mutagenesis indicated that the four CpG dinucleotides play a role in the promoter activity of the NOLC1 gene. The expression of NOLC1 and DNA methylation of its promoter affected cell proliferation and apoptosis. The expression of NOLC1 in hepatoma cell lines was restored following exposure to the demethylation agent, 5-azacytidine. Low expression of NOLC1 in hepatoma cell lines and liver cancer tissues was associated with cyclinD3. In conclusion, our study demonstrated that DNA methylation is a key mechanism of silenced NOLC1 expression in human hepatocellular carcinoma cells, and NOLC1 gene hypermethylation of the four CpG dinucleotides is a potential biomarker for hepatocellular carcinoma.

Hepatic and renal functions in growing male rats after bisphenol A and octylphenol exposure

This study aimed to determine the effects of 13-week bisphenol A (BPA) and octylphenol (OP) exposure on the liver, kidney, and spleen of growing male rats. A total of 29 male Wistar rats aged 4-5 weeks were divided into five groups. The treatment groups were given low-dose (125 mg/kg bw/day) or high-dose (250 mg/kg bw/day) BPA or OP. These compounds were dissolved in corn oil and given via oral route for 13 weeks. Rats in the control group received corn oil for 13 weeks, as well. After 13 weeks of treatment, blood samples were analyzed for biochemical parameters. Tissue samples from the liver, kidney, and spleen were histopathologically and histomorphometrically examined. Liver tissue specimens were also stained by immunohistochemically; the number of apoptotic cells was counted, and the apoptotic indices were calculated. There were significant differences between the control and treatment groups with respect to the following parameters: body weight, relative left kidney weight, and total protein, glucose, and alkaline phosphatase levels. Edema and parenchymal degeneration in the liver and tubular degeneration in the kidney were more frequent in the treatment groups. The control and treatment groups were comparable with respect to the frequency of histopathological lesions in the spleen. Glomerular histomorphometry revealed no significant differences between the control and treatment groups. No significant differences existed between the control and treatment groups with respect to the number of apoptotic cells and apoptotic indices. Subchronic exposure to BPA and OP induced functional and structural changes in the liver, kidney, and spleen of growing male rats.

Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma

The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection. One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured. The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival. Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.

Thermal Conductivity Measurements of Thin Biological Tissues Using a Microfabricated 3-Omega Sensor

Thermal Conductivity Measurements of Thin Biological Tissues Using a Microfabricated 3-Omega Sensor

398 VIRAL REPLICATION IN HBV-TRANSGENIC MICE LACKING THE HBsAg SIGNIFICANTLY INDUCES INTERFERON RESPONSES

Methods: Explanted and transplanted liver from 21 patients (5 with HBV-related, 6 with HBV/HDV-related and 10 with HCVrelated chronic liver disease) were analysed. All but one donor were HBsAg negative, 6 were anti-HBc positive, 14 were negative for all serum markers. From transplanted livers, biopsy specimens obtained before LT, in post-perfusion period and at end of LT were available. HBVDNA was tested in all liver tissue specimens by nested-PCR amplifications specific for 4 different HBV genomic regions. Total HBVDNA, HBV cccDNA and HDV RNA were quantified by specific real time-PCR approaches. Results: At the end of surgery, two of the 5 HBsAg-positive patients (both donors were anti-HBc positive), 1 of the 6 HBV/HDV coinfected patients (the donor was HBsAg-positive) and 2 of the 10 HCV-infected patients (one donor was anti-HBc positive and the other anti-HBc negative) showed the presence of quantifiable amounts of HBVDNA in the liver (range: 6x10-1x10 copies/cells). Sequencing analysis of the isolated HBV genomes showed that they were donor viral strains. HBV cccDNA could be detected and quantified (range: 2x10-2x10 copies/cell) in all the HBV-positive patients. None of the HBV/HDV-infected patients showed HDV RNA in the transplanted liver. Conclusions: 1. HBV genomes infecting the transplanted liver cause the reinfection of the recipients in the course of LT; 2. HDV does not re-infect the transplanted liver at the time of LT; 3. occult HBV infection (namely, presence of intrahepatic HBVDNA in HBsAg negative individuals) may be present in trasplanted liver and may persist during LT independently of the anti-HBc status of the donor.

Expression of Aminopeptidase N (CD13) and its significance in hepatocellular carcinoma

Objective To explore the expression and clinical significance of Aminopeptidase N (CD13) in hepatocellular carcinoma (HCC).Methods The CD13 expressions from 55 cases of hepatocellular carcinoma with corresponding paracancerous tissue and 13 cases of normal liver tissue specimens were detected by immunohistochemical staining.The correlations of CD13 expression and clinicopathological characteristics were analyzed by Chi-squared test and survival curves were generated according to the Kaplan Meier method.Results The positive rate of CD13 protein was 72.73％ (40/55) in hepatocellular carcinoma tissue,21.81％ (12/55) in adjacent non-tumor tissue and 7.69 ％ (1/13) in normal liver tissue.The expression of CD13 was up-regulated significantly in HCC with statistically significant differences (P＜0.05).Statistical analysis revealed that CD13 expression was correlated with histological differentiation,capsule invasion,portal vein tumor thrombus,lymph node metastasis and clinical stages in HCC.The survival curves showed that the survival rate was significantly lower in patients with positive CD13 expression compared to negative expression (P＜0.05).Also,the mul tivariate COX proportional hazard model showed that CD13 expression was an independent predictor of overall survival (P＜0.05).Conclusion Therefore,CD13 plays a mutually promoting role in the progression and development of HCC and may be a diagnostic and prognostic indicator for HCC patients. Key words: Hepatocellular carcinoma; Aminopeptidase N(CD13); Prognosis

The protective effects of ω-3 fatty acids on doxorubicin-induced hepatotoxicity and nephrotoxicity in rats

This study aims to evaluate the protective effects of ω-3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats. A total of 24 adult male Sprague Dawley rats were divided into three groups. Control group was given only saline by intragastric gavage. DOX group received DOX at the dose of 30mg/kg intraperitoneally on day 28. DOX-ω-3 FA group was given as ω-3 FAs at the dose of 400mg/kg daily by intragastric gavage for 30days and received DOX at the dose of 30mg/kg intraperitoneally on day 28. At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia. Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically. In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group. In addition, a significant decrease in MDA levels was observed in rats when a dose of ω-3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group. We concluded that ω-3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.

Characterising soft tissues under large amplitude oscillatory shear and combined loading

Characterising soft biological tissues outside the linear viscoelastic regime is challenging due to their complex behaviour. In addition, the viscoelastic properties of tissues have been shown to be sensitive to sample preparation and loading regime resulting in inconsistent data varying by orders magnitude in the literature. This paper presents a novel technique to characterise the non-linear behaviour of tissues which uses Fourier Transformation to decompose the stress output waveform under large amplitude oscillatory shear (LAOS) into harmonic contributions. The effect of varying preload, the compressive strain exerted on a liver tissue specimen prior to shear testing to minimise slip, was also investigated. Results showed that in the linear regime, preload affects the viscoelastic response of liver. Histological analysis indicated that there were structural changes as a result of the preload that may be linked to the differences in observed behaviour. Fourier analysis was used to extract the first and third harmonic components of the shear moduli at large strain. At 50% shear strain, a change in the third harmonic component of the shear moduli was accompanied by a marked change in the micro-structural arrangement of the sinusoids. This paper demonstrates a method of efficiently characterising soft biological tissues under large amplitude oscillatory shear under combined loading.

Hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis: 72 cases (1980–2010)

To evaluate differences in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis. etrospective case-control study. Liver tissue specimens from 36 Labrador Retrievers with chronic hepatitis and 36 age- and sex-matched Labrador Retrievers without chronic hepatitis (control dogs). Liver tissue specimens were obtained during 2 study periods (1980 to 1997 and 1998 to 2010). For each tissue specimen, a histologic score was assigned independently by each of 2 interpreters, and the hepatic copper concentration was qualitatively determined via rhodanine staining and quantitatively determined via atomic absorption spectroscopy. Mean hepatic copper concentration was significantly higher in dogs with chronic hepatitis (614 μg/g of dry weight [range, 104 to 4,234 μg/g of dry weight]), compared with that in control dogs (299 μg/g of dry weight [range, 93 to 3,810 μg/g of dry weight]), and increased significantly over time. A higher proportion of liver tissue specimens collected during the 1998-2010 study period had hepatic copper concentrations > 400 μg/g of dry weight (the upper limit of the reference range), compared with the proportion of liver tissue specimens collected during the 1980-1997 study period. The qualitative copper score did not accurately predict quantitative hepatic copper concentration in 33% of study dogs. Results suggested that the increase in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis over time may be the result of increased exposure of dogs to environmental copper, most likely via the diet.

Protein Globule Formation in the Liver Graft during Cold Preservation for Liver Transplantation: Its Clinical and Pathological Significance

In liver transplantation, liver graft ischemia-reperfusion injury occurs mainly due to cold preservation and warm reperfusion. In this research, we study the affection of plasma protein of the donor on liver graft during cold preservation and warm reperfusion. In this study, 34 liver transplantations were performed from 2007 to 2010, and the clinical data were collected retrospectively from the Dongfang Hospital database. 34 specimens were harvested from 34 liver grafts when graft trimming as Group A and 34 specimens harvested from the same 34 liver grafts during liver transplantation surgery but before abdominal closure as B group. All liver tissue specimens were fixed with 40 g/L neutral formalin, embedded in paraffin. Light microscopy, transmission electron microscopy, Periodic Acid-Schiff (PAS) stain and immunohistochemical stain of IgG, IgM, IgA, C3d, C4d, Fib, C1q, and CD61 were used. In this study, we found that eosinophilic bodies emerged in liver lobes during liver transplantation which had not been reported previously in the literature. 1) Protein globules were found exclusively in liver graft specimens. The globules were round or oval with sharp edges, measured approximately 1.59 to 9.41 μm in diameter, and were scattered in the liver sinusoids or space of Disse or hepatocyte cytoplasm, were stained with IgG, IgM, IgA, Fib, C3d by immunohistochemical staining; 2) There was no statistical significant difference of protein globules number between A group and B group (P > 0.05); 3) IRI score of B group was not correlated with protein globules number (P > 0.05). Protein globules contain plasma composition, and may form during cold preservation.