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Sample records for normal rabbit liver

  1. THE RETENTION OF S35-LABELLED BOVINE SERUM ALBUMIN IN NORMAL AND IMMUNIZED RABBIT LIVER TISSUE

    PubMed Central

    Garvey, Justine S.; Campbell, Dan H.

    1957-01-01

    The S35-label of S35-BSA was detected in the liver tissue of rabbits to the extent of 0.02 per cent (10 µg or ≃ 1014 molecules) of the injected material at 140 days after injection. The rate of loss of antigen at the termination of the experiment was of such an order that significant amounts would be expected to persist for at least several years. Data are reported which extend the retention data previously reported on S35-labelled hemocyanin. They indicate that amounts of the order of 0.05 per cent (25 µg.) of antigen material persist at 330 days after injection. All of the radioactivity of material retained in the liver tissue 6 weeks after injection was immunologically related to the original S35-BSA antigen. Preliminary studies are reported which indicate that the retained antigen is bound to ribonucleic acid. A new method is described for the isolation of p-azophenylsulfonate bovine serum albumin from tissue extracts by means of a Dowex 2 adsorbent. PMID:13416473

  2. Disposition of human fibrinopeptide A in normal and nephrectomized rabbits

    SciTech Connect

    Harenberg, J.; Stehle, G.; Waibel, S.; Hermann, H.J.; Eisenhut, M.; Zimmermann, R.

    1983-10-01

    The distribution, elimination, and metabolism of human fibrinopeptide A (FPA) were studied in normal and nephrectomized rabbits. The activity of /sup 125/I-labeled desamino-tyrosyl human FPA (DAT-FPA) was followed over 4 hours after i.v. administration. Results show that in normal rabbits (n . 10) DAT-FPA is eliminated from plasma in four phases with half-lives of 30 sec, 3.5 min, 15 min, and 90 min. The distribution of /sup 123/I-labeled DAT-FPA in plasma was determined in 15 control rabbits with scintigraphy over 2 hours. DAT-FPA was distributed primarily in the cardiovascular system, liver, and kidneys. In some animals minimal radioactivity was detected over the gall bladder. Radioactivity accumulated rapidly in the urinary bladder, approximately 50% being recorded after 15 min and 90% after 120 min. In the heart area radioactivity decreased with half-lives of 25 sec, 7.5 min, 25 min, and 180 min. Nephrectomized rabbits had similar initial fast distribution of DAT-FPA after administration of /sup 125/I-labeled (n . 10) and /sup 123/I-labeled peptide (n . 10). The estimated half-life of the slow component was in the order of several hours. The results of the scintigraphic and gel chromatographic studies show that FPA is primarily excreted in the urine. Previously reported half-lives of FPA reflect distribution rather than steady state conditions.

  3. Pharmacokinetics of trimethoprim (TMP) in normal and febrile rabbits.

    PubMed

    Ladefoged, O

    1977-11-01

    The pharmacokinetics of trimethoprim (TMP) were investigated in normal and febrile rabbits. The half-life of TMP in rabbits is about 40 minutes and no differences were found between the half-life in normal and febrile rabbits. A significantly greater volume of distribution of TMP, however, was found in the febrile rabbits. Analysis according to the two-compartment model showed that the differences are due to a change in the distribution of TMP towards the peripheral compartments.

  4. Apparent diffusion coefficient normalization of normal liver

    PubMed Central

    Zhu, Jie; Zhang, Jie; Gao, Jia-Yin; Li, Jin-Ning; Yang, Da-Wei; Chen, Min; Zhou, Cheng; Yang, Zheng-Han

    2017-01-01

    Abstract Apparent diffusion coefficient (ADC) measurement in diffusion-weighted imaging (DWI) has been reported to be a helpful biomarker for detection and characterization of lesion. In view of the importance of ADC measurement reproducibility, the aim of this study was to probe the variability of the healthy hepatic ADC values measured at 3 MR scanners from different vendors and with different field strengths, and to investigate the reproducibility of normalized ADC (nADC) value with the spleen as the reference organ. Thirty enrolled healthy volunteers received DWI with GE 1.5T, Siemens 1.5T, and Philips 3.0T magnetic resonance (MR) systems on liver and spleen (session 1) and were imaged again after 10 to 14 days using only GE 1.5T MR and Philips 3.0T MR systems (session 2). Interscan agreement and reproducibility of ADC measurements of liver and the calculated nADC values (ADCliver/ADCspleen) were statistically evaluated between 2 sessions. In session 1, ADC and nADC values of liver were evaluated for the scanner-related variability by 2-way analysis of variance and intraclass correlation coefficients (ICCs). Coefficients of variation (CVs) of ADCs and nADCs of liver were calculated for both 1.5 and 3.0-T MR system. Interscan agreement and reproducibility of ADC measurements of liver and related nADCs between 2 sessions were found to be satisfactory with ICC values of 0.773 to 0.905. In session 1, the liver nADCs obtained from different scanners were consistent (P = 0.112) without any significant difference in multiple comparison (P = 0.117 to >0.99) by using 2-way analysis of variance with post-hoc analysis of Bonferroni method, although the liver ADCs varied significantly (P < 0.001). nADCs measured by 3 scanners were in good interscanner agreements with ICCs of 0.685 to 0.776. The mean CV of nADCs of both 1.5T MR scanners (9.6%) was similar to that of 3.0T MR scanner (8.9%). ADCs measured at 3 MR scanners with different field strengths and vendors

  5. HYPERVASCULAR LIVER LESIONS IN RADIOLOGICALLY NORMAL LIVER.

    PubMed

    Amico, Enio Campos; Alves, José Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; João, Samir Assi; Liguori, Adriano de Araújo Lima

    2017-01-01

    The hypervascular liver lesions represent a diagnostic challenge. To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Eighty-eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine aminotransaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. As lesões hepáticas hipervasculares representam um desafio diagnóstico. Identificar fatores de risco para câncer em pacientes portadores de lesão hepática hipervascular não-hemangiomatosa em fígado radiologicamente normal. Estudo prospectivo que incluiu pacientes com lesões hepáticas hipervasculares em que o diagnóstico final foi obtido por exame anatomopatológico ou, presumido a partir de seguimento mínimo de um ano. Diagnóstico prévio de cirrose ou radiológico de hemangioma foram considerados critérios de exclusão. Oitenta e oito pacientes foram incluídos. A relação mulher/homem foi de 5,3/1. A idade média foi de 42,4 anos. Na

  6. Quantitative evaluation of fatty liver by computed tomography in rabbits

    SciTech Connect

    Kawata, R.; Sakata, K.; Kunieda, T.; Saji, S.; Doi, H.; Nozawa, Y.

    1984-04-01

    Biochemical, histologic, and computed tomographic (CT) examinations of the liver were performed in 32 rabbits in which fatty liver was induced by prolonged intravenous fat infusion. In two groups of rabbits, in which 2 and 4 g/kg/day of fat emulsion was administered, respectively, posttreatment reduction in CT value of mild degree was observed. In the group that received 8 g/kg/day of fat emulsion, posttreatment change in CT value was sufficient for a diagnosis of fatty liver of moderate degree. Reduction in CT value in fatty liver might be due largely to accumulation of triglyceride and cholesterol in the liver cells. Significant correlation was found between changes in CT value of the liver and degrees of histological fat accumulation in the liver cells. Consecutive measurement of CT values of the liver during prolonged intravenous hyperalimentation is a nonagressive method of diagnosing fatty liver.

  7. Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

    PubMed

    Parvinian, Ahmad; Casadaban, Leigh C; Hauck, Zane Z; van Breemen, Richard B; Gaba, Ron C

    2015-01-01

    Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

  8. Low-density-lipoprotein receptors in different rabbit liver cells.

    PubMed Central

    Nenseter, M S; Myklebost, O; Blomhoff, R; Drevon, C A; Nilsson, A; Norum, K R; Berg, T

    1989-01-01

    Receptor-dependent uptake mechanisms for low-density lipoprotein (LDL) were studied in rabbit liver parenchymal and non-parenchymal cells. Hybridization studies with a cDNA probe revealed that mRNA for the apo (apolipoprotein) B,E receptor was present in endothelial and Kupffer cells as well as in parenchymal cells. By ligand-blotting experiments we showed that apo B,E-receptor protein was present in both parenchymal and non-parenchymal cells. Studies of binding of homologous LDL in cultured rabbit parenchymal cells suggested that about 63% of the specific LDL binding was mediated via the apo B,E receptor. Approx. 47% of the specific LDL binding was dependent on Ca2+, suggesting that specific Ca2+-dependent as well as Ca2+-independent LDL-binding sites exist in liver parenchymal cells. Methylated LDL bound to the parenchymal cells in a saturable manner. Taken together, our results showed that apo B,E receptors are present in rabbit liver endothelial and Kupffer cells as well as in the parenchymal cells, and that an additional saturable binding activity for LDL may exist on rabbit liver parenchymal cells. This binding activity was not inhibited by EGTA or reductive methylation of lysine residues in apo B. LDL degradation in parenchymal cells was mainly mediated via the apo B,E receptor. Images Fig. 1. Fig. 2. PMID:2549976

  9. Age dependency of base modification in rabbit liver DNA

    NASA Technical Reports Server (NTRS)

    Yamamoto, O.; Fuji, I.; Yoshida, T.; Cox, A. B.; Lett, J. T.

    1988-01-01

    Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

  10. Age dependency of base modification in rabbit liver DNA

    NASA Technical Reports Server (NTRS)

    Yamamoto, O.; Fuji, I.; Yoshida, T.; Cox, A. B.; Lett, J. T.

    1988-01-01

    Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

  11. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis

    PubMed Central

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-01-01

    AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365

  12. [Effect of lipiodol emulsion and local hyperthermia on hepatic tissue blood flow in rabbits with VX-2 liver tumor].

    PubMed

    Suzuki, K; Tada, I; Okada, K; Kim, Y I; Kobayashi, M

    1988-08-01

    The effect of intra-arterial infusion of lipiodol-emulsion and local hyperthermia on tissue blood flow was examined in experimental hepatic tumor and normal liver of rabbits. VX-2 tumor was implanted in liver of rabbit. The tissue blood flow was estimated by hydrogen gas clearance method when the tumor grew to about 2 cm. Tissue blood flow in tumor (64.5 ml/min/100 g) was significantly less than in normal liver (90.8 ml/min/100 g) (p less than 0.005). The intra-arterial infusion of lipiodol-emulsion did not alter the flow in either tissue. However, the addition of hyperthermia induced a substantial rise of tissue blood flow in normal liver (35% increase, from 93.8 to 127 ml/min/100 g) when compared with in VX-2 tumor (8.9% increase, from 65.1 to 71.8 ml/min/100 g). These were accompanied by a selective heating of liver tumor; the tumor temperature rose to 43 degrees C, although that of normal liver remained at 38 degrees C. Our results suggested that a specific temperature rise of liver tumor after infusion of lipiodol-emulsion and local heating might be related to a different response of microcirculation in tumor and normal liver to the hyperthermia.

  13. Histologic analysis of rabbit liver cancer treated by bulk ultrasound ablation

    NASA Astrophysics Data System (ADS)

    Karunakaran, Chandra Priya; Rudich, Steven M.; Alqadah, Amel; Burgess, Mark T.; Narmoneva, Daria A.; Mast, T. Douglas

    2012-10-01

    VX2 rabbit liver cancer, treated in vivo using bulk ultrasound ablation by miniaturized image-ablate arrays, was histologically analyzed using TTC vital stain and DAPI nucleic acid stain. VX2 cells were implanted into rabbit liver lobes and allowed to grow for 11-21 days. Liver lobes containing solid VX2 tumors were then treated with 4.8 MHz, 22.5-38.5 W/cm2 in situ intensity, unfocused ultrasound for exposure times of 20-120 s. After animal sacrifice, thermal lesions were bisected along the imaging/treatment plane, one face stained with TTC, and the other with DAPI. Levels of TTC uptake (no uptake, partial uptake, and complete uptake) in liver parenchyma corresponded to three discrete regions of tan, pink and red color. By processing images of DAPI-stained parenchymal tissue from these three regions, cellular damage was quantified. A viability index parameter incorporating the size and shape of DAPI-stained nuclei correlated significantly with levels of TTC uptake, and thus with local tissue viability. For ablation of normal liver, viability indices for parenchymal regions of no TTC uptake and partial TTC uptake were significantly different from those for viable tissue. For ablation of VX2 tumor, differences in viability index between regions of no TTC uptake and complete TTC uptake were smaller, but significant overall.

  14. Combined radiofrequency ablation and hot saline injection in rabbit liver.

    PubMed

    Kim, Young Kon; Lee, Jeong Min; Kim, Sang Won; Kim, Chong Soo

    2003-11-01

    To determine whether combining hot saline injection (HSI) and radiofrequency ablation (RFA) can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. In 66 rabbits, RF energy and/or hot saline-induced coagulations were produced using a 17-gauge cooled electrode or 21-gauge needle under ultrasound guidance. Rabbits were allocated into 1 of 5 groups: group A, RFA alone (n = 15); group B, HSI (1 mL hot saline infused, n = 10); group C, combined therapy for HSI followed by RFA (n = 21); group D, combined therapy for RFA immediately followed by HSI (n = 10); and group E, 1 mL room temperature saline infusion before RFA (n = 10). RF energy (30 W) was applied for 3 minutes. The changes in tissue impedance, current, power output, and temperature of the electrode tip were automatically measured. Before RFA, precontrast computed tomography was performed, and after RFA, pre- and postcontrast spiral computed tomographic scans were acquired. The maximum diameters of the thermal lesions on the gross specimens and complications of each group were compared. All procedures were technically successful. There were 9 of 61 procedure-related complications (14.8%) including 6 localized hematomas and 3 thermal injuries to the diaphragm and the stomach. In rabbits in groups C and E, a marked decrease of tissue impedance (43.4 omega, 44.1 omega) and an increase of current (709 mA, 722 mA) occurred with instillation of saline infusion compared with RFA only. Combined therapy for HSI followed by RFA produced a greater short-axis mean diameter of coagulation (14.6 +/- 4.3 mm) than that in rabbits of other groups, for RFA only (10.4 +/- 2.4 mm), HSI only (8.7 +/- 3.3 mm), and combined therapy for RFA immediately followed by HIS (12.0 +/- 1.4 mm; P < 0.05). Combined therapy for HSI followed by RFA can increase the volume of RFA-induced coagulation in the liver with a single application, and therefore may improve the results of RFA for the treatment of larger

  15. Effect of excessive saccharose administration on metabolic processes in the liver of rabbits with restricted mobility

    NASA Technical Reports Server (NTRS)

    Rylnikov, Y. P.

    1980-01-01

    The administration of saccharose (3 g per 1 kg for 2 months) intensified changes encountered in hypokinesia. There was a more marked increase in the content of cholesterol, pre-beta and beta-lipoproteins, phospholipids, and glycosaminoglycans in the blood. At the same time, the administration of saccharose improved the course of metabolic processes in the liver of immobilized rabbits, restored to normal levels the reduced glycogen level, the rate of glycolysis and the conversion of cholesterol to bile acids and their discharge in the cystic bile.

  16. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  17. The presence of liver auto-antibodies induced by Entamoeba histolytica in the sera from both naturally infected humans and immunized rabbits.

    PubMed

    Faubert, G M; Meerovitch, E; McLaughlin, J

    1978-09-01

    Auto-antibodies against normal human liver have been detected in the sera of humans with highly positive indirect hemagglutination (IHA) amebiasis titers and with clinically-proven amebic liver abscess. Sera of amebiasis patients and rabbits immunized with killed Entamoeba histolytica were tested for anti-amebic antibodies by the IHA test and for auto-antibodies by the complement fixation test, using the antigens prepared from extracts of human liver and rabbit liver. A direct correlation was found to exist between high anti-Entamoeba antibody titers and the presence of anti-liver antibody in the serum. It is proposed that, in addition to direct parasite damage to host tissue, immunological damage could result from the attachment of circulating antigen to the cell surfaces of host tissues such as the liver.

  18. Concentrations of vancomycin in bone and serum of normal rabbits and those with osteomyelitis.

    PubMed Central

    Wilson, K J; Mader, J T

    1984-01-01

    The concentrations of vancomycin in the bone and serum of rabbits with Staphylococcus aureus osteomyelitis were assessed after each rabbit was given a single dose of vancomycin. Simultaneous mean concentrations of vancomycin in infected rabbits 1 h after administration of the antibiotic were 36.4 +/- 4.6 micrograms/ml (serum), 5.3 +/- 0.8 microgram/g (infected bone), and 3.0 +/- 0.2 micrograms/g (noninfected bone). Concentrations of vancomycin in serum of normal controls were higher than concentrations of vancomycin in serum of osteomyelitic rabbits after 1, 2, 3, and 6 h. PMID:6703678

  19. Obtaining liver tridimensional scaffold through the decellularization of rabbit whole liver in 24 hours

    NASA Astrophysics Data System (ADS)

    Federico, Schliamser; Ayelen, Rinaldi; Romina, Comin; Alba Nelly, Borchert; Adrian, Nari Gustavo; Alicia, Salvatierra Nancy; Mariana Paula, Cid

    2016-04-01

    In the present work, we development a new protocol for liver decellularization in which the hole decellularization was reached over 24 h. Introduction: the availability of transplantable livers is not sufficient to fulfill the current demand for grafts, with the search for therapeutic alternatives having generated different lines of research, one of which is the use of decellularized three-dimensional biological matrices and subsequent cell seeding to obtain a functional organ. Objective: to produce a decellularization protocol from rabbit liver to generate a three-dimensional matrixin which the time period involved didn't pass 24 h. Methods: The decellularization is obtained through the use of water and SDS (0,1-0,3 %), after freezing at -80 degrees, is the best alternative of different physical and/or chemical mechanisms to break down organ cells and leave only the extracellular matriz. After 24 h of retrograde perfusion, a decellularized translucent matrix was generated. To evaluate if the decellularization protocol was successful, with the extracellular matrix being preserved, we carried out histological (light microscopy) and biochemical (DNA quantification) studies. Results: the decellularization process was verified by macroscopic observation of the organ using microscopic observation corroborated the macroscopic results, with the hematoxylin-eosin and Masson staining showing no cells or nuclear material. In addition, the DNA quantification was less than 10% in the decellularized liver compared to control. Finally,the time taken to develop the decellularization protocol was less than 24 hours.

  20. Experiment studies of iodinated oil nanometer ferrofluid retention in rabbit liver.

    PubMed

    Zhang, X; Lin, R; Lin, Y; Wu, R H

    2005-01-01

    To study possibility for iodinated oil nanometer ferrofluid retention in rabbit liver. 131I- iodinated oil nanometer ferrofluid were injected into liver right lobe through portal vein in 5 rabbits... - calibrate meter showed continuous.. counts in the region injected. Then the relative metabolic parameters were calculated. Left lobe livers, right lobe livers and lungs of the rabbits were examined in pathology, and the right lobe livers were examined by electron microscope. Five rabbits injected purely 131Iiodinated oil were designated as control group. Single metabolic mode was found in the rabbits in nanometer ferrofluid group. The biological half-life of 131I- iodinated oil nanometer ferrofluid was not different from control group's slow metabolic portion. But control group's rapid metabolic portion were eliminated in a higher speed, range from 8% to 44%. More damage was found in nanometer ferrofluid group's right lobe livers. 131I- iodinated oil nanometer ferrofluid possess the opportunity of local retention in human body and further study is worthwhile.

  1. Lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta.

    PubMed

    Li, Zhong

    2013-05-13

    To discuss the value of lymph node mapping in rabbit liver cancer with nanocarbon and methylene blue injecta. Rabbit liver cancer model was established by transplanting VX2 cells with laparotomy in celiac planting method. Twenty Japan white rabbits were divided into two groups randomly. Each group had 10 rabbits. Lymph node mapping in two groups rabbit liver cancer were observed. Two groups rabbit liver cancer and local lymph nodes were removed. The number and location of local lymph nodes were recorded, and then the samples were obtained from both groups. The lymph nodes dyed time was (100.50±29.92) s in nanocarbon group, and (11.20±4.18) s in methylene blue group with statistical significance between two groups (P=0.000). In the comparison of lymph node fading time, nanocarbon group was (2.22±0.74) h, methylene blue group was (1.63±0.54) h, nanocarbon group was longer than the methylene blue group, but without statistical significance (P=0.058). The accuracy was 87.5% (35/40) in methylene blue group, while, the nanocarbon group was 87.2% (34/39), with statistical significance (P=1.000). Experimental results show that application of nanocarbon injection and methylene blue injection during resection of liver cancer and local lymph nodes in rabbit liver cancer model has obvious tracer function in liver cancer and lymphatic drainage. It can reduce the complexity and risk of the operation, and avoid the blindness in the process of traditional lymph node dissection surgery. Besides, they can effectively reduce the number of residual lymph nodes after operation. It can achieve the lymph node dissection more thoroughly, promptly, easily and safely. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  2. Selective inactivation by 21-chlorinated steroids of rabbit liver and adrenal microsomal cytochromes P-450 involved in progesterone hydroxylation.

    PubMed

    Halpert, J; Jaw, J Y; Balfour, C; Mash, E A; Johnson, E F

    1988-08-01

    The inactivation by 21-chlorinated steroids of rabbit liver cytochromes P-450 involved in the hydroxylation of progesterone has been investigated in intact microsomes encompassing two phenotypes of 21-hydroxylase activity, two phenotypes of 16 alpha-hydroxylase activity, and three phenotypes of 6 beta-hydroxylase activity. In liver microsomes from outbred New Zealand White male rabbits exhibiting a high content of cytochrome P-450 1, 21,21-dichloropregnenolone caused a time- and NADPH-dependent loss of 21-hydroxylase activity. This loss of activity exhibited a number of characteristics of mechanism-based inactivation, including irreversibility, saturation with increasing inhibitor concentrations, and protection by substrate, and was also documented with purified P-450 1 in a reconstituted system. 21,21-Dichloropregnenolone caused no time-dependent loss of 6 beta-hydroxylase activity in microsomes from the New Zealand White rabbits or from control or rifampicin-treated rabbits of the inbred B/J strain. In contrast, in the microsomes from the B/J rabbits, some inactivation of the 16 alpha-hydroxylase was observed (k = 0.04 min-1), regardless of the rifampicin treatment. The other two compounds tested, 21-chloropregnenolone and 21,21-dichloroprogesterone, were less effective than the dichloropregnenolone as inactivators of cytochrome P-450 1. On the other hand, 21,21-dichloroprogesterone, but not 21,21-dichloropregneolone, caused a rapid time-dependent loss of 21-hydroxylase activity in rabbit adrenal microsomes. The results indicate that the introduction of a dichloromethyl group into a substrate bearing a methyl group normally hydroxylated by only one or a few forms of cytochrome P-450 may be a rational means of designing selective inhibitors of the enzyme.

  3. Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect.

    PubMed

    Kim, Gyoung Min; Kim, Man Deuk; Kim, Do Young; Kim, Se Hoon; Won, Jong Yun; Park, Sung Il; Lee, Do Yun; Shin, Wonseon; Shin, Minwoo

    2016-07-01

    To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model. New Zealand White rabbits (n = 20) with a VX2 tumor were divided into two groups; one group was treated with hepatic arterial administration of 0.5 mL ethiodized oil alone (Lipiodol; Guerbet, Aulnay-sous-Bois, France) (transarterial embolization with Lipiodol [TAE-L] group), and one group was treated with 0.5 mL ethiodized oil plus 10 mg sorafenib (transarterial embolization with sorafenib [TAE-S] group). Liquid chromatography tandem mass spectrometry was used to measure sorafenib concentration in peripheral blood and tissue. Hepatic enzymes, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were measured at 0, 24, and 72 hours after treatment. Histopathologic examination was performed to evaluate extent of tumor necrosis and normal parenchymal damage. Serum sorafenib concentration peaked at 2 hours after treatment. The mean tissue concentration was 406.8 times greater than the serum concentration. Aspartate aminotransferase and alanine aminotransferase levels were significantly elevated in the TAE-S group at 24 hours after treatment. Serum VEGF and HIF-1α concentrations were not significantly different between the TAE-L and TAE-S groups. Hepatic parenchymal damage was more severe in the TAE-S group. Mean fraction of tumor necrosis after treatment was significantly greater in the TAE-S group. Transarterial chemoembolization using sorafenib resulted in a high intrahepatic concentration of sorafenib. The degree of tumor necrosis was significantly greater in the TAE-S group compared with the TAE-L group, but more severe toxicity of normal liver tissue also occurred. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  4. Increased blood-brain transfer in a rabbit model of acute liver failure

    SciTech Connect

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-05-01

    The blood-to-brain transfer of (/sup 14/C)alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of (/sup 14/C)alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of (/sup 14/C)galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

  5. Effect of vitamin C in reducing the toxicity of endosulfan in liver in rabbits.

    PubMed

    Mor, Firdevs; Ozmen, Ozlem

    2010-01-01

    In this study, the effect of endosulfan, an organochlorine pesticide, and the ameliorating effect of vitamin C on the livers of New Zealand white rabbits were studied. Livers of the rabbits were examined grossly and histopathologically, and caspase-3 activity was detected by immunohistochemical methods. A total of twenty-four rabbits were divided into four groups (n=6). Rabbits in Group I (END) were daily given a sublethal dose of endosulfan (1mg/kgbw) in corn oil by oral gavage for 6 weeks. Group II (END+C) received the same dose of endosulfan and additionally Vit C (20mg/kgbw) every other day during this period. Group III (OIL+C) received corn oil daily by oral gavage and vitamin C every other day for 6 weeks. Group IV (OIL), the control group, received only corn oil daily, by oral gavage throughout the experiment. The concentration of alpha-endosulfan in the END group was higher in livers (0.102+/-0.012ppb) than the beta-endosulfan (0.072+/-0.001ppb). Decreased accumulation of alpha and beta endosulfan was observed in the END+C group (0.025+/-0.003 and 0.016+/-0.002ppb, respectively) (p<0.0001). The most prominent gross findings at the necropsy were seen in the END group, in which swollen and pale livers were commonly observed. Hemorrhages, degenerations, necrosis, and in some rabbits bile duct hyperplasia were the marked histopathological findings of the END group. Caspase-3 positive reaction was more severe in this group than in the others. An ameliorating effect of Vit C on gross, histopathological and immunohistochemical findings was observed in the END+C group. The results revealed that endosulfan is highly toxic for rabbit livers. However, toxicity was decreased by Vit C treatment, which reduced the accumulation of endosulfan in livers four-fold. Copyright 2009 Elsevier GmbH. All rights reserved.

  6. Liver and kidney lesions and associated enzyme changes induced in rabbits by chronic cyanide exposure.

    PubMed

    Okolie, N P; Osagie, A U

    1999-07-01

    The effect of prolonged chronic cyanide exposure on liver and kidney integrity, as well as some associated enzyme and metabolite changes, were investigated in New Zealand white rabbits (initial mean weight 1.52 kg) using a combination of colorimetric, spectrophotometric, enzymatic, gravimetric and histological procedures. Two groups of rabbits were fed for 40 weeks on either pure growers' mash or growers' mash containing 702 ppm inorganic cyanide. Results obtained indicate that the cyanide-fed rabbits had significantly decreased liver activities of alkaline phosphatase, glutamate pyruvate transaminase and sorbitol dehydrogenase relative to controls (P<0.05). On the other hand, there were significant increases (P<0.05) in the serum activities of these enzymes in the cyanide-treated group. Kidney alkaline phosphatase activity was significantly decreased (P<0.05), while serum urea and creatinine were significantly higher (P<0.05) in the cyanide group relative to controls. The cyanide treatment led to significant increases in both tissue and serum activities of lactate dehydrogenase. In addition, liver and kidney rhodanese activities were significantly raised in the cyanide-fed group. There were marked degenerative changes in the liver and kidney sections from the cyanide-treated rabbits. These results suggest that chronic cyanide exposure may be deleterious to liver and kidney functions.

  7. Focused liver ablation by cavitation in the rabbit: a potential new method of extracorporeal treatment.

    PubMed Central

    Prat, F; Chapelon, J Y; Abou el Fadil, F; Sibille, A; Theillière, Y; Ponchon, T; Cathignol, D

    1994-01-01

    A new device was used to achieve focused tissue ablation by shockwave induced cavitation. The device produced a half cycle of negative pressure followed by a shock wave, thus enhancing cavitation. Twenty eight New Zealand rabbits were treated. Therapeutic ultrasound was targeted at the centre of the liver under ultrasound guidance. The focal volume was scanned with a computer operated x-y-z micropositioner. The number and frequency of bursts as well as the distance between two x-y-z displacements were preselected. The relation of tissue ablation seen to preselected parameters, effects on surrounding tissues, biological side effects, and mode of healing were studied. Macroscopy, planimetry, and quantitative microscopy were used. Focused and homogeneous tissue ablation was achieved within well defined limits. Maximal tissue ablation was seen in the centre of the target. Liver surrounding the target remained unaffected. Lesions were made of a-cellular spots surrounded by disorganised rims of necrotic hepatocytes; 24 hours after treatment, the changes (mean (SEM)) in alanine transaminase and haemoglobin were +225 (36)% and -2.4 (2)% respectively. Serum transaminases, haemoglobinaemia, and packed cell volume were normal 21 days after treatment and the target area was replaced by a fibrous scar. It is concluded that ultrasound cavitation may achieve extracorporeal intrahepatic tissue ablation inside a predetermined target. This technique should now be tested in an animal hepatic tumour model. Images Figure 2 Figure 3 PMID:8150355

  8. Anaerobic coryneform bacteria as normal flora of rabbit skin and regression of Shope papillomas.

    PubMed

    Seto, A; Salehi, S A; Miyanomae, K; Ushijima, T; Ito, Y

    1980-01-01

    Adult domestic rabbits were found to harbor anaerobic coryneform bacteria and possess serum agglutinins against these bacteria. The isolates from rabbit skin were characterized by morphology, anaerobiosis, catalase test, and gas chromatographic analysis of volatile acid products. Preliminary findings on the effect of anaerobic coryneforms on the regression of Shope papillomas have suggested that the life of such bacteria as normal flora enhances the regression.

  9. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    PubMed Central

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  10. Collagen polymorphism in normal and cirrhotic human liver.

    PubMed Central

    Seyer, J M; Hutcheson, E T; Kang, A H

    1977-01-01

    Collagens in normal human liver and in alcoholic cirrhotic liver were investigated. Collagens were solubilized by limited proteolysis with pepsin under nondenaturing conditions, and after purification, were fractionated into types I and III by selective precipitation with NaCl. After carboxymethyl cellulose and agarose chromatography, the resulting alpha-chains from each of the collagen types were analyzed with respect to their amino acid and carbohydrate compositions. A comparison of the results obtained from normal liver with those from the diseases organ revealed no significant differences. The isolated human liver alpha1(I) and alpha1(III) chains were digested with CNBr and the generated peptides were separated and purified by a combination of ion-exchange and molecular sieve chromatography. The molecular weight and the amino acid and the carbohydrate compositions of each of the peptides were identical to those of the corresponding human skin peptides except for the slightly higher content of hydroxylysine in some of the peptides. The relative content of type III in relation to type I collagen in both normal anc cirrhotic liver was determined by digesting washed liver homogenates directly with CNBr and quantitating the resultant alpha1(I) and alpha 1(III) peptides after chromatographic separation. The relative quantities of these peptides indicated that normal human liver contained an average of 47% type III, with the remainder being type I. Cirrhotic liver, on the other hand, contained a significantly smaller proportion of type III, ranging from 18 to 34% in different samples, with a corresponding increase in type I. These findings indicate that although the amino acid and carbohydrate compositions of collagens deposited in cirrhotic liver are normal, the fibrotic process of alcoholic liver disease in humans is accompanied by an alteration in tissue collagen polymorphism, and suggest that the observed alterations may have pathogenetic implications. PMID:833273

  11. Initial plasma disappearance and tissue uptake of 131I-albumin in normal rabbits

    SciTech Connect

    Bent-Hansen, L. )

    1991-05-01

    The simultaneous plasma disappearance curves of 131I-albumin and 125I-fibrinogen were recorded in normal rabbits for 1 hr. Using fibrinogen as a plasma reference, the disappearance curves of albumin were shown to contain two separate phases of efflux: one fast from zero to 10 min. comprising 8% of the total tracer; and one slow appearing in the interval of 10 to 60 min. containing another 9% of the tracer. Total albumin escape was analyzed to yield an initial slope of 0.024 {plus minus} 0.004 min-1, corresponding to a wholebody unidirectional albumin clearance (Cl(0)) of 0.090 {plus minus} 0.009 ml(min{asterisk}100 g)-1. The distribution of efflux was assessed by biopsy uptakes using the same tracers in spleen, kidney, heart, lung, liver, intestine, skin, muscle, and brain. The disappearance curve generally reflects a biphasic pattern of uptake in peripheral tissue, predominantly by muscle and lung. The rapid phase has contributions from the fast near equilibration of liver, and intestine and skin are significant codeterminants of the slow phase. Due to their low body masses highly perfused organs such as kidney, spleen, and heart have little influence on the plasma disappearance. In accordance, the Cl(0) determined for the wholebody was higher than initial clearances found in skin (0.053 ml(min{asterisk}100 g)-1) and muscle (0.054 ml(min{asterisk}100 g)-1), but much lower than those found in the highly perfused organs. The initial (unidirectional) rates of peripheral albumin transfer demonstrated, ranged from 10 to 30 times higher than estimates of lymphatic return, suggesting that transcapillary albumin exchange is mediated by high-rate bidirectional diffusion. The rapid decrease of net albumin exchange rates suggests a second, highly significant barrier located within the interstitial matrix, which restricts plasma escape and reduces plasma to lymph albumin transport.

  12. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Rao, Pramod P.; Pascale, Florentina; Seck, Atman; Auperin, Anne; Drouard-Troalen, Laurence; Deschamps, Frederic; Teriitheau, Christophe; Paci, Angelo; Denys, Alban; Bize, Pierre; Baere, Thierry de

    2012-12-15

    Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

  13. LIPH Expression in Skin and Hair Follicles of Normal Coat and Rex Rabbits

    PubMed Central

    Diribarne, Mathieu; Mata, Xavier; Rivière, Julie; Bouet, Stéphan; Vaiman, Anne; Chapuis, Jérôme; Reine, Fabienne; Fleurot, Renaud; Auvinet, Gérard; Deretz, Séverine; Allain, Daniel; Schibler, Laurent; Cribiu, Edmond-Paul; Guérin, Gérard

    2012-01-01

    Natural mutations in the LIPH gene were shown to be responsible for hair growth defects in humans and for the rex short hair phenotype in rabbits. In this species, we identified a single nucleotide deletion in LIPH (1362delA) introducing a stop codon in the C-terminal region of the protein. We investigated the expression of LIPH between normal coat and rex rabbits during critical fetal stages of hair follicle genesis, in adults and during hair follicle cycles. Transcripts were three times less expressed in both fetal and adult stages of the rex rabbits than in normal rabbits. In addition, the hair growth cycle phases affected the regulation of the transcription level in the normal and mutant phenotypes differently. LIPH mRNA and protein levels were higher in the outer root sheath (ORS) than in the inner root sheath (IRS), with a very weak signal in the IRS of rex rabbits. In vitro transfection shows that the mutant protein has a reduced lipase activity compared to the wild type form. Our results contribute to the characterization of the LIPH mode of action and confirm the crucial role of LIPH in hair production. PMID:22272275

  14. LIPH expression in skin and hair follicles of normal coat and Rex rabbits.

    PubMed

    Diribarne, Mathieu; Mata, Xavier; Rivière, Julie; Bouet, Stéphan; Vaiman, Anne; Chapuis, Jérôme; Reine, Fabienne; Fleurot, Renaud; Auvinet, Gérard; Deretz, Séverine; Allain, Daniel; Schibler, Laurent; Cribiu, Edmond-Paul; Guérin, Gérard

    2012-01-01

    Natural mutations in the LIPH gene were shown to be responsible for hair growth defects in humans and for the rex short hair phenotype in rabbits. In this species, we identified a single nucleotide deletion in LIPH (1362delA) introducing a stop codon in the C-terminal region of the protein. We investigated the expression of LIPH between normal coat and rex rabbits during critical fetal stages of hair follicle genesis, in adults and during hair follicle cycles. Transcripts were three times less expressed in both fetal and adult stages of the rex rabbits than in normal rabbits. In addition, the hair growth cycle phases affected the regulation of the transcription level in the normal and mutant phenotypes differently. LIPH mRNA and protein levels were higher in the outer root sheath (ORS) than in the inner root sheath (IRS), with a very weak signal in the IRS of rex rabbits. In vitro transfection shows that the mutant protein has a reduced lipase activity compared to the wild type form. Our results contribute to the characterization of the LIPH mode of action and confirm the crucial role of LIPH in hair production.

  15. STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : IV. CONSECUTIVE NEUTROPHILE, BASOPHILE, AND EOSINOPHILE OBSERVATIONS ON GROUPS OF NORMAL RABBITS.

    PubMed

    Pearce, L; Casey, A E

    1930-07-31

    Consecutive weekly observations on the neutrophile, the basophile, and the eosinophile counts of the peripheral blood were made on 5 groups of normal rabbits, a total of 45 animals, during a period of 20 months from October, 1927 to July, 1929. Individual groups were examined 8 to 35 weeks. In the case of the 4 groups followed 13 to 35 weeks, the general trend of the neutrophile cells was towards increased mean values; with the group followed 8 weeks, decreasing values were found. An increase in the mean values of the basophile cells was observed in the two groups of rabbits followed in 1927-28; in the groups of 1928-29, the mean values decreased. The mean values of the eosinophile cells showed no definite trends but the findings were characterized by abrupt and marked fluctuations. The periods of greatest irregularity in mean neutrophile and eosinophile values occurred in the fall and the late winter and spring months of both years, but in the case of the basophiles, the irregularities were distributed throughout the first year and occurred chiefly in the winter months of the second year. The major trends and many of the minor fluctuations as well which were observed in the mean cell values of one group of rabbits were also generally seen in another group examined during the same months. The general levels of the neutrophile, the basophile, and the eosinophile mean values in the groups examined during 1927-28 were higher than in the groups of 1928-29.

  16. Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.

    PubMed

    Quinet, E M; Agellon, L B; Kroon, P A; Marcel, Y L; Lee, Y C; Whitlock, M E; Tall, A R

    1990-02-01

    Cholesteryl ester transfer activity is increased in plasma of cholesterol-fed rabbits. To investigate the mechanisms leading to changes in activity, we measured cholesteryl ester transfer protein (CETP) mass by RIA and CETP mRNA abundance by Northern and slot blot analysis using a human CETP cDNA probe in control (n = 8) and cholesterol-fed rabbits (n = 10). Cholesterol feeding (chow plus 0.5% cholesterol, 10% corn oil) for 30 d increased CETP mass in plasma 3.2-fold in the cholesterol-fed rabbits (12.45 +/- 0.82 micrograms/ml) compared with controls (3.86 +/- 0.38 micrograms/ml). In the hypercholesterolemic rabbit, liver CETP mRNA levels were increased 2.8 times control mRNA levels. Actin, apo E, lecithin-cholesterol acyltransferase, and albumin mRNA abundances were unchanged. In contrast to the widespread tissue distribution in humans, CETP mRNA was not detected in extrahepatic tissues of either control or cholesterol-fed animals. Using a sensitive RNase protection assay, the increase in liver CETP mRNA was detectable within 3 d of beginning the high cholesterol diet. Thus, in response to the atherogenic diet there is an early increase in liver CETP mRNA, probably causing increased CETP synthesis and secretion, and increased plasma CETP. The results indicate that the CETP gene may be regulated by diet-induced changes in lipid metabolism.

  17. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints.

    PubMed

    Lindenhayn, K; Heilmann, H H; Niederhausen, T; Walther, H U; Pohlenz, K

    1997-05-01

    The half-life of [3H]hyaluronic acid in rabbit knee joints was estimated using two methods: (i) by following the [3H]hyaluronan content of the synovial fluid after intra-articular injection and (ii) by following the 3H2O radioactivity of plasma after intra-articular injection of [3H]hyaluronan. For normal rabbits we obtained a half-life of 15.8 hours (method I) and 17.5 +/- 1.0 hours (mean +/- SEM, method II), respectively. The second method was used to estimate the kinetics of the hyaluronan elimination from normal, sham-operated, as well as from osteoarthritic rabbit knee joints (Colombo model of osteoarthritis). Four weeks after injury, during the developing phase of osteoarthritis, the half-life of hyaluronan rose significantly to 23.5 +/- 2.1 hours and returned to normal levels (17.4 +/- 2.7 hours) 12 weeks after the operation (osteoarthritis developed). At the stage of developed osteoarthritis, the clearance rates were considerably higher than in normal rabbits.

  18. Heme synthesis in normal mouse liver and mouse liver tumors

    SciTech Connect

    Stout, D.L.; Becker, F.F. )

    1990-04-15

    Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors {sup 55}FeCl3 and (2-{sup 14}C)glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated (2-14C)glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool.

  19. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    PubMed

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  20. Comparison between cryoablation and irreversible electroporation of rabbit livers at a location close to the gallbladder

    PubMed Central

    Qin, Zilin; Zhou, Liang; Fang, Gang; Chen, Jibing; Li, Jialiang; Niu, Lizhi; Liang, Bing; Xu, Kecheng

    2017-01-01

    Abstract Background The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder. Materials and methods We performed cryoablation (n = 12) and IRE (n = 12) of the area of the liver close to the gallbladder in 24 New Zealand white rabbits in order to ensure gallbladder damage. Serum aminotransferase and serum bilirubin levels were measured before and after the ablation. Histopathological examination of the ablation zones in the liver and gallbladder was performed on the 7th day after the ablation. Result Seven days after the ablation, all 24 animals were alive. Gallbladder perforation did not occur in the IRE group; only mucosal epithelial necrosis and serous layer edema were found in this group. Gallbladder perforation occurred in four rabbits in the cryoablation group. Serum aminotransferase and serum bilirubin levels obviously increased in both groups by Day 3 and decreased gradually thereafter. The elevation in aminotransferase and bilirubin levels was greater in the cryoablation group than the IRE group. Pathological examination revealed complete necrosis of the liver parenchyma from the ablation center to the gallbladder in both groups, but bile duct and granulation tissue hyperplasia were observed in only the IRE group. Full-thickness gallbladder-wall necrosis was seen in the cryoablation group. Conclusions For ablation of the liver area near the gallbladder, IRE is superior to cryoablation, both in terms of safety (no gallbladder perforation in the IRE group) and efficacy (complete necrosis and rapid recovery in the IRE group). PMID:28265231

  1. [Effects of needle heating: studies in normal canine liver].

    PubMed

    Harihara, Y

    1988-03-01

    Hyperthermia has great potential as an anti-hepatic tumor agent because it has not only direct anti-tumor effect by itself but also synergistic effect in combination with radiotherapy or chemotherapy. Focal hyperthermia can be produced by needle-type heater implanted directly into the tumor. Hyperthermic effect of this needle heating and the influence of tissue blood flow on it were studied in normal canine liver. Fifty V heating for 10 minutes (5208 joule) by needle-type heater produced the effective thermal field, 27mm in diameter, above 42 degrees C. Tissue temperature dropped rapidly with the increase of distance from the heater, which reveals that hepatic tumor can be heated selectively by this method. The relation between the tissue blood flow and hyperthermic effect was investigated in the conditions that hepatic perfusion was controlled by clamping either hepatic artery or portal vein, or both of them. The effective thermal volume, 24.4cc, in normal liver tissue with no perfusion was compared with 10.3cc in normal liver tissue with normal perfusion (88.1ml/min/100g), which means that heat delivered in tissue by needle heater is rapidly dissipated by the flowing blood. The microscopical findings one week after heating revealed that normal liver tissue was irreversibly damaged by heating above 46 degrees C for more than 5 minutes.

  2. Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits.

    PubMed

    Gong, Yuping; Wang, Zhigang; Dong, Guifang; Sun, Yang; Wang, Xi; Rong, Yue; Li, Maoping; Wang, Dong; Ran, Haitao

    2016-09-01

    To explore the antitumor effects of low-intensity focused ultrasound (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA nanoparticle complexes on rabbits VX2 liver tumor. ADM-NMCs were prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of the microbubbles. A fixed water bag filled with microbubbles was subjected to LIFU and non-focused ultrasound respectively, and the ultrasound images of which were recorded before and after ultrasonication. A total of 54 VX2 liver tumor-burdened rabbits were divided into six groups randomly, including control, ADM-NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non-FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine nick end. Proliferating cell nuclear antigen was detected by immunohistochemistry. The median survival time of the animals were recorded and compared. ADM-NMCs were successfully prepared with an average diameter of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was simultaneously observed in this group. The median survival time of the rabbits in the ADM-NMCs combined with LIFU group was the longest (71days) among all groups. ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver tumor progress by delaying the tumor proliferation and accelerating apoptosis, which presents a novel process for liver tumor targeting chemotherapy.

  3. Effect of hydrocortisone on the metabolism of phosphatidylcholine in maternal and fetal rabbit lungs and livers.

    PubMed

    Tsao, F H; Gutcher, G R; Zachman, R D

    1979-09-01

    Administration of hydrocortisone to pregnant rabbits caused a decrease in weights of fetal body and lung and an increase in the incorporation of choline into fetal lung PC. The authors found no induction of the enzymes related to the incorporation of choline into PC in fetal lung. Also, there was no stimulation of any enzymatic activity of CDP-choline pathway or PC-lysoPC cycle pathway in maternal lung and liver or fetal liver. In addition to the acceleration of choline incorporation into fetal lung PC by the cortisol, hydrocortisone also significantly stimulated the secretion of lung PC affected by glucocorticoids may also be related to apparent fetal lung maturation.

  4. Functions of autophagy in normal and diseased liver

    PubMed Central

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  5. Magnetic resonance elastography in a rabbit model of liver fibrosis: a 3-T longitudinal validation for clinical translation.

    PubMed

    Zou, Liqiu; Jiang, Jinzhao; Zhong, Wenxin; Wang, Chunrong; Xing, Wei; Zhang, Zhuoli

    2016-01-01

    This study aimed to determine the relationships between magnetic resonance elastography (MRE) imaging biomarkers and the stages of liver fibrosis in a rabbit model of liver fibrosis, a longitudinal validation for clinical translation. Liver fibrosis was induced in 38 male New Zealand rabbits by weekly subcutaneous injections of 0.1 ml 50% carbon tetrachloride oily solution per kilogram of body weight for 4 to 10 weeks to produced varying degrees of liver fibrosis. The values for the liver stiffness (LS) MRE imaging biomarkers were measured at different stages of liver fibrosis. Masson trichrome staining of liver tissue was used to identify collagen tissue. Among the 38 rabbits, the histological studies showed liver fibrosis stage 1 (F1, n = 11), liver fibrosis stage 2 (F2, n = 8), liver fibrosis stage 3 (F3, n = 7), and liver fibrosis stage 4 (F4, liver cirrhosis, n = 12). Additional healthy rabbits served as controls (F0, n = 15). During liver fibrosis progression, the mean LS values increased during liver fibrosis progression. There were significant differences in LS values between (F0 and F1) and (F2 and F3), (F2 and F3) and (F4), and (F0 and F1) and (F4), which are three clinically relevant fibrosis groups. There was a high correlation between the LS values measured by MRE and the stages of liver fibrosis determined by histology (R(2) = 0.67, P < 0.001). MRE imaging has the potential to serve as a noninvasive, unenhanced imaging technique for liver fibrosis diagnosis and staging.

  6. Magnetic resonance elastography in a rabbit model of liver fibrosis: a 3-T longitudinal validation for clinical translation

    PubMed Central

    Zou, Liqiu; Jiang, Jinzhao; Zhong, Wenxin; Wang, Chunrong; Xing, Wei; Zhang, Zhuoli

    2016-01-01

    This study aimed to determine the relationships between magnetic resonance elastography (MRE) imaging biomarkers and the stages of liver fibrosis in a rabbit model of liver fibrosis, a longitudinal validation for clinical translation. Liver fibrosis was induced in 38 male New Zealand rabbits by weekly subcutaneous injections of 0.1 ml 50% carbon tetrachloride oily solution per kilogram of body weight for 4 to 10 weeks to produced varying degrees of liver fibrosis. The values for the liver stiffness (LS) MRE imaging biomarkers were measured at different stages of liver fibrosis. Masson trichrome staining of liver tissue was used to identify collagen tissue. Among the 38 rabbits, the histological studies showed liver fibrosis stage 1 (F1, n = 11), liver fibrosis stage 2 (F2, n = 8), liver fibrosis stage 3 (F3, n = 7), and liver fibrosis stage 4 (F4, liver cirrhosis, n = 12). Additional healthy rabbits served as controls (F0, n = 15). During liver fibrosis progression, the mean LS values increased during liver fibrosis progression. There were significant differences in LS values between (F0 and F1) and (F2 and F3), (F2 and F3) and (F4), and (F0 and F1) and (F4), which are three clinically relevant fibrosis groups. There was a high correlation between the LS values measured by MRE and the stages of liver fibrosis determined by histology (R2 = 0.67, P < 0.001). MRE imaging has the potential to serve as a noninvasive, unenhanced imaging technique for liver fibrosis diagnosis and staging. PMID:27904692

  7. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique

    PubMed Central

    Sun, Di; Wei, Cong; Shen, E.; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

  8. Effects of synthetic androgens on liver function using the rabbit as a model.

    PubMed

    Hild, Sheri Ann; Attardi, Barbara J; Koduri, Sailaja; Till, Bruce A; Reel, Jerry R

    2010-01-01

    The objective of this study was to determine whether the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0-13 with 17α-methyltestosterone (MT) as a positive control and testosterone (T) as a negative control to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7, and 14, were determined. As expected, T (10 mg/kg/d) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/d) increased BSP retention, and AST, ALT, GGT, and SDH levels, indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/d) increased BSP retention and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/d did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/d. For the androgens that exhibited liver toxicity at 10 mg/kg/d (MT, DMAU, and MENT), a no-observed-effect level of 1 mg/kg/d was established. Overall ranking of the synthetic androgens from most to least hepatotoxic on the basis of percent BSP retention was: MT & DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury.

  9. Effects of Synthetic Androgens on Liver Function Using the Rabbit as a Model*†

    PubMed Central

    Hild, Sheri Ann; Attardi, Barbara J.; Koduri, Sailaja; Till, Bruce A.; Reel, Jerry R.

    2010-01-01

    The objective of this study was to determine if the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0–13 with 17α-methyltestosterone (MT), as a positive control, and testosterone (T), as a negative control, to validate this model. Synthetic androgens tested were: 7α-methyl-19-nortestosterone (MENT), dimethandrolone-undecanoate (DMAU), and 11β-methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7 and 14, were determined. As expected, T (10 mg/kg/day) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/day) increased BSP retention, and AST, ALT, GGT, and SDH levels indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/day), increased BSP retention, and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11β-MNTDC at 10 mg/kg/day did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/day. For the androgens that exhibited liver toxicity at 10 mg/kg/day (MT, DMAU, and MENT), a no observed effect level (NOEL) of 1 mg/kg/day was established. Overall ranking of the synthetic androgens from most to least hepatotoxic based on %BSP retention was: MT ≫ DMAU > MENT > 11β-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury. PMID:20378929

  10. Normal temperature variation in New Zealand white rabbits during restraint for preliminary pyrogen test.

    PubMed

    Caldeira, C; Freitas, J C B R; Gimenes, I; Silva, S A; Cabello, P; Presgrave, O A F

    2014-01-01

    The in vivo pyrogen test is the main toxicological assay used in the quality control of injectable products, especially immunobiologicals. Pharmacopoeias state that, before the main test, a preliminary test must be conducted on all animals, and must follow the same conditions as the main test. The aim of this study was to determine the normal temperature variation in New Zealand white rabbits during restraint and propose a limit value for considering an animal as suitable for testing. Results of the temperature variation in 4,689 rabbits during preliminary tests were obtained from the routine database of the Pharmacology and Toxicology Department of the National Institute of Quality Control in Health (INCQS/FIOCRUZ), Brazil. From these preliminary tests, 3,364 rabbits were considered suitable for testing according to the Brazilian Pharmacopoeia criteria (temperature variation < 0.5 °C). Results showed that about 92 per cent of the rabbits presented a normal individual temperature variation equal to or below 0.30 °C. Animals presenting a temperature variation close to the fever temperature must not be included in the main test, since they can be stressed or sick. Consequently, the temperature variation of 0.30 °C could be adopted by pharmacopoeias as a limit temperature to be considered in the preliminary test to determine which animals can be used in the main rabbit pyrogen test. Animals can be pre-tested until presenting this safe variation, in order to ensure they are healthy and minimise interference in the result.

  11. [Action of DDPH in the interventional treatment of portal hypertension induced by liver cirrhosis in rabbits].

    PubMed

    Qian, J; Feng, G; Liang, H

    1998-01-01

    To explore a new way of utilizing intervential treatment to effectively decrease the portal hypertension, the animal models of liver cirrhosis accompanying portal hypertension were set up by intraportal vein injection of suspensions of Bletilla striata to 10 rabbits by means of prospective investigational method. The catheter filled with heparin solution was remained in theportal vein for infusion of drugs. Three weeks later, DDPH solution was injected into the portal vein via the catheter to determine its effect of decreasing portal vein pressure and its influence of peripheral blood pressure and heart rate. At the same time, other 10 rabbits with liver cirrhosis associated with portal hypertension were subjected to the injection of DDPH solution via the ear vein served as control group. The results showed that administration of DDPH by portal vein could rapidly, safely and effectively decrease the portal hypertenive pressure without side effects and partially reverse liver cirrhosis, as compared with injection of DDPH via peripheral veins. It was concluded that DDPH exerted its alpha 1-adrenoceptor blocking and calcium antagonistic effects, thereby significantly reduce the portal hypertension. Injection of DDPH via portal vein is a completely new and relaible method for the treatment of liver cirrhosis with portal hypertension.

  12. Hepatic Overexpression of GRP94 in a Rabbit Model of Parenteral Nutrition-Associated Liver Disease

    PubMed Central

    Zhu, Xueping; Zhang, Xiaomin; Yu, Lingling; Xu, Yumin; Feng, Xing; Wang, Jian

    2015-01-01

    Objective. To use a rabbit model of parenteral nutrition-associated liver disease (PNALD) to study changes of the endoplasmic reticulum stress (ERS) marker glucose regulatory protein 94 (GRP94) and determine its role in the pathogenesis of PNALD. Methods. A rabbit PNALD model total parenteral nutrition (TPN) group was established. A corresponding control group received breast-feeding for one week. Serum biochemical parameters were measured and liver histological examinations were performed. The level of GRP94 mRNA and protein were measured. Results. The results showed that the serum TBIL, DBIL, and γ-GT levels in the TPN group were significantly higher than those in the control group, while levels of serum ALB in TPN group were significantly lower than those in the control group. The immunohistochemistry results showed that the protein expression level of GRP94 in the liver of TPN group was significantly increased compared with the control group. The RT-PCR results showed that the level of GRP94 mRNA in the liver of the TPN group was significantly higher compared with the control group. Conclusions. The mRNA and protein levels of GRP94 in the TPN group were both significantly increased, indicating that ERS may be directly related to the occurrence and development of PNALD. PMID:25918521

  13. Choledocholithiasis in patients with normal serum liver enzymes.

    PubMed

    Goldman, D E; Gholson, C F

    1995-05-01

    Retrospective chart review of 330 patients undergoing ERCP over a two-year period yielded five patients with choledocholithiasis whose serum liver enzyme and total bilirubin levels were repeatedly normal. All were female, three were elderly, and the gallbladder was in situ in three of the five, one of whom had a large gallbladder remnant. In four patients, the common bile duct was dilated (> 10 mm), whereas none had intrahepatic duct dilatation. Four patients had a prominent ampulla, and stone size varied widely. Each patient was managed with endoscopic sphincterotomy and stone extraction followed by cholecystectomy for the four patients with the gallbladder or its remnant in situ. This small series proves that common duct stones may exist in patients with repeatedly normal serum liver enzyme and total bilirubin levels. We hypothesize that marked dilatation of the common bile duct or gallbladder may serve as a pressure sump and blunt liver enzyme elevation. Normal liver enzymes should not dissuade one from performing cholangiography in patients with suspected choledocholithiasis.

  14. The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits.

    PubMed

    Jahan, Sarwat; Khan, Moosa; Imran, Sana; Sair, Mohammad

    2015-06-01

    To evaluate the hepatoprotective role of Silymarin against isonicotinylhydrazine-induced hepatotoxicity in rabbit model. The experimental animal study was held at Jinnah Postgraduate Medical Centre, Karachi, from April to September 2013 and comprised rabbits weighing 1-1.5kgof either gender. The animals were divided randomly into equal groups: group I underwent liver function test without any drug; in group II effects of Silymarin (50mg/kg/day orally) was observed; in group III isoniazid (50mg/kg/dayorally) was administered; and in group IV combined effects of isoniazid and silymarin were observed. Liver function tests were performed at day0 and after the treatment at day19. SPSS 16 was used for statistical analysis. The 28 rabbits in the study were divided in four groups of 7(25%) each. No mortality was recorded in any group. In group III, bilirubin level was increased and alanine transaminase was decreased significantly (p<0.05 each). In group IV, there was significant improvement in serum billirubin and serum alanine transaminase (p<0.05 each). Isonicotinylhydrazine-induced hepatotoxicity was well treated by concurrent administration of Silymarin.

  15. Experimental chronic active hepatits in rabbits following immunization with human liver proteins

    PubMed Central

    Büschenfelde, K. H. Meyer Zum; Kössling, F. K.; Miescher, P. A.

    1972-01-01

    Two liver-specific antigens are known: a water soluble protein (LP-2) and a water insoluble macromolecular low density lipoprotein (LP-1). In this paper the relative role of the two antigens in the development of experimental immune hepatitis has been investigated. Immunization of rabbits with a human preparation containing both antigens, led in all animals to lesions characteristic of an immune hepatitis. Immunization of the animals with a purified water soluble liver protein proved less efficient: only two out of six animals developed characteristic lesions which were less severe than those in the first group. It was deduced that although not a prerequisite, the liver-specific lipoprotein plays an important supportive role in the development of immune hepatitis. ImagesFig. 2Fig. 1Fig. 3 PMID:4338952

  16. Combined Therapy of Radiofrequency Ablation and Ethanol Injection of Rabbit Liver: An In Vivo Feasibility Study

    SciTech Connect

    Lee, Jeong Min; Lee, Young Hwan; Kim, Young Kon; Kim, Sang Won; Kim, Chong Soo

    2004-03-15

    Our purpose was to compare the effects of percutaneous radiofrequency ablation (RFA) combined with percutaneous ethanol injection (PEI) on the extent of ablation in in vivo rabbit liver tissue as compared with either therapy alone. Twenty-two New Zealand white rabbits were included in this study and allocated into three groups: group A: conventional RFA (n = 6); group B: PEI (n = 6); group C: combined RFA and PEI (n = 10). For combined RFA and PEI, under ultrasound guidance, 1 mL of absolute ethanol was injected into the target area of the liver parenchyma through a 21-gauge Chiba needle before performing RFA. RFA was performed using a 17- gauge internally cooled electrode with 1-cm active tip, and RF energy (30 W) was applied for 3 minutes, with or without ethanol injection. After RFA or PEI, contrast-enhanced computed tomography and CT-pathologic correlation were performed. The short- axis and long-axis diameters of thermal lesions of each group were compared. All procedures were technically successful and a total of 38 lesions were produced. The mean short-axis and long-axis diameter of the coagulation necrosis in rabbits of group C (combination of RFA and PEI), were significantly larger than those of other groups: group A: 10.3 {+-} 2 mm and 11.4 {+-} 2 mm; group B: 3.1 {+-} 1 mm and 4.3 {+-} 2 mm; group C: 12.8 {+-} 3 mm and 17.8 {+-} 6 mm (p < 0.05). On contrast-enhanced CT scan, the lesions of rabbits of the group C appeared to be more frequently irregular compared to those of group A (20% in group A vs. 67% in group C). There were three complications including two localized hematomas and one cardiopulmonary failure. Combined RFA and PEI could increase the dimension of coagulation necrosis without increasing complications and therefore, may be successfully used for treating larger lesions.

  17. Fetal Liver-Derived Mesenchymal Stem Cell Engraftment After Allogeneic In Utero Transplantation into Rabbits

    PubMed Central

    Moreno, Rafael; Martínez-González, Itziar; Rosal, Marta; Nadal, Marga; Petriz, Jordi; Gratacós, Eduard

    2012-01-01

    Prenatal transplantation of genetically engineered mesenchymal stem cells (MSCs) might benefit prevention or treatment of early-onset genetic disorders due to the cells' intrinsic regenerative potential plus the acquired advantage from therapeutic transgene expression. However, a thorough assessment of the safety, accessibility, and behavior of these MSCs in the fetal environment using appropriate animal models is required before we can advance toward a clinical application. We have recently shown that fetal rabbit liver MSCs (fl-MSCs) have superior growth rate, clonogenic capability, and in vitro adherence and differentiation abilities compared with adult rabbit bone marrow MSCs. In this follow-up study, we report safe and widespread distribution of recombinant pSF-EGFP retrovirus-transduced fl-MSCs (EGFP+-fl-MSCs) in neonatal rabbit tissues at 10 days after fetal allogeneic transplantation through both intrahepatic and intra-amniotic administration. Conversely, a more restricted biodistribution pattern according to the route of administration was apparent in the young rabbits intervened at 16 weeks after fetal EGFP+-fl-MSC transplantation. Furthermore, the presence of these cells in the recipients' tissues, tracked with the reporter provirus, was inversely related to the developmental stage of the fetuses at the time of intervention. Long-term engraftment was confirmed both by fluorescence in situ hybridization analysis on touch tissue imprints using a chromosome Y-specific BAC probe, and by immunohistochemical localization of EGFP expression. Finally, there was no evidence of immune responses against the transplanted EGFP+-fl-MSCs or the EGFP transgenic product in the treated young rabbits. Thus, cell transplantation approaches using genetically engineered fetal MSCs may prove particularly valuable to frontier medical treatments for congenital birth defects in perinatology. PMID:21495909

  18. Comparison of the effects of surgical dissection devices on the rabbit liver.

    PubMed

    MacDonald, Joel D; Bowers, Christian A; Chin, Steven S; Burns, Greg

    2014-06-01

    Multiple energy-based surgical dissection and coagulation modalities are available to facilitate surgical dissection and hemostasis, but there is limited information regarding the acute tissue effects of these devices. Our objective was to compare the functional characteristics and tissue effects of four energy-based surgical dissection and coagulation modalities on the rabbit liver. Linear incisions were created in the rabbit liver using monopolar electrocautery, a harmonic scalpel, a PlasmaBlade and a new ferromagnetic induction loop device. Subjective cutting and coagulation characteristics for each device were recorded, and the histological tissue effects were evaluated. Each of the modalities successfully incised the liver tissue. The PlasmaBlade and the ferromagnetic induction loop exhibited significantly less perceived tissue drag during the incision, significantly less collateral tissue damage and significantly better margin uniformity than the monopolar electrocautery device. Each device showed comparable subjective hemostasis. The harmonic scalpel did not demonstrate a significant difference compared with any of the other devices in any of the parameters examined. The histological analysis revealed that the least lateral thermal damage resulted when the PlasmaBlade, harmonic scalpel and ferromagnetic induction loop were used, and the most damage occurred with the use of monopolar electrocautery. Each of the newer energy-based surgical tools showed improvement over monopolar electrocautery with regard to lateral thermal injury, and the ferromagnetic induction device and the PlasmaBlade demonstrated superior surgical tissue handling characteristics to the monopolar electrocautery device.

  19. [Liver hemostasis using a dry electrocautery or greased with lidocaine or neomycin or glycerin or vaseline, in rabbit].

    PubMed

    de Matos Filho, Argos Soares; Petroianu, Andy; Alberti, Luiz Ronaldo; Vidigal, Paula Vieira Teixeira; dos Reis, Daniel Cruz Ferreira; de Souza, Davi Machado

    2009-10-01

    To assess the hemostasis and healing of the hepatic parenchyma after segmental hepatectomy, using a dry electrocautery or an electrocautery greased with lidocaine gel, neomycin pomade, glycerin lotion, or a vaseline pomade. Rabbits were submitted to partial hepatectomy and divided into six groups of 10 animals each: Group 1: untreated; Group 2: treated with a dry electrocautery; Group 3: treated with an electrocautery greased with lidocaine gel; Group 4: with neomycin pomade; Group 5: with glycerine lotion; Group 6: with vaseline pomade. Resected liver weight, bleeding volume and time spent to achieve hemostasis were determined. Five rabbits from each group were re-operated upon after 24 hours and five after 7 days in order to obtain a biopsy of the hepatic wound and to explore he abdominal cavity. Red blood cell levels and markers of hepatic function and injury were determined before surgery and before re-operation. Lidocaine gel and glycerine lotion reduced the bleeding volume and the time to achieve hemostasis and conducted the thermal energy of the electrocautery, causing hydropic cell degeneration after 24 hours and deeper necrosis of hepatic tissue after 7 days. All substances increased the aminotransferase concentrations. These values returned to normal after a maximum of seven days. The electrocautery coated with lidocaine gel and glycerine lotion were the most effective methods for the hemostasis of hepatic parenchyma.

  20. Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum.

    PubMed

    Zira, Athina; Mikros, Emmanuel; Giannioti, Konstantina; Galanopoulou, Panagiota; Papalois, Apostolos; Liapi, Charis; Theocharis, Stamatios

    2009-07-01

    The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by (1)H-NMR spectroscopy, on serum samples in acetaminophen (APAP)-induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote N-acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL/CIM was also investigated. A single dose of APAP (2 g kg(-1) b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC. Animals were sacrificed at 24 h post-APAP treatment. Healthy untreated animals served as controls. (1)H-NMR spectra of serum samples were acquired and underwent principal component analysis (PCA). Acute liver injury was verified by histopathological examination and the alterations of serum biochemical enzymes AST and ALT. (1)H-NMR spectroscopy revealed variations in the serum metabolic profile of APAP-intoxicated rabbits compared with controls. Co-administration of APAP with NAC, CIM and SIL + CIM seems to ameliorate the metabolic profile of animals compared with simply APAP-treated ones. In this study, the model of APAPinduced liver injury was successfully described using the (1)H-NMR based metabonomic approach in serum. Furthermore, the use of antidotes that reduced the toxic insult was also recorded using this technique. The combination of NMR spectroscopy and PCA is a rapid methodology, capable of detecting alterations in the metabolic profile, and produces adequate models that could be used for the characterization of unknown samples, both experimental and clinical, reinforcing its future use in clinical settings.

  1. Brain death induces the alteration of liver protein expression profiles in rabbits.

    PubMed

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  2. Comparative gene expression profiling of normal and degenerative discs: analysis of a rabbit annular laceration model.

    PubMed

    Anderson, D Greg; Izzo, Marc W; Hall, David J; Vaccaro, Alexander R; Hilibrand, Alan; Arnold, William; Tuan, Rocky S; Albert, Todd J

    2002-06-15

    A rabbit annular laceration model was used to investigate intervertebral disc gene expression in normal and lacerated discs. To determine and compare the pattern of expression of potentially important genes in normal and lacerated discs and to determine if the changes in gene expression were similar to human degenerative discs. Little is known regarding gene expression in normal or degenerating disc tissue. Eighteen rabbits were subjected to annular laceration of the L1-L2 and L2-L3 discs while two rabbits served as sham controls. Control and lacerated discs were harvested 1 week, 3 weeks, and 6 weeks following surgery and subjected to histologic examination and gene expression analysis using the reverse transcription-polymerase chain reaction (RT-PCR). The genes studied included collagen Type I (Col I), collagen Type II (Col II), decorin, fibronectin (FN), interleukin-1a (IL-1alpha), bone morphogenetic protein 2 (BMP-2), Fas, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 13 (MMP-13), and tumor necrosis factor (TNF). Expression levels of each gene were normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GADPH), a constitutively expressed gene. Histology confirmed progressive degeneration of the discs over the 6-week study period. Different patterns of gene expression were observed in control and lesioned discs. Annular laceration caused a marked upregulation (two- to eightfold) of the expression of Col I, Col II, FN, MMP-1, MMP-9, MMP-13, and Fas genes, whereas that of BMP-2, IL-1alpha, and TNF genes was unaffected. Expression of the decorin gene was downregulated approximately sixfold after annular laceration. Annular laceration in this animal model resulted in marked changes in gene expression. Upregulation of gene expression was observed for some molecules found at high concentration in human degenerated discs, suggesting similarities to human disc degeneration at the molecular level. This supports

  3. Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and Liver during Primoinfection Outbreak in Rabbits

    PubMed Central

    Rodríguez-Tovar, Luis E.; Nevárez-Garza, Alicia M.; Trejo-Chávez, Armando; Hernández-Martínez, Carlos A.; Zarate-Ramos, Juan J.; Castillo-Velázquez, Uziel

    2016-01-01

    This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen. PMID:27022485

  4. Encephalitozoon cuniculi: Grading the Histological Lesions in Brain, Kidney, and Liver during Primoinfection Outbreak in Rabbits.

    PubMed

    Rodríguez-Tovar, Luis E; Nevárez-Garza, Alicia M; Trejo-Chávez, Armando; Hernández-Martínez, Carlos A; Hernández-Vidal, Gustavo; Zarate-Ramos, Juan J; Castillo-Velázquez, Uziel

    2016-01-01

    This is the first confirmed report of Encephalitozoon cuniculi (E. cuniculi) in farm meat rabbits located in Northern Mexico. Eighty young rabbits exhibited clinical signs of this zoonotic emerging disease, like torticollis, ataxia, paresis, circling, and rolling. Samples of brain, kidney, and liver were examined for histology lesions. For the first time the lesions caused by E. cuniculi were graded according to their severity (I, II, and III) and the size of the granulomas (Types A, B, and C). The main cerebral injuries were Grade III, coinciding with the presence of Type C granulomas. The cerebral lesions were located in the cortex, brain stem, and medulla. The renal lesions were also Grade III distributed throughout cortex and renal medulla, with no granuloma formation. The involvement of hypersensitivity Types III and IV is suggested. All of the rabbits were seropositive to E. cuniculi by CIA testing, suggesting that this zoonotic and emerging pathogen is widely distributed among animals intended for human consumption. We believe this work could be used as a guide when examining E. cuniculi and will provide direction to confirm the diagnosis of this pathogen.

  5. Real-time MR temperature mapping of rabbit liver in vivo during thermal ablation.

    PubMed

    Weidensteiner, Claudia; Quesson, Bruno; Caire-Gana, Bénédicte; Kerioui, Noureddine; Rullier, Anne; Trillaud, Hervé; Moonen, Chrit T W

    2003-08-01

    It has been shown that quantitative MRI thermometry using the proton resonance frequency (PRF) method can be used to noninvasively monitor the evolution of tissue temperature, and to guide minimally-invasive tumor ablation based on local hyperthermia. Although hepatic tumors are among the main targets for thermal ablation, PRF-based temperature MRI of the liver is difficult to perform because of motion artifacts, fat content, and low T(*) (2). In this study the stability of real-time thermometry was tested on a clinical 1.5 T scanner for rabbit liver in vivo. The fast segmented EPI principle was used together with respiratory gating to limit respiratory motion artifacts. Lipid signal suppression was achieved with a binomial excitation pulse. Saturation slabs were applied to suppress artifacts due to flowing blood. The respiratory-gated MR thermometry in the rabbit liver in vivo showed a standard deviation (SD) of 1-3 degrees C with a temporal resolution of 3 s per slice and 1.4 mm x 1.9 mm spatial resolution in plane (slice thickness = 5 mm). The method was used to guide thermal ablation experiments with a clinical infrared laser. The estimated size of the necrotic area, based on the thermal dose calculated from MR temperature maps, corresponded well with the actual lesion size determined by histology and conventional MR images obtained 5 days posttreatment. These results show that quantitative MR temperature mapping can be obtained in the liver in vivo, and can be used for real-time control of thermal ablation and for lesion size prediction. Copyright 2003 Wiley-Liss, Inc.

  6. Hypoglycaemic effects of methanolic extract of Canscora decussata (Schult) whole-plant in normal and alloxan-induced diabetic rabbits.

    PubMed

    Irshad, Nadeem; Akhtar, Muhammad Shoaib; Bashir, Sajid; Hussain, Azhar; Shafiq, Muhammad; Iqbal, Javeid; Malik, Abdul

    2015-01-01

    In present study hypoglycaemic effects of the crude powdered C. decussata and its methanolic extract (ME) in alloxan diabetic rabbits were evaluated. The hypoglycaemic effect was measured by blood glucose, insulin level, HbA1c and his to pathology of pancreas. Glucose lowering effect of the ME was studied in diabetic rabbits. The effects of extract on blood glucose, body weight, food in take, fluid intake, OGTT were also evaluated. The results showed that 0.5,1 and 2g/kg of the powder significantly decreased blood glucose levels in normal rabbits and diabetic rabbits at the intervals checked. Oral intake of pioglitazone also reduced the levels in these rabbits. Synergistic hypoglycaemic effect of 600mg/kg of ME with different doses of insulin (2 & 3unit/kg, s/c) further reduced blood glucose levels of treated alloxan-diabetic rabbits. The oral glucose tolerance test revealed lowered area under curve values in ME treated rabbits. Treatment with ME (400 and 600 mg/kg) for 30 days showed highly significant decrease in blood glucose level by augmenting insulin secretion, HbA1cand significant increase in body weight, serum insulin levels in treated diabetic rabbits. Histopathology study showed regeneration of β-cells. These studies have, therefore, supported the traditional use of this herb in diabetic patients.

  7. Conjunctival structural and functional reconstruction using acellular bovine pericardium graft (Normal GEN®) in rabbits.

    PubMed

    Huang, Danping; Xu, Bing; Yang, Xiaonan; Xu, Binbin; Zhao, Jing

    2016-04-01

    To evaluate the effectiveness of acellular bovine pericardium grafts (Normal GEN®) used as scaffolds for conjunctival reconstruction. The acellular bovine pericardium graft and the amnion graft were implanted into the bulbar conjunctival defects of adult rabbits. Conjunctival samples of implanted materials and blank defect controls were observed at day 3, 7, 14, 21, 28, and 56 postoperatively. Histological examination was observed at day 14, 28, and 56 of surgery, including hematoxylin-eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining, while immunofluorescent microscopy was observed at 14 days and 28 days after surgery. Results were compared among the Normal GEN®, amnion, and blank defect controls. All three groups showed complete conjunctival reconstruction. Wounds that were not grafted closed by formation of conjunctival scar characterized by a linear array of densely packed collagen fibers in Tenon's capsule. Subepithelial tissue in the grafted groups comprised a loosely organized network of randomly oriented collagen that resembled that of the normal bulbar conjunctiva. However, there was a dense layer of aligned collagen between the conjunctival Tenon's capsule and the sclera in the NormalGEN® group, about 250 μm in thickness. Implantation of the NormalGEN® graft promoted the formation of conjunctiva as a kind of scaffold both in structure and in function. It had more advantageous mechanical properties than the amnion, strong and elastic, during the period of conjunctival reconstruction.

  8. Intraocular pressure effects of water loading and venous compression tests in normal and denervated pigmented rabbits.

    PubMed

    Gual, A; Mintenig, G M; Belmonte, C

    1989-03-01

    We have compared IOP elevations induced by water-loading and by increased cephalic venous pressure in normal and denervated pigmented rabbits. Denervations were performed by sympathetic ganglionectomy and/or blockade of the sensory and autonomic innervation of the eye through retrobulbar anesthesia; retrobulbar anesthesia induced significant decreases of the basal IOP in control but not in ganglionectomized eyes. The water-loading test induced a peak pressure elevation approximately 30 min after water administration that could be counteracted by retrobulbar anesthesia. Ganglionectomized rabbits exhibited steeper IOP rises and greater IOP increases following water-loading than the control eyes; retrobulbar anesthesia in ganglionectomized eyes delayed the IOP response to water-loading. Compressions of the neck lasting 30 min elicited significant IOP elevations that were more pronounced in ganglionectomized eyes. In these eyes, retrobulbar anesthesia further increased the IOP rise elicited by neck compression. An IOP decrease below control values was observed at the end of the venous compression. The results indicate that an intact efferent innervation of the eye contributes to buffer IOP elevations induced by water-loading or cephalic venous stasis, presumably through the vascular effects of the ocular autonomic nerves.

  9. Absorption of inhaled antigen into the circulation of isolated lungs from normal and immunized rabbits.

    PubMed Central

    Braley, J F; Dawson, C A; Moore, V L; Cozzini, B O

    1978-01-01

    The purpose of this study was to determine whether the absorption of inhaled antigen (Ag) across the pulmonary air-blood barrier of the isolated perfused lung can be modulated by immunologic mechanisms. Lungs from immunized or nonimmunized rabbits were removed, ventilated, and perfused with autochthonous blood. Radioiodinated Ag (human serum albumin or ovalbumin) was introduced as an aerosol into the isolated lung for 15 min and blood samples were taken over a 4-h period. The results showed that radioactivity fom inhaled Ag entered the perfusing blood as two fractions. One fraction was precipitable by 5% trichloroacetic acid or antiserum. The TCA-soluble fraction chromatographed differently from iodide and may have represented metabolites of the Ag. Immunization specifically reduced the amount of antigenically intact protein entering the blood. On the other hand, the metabolite reached higher concentrations in the blood of immunized lungs. We conclude that the alveolar capillary barrier of the normal rabbit lung could provide a significant route of entry for inhaled antigen into the systemic circulation and that immunization reduces absorption via this route and enhances pulmonary metabolism of the Ag. PMID:678344

  10. ELISA for detection of variant rabbit haemorrhagic disease virus RHDV2 antigen in liver extracts.

    PubMed

    Dalton, K P; Podadera, A; Granda, V; Nicieza, I; Del Llano, D; González, R; de Los Toyos, J R; Ocaña, M García; Vázquez, F; Alonso, J M Martin; Prieto, J M; Parra, F; Casais, R

    2017-09-20

    The emergence and rapid spread of variant of the rabbit hemorrhagic disease virus (RHDV2) require new diagnostic tools to ensure that efficient control measures are adopted. In the present study, a specific sandwich enzyme-linked immunosorbent assay (ELISA) for detection of RHDV2 antigens in rabbit liver homogenates, based on the use of an RHDV2-specific monoclonal antibody (Mab) 2D9 for antigen capture and an anti-RHDV2 goat polyclonal antibody (Pab), was developed. This ELISA was able to successfully detect RHDV2 and RHDV2 recombinant virions with high sensitivity (100%) and specificity (97.22%). No cross-reactions were detected with RHDV G1 viruses while low cross-reactivity was detected with one of the RHDVa samples analyzed. The ELISA afforded good repeatability and had high analytical sensitivity as it was able to detect a dilution 1:163,640 (6.10ng/mL) of purified RHDV-N11 VLPs, which contained approximately 3.4×10(8)molecules/mL particles. The reliable discrimination between closely related viruses is crucial to understand the epidemiology and the interaction of co-existing pathogens. In the work described here we design and validate an ELISA for laboratory based, specific, sensitive and reliable detection of RHDV2/RHDV2. This ELISA is a valuable, specific virological tool for monitoring virus circulation, which will permit a better control of this disease. Copyright © 2017. Published by Elsevier B.V.

  11. Effect of garlic extract on blood glucose level and lipid profile in normal and alloxan diabetic rabbits.

    PubMed

    Sher, Alam; Fakhar-ul-Mahmood, Muhammad; Shah, Syed Nisar Hussain; Bukhsh, Sattar; Murtaza, Ghulam

    2012-01-01

    Comparative hypoglycemic and hypolipidaemic activity of garlic (ethanol) extract and metformin was the aim of the study in 24 normal and diabetic rabbits. In group A of 12 rabbits, the influence of different doses (250, 300 and 350 mg/kg body weight) of garlic extract was evaluated, six of them were kept normal, while six were caused to be diabetic with alloxan (150 mg/kg body weight). In another group B of 12 rabbits, the influence of various doses of metformin (250, 375 and 500 mg/kg body weight) was also assessed in the similar grouping of six normal and six diabetic rabbits. The maximum hypoglycemic response was observed with highest doses of garlic extract (350 mg/kg body weight) in normal rabbits 4 h after garlic extract administration, while in diabetic rabbits, blood glucose level (270.3 ± 0.8 mg/dl) was significantly (p < 0.05) lowered as compared to the control level (303.8 ± 1.8 mg/dl). The levels of triglycerides (44.0 ± 0.9 mg/dl) and cholesterol (32.8 ± 0.7 mg/dl) also significantly (p < 0.05) decreased in normal rabbits after 4 h of extract administration as compared to that of 0 h samples (triglycerides 66.0 ± 1.5 mg/dl and cholesterol 47.5 ± 0.5 mg/dl). In diabetic rabbits, 0 h level of triglyceride and cholesterol was found to be 86.5 ± 1.1 mg/dl and 93.8 ± 0.9 mg/dl, respectively and levels seen in 4 h sample were 61.3 ± 1.2 mg/dl and 57.0 ± 1.8 mg/dl, respectively. In normal as well as diabetic rabbits, garlic extract produced hypoglycemia as well as hypolipidaemia like metformin, but the hypoglycemic effect was more pronounced with metformin, whereas garlic extract was more effective in causing hypolipidaemia as compared to metformin.

  12. Rabbit liver tRNA1Val:I. Primary structure and unusual codon recognition.

    PubMed

    Jank, P; Shindo-Okada, N; Nishimura, S; Gross, H J

    1977-06-01

    The major valine acceptor tRNA1Val from rabbit liver was purified and its nucleotide sequence determined by in vitro [32P] - labeling with T4 phage induced polynucleotide kinase and finger-printing techniques. Its primary structure was found to be identical with the major valine tRNA from mouse myeloma cells. According to the wobble hypothesis this tRNA, which exclusively has an IAC anticodon, should decode the valine codons GUU, GUC and GUA only. However, this tRNA recognizes all four valine codons with a surprising preference for GUG. It is unknown whether this is due to the lack of A37 modification next to the 3' end of the anticodon IAC. The nature of the inosine-guanosine interaction remains to be clarified.

  13. Valproate-induced hyperammonemic encephalopathy with normal liver function.

    PubMed

    Rath, Amitav; Naryanan, T Jaishree; Chowdhary, G V S; Murthy, J M K

    2005-06-01

    Hyperammonemic encephalopathy with normal liver function is an uncommon serious adverse effect of valproate therapy. We retrospectively analyzed the case records of 5 patients of epilepsy on valproate with hyperammonemic encephalopathy. Of the 5 patients, 3 were on monotherapy. The mean valproate dose was 1250 mg/day and the duration of therapy ranged between 4 and 90 days. Alteration in the sensorium was the presenting clinical feature. The risk factors included high initial dose (2), long-term valproate therapy (1), and long-term valproate therapy with concomitant topiramate (1). There was good correlation between the fall in serum ammonia levels and clinical improvement. Hyperammonemic encephalopathy should be suspected in patients on valproate with altered sensorium. Response to treatment is rewarding.

  14. Blood oxygenation during hyperpressure intraperitoneal fluid administration in a rabbit model of severe liver injury: Evaluation of a novel concept for control of pre-hospital liver bleeding.

    PubMed

    Ahmadi-Noorbakhsh, Siavash; Azizi, Saeed; Dalir-Naghadeh, Bahram; Maham, Masoud

    2012-01-01

    Oxygen is an essential part of the most important metabolic pathways in aerobic organisms. Oxygen delivery is merely dependent on blood, rendering blood loss a devastating event. Traumatic pre-hospital liver bleeding is a major cause of early trauma deaths in human and animals, with no established therapeutic method yet. Increasing intra-abdominal pressure (IAP) has been shown to reduce liver bleeding by half. Although reduction of blood loss could be in favor of blood oxygen delivery, however, the complex interaction between increased IAP and respiratory mechanics during severe hemorrhagic shock remained unclear. We used a novel model of liver trauma in 16 rabbits and randomly assigned them to either normotensive abdomen group or increased IAP by fluid infusion (HA) groups (n=8 each). Liver size and the amount of liver injury were evaluated. Various blood oxygenation parameters were recorded. Both groups were identical in terms of the liver size and injury. The HA group had significantly lower shock index. Arterial oxygen capacity and oxygen content were higher in the HA group. No significant statistical difference was seen between groups in terms of abdominal perfusion pressure; alveolar pressure of oxygen; dissolved oxygen in blood plasma; alveolar to arterial oxygen tension gradient; arterial to alveolar oxygen pressure ratio; the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen; and respiratory index. In conclusion, the novel therapeutic method of increasing IAP by fluid infusion in a rabbit model of liver hemorrhage preserved blood oxygenation better than the classic therapeutic method.

  15. Transarterial Chemoembolization Using Cisplatin Powder in a Rabbit Model of Liver Cancer

    SciTech Connect

    Morimoto, Kengo Sakaguchi, Hiroshi; Tanaka, Toshihiro; Yamamoto, Kiyosei; Anai, Hiroshi; Hayashi, Takayuki; Satake, Mitsuo; Kichikawa, Kimihiko

    2008-09-15

    The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 {mu}g/ml for the cisplatin-HAI group, 1.23 {mu}g/ml for the cisplatin-GS-TACE group, and 12.65 {mu}g/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 {mu}g/ml for the cisplatin-HAI group, 1.13 {mu}g/ml for the cisplatin-GS-TACE group, and 1.09 {mu}g/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

  16. Biomagnetic detection of gastric electrical activity in normal and vagotomized rabbits.

    PubMed

    Bradshaw, L A; Myers, A G; Redmond, A; Wikswo, J P; Richards, W O

    2003-10-01

    We recorded the vector magnetogastrogram (MGG) due to gastric electrical activity (GEA) in normal rabbits using a Superconducting QUantum Interference Device (SQUID) magnetometer and measured the degree of correlation of the MGG with 24 channels of serosal electrodes. The vector magnetometer allows us to non-invasively record three orthogonal magnetic field components and project the recorded magnetic field vector into arbitrary directions. We optimized the magnetic field vector direction to obtain the highest possible correlation with each serosal electrode recording. We performed a vagotomy and examined spatial and temporal changes in the serosal potential and in the transabdominal magnetic field. We obtained spatial information by mapping the recorded signals to the electrode positions in the gastric musculature. Temporal evidence of uncoupling was observed in spectral analyses of both serosal electrode and SQUID magnetometer recordings. We conclude that non-invasive recordings of the vector magnetogastrogram reflect underlying serosal potentials as well as pathophysiological changes following vagotomy.

  17. Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

    SciTech Connect

    Jorge E. Cardoso; Elisa M. Heber; David W. Nigg; Osvaldo Calzetta; Herman Blaumann; Juan Longhino; Maria E. Itoiz; Eduardo Bumaschny; Emiliano Pozzi; Amanda E.Schwint; Verónica A. Trivillin

    2007-10-01

    The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis is that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.

  18. Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation

    PubMed Central

    Lee, Jae Geun; Lee, Juhan; Lee, Jung Jun; Song, Seung Hwan; Ju, Man Ki; Choi, Gi Hong; Kim, Myoung Soo; Choi, Jin Sub; Kim, Soon Il; Joo, Dong Jin

    2016-01-01

    Abstract Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child–Turcotte–Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients’ median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver

  19. [Expression profiling and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum in the liver of infected New Zealand white rabbits].

    PubMed

    Xia, Dan; Deng, Ganming; Teng, Pingying; Xie, Yu; Li, Yaomin; Wang, Chunmei; Chen, Shujie; Chen, Minfang; Mai, Rongjia; Liao, Haiyan; Shi, Lingyu; Ou, Liyan; Chen, Qiwei; Chen, Xiaoguang; Zhou, Xiaohong

    2015-06-01

    To examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits. New Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas. The level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas. The transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.

  20. Isolation and characterization of a constitutive form of rabbit liver microsomal cytochrome P-450.

    PubMed

    Johnson, E F

    1980-01-10

    A heretofore unrecognized form of cytochrome P-450 was purified from rabbit liver microsomes with an average yield and purity similar to that of other highly purified forms of cytochrome P-450. Several properties of this cytochrome are contrasted with those of form 2, the major phenobarbital-inducible cytochrome P-450, form 4, the major 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome, and form 6, a cytochrome that is selectively induced in liver microsomes by 2,3,7,8-tetrachlorodibenzo-p-dioxin during the perinatal period. Thes four forms can be distinguished by virtue of their molecular weights as determined using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, by their respective peptide fingerprints, and by the monospecificity of their antisera. Since the enumerated properties are thought to reflect the primary structure of the cytochromes and since the observed differences are extensive, we suggest that these four forms are not derived from a common protein precursor.

  1. Isolation of mast cells from rabbit lung and liver: comparison of histamine release induced by the hypnotics Althesin and propanidid.

    PubMed

    Ennis, M; Lorenz, W; Gerland, W; Heise, J

    1987-04-01

    The enzyme collagenase was used to disperse rabbit lung and liver into their component cells. The resulting cell suspensions contained ca. 6.9% (lung) or 6.5% (liver) mast cells and were used in studies of histamine release without further purification. Both cell suspensions exhibited a low spontaneous release of histamine (ca. 6.6% lung, ca. 7.2% liver). Both cell types responded to challenge with anti-rabbit serum with a maximum release of the amine of ca. 22% (lung) and ca. 45% (liver). Concanavalin A challenge generally resulted in bell-shaped dose response curves, however some lung preparations did not respond. The rabbit cells were refractory to stimulation by Compound 48/80 and dextran. However a dose-dependent release of histamine was elicited after challenge with the detergents cremophor El, TN (12-hydroxystearic acid polymerized with ethylene oxide, degree of polymerization 15) and the hypnotics Althesin and propanidid. The maximum release observed depended on which cell preparation had been used. These results further emphasize the functional heterogeneity of mast cells from both different species and from different organs within the same species.

  2. In vivo oxygen transport in the normal rabbit femoral arterial wall.

    PubMed Central

    Crawford, D W; Back, L H; Cole, M A

    1980-01-01

    In vivo measurements of tissue oxygen tension were made at 10-micrometer intervals through functioning in situ rabbit femoral arterial walls, using inhalation anesthesia and recessed microcathodes with approximately 4-micrometer external diameters. External environment was controlled with a superfusion well at 30 torr PO2, 35 torr PCO2. Blood pressure, gas tension levels, and blood pH were held within the normal range. Radial PO2 measurements closely fit a mathematical model for unidimensional diffusion into a thick-walled artery with uniform oxygen consumption, and the distances traversed fit measured dimensions of quick-frozen in vivo sections. Using standard values of diffusion and solubility coefficients, mean calculated medial oxygen consumption was 99 nl0/ml-s. Mural oxygen consumption appeared to be related linearly to mean tangential wall stress. Differences in experimental design and technique were compared with previous in vivo and in vitro measurements of wall oxygenation, and largely account for the varying results obtained. Control of environment external to the artery, and maintenance of normally flowing blood in the lumen in vivo appeared critical to an understanding of mural oxygenation in life. If the conditions of this experiment prevailed in arteries with thicker avascular layers, PO2 could have been 20 torr at approximately 156 micrometer and 10 torr at 168 micrometer from blood (average values). Images PMID:7410554

  3. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors.

    PubMed

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-11-08

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.

  4. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors

    PubMed Central

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-01-01

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy. PMID:27602579

  5. Clinical Application of Cone-Beam Computed Tomography of the Rabbit Head: Part 1 – Normal Dentition

    PubMed Central

    Riggs, G. G.; Arzi, Boaz; Cissell, Derek D.; Hatcher, David C.; Kass, Philip H.; Zhen, Amy; Verstraete, Frank J. M.

    2016-01-01

    Domestic rabbits (Oryctolagus cuniculus) are increasingly popular as household pets; therefore, veterinarians need to be familiar with the most common diseases afflicting rabbits including dental diseases. Diagnostic approaches for dental disease include gross oral examination, endoscopic oral examination, skull radiography, and computed tomography (CT). CT overcomes many limitations of standard radiography by permitting cross-sectional images of the rabbit head in multiple planes without superimposition of anatomic structures. Cone-beam CT (CBCT) is an oral and maxillofacial imaging modality that produces high-resolution images. The objective of this study was to describe and compare the normal anatomic features of the dentition and surrounding maxillofacial structures in healthy rabbits on CBCT and conventional CT. Ten New Zealand white rabbit cadaver heads were scanned using CBCT and conventional CT. Images were evaluated using Anatomage Invivo 5 software. The maxillofacial anatomy was labeled on CBCT images, and the mean lengths and widths of the teeth were determined. The visibility of relevant dental and anatomic features (pulp cavity, germinal center, tooth outline, periodontal ligament) were scored and compared between conventional CT and CBCT. The thinnest teeth were the maxillary second incisor teeth at 1.29 ± 0.26 mm and the maxillary third molar teeth at 1.04 ± 0.10 mm. In general, it was found that CBCT was superior to conventional CT when imaging the dentition. Importantly, the periodontal ligament was significantly (P < 0.01) more visible on CBCT than on conventional CT. Ability to see the periodontal ligament with such detail may allow earlier detection and treatment of periodontal disease in rabbits. This study is the first of its kind and shows the feasibility and yield of CBCT when evaluating the maxillofacial features and dentition in rabbits. PMID:27800485

  6. Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma

    PubMed Central

    Song, Dongda; Hu, Minggen; Guo, Weichang

    2017-01-01

    Background The concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model. Material/Methods Rabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed. Results Plasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis. Conclusions The liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis. PMID:28344313

  7. Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma.

    PubMed

    Song, Dongda; Hu, Minggen; Guo, Weichang

    2017-03-27

    BACKGROUND The concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model. MATERIAL AND METHODS Rabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed. RESULTS Plasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis. CONCLUSIONS The liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis.

  8. Vitamin K antagonist therapy and liver transplantation: two cases managed without normalizing the international normalized ratio.

    PubMed

    Sabate, Antoni; Contreras, Laura; Aparicio, Idoia; Costa, Marta; Reyes, Raquel

    2016-12-01

    Guidelines for surgery in patients treated with vitamin K antagonist recommends to correct international normalized ratio (INR), although they do not focus on liver transplantation candidates. We report two patients treated with vitamin K antagonist, monitored by thromboelastometry during liver transplantation. Case 1: basal INR was 3.15. Extem coagulation time was 83 s and maxim clot firmness was 60 mm. The surgical procedure did not show bleeding. Two red blood cells were transfused and no other blood products were administered. Last INR was 3.17. Case 2: basal INR was 2.79. A thrombocytopenia of 58 000/mm was detected. Extem coagulation time was 176 s, and maxim clot firmness was 40 mm. Fibtem maxim clot firmness was 11 mm. The surgical procedure did not show bleeding. No blood product was administered. Last INR was 2.1. Although thromboelastometry did not correlate with INR, monitoring of the coagulation using thromboelastometry in combination with surgery helped to conduct hemostatic corrections.

  9. Cell death during the postnatal morphogenesis of the normal rabbit kidney and in experimental renal polycystosis.

    PubMed Central

    García-Porrero, J A; Ojeda, J L; Hurlé, J M

    1978-01-01

    We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:670065

  10. Aldehyde oxidase-catalysed oxidation of methotrexate in the liver of guinea-pig, rabbit and man.

    PubMed

    Jordan, C G; Rashidi, M R; Laljee, H; Clarke, S E; Brown, J E; Beedham, C

    1999-04-01

    Although 7-hydroxymethotrexate is a major metabolite of methotrexate during high-dose therapy, negligible methotrexate-oxidizing activity has been found in-vitro in the liver in man. The goals of this study were to determine the role of aldehyde oxidase in the metabolism of methotrexate to 7-hydroxymethotrexate in the liver and to study the effects of inhibitors and other substrates on the metabolism of methotrexate. Methotrexate, (+/-)-methotrexate and (-)-methotrexate were incubated with partially purified aldehyde oxidase from the liver of rabbit, guinea-pig and man and the products analysed by HPLC. Rabbit liver aldehyde oxidase was used for purposes of comparison. In-vitro aldehyde oxidase from the liver of man catalyses the oxidation of methotrexate to 7-hydroxymethotrexate, but the turnover is low. However, formation of 7-hydroxy-methotrexate from all forms of methotrexate by the liver in guinea-pig and man was significantly inhibited in the presence of 100 microM menadione and chlorpromazine, potent inhibitors of aldehyde oxidase. Allopurinol (100 microM) had a negligible inhibitory effect on liver aldehyde oxidase from guinea-pig and man. Allopurinol is a xanthine oxidase inhibitor. The production of 7-hydroxymethotrexate was enhanced in the presence of allopurinol. Although aldehyde oxidase is also responsible for some of this conversion, it is also possible that the closely related xanthine oxidase is responsible for the formation of 7-hydroxymethotrexate. By employing potent selective inhibitors of aldehyde oxidase, menadione and chlorpromazine, we have demonstrated for the first time that liver aldehyde oxidase from man is minimally involved in methotrexate oxidation.

  11. Ultrasound examination of the liver: Normal vascular anatomy

    PubMed Central

    Draghi, F.; Rapaccini, G.L.; Fachinetti, C.; de Matthaeis, N.; Battaglia, S.; Abbattista, T.; Busilacchi, P.

    2007-01-01

    Various treatments for liver diseases, including liver transplant (particularly partial liver resection from a living donor), treatment of liver tumors, and TIPS, require detailed knowledge of the complex vascular anatomy of the liver. The hepatic artery and portal vein provide the organ with a double blood supply whereas venous drainage is furnished by the hepatic veins. Multislice computed tomography and magnetic resonance imaging provide undeniably excellent information on these structures. On ultrasound, the inferior vena cava, the openings of the hepatic veins, and the main branch of the portal vein can always be visualized, but intrasegmental vessels (portal, arterial, accessory hepatic venous branches) can be only partially depicted and in some cases not at all. In spite of its difficulty and limitations, hepatic sonography is frequently unavoidable, particularly in critically ill patients, and the results are essential for defining diagnostic and therapeutic strategies. For this reason, a thorough knowledge of the sonographic features of hepatic vascular anatomy is indispensable. PMID:23396216

  12. A study of the effects of photodynamic therapy on the normal tissues of the rabbit jaw.

    PubMed Central

    Meyer, M.; Speight, P.; Bown, S. G.

    1991-01-01

    Photodynamic therapy (PDT) is an anti-cancer treatment which involves the systemic administration of a photosensitising drug which is preferentially absorbed by tumour tissue. Relatively little drug should be absorbed by the surrounding normal tissues. Tumour destruction is achieved when the tumour is illuminated with light of a wavelength which activates the photosensitising drug thereby inducing a cytotoxic reaction. However studies in many tissues have shown that the hoped for tumour selectivity is rarely achieved. Using the rabbit mandible and gingiva as our models we have studied the effects of various doses of PDT on the tissues of the oral cavity, namely mucosa, bone, muscle and salivary gland. The photosensitiser used was di-sulphonated aluminium phthalocyanine. Results show that whereas bone is extremely resistant to PDT the other tissues are vulnerable to it. In the case of muscle and salivary gland this susceptibility is very much dose related. In salivary tissue necrotising sialometaplasia was observed in areas of the gland adjacent to those that had undergone necrosis. All tissues were noted to heal or regenerate well following PDT injury. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:1764372

  13. Integration and expression of a rabbit liver cytochrome P-450 gene in transgenic Nicotiana tabacum.

    PubMed Central

    Saito, K; Noji, M; Ohmori, S; Imai, Y; Murakoshi, I

    1991-01-01

    Cytochrome P-450 is involved in the oxidative metabolism of a broad range of substrates. We have made a chimeric construct, pSN002, containing the cDNA for rabbit liver cytochrome P-450 (IIC14) under the control of the TR2' promoter for mannopine synthase in the Agrobacterium Ti plasmid. Nicotiana tabacum was transformed with Agrobacterium tumefaciens harboring a cointegrated plasmid pSN002::pGV2260. The presence of mRNA and of the translated protein from the chimeric cytochrome P-450 gene in transgenic plants was confirmed by RNA blot hybridization and by Western blot and immunohistochemical analyses, respectively. The transformants in which the foreign cytochrome P-450 protein is expressed show marked phenotypic changes, notably a tendency rapidly to senesce. We detected 2-propenylpyrrolidine, a degradative metabolite of nicotine alkaloids, in transgenic tobacco showing this pronounced phenotypic change. Such metabolism is likely to be due to the effect of senescence and not directly to the presence of the cytochrome P-450. Images PMID:1714583

  14. Triglycerides produced in the livers of fasting rabbits are predominantly stored as opposed to secreted into the plasma

    PubMed Central

    Tuvdendorj, Demidmaa; Zhang, Xiao-jun; Chinkes, David L.; Wang, Lijian; Wu, Zhanpin; Rodriguez, Noe A.; Herndon, David N.; Wolfe, Robert R.

    2015-01-01

    Objective The liver plays a central role in regulating fat metabolism; however, it is not clear how the liver distributes the synthesized triglycerides (TGs) to storage and to the plasma. Materials and Methods We have measured the relative distribution of TGs produced in the liver to storage and the plasma by means of U-13C16-palmitate infusion in anesthetized rabbits after an overnight fast. Results The fractional synthesis rates of TGs stored in the liver and secreted into the plasma were not significantly different (Stored vs. Secreted: 31.9 ± 0.8 vs. 27.7 ± 2.6 %•h−1, p > 0.05. However, the absolute synthesis rates of hepatic stored and secreted TGs were 543 ± 158 and 27 ± 7 nmol·kg−1·min−1 respectively, indicating that in fasting rabbits the TGs produced in the liver were predominately stored (92±3%) rather than secreted (8±3%) into the plasma. This large difference was mainly due to the larger pool size of the hepatic TGs which was 21±9-fold that of plasma TGs. Plasma free fatty acids (FFAs) contributed 47±1% of the FA precursor for hepatic TG synthesis, and the remaining 53±1% was derived from hepatic lipid breakdown and possibly plasma TGs depending on the activity of hepatic lipase. Plasma palmitate concentration significantly correlated with hepatic palmitoyl-CoA and TG synthesis. Conclusion In rabbits, after an overnight fast, the absolute synthesis rate of hepatic stored TGs was significantly higher than that of secreted due to the larger pool size of hepatic TGs. The net synthesis rate of TG was approximately half the absolute rate. Plasma FFA is a major determinant of hepatic TG synthesis, and therefore hepatic TG storage. PMID:25682063

  15. Normal Liver Tissue Density Dose Response in Patients Treated With Stereotactic Body Radiation Therapy for Liver Metastases

    SciTech Connect

    Howells, Christopher C.; Stinauer, Michelle A.; Diot, Quentin; Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Miften, Moyed

    2012-11-01

    Purpose: To evaluate the temporal dose response of normal liver tissue for patients with liver metastases treated with stereotactic body radiation therapy (SBRT). Methods and Materials: Ninety-nine noncontrast follow-up computed tomography (CT) scans of 34 patients who received SBRT between 2004 and 2011 were retrospectively analyzed at a median of 8 months post-SBRT (range, 0.7-36 months). SBRT-induced normal liver tissue density changes in follow-up CT scans were evaluated at 2, 6, 10, 15, and 27 months. The dose distributions from planning CTs were mapped to follow-up CTs to relate the mean Hounsfield unit change ({Delta}HU) to dose received over the range 0-55 Gy in 3-5 fractions. An absolute density change of 7 HU was considered a significant radiographic change in normal liver tissue. Results: Increasing radiation dose was linearly correlated with lower post-SBRT liver tissue density (slope, -0.65 {Delta}HU/5 Gy). The threshold for significant change (-7 {Delta}HU) was observed in the range of 30-35 Gy. This effect did not vary significantly over the time intervals evaluated. Conclusions: SBRT induces a dose-dependent and relatively time-independent hypodense radiation reaction within normal liver tissue that is characterized by a decrease of >7 HU in liver density for doses >30-35 Gy.

  16. What do we know about shear wave dispersion in normal and steatotic livers?

    PubMed

    Parker, Kevin J; Partin, Alexander; Rubens, Deborah J

    2015-05-01

    A number of new approaches to measure the viscoelastic properties of the liver are now available to clinicians, many involving shear waves. However, we are at an early stage in understanding the physical processes that govern shear wave propagation in normal liver, with more unknowns added when pathologies such as steatosis are present. This technical note focuses on what is known about the characterization of normal and steatotic (or fatty) livers, with a particular focus on dispersion. Some studies in phantoms and mouse livers support the hypothesis that, starting with a normal liver, increasing accumulations of micro- and macrosteatosis will increase the lossy viscoelastic properties of shear waves in a medium. This results in an increased dispersion (or slope) of shear wave speed and attenuation in the steatotic livers. Theoretical and empirical findings across a number of studies are summarized.

  17. Tracing multiscale mechanisms of drug disposition in normal and diseased livers.

    PubMed

    Park, Sunwoo; Kim, Sean H J; Ropella, Glen E P; Roberts, Michael S; Hunt, C Anthony

    2010-07-01

    Hepatic drug disposition is different in normal and diseased livers. Different disease types alter disposition differently. What are the responsible micromechanistic changes and how do they influence drug movement within the liver? We provide plausible, concrete answers for two compounds, diltiazem and sucrose, in normal livers and two different types of cirrhotic rat livers: chronic pretreatment of rats with carbon tetrachloride (CCl(4)) and alcohol caused different types of cirrhosis. We started with simulated disposition data from normal, multilevel, physiologically based, object-oriented, discrete event in silico livers (normal ISLs) that validated against diltiazem and sucrose disposition data from normal livers. We searched the parameter space of the mechanism and found three parameter vectors that enabled matching the three wet-lab data sets. They specified micromechanistic transformations that enabled converting the normal ISL into two different types of diseased ISLs. Disease caused lobular changes at three of six levels. The latter provided in silico disposition data that achieved a prespecified degree of validation against wet-lab data. The in silico transformations from normal to diseased ISLs stand as concrete theories for disease progression from the disposition perspective. We also developed and implemented methods to trace objects representing diltiazem and sucrose during disposition experiments. This allowed valuable insight into plausible disposition details in normal and diseased livers. We posit that changes in ISL micromechanistic details may have disease-causing counterparts.

  18. The influence of protein and carbohydrate type on serum and liver lipids and lipoprotein cholesterol in rabbits.

    PubMed

    Bauer, J E; Covert, S J

    1984-11-01

    The non-lipid portions of semi-synthetic diets appear to be important determinants of hypercholesterolemia and atherosclerosis in the rabbit. Serum and liver lipid concentrations were determined in rabbits which had been pair-fed various protein (casein or soy protein isolate) and carbohydrate (sucrose or dextrose) sources as part of low fat, low cholesterol, semi-synthetic diets. It was verified that casein-containing diets render rabbits hypercholesterolemic, while soy protein caused a degree of hypocholesterolemia. Additionally, sucrose, when fed in conjunction with casein, appears to augment this hypercholesterolemic effect. The distribution of total cholesterol among lipoprotein subclasses was increased in both the intermediate density lipoprotein (IDL) (1.006-1.019 g/ml) and low density lipoprotein (LDL) (1.019-1.063 g/ml) fractions and decreased in the high density lipoprotein (HDL) (1.063-1.21 g/ml) fraction when casein is fed. Soy protein feeding caused relatively more cholesterol to appear only in the IDL fraction when compared with commercial chow fed rabbits. Reasons for these differences may involve the saturation or suppression of endogenous lipoprotein hepatic receptors.

  19. Corneal temperatures--a study of normal and laser-injured corneas in the Dutch belted rabbit.

    PubMed

    Mikesell, G W

    1978-02-01

    Air Force laser safety standards are developed from laser-exposure data obtained in studies using experimental animals and from biomathematical modeling procedures. Interpretation of research data and predictive modeling calculations are enhanced by knowledge of the temperature values of the tissue absorption sites. Corneal temperature values for the normal, the anesthetized, and the laser-injured Dutch belted rabbit are presented and compared with values obtained in other studies. The corneal temperatures were measured by infrared radiometry.

  20. Analysis of LIF-Raman spectroscopy for the diagnosis of normal and liver diseases

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Sun, Ruomin; Li, Siqi

    2011-07-01

    In this paper, 514.5nm argon ion laser induced human serum Raman and auto-fluorescence spectra of normal, liver cirrhosis and liver cancer were measured and analyzed. The spectral differences between these three types of serums were observed and given brief explanations. Three parameters α, φ and Δλ were introduced to describe characteristics of each type of spectrum. Experimental results showed that these parameters might be applicable for discrimination of normal, liver cirrhosis and liver cancer, which will provide some reference values to explore the method of laser spectral diagnosis of cancer.

  1. Acute serum sickness in normal and C6 deficient rabbits: role of membrane attack complex.

    PubMed Central

    Parra, G.; Takekoshi, Y.; Striegel, J.; Vernier, R. L.; Michael, A. F.

    1992-01-01

    Acute serum sickness was induced in New Zealand White (NZW) and in C6 deficient (C6D) rabbits, to compare the histology, immunofluorescence, especially distribution of poly C9 (MAC), and electron microscopic characteristics of the disease in each strain. Glomerulonephritis and albuminuria of comparable extent occurred in 13/17 NZW and 4/8 C6D rabbits. In NZW rabbits with albuminuria an early intense glomerular infiltration by mononuclear cells was associated with focal small fine granular glomerular basement membrane (GBM) deposits of IgG and BSA and more diffuse and larger deposits of C3 and MAC. After the disappearance of monocytes and decrease in mesangial cell proliferation, development of large subepithelial GBM deposits rich in all immune reactants was observed in NZB rabbits. In C6D rabbits with albuminuria a similar monocytic infiltrate occurred, but no association with IgG and C3 GBM immune deposits was noted. No deposits of MAC and no large subepithelial GBM 'humps' were observed in C6D rabbits. We conclude that the exudative (monocytic) phase of glomerular injury and albuminuria in acute serum sickness nephritis are not dependent upon terminal complement components, but the subsequent formation of large subepithelial GBM deposits does not occur in this model in the absence of MAC. Images Fig. 2 Fig. 3 Fig. 4 PMID:1622842

  2. Heterogeneous delayed enhancement of the liver after ultrasound contrast agent injection--a normal variant.

    PubMed

    Okada, Masahiro; Albrecht, Thomas; Blomley, Martin J; Heckemann, Rolf A; Cosgrove, David O; Wolf, Karl-Jürgen

    2002-08-01

    We report a characteristic heterogeneous delayed liver enhancement pattern that we have encountered in a total of 6 of approximately 1500 subjects who underwent contrast-enhanced liver ultrasonography. The heterogeneous enhancement occurred several min after contrast injection and persisted for up to 1 h. It was seen in diseased as well as healthy livers and appears to represent a "normal variant" of liver enhancement. It was observed with two different contrast agents. The cause of the described effect is unknown; it may be related to the formation of large bubbles and vascular entrapment of these bubbles in the liver.

  3. Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

    PubMed Central

    Seidensticker, Max; Streit, Sebastian; Nass, Norbert; Wybranski, Christian; Jürgens, Julian; Brauner, Jan; Schulz, Nadine; Kalinski, Thomas; Seidensticker, Ricarda; Garlipp, Benjamin; Steffen, Ingo; Ricke, Jens; Dudeck, Oliver

    2016-01-01

    PURPOSE We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model. METHODS VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy. RESULTS The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE. CONCLUSION SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity. PMID:27328720

  4. Study on construction of cDNA libraries from rat normal liver and regeneration liver with smart technique.

    PubMed

    Jun-Tang, Lin; Cong-Rui, Wang; Pramanik, Jogenananda; Hui-Yong, Zhang; Hui-Gen, Feng; Bao-Sheng, Yang; Yu-Chang, L I; Cun-Shuan, Xu

    2004-07-01

    The aim of the study is to construct cDNA libraries from the normal liver and regeneration liver of rat by SMART (switching mechanism at 5' end of RNA transcript) technique and analyze their quality. The total RNA was separated from the normal liver and regeneration liver of rat and the frist-strand cDNA was synthesized through reverse transcription by a modified oligo (dT) primer (contained sfi IB site) while the SMART oligonucleotide (contained sfi IA site) was utilized as a template so that the first-strand cDNA could be extended over the 5' end of mRNA. The double-strand cDNA was amplified by LD-PCR (long-distance PCR) with the above two primers and then digested by sfi I (IA & IB) restriction, enzyme. After cDNA size fractionation through Chroma Spin 400 column, the double-strand cDNA was ligated into the sfi I-digested lambda TripIEx2 vector and then the recombinant DNA was packagedin vitro. The unamplified rat normal liver cDNA library consists of 1.3×10(7) pfu/ml, and regeneration liver cDNA library consists of 1.6×10(7) pfu/ml in which the percentage of recombinant clones both are about 100%. Through testing, the high quality cDNA libraries containing full-length cDNA of rat normal liver and regeneration liver have been constructed. The titer of the amplified cDNA library is 4.5×10(10) pfu/ml and 3.6×10(10) pfu/ml. the average exogenous inserts of the recombinants both are about 1.5 kb. These results show that the normal liver and regeneration liver of rat cDNA libraries both have an excellent quality and lay solid foundation to study liver functions and the mechanism of liver regeneration.

  5. L-carnitine administration and withdrawal affect plasma and hepatic carnitine concentrations, plasma lipid and lipoprotein composition, and in vitro hepatic lipogenesis from labeled mevalonate and oleate in normal rabbits.

    PubMed

    Bell, F P; Vidmar, T J; Raymond, T L

    1992-04-01

    Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-14C]mevalonate and [1-14C]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [14C]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [14C]cholesterol to [14C]squalene derived from [14C]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.

  6. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization (90)Y PET.

    PubMed

    Srinivas, Shyam M; Natarajan, Navin; Kuroiwa, Joshua; Gallagher, Sean; Nasr, Elie; Shah, Shetal N; DiFilippo, Frank P; Obuchowski, Nancy; Bazerbashi, Bana; Yu, Naichang; McLennan, Gordon

    2014-01-01

    Radioembolization with Yttrium-90 ((90) Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment (90) Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of (90) Y delivered to liver and treated tumors. This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres(®)) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). (90) Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy; range 0-570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). Our cohort of patients showed a possible dose-response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the

  7. Determination of vitamin A in liver and liver-containing products using narrow-bore normal, phase HPLC.

    PubMed

    Brinkmann, E; Mehlitz, I; Oei, H B; Tiebach, R; Baltes, W

    1994-09-01

    Vitamin A concentrations in livers of fattening animals and liver-containing products may reach much higher values than was assumed up to now. This effect may be caused by animal feed, which is usually supplemented with vitamins. To support this supposition, 57 liver samples of different species of animals, 97 liver sausages and 106 samples of liver-containing infant food were analysed. For isolation of retinol from the sample matrix the sample was saponified for 16 h under a nitrogen atmosphere at room temperature. Retinol was extracted from the saponification solution by using disposable cartridges. For chromatographic determination a normal-phase HPLC system using a narrow-bore analytical column and a photodiode array detector was used. It was possible to separate all-trans-retinol from other isomers. The identity of the peaks could be confirmed by recording the UV spectra.--The results of the retinol contents found in the analysed samples ranged from 11.6 to 160.7 mg/100 g in liver, from 1.4 to 31.1 mg/100 g in liver sausages and from 0.5 to 3.8 mg/100 g in infant food containing between 5 and 11% liver. By consuming liver-containing meals frequently a multiple amount of the recommended dietary intake ranging from 0.375 mg for infants to 0.8 mg for adults may be taken up. Also the recommended daily intakes of the Deutsche Gesellschaft für Ernährung can be exceeded.--The carry-over effect of daily vitamin A consumption of pigs and their liver vitamin A was investigated by parallel determination of the retinol content in the liver after slaughtering and the vitamin A content in the pig-feed during the fattening period. A clear correlation between their daily vitamin A intake and the resulting retinol content in the livers was found.

  8. Classification of normal and diseased liver shapes based on Spherical Harmonics coefficients.

    PubMed

    Mofrad, Farshid Babapour; Zoroofi, Reza Aghaeizadeh; Tehrani-Fard, Ali Abbaspour; Akhlaghpoor, Shahram; Sato, Yoshinobu

    2014-05-01

    Liver-shape analysis and quantification is still an open research subject. Quantitative assessment of the liver is of clinical importance in various procedures such as diagnosis, treatment planning, and monitoring. Liver-shape classification is of clinical importance for corresponding intra-subject and inter-subject studies. In this research, we propose a novel technique for the liver-shape classification based on Spherical Harmonics (SH) coefficients. The proposed liver-shape classification algorithm consists of the following steps: (a) Preprocessing, including mesh generation and simplification, point-set matching, and surface to template alignment; (b) Liver-shape parameterization, including surface normalization, SH expansion followed by parameter space registration; (c) Feature selection and classification, including frequency based feature selection, feature space reduction by Principal Component Analysis (PCA), and classification. The above multi-step approach is novel in the sense that registration and feature selection for liver-shape classification is proposed and implemented and validated for the normal and diseases liver in the SH domain. Various groups of SH features after applying conventional PCA and/or ordered by p-value PCA are employed in two classifiers including Support Vector Machine (SVM) and k-Nearest Neighbor (k-NN) in the presence of 101 liver data sets. Results show that the proposed specific features combined with classifiers outperform existing liver-shape classification techniques that employ liver surface information in the spatial domain. In the available data sets, the proposed method can successful classify normal and diseased livers with a correct classification rate of above 90 %. The performed result in average is higher than conventional liver-shape classification method. Several standard metrics such as Leave-one-out cross-validation and Receiver Operating Characteristic (ROC) analysis are employed in the experiments and

  9. Purification, characterization and partial primary structure of morphine 6-dehydrogenase from rabbit liver cytosol.

    PubMed

    Yamano, S; Ito, K; Ogata, S; Toki, S

    1997-05-01

    Morphinone, a toxic metabolite, was formed from morphine by NAD(P)-dependent morphine 6-dehydrogenase(s) in both the cytosol and microsomal fractions of the rabbit liver at pH 7.4. The enzyme activity in the cytosol fraction was about twice that in the microsomal fraction and NAD served as the preferred cofactor in both fractions. The enzyme in the cytosol fraction was purified to a homogeneous protein by the use of various chromatographic techniques. The enzyme is a monomeric protein with a molecular weight of 36,000 and an isoelectric point of 6.4. The enzyme had a dual cofactor specificity but NAD was more efficiently utilized than NADP. With NAD, the enzyme showed an optimal pH of 9.4, and the Km and Vmax values toward morphine were 0.72 mM and 0.59 unit/mg protein, respectively. The enzyme also exhibited a significant activity for morphine analogs having an unsaturated bond at C-7,8 (codeine, ethylmorphine, and normorphine), alicyclic alcohols (3-hydroxyhexobarbital, 1-indanol, and cyclohexene-2-ol) and benzenedihydrodiol. In the reverse reaction, the enzyme exhibited highly restricted specificity for o-quinones. Sulfhydryl re-agents and quercetin inhibited the enzyme but pyrazole, barbital, and indomethacin had little effect on the enzyme activity. Androstanes, lithocholic acid, and estradiol potently inhibited the enzyme in a competitive manner toward morphine binding. The partial amino acid sequence of the random peptides obtained by the proteolytic digestion of the enzyme, which comprised about 40% of the whole protein, revealed a significant homology to the corresponding regions in the members of the aldo-keto reductase family. These results therefore indicate that the present enzyme is a new and unique member of the aldo-keto reductase family.

  10. Inhibition of two monomeric butyrylcholinesterases from rabbit liver by chlorpromazine and other drugs.

    PubMed

    Rush, R S; Main, A R; Kilpatrick, B F; Faulkner, G D

    1981-03-01

    A new form of cholinesterases has been discovered in rabbit liver; the new enzymes are monomeric butyrylcholinesterases (EC 3.1.1.8), mBuChE I and mBuChE II. These enzymes are inhibited reversibly by chlorpromazine in the pharmacologically active concentration range and they exhibit mixed competitive-noncompetitive inhibition patterns. The apparent competitive inhibition constants, Ki with chlorpromazine, are 1.8 x 10(-6) M for mBuChE I and 7.6 x 10(-6) M for mBuChE II, whereas the noncompetitive inhibition constant is 1.1 x 10(-5) M for mBuChE II as determined by spectrophotometric assay with n-butyrylthiocholine iodide substrate. Although inhibition of mBuChE I also exhibited noncompetitive behavior, a binding constant could not be determined. Human serum oligometric butyrylcholinesterase (oBuChE) was employed as a control cholinesterase and also demonstrated mixed inhibition kinetics. The competitive inhibition constant for the oBuChE was 5.5 x 10(-7) M in the low substrate region, whereas the apparent noncompetitive binding constant was 1.6 x 10(-5) M in the activated higher substrate region with n-butyrylthiocholine iodide as the substrate and chlorpromazine as the reversible inhibitor. The presence of a noncompetitive binding component indicates the presence of an operative modifier or allosteric site binding the inhibitor on both mBuChEs and the oBuChE. The inhibition constants were calculated assuming that the enzymes followed simple Michaelian kinetics.

  11. Multimodality Imaging of Ethiodized Oil–loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors

    PubMed Central

    Tacher, Vania; Duran, Rafael; Lin, MingDe; Sohn, Jae Ho; Sharma, Karun V.; Wang, Zhijun; Chapiro, Julius; Gacchina Johnson, Carmen; Bhagat, Nikhil; Dreher, Matthew R.; Schäfer, Dirk; Woods, David L.; Lewis, Andrew L.; Tang, Yiqing; Grass, Michael; Wood, Bradford J.

    2016-01-01

    Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor-bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70–150-μm radiopaque microspheres in saline (radiopaque microsphere group), 70–150-μm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70–150-μm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone-beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement

  12. Glycoconjugate histochemistry in the small and large intestine of normal and Solanum glaucophyllum-intoxicated rabbits.

    PubMed

    Zanuzzi, C N; Barbeito, C G; Ortíz, M L; Lozza, F A; Fontana, P A; Portiansky, E L; Gimeno, E J

    2010-10-01

    Vitamin D participates in mineral homeostasis, immunomodulation, cell growth and differentiation. The leaves of Solanum glaucophyllum contain high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives and their chronic ingestion generates a hypervitaminosis D-like state. We analyzed changes on carbohydrate expression as a cell differentiation indicator on samples of the small and large intestine of S. glaucophyllum-intoxicated rabbits, using conventional and lectin histochemistry. Male New Zealand white rabbits were intoxicated with S. glaucophyllum during two or four weeks and killed the day after. A group of animals ("possibly recovered group") were intoxicated during 15 days and killed at day 45 of the beginning of the experiment. We found changes in the lectin binding pattern in the small and large intestine of the intoxicated rabbits. Some of these changes were reverted in the possibly recovered group. Vitamin D could be a new regulator factor of the intestinal glycosylation process.

  13. Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load

    SciTech Connect

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Itoh, T.; Sano, A.

    1988-11-01

    Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of /sup 3/H/sub 2/O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the /sup 3/H/sub 2/O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc.

  14. Analysis of normal and diseased liver tissue using auto-fluorescence and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Jia, Chunde; Lin, Junxiu; Kang, Youping

    2003-12-01

    In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver cancer patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5 nm is higher than that excited by 488.0 nm. However, for the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. These results have important reference values to explore the method of laser spectrum diagnosis.

  15. Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry.

    PubMed

    Luo, Wen; Zhou, Xiaodong; Yu, Ming; He, Guangbin; Zheng, Xiaoying; Li, Qiuyang; Liu, Qing; Han, Zenghui; Zhang, Jun; Qian, Yunqiu

    2009-08-01

    We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry. Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed. The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05). Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.

  16. Survival Motor Neuron (SMN) protein is required for normal mouse liver development

    PubMed Central

    Szunyogova, Eva; Zhou, Haiyan; Maxwell, Gillian K.; Powis, Rachael A.; Francesco, Muntoni; Gillingwater, Thomas H.; Parson, Simon H.

    2016-01-01

    Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA. PMID:27698380

  17. Comprehensive echocardiographic assessment of biventricular function in the rabbit, animal model in cardiovascular research: feasibility and normal values.

    PubMed

    Ramos, Sara Roldan; Pieles, Guido; Hui, Wei; Ishii, Ryo; Slorach, Cameron; Friedberg, Mark K

    2017-08-24

    Quantification of cardiac structure and function is central in cardiovascular research. Rabbits are valuable research models of cardiovascular human disease; however, there is little normal data available. The aim of this study was to investigate feasibility and provide normal values for comprehensive echocardiographic assessment of biventricular function in rabbits. New Zealand white rabbits underwent trans-thoracic echocardiography using a general electric (GE) Vivid 7/E9 system with a 10 MHz transducer, under light sedation, to evaluate biventricular function and dimensions. Images for two-dimensional, M-mode, tissue Doppler imaging (TDI) and speckle-tracking strain echocardiography were acquired and analysed. 55 male rabbits (sized matched with a newborn human baby) were studied, mean weight was 2.9 ± 0.23 kg. Adequate images were obtained in 90% for the left ventricle (LV) and 80% for the right ventricle (RV). Two-dimensional speckle-tracking strain was feasible in 60%. Average heart rate was 248 ± 36 beats per minute; LV ejection faction 72 ± 8.0; RV fractional area change 45.9 ± 9.0%; RV myocardial performance index 0.39 ± 0.35; tricuspid annular planar systolic excursion 0.60 ± 0.24 cm. LV TDI parameters were S' 8.6 ± 3.1 cm/s; E' 12.0 ± 4.46 cm/s. RV TDI parameters were S' 10.49 ± 3.18; E' 14.95 ± 4.64 cm/s. LV and RV global peak systolic longitudinal strain were -17 ± 5 and -22 ± 8%, respectively. Comprehensive investigation of biventricular dimensions and function by echocardiography is feasible in the rabbit. Apical views and strain imaging have lower feasibility. Normal values of LV and RV functional parameters are with comparable values to human children. Animal cardiovascular research is key to develop new goals in clinical practice.

  18. Effects of electromagnetic extracorporeal shock wave lithotripsy on the fine structure of the liver and gallbladder of the rabbit.

    PubMed

    Larriva-Sahd, J; Angeles Angeles, A; Bosques, F; Robledo, J; Acosta, V; Castorena, G; Sánchez, C; Uribe, M

    1990-07-01

    The fine structure of the liver and gallbladder of rabbits submitted to lithotripsy was studied with transmission electron microscopy. Alterations found in both organs involved capilaries, venules and small veins as well as neighboring tissues. In the liver the most important alterations were seen in those areas located about central veins. These consisted in mitochondrial vacuolation, increase in the cytoplasmic electrondensity, and necrosis. In the gallbladder different stages of epithelial damage and regeneration (i.e. mitoses) were observed. Vascular damage was characterized by mitochondrial swollen and increase of nuclear and cytoplasmic electrondensities. The gallbladder's stroma displayed cell vacuolation, pyknosis, and edema. It is proposed that the damage produced by lithotripsy results from a direct colision of red blood cells upon blood vessels. Tissue damage was considered focal and in most cases reversible.

  19. Magnetic field dependence of proton relaxation rates in tissue with added Mn2+: rabbit liver and kidney.

    PubMed

    Koenig, S H; Brown, R D; Goldstein, E J; Burnett, K R; Wolf, G L

    1985-04-01

    Since contrast in magnetic resonance imaging (MRI) is so sensitive to the magnetic relaxation rates of tissue protons, the use of paramagnetic ions to alter contrast in a tissue-specific fashion is an alluring prospect. The influence of these ions on the proton relaxation rates in homogeneous solutions is known to vary dramatically according to whether the ions are present as hydrated aquoions, in solute chelate, or immobilized in macromolecules. In tissue, there is the additional complication of access of water to the ions. In the present study, Mn2+ ions were introduced into rabbits both orally and intravenously in various chemical complexes. Accumulation of these ions in rabbit liver is demonstrated here, qualitatively, by MRI. The quantitation of the change in relaxation rates is investigated in excised samples of liver and kidney by study of the magnetic field dependence (dispersion) of the relaxation rates of the protons (NMRD profiles) of tissue water. Results are presented for several sets of experiments, including dose-response data for weakly chelated Mn2+ and time-response data for free and complexed Mn2+. The general findings are that, for liver, the response (the increment in the NMRD profile) is relatively rapid (less than 2 m); that it is relatively independent of how, or in what form, the Mn2+ is introduced; that it persists for several hours (at least); and that it saturates with increasing body load of Mn2+. Moreover, from the form of the NMRD profiles of liver, it is clear that the Mn2+ ions are bound irrotationally, perhaps to cell membrane, and, when introduced in chelated form, can become separated even from strongly associated chelate complexes. For kidney, the results are qualitatively similar, though different in detail.

  20. Expression of P450 and nuclear receptors in normal and end-stage Chinese livers.

    PubMed

    Chen, Hong; Shen, Zhong-Yang; Xu, Wang; Fan, Tie-Yan; Li, Jun; Lu, Yuan-Fu; Cheng, Ming-Liang; Liu, Jie

    2014-07-14

    To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers. The end-stage liver disease samples [n = 93, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis] and trimmed normal Chinese donor livers (n = 35) from The Institute of Organ Transplantation in Beijing, China. Total RNA was extracted, purified, and subjected to real-time RT-PCR analysis. For cytochrome P450 enzymes 1 (CYP1) family, the expression of CYP1A2 was decreased 90% in HCC, 80% in alcoholic cirrhosis, and 65% in severe cirrhosis. For CYP2 family, the expression of CAR was decreased 50% in HCC, but increased 50% in peri-HCC tissues. Similar decreases (about 50%) of CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 were observed in HCC, as compared to peri-HCC tissues and normal livers. CYP2C19 were decreased in all end-stage liver diseases and CYP2E1 also decreased in alcoholic cirrhosis and severe cirrhosis. For CYP3 family, the expression of PXR was decreased 60% in HCC, together with decreases in CYP3A4, CYP3A5, and CYP3A7. In contrast, the expression of CYP3A7 was slightly increased in HBV cirrhosis. The expression of CYP4A11 was decreased 85% in HCC, 7% in alcoholic cirrhosis and severe liver cirrhosis, along with decreases in PPARα. The 93 end-stage livers had much higher inter-individual variations in gene expression than 35 normal livers. The expression of CYP enzyme genes and corresponding nuclear receptors was generally decreased in end-stage liver diseases, and significant differences in gene expression were evident between peri-HCC and HCC.

  1. Expression of P450 and nuclear receptors in normal and end-stage Chinese livers

    PubMed Central

    Chen, Hong; Shen, Zhong-Yang; Xu, Wang; Fan, Tie-Yan; Li, Jun; Lu, Yuan-Fu; Cheng, Ming-Liang; Liu, Jie

    2014-01-01

    AIM: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers. METHODS: The end-stage liver disease samples [n = 93, including hepatocellular carcinoma (HCC), peri-HCC tissue, hepatitis B virus cirrhosis, alcoholic cirrhosis, and severe cirrhosis] and trimmed normal Chinese donor livers (n = 35) from The Institute of Organ Transplantation in Beijing, China. Total RNA was extracted, purified, and subjected to real-time RT-PCR analysis. RESULTS: For cytochrome P450 enzymes 1 (CYP1) family, the expression of CYP1A2 was decreased 90% in HCC, 80% in alcoholic cirrhosis, and 65% in severe cirrhosis. For CYP2 family, the expression of CAR was decreased 50% in HCC, but increased 50% in peri-HCC tissues. Similar decreases (about 50%) of CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 were observed in HCC, as compared to peri-HCC tissues and normal livers. CYP2C19 were decreased in all end-stage liver diseases and CYP2E1 also decreased in alcoholic cirrhosis and severe cirrhosis. For CYP3 family, the expression of PXR was decreased 60% in HCC, together with decreases in CYP3A4, CYP3A5, and CYP3A7. In contrast, the expression of CYP3A7 was slightly increased in HBV cirrhosis. The expression of CYP4A11 was decreased 85% in HCC, 7% in alcoholic cirrhosis and severe liver cirrhosis, along with decreases in PPARα. The 93 end-stage livers had much higher inter-individual variations in gene expression than 35 normal livers. CONCLUSION: The expression of CYP enzyme genes and corresponding nuclear receptors was generally decreased in end-stage liver diseases, and significant differences in gene expression were evident between peri-HCC and HCC. PMID:25024626

  2. From vitamin K antagonists to liver international normalized ratio: a historical journey and critical perspective.

    PubMed

    Gatt, Alexander; Chen, Dong; Pruthi, Rajiv K; Kamath, Patrick S; Leise, Michael D; Ashrani, Aneel A; Nichols, William L; He, Rong

    2014-11-01

    Adoption of international normalized ratio (INR) to harmonize prothrombin time has greatly improved the safety and effectiveness of vitamin K antagonists (VKA) oral anticoagulant therapy. INR is also a major laboratory variable in calculating the widely used Model for End-Stage Liver Disease (MELD) score for liver transplant organ prioritization. However, since the conventional INR (INRVKA) is calibrated specifically for VKA patients, its interlaboratory variation has a significant impact on the accuracy of MELD score. Though still requiring further clinical validation in large numbers of waitlisted patients, the alternative liver INR calibrated by using plasma from liver disease patients instead of VKA patients may harmonize the differences and thus more suitable for MELD score calculation. The objective of this article is to review the history of INR, MELD score, and liver INR, and discuss the challenges and solutions of liver INR implementation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Comparison of the metabolism of ethylene glycol and glycolic acid in vitro by precision-cut tissue slices from female rat, rabbit and human liver.

    PubMed

    Booth, E D; Dofferhoff, O; Boogaard, P J; Watson, W P

    2004-01-01

    1. The metabolism of [1,2-(14)C]-ethylene glycol and [1,2-(14)C]-glycolic acid was studied in vitro using precision-cut tissue slices prepared from the livers of female Sprague-Dawley rats, New Zealand white rabbits and humans. The time-course for production of metabolites formed from ethylene glycol at concentrations from 3 to 40 mM was determined to compare quantitatively the differences between species in the rates and amounts of formation of glycolic acid, the presumed developmental toxicant of ethylene glycol. The rates of metabolism of glycolic acid to glyoxylic acid at concentrations from 0.05 to 16 mM by liver tissue from the different species were also determined. The apparent V(max)/K(m) for the metabolic conversions of ethylene glycol to glycolic acid and for glycolic acid to glyoxylic acid in liver tissue from the different species were obtained. 2. There were qualitative differences in the metabolic profiles and quantitative differences in the formation of glycolic acid between the mammalian liver systems. There was an average of 10-fold less glycolic acid produced by liver slices from rabbits compared with rats. With the human liver, the formation of glycolic acid was not detectable using tissue from three of four human donors. A low level of glycolic acid was detected in one liver slice incubation from one of the four subjects, but only at one extended time point; glyoxylate was detected with liver slices from all four humans. 3. Liver slices prepared from female Sprague-Dawley rats, female New Zealand White rabbits and three female human subjects all metabolized glycolic acid to glyoxylic acid. Human liver tissue was the most effective at further metabolizing glycolic acid to glyoxylic acid. The ratios of V(max)/K(m), representing the relative clearance of glycolic acid from liver tissue, were approximately 14:9:1 for human, rat and rabbit liver, respectively. 4. Precision-cut liver slices maintained in dynamic organ culture are good predictors of

  4. Evaluation of Pistacia lentiscus fatty oil effects on glycemic index, liver functions and kidney functions of New Zealand rabbits.

    PubMed

    Djerrou, Zouhir; Hamdi-Pacha, Y; Belkhiri, A M; Djaalab, H; Riachi, F; Serakta, M; Boukeloua, A; Maameri, Z

    2011-01-01

    Pistacia lentiscus fatty oil (PLFO) is a well known natural remedy in eastern Algeria folk medicine. It is widely used in the treatment of respiratory disorders and dermal burns. The present study has been carried out to investigate effects of this oil on fasting glucose and some functional parameters of the liver and kidney in white male New Zealand rabbits (Initial mean weight 1.95 Kg). PLFO was applied to tested rabbits (PLFO group) via rectal route, once daily 5-day per week, for six consecutive weeks at the dose of 1 ml/Kg body weight. The same number of animals (n=6) was not treated and served as control (CRL group). The results showed that PLFO was tolerated by rectal route. No significant differences were observed in body weights of the two groups. Biochemical analysis showed that aspartate transaminase (AST) and alanine transaminase (ALT) were significantly decreased in blood plasma at (P< 0.05) and (P< 0.01) respectively in PLFO group (Mann-Whitney test). On the other hand, the fasting glucose level (GLU) was significantly increased (Mann-Whitney test, P< 0.05), while the rest of the tested parameters (Albumin, total proteins, creatinine, urea) was not significantly affected. However, these variations have not biologic signification toxicity. The study concludes that PLFO is tolerable via rectal route; it is safe with no adverse effect on liver functions and renal functions with possible anti-glycogenesis activity.

  5. Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit's Kidney and Liver: Protection by Ginger (Zingiber officinale).

    PubMed

    Baiomy, Ahmed A; Mansour, Ahmed A

    2016-04-01

    This study aimed to examine the protective effects of ginger (G) on the genetic response induced by cadmium (Cd) and immunohistochemical expression of Caspase3 and MKI67 in the kidney and liver of rabbits. Male rabbits were divided into three groups; each group contains 10 animals: group (C) received basic diet and tap water for 12 weeks, the second group (Cd) received 200 mg/kg b.w CdCl2 in water for 12 weeks, group (Cd + G) was given 200 mg/kg b.w CdCl2 in water and 400 mg ginger/kg b.w in food for 12 weeks. Cd administration increased the activity of mRNA expression of the examined apoptotic (Caspase3), proliferation (MKI67), proto-oncogene (C-fos), and antioxidant (GST), while decreased the expression of anti-apoptotic (Bcl2). Ginger counteracted the effects of Cd in (Cd + G) group and downregulated the previously upregulated genes under Cd administration appeared in (Cd) group. The immunohistochemical expression of Caspase3 and MKI67 in the liver and kidney cells of the (C) group was shown very faint to negative reactions, strong staining in hepatocytes and the tubular epithelium in cadmium-treated group, while slight staining in some hepatocytes and tubular epithelium in co-administration with ginger in (Cd + G) group. In conclusion, ginger administration showed a protective effect against cadmium toxicity.

  6. Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

    SciTech Connect

    Konya, Andras; Stephens, L. Clifton; Wright, Kenneth C.

    2011-10-15

    Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization and coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.

  7. Hazelnut oil administration reduces aortic cholesterol accumulation and lipid peroxides in the plasma, liver, and aorta of rabbits fed a high-cholesterol diet.

    PubMed

    Hatipoğlu, Aydan; Kanbağli, Oznur; Balkan, Jale; Küçük, Mutlu; Cevikbaş, Uğur; Aykaç-Toker, Gülçin; Berkkan, Hakan; Uysal, Müjdat

    2004-10-01

    Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet. An HC diet caused significant increases in lipids and lipid peroxide levels in the plasma, liver, and aorta together with histopathological atherosclerotic changes in the aorta. Glutathione levels, glutathione peroxidase, and glutathione transferase activities decreased significantly, but superoxide dismutase activity and vitamin E and C levels remained unchanged in the livers of rabbits following HC diet. HO supplementation reduced plasma, liver, and aorta lipid peroxide levels and aorta cholesterol levels together with amelioration in atherosclerotic lesions in the aortas of rabbits fed an HC diet, without any decreasing effect on cholesterol levels in the plasma or liver. HO did not alter the antioxidant system in the liver in the HC group. Our findings indicate that HO reduced oxidative stress and cholesterol accumulation in the aortas of rabbits fed an HC diet.

  8. Expression and function of thyroid hormone receptor variants in normal and chronically diseased human liver.

    PubMed

    Chamba, A; Neuberger, J; Strain, A; Hopkins, J; Sheppard, M C; Franklyn, J A

    1996-01-01

    As the liver represents a major target organ for thyroid hormone action, we compared the expression of thyroid hormone receptor (TR) alpha and beta variants in normal human liver and liver affected by primary biliary cirrhosis, sclerosing cholangitis, cryptogenic cirrhosis, and alcoholic cirrhosis (n = 6 in each group). Western blot analysis using specific polyclonal antibodies to alpha 1 or beta 1 TRs or to the related non-T3-binding c-erbA alpha 2 variant revealed abundant expression of TRs in normal and diseased liver, with no difference in size or abundance of TR proteins. Immunocytochemistry likewise revealed abundant nuclear expression of TR proteins in normal and diseased liver, with similar patterns and intensity of staining. Despite abundant TR protein expression, Northern blot hybridization of polyadenylated ribonucleic acid (RNA; 10 micrograms) to TR complementary DNAs revealed only a weak signal for c-erbA alpha 2 messenger RNA (mRNA). Comparison of the level of expression of the thyroid hormone-regulated mRNAs encoding T4-binding globulin, sex hormone-binding globulin, cortisol-binding globulin, and transthyretin in normal and diseased tissue revealed no significant difference, suggesting that hepatocellular expression of these mRNAs is maintained in chronic liver disease despite a marked reduction in circulating T3 concentrations.

  9. Elevation of molybdenum hydroxylase levels in rabbit liver after ingestion of phthalazine or its hydroxylated metabolite.

    PubMed

    Johnson, C; Stubley-Beedham, C; Stell, J G

    1984-11-15

    Oral administration of phthalazine (50 mg/kg/day) or 1-hydroxyphthalazine (10 mg/kg/day) to female rabbits caused an increase in the specific activity of the hepatic molybdenum hydroxylases aldehyde oxidase and xanthine oxidase, whereas no effect on microsomal cytochrome P-450 activity was observed. The rise in the specific activity of purified aldehyde oxidase fractions was accompanied by a similar increase in molybdenum content. A significant lowering of the Km value for phthalazine was demonstrated with enzyme from treated rabbits whereas Km values for structurally similar substrates such as isoquinoline were unchanged from control values. Iso-electric focusing of DEAE-cellulose fractions showed the presence of an additional band of activity indicating that genuine induction of aldehyde oxidase had occurred in rabbits treated with phthalazine or 1-hydroxyphthalazine.

  10. A CHEMICAL AND PATHOLOGIC STUDY OF THE EFFECTS OF COPPER ON THE LIVER

    PubMed Central

    Flinn, Frederick B.; VonGlahn, William C.

    1929-01-01

    From the above studies the following conclusions have been reached: 1. That copper or its compounds used does not cause the deposition of pigment in the livers of rabbits, guinea pigs or rats. Neither does it produce a cirrhosis in these animals. 2. That spontaneous deposition of pigment occurs frequently in the livers of normal rabbits on the usual laboratory diet. 3. That the feeding of a diet of carrots exclusively will produce pigment deposition in the livers of rabbits, in every way identical with that ascribed to copper. 4. That the pigment deposited in the livers of rabbits is probably of exogenous origin. PMID:19869536

  11. Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.

    PubMed

    Vali, Mustafa; Vossen, Josephina A; Buijs, Manon; Engles, James M; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Ganapathy-Kanniappan, Shanmugasundaram; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L; Geschwind, Jean-Francois H

    2008-10-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of (14)C-labeled 3-bromopyruvate ([(14)C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [(14)C]3-BrPA on tumor and healthy tissue glucose metabolism by determining (18)F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [(14)C]3-BrPA i.a., 1.75 mM [(14)C]3-BrPA i.v., 20 mM [(14)C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [(14)C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [(14)C]3-BrPA was 1.8 +/- 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [(14)C]3-BrPA was 0.03 +/- 0.01% ID/g. After i.a. administration of [(14)C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [(14)C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit.

  12. Augmentation of Chemotherapeutic Infusion Effect by TSU-68, an Oral Targeted Antiangiogenic Agent, in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Kim, Hyo-Cheol; Chung, Jin Wook Choi, Seung Hong; Im, Seock-Ah; Yamasaki, Yasundo; Jun, Suryoung; Jae, Hwan Jun; Park, Jae Hyung

    2012-02-15

    Purpose: This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model. Methods: This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performed before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections. Results: According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02). Conclusions: Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.

  13. Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

    PubMed Central

    Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

    2016-01-01

    Objective To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). Methods The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. Results The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. Conclusion The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level. PMID:27120181

  14. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    SciTech Connect

    Hingorani, V.; Brecher, P.

    1987-05-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

  15. Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT)

    SciTech Connect

    Chromheecke, M.; Oldhoff, J.; Hoekstra, H.J.; Vermeij, J.; Grond, A.J.K. ); Konings, A.W.T. )

    1993-12-01

    The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. The feasibility of delivering a single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated. 34 refs., 6 figs., 1 tab.

  16. Threshold doses and prediction of visually apparent liver dysfunction after stereotactic body radiation therapy in cirrhotic and normal livers using magnetic resonance imaging

    PubMed Central

    Doi, Hiroshi; Shiomi, Hiroya; Masai, Norihisa; Tatsumi, Daisaku; Igura, Takumi; Imai, Yasuharu; Oh, Ryoong-Jin

    2016-01-01

    The purpose of the present study was to investigate the threshold dose for focal liver damage after stereotactic body radiation therapy (SBRT) in cirrhotic and normal livers using magnetic resonance imaging (MRI). A total of 64 patients who underwent SBRT for liver tumors, including 54 cirrhotic patients with hepatocellular carcinoma (HCC) and 10 non-cirrhotic patients with liver metastases, were analyzed. MRI was performed 3−6 months after SBRT, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1-weighted sequences. All MRI datasets were merged with 3D dosimetry data. All dose distributions were corrected to the biologically effective dose using the linear–quadratic model with an assumed α/β ratio of 2 Gy. The development of liver dysfunction was validly correlated with isodose distribution. The median biologically effective dose (BED2) that provoked liver dysfunction was 57.3 (30.0−227.9) and 114.0 (70.4−244.9) Gy in cirrhotic and normal livers, respectively (P = 0.0002). The BED2 associated with a >5% risk of liver dysfunction was 38.5 in cirrhotic livers and 70.4 Gy in normal livers. The threshold BED2 for liver dysfunction was not significantly different between Child−Pugh A and B patients (P = 0.0719). Moreover, the fractionation schedule was not significantly correlated with threshold BED2 for liver dysfunction in the cirrhotic liver (P = 0.1019). In the cirrhotic liver, fractionation regimen and Child−Pugh classification did not significantly influence the threshold BED2 for focal liver damage after SBRT. We suggest that the threshold BED2 for liver dysfunction after SBRT is 40 and 70 Gy in the cirrhotic and normal liver, respectively. PMID:26983986

  17. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    NASA Astrophysics Data System (ADS)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  18. Enhanced Antitumor Effect of Tirapazamine Delivered Intraperitoneally to VX2 Liver Tumor-Bearing Rabbits Subjected to Transarterial Hepatic Embolization

    SciTech Connect

    Sonoda, Akinaga Nitta, Norihisa Ohta, Shinich Nitta-Seko, Ayumi Nagatani, Yukihiro Takahashi, Masashi Murata, Kiyoshi

    2011-12-15

    Purpose: We evaluated the effects of the combination of Tirapazamine (TPZ), activated preferentially under hypoxic conditions, and gelatin microspheres (GMS) on the tumor growth ratio in rabbits. Methods: We assigned 20 liver tumor-bearing Japanese white rabbits to 4 equal groups. Group 1 received 1 ml of saline intra-arterially (i.a.) and 20 ml of saline intraperitoneally (i.p.; saline group). Group 2 was injected with GMS i.a. and 20 ml saline i.p. (GMS group). Group 3 received 1 ml of saline i.a. and 300 mg/m{sup 2} of TPZ i.p. (TPZ group), and group 4 was treated with GMS i.a. and 300 mg/m{sup 2} of TPZ i.p. (GMS + TPZ group). The infusion of GMS was stopped when the blood flow stagnated. Before and 7 days after treatment, the liver tumor volumes were measured as the total number of pixels on 0.3Tesla (T) magnetic resonance imaging (MRI) scans. Results: The tumor growth ratio (mean {+-} standard deviation) of the saline, GMS, TPZ, and GMS + TPZ groups was 519.15 {+-} 93.78, 279.24 {+-} 91.83, 369.78 {+-} 95.73, and 119.87 {+-} 17.62, respectively. The difference between the GMS + TPZ group and the other groups was statistically significant (P < 0.05). Conclusions: Our results show that the combination of TPZ i.p. and GMS i.a. enhanced the antitumor effect of TPZ. This procedure may represent a new alternative treatment for patients with hepatic cell carcinoma.

  19. Effects of vitamin C and E on liver enzymes and biochemical parameters of rabbits exposed to aflatoxin B1.

    PubMed

    Karakilcik, Ali Ziya; Zerin, Mustafa; Arslan, Oktay; Nazligul, Yasar; Vural, Huseyin

    2004-08-01

    Hepatotoxic substances such as aflatoxin B1 (AFB1) produce free radical reactions during biotransformation damage to liver cells. Vitamins C and E are important natural antioxidants suppressing free radicals. This study investigated the effects of vitamins C and E on liver enzymes and other biochemical parameters in rabbits experimentally exposed to AFB1. The first group was control and fed the diet with dimethyl sulfoxide; the second group received 0.1 mg AFB1/kg diet; the third group received vitamin C (100 mg L-ascorbic acid/kg diet); the fourth group received vitamin E (100 mg alpha-tocopherol/kg diet); and the fifth group received vitamin C+vitamin E (100 mg L-ascorbic acid/kg diet+100 mg alpha-tocopherol/kg diet). Diets of the second, third, fourth and fifth groups were mixed with 0.1 mg AFB/kg diet) and feedings were continued for 10 w. Levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatine phosphokinase and lactate dehydrogenase after receiving AFB1 were significantly increased, while activities of aspartate transaminase, alanine transaminase, amylase, creatine phosphokinase and lactate dehydrogenase in groups receiving AFB1 + vitamins C, E or C+E were significantly lower than that of the AFB1-alone group. Although of the activity of alkaline phosphatase increased with AFB1 exposure, it decreased with vitamin C administration. Levels of urea, triglyceride, cholesterol and albumin were affected by AFB1 and AFB1+vitaminC. AFB1 affected some liver enzymes and other biochemical parameters, but vitamins C, E and C+E partially prevented an increase in these liver enzymes and some the biochemical parameters induced by AFB1.

  20. Fluorodeoxyglucose Positron Emission Tomography Response and Normal Tissue Regeneration After Stereotactic Body Radiotherapy to Liver Metastases

    SciTech Connect

    Stinauer, Michelle A.; Diot, Quentin; Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.

    2012-08-01

    Purpose: To characterize changes in standardized uptake value (SUV) in positron emission tomography (PET) scans and determine the pace of normal tissue regeneration after stereotactic body radiation therapy (SBRT) for solid tumor liver metastases. Methods and Materials: We reviewed records of patients with liver metastases treated with SBRT to {>=}40 Gy in 3-5 fractions. Evaluable patients had pretreatment PET and {>=}1 post-treatment PET. Each PET/CT scan was fused to the planning computed tomography (CT) scan. The maximum SUV (SUV{sub max}) for each lesion and the total liver volume were measured on each PET/CT scan. Maximum SUV levels before and after SBRT were recorded. Results: Twenty-seven patients with 35 treated liver lesions were studied. The median follow-up was 15.7 months (range, 1.5-38.4 mo), with 5 PET scans per patient (range, 2-14). Exponential decay curve fitting (r=0.97) showed that SUV{sub max} declined to a plateau of 3.1 for controlled lesions at 5 months after SBRT. The estimated SUV{sub max} decay half-time was 2.0 months. The SUV{sub max} in controlled lesions fluctuated up to 4.2 during follow-up and later declined; this level is close to 2 standard deviations above the mean normal liver SUV{sub max} (4.01). A failure cutoff of SUV{sub max} {>=}6 is twice the calculated plateau SUV{sub max} of controlled lesions. Parenchymal liver volume decreased by 20% at 3-6 months and regenerated to a new baseline level approximately 10% below the pretreatment level at 12 months. Conclusions: Maximum SUV decreases over the first months after SBRT to plateau at 3.1, similar to the median SUV{sub max} of normal livers. Transient moderate increases in SUV{sub max} may be observed after SBRT. We propose a cutoff SUV{sub max} {>=}6, twice the baseline normal liver SUV{sub max}, to score local failure by PET criteria. Post-SBRT values between 4 and 6 would be suspicious for local tumor persistence or recurrence. The volume of normal liver reached nadir 3

  1. Data on expression of lipoxygenases-5 and -12 in the normal and acetaminophen-damaged liver.

    PubMed

    Suciu, Maria; Gruia, Alexandra T; Nica, Dragos V; Azghadi, Seyed M R; Mic, Ani A; Mic, Felix A

    2016-06-01

    Here we present additional data on the expression of lipoxygenases -5 and -12 in the normal and acetaminophen-damaged liver, which are associated with our manuscript recently published in Chemico-Biological Interactions on lipid metabolism and eicosanoid signaling pathways involved in acetaminophen-induced liver damage in a mouse model (http://dx.doi.org/10.1016/j.cbi.2015.10.019 [1]). It has been demonstrated that the expression of lipoxygenase-5 and leukotriene formation are increased in the livers of rats with carbon tetrachloride (CCl4)-induced cirrhosis (http://dx.doi.org/10.1053/gast.2000.17831 [2]). In addition, the lipoxygenase-12 is known to be expressed in the resident macrophage population of the liver (http://dx.doi.org/10.1016/S0014-5793(99)00396-8 [3]). Mice were injected with acetaminophen, and at 48 h their livers were processed for immunohistochemistry with anti-mouse lipoxygenase-5 and -12 antibodies. At the same time point, the RNA was also extracted from the liver to assess the expression of lipoxygenase-5 and -12 genes via qPCR analysis. Our results show that lipoxygenase-5 expression, but not that of lipoxygenase-12, changes significantly in the acetominophen-damaged liver.

  2. Histological evaluation of high-intensity focused ultrasound with lower-intensity focused ultrasound pre-exposure on the treatment of rabbit VX2 liver tumors

    SciTech Connect

    Zou Hairong; Zou Jianzhong; Wang Yan; Ou Xia

    2012-10-03

    This study was to evaluate the effect of pre-exposure lower-intensity focused ultrasound(US), or LIFU, in high-intensity focused ultrasound(HIFU) ablation of rabbit VX2 liver tumors . Liver VX2 tumor models were established in 30 rabbits, which were divided randomly into two groups. The liver tumors of rabbits in Group A underwent single HIFU ablation; those in Group B were given LIFU exposure before HIFU treatment. Five rabbits from each of the two groups were sacrificed at 0 hours, 3 days, and 7 days after HIFU ablation. Tissue samples that included targeted and short-range sounding (s-RS, within 5 mm of the targeted) and far-range sounding (f-RS, more than 5 mm of the targeted) tissues were observed using light microscope and transmission electron microscopy. The histological examination indicated that not only the targeted tumor cells became irreversible damage, but also the short-range sounding tumors were severely damaged by the HIFU with LIFU pre-exposure in group B. It is concluded that LIFU pre-exposure can enhance the effects of HIFU ablation on the destruction of cell ultrastructures and can enlarge the region of HIFU ablation.

  3. Extrapolation of Normal Tissue Complication Probability for Different Fractionations in Liver Irradiation

    SciTech Connect

    Tai An; Erickson, Beth; Li, X. Allen

    2009-05-01

    Purpose: The ability to predict normal tissue complication probability (NTCP) is essential for NTCP-based treatment planning. The purpose of this work is to estimate the Lyman NTCP model parameters for liver irradiation from published clinical data of different fractionation regimens. A new expression of normalized total dose (NTD) is proposed to convert NTCP data between different treatment schemes. Method and Materials: The NTCP data of radiation- induced liver disease (RILD) from external beam radiation therapy for primary liver cancer patients were selected for analysis. The data were collected from 4 institutions for tumor sizes in the range of of 8-10 cm. The dose per fraction ranged from 1.5 Gy to 6 Gy. A modified linear-quadratic model with two components corresponding to radiosensitive and radioresistant cells in the normal liver tissue was proposed to understand the new NTD formalism. Results: There are five parameters in the model: TD{sub 50}, m, n, {alpha}/{beta} and f. With two parameters n and {alpha}/{beta} fixed to be 1.0 and 2.0 Gy, respectively, the extracted parameters from the fitting are TD{sub 50}(1) = 40.3 {+-} 8.4Gy, m =0.36 {+-} 0.09, f = 0.156 {+-} 0.074 Gy and TD{sub 50}(1) = 23.9 {+-} 5.3Gy, m = 0.41 {+-} 0.15, f = 0.0 {+-} 0.04 Gy for patients with liver cirrhosis scores of Child-Pugh A and Child-Pugh B, respectively. The fitting results showed that the liver cirrhosis score significantly affects fractional dose dependence of NTD. Conclusion: The Lyman parameters generated presently and the new form of NTD may be used to predict NTCP for treatment planning of innovative liver irradiation with different fractionations, such as hypofractioned stereotactic body radiation therapy.

  4. Monitoring of VX2 tumor growth in rabbit liver using T2-weighted and dynamic contrast-enhanced magnetic resonance imaging at 1.5T

    NASA Astrophysics Data System (ADS)

    Jao, Jo-Chi; Mac, Ka-Wai; Chang, Chiung-Yun; Wu, Yu-Chiuan; Hsiao, Chia-Chi; Chen, Po-Chou

    2017-03-01

    This study aimed to investigate the VX2 tumor growth in rabbit liver using T2-weighted imaging (T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Five New Zealand white (NZW) rabbits were implanted with VX2 cell suspension in liver. Afterwards, MRI was performed 7, 14, 21 and 28 days after tumor implantation. A 1.5T clinical MRI scanner was used to perform scans. After 3-plane localizer, T1 weighted imaging (T1WI), T2WI, and DCE-MRI using a three-dimensional gradient echo pulse sequence was performed. After 4 pre-contrast images were acquired, each rabbit was injected i.v. with 0.1 mmol/kg Dotarem. The total scan time after Dotarem administration was 30 minutes. All acquired images were analyzed using ImageJ software. Several regions of interest were selected from the rims of tumor, liver, and muscle. The enhancement ratio (ER) was calculated by dividing the MR signal after Dotarem injection to the MR signal before Dotarem injection. The maximum ER (ER_max) value of tumor for each rabbit was observed right after the Dotarem injection. The T2W MR signal intensities (T2W_SI) and the ER_max values obtained 7, 14, 21 and 28 days after tumor implantation were analyzed with a linear regression algorithm. Both T2W_SI and ER_max of tumors increased with time. The changes for T2W_SI and ER_max of tumors between 7 and 28 days after tumor implantation were 32.66% and 18.14%, respectively. T2W_SI is more sensitive than ER_max for monitoring the growth of VX2 tumor in a rabbit liver model.

  5. Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle: From normal tissue to VX2 tumor.

    PubMed

    Sun, Yao; Xiong, Xiaobing; Pandya, Darpan; Jung, Youngkyoo; Mintz, Akiva; Hayasaka, Satoru; Wadas, Thaddeus J; Li, King C P

    2017-06-28

    High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, (111)In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of (111)In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24h after systematic delivery of (111)In-DOTA-IA in VX2 tumors pretreated by pHIFU compared

  6. Nonsaturable amino acid reabsorption in kidneys of normal and mercury-poisoned rabbits

    SciTech Connect

    Foulkes, E.C.; Blanck, S. )

    1988-11-01

    At high plasma concentrations, a high-capacity, low-affinity or nonsaturable flux (J{sub hc}) accounts for a residual fractional reabsorption of cycloleucine, aspartate, and AIB of approximately 50% of the filtered load in rabbits; J{sub hc} in micromoles per milliliter glomerular filtrate is reduced in Hg-poisoned animals. The nonsaturable flux of cycloleucine is characterized by a transepithelial transit time (TET) of approximately 2 min in control animals; it was consistently much longer in Hg-poisoned animals. The clearance ratio of creatinine/inulin averaged 1.0, and no J{sub hc} could be demonstrated for glucose. We conclude that J{sub hc} is a high-capacity, low-affinity amino acid flux which passes through an intracellular solute pool, and which is sensitive to Hg at both the brush border and the basolateral cell membrane. If calculation of the saturation constants of aspartate reabsorption is restricted to experiments in which U/P <1.0, i.e. where J{sub hc} is unlikely too contribute greatly to reabsorption, values some 20% lower than those previously reported are obtained; the Hg inhibition still is apparently uncompetitive in nature.

  7. Single photon emission computed tomograms of the liver: normal vascular intrahepatic structures.

    PubMed

    Pettigrew, R I; Witztum, K F; Perkins, G C; Johnson, M L; Burks, R N; Verba, J W; Halpern, S E

    1984-01-01

    Because of the high target-to-background contrast obtained with single photon emission computed tomography (SPECT), normal intrahepatic vessels approximately 2 cm in diameter may appear as distinct focal defects in tomographic sections throughout the liver even though normal vessels rarely cause such defects on planar images. To assess this problem, five subjects without evidence of liver disease underwent tomography of the liver with Tc-99m sulfur colloid (TSC) and on a separate occasion tomography of the intrahepatic blood pool with Tc-99m autologous red blood cells (RBC). In each case, well demarcated defects were obvious in contiguous TSC liver tomograms in various planes. Direct comparison with RBC tomograms showed that all of these defects corresponded to intrahepatic veins, typically the right portal vein, its posterior branch, and the left portal vein. Knowledge of the intrahepatic vascular anatomy in a variety of tomographic planes, with examination of each defect in multiple orthogonal planes is necessary to avoid false positive interpretations. In some instances a study with RBC may also be required for more conclusive evaluation of defects seen on TSC liver tomograms.

  8. Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

    SciTech Connect

    McCallum, Gordon P.; Siu, Michelle; Sweeting, J. Nicole; Wells, Peter G.

    2011-01-15

    In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.

  9. Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates.

    PubMed

    McCallum, Gordon P; Siu, Michelle; Sweeting, J Nicole; Wells, Peter G

    2011-01-15

    In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO₃; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation. © 2010 Elsevier Inc. All rights reserved.

  10. Tumor Uptake of Hollow Gold Nanospheres after Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

    PubMed Central

    Tian, Mei; Lu, Wei; Zhang, Rui; Xiong, Chiyi; Ensor, Joe; Nazario, Javier; Jackson, James; Shaw, Colette; Dixon, Katherine A.; Miller, Jennifer; Wright, Kenneth; Li, Chun; Gupta, Sanjay

    2014-01-01

    Purpose This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Materials and Methods Fifteen VX2 tumor-bearing rabbits were randomized into five groups (N=3 in each group) that received either IV 64Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA 64Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated 64Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated 64Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA 64Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 hour after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 hours after injection, and tissues were evaluated for radioactivity. Results At 1 hour after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 hours after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 hours, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 %ID/g vs. 0.099 %ID/g; P < 0.001). Conclusion Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection. PMID:23608932

  11. Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia.

    PubMed Central

    Newman, K D; Dunn, P F; Owens, J W; Schulick, A H; Virmani, R; Sukhova, G; Libby, P; Dichek, D A

    1995-01-01

    Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease. However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype. In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus. Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia. These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology. Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors. Images PMID:8675667

  12. Differential Expression of Matrix-Metalloproteinase-1 and -2 Genes in Normal and Fibrotic Human Liver

    PubMed Central

    Milani, Stefano; Herbst, Hermann; Schuppan, Detlef; Grappone, Cecilia; Pellegrini, Giulia; Pinzani, Massimo; Casini, Alessandro; Calabró, Antonio; Ciancio, Giuseppe; Stefanini, Francesco; Ciancio, Andrew K.; Surrenti, Calogero

    1994-01-01

    Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We investigated levels and cellular sites of gene expression of two major collagebn-degrading enzymes, matrix-metalloproteinase (MMP)-l (fibroblast type-interstitial collagenase)and MMP-2 (72-kd gelatinase, type IV collagenase) in five normal and 18 fibrotic human livers as well as in cultured human hepatic fat-storing cells by Northern blot analysis and in situ hybridization. Fatstoring cells expressed both MMP-1 and MMP-2 RNA in vitro. In vivo, MMP-1 was undetectable in mesenchymal and parenchymal cells of all liver specimens, whereas MMP-2 transcripts were expressed in all livers by vimentin-positive, CD68 negative mesenchymal cells. Mesenchymal cells of all fibrotic livers displayed high transcript levels of transforming growth factor-β1, which is known to modulate MMP expression. Along with de novo fibrogenesis and possibly influenced by transforming growth factor-β1, expression of MMP-2 in the absence of MMP-1 expression may be responsible for the quantitative and qualitative changes of extracellular matrix observed in chronic liver disease. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 7 PMID:8129038

  13. The natural olive constituent oleuropein induces nutritional cardioprotection in normal and cholesterol-fed rabbits: comparison with preconditioning.

    PubMed

    Andreadou, Ioanna; Benaki, Dimitra; Efentakis, Panagiotis; Bibli, Sofia-Iris; Milioni, Alkistis-Ioanna; Papachristodoulou, Anastasia; Zoga, Anastasia; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Iliodromitis, Efstathios K

    2015-06-01

    Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol

  14. Effect of cholera enterotoxin on carbohydrate metabolism in the liver and small intestinal mucosa of rabbits

    SciTech Connect

    Vengrov, P.R.; Cherkasova, T.D.; Yurkiv, V.A.; Pokrovskii, V.I.

    1987-09-01

    The effect of cholera enterotoxin injected in vivo on glucose formation from alanine, and also on glucose-6-phosphatase activity in the liver and mucosa of the small intestine was studied. L-(2,3-/sup 3/H)-alanine was added to the incubation medium. Chromatograms were developed with 5% AgNO/sub 3/ with the addition of an aqueous solution of ammonia. The quantity of radioactive glucose was determined in a scintillation counter.

  15. The fractionation of isolated liver cells from normal and carcinogen treated rats.

    PubMed Central

    Horsfall, A. C.; Ketterer, B.

    1976-01-01

    Suspensions of isolated cells were obtained from livers of normal rats and rats treated with the hepatocarcinogen N,N-dimethyl-4-aminoazobenzene. Differential centrifugation of dispersed cells yielded a large parenchymal cell fraction and a small non-parencymal cell fraction. By means of rate sedimentation through different concnetrations of Ficoll, parenchymal cells were separated into cells with fast, intermediate and slow rates of sedimentation. Periods of sedimentation were brief and centrifugal forces low in order to retain the best possible state of preservation of cells. DNA, RNA and protein contents, acid phosphatase activity, cell size and nucleocytoplasmic ratios of parenchymal cells sedimenting at fast, intermediate and slow rates were measured. Cell fractions from normal livers had properties suggesting that faster sedimenting cells were derived from the centre and middle of the lobule whereas slowly sedimenting cells were periportal; however, much of the periportal cell population remained in a residue of undissociated tissue. Compared with normal cells, carcinogen treated cells appeared to fractionate according to different physical and chemical criteria and could not be related to their origin within the liver lobule. They were smaller, slower sedimenting, lower in protein and RNA content and acid phosphatase activity. The tissue residue contained abnromal histological structures. PMID:814912

  16. Effect of combined therapy of diabinese and nicotinic acid on liver enzymes in rabbits with dithizone-induced diabetes.

    PubMed

    Monago, Comfort C; Onwuka, Frank; Osaro, Erhabor

    2010-01-01

    The effects of diabinese, a known antidiabetic drug, and the combined effects of diabinese and nicotinic acid, a vitamin and antilipidemic drug, were studied in rabbits with dithizone-induced diabetes. Side effects of diabinese include hypoglycemia and liver toxicity. Dithizone was used to induce partial experimental diabetes and to increase blood glucose significantly (P < 0.05) by 31.3%, 23.5%, 19.5, 24.7%, and 23.9% in groups A (single therapy of diabinese 10 mg/kg body weight), B (10 mg of diabinese and nicotinic acid 150 mg/kg), C (10 mg diabinese and nicotinic acid 200 mg/kg), D (10 mg diabinese and nicotinic acid 250 mg/kg) and E control (distilled water 5 mL), respectively. Dithizone administration also increased bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels by 28.9%-35.6%, 41.2%-54.8%, 40.1%-46.1%, and 60.9%-68.4%, respectively. Diabinese monotherapy reduced bilirubin levels, while combined therapy reduced glucose, ALP, AST, and ALT levels more than single therapy. Reduction from the hyperglycemic level 48 hours after drug administration was 20.0%, 24.6%, 41.0%, and 42.0% for groups A, B, C, and D, respectively, and was concentration-dependent. Also, combined therapy produced a significant (P < 0.05) decrease in AST and ALT levels, especially at 72 hours after drug administration, but did not affect ALP levels. No significant changes in glucose, bilirubin, ALP, AST, and ALT levels were observed in Group E (control). This study shows that liver toxicity and the hypoglycemic side effects of diabinese could be managed by the concomitant administration of nicotinic acid.

  17. Precipitating antibodies to rabbit thymus extractable antigens in chronic liver disease: relationship with anti-actin antibodies.

    PubMed Central

    Cassani, F; Fusconi, M; Bianchi, F B; Selleri, L; Baffoni, L; Lenzi, M; Pisi, E

    1987-01-01

    Using counterimmunoelectrophoresis (CIE), serum antibodies to rabbit thymus extractable antigens were detected in 15% (38/259) of patients with chronic liver disease (CLD) of various aetiologies and 33% (41/124) of patients with miscellaneous connective tissue diseases (CTD). A remarkable diversity of precipitating systems was apparent among cases with the two classes of disorders. All the five systems found in CLD (XR, XR2, SS-B, XR3, XR4) were associated mostly with immunological hepatic disorders. In the 52 autoimmune hepatitis cases, XR was mainly detected (29%), whereas in the 82 primary biliary cirrhosis patients the whole spectrum of reactivities was represented (XR: 11%, XR2: 10%, SS-B and XR3: 2% each, XR4: 1%). XR proved to be closely associated with smooth muscle antibodies (SMA, detected by indirect immunofluorescence on rat kidney sections) both qualitatively and quantitatively. Since all SMA positive sera with anti-actin specificity (SMAT, SMAG) were XR positive and purified actin could absorb out XR CIE reactivity, the hypothesis is made that a cross-reaction occurs between XR antigen and actin epitope(s). Images Fig. 1 PMID:3308218

  18. The action of progesterone and diethylstilboestrol on the dehydrogenase and esterase activities of a purified aldehyde dehydrogenase from rabbit liver.

    PubMed Central

    Julian, R; Duncan, S

    1977-01-01

    A steroid-sensitive aldehyde dehydrogenase (EC 1.2.1.3) was purified from rabbit liver and is homogeneous by the criterion of electrophoresis in polyacrylamide gels with or without sodium dodecyl sulphate. The enzyme is tetrameric, of subunit mo.wt. 48 300, and contains no tightly bound zinc. The fluorescence of the protein is decreased in the presence of progesterone, which is inhibitory to the reactions catalysed by the enzyme. When NADH is bound to the enzyme, the fluorescence of the coenzyme is augmented to an extent independent of the presence of steroids or acetaldehyde. The purified enzyme catalyses the oxidation of acetaldehyde and glucuronolactone, and the hydrolysis of 4-nitrophenyl acetate. Each of these reactions is inhibited by progesterone in such a manner as to suggest the formation of a catalytically active enzyme-hormone complex. Diethylstilboestrol inhibits the hydrolysis of esters by this enzyme, but stimulates the oxidation of aldehydes, except at low aldehyde concentrations; the ligand is then inhibitory. NADH inhibits the hydrolysis of 4-nitrophenyl acetate by the enzyme in a partially competitive fashion. PMID:192192

  19. The isolation, identification and synthesis of two metabolites of guanethidine formed in pig and rabbit liver homogenates

    PubMed Central

    Abramson, F. B.; Furst, C. I.; McMartin, C.; Wade, Roy

    1969-01-01

    1. Two metabolites of radioactively labelled guanethidine were isolated from rabbit and pig liver homogenates by ion-exchange chromatography on a sulphonic acid resin. 2. One of the metabolites was eluted from the column with ammonia and identified as 2-(6-carboxyhexylamino)ethylguanidine on the basis of the elemental analysis, i.r. spectrum and pH titration curve of the pure compound, and the observed partial loss of tritium for ring-labelled guanethidine during the formation of this metabolite. 3. This identification was confirmed by synthesis. 4. 2-(6-Carboxyhexylamino)ethylguanidine underwent ring-closure in hot alkaline solution to 1-(6-carboxyhexyl)-2-iminoimidazolidine. 5. The other metabolite of guanethidine was eluted from the ion-exchange column with 6m-hydrochloric acid along with the unchanged drug. It was purified by countercurrent distribution and shown to be identical with synthetic guanethidine N-oxide. 6. The two metabolites and the product of ring-closure had less than one-tenth of the antihypertensive activity of guanethidine in the renal-hypertensive rat and are unlikely to contribute to the pharmacological properties of the drug. PMID:5806387

  20. Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model

    SciTech Connect

    Gupta, Sanjay Wright, Kenneth C.; Ensor, Joe; Van Pelt, Carolyn S.; Dixon, Katherine A.; Kundra, Vikas

    2011-10-15

    Objectives: The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods: Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results: The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions: Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.

  1. Side effects of immunization with liver attenuated Trypanosoma cruzi in mice and rabbits.

    PubMed Central

    Basombrío, M A; Besuschio, S; Cossio, P M

    1982-01-01

    Immunity against lethal, bloodstream forms of Trypanosoma cruzi was achieved in mice by preinoculation of approximately equal to 10(5) culture epimastigotes of an attenuated T. cruzi strain (TCC). The risks of TCC inoculation in terms of pathogenicity or eventual increase in virulence of TCC progeny were evaluated. No pathogenic parasites could be selected from TCC progeny by either mouse, triatome, or culture passages. Immunizing doses of live TCC did not induce in adult mice alterations resembling chronic Chagas' disease, as judged by patterns of mortality, tissue damage, autoantibodies, or parasite recovery. On the basis of the same criteria, However, a remarkable similarity could be established between the disease caused in mice by inoculation of low numbers (10(2)) of pathogenic trypomastigotes and human chronic Chagas' disease. Although patent parasitemias were never revealed in fresh blood mounts obtained from TCC-inoculated mice, a few hemocultures and xenodiagnoses gave positive results, particularly soon after inoculations at birth. The parasites recovered by either method remained in the attenuated, epimastigote stage. In rabbits, no local lesions, fever, weight loss, or histopathological alterations were detected after subcutaneous inoculation of 10(7) TCC organisms, although one fifth of the animals yielded positive hemocultures of epimastigotes. The contrasting host response to cultured epimastigotes as compared with blood trypomastigotes indicates that, in experimental Chagas' disease, immunoprotection is not necessarily associated with immunopathology. Images PMID:6804389

  2. Cellular Organization of Normal Mouse Liver: A Histological, Quantitative Immunocytochemical, and Fine Structural Analysis

    PubMed Central

    Baratta, Janie L.; Ngo, Anthony; Lopez, Bryan; Kasabwalla, Natasha; Longmuir, Kenneth J.; Robertson, Richard T.

    2009-01-01

    The cellular organization of normal mouse liver was studied using light and electron microscopy and quantitative immunocytochemical techniques. The general histological organization of the mouse liver is similar to livers of other mammalian species, with a lobular organization based on the distributions of portal areas and central venules. The parenchymal hepatocytes were detected with immunocytochemical techniques to recognize albumin or biotin containing cells. The macrophage Kupffer cells were identified with F4-80 immunocytochemistry, Ito stellate cells were identified with GFAP immunocytochemistry, and endothelial cells were labeled with the CD-34 antibody. Kupffer cells were labeled with intravascularly administered fluorescently labeled latex microspheres of both large (0.5 μm) and small (0.03 μm) diameters, while endothelial cells were labeled only with small diameter microspheres. Neither hepatocytes nor Ito stellate cells were labeled by intravascularly administered latex microspheres. The principal fine structural features of hepatocytes and non-parenchymal cells of mouse liver are similar to those reported for rat. Counts of immunocytochemically labeled cells with stained nuclei indicated that hepatocytes constituted approximately 52% of all labeled cells, Kupffer cells about 18%, Ito cells about 8%, and endothelial cells about 22% of all labeled cells. Approximately 35% of the hepatocytes contained two nuclei; none of the Kupffer or Ito cells were double nucleated. The presence of canaliculi and a bile duct system appear similar to that reported for other mammalian species. The cellular organization of the mouse liver is quite similar to that of other mammalian species, confirming that the mouse presents a useful animal model for studies of liver structure and function. PMID:19255771

  3. Effect of benzalkonium chloride/EDTA on the ocular bioavailability of ketorolac tromethamine following ocular instillation to normal and de-epithelialized corneas of rabbits.

    PubMed

    Madhu, C; Rix, P J; Shackleton, M J; Nguyen, T G; Tang-Liu, D D

    1996-04-01

    This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formulations was measured in flow-through perfusion chambers. For in vivo studies, a 35 microL dose of 0.5% ketorolac tromethamine with or without BAK/EDTA was instilled into rabbit eyes with intact or de-epithelialized corneas. At 0.5, 1, 2, 4, 6, and 8 h postdose, rabbits were euthanized, and the corneas and aqueous humor were collected from both eyes. The ketorolac concentrations from both in vivo and in vitro samples were quantified by reversed-phase high-performance liquid chromatography. The in vitro study results indicated that BAK/EDTA statistically significantly increased the Focular of ketorolac through de-epithelialized corneas but not through intact corneas. The in vivo study results showed that BAK/EDTA had no effect on the Focular of ketorolac in rabbits with intact corneas, based on the values of the area under the aqueous humor concentration versus time curves (AUC0-6h) of ketorolac. As expected, de-epithelialization of the corneas produced a faster and greater ocular absorption of ketorolac as evidenced by the smaller Tmax and larger AUC values compared to those for the intact corneas in vivo. However, BAK/EDTA decreased the ocular absorption of ketorolac in rabbits with de-epithelialized corneas. The half-lives (t 1/2) of ketorolac in corneal tissue and aqueous humor were longer in rabbits with intact corneas than those in rabbits with de-epithelialized corneas. In conclusion, the in vivo Focular of ketorolac was not altered by BAK/EDTA in rabbits with intact corneas, but it was decreased by BAK/EDTA in rabbits with de-epithelialized corneas. Therefore, the formulation with ketorolac alone may be better as a post-operative ocular analgesic.

  4. Rebamipide increases mucin-like substance contents and periodic acid Schiff reagent-positive cells density in normal rabbits.

    PubMed

    Urashima, Hiroki; Takeji, Yasuhiro; Okamoto, Takashi; Fujisawa, Shigeki; Shinohara, Hisashi

    2012-06-01

    The effects of rebamipide on the number of periodic acid Schiff reagent (PAS)-positive cells in the conjunctiva, the mucin content in the cornea and conjunctiva of normal rabbits, and desiccation-induced corneal damage in vivo were examined. Rebamipide (0.1%-3%) was applied 6 times a day for 14 days, and the PAS-positive cell count in the bulbar conjunctiva was measured by impression cytology. The amount of conjunctival and corneal mucin-like substances was measured by Alcian blue binding. The corneal damage model was created by desiccation from air flow at room temperature. The level of corneal damage was determined by scoring the area stained with rose bengal and fluorescein dye. Rebamipide increased the number of PAS-positive cells in the conjunctiva when instilled at concentrations of 0.3% or higher, and 1% rebamipide increased the amount of mucin-like substances of the conjunctiva and cornea. Moreover, 1% rebamipide was also found to lower the rose bengal scores of the cornea in the corneal damage model by desiccation. Rebamipide is a possible candidate drug for treatment of cornea and conjunctival epithelial damage due to its mucin-like substance increasing action, for instance, in the treatment of dry eye disease.

  5. Analysis of rabbit doe longevity using a semiparametric log-Normal animal frailty model with time-dependent covariates

    PubMed Central

    Sánchez, Juan Pablo; Korsgaard, Inge Riis; Damgaard, Lars Holm; Baselga, Manuel

    2006-01-01

    Data on doe longevity in a rabbit population were analysed using a semiparametric log-Normal animal frailty model. Longevity was defined as the time from the first positive pregnancy test to death or culling due to pathological problems. Does culled for other reasons had right censored records of longevity. The model included time dependent covariates associated with year by season, the interaction between physiological state and the number of young born alive, and between order of positive pregnancy test and physiological state. The model also included an additive genetic effect and a residual in log frailty. Properties of marginal posterior distributions of specific parameters were inferred from a full Bayesian analysis using Gibbs sampling. All of the fully conditional posterior distributions defining a Gibbs sampler were easy to sample from, either directly or using adaptive rejection sampling. The marginal posterior mean estimates of the additive genetic variance and of the residual variance in log frailty were 0.247 and 0.690. PMID:16635450

  6. Methylation of tRNA by normal mouse liver and Erhlich ascites cell extracts

    SciTech Connect

    Smith, S.D.; Sitz, T.O.

    1986-05-01

    When Erhlich ascites tumor and normal mouse liver extracts were incubated with (/sup 3/H-CH/sub 3/)-S-adenosylmethionine and E. coli tRNA, the tumor extracts had a ten-fold higher methyltransferase activity than mouse liver extracts. However, only a two-fold higher methyltransferase activity was observed when methyl deficient mouse liver tRNA was used as a substrate. DEAE-Sephadex chromatography of alkaline hydrolysates of methyl deficient mouse liver tRNA (tRNA isolated from mice treated with ethionine) showed 70% of the /sup 3/H-methyl groups in the mononucleotide peak and 30% in alkaline stable di-, tri- and oligonucleotide peaks demonstrating methylation of both the base and ribose moieties. Perchloric acid digest of material isolated from the di-, tri- and oligonucleotide peaks confirm that the /sup 3/H-methyl groups are on the ribose moieties. In hydrolysates of E. coli tRNA /sup 3/H-methyl groups appeared in only the mononucleotide peak, i.e. only base methylation. These data, from Erhlich ascites cells, suggest that ribose methyltransferases may have greater RNA substrate specificity than the base methyltransferases and may act processively to produce alkaline stable oligonucleotides.

  7. Expression of constitutive heat shock protein-70 in normal (non-stressed) rabbit urinary bladder tissue.

    PubMed

    Zhao, Y; Levin, R M; Monson, F C; Chacko, S

    1993-04-07

    The expression of constitutive HSP-70 in the urinary bladder was determined by SDS-PAGE and western blotting using a mouse monoclonal antibody against HSP-70. The western blot analysis showed that the mouse anti-HSP-70 cross-reacted with a 70 kDa protein present in the extracts of the urinary bladder muscle and mucosa. Densitometric scanning of the western blots allowed us to specifically quantitate the relative amounts of the HSP-70. The quantitation of the HSP-70 by combining immunoblotting and densitometry using a laser scanner is reproducible and this technique requires only a small amount of tissue. The amounts of HSP-70 can be estimated from a standard curve of nanogram(ng) of HSP-70 vs absorption from the immunoblots. The amounts of HSP-70 in the muscular and mucosal layers in the body of the urinary bladder are more than those in the base of the bladder. The presence of HSP-70 in the muscle and mucosal epithelium of the bladder was demonstrated by immunohistochemical analysis of freshly removed tissue from the base and the body of bladder from normal animals.

  8. Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis.

    PubMed

    Bardou-Jacquet, Edouard; Philip, Julie; Lorho, Richard; Ropert, Martine; Latournerie, Marianne; Houssel-Debry, Pauline; Guyader, Dominique; Loréal, Olivier; Boudjema, Karim; Brissot, Pierre

    2014-03-01

    Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE-related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology. Patients (n=18) homozygous for the p.Cys282Tyr mutation in the HFE gene underwent LT between 1999 and 2008. Serum iron, serum hepcidin, and hepatic iron concentrations were determined before LT and at the end of follow-up (median 57 months). Mortality and causes of death were determined. Survival was compared to that of the overall patient population that received LT. Before LT, serum hepcidin levels were low (0.54 ± 2.5 nmol/L; normal range: 4-30 nmol/L). After LT, 11 patients had iron evaluations; none received iron depletion therapy; all had normal transferrin saturation. The mean serum ferritin was 185 (± 99) μg/L. Magnetic resonance imaging showed that iron overload was absent in nine patients, mild in one patient with metabolic syndrome, and high (180 μmol/g) in one patient with hereditary spherocytosis discovered after LT. At the end of follow-up, serum hepcidin was normal in 10 patients (11.12 ± 7.6 nmol/L; P<0.05) and low in one patient with iron deficiency anemia. Survival was 83% and 67% at 1 and 5 years, respectively. Survival was similar for patients with HH and patients that received LT for other causes. In HH, LT normalized hepcidin secretion and prevented recurrence of hepatic iron overload. Survival was similar to that of patients who received LTs for other liver diseases. © 2014 by the American Association for the Study of Liver Diseases.

  9. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats.

    PubMed

    Zhao, Z G; Zhang, L L; Niu, C Y; Zhang, J

    2014-02-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis.

  10. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    PubMed Central

    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

    2014-01-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis. PMID:24519128

  11. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

    PubMed Central

    Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B.; Janmey, Paul A.; Wells, Rebecca G.

    2016-01-01

    Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver. PMID:26735954

  12. Imaging of the postoperative liver: review of normal appearances and common complications.

    PubMed

    Mulé, S; Colosio, A; Cazejust, J; Kianmanesh, R; Soyer, P; Hoeffel, C

    2015-10-01

    Several benign and malignant liver diseases may require surgical treatment for cure, including anatomical resections based on the segmental anatomy of the liver, non-anatomical (wedge) resections, and surgical management of biliary cysts. The type of surgery depends not only on the location and the nature of the disease, but also on the expertise of the surgeon. Whereas ultrasonography is often the first-line imaging examination in case of suspected postoperative complication, multidetector computed tomography (MDCT) is of greater value for identifying normal findings after surgery, early postoperative pathologic fluid collections and vascular thromboses, and tumor recurrence in patients who have undergone hepatic surgery. Magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice for depicting early postoperative bile duct injuries and ischemic cholangitis that may occur in the late postoperative phase. Both MDCT and MRCP can accurately depict tumor recurrence. Radiologists should become familiar with these surgical procedures to better understand postoperative changes, and with the normal imaging appearances of various postoperative complications to better differentiate between complications and normal findings.

  13. Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal.

    PubMed

    Vatarescu, Maayan; Bechor, Sapir; Haim, Yulia; Pecht, Tal; Tarnovscki, Tanya; Slutsky, Noa; Nov, Ori; Shapiro, Hagit; Shemesh, Avishai; Porgador, Angel; Bashan, Nava; Rudich, Assaf

    2017-06-01

    Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages. © 2017 The authors.

  14. Antioxidant activity of white rice, brown rice and germinated brown rice (in vivo and in vitro) and the effects on lipid peroxidation and liver enzymes in hyperlipidaemic rabbits.

    PubMed

    Mohd Esa, Norhaizan; Abdul Kadir, Khairul-Kamilah; Amom, Zulkhairi; Azlan, Azrina

    2013-11-15

    Antioxidant activity of different rice extract and the effect on the levels of antioxidant enzyme activity, superoxide dismutase (SOD) and glutathione peroxidase (GPx), vitamin E, lipid peroxidation and liver enzymes in hyperlipidaemia rabbits were investigated. Germinated brown rice (GBR) has the highest antioxidant activity compared to white rice (WR) and brown rice (BR). All rice grains increased the activity of SOD and GPx. However, vitamin E levels increased only in the groups that received the BR and GBR diets. The reduction of lipid peroxidation levels and activity of hepatic enzymes (alanine transferase, ALT and aspartate transaminase, AST) were only significantly observed in the GBR group. In conclusion, GBR supplementation has the greatest impact on increasing antioxidant enzyme activity and vitamin E level and on reducing lipid peroxidation in hypercholesterolaemia rabbit, thereby preventing the formation of atherosclerotic plaques. Furthermore, GBR diet can also reduce the level of hepatic enzymes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Chronological changes of radiofrequency ablation zone in rabbit liver: an in vivo correlation between gross pathology and histopathology.

    PubMed

    Song, Kyoung D; Lee, Min Woo; Rhim, Hyunchul; Kang, Tae Wook; Cha, Dong Ik; Yang, Jehoon

    2017-03-01

    To examine the gross pathology and histopathology of ablation zones created from radiofrequency (RF) ablation and to correlate their chronological changes. A total of 48 in vivo ablation zones (16 rabbit livers) were obtained immediately after and also 30 min, 1 h and 2 h after RF ablation and were subjected to haematoxylin and eosin (H&E) staining, nicotinamide adenine dinucleotide (NADH) diaphorase staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. Chronological changes in gross pathology and histopathology were evaluated and correlated with each other. Peripheral red zones on gross pathology correlated with peripheral zones on H&E staining, lightly stained peripheral zones on NADH staining and peripheral positive zones on TUNEL staining. Central white zones on gross pathology correlated with combined central and border zones on H&E staining, central negative zones on NADH staining and combined central-positive and middle-negative zones on TUNEL staining. Boundary visibility between central white and peripheral red zones on gross pathology was significantly higher at 1 and 2 h than immediately after RF ablation. As time increased after RF ablation, visibility of the border zone on H&E staining and the grade of positively stained hepatocytes in the peripheral zone on TUNEL staining increased. Chronological changes in gross pathology of RF ablation zones correlated well with histopathology. The boundary between the central white and peripheral red zones tended to become clear at 1 h after RF ablation. Advances in knowledge: (1) RF ablation zones show chronological changes on gross pathology and histopathology. (2) Gross pathology and histopathology correlate well with each other.

  16. Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line

    PubMed Central

    Tsuji, P. A.; Walle, T.

    2008-01-01

    Many flavonoids have been shown to possess prooxidant properties, capable of causing oxidative stress, especially at larger doses. Here, we examined the potential cell toxicity caused by exposure to the hydroxylated flavones chrysin, apigenin, luteolin and quercetin in comparison to the methylated flavones 5,7-dimethoxyflavone and 3’,4’-dimethoxyflavone in normal rainbow trout hepatocytes. The hydroxylated flavones, especially chrysin, demonstrated cell toxicity and inhibition of DNA synthesis at very low (2 μM) concentrations. The cytotoxicity of chrysin may partially be due to its metabolism by myeloperoxidase, which was shown to be present in these normal trout liver cells (164 pmol/min/mg protein). In contrast, methylated flavones showed no significant metabolism by myeloperoxidase and no signs of toxicity, even at much higher concentrations. These results may be useful for further investigations of cytotoxicity of dietary flavonoids. PMID:17884029

  17. Effects of diagnostic ultrasound-targeted microbubble destruction on permeability of normal liver in rats.

    PubMed

    Yang, Dan; Tan, Kai-Bin; Gao, Yun-Hua; Liu, Hong; Yang, Wei-Xiao

    2012-12-01

    This work investigated the effect of diagnostic ultrasound-targeted microbubble destruction (UTMD) on the permeability of normal liver tissue and the safety of this technique. One hundred and four rats were divided into four groups: the control group, the microbubble-only (MB) group, the ultrasound-only (US) group, and the ultrasound-targeted microbubble destruction group (UTMD). The permeabilities of capillaries and cell membranes were determined using Evans blue and lanthanum nitrate as tracers, respectively. The amount of Evans blue was approximately fourfold higher in the UTMD group than in the control, MB-only, and US-only groups (all P<0.01). Evans blue extravasation, visualized as red fluorescence, was detectable by laser confocal scanning microscopy in the parenchyma only in the UTMD group. Lanthanum nitrate-tracing transmission electron microscopy examination indicated that intracellular lanthanum was detectable in the cytoplasm only in the UTMD group. Blood chemical analysis indicated that the effect of diagnostic ultrasound-targeted microbubble destruction on the rats' serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was transient and recoverable and that this technique had no obvious effect on renal function. Cellular swelling was observed in liver cells in the UTMD group at 0.5 h, but this swelling was no longer apparent after 1 week. These results suggest that diagnostic ultrasound-targeted microbubble destruction can increase the capillary and cell membrane permeabilities in normal liver tissue without a significant increase in hepatic and renal toxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Expression of CYP1A1 and CYP1A2 in the liver and kidney of rabbits after prolonged infusion of propofol.

    PubMed

    Campos, Sónia P; de Lurdes Pinto, Maria; Gomes, Gabriela; de Pinho, Paula Guedes; Monteiro, Joaquim A; Félix, Luis M; Branco, Paula S; Ferreira, Luísa M; Antunes, Luís M

    2016-10-01

    Propofol biotransformation occurs in the liver via hydroxylation by CYP450 enzymatic complex and by glucuronidation, however extra-hepatic metabolism has also been described. To better understand the metabolic pathways involved in propofol biotransformation, the expression of CYP1A1, CYP1A2, the enzymatic and non-enzymatic antioxidant activity and the amount of propofol and its non-conjugated metabolites were investigated. Twenty-one NewZealand rabbits were allocated into three groups continuously treated for 20h. Each group received: NaCl 0.9%, vehicle (SMOFlipid) and propofol 2% (Lipuro). At the end, liver and kidney samples were collected for histopathology and immunohistochemistry and plasma for quantification of propofol and its metabolites. CYP1A1 and CYP1A2 were observed in zone 1 and zone 3 regions of the liver acinus. The propofol and saline groups showed a higher expression of CYP1A1 when compared to vehicle group. Propofol significantly increased CYP1A2 expression, compared to saline. CYP1A1 and CYP1A2 immunoexpression were observed in the kidney but no differences were registered between groups. This suggests that propofol may act as selective inhibitor of CYP1A1 and an inducer of CYP1A2 expression in different regions of the liver. Propofol seems to have an antioxidative protective effect on liver parenchyma, comparatively to the emulsion alone. In the rabbit, extra-hepatic propofol biotransformation may also occur in the kidney. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  20. Preventative effects of prostaglandin E1 in combination with iodized olive oil on liver fibrosis after transcatheter arterial chemoembolization in a rabbit model of CCl4-induced liver fibrosis.

    PubMed

    Jin, Shuqiang; Cao, Haili; Wang, Kaibing; Li, Ying; Bai, Bin

    2015-06-01

    To explore the preventative effects of prostaglandin E1 (PGE1) on a rabbit model of CCl4-induced liver fibrosis after transcatheter arterial chemoembolization (TACE), we generated a rabbit model of CCl4-induced liver fibrosis by treatment with 40% CCl4 in iodized olive oil for 16 weeks. Body mass and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), albumin:globulin ratio (A:G), total bilirubin (TBIL), and direct bilirubin (DBIL) were measured. After TACE, the levels of hyaluronic acid (HA), procollagen III (PC III), laminin (LN), and collagen IV (IV-C) were measured, and the severity of liver fibrosis as well as the morphology of liver tissues were determined. Body mass in the model group was significantly decreased from 10 to 16 weeks, and the serum levels of ALT, AST, TP, TBIL, and DBIL levels were significantly increased while the model was being generated; the levels of ALB and A:G were significantly decreased. After TACE, serum levels of HA, PC III, and LN in the group injected with 1.0 mL iodized olive oil (Group B) were higher than in the group that were injected with 1.0 mL iodized olive oil + 0.2 mL PGE1 (Group C), whereas the serum levels of IV-C were lower. The severity of liver fibrosis was ameliorated in Group C. The combination of PGE1 and iodized olive oil prevented the development of liver fibrosis following TACE.

  1. [Factors related to renal dysfunction after liver transplantation in patients with normal preoperative function].

    PubMed

    Koo, M; Sabaté, A; Ramos, E; Dalmau, A; León, E; Fabregat, J; Rafecas, A

    2006-11-01

    To determine perioperative factors related to postoperative renal dysfunction in patients receiving liver transplants who had normal renal function before surgery. We analyzed the cases of 189 consecutive patients. Patients with hepatorenal syndrome and previously diagnosed renal insufficiency were excluded, as were patients undergoing a second transplant operation. Postoperative renal dysfunction was diagnosed when creatinine levels exceeded 1.5 mg x dL(-1) in the first postoperative week. Multivariate analysis of preoperative variables (patient characteristics; Child-Pugh score; status with the United Network for Organ Sharing; and sodium, coagulation, hemoglobin, and creatinine levels); intraoperative variables (blood product units required, duration of surgery, reperfusion syndrome, surgical technique, and crystalloids required); and postoperative variables (hemodialysis or filtration, reoperation, mortality, creatinine levels at 6 and 12 months). One hundred fifty patients with normal kidney function were included. Postoperative renal dysfunction developed in 45 (30%). Differences between patients with and without postoperative renal dysfunction were found for weight; sex; Child-Pugh score; blood transfusion requirements (mean [SD] of 2.36 [2.4] units of packed red cells in the group of patients with renal dysfunction vs 1.3 [1.8] in the patients with normal function); and reperfusion syndrome (26 [66.7%] patients with renal dysfunction and 35 [21.5%] without). The last 2 variables continued to be significantly correlated with renal dysfunction in the multivariate analysis with a relative risk of 1.25, (95% confidence interval [CI], 1.01-1.55) for units of blood transfusion and 2.41 (95% CI, 1.04-5.57) for reperfusion syndrome. Renal replacement therapy was used in 4 patients (2.7%). Mortality rates were similar. At 6 and 12 months, 26 (17.3%) and 18 (12%) patients had renal dysfunction. Acute renal dysfunction is a frequent complication following a liver

  2. 78 FR 5817 - Detecting and Evaluating Drug-Induced Liver Injury; What's Normal, What's Not, and What Should We...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... Normal, What's Not, and What Should We Do About It?; Public Conference; Request for Comments AGENCY: Food... Evaluating Drug-Induced Liver Injury; What's Normal, What's Not, and What Should We Do About It?'' This... prevented the approval of others. It ] discusses methods of detecting DILI by periodic tests of serum enzyme...

  3. L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets.

    PubMed

    Diaz, M; Lopez, F; Hernandez, F; Urbina, J A

    2000-06-01

    L-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of L-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL + LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of L-carnitine on this parameter. The reduction of total cholesterol in VLDL + LDL particles in animals fed a cholesterol-rich diet plus L-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. L-Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18 fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol

  4. Combining dynamic contrast enhanced magnetic resonance imaging and microvessel density to assess the angiogenesis after PEI in a rabbit VX2 liver tumor model.

    PubMed

    Chen, Juan; Qian, Ting; Zhang, Huanhuan; Wei, Chunxiao; Meng, Fanhua; Yin, Huabin

    2016-02-01

    To evaluate the correlation between parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and microvessel density (MVD) measurements in rabbit VX2 liver tumor models after percutaneous ethanol injection (PEI) and to observe influence of PEI on angiogenesis in a rabbit VX2 liver tumor model with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Forty five New Zealand white rabbits were used in this study. VX2 tumor tissue blocks were implanted in the left lobe of liver by percutaneous puncture under CT guidance. 2 weeks later, all rabbits underwent conventional MRI (T1WI, T2WI) to determine the successful models. Then those successful implanted VX2 liver tumor models in the study were randomly divided into the control group and the experimental group, the former did not have processing, and the latter underwent PEI under CT guidance. MRI (T1WI, T2WI and DCE-MRI) was performed 1 week later again, the parameters of DCE-MRI (Ktrans, Kep, Ve and iAUC60) of viable tumor portions were observed. Then all the liver samples were processed for hematoxylin and eosin (H&E) staining and immunohistochemical staining for CD31 to determine MVD. At last, data (including DCE-MRI perfusion parameters and MVD) were compared between experimental and control groups, correlation of DCE-MRI perfusion parameters and MVD was evaluated. Twenty six VX2 liver tumor models underwent all examinations (thirteen models for each group) 1 week later after PEI. For the experimental group, the parameters Ktrans (r=0.6382, P=0.0189) and iAUC60 (r=0.6591, P=0.0143) in viable tumor portions were positively moderately correlated with MVD, whereas the parameters Kep (r=0.4656, P=0.1088) and Ve (r=0.2918, P=0.3333) were not correlated with MVD. For the control group, the parameters Ktrans (r=0.6385, P=0.0188) and iAUC60 (r=0.6391, P=0.0187) in viable tumor portions were also positively moderately correlated with MVD, while the parameters Kep (r=0.5518, P=0.0506) and Ve (r

  5. Evaluation of 70-150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model.

    PubMed

    Gholamrezanezhad, Ali; Mirpour, Sahar; Geschwind, Jean-Francois H; Rao, Pramod; Loffroy, Romaric; Pellerin, Olivier; Liapi, Eleni A

    2016-10-01

    To evaluate the pharmacokinetic profile (PK) and embolization effect of 70-150-μm doxorubicin eluting beads (DEBs) following intra-arterial injection (i.a.) in the rabbit liver VX2 tumour model. In this ACUC-approved study, 25 white New Zealand rabbits were randomly assigned into a small DEB group (SDB, n = 7, 70-150-μm DEBs), large DEB group (LDB, n = 7, 100-300-μm DEBs), untreated controls (n = 7), and doxorubicin controls (n = 4, without tumour, received i.a. 12.5 mg doxorubicin). Plasma PK was assessed up to 180 min post-injection. Drug tissue and liver enzyme levels, radiologic tumor response and histopathologic tumour necrosis were assessed at 7 days. Mean tumour doxorubicin concentrations were 922.83 nM (SD = 722.05) and 361.48 nM (SD = 473.23) for the SDB and LDB, respectively (p = 0.005). There was no statistically significant difference in tumour doxorubicinol, plasma doxorubicin and doxorubicinol PK values. More beads were observed in the SDB tumours (p = 0.01). Liver enzymes increased and gradually declined over the observation period, with significantly higher values in the SDB. In this preclinical study, plasma PK of i.a.-injected 70-150-μm DEBs was not different than that of 100-300-μm DEBs. More beads and higher tissue doxorubicin levels were observed in the SDB tumours. • Small and large doxorubicin-eluting beads show similar plasma pharmacokinetic profiles. • Higher tissue doxorubicin levels were observed in the small bead group. • Liver enzymes were overall significantly higher in the small bead group.

  6. Lipocytes from normal rat liver release a neutral metalloproteinase that degrades basement membrane (type IV) collagen.

    PubMed Central

    Arthur, M J; Friedman, S L; Roll, F J; Bissell, D M

    1989-01-01

    We report a proteinase that degrades basement-membrane (type IV) collagen and is produced by the liver. Its cellular source is lipocytes (fat-storing or Ito cells). Lipocytes were isolated from normal rat liver and established in primary culture. The cells synthesize and secrete a neutral proteinase, which by gelatin-substrate gel electrophoresis and gel filtration chromatography, has a molecular mass of 65,000 D. The enzyme is secreted in latent form and is activated by p-aminophenylmercuric acetate but not by trypsin. Enzyme activity in the presence of EDTA is restored selectively by zinc and is unaffected by serine-protease inhibitors. In assays with radiolabeled soluble substrates, it degrades native type IV (basement membrane) collagen but not interstitial collagen types I or V and exhibits no activity against laminin or casein. At temperatures causing partial denaturation of soluble collagen in vitro, it rapidly degrades types I and V. Thus, it is both a type IV collagenase and gelatinase. The enzyme may play a role in initiating breakdown of the subendothelial matrix in the Disse space as well as augmenting the effects of collagenases that attack native interstitial collagen. Images PMID:2551922

  7. Effects of superparamagnetic iron oxide on radio-frequency-induced temperature distribution: in vitro measurements in polyacrylamide phantoms and in vivo results in a rabbit liver model.

    PubMed

    Merkle, E M; Goldberg, S N; Boll, D T; Shankaranarayanan, A; Boaz, T; Jacobs, G H; Wendt, M; Lewin, J S

    1999-08-01

    To determine whether contrast medium containing superparamagnetic iron oxide (SPIO) alters radio-frequency (RF)-related temperature distribution in acrylamide phantoms and in an in vivo model. In nine acrylamide phantoms with increasing SPIO content, RF was applied with simultaneous measurement of temperature profile along the probe track. Additionally, magnetic resonance imaging-guided RF ablation was performed in the liver of six rabbits after the intravenous administration of SPIO (0.05 mL per kilogram of body weight) 40 minutes prior to ablation (SPIO group) and in another six rabbits without prior SPIO administration (control group). Coagulation diameter was evaluated on the basis of postprocedural imaging and subsequent gross pathologic findings. Statistical analysis was performed with the Student t test. In the phantoms, progressive increases in iron content resulted in higher temperatures along the RF electrode track (P < .05). In the in vivo model, however, SPIO at physiologic concentrations did not significantly increase the diameter of coagulation on the basis of either postprocedural imaging or subsequent gross pathologic findings. Additionally, no significant differences were seen in other RF-related parameters including impedance, voltage, current, and grounding pad temperature. Administration of SPIO in conjunction with RF ablation of focal liver lesions is feasible and safe, but no significant difference in the extent of induced coagulation can be expected.

  8. Use of palm-oil by-products in chicken and rabbit feeds: effect on the fatty acid and tocol composition of meat, liver and plasma.

    PubMed

    Tres, A; Nuchi, C D; Magrinyà, N; Guardiola, F; Bou, R; Codony, R

    2012-06-01

    This study was undertaken in the framework of a larger European project dealing with the characterization of fat co- and by-products from the food chain, available for feed uses. In this study, we compare the effects, on the fatty acid (FA) and tocol composition of chicken and rabbit tissues, of the addition to feeds of a palm fatty acid distillate, very low in trans fatty acids (TFA), and two levels of the corresponding hydrogenated by-product, containing intermediate and high levels of TFA. Thus, the experimental design included three treatments, formulated for each species, containing the three levels of TFA defined above. Obviously, due to the use of hydrogenated fats, the levels of saturated fatty acids (SFA) show clear differences between the three dietary treatments. The results show that diets high in TFA (76 g/kg fat) compared with those low in TFA (4.4 g/kg fat) led to a lower content of tocopherols and tocotrienols in tissues, although these differences were not always statistically significant, and show a different pattern for rabbit and chicken. The TFA content in meat, liver and plasma increased from low-to-high TFA feeds in both chicken and rabbit. However, the transfer ratios from feed were not proportional to the TFA levels in feeds, reflecting certain differences according to the animal species. Moreover, feeds containing fats higher in TFA induced significant changes in tissue SFA, monounsaturated fatty acids and polyunsaturated fatty acids composition, but different patterns can be described for chicken and rabbit and for each type of tissue.

  9. Selection of Suitable Reference Genes for Normalization of Quantitative Real-Time PCR in Cartilage Tissue Injury and Repair in Rabbits

    PubMed Central

    Peng, Xiao-Xiang; Zhao, Rong-Lan; Song, Wei; Chu, Hai-Rong; Li, Meng; Song, Shu-Ya; Li, Guang-Zhou; Liang, Dong-Chun

    2012-01-01

    When studying the altered expression of genes associated with cartilage regeneration by quantitative real-time RT-PCR (RT-qPCR), reference genes with highly stable expression during different stages of chondrocyte developmental are necessary to normalize gene expression accurately. Until now, no reports evaluating expression changes of commonly used reference genes in rabbit articular cartilage have been published. In this study, defects were made in rabbit articular cartilage, with or without insulin-like growth factor 1 (IGF-1) treatment, to create different chondrocyte living environments. The stability and intensity of the expressions of the candidate reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S Ribosomal RNA (18S rRNA), cyclophilin (CYP), hypoxanthine phosphoribosyl transferase (HPRT1), and β-2-microglobulin (B2M) were evaluated. The data were analyzed by geNorm and NormFinder. B2M and 18S rRNA were identified to be suitable reference genes for rabbit cartilage tissues. PMID:23203068

  10. cDNA and derived amino acid sequence of ethanol-inducible rabbit liver cytochrome P-450 isozyme 3a (P-450ALC).

    PubMed Central

    Khani, S C; Zaphiropoulos, P G; Fujita, V S; Porter, T D; Koop, D R; Coon, M J

    1987-01-01

    Administration of ethanol to rabbits is known to induce a unique liver microsomal cytochrome P-450, termed isozyme 3a or P-450ALC, which is responsible for the increased oxidation of ethanol and other alcohols and the activation of toxic or carcinogenic compounds such as acetaminophen and N-nitrosodimethylamine. To further characterize this cytochrome P-450 we have identified cDNA clones to isozyme 3a by immunoscreening, DNA hybridization, and hybridization-selection. The cDNA sequence determined from two overlapping clones contains an open reading frame of 1416 nucleotides, and the first 25 amino acids of this reading frame correspond to residues 21-45 of cytochrome P-450 3a. The complete polypeptide, including residues 1 to 20, contains 492 amino acids and has a molecular weight of 56,820. Cytochrome P-450 3a is approximately 55% identical in sequence to P-450 isozymes 1 and 3b and 48% identical to isozyme 2. Hybridization of clone p3a-2 to electrophoretically fractionated rabbit liver poly(A)+ RNA revealed multiple bands, but, with a probe derived from the 3' nontranslated portion of this cDNA, only a 1.9-kilobase band was observed. Treatment of rabbits with imidazole, which increases the content of isozyme 3a, resulted in a transient increase in form 3a mRNA, but this was judged to be insufficient to account for the known 4.5-fold increase in form 3a protein. Genomic DNA analysis indicated that the cytochrome P-450 3a gene does not belong to a large subfamily. Images PMID:3027695

  11. Converging Stereotactic Radiotherapy Using Kilovoltage X-Rays: Experimental Irradiation of Normal Rabbit Lung and Dose-Volume Analysis With Monte Carlo Simulation

    SciTech Connect

    Kawase, Takatsugu; Kunieda, Etsuo Deloar, Hossain M.; Tsunoo, Takanori; Seki, Satoshi; Oku, Yohei; Saitoh, Hidetoshi; Saito, Kimiaki; Ogawa, Eileen N.; Ishizaka, Akitoshi; Kameyama, Kaori; Kubo, Atsushi

    2009-10-01

    Purpose: To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. Methods and Materials: A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. Results: A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. Conclusions: A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

  12. Bilirubin conjugates in bile of man and rat in the normal state and in liver disease

    PubMed Central

    Fevery, J.; Damme, B. Van; Michiels, R.; Groote, J. De; Heirwegh, K. P. M.

    1972-01-01

    Conjugates of bilirubin were studied in normal bile of man and rat, and in bile of liver patients. In general human bile was obtained by duodenal intubation. In addition T-tube bile was examined in patients operated on for mechanical obstruction. The bile pigment compositions of duodenal and T-tube bile were similar in two patients where comparison was possible. Obstruction of the bile duct in rats was used as an animal model for obstructive jaundice. Diazotized ethyl anthranilate was used for determination of total conjugated bile pigment and for thin-layer chromatography (t.l.c.) analysis of the derived azopigments. The available t.l.c. procedures are versatile and allow rapid and quantitative analysis. A variety of conjugated azopigments can be distinguished. With chloroform, negligible amounts of unconjugated bilirubin are extracted from bile of man. Therefore, the percentage of monoconjugated bile pigments present in the initial bile sample can be calculated from the percentage of azodipyrrole found after diazotization. Normal bile from man and rat yields similar azopigment patterns. The dominant component is azopigment-δ (azodipyrrole β-D-monoglucuronoside). Small amounts of azopigments with complex conjugating structures (γ-azopigments) are present in both cases. Human bile further yields small amounts of azopigments containing xylose or glucose (called azopigments-α2 and -α3, respectively). Monoconjugated bilirubin (estimated from the percentage of azodipyrrole) amounts of 22% of total bile pigments in human bile and to 39% in murine bile. In both, the bulk of bile pigment is bilirubin diglucuronoside. From bile of patients with acquired liver diseases a new azopigment group (β-azopigment) was derived. The γ-azopigment group was increased; the δ-azopigment group (containing azodipyrrole β-D-monoglucuronoside) was decreased. No differentiation was possible between intra- and extrahepatic cholestasis. The percentage of β-azopigment showed a positive

  13. Yucca schidigera can promote rabbit growth, fecundity, affect the release of hormones in vivo and in vitro, induce pathological changes in liver, and reduce ovarian resistance to benzene.

    PubMed

    Földešiová, Martina; Baláži, Andrej; Chrastinová, Ľubica; Pivko, Juraj; Kotwica, Jan; Harrath, Abdel Halim; Chrenek, Peter; Sirotkin, Alexander V

    2017-08-01

    This study evaluated the effect of Yucca schidigera (YS) extract on the physiological, reproductive, and endocrine indexes of New Zealand White rabbit does. Six-week-old rabbit does were fed a standard diet (control group) or a diet enriched with 5 or 20g of Y powder extract per 100-kg feed mixture for 350days. The does were artificially inseminated after induction of superovulation. Weight gain; conception and kindling rate; viability of pups and mothers; histopathological state of liver and muscle; plasma levels of progesterone (P4), oxytocin (OT), and prostaglandin F (PGF); and the release of P4, insulin-like growth factor I (IGF-I), OT, and PGF by isolated ovarian fragments and their response to the addition of benzene were analyzed. YS extract supplementation promoted weight gain and induced histopathological changes in the liver (creased vacuolization and occurrence of fuchsinophile inclusions in hepatocytes, liver fibrosis, hyperemia, occurrence of Kupffer cells, signs of necrosis and inflammation). YS consumption was not associated with changes in muscle (occurrence of fuchsinophile inclusions and signs of atrophy, interstitial edema, and inflammation), although Y2 increased muscle vascularization. YS supplementation increased conception and kindling rates but did not affect viability of pups or adult animals. Moreover, it enhanced plasma OT and PGF levels; plasma P4 concentration was increased by low-dose YS, but decreased by high-dose YS. Cultured ovarian fragments isolated from YS-fed does released more P4 and PGF and less IGF-I than ovarian fragments of control animals. However, YS supplementation did not affect ovarian OT release. Benzene alone did not influence the release of hormones by ovaries of control does. YS supplementation induced the inhibitory effect of benzene on the release of PGF, but not on other ovarian hormones. Collectively, these results suggest that dietary supplementation of YS extract can stimulate rabbit performance (growth and

  14. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits.

    PubMed

    Hassan, Anwar S; Ahmed, Jawad H; Al-Haroon, Sawsan S

    2012-01-01

    To investigate the possibility of hepatoprotective effect of Nigella sativa (NS) in INH-induced hepatotoxicity. The experiments were carried out on 24 male rabbits. They were divided into 4 groups (6 each); rabbits in group 1 were treated with INH following a standard protocol to induce hepatotoxicity. Rabbits in group 2 received starch. Group 3 received NS 1 g/kg/day before INH treatment. Group 4 rabbits were treated with NS only. Phenobarbital sodium (IP) was given to induce metabolism of INH. INH and NS were given orally. The experiment continued for 12 days; at day 13, animals were sacrificed. Liver function tests, malondialdehyde (MDA) were estimated in serum and in liver homogenates. Liver histopathological examinations were performed. Histopathological changes of hepatotoxicity were found in all INH-treated rabbits. The histopathological findings were normal in three rabbits treated with NS before INH, very mild in two, and with moderate changes in one rabbit. Serum alanine aminotransferase (S.ALT) was elevated after INH treatment and returned back to the control value when NS was given before INH. Similar pattern of effect was noticed with serum aspartate aminotransferase (S.AST), S. total bilirubin, S. MDA, and Serum alkaline phosphatase.In liver homogenate, AST, ALT, and MDA were increased with INH treatment compared to the control, then decreased with NS treatment given before INH CONCLUSIONS: NS has hepatoprotective effects against INH-induced hepatotoxicity in rabbits. NS 1 g/kg proved safe, no adverse effects; no histopathological or biological abnormalities were seen.

  15. Comparison of polysomal and nuclear poly(A)-containing RNA populations from normal rat liver and Novikoff hepatoma.

    PubMed Central

    Capetanaki, Y G; Alonso, A

    1980-01-01

    Polysomal and nuclear poly(A)-containing RNA of normal rat liver and Novikoff hepatoma cells have been compared by cDNA.RNA hybridization kinetics. Homologous hybridization reactions revealed at total kinetic complexity of about 1.6 X 10(10) and 1.38 X 10(10) daltons for liver and Novikoff mRNA respectively. The high abundance component present in liver cannot be detected in Novikoff. It was found from heterologous reactions that about 30% by weight of mRNA sequences are specific to liver. Determination of the nuclear poly(A)-containing RNA complexities revealed that about 5.5% and 4% of the haploid genome is expressed in the liver and Novikoff respectively. In a heterologous reaction, up to 30% of the liver cDNA failed to form hybrids with Novikoff nuclear RNA. Cross hybridizations have further revealed abundance shifts in both nuclear and polysomal RNA populations. Some sequences abundant in liver are less abundant in Novikoff and some rare liver sequences are relatively abundant in Novikoff. PMID:6160467

  16. Evaluation of Lacrimation Characteristics in Clinically Normal New Zealand White Rabbits by Using the Schirmer Tear Test I.

    PubMed

    Whittaker, Alexandra L; Williams, David L

    2015-11-01

    Rabbits are a common animal model in eye research and in safety testing of novel chemical agents. In addition, ocular disease is a routine presentation in clinical practice. However, few studies have quantitatively examined lacrimation kinetics in this species. This study used a noninvasive method of tear measurement (the Schirmer tear test, STT) to quantify values for basal and reflex tearing and to determine the kinetic nature of tear production in 76 New Zealand white rabbits. We obtained a value of 7.58 ± 2.3 mm/min for the standard 1-min STT. Calculated values for mean residual tear volume and reflex tear flow were 1.95 μL and 0.035 μL/s, respectively. In addition, this study provides preliminary evidence for an interaction effect between eyes given that higher STT values were obtained from the second eye tested.

  17. Evaluation of Lacrimation Characteristics in Clinically Normal New Zealand White Rabbits by Using the Schirmer Tear Test I

    PubMed Central

    Whittaker, Alexandra L; Williams, David L

    2015-01-01

    Rabbits are a common animal model in eye research and in safety testing of novel chemical agents. In addition, ocular disease is a routine presentation in clinical practice. However, few studies have quantitatively examined lacrimation kinetics in this species. This study used a noninvasive method of tear measurement (the Schirmer tear test, STT) to quantify values for basal and reflex tearing and to determine the kinetic nature of tear production in 76 New Zealand white rabbits. We obtained a value of 7.58 ± 2.3 mm/min for the standard 1-min STT. Calculated values for mean residual tear volume and reflex tear flow were 1.95 µL and 0.035 µL/s, respectively. In addition, this study provides preliminary evidence for an interaction effect between eyes given that higher STT values were obtained from the second eye tested. PMID:26632789

  18. Differential analysis of D-{beta}-Asp-containing proteins found in normal and infrared irradiated rabbit lens

    SciTech Connect

    Takata, Takumi; Shimo-Oka, Tadashi; Kojima, Masami; Miki, Kunio; Fujii, Noriko . E-mail: nfujii@HL.rri.kyoto-u.ac.jp

    2006-05-26

    Although proteins are generally composed of L-{alpha}-amino acids, D-{beta}-aspartic acid (Asp)-containing proteins have been reported in various elderly tissues. Our previous study detected several D-{beta}-Asp-containing proteins in a rabbit lens derived from epithelial cell line by Western blot analysis of a 2D-gel using a polyclonal antibody that is highly specific for D-{beta}-Asp-containing proteins. The identity of each spot was subsequently determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the Ms-Fit online database searching algorithm. In this study, we discovered novel D-{beta}-Asp-containing proteins from rabbit lens. The results indicate that {beta}-crystallin A3, {beta}-crystallin A4, {beta}-crystallin B1, {beta}-crystallin B2, {beta}-crystallin B3, {gamma}-crystallin C, {gamma}-crystallin D, and {lambda}-crystallin in rabbit lens contain D-{beta}-Asp residues. Furthermore, the occurrence of D-{beta}-Asp residues increases with infrared ray (IR) irradiation. Additionally, some D-{beta}-Asp-containing proteins only appear after IR irradiation. One such protein is the {alpha}-enolase, which shows homology to {tau}-crystallin.

  19. Mössbauer spectroscopic study of the forms of iron in normal human liver and spleen tissue

    NASA Astrophysics Data System (ADS)

    Chua-Anusorn, W.; Pierre, T. G. St.; Webb, J.; Macey, D. J.; Yansukon, P.; Pootrakul, P.

    1994-12-01

    Mössbauer spectra of 12 normal human spleen and 12 normal human liver samples ( post mortem) from Australia and Thailand have been recorded at 78 K. The spectra show the presence of iron in the form of ferrihydrite, together with some deoxyhemoglobin and methemoglobin in some samples. The spectra were used in conjunction with elemental analysis to calculate the non-heme iron concentrations in the tissues. The mean non-heme iron concentration in the Thai livers was significantly less than that for the Australian samples. The goethite-like form of hemosiderin that has been observed in some pathological tissues was not detected.

  20. The international normalized ratio according to Owren in liver disease: interlaboratory assessment and determination of international sensitivity index.

    PubMed

    Magnusson, Maria; Sten-Linder, Margareta; Bergquist, Annika; Rajani, Rupesh; Kechagias, Stergios; Fischler, Björn; Németh, Antal; Lindahl, Tomas L

    2013-09-01

    The international normalized ratio (INR) is used to prioritize liver disease patients for transplantation. Previous studies have shown high interlaboratory variability in Quick-based INR determinations in samples of patients with liver disease. We assessed Owren-based INR reagents for analyzing INR in patients with liver disease. Further, we determined the difference between international sensitivity index (ISI) for patients on vitamin K antagonists (ISIVKA) and ISI for patients with liver disease (ISIliver). Twenty patients with liver disease were included, 10 with INR 1.8-3.6 (group A1) and 10 with INR 1.2-1.5 (group C1). Plasma from these patients was analyzed for Owren-based INR in eight Swedish laboratories using either of following reagents: SPA+, Owrens PT or Nycotest PT. To determine ISI liver, the reference thromboplastin RBT/05 and additional 41 patients with liver disease and 20 normal controls were included. ISIVKA was determined according to the WHO procedure. The difference between the ISIVKA and ISIliver was calculated. The coefficients of variance for the Owren based INR methods were 6.2% in group A1, 3.9 % in group C1 and 5.3% for all patients. The difference between ISIVKA and ISIliver were -0.4%, -0.7% and -0.2% for SPA+, Owrens PT and Nycotest PT respectively. Interlaboratory variation in INR analyses according to Owren in patients with liver disease is low and the difference between ISIVKA and ISIliver is below 10% with this method. ISIVKA can therefore be used in the INR calibration, for the Owren reagents studied, when analyzing plasma from patients with liver disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women.

    PubMed

    Terra, Ximena; Auguet, Teresa; Broch, Montserrat; Sabench, Fàtima; Hernández, Mercè; Pastor, Rosa M; Quesada, Isabel M; Luna, Anna; Aguilar, Carmen; del Castillo, Daniel; Richart, Cristóbal

    2013-01-01

    We aimed to analyze the retinol binding protein-4 (RBP4) messenger RNA (mRNA) expression profiles in adipose tissues and liver of morbidly obese (MO) women with or without nonalcoholic fatty liver disease (NAFLD), and to study the relationships with other pro- and anti-inflammatory adipokines in vivo and in vitro. We performed a cross-sectional analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and liver samples from four lean and 45 MO women with or without NAFLD by enzyme-linked immunosorbent assay and real-time reverse transcription-PCR. We also studied RBP4 expression in HepG2 hepatocytes under various inflammatory stimuli. Circulating RBP4 levels were higher in MO women, and specifically, in MO subjects with NAFLD compared with normal liver controls (lean and MO). RBP4 liver expression was higher in nonalcoholic steatohepatitis (NASH)-moderate/severe than in NASHmild. Overall RBP4 gene expression was higher in liver than in adipose tissues. Among them, the higher expression corresponded to SAT. VAT expression was lower in the MO cohort. In HepG2, RBP4 mRNA expression was reduced by tumor necrosis factor (TNF)-α and increased by adiponectin treatment. The results obtained in MO women with NAFLD, brings up the use of RBP4 and other adipokines as a panel of noninvasive molecular biomarkers when NAFLD is suspected. Further studies are needed with other obesity groups. Copyright © 2012 The Obesity Society.

  2. Effect of Transcatheter Intra-Arterial Therapies on Tumor Interstitial Fluid Pressure and Its Relation to Drug Penetration in a Rabbit Liver Tumor Model.

    PubMed

    Liang, Bin; Chen, Shaofeng; Li, Lin; Liu, Yiming; Xiong, Fu; Dong, Xiangjun; Feng, Gansheng; Gupta, Sanjay; Zheng, Chuansheng

    2015-12-01

    To determine the change in tumor interstitial fluid pressure (IFP) after transcatheter intra-arterial (IA) therapies and its relation to drug penetration in liver cancer. VX2 tumors were grown in the livers of 16 rabbits. The rabbits were treated with intravenous injection of doxorubicin (group 1; n = 4), hepatic IA injection of doxorubicin (group 2; n = 4), hepatic IA injection of doxorubicin followed by embolization with polyvinyl alcohol particles (group 3; n = 4), or hepatic IA injection of doxorubicin mixed with Lipiodol followed by polyvinyl alcohol embolization (group 4; n = 4). Tumor IFP was measured with a Mikro-Tip pressure catheter before and 1 hour after treatment. Doxorubicin penetration was evaluated by immunofluorescence. Tumor IFP after treatment decreased by 5.0% ± 2.8, 3.9% ± 9.0, 27.1% ± 5.2, and 31.8% ± 7.4 in groups 1-4, respectively. The difference in IFP reduction between embolization-treated groups (groups 3 and 4) and nonembolized groups (groups 1 and 2) was significant (P < .001). Doxorubicin penetration distances were 20.3 μm ± 3.7, 45.7 μm ± 10.5, 69.5 μm ± 9.3, and 47.9 μm ± 6.4 in groups 1-4, respectively. IFP reduction was significantly correlated with doxorubicin penetration distance (r = .671, P = .004). A greater reduction of tumor IFP was associated with embolization in a preclinical liver tumor model, and embolization may indirectly contribute to increased drug penetration. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  3. Enzymatic stability of 2'-ethylcarbonate-linked paclitaxel in serum and conversion to paclitaxel by rabbit liver carboxylesterase for use in prodrug/enzyme therapy.

    PubMed

    Tanino, Tadatoshi; Nawa, Akihiro; Miki, Yasuyoshi; Iwaki, Masahiro

    2008-07-01

    In prodrug/enzyme therapy for cancer, information on the sensitivity of hydrolytic enzymes to prodrug is required to reduce adverse effects of the parental drug and to find the activating enzyme. The aim of this study was to characterize the enzymatic stability of 2'-ethylcarbonate-linked paclitaxel (TAX-2'-Et) in the sera of several different species including humans. TAX-2'-Et disposition in serum was kinetically analysed using models with hydrolytic and/or degradation processes. To further evaluate the capability of liver carboxylesterases (CESs) in TAX-2'-Et hydrolysis, a CES isolated from rabbit liver (Ra-CES) was utilized as a model enzyme. Rat serum provided rapid enzymatic hydrolysis of TAX-2'-Et with a half-life of 4 min. The degradation of paclitaxel (TAX) (degradation rate constant, 0.16 h(-1)) was accompanied by the formation of an unknown compound. The conversion to TAX was almost completely inhibited by phenylmethyl sulfonylfluoride (PMSF) and bis(p-nitrophenyl) phosphate (BNPP). In human and rabbit sera, the degradation rate constant of TAX-2'-Et was 5.1 x 10(-2) and 0.15 h(-1), respectively, when excepting hydrolysis. The degradation products had the same molecular weight as TAX-2'-Et. The amount of TAX produced accounted for only 8-11% of the decrease in TAX-2'-Et after a 9 h exposure to rabbit or human serum. PMSF, but not BNPP, inhibited more than 90% of the TAX production in a 1.5 h incubation with human or rabbit serum. Ra-CES enzyme converted TAX-2'-Et to TAX with V(max) and K(m) of 74.7+/-13.8 nmol/min/mg protein and 8.8+/-2.8 microM, respectively. These results indicate that TAX-2'-Et is sensitive to serum CESs, but not cholinesterases. However, serum CESs show species-dependent hydrolysis of TAX-2'-Et. Although human serum allows the slow release of TAX, TAX-2'-Et is expected to reduce the side-effects of TAX. The Ra-CES enzyme is capable of hydrolysing TAX-2'-Et, which may be beneficial for the development of a TAX-2'-Et/enzyme therapy

  4. Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma.

    PubMed

    Tres, A; Bou, R; Guardiola, F; Nuchi, C D; Magrinyà, N; Codony, R

    2013-03-01

    The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol + tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The α-tocopherol (αT) content of tissues was reduced in response to the lower αT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species

  5. Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers.

    PubMed

    Bautista, Wendy; Lipschitz, Jeremy; McKay, Andrew; Minuk, Gerald Y

    2017-01-01

    The inability to distinguish cancer (CSCs) from normal stem cells (NSCs) has hindered attempts to identify safer, more effective therapies for hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potential differences (PDs) of CSCs and NSCs derived from human HCC and healthy livers respectively and determine whether altered GABAergic innervation could explain the differences. Epithelial cell adhesion molecule (EpCAM) positive stem cells were isolated from human liver tissues by magnetic bead separations. Cellular PDs were recorded by microelectrode impalement of freshly isolated cells. GABAA receptor subunit expression was documented by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence. CSCs were significantly depolarized (-7.0 ± 1.3 mV) relative to NSCs (-23.0 ± 1.4 mV, p &lt; 0.01). The depolarized state was associated with different GABAA receptor subunit expression profiles wherein phasic transmission, represented by GAGAA α3 subunit expression, was prevalent in CSCs while tonic transmission, represented by GABAA α6 subunit expression, prevailed in NSCs. In addition, GABAA subunits α3, β3, ϒ3 and δ were strongly expressed in CSCs while GABAA π expression was dominant in NSCs. CSCs and NSCs responded similarly to GABAA receptor agonists (ΔPD: 12.5 ± 1.2 mV and 11.0 ± 3.5 mV respectively). The results of this study indicate that CSCs are significantly depolarized relative to NSCs and these differences are associated with differences in GABAA receptor subunit expression. Together they provide new insights into the pathogenesis and possible treatment of human HCC.

  6. Hepatitis B Virus X Protein Driven Alpha Fetoprotein Expression to Promote Malignant Behaviors of Normal Liver Cells and Hepatoma Cells

    PubMed Central

    Zhu, Mingyue; Lu, Yan; Li, Wei; Guo, Junli; Dong, Xu; Lin, Bo; Chen, Yi; Xie, Xieju; Li, Mengsen

    2016-01-01

    Background: The infection of Hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma(HCC), HBV-X protein(HBx) is able to induce expression of alpha-fetoprotein(AFP) in normal liver cells, and AFP harbors a function to promote malignant transformation of normal liver cells, but the role AFP playing in malignant behaviors of HCC cells is still unclear. Methods: Fifty-six liver tissue samples were collected from the clinical patients through hepatectomy(include normal liver tissues, HBV-related hepatitis liver tissues and HBV-related HCC tissues), and diagnosis of these tissues by pathology section, expression of AFP, Ras and CXCR4 were evidenced by immunohisochemical staining and Western blotting; The proliferation of human normal liver cells line L-02 cells and human hepatoma cells line, HLE cells(non AFP-producing) were performed by MTT method; Repaired capacity of L-02 and HLE cells were compared by wound healing assay; Migration and invasion of these cells were analyzed by Transwell chamber assay; HBx expressed vectors(pcDNA3.1-HBx) were constructed and transfected into L-02 and HLE cells, effects of pcDNA3.1-HBx on the malignant behaviors were also detected by MTT, Transwell chamber assay and the expression of AFP, Ras and CXCR4 were evidenced by Western blotting. Results: we found that expression of AFP, Ras and CXCR4 in HBV-related HCC and lymph nodes metastasis tissues were significantly elevated compared with HBV-related HCC, non metastasis tissues and HBV-related hepatitis tissues; Expression of AFP, Ras and CXCR4 in HBV-related hepatitis tissues were significantly enhanced compared with normal liver tissues; The growth ratio, migratory and invasive ability, expression of AFP, Ras and CXCR4 of the cells were outstanding promoted while L-02 and HLE cells were transfected with pcDNA3.1-HBx vectors. The proliferation ratio, migration and invasion ability, and expression of Ras and CXCR4 were significantly inhibited while

  7. Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD—A Systematic Review

    PubMed Central

    Petäjä, Elina M.; Yki-Järvinen, Hannele

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and fibrosis. “Obese/Metabolic NAFLD” is closely associated with obesity and insulin resistance and therefore predisposes to type 2 diabetes and cardiovascular disease. NAFLD can also be caused by common genetic variants, the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2). Since NAFL, irrespective of its cause, can progress to NASH and liver fibrosis, its definition is of interest. We reviewed the literature to identify data on definition of normal liver fat using liver histology and different imaging tools, and analyzed whether NAFLD caused by the gene variants is associated with insulin resistance. Histologically, normal liver fat content in liver biopsies is most commonly defined as macroscopic steatosis in less than 5% of hepatocytes. In the population-based Dallas Heart Study, the upper 95th percentile of liver fat measured by proton magnetic spectroscopy (1H-MRS) in healthy subjects was 5.6%, which corresponds to approximately 15% histological liver fat. When measured by magnetic resonance imaging (MRI)-based techniques such as the proton density fat fraction (PDFF), 5% macroscopic steatosis corresponds to a PDFF of 6% to 6.4%. In contrast to “Obese/metabolic NAFLD”, NAFLD caused by genetic variants is not associated with insulin resistance. This implies that NAFLD is heterogeneous and that “Obese/Metabolic NAFLD” but not NAFLD due to the PNPLA3 or TM6SF2 genetic variants predisposes to type 2 diabetes and cardiovascular disease. PMID:27128911

  8. Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid.

    PubMed Central

    Koop, D R; Crump, B L; Nordblom, G D; Coon, M J

    1985-01-01

    Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450ALC, was previously isolated in this laboratory from animals administered ethanol or imidazole, and the purified cytochrome was shown to function in the reconstituted system as an oxygenase in catalyzing the oxidation of ethanol and other alcohols. Although liver microsomes from animals treated in various ways exhibit increased alcohol-oxidizing activity, evidence was not available as to whether this was due to enzyme induction or to other factors influencing the activity. Immunochemical quantitation of P-450 isozyme 3a has now been achieved by use of purified antibody to this cytochrome in NaDodSO4/PAGE/blotting and dot-blotting techniques. The specific content of isozyme 3a in liver microsomes was found to be increased from 2- to greater than 4-fold by administration of the following agents, in increasing order of effectiveness as inducers: isoniazid, trichloroethylene, pyrazole, ethanol, imidazole, and acetone. Isozyme 3a represents about 5% of the total P-450 in control animals and is increased to as high as 27% by acetone treatment. Isozyme 3a-dependent butanol-oxidation activity, determined by the inhibitory effect of antibody on the various microsomal preparations, was found to increase proportionally with increased content of this cytochrome. Images PMID:3858864

  9. Moderately oxidized oils and dietary zinc and α-tocopheryl acetate supplementation: effects on the oxidative stability of rabbit plasma, liver, and meat.

    PubMed

    Tres, Alba; Bou, Ricard; Codony, Rafael; Guardiola, Francesc

    2010-08-25

    The aim of this study was to assess the alterations in plasma, liver, and meat oxidative stability and α-tocopherol content when moderately oxidized sunflower oils were added to feeds and when feeds were supplemented with α-tocopheryl acetate (100 mg/kg) and Zn (200 mg/kg). The effects of cooking the meat and its subsequent refrigeration were also studied. When the content of primary oxidation compounds of the oil was high, rabbit plasma, liver, and meat α-tocopherol content was reduced and meat susceptibility to oxidation increased. The addition of oil with a high content of secondary oxidation compounds (oil heated at 140 °C, 31 h) to feed also led to an increase in meat susceptibility to oxidation, although it presented an α-tocopherol content similar to that of nonheated oil. Feed supplementation with α-tocopheryl acetate increased tissue α-tocopherol content and improved the oxidative stability of liver and meat. However, in the latter, it was less effective when oil heated at 55 °C was added.

  10. Laminin alpha 5, a major transcript of normal and malignant rat liver epithelial cells, is differentially expressed in developing and adult liver.

    PubMed

    Seebacher, T; Medina, J L; Bade, E G

    1997-11-25

    The laminin family of extracellular matrix glycoproteins plays a major role in cell migration and differentiation and in tumor cell invasion. As previously shown, the laminin deposited by normal and malignant rat liver epithelial cells in their extracellular matrix (ECM) and into their ECM migration tracks does not contain a typical (EHS-like) alpha 1 heavy chain. By RT-PCR screening we have now identified two alpha chains among a total of five additional laminin chains produced by these cells. Three of the newly identified chains were not previously known for the rat. Their sequences have been deposited in the EMBL nucleotide sequence data bank. The alpha 5 chain now identified is expressed at comparably high levels by both the normal and the malignant liver epithelial cells. The chain is also expressed in fetal liver together with the alpha 2 and beta 2 chains, but it is only vestigially expressed in the mature organ as shown by RT-PCR. These results suggest for alpha 5 a role in development and production of the chain by only a small subset of cells in adult liver. At the level of detection used, no changes were observed in regenerating liver after partial hepatectomy. In addition to the alpha 5 chain, the cultured cells express the beta 1 and beta 2 light chains, indicating the expression of more than one laminin isoform by the same cell line. The expression of the alpha 5 chain and of the other new non-EHS isoform chains was also analyzed in various tissues. The malignant liver epithelial cells, but not their nontumorigenic parental cells, also express, in addition to the alpha 5 chain the alpha 2 chain, which is expressed at high level by the NBT II bladder carcinoma cell line, suggesting a relationship with malignancy.

  11. TNF-{alpha} similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts

    SciTech Connect

    Mueller, Lars; Seggern, Lena von; Schumacher, Jennifer; Goumas, Freya; Wilms, Christian; Braun, Felix; Broering, Dieter C.

    2010-07-02

    Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-{alpha} on the transcript and protein level, whereas PDGF-BB, TGF-{beta}1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-{alpha}, and of alpha-smooth muscle actin, by TGF-{beta}1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.

  12. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  13. [Association of intestinal epithelial tight junctions, E.coli, intestinal mucosa Toll-like receptor-4 and tumor necrosis factor-alpha in rabbit with non-alcoholic fatty liver disease].

    PubMed

    Wang, Haikun; Gao, Hongliang; Yao, Ping

    2014-12-01

    To explore the variation and association of intestinal epithelial tight junctions, E.coli, and expression of Toll-like receptor-4 (TLR-4) and tumor necrosis factor-alpha (TNFα) in a rabbit model of non-alcoholic fatty liver disease (NAFLD). Fourteen male New Zealand rabbits were randomly divided into two groups. The control group was given a normal diet, while the NAFLD group was given a high-fat diet. After 12 weeks, the two groups were sacrificed. Both length and width of the tight junctions of ileum epithelial cells were measured by electron microscopy. Enzyme-linked immunosorbent assay was used to detect the concentration of TNFα in venous blood serum. Location and expression of TLR-4 were observed by immunohistochemical staining. Copies of E.coli genes were measured by RT-PCR. The relationship between TNFα and tight junctions, TLR-4, and E.coli were respectively analyzed by stepwise multiple linear regression. Compared with the control group, the NAFLD group has significantly shortened ileum epithelial fight junctions (t=5.031, P<0.01), increased copies of E. coli genes (t=-3.492, P<0.01), and increased ileal expression of TLR-4 (t=-44.089, P<0.01). A significant increase of TNFα was also observed in the NAFLD group (t=-17.768, P<0.01). Regression analysis showed that E.coli and intestinal epithelial tight junctions were correlated (standardized beta=-0.385), and showed a positive correlation between E. coli and TLR-4 (standardized beta=0.332 and 0.427). Damage to the intestine as a physical barrier, biological barrier and immune barrier is closely related to TNFα expression, and the relation between the immune barrier and TNFα is more significant.

  14. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue.

    PubMed

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-02-01

    To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role.

  15. Accurate quantitation of Ki67-positive proliferating hepatocytes in rabbit liver by a multicolor immunohistochemical (IHC) approach analyzed with automated tissue and cell segmentation software.

    PubMed

    van der Loos, Chris M; de Boer, Onno J; Mackaaij, Claire; Hoekstra, Lisette T; van Gulik, Thomas M; Verheij, Joanne

    2013-01-01

    Determination of hepatocyte proliferation activity is hampered by the presence of Ki67-positive non-parenchymal cells. We validated a multicolor immunohistochemical (IHC) approach using multispectral tissue and cell segmentation software. Portal vein branches to the cranial liver lobes of 10 rabbits were embolized, leading to atrophy of the cranial lobes and hyperplasia of the caudal lobes. Slides from cranial and caudal lobes (n=20) were double-stained (CK8+18 and Ki67) and triple-stained (CK8+18, Ki67, and CD31). The Ki67 proliferation index was calculated using automated tissue and cell segmentation software and compared with manual counting by two independent observers. A substantial variation was seen in the number of Ki67-positive hepatocytes in the different specimens in both double and triple staining (range, 0-50). Correlation coefficients between manual counting and the digital analysis were 0.76 for observer 1 (p<0.001) and 0.78 for observer 2 (p<0.001) with double staining and R(2) = 0.91 for observer 1 and R(2) = 0.89 for observer 2, p<0.001 with triple staining. In conclusion, in rabbit, the hepatocellular proliferation index can be reliably determined using automated tissue and cell segmentation software in combination with IHC multiple staining. Our findings may be useful in clinical practice when Ki67 proliferation index yields prognostic significance.

  16. Ex-Vivo Characterization of Bioimpedance Spectroscopy of Normal, Ischemic and Hemorrhagic Rabbit Brain Tissue at Frequencies from 10 Hz to 1 MHz

    PubMed Central

    Yang, Lin; Zhang, Ge; Song, Jiali; Dai, Meng; Xu, Canhua; Dong, Xiuzhen; Fu, Feng

    2016-01-01

    Stroke is a severe cerebrovascular disease and is the second greatest cause of death worldwide. Because diagnostic tools (CT and MRI) to detect acute stroke cannot be used until the patient reaches the hospital setting, a portable diagnostic tool is urgently needed. Because biological tissues have different impedance spectra under normal physiological conditions and different pathological states, multi-frequency electrical impedance tomography (MFEIT) can potentially detect stroke. Accurate impedance spectra of normal brain tissue (gray and white matter) and stroke lesions (ischemic and hemorrhagic tissue) are important elements when studying stroke detection with MFEIT. To our knowledge, no study has comprehensively measured the impedance spectra of normal brain tissue and stroke lesions for the whole frequency range of 1 MHz within as short as possible an ex vivo time and using the same animal model. In this study, we established intracerebral hemorrhage and ischemic models in rabbits, then measured and analyzed the impedance spectra of normal brain tissue and stroke lesions ex vivo within 15 min after animal death at 10 Hz to 1 MHz. The results showed that the impedance spectra of stroke lesions significantly differed from those of normal brain tissue; the ratio of change in impedance of ischemic and hemorrhagic tissue with regard to frequency was distinct; and tissue type could be discriminated according to its impedance spectra. These findings further confirm the feasibility of detecting stroke with MFEIT and provide data supporting further study of MFEIT to detect stroke. PMID:27869707

  17. Normal Organ Weights in Women: Part II-The Brain, Lungs, Liver, Spleen, and Kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2015-09-01

    Organomegaly can be a sign of disease and pathology, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human females. A prospective study was undertaken of healthy females who had sudden, traumatic deaths at age 18 to 35 years. Cases were excluded if there was a history of medical illness including illicit drug use, prolonged medical treatment was performed, there was a prolonged period between the time of injury and death, body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ that could have affected the weight. A total of 102 cases met criteria for inclusion in the study during the approximately 10-year period of data collection from 2004 to 2014. The decedents had an average age of 24.4 years and ranged in length from 141 to 182 cm (56.4-72.8 inches) with an average length of 160 cm (64 inches). The weight ranged from 35.9 to 152 kg (79-334 lb) with an average weight of 65.3 kg (143 lb). The majority of the decedents (86%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean brain weight was 1233 g (range, 1000-1618 g); liver mean weight, 1288 g (range, 775-2395 g); spleen mean weight, 115 g (range, 51-275 g); right lung mean weight, 340 g (range, 142-835 g); left lung mean, 299 g (range, 108-736 g); right kidney mean weight, 108 g (range, 67-261 g); and the left kidney mean weight, 116 g (range, 55-274 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors therefore propose establishing a reference range for organ weights in

  18. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

    PubMed

    Molina, D Kimberley; DiMaio, Vincent J M

    2012-12-01

    Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use

  19. Physiological Content and Intrinsic Activities of 10 Cytochrome P450 Isoforms in Human Normal Liver Microsomes.

    PubMed

    Zhang, Hai-Feng; Wang, Huan-Huan; Gao, Na; Wei, Jun-Ying; Tian, Xin; Zhao, Yan; Fang, Yan; Zhou, Jun; Wen, Qiang; Gao, Jie; Zhang, Yang-Jun; Qian, Xiao-Hong; Qiao, Hai-Ling

    2016-07-01

    Due to a lack of physiologic cytochrome P450 (P450) isoform content, P450 activity is typically only determined at the microsomal level (per milligram of microsomal protein) and not at the isoform level (per picomole of P450 isoform), which could result in the misunderstanding of variations in P450 activity between individuals and further hinder development of personalized medicine. We found that there were large variations in protein content, mRNA levels, and intrinsic activities of the 10 P450s in 100 human liver samples, in which CYP2E1 and CYP2C9 showed the highest expression levels. P450 gene polymorphisms had different effects on activity at two levels: CYP3A5*3 and CYP2A6*9 alleles conferred increased activity at the isoform level but decreased activity at the microsomal level; CYP2C9*3 had no effect at the isoform level but decreased activity at the microsomal level. The different effects at each level stem from the different effects of each polymorphism on the resulting P450 protein. Individuals with CYP2A6*1/*4, CYP2A6*1/*9, CYP2C9*1/*3, CYP2D6 100C>T TT, CYP2E1 7632T>A AA, CYP3A5*1*3, and CYP3A5*3*3 genotypes had significantly lower protein content, whereas CYP2D6 1661G>C mutants had a higher protein content. In conclusion, we first offered the physiologic data of 10 P450 isoform contents and found that some single nucleotide polymorphisms had obvious effects on P450 expression in human normal livers. The effects of gene polymorphisms on intrinsic P450 activity at the isoform level were quite different from those at the microsomal level, which might be due to changes in P450 protein content. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Apparent diffusion coefficient normalization of normal liver: Will it improve the reproducibility of diffusion-weighted imaging at different MR scanners as a new biomarker?

    PubMed

    Zhu, Jie; Zhang, Jie; Gao, Jia-Yin; Li, Jin-Ning; Yang, Da-Wei; Chen, Min; Zhou, Cheng; Yang, Zheng-Han

    2017-01-01

    Apparent diffusion coefficient (ADC) measurement in diffusion-weighted imaging (DWI) has been reported to be a helpful biomarker for detection and characterization of lesion. In view of the importance of ADC measurement reproducibility, the aim of this study was to probe the variability of the healthy hepatic ADC values measured at 3 MR scanners from different vendors and with different field strengths, and to investigate the reproducibility of normalized ADC (nADC) value with the spleen as the reference organ. Thirty enrolled healthy volunteers received DWI with GE 1.5T, Siemens 1.5T, and Philips 3.0T magnetic resonance (MR) systems on liver and spleen (session 1) and were imaged again after 10 to 14 days using only GE 1.5T MR and Philips 3.0T MR systems (session 2). Interscan agreement and reproducibility of ADC measurements of liver and the calculated nADC values (ADCliver/ADCspleen) were statistically evaluated between 2 sessions. In session 1, ADC and nADC values of liver were evaluated for the scanner-related variability by 2-way analysis of variance and intraclass correlation coefficients (ICCs). Coefficients of variation (CVs) of ADCs and nADCs of liver were calculated for both 1.5 and 3.0-T MR system. Interscan agreement and reproducibility of ADC measurements of liver and related nADCs between 2 sessions were found to be satisfactory with ICC values of 0.773 to 0.905. In session 1, the liver nADCs obtained from different scanners were consistent (P = 0.112) without any significant difference in multiple comparison (P = 0.117 to >0.99) by using 2-way analysis of variance with post-hoc analysis of Bonferroni method, although the liver ADCs varied significantly (P < 0.001). nADCs measured by 3 scanners were in good interscanner agreements with ICCs of 0.685 to 0.776. The mean CV of nADCs of both 1.5T MR scanners (9.6%) was similar to that of 3.0T MR scanner (8.9%). ADCs measured at 3 MR scanners with different field strengths and vendors could

  1. Hypolipidaemic effects of Ballota undulata in rabbits.

    PubMed

    Qazan, Walid Sh

    2008-04-15

    The aim of to study the effect of Ballota undulata (70% EtOH) extract on lipid profile on Rabbits. The plant extract was orally administered to the atherogenic rabbits (atherogenic diet + cholesterol powder supplement 400 mg/kg/body weight/day dissolved in 5 mL coconut oil) at dose of 1.2 g kg(-1) body weight/day. During the overall period of the experiment blood was collected and serum was analyzed for lipid profile. Animals were sacrificed; the heart and the liver were collected and kept at -20 degrees C until assayed. Biochemical analysis of blood serum and tissue (liver and heart muscle) level were made for cholesterol, phospholipids and triglycerides. In addition blood serum was analyzed further for HDL-Cholesterol. All the results were statistically analyzed using students t-test. Hypolipidaemic nature of Ballota undulata (70% EtOH) extract was studied in hyperlipidaemic Rabbits. The increased cholesterol levels were brought to normal by administration of Ballota undulata. Serum cholesterol levels dropped from 940.7 to 230.41 (75.55%) and further to 119.2 (87.32%) by the end of the experiment. Similarly, phospholipids and triglycerides levels were observed to be also reduced. The tissues lipids profiles of liver and heart muscle showed similar changes in those noticed in serum lipids. Ballota undulata possesses active hypolipidaemic constituents.

  2. Ethacrynic-acid-induced glutathione depletion and oxidative stress in normal and Mrp2-deficient rat liver.

    PubMed

    Ji, Bin; Ito, Kousei; Sekine, Shuichi; Tajima, Ai; Horie, Toshiharu

    2004-12-01

    Oxidative stress in the liver is sometimes accompanied by cholestasis. We investigated the localization and role of multidrug-resistance-associated protein (Mrp) 2, a biliary transporter involved in bile-salt-independent bile flow, under ethacrynic acid (EA)-induced acute oxidative stress. Normal Sprague-Dawley rat (SDR) and Mrp2-deficient Eisai hyperbilirubinemic rat (EHBR) livers were perfused with 500 microM EA. The release of glutamic pyruvic transaminase (GPT) and thiobarbituric-acid-reactive substances (TBARS) from EHBR liver was markedly delayed compared with that from SDR liver. This is mainly due to the higher basal level of glutathione (GSH) in EHBR liver (59.1 +/- 0.3 nmol/mg protein) compared with SDR liver (39.7 +/- 1.5 nmol/mg protein). EA similarly induced a rapid reduction in GSH followed by mitochondrial permeability transition in the isolated mitochondria from both SDR and EHBR. Internalization of Mrp2 was detected before nonspecific disruption of the canalicular membrane and GPT release in SDR liver perfused with 100 microM EA. SDR liver preperfused with hyperosmolar buffer (405 mosmol/L) for 30 min induced internalization of Mrp2 without changing the basal GSH level, while elimination of hepatic GSH by 300 microM EA perfusion was significantly delayed thereafter. Concomitantly, hepatotoxicity assessed by the release of GPT and TBARS was also significantly attenuated under hyperosmolar conditions. In conclusion, preserved cytosolic and intramitochondrial GSH is the key factor involved in the acute hepatotoxicity induced by EA and its susceptibility could be altered by the presence of Mrp2.

  3. Radiosensitivity of hepatoma cell lines and human normal liver cell lines exposed to 12C6+ ions

    NASA Astrophysics Data System (ADS)

    Jing, X.; Yang, J.; Li, W.; Guo, C.; Dang, B.; Wang, J.; Zhou, L.; Wei, W.; Gao, Q.

    AIM To investigate the radiosensitivity of hepatoma cell lines and human normal liver cell lines METHODS Accelerated carbon ions by heavy ion research facility in Lanzhou HIRFL have high LET We employed it to study the radiosensitivity of hepatoma cell lines SMMC-7721 and human normal liver cell lines L02 using premature chromosome condensation technique PCC Cell survive was documented by a colony assay Chromatid breaks were measured by counting the number of chromatid breaks and isochromatid breaks immediately after prematurely chromosome condensed by Calyculin-A RESULTS The survival curve of the two cell lines presented a good linear relationship and the survival fraction of L02 is higher than that of SMMC-7721 Additionally the two types of G 2 phase chromosome breaks chromatid breaks and isochromatid breaks of L02 are lower than that of SMMC-7721 CONCLUSION Human normal liver cell line have high radioresistance than that of hepatoma cell line It imply that it is less damage to normal organs when radiotherapy to hepatoma

  4. Expression of kappa chain allotypes at the cell surface and in serum immunoglobulins of normal and allotype-suppressed heterozygous rabbits.

    PubMed Central

    Abdi, H B; Simons, M A; Young-Cooper, G O; Mage, R G

    1982-01-01

    The kappa light chain allotypes b4 and b5 were measured in the serum and on the surfaces of peripheral blood lymphocytes of normal and allotype-suppressed heterozygous rabbits. Surface immunoglobulins (sIg) were detected by fluorescence microscopy and additional quantitative data were obtained by flow microfluorometry. Although a few b5-suppressed animals had no b5 in serum or on cell surfaces for years, most b5-suppressed and all b4-suppressed animals studied had some cells with sIg of the suppressed type by 1 year of age. In suppressed animals the level of serum Ig remained depressed throughout life but cells with sIg appeared in disproportionately large numbers. The effect was particularly striking in those animals suppressed for the b4 type. PMID:6807841

  5. Multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions

    SciTech Connect

    St-Pierre, M.V.; Schwab, A.J.; Goresky, C.A.; Lee, W.F.; Pang, K.S.

    1989-02-01

    The technique of normal and retrograde rat liver perfusion has been widely used to probe zonal differences in drug-metabolizing activities. The validity of this approach mandates the same tissue spaces being accessed by substrates during both normal and retrograde perfusions. Using the multiple-indicator dilution technique, we presently examine the extent to which retrograde perfusion alters the spaces accessible to noneliminated references. A bolus dose of 51Cr-labeled red blood cells, 125I-albumin, 14C-sucrose and 3H2O was injected into the portal (normal) or hepatic (retrograde) vein of rat livers perfused at 10 ml per min per liver. The outflow perfusate was serially collected over 220 sec to characterize the transit times and the distribution spaces of the labels. During retrograde perfusion, red blood cells, albumin and sucrose profiles peaked later and lower than during normal perfusion, whereas the water curves were similar. The transit times of red blood cells, albumin and sucrose were longer (p less than 0.005), whereas those for water did not change. Consequently, retrograde flow resulted in significantly larger sinusoidal blood volumes (45%), albumin Disse space (42%) and sucrose Disse space (25%) than during normal flow, whereas the distribution spaces for total and intracellular water remained unaltered. The distension of the vascular tree was confirmed by electron microscopy, by which occasional isolated foci of widened intercellular recesses and spaces of Disse were observed. Cellular ultrastructure was otherwise unchanged, and there was no difference found between normal and retrograde perfusion for bile flow rates, AST release, perfusion pressure, oxygen consumption and metabolic removal of ethanol, a substrate with flow-limited distribution, which equilibrates rapidly with cell water (hepatic extraction ratios were virtually identical: normal vs. retrograde, 0.50 vs. 0.48 at 6 to 7.4 mM input concentration).

  6. Comparison of the effects of intra-articular injections of Hyaluronan and its chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee joints.

    PubMed

    Schiavinato, A; Finesso, M; Cortivo, R; Abatangelo, G

    2002-01-01

    Intraarticular injection of native hyaluronan (HA) or a cross-linked derivative are commonly utilized in the treatment of osteoarthritis. Unlike from native hyaluronan, the crosslinked HA derivative is a gel containing also other chemical entities. This study compares the local tolerability of these different preparations in normal rabbit knees, in order to provide further information on their biological effects. Synovial fluids were aspirated after single or repeated weekly injections (up to three) of the therapeutic agents and cell count was determined in a Burker chamber and in an automatic cell counter. The percentage of the different cell types was determined by light microscopy in semithin sections of fixed synovial fluid cytocentrifugate. Fragments of synovial membrane were also morphologically analyzed. In the synovial membrane no signs of inflammation were evident either after a single or repeated injections of native Hyaluronan (Hyalgan or Artz). In addition, the cell recruitment and the percentage of cell types in the synovial fluid was not statistically different from saline treated joints. After 3 weekly injections of the crosslinked HA derivative (Hylan G-F20, Synvisc) about 50% of the treated joints appeared slightly inflamed and in these joints a statistically significantly higher cell content was determined in the synovial fluid compared to placebo and native Hyaluronan treatment. In addition an unexpectedly high percentage of eosinophils was found in the synovial fluid and in the synovial membrane of slightly inflamed joints treated with crosslinked HA. The data obtained after repeated intra-articular injections in normal rabbit knee joints confirm the safety profile of native Hyaluronan.

  7. ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN CLINICALLY NOR-MAL BEAGLE DOGS [corrected].

    PubMed

    Jeon, Sunghoon; Lee, Gahyun; Lee, Sang-Kwon; Kim, Hyunwoo; Yu, Dohyeon; Choi, Jihye

    2015-01-01

    Standard ultrasonography is often insensitive for distinguishing normal vs. diseased states for canine abdominal organs. Ultrasonographic elastography is a new technique that is becoming increasingly available and may help to improve sensitivity. This study evaluated the feasibility, repeatability, and reproducibility of strain elastography of the liver, spleen, kidneys, and prostate in healthy dogs and described the elasticity of each organ using strain values and strain ratios. The reproducibility of strain elastography was excellent, and intraobserver repeatability was moderate to excellent. The strain value of each organ was not significantly different among dogs (liver = 143.38 ± 7.41, spleen = 141.04 ± 9.03, left renal cortex = 141.26 ± 7.50, right renal cortex = 145.80 ± 7.79, and prostate = 135.46 ± 5.80), except for the renal medulla (left = 51.19 ± 4.54 and right = 51.93 ± 5.09) (P < 0.05). The strain ratios for the liver, spleen, renal cortex, and prostate were similar with no significant difference (liver = 10.20 ± 1.47, spleen = 8.40 ± 1.53, left renal cortex = 9.62 ± 1.56, right renal cortex = 8.29 ± 1.63, and prostate = 8.20 ± 1.21), except for the renal medulla (left = 3.48 ± 0.68 and right = 2.95 ± 0.63) (P < 0.05). Our results indicated that strain elastography was feasible for estimating tissue stiffness in the canine liver, spleen, kidneys, and prostate. This study provides basic information for strain values and strain ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs.

  8. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis.

    PubMed Central

    Pinzani, M.; Milani, S.; Herbst, H.; DeFranco, R.; Grappone, C.; Gentilini, A.; Caligiuri, A.; Pellegrini, G.; Ngo, D. V.; Romanelli, R. G.; Gentilini, P.

    1996-01-01

    Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8774134

  9. Concentration of biologically active polyamines in rabbit meat, liver and kidney after slaughter and their changes during meat storage and cooking.

    PubMed

    Dadáková, Eva; Pelikánová, Tamara; Kalač, Pavel

    2012-03-01

    The concentration of putrescine (PUT), spermidine (SPD) and spermine (SPM) was determined in chilled meat and kidneys of 18 rabbits and in liver of 12 animals 24h after slaughter. Very low PUT concentrations were detected only in kidneys. Mean SPD levels were 2.2, 2.2, 61.7 and 32.7mgkg(-1) in saddle, leg, liver and kidneys, respectively. The respective SPM concentrations were 14.7, 8.0, 115 and 88.4mgkg(-1). SPD and SPM losses of about one third of the initial levels were apparent in saddles stored at -18°C for 8months. Losses of both polyamines of about 15-20% of the initial concentrations were found in saddles stored aerobically at +2°C for up to 9days. Stewing of saddles caused significant SPD and SPM losses of about 20-25%, while upon roasting and pan-roasting without oil a decrease of about 50% of the initial concentration was observed.

  10. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

    PubMed

    Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

  11. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

    PubMed

    Portillo Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

    2014-10-10

    NAFLD, and its more severe form with steatohepatitis (NASH), are common in patients with T2DM. However, they are usually believed to affect largely those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD (by the gold-standard liver magnetic resonance and spectroscopy or (1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age: 60±8 years, BMI: 33±5 kg/m(2), A1c: 7.6±1.3%). We measured: i) liver triglyceride content by (1)H-MRS; ii) systemic insulin sensitivity (HOMA-IR), and iii) adipose tissue insulin resistance (IR), both fasting (as the adipose tissue IR index: fasting plasma FFA x insulin) and during an OGTT (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (76% and 56%, respectively). The prevalence of NAFLD was higher in obese compared to non-obese patients, as well as with increasing BMI (p=0.03 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (p<0.01). Compared to non-obese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle), and particularly, adipose tissue (fasting/postprandial) insulin resistance (all p<0.01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of severe liver disease (NASH). Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

  12. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers.

    PubMed Central

    Schmitt-Gräff, A.; Krüger, S.; Bochard, F.; Gabbiani, G.; Denk, H.

    1991-01-01

    It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs. Images Figure 1 Figure 2 PMID:2024709

  13. Normal HDL-apo AI turnover and cholesterol enrichment of HDL subclasses in New Zealand rabbits with partial nephrectomy.

    PubMed

    Toledo-Ibelles, Paola; Franco, Martha; Carreón-Torres, Elizabeth; Luc, Gérald; Tailleux, Anne; Vargas-Alarcón, Gilberto; Fragoso, José Manuel; Aguilar-Salinas, Carlos; Luna-Luna, María; Pérez-Méndez, Oscar

    2013-04-01

    The kidney has been proposed to play a central role in apo AI catabolism, suggesting that HDL structure is determined, at least in part, by this organ. Here, we aimed at determining the effects of a renal mass reduction on HDL size distribution, lipid content, and apo AI turnover. We characterized HDL subclasses in rabbits with a 75% reduction of functional renal mass (Nptx group), using enzymatic staining of samples separated on polyacrylamide electrophoresis gels, and also performed kinetic studies using radiolabeled HDL-apo AI in this animal model. Creatinine clearance was reduced to 35% after nephrectomy as compared to the basal values, but without increased proteinuria. A slight, but significant modification of the relative HDL size distribution was observed after nephrectomy, whereas cholesterol plasma concentrations gradually augmented from large HDL2b (+54%) to small HDL3b particles (+150%, P<0.05). Cholesteryl esters were the increased fraction; in contrast, free cholesterol phospholipids and triglycerides of HDL subclasses were not affected by nephrectomy. HDL-apo AI fractional catabolic rates were similar to controls. Reduction of functional renal mass is associated to enrichment of HDL subclasses with cholesteryl esters. Structural abnormalities were not related to a low apo AI turnover, suggesting renal contribution to HDL remodeling beyond being just a catabolic site for these lipoproteins. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Analysis of rabbit intervertebral disc physiology based on water metabolism. I. Factors influencing metabolism of the normal intervertebral discs

    SciTech Connect

    Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Sano, A.

    1988-11-01

    Basic factors influencing the metabolism of intervertebral discs of rabbits were quantitatively analyzed based on the water metabolism. The blood flow surrounding the intervertebral disc was calculated using pharmacokinetic concepts from the data obtained by time-related tritiated water distribution analyses. The blood flow was estimated as 0.056 (mg/min/mg tissue) in the anterior annulus, 0.106 in the posterior annulus, 0.120 in the lateral annulus, and 0.084 in the nucleus pulposus, respectively (Experiment 1). Water content and fixed charge density in the intervertebral disc fractions also were measured (Experiment 2). The cations and uncharged small solutes transported into the disc tissue ranged in descending order from nucleus pulposus, lateral annulus, posterior annulus, to anterior annulus. The authors also calculated theoretically the swelling pressure of the proteoglycan in the intervertebral disc fractions from the results of Experiment 2. It was concluded that swelling pressure was highest in the nucleus pulposus, and lowest in the anterior annulus. The water in the posterior annulus is less exchangeable than in the other disc tissue fractions.

  15. Interaction of Lens culinaris lectin, concanavalin A, Ricinus communis agglutinin and wheat germ agglutinin with the cell surface of normal and transformed rat liver cells.

    PubMed

    Roth, J; Neupert, G; Thoss, K

    1975-01-01

    The observation of BOREK et al. (1973) on nonagglutinability of transformed rat liver cells by Lens culinaris lectin and our ultrastructural findings of a greater mobility of the Lens culinaris lectin receptors on transformed rat liver cells as compared to normal rat liver cells (ROTH 1975) initiated the present agglutination experiments on liver cells with lectins. For agglutination assay the microhemadsorption technique after FURMANSKI et al. (1973) was used with exception of several tests on EDTA-detached cells. The transformed rat liver cells exhibited, in contrast to the findings of BOREK et al. (1973), a positive microhemadsorption with Lens culinaris lectin as well as with Concanavalin A, Ricinus communis lectin and wheat germ agglutinin whereas the normal rat liver cells became positive only after a brief trypsin treatment. The significance of the difference in agglutinability of rat liver cells with Lens culinaris lectin and the other lectins used is discussed with regard to the cell-cell interaction mediated by lectins.

  16. The Effect of Intraoperative Restricted Normal Saline during Orthotopic Liver Transplantation on Amount of Administered Sodium Bicarbonate

    PubMed Central

    Sahmeddini, Mohammad Ali; Janatmakan, Farahzad; Khosravi, Mohammad Bagher; Ghaffaripour, Sina; Eghbal, Mohammad Hossein; Shokrizadeh, Sakine

    2014-01-01

    Background: Severe metabolic acidosis occurs during orthotopic liver transplantation (OLT) particularly during the anhepatic phase. Although NaHCO3 is considered as the current standard therapy, there are numerous adverse effects. The aim of this study was to determine whether the restricted use of normal saline during anesthesia could reduce the need for NaHCO3. Methods: In this study we enrolled 75 patients with end-stage liver disease who underwent OLT from February 2010 until September 2010 at the Shiraz Organ Transplantation Center. Fluid management of two different transplant anesthetics were compared. The effect of restricted normal saline fluid was compared with non-restricted normal saline fluid on hemodynamic and acid-base parameters at three times during OLT: after the skin incision (T1), 15 min before reperfusion (T2), and 5 min after reperfusion (T3). Results: There were no significant differences in demographic characteristics of the donors and recipients (P>0.05). In the restricted normal saline group there was significantly lower central venous pressure (CVP) than in the non-restricted normal saline group (P=0.002). No significant differences were noted in the other hemodynamic parameters between the two groups (P>0.05). In the non-restricted normal saline group arterial blood pH (P=0.01) and HCO3 (P=0.0001) were significantly less than the restricted normal saline group. The NaHCO3 requirement before reperfusion was significantly more than with the restricted normal saline group (P=0.001). Conclusion: Restricted normal saline administration during OLT reduced the severity of metabolic acidosis and the need for NaHCO3 during the anhepatic phase. Trial Registration Number: IRCT2013110711662N5 PMID:24850981

  17. Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits.

    PubMed

    Zhang, Shidong; Wang, Dongsheng; Wang, Xurong; Li, Shihong; Li, Jingyu; Li, Hongsheng; Yan, Zuoting

    2013-08-26

    Bai-Hu-Tang (BHT) was traditionally used to reduce fever heat and promote generation of body fluids. To investigate the effect and mechanism of BHT in the prevention of lipopolysaccharide (LPS) fever in manners of immune modulation. The model of fever syndrome of Chinese medicine pattern was imitated by LPS injection i.v. in rabbits, and BHT was gavaged. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6, 10) and immunoglobulin (IgG, IgA, and IgM) were determined by enzyme-linked immunosorbent assay (ELISA); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested by biochemical methods. Liver tissue damage was detected by hematoxylin-eosin (H&E) stain. Subpopulation of T cells was detected by Fluorescence Activated Cell Sorter (FACS). Genes expression of Toll-like receptor 4 (TLR4) and lipopolysaccharide binding protein (LBP) in liver tissue were assayed by real-time polymerase chain reaction (RT-PCR). The results demonstrated that BHT prevented sudden increase of IL-10, TNF-α, ALT and AST, and liver damage induced by LPS. BHT also prevented significant decrease of the percentage of CD(8+) T cells since LPS injection. At the same time, BHT did not affect the gene expression of TLR4 and serum concentration of three immunoglobulins, which were increased by LPS, but made gene expression of LBP higher. The results of this study indicated that BHT played an important role in immunity protection and anti-injury through preventing immunoinflammatory damage by LPS. The achievement thereby scientifically provided mechanism of BHT in the prevention of febrile disease, and supported its traditional use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver: Effect of lactate

    SciTech Connect

    Cerbon-Ambriz, J.; Cerbon-Solorzano, J.; Rojkind, M. )

    1991-03-01

    Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats. The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis. It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium. These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells.

  19. Normal and toxic zinc concentrations in serum/plasma and liver of psittacines with respect to genus differences.

    PubMed

    Puschner, B; St Leger, J; Galey, F D

    1999-11-01

    Determination of zinc concentration in serum/plasma and tissue of caged and aviary birds is commonly requested by practitioners because of an increased awareness of zinc toxicity. However, interpretation of zinc levels is often based on normal zinc concentrations established for poultry. Also, it is likely that intergenus differences exist in normal zinc concentrations of pet birds. In an attempt to determine normal and toxic concentration ranges, zinc concentrations in liver (n = 276) and serum/plasma (n = 260) collected from psittacines between 1990 and 1998 were analyzed. Zinc concentrations were determined by inductively coupled argon plasma emission spectroscopy analysis. The results were categorized by genus and, when available, by history. Birds that were diagnosed with zinc toxicosis (on the basis of history, clinical examination, pathology, and laboratory findings) were exempt and not included in establishing normal ranges. The results indicate that important differences occur with respect to genera. For example, cockatoos and Eclectus parrots have higher normal zinc concentrations in serum or plasma than other psittacines. In addition, analysis of all the submitted cases suggests that potentially toxic zinc concentrations in livers of psittacines can be well below the range considered toxic in chickens (> 200 ppm).

  20. The selective effect of plasma activated medium in an in vitro co-culture of liver cancer and normal cells

    NASA Astrophysics Data System (ADS)

    Duan, J.; Lu, X.; He, G.

    2017-01-01

    In this work, a co-culture system with liver cancer cell line HepG2 and normal cell line L02 is used to investigate the selective effect on cancer and normal cells by plasma activated medium (PAM), which is closer to the real environment where cancer cells develop. Besides, the co-culture system is a better model to study the selective effect than the widely used separate culture systems, where the cancer cell line and normal cell line are cultured independently. By using the co-culture system, it is found that there is an optimum dose of PAM to induce significant cancer cell apoptosis while keeping minimum damage to normal cells.

  1. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue

    PubMed Central

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-01-01

    Aim To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Methods Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. Results The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Conclusion Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role. PMID:23444241

  2. Reevaluation of sst₁ somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-7.

    PubMed

    Lupp, Amelie; Nagel, Falko; Schulz, Stefan

    2013-05-10

    The somatostatin receptor 1 (sst1) is widely distributed throughout the body and is also present in neoplastic tissues. However, little is known about its precise tissue distribution, regulation and function, which may in part be due to the lack of specific monoclonal anti-sst1 antibodies. We have characterized the novel rabbit monoclonal anti-human sst1 antibody UMB-7 using sst1-expressing cells and human pituitary samples. The antibody was then used for immunohistochemical staining of a large panel of formalin-fixed, paraffin-embedded human tissues. Western blot analyses of BON-1 cells and human pituitary revealed a broad band migrating at a molecular weight of 45,000-60,000. After enzymatic deglycosylation the size of this band decreased to a molecular weight of 45,000. UMB-7 yielded an efficient immunostaining of distinct cell populations in the human tissue samples with a predominance of plasma membrane staining, which was completely abolished by preadsorption of UMB-7 with its immunizing peptide. The sst1 receptor was detected in anterior pituitary, pancreatic islets, distal tubules, enteric ganglion cells and nerve fibers, chief cells of the gastric mucosa, macrophages and mast cells. In addition, sst1 was observed in pituitary adenomas, gastrointestinal neuroendocrine tumors and pheochromocytoma as well as in pancreatic adenocarcinomas, gastric carcinomas, urinary bladder carcinomas and sarcomas. UMB-7 may prove of great value in the identification of sst1-expressing tumors during routine histopathological examinations. This may open up new routes for diagnostic and therapeutic intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Identification and Characterization of Mesenchymal-Epithelial Progenitor-Like Cells in Normal and Injured Rat Liver

    PubMed Central

    Liu, Daqing; Yovchev, Mladen I.; Zhang, Jinghang; Alfieri, Alan A.; Tchaikovskaya, Tatyana; Laconi, Ezio; Dabeva, Mariana D.

    2016-01-01

    In normal rat liver, thymocyte antigen 1 (Thy1) is expressed in fibroblasts/myofibroblasts and in some blood progenitor cells. Thy1-expressing cells also accumulate in the liver during impaired liver regeneration. The origin and nature of these cells are not well understood. By using RT-PCR analysis and immunofluorescence microscopy, we describe the presence of rare Thy1+ cells in the liver lobule of normal animals, occasionally forming small collections of up to 20 cells. These cells constitute a small portion (1.7% to 1.8%) of nonparenchymal cells and reveal a mixed mesenchymal-epithelial phenotype, expressing E-cadherin, cytokeratin 18, and desmin. The most potent mitogens for mesenchymal-epithelial Thy1+ cells in vitro are the inflammatory cytokines interferon γ, IL-1, and platelet-derived growth factor-BB, which are not produced by Thy1+ cells. Thy1+ cells express all typical mesenchymal stem cell and hepatic progenitor cell markers and produce growth factor and cytokine mRNA (Hgf, Il6, Tgfa, and Tweak) for proteins that maintain oval cell growth and differentiation. Under appropriate conditions, mesenchymal-epithelial cells differentiate in vitro into hepatocyte-like cells. In this study, we show that the adult rat liver harbors a small pool of endogenous mesenchymal-epithelial cells not recognized previously. In the quiescent state, these cells express both mesenchymal and epithelial cell markers. They behave like hepatic stem cells/progenitors with dual phenotype, exhibiting high plasticity and long-lasting proliferative activity. PMID:25447047

  4. The influence of rich-in-cholesterol diet and fluoride ions contained in potable water upon the concentration of malondialdehyde and the activity of selected antioxidative enzymes in rabbit liver.

    PubMed

    Birkner, Ewa; Grucka-Mamczar, Ewa; Stawiarska-Pieta, Barbara; Birkner, Katarzyna; Zalejska-Fiolka, Jolanta; Kasperczyk, Sławomir; Kasperczyk, Aleksandra

    2009-01-01

    Two experiments have been carried out, each on 18 (male) rabbits of the New Zealand breed. In each of them, animals were divided into three groups of six: control group, cholesterol group (CH), and cholesterol + fluoride group (CH+F). Experimental hypercholesterolemia has been induced in the animals with the diet enriched with 0.5 and 2 g% of cholesterol/100 g of fodder/24 h. The rabbits from CH+F groups have also been administered fluoride ions contained in drinking water (3 mg F(-)/kg of body mass/24 h). The influence of fluoride ions upon the concentrations of malondialdehyde (MDA) and activity of antioxidative enzymes, superoxide dismutase (SOD), mitochondrial enzyme (MnSOD), cytoplasmatic enzyme (ZnCuSOD), and glutathione peroxidase (GPX), has been examined in liver of rabbits. An increase (in comparison with cholesterol groups) in the concentration of MDA in both (CH+F) groups in rabbit liver has been noted. Moreover, a decrease (statistically significant) of SOD and MnSOD has been found in cholesterol groups, as well as in groups (CH+F) in comparison with control group. Furthermore, a decrease in the activity of SOD under the influence of F(-) together with increased activity of MnSOD (statistically significant in comparison with cholesterol groups) have been observed. The activity of ZnCuSOD increased in statistically significant manner in (CH) groups vs control group and decreased (statistically significantly in relation to cholesterol groups) under the influence of F(-).

  5. Doppler ultrasound velocities and resistive indexes immediately after pediatric liver transplantation: normal ranges and predictors of failure.

    PubMed

    Jamieson, Lucy H; Arys, Bo; Low, Gavin; Bhargava, Ravi; Kumbla, Surekha; Jaremko, Jacob L

    2014-07-01

    We sought to determine the ranges of Doppler ultrasound findings immediately after pediatric liver transplantation that are associated with successful outcomes or postoperative complications. This study included consecutive children who underwent Doppler ultrasound less than 48 hours after liver transplantation from 2001 to 2011. Operative reports and clinical outcome data were recorded. We had 110 patients (54% girls) with mean age at transplantation of 2.9 years (median, 1.3 years; range, 0-14 years) and a median follow-up interval of 3.5 years. Two pediatric radiologists reviewed ultrasound images in consensus. We computed descriptive statistics, interindex correlations, and analysis of variance. Twenty-four of 110 patients had a vascular complication, most commonly hepatic arterial thrombosis (seven patients). Compared with published adult normal values, normal pediatric Doppler parameters at postoperative day 1 trended toward higher normal velocities and resistive indexes (up to 0.95). Absent or low-velocity common hepatic artery flow less than 50 cm/s or a common hepatic artery resistive index less than 0.50 were significantly associated with hepatic artery thrombosis, whereas absent or low-velocity portal venous flow less than 30 cm/s or low-velocity hepatic venous flow less than 25 cm/s were significantly associated with vascular complications and a monotonic hepatic venous waveform was significantly associated with venous complications. Flow in a pediatric liver on the first day after transplantation is normally hyperdynamic, especially in the youngest transplant recipients, and, as a result, low velocities or resistive indexes are particularly concerning for complications. The pediatric-specific ranges of expected posttransplantation Doppler ultrasound findings presented in this article should assist in identifying normal variation and potentially life-threatening complications.

  6. Preexisting epithelial diversity in normal human livers: a tissue-tethered cytometric analysis in portal/periportal epithelial cells.

    PubMed

    Isse, Kumiko; Lesniak, Andrew; Grama, Kedar; Maier, John; Specht, Susan; Castillo-Rama, Marcela; Lunz, John; Roysam, Badrinath; Michalopoulos, George; Demetris, Anthony J

    2013-04-01

    Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. "Virtually digested" WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa. Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here. Copyright © 2012 American Association for the Study of Liver Diseases.

  7. Pet rabbits.

    PubMed

    Hillyer, E V

    1994-01-01

    Pet rabbits are becoming more common, and rabbit owners are demanding quality veterinary care. This article provides a broad overview of pet rabbit medicine, which is a relatively new field compared to laboratory and farm rabbit medicine. The most common differential diagnoses for presenting complaints are summarized in table form. Disease conditions are reviewed individually in the text. Sources of further information on veterinary care of rabbits are listed throughout the text, in an appendix, and in the references.

  8. Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

    SciTech Connect

    East, C.; Grundy, S.M.; Bilheimer, D.W.

    1986-11-28

    Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia.

  9. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    SciTech Connect

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-03-15

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19{sup ARF} induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53.

  10. The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

    PubMed

    McKay, J; Rawlings, M D; Cobden, I; James, O F

    1982-10-01

    1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications.

  11. The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

    PubMed

    Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

    2017-03-20

    The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis.

  12. Optical properties of normal and thermally coagulated chicken liver tissue measured ex-vivo with diffuse reflectance

    NASA Astrophysics Data System (ADS)

    Hafeez-Ullah; Atif, M.; Firdous, S.; Mehmood, M. S.; Hamza, M. Y.; Imran, M.; Hussain, G.; Ikram, M.

    2011-02-01

    The purpose of the present study is to determine the optical properties of normal and thermally coagulated chicken liver at 720, 740, 770, 810, 825 and 840 nm wavelengths of laser irradiation. So, we were able to evaluate these optical properties (absorption and scattering coefficients) with ex-vivo study using Kubelka Munk Model (KMM) from the radial dependence of the diffuse reflectance with femtosecond pulsed laser in near IR region. These coefficients were significantly increased with coagulation. The penetration depths of the diffused light have been reported to a maximum value of 8.12 ± 0.36 mm in normal liver and 2.49 ± 0.17 mm in coagulated liver at 840 nm showing increasing behavior towards IR region. The Monte Carlo simulation was used to check the theoretical validation of measured optical properties of the tissue that showed a good match with our experimental results. We believe that these differences in optical properties will be helpful for the understanding arid optimal use of laser applications in medicine and differential diagnosis of tissues by using different optical methods. Especially for the investigation of biological tissue for photodynamic therapy (PDT), the knowledge of the specific optical properties and their thermo-induced changes is important.

  13. Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis

    PubMed Central

    Ulbrich, Friederike; Sticht, Carsten; Demory, Alexandra; Henzler, Thomas; Meyer, Mathias; Zierow, Johanna; Schneider, Sven; Breitkopf-Heinlein, Katja; Gaitantzi, Haristi; Spencer-Dene, Bradley; Arnold, Bernd; Klapproth, Kay; Géraud, Cyrill

    2017-01-01

    Microvascular endothelial cells (ECs) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific ECs control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSECs. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSECs using EC subtype-specific Stab2-Cre mice. Genetic inactivation of hepatic angiocrine Bmp2 signaling in Stab2-Cre;Bmp2fl/fl (Bmp2LSECKO) mice caused massive iron overload in the liver and increased serum iron levels and iron deposition in several organs similar to classic hereditary hemochromatosis. Iron overload was mediated by decreased hepatic expression of hepcidin, a key regulator of iron homeostasis. Thus, angiocrine Bmp2 signaling within the hepatic vascular niche represents a constitutive pathway indispensable for iron homeostasis in vivo that is nonredundant with Bmp6. Notably, we demonstrate that organ-specific angiocrine signaling is essential not only for the homeostasis of the respective organ but also for the homeostasis of the whole organism. PMID:27903529

  14. Controlled Release and Antitumor Effect of Pluronic F127 Mixed with Cisplatin in a Rabbit Model

    SciTech Connect

    Sonoda, Akinaga Nitta, Norihisa; Ohta, Shinich; Nitta-Seko, Ayumi; Morikawa, Shigehiro; Tabata, Yasuhiko; Takahashi, Masashi; Murata, Kiyoshi

    2010-02-15

    The purpose of this study was to evaluate pluronic F127 for the controlled release of cisplatin in a rabbit model. Pluronic F127 becomes liquid at temperatures <25{sup o}C and converts to a gelatinous state at temperatures between 25 and 60{sup o}C. Six Japanese white rabbits were injected with pluronic + cisplatin (n = 3, renal group A) or saline + cisplatin (n = 3, renal group B) to measure the platinum concentration in kidneys. Another 25 rabbits with VX2 liver tumors were divided into five equal groups. They were injected with saline, saline + cisplatin, iodized oil + cisplatin, pluronic alone, or pluronic + cisplatin and labeled as liver groups A, B, C, D, and E, respectively. The antitumor effect of pluronic was then assessed. In the presence of pluronic, the platinum concentration in the kidneys of rabbits remained relatively high. In animals with liver tumors, the delivery of pluronic + cisplatin produced higher tumor reduction rates (P < 0.05) than in the other groups, without apparent damage to normal liver tissue. We conclude that pluronic is useful for the controlled release of cisplatin in a rabbit model.

  15. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels.

    PubMed

    Bikle, D D; Halloran, B P; Gee, E; Ryzen, E; Haddad, J G

    1986-09-01

    We determined the free fraction of 25-dihydroxyvitamin D (25OHD) in the serum of subjects with clinical evidence of liver disease and correlated these measurements to the levels of vitamin D binding protein and albumin. These subjects when compared to normal individuals had lower total 25OHD levels, higher percent free 25OHD levels, but equivalent free 25OHD levels. These subjects also had reduced vitamin D binding protein and albumin concentrations. The total concentration of 25OHD correlated positively with both vitamin D binding protein and albumin, whereas the percent free 25OHD correlated negatively with vitamin D binding protein and albumin. The free 25OHD levels did not correlate with either vitamin D binding protein or albumin. We conclude that total vitamin D metabolite measurements may be misleading in the evaluation of the vitamin D status of patients with liver disease, and recommend that free 25OHD levels also be determined before making a diagnosis of vitamin D deficiency.

  16. Distribution of albumin and alpha-fetoprotein mRNAs in normal, hyperplastic, and preneoplastic rat liver.

    PubMed Central

    Alpini, G.; Aragona, E.; Dabeva, M.; Salvi, R.; Shafritz, D. A.; Tavoloni, N.

    1992-01-01

    The nature of bile duct-like (oval) cells proliferating during chemical hepatocarcinogenesis has been controversial. To investigate this issue further, the authors compared the hepatic distribution of albumin (ALB) and alpha-fetoprotein (AFP) mRNAs in rats in which oval cell proliferation was induced by feeding a choline-devoid diet containing 0.1% ethionine (CDE, a hepatocarcinogenic diet) with that in normal rats and in rats in which biliary epithelial cell hyperplasia was induced by either bile duct ligation or feeding alpha-naphthylisothiocyanate (ANIT). Northern blot analysis in parenchymal and nonparenchymal liver cells isolated from these animals demonstrated that ALB mRNA was present in the hepatocytes of both control and experimental animals, whereas this transcript was detected in nonparenchymal epithelial cells only in CDE-fed rats. Alpha-fetoprotein mRNA was not seen in either parenchymal or nonparenchymal cells isolated from normal or hyperplastic livers induced by bile duct ligation or ANIT feeding. In CDE-fed rats, however, both parenchymal and nonparenchymal cell populations displayed AFP message. In situ hybridization directly demonstrated nonparenchymal cell expression of both ALB and AFP transcripts in CDE-fed rats. Most surprisingly, ALB and AFP mRNAs were also detected by in situ hybridization in occasional nonparenchymal cells located in portal tracts near the limiting plate in normal liver, as well as under conditions associated with bile duct hyperplasia. Immunohistochemical studies of intermediate filament proteins, cytokeratin 19 (a marker of glandular epithelia), vimentin (a marker of mesenchymal lineage), and desmin (a marker of muscle cell differentiation) demonstrated that oval cells, as well as normal and hyperplastic bile duct cells, were positive for cytokeratin 19 and negative for both vimentin and desmin. Cytokeratin-positive oval cells formed duct profiles and were connected to preexisting ductules and ducts. These results are

  17. Spatial Distribution of Iron Within the Normal Human Liver Using Dual-Source Dual-Energy CT Imaging.

    PubMed

    Abadia, Andres F; Grant, Katharine L; Carey, Kathleen E; Bolch, Wesley E; Morin, Richard L

    2017-05-29

    Explore the potential of dual-source dual-energy (DSDE) computed tomography (CT) to retrospectively analyze the uniformity of iron distribution and establish iron concentration ranges and distribution patterns found in healthy livers. Ten mixtures consisting of an iron nitrate solution and deionized water were prepared in test tubes and scanned using a DSDE 128-slice CT system. Iron images were derived from a 3-material decomposition algorithm (optimized for the quantification of iron). A conversion factor (mg Fe/mL per Hounsfield unit) was calculated from this phantom study as the quotient of known tube concentrations and their corresponding CT values. Retrospective analysis was performed of patients who had undergone DSDE imaging for renal stones. Thirty-seven patients with normal liver function were randomly selected (mean age, 52.5 years). The examinations were processed for iron concentration. Multiple regions of interest were analyzed, and iron concentration (mg Fe/mL) and distribution was reported. The mean conversion factor obtained from the phantom study was 0.15 mg Fe/mL per Hounsfield unit. Whole-liver mean iron concentrations yielded a range of 0.0 to 2.91 mg Fe/mL, with 94.6% (35/37) of the patients exhibiting mean concentrations below 1.0 mg Fe/mL. The most important finding was that iron concentration was not uniform and patients exhibited regionally high concentrations (36/37). These regions of higher concentration were observed to be dominant in the middle-to-upper part of the liver (75%), medially (72.2%), and anteriorly (83.3%). Dual-source dual-energy CT can be used to assess the uniformity of iron distribution in healthy subjects. Applying similar techniques to unhealthy livers, future research may focus on the impact of hepatic iron content and distribution for noninvasive assessment in diseased subjects.

  18. SERUM SICKNESS IN RABBITS

    PubMed Central

    Fleisher, Mover S.; Jones, Lloyd

    1931-01-01

    1. The injection of a single large dose of normal horse serum into rabbits results in the appearance 3 to 8 days later of erythematous and edematous reactions on the ears in 68.9 per cent of the animals. 2. The injections may be given by any of several routes and reactions appear when the site of injection is definitely distant from the ears. 3. Injections of various antisera into rabbits cause the appearance of similar reactions. 4. These reactions can be considered as manifestations of serum sickness in rabbits. PMID:19869943

  19. Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits.

    PubMed

    Vardavas, Alexander I; Stivaktakis, Polychronis D; Tzatzarakis, Manolis N; Fragkiadaki, Persefoni; Vasilaki, Fotini; Tzardi, Maria; Datseri, Galateia; Tsiaoussis, John; Alegakis, Athanasios K; Tsitsimpikou, Christina; Rakitskii, Valerii N; Carvalho, Félix; Tsatsakis, Aristidis M

    2016-08-01

    Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Comparison of Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris, Spodoptera frugiperda, and COS7 cells for recombinant gene expression. Application to a rabbit liver carboxylesterase.

    PubMed

    Morton, C L; Potter, P M

    2000-11-01

    Expression of a rabbit liver carboxylesterase has been achieved in several different model systems including Escherichia coli, Pichia pastoris, Saccharomyces cerevisiae, Spodoptera frugiperda, and COS7 cells. Although, recombinant protein was observed in E. coli sonicates, little or no enzymatic activity was detected. Similarly, no activity was observed following expression in S. cerevisiae. In contrast, active protein was produced in P. pastoris, from S. frugiperda following baculoviral infection and in COS7 cells following transient transfection of plasmid DNA. For the preparation of small amounts of protein for kinetic and biochemical studies, enzyme expressed in P. pastoris has proved sufficient. However, to produce large amounts of carboxylesterase for structural studies, baculoviral-mediated expression of a secreted form of the protein in S. frugiperda was the most efficient. Using this system, we have generated and purified milligram quantities of essentially pure protein. These results demonstrate that the choice of in vitro system for the generation of large amounts of active carboxylesterase, and probably most endoplasmic reticulum processed proteins, is crucial for high level expression and subsequent purification.

  1. Levels of liver glycogen during normal and radiation-induced metamorphosis in Rana cyanophlyctis.

    PubMed

    Ahmad, M; Ashraf, J; Siddiqui, P Q; Khan, K R

    1979-01-01

    This study shows that significant changes in the pattern of glycogen deposition are brought about by irradiation with 2,000 R gamma-rays. The sharp fall during the 1st week can be attributed to its emergent mobilization. However, glycogen stored in the liver during the 2nd and 3rd week prior to the resorptive process substantiates the fact that tadpoles complete metamorphic transformations in spite of sublethal irradiation.

  2. Estimating Functional Liver Reserve Following Hepatic Irradiation: Adaptive Normal Tissue Response Models

    PubMed Central

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and Methods From 2005–2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1−(ICG-R15pre-RT/ICG-R15post-RT)] where no toxicity was observed using a beta distribution function. Results Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ≥78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p<0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation. PMID:24813090

  3. An ultrastructural and morphometric study of the liver of normal and copper-poisoned sheep.

    PubMed Central

    Gooneratne, S. R.; Howell, J. M.; Cook, R. D.

    1980-01-01

    In sheep given copper (Cu) at the level of 10 ml of a 0.2% solution of CuSO4.5H2O/kg body weight, the volume density of nuclei and cytoplasm of hepatocytes increased and the volume density of the sinusoids and the space of Disse decreased. These changes were interpreted as an indication of cellular swelling. There was a significant increase in volume density, number, and absolute volume of lysosomes when Cu was given. The greatest increase in number occurred during the pre-hemolytic period (mean = 48 days), and the highest increase in volume occurred thereafter. Thus, the most extensive proliferation of lysosomes occurred in livers of the pre-hemolytic sheep, and the hemolytic sheep had the largest and heaviest lysosomes. The liver necrosis in sheep undergoing hemolysis was possible caused by hydrolytic enzymes released by the rupture of the enclosing lysosomal membranes. The significant increase in volume density of mitochondria observed in livers of sheep given Cu was due to an increase in volume (swelling) rather than an increase in number. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7377289

  4. Low-level direct electrical current therapy for hepatic metastases. I. Preclinical studies on normal liver.

    PubMed Central

    Griffin, D. T.; Dodd, N. J.; Zhao, S.; Pullan, B. R.; Moore, J. V.

    1995-01-01

    Low-level direct electrical current has shown promise as a potential therapeutic modality (direct current therapy; DCT) in the treatment of malignant disease, including metastases, but to date much experimental work has been empirical and has added little to our knowledge of the mechanisms involved. As a prerequisite to a clinical trial for metastases in the liver, we have employed an in vivo liver model to examine the quantitative and qualitative relationships between electrode polarity, charge and tissue necrosis. Two distinct regions of necrosis were induced, distinguishable histologically and by magnetic resonance imaging: (i) a cylindrical region of primary necrosis centred on the electrode, its volume directly proportional to the charge passed, but greater at the anode than cathode; and (ii) a wedge-shaped infarct, apex at the electrode and base extending to the liver edge. The extent of this infarct was again greater at the anode than the cathode, but showed a sigmoidal relationship with charge. Results indicate pH changes at the electrodes as likely mediators of tissue injury, but show also that significant distant ischaemic injury can occur as a consequence of primary damage. These findings should be considered when selecting tumours for possible direct current therapy and when determining the sites of electrode placement. Images Figure 1 PMID:7599063

  5. Ca/P concentration ratio at different sites of normal and osteoporotic rabbit bones evaluated by Auger and energy dispersive X-ray spectroscopy.

    PubMed

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Tzaphlidou, Margaret

    2012-03-01

    Osteoporosis is a systemic skeletal disorder associated with reduced bone mineral density and the consequent high risk of bone fractures. Current practice relates osteoporosis largely with absolute mass loss. The assessment of variations in chemical composition in terms of the main elements comprising the bone mineral and its effect on the bone's quality is usually neglected. In this study, we evaluate the ratio of the main elements of bone mineral, calcium (Ca), and phosphorus (P), as a suitable in vitro biomarker for induced osteoporosis. The Ca/P concentration ratio was measured at different sites of normal and osteoporotic rabbit bones using two spectroscopic techniques: Auger electron spectroscopy (AES) and energy-dispersive X-ray spectroscopy (EDX). Results showed that there is no significant difference between samples from different genders or among cortical bone sites. On the contrary, we found that the Ca/P ratio of trabecular bone sections is comparable to cortical sections with induced osteoporosis. Ca/P ratio values are positively related to induced bone loss; furthermore, a different degree of correlation between Ca and P in cortical and trabecular bone is evident. This study also discusses the applicability of AES and EDX to the semiquantitative measurements of bone mineral's main elements along with the critical experimental parameters.

  6. The pentose phosphate pathway in rabbit liver. Studies on the metabolic sequence and quantitative role of the pentose phosphate cycle by using a system in situ

    PubMed Central

    Williams, J. F.; Rienits, K. G.; Schofield, P. J.; Clark, M. G.

    1971-01-01

    1. The reactions of the pentose phosphate cycle were investigated by the intraportal infusion of specifically labelled [14C]glucose or [14C]ribose into the liver of the anaesthetized rabbit. The sugars were confined in the liver by haemostasis and metabolism was allowed to proceed for periods up to 5min. Metabolism was assessed by measuring the rate of change of the specific radioactivity of CO2, the carbon atoms of glucose 6-phosphate, fructose 6-phosphate and tissue glucose. 2. The quotient oxidation of [1-14C]glucose/oxidation of [6-14C]glucose as measured by the incorporation into respiratory CO2 was greater than 1.0 during most of the time-course and increased to a maximum of 3.1 but was found to decrease markedly upon application of a glucose load. 3. The estimate of the pentose phosphate cycle from C-1/C-2 ratios generally increased during the time-course, whereas the estimate of the pentose phosphate cycle from C-3/C-2 ratios varied depending on whether the ratios were measured in glucose or hexose 6-phosphates. 4. The distribution of 14C in hexose 6-phosphate after the metabolism of [1-14C]ribose showed that 65–95% of the label was in C-1 and was concluded to have been the result of a rapidly acting transketolase exchange reaction. 5. Transaldolase exchange reactions catalysed extensive transfer of 14C from [2-14C]glucose into C-5 of the hexose 6-phosphates during the entire time-course. The high concentration of label in C-4, C-5 and C-6 of the hexose 6-phosphates was not seen in tissue glucose in spite of an unchanging rate of glucose production during the time-course. 6. It is concluded that the reaction sequences catalysed by the pentose phosphate pathway enzymes do not constitute a formal metabolic cycle in intact liver, neither do they allow the definition of a fixed stoicheiometry for the dissimilation of glucose. PMID:5124395

  7. Factorial experiment to determine influence of fish protein and fish oil on serum and liver lipids in rabbits.

    PubMed

    Bergeron, N; Deshaies, Y; Jacques, H

    1992-01-01

    Rabbits were fed purified diets consisting of casein (CA), fish protein (FP), and soy protein (SP) combined with MaxEpa oil (ME) or corn oil (CN) to determine the effects of dietary protein and lipid sources on serum total, lipoprotein, and hepatic lipid levels. Dietary proteins and lipids exerted significant (p < 0.05) separate effects on serum total cholesterol (TC) (p < 0.005), very-low-density lipoprotein cholesterol (VLDL-C) (p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (p < 0.001), whereas only dietary proteins significantly affected low-density lipoprotein cholesterol (LDL-C) (p < 0.001) and the LDL-C/HDL-C ratio (p < 0.05). Hence, FP induced serum TC (233 mg/dl), VLDL-C (22 mg/dl), and LDL-C (151 mg/dl) intermediary to hypercholesterolemic CA (TC, 319 mg/dl; VLDL-C, 57 mg/dl; LDL-C, 204 mg/dl) and cholesterol-lowering SP (TC, 129 mg/dl; VLDL-C 19 mg/dl; LDL-C, 84 mg/dl). The twofold rise in HDL-C on feeding FP (35 mg/dl), compared with CA (20 mg/dl) and SP (16 mg/dl), resulted in a drop in LDL-C/HDL-C to a level similar to that of SP groups. The cholesterol-lowering action of ME (188 mg/dl), in contrast to CN (266 mg/dl), was reflected mainly in VLDL (ME, 15 mg/dl; CN, 50 mg/dl) but also in HDL (ME, 16 mg/dl; CN, 31 mg/dl) fractions. Compared with CN, the significant (p < 0.05) ME-induced rise in serum and VLDL triglycerides was accompanied by a significant (p < 0.001) drop in lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

    When filling prescriptions for a rabbit, it is important to know whether the rabbit is a pet or is being raised as a source of food for human consumption. Several drugs widely used for pet rabbits are prohibited from exralabel use in animals raised for food production. The list of banned drugs should always be perused prior to filling a prescription for a rabbit being raised for food production. Since no veterinary-approved products exist for rabbits and most medications must be compounded, pharmacists are likely to encounter prescriptions for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy and common diseases will assist pharmacists in distinguishing between safe and dangerous drugs for administration to rabbits.

  9. Modulated expression of a nuclear-associated glycoprotein during normal rat liver development and in various hepatoma cells.

    PubMed

    Goulet, Francine; Napa, Ioana Diana; Solomon, Luc; Morin, Odette; Islam, Nazrul

    2006-01-01

    Liver plays a major role in systemic detoxification and drug metabolism. NF-164, a protein of 164 kDa predominantly localized in hepatocyte nuclei, was found to be present in increasing amounts during liver maturation. In addition, fetal rat hepatocytes had ten times, and neonatal five times less of this protein than adult hepatocytes. It was also detected in an albumin producing hepatoma cell line, but not in three other lines that have lost several differentiated functions. These data suggest that NF-164 expression is development-dependent and that it may be a marker for both normal and malignant hepatocyte differentiation. NF-164 seems to be liver-specific, since it was not detected in rat brain, spleen, kidney, lung and bovine thymus. It was purified from adult rat hepatocyte nuclei. Its estimated pI is 6.8. Its total amino acid composition and partial amino acid sequence is also being reported. Despite major differences between their respective contents in amino acids, partial sequences showed homologies with carbamyl phosphate synthetase I (CPSI). These observations may suggest that NF-164 also shares some functional features with this enzyme.

  10. Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens.

    PubMed Central

    Pfeifer, A M; Cole, K E; Smoot, D T; Weston, A; Groopman, J D; Shields, P G; Vignaud, J M; Juillerat, M; Lipsky, M M; Trump, B F

    1993-01-01

    Normal human liver tissue and cultured human hepatocytes are valuable models to study xenobiotic metabolism and toxicity, but they only have a limited in vitro life-span and are not readily available. This report describes the establishment of replicative cultures of human adult liver epithelial cells in serum-free medium. The longevity of three of these cultures, derived from different donors, was extended by introduction of the simian virus 40 large T antigen gene. Two cell lines, THLE-2 and -3, established with a recombinant simian virus 40 large T antigen virus have undergone > 100 population doublings, are nontumorigenic when injected into athymic nude mice, have near-diploid karyotypes, and do not express alpha-fetoprotein. The cells express cytokeratin 18 and albumin in early passage, whereas higher-passage cells in logarithmic-phase growth also express cytokeratin 19. THLE-2 and -3 cells metabolize benzo[a]pyrene, N-nitrosodimethylamine, and aflatoxin B1 to their ultimate carcinogenic metabolites that adduct DNA, which indicates functional cytochrome P450 pathways. Other enzymes involved in metabolism of chemical carcinogens, such as epoxide hydrolase, NADPH cytochrome P450 reductase, superoxide dismutase, catalase, glutathione S-transferases, and glutathione peroxidase are also retained by THLE cells. Thus, these immortalized human liver cells constitute an in vitro model for pharmacotoxicological studies and for the investigation of etiology and pathogenesis of human hepatocellular carcinoma. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7685115

  11. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    SciTech Connect

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang . E-mail: jianggl@21cn.com

    2006-05-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD{sub 5} (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD{sub 5}) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended.

  12. [Enzyme levels and morphological picture of normal and cirrhotic rat livers following portal vein ligation and subcutaneous transposition of the spleen].

    PubMed

    Zelder, O; Dorn, R; Bürcklein, H H; Bode, Ch; Bode, J C; Jerusalem, C R

    1975-01-01

    The effect of portal vein ligation after subcutaneous transposition of the spleen is investigated on enzyme-activities. and morphological pattern of the normal and cirrhotic rat-liver. The increase of glycolytic enzyme-activities and the decrease of enzyme-activities of oxidative metabolic pathways can be explained by adaptation on throttled blood supply of the liver. Significant decrease of arginase-activity (urea-cycle) can not be explained by reduced protein content of food (pair-fed-animals). Diminished substrate (ammonia)-level (NH3/t/hepatocytes) may be an explanation. Histological pattern of normal and cirrhotic rat liver is nearly unchanged after portal vein ligation.

  13. Partial characterization of a highly conserved aspartyl kinase (AK) in normal human liver.

    PubMed

    Arenas-Díaz, G; Marshall, S H

    1990-01-01

    Subcellular fractions from human liver were assayed for aspartyl kinase (AK) activity measured by standard spectrophotometric methods. Along the purification procedure three different fractions displayed the expected enzyme activity. Interestingly, two of these fractions were specifically recognized by antibodies raised against E. coli aspartate kinases, suggesting a high degree of evolutionary conservation for these ubiquitous enzymes for prokaryotes. Since their known function in bacteria is not strictly required in eukaryotes, these observation imply that the presence and activity of aspartyl kinase(s) in mammals might represent putative regulatory roles for these enzymes in eukaryotic cell metabolism.

  14. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

    PubMed

    Lee, Jieun; Yoon, Kijung; Ryu, Seungho; Chang, Yoosoo; Kim, Hyoung-Ryoul

    2017-01-01

    We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001). As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development.

  15. Impact of PET/CT image reconstruction methods and liver uptake normalization strategies on quantitative image analysis.

    PubMed

    Kuhnert, Georg; Boellaard, Ronald; Sterzer, Sergej; Kahraman, Deniz; Scheffler, Matthias; Wolf, Jürgen; Dietlein, Markus; Drzezga, Alexander; Kobe, Carsten

    2016-02-01

    In oncological imaging using PET/CT, the standardized uptake value has become the most common parameter used to measure tracer accumulation. The aim of this analysis was to evaluate ultra high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on quantification. We analyzed 40 PET/CT scans of lung cancer patients who had undergone PET/CT. Standardized uptake values corrected for body weight (SUV) and lean body mass (SUL) were determined in the single hottest lesion in the lung and normalized to the liver for UHD and OSEM reconstruction. Quantitative uptake values and their normalized ratios for the two reconstruction settings were compared using the Wilcoxon test. The distribution of quantitative uptake values and their ratios in relation to the reconstruction method used were demonstrated in the form of frequency distribution curves, box-plots and scatter plots. The agreement between OSEM and UHD reconstructions was assessed through Bland-Altman analysis. A significant difference was observed after OSEM and UHD reconstruction for SUV and SUL data tested (p < 0.0005 in all cases). The mean values of the ratios after OSEM and UHD reconstruction showed equally significant differences (p < 0.0005 in all cases). Bland-Altman analysis showed that the SUV and SUL and their normalized values were, on average, up to 60 % higher after UHD reconstruction as compared to OSEM reconstruction. OSEM and HD reconstruction brought a significant difference for SUV and SUL, which remained constantly high after normalization to the liver, indicating that standardization of reconstruction and the use of comparable SUV measurements are crucial when using PET/CT.

  16. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    PubMed Central

    Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

    2016-01-01

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage. PMID:27148080

  17. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men

    PubMed Central

    Lee, Jieun; Yoon, Kijung; Ryu, Seungho; Chang, Yoosoo; Kim, Hyoung-Ryoul

    2017-01-01

    We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001). As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development. PMID:28234943

  18. Penicillamine as an adjuvant to antimonial therapy of schistosomiasis: effect on liver function tests in rabbits and on antischistosomal activity*

    PubMed Central

    Khayyal, M. T.; Saleh, S.; El Masri, A. M.

    1973-01-01

    Earlier work has shown that penicillamine reduces the acute toxicity of antimonyl potassium tartrate (APT) as well as the abnormal ECG changes it induces. In the present study, the possible protective effect of penicillamine on the hepatic toxicity of APT was investigated. Tests of liver function showed changes in the level of serum aspartate and alanine aminotransferase and of alkaline phosphatase, and in the beta-/alpha-lipoprotein ratio, in response to antimony treatment. The changes were significantly reduced by penicillamine, though the effect depended on the dose. Penicillamine was found to give the best overall protection without affecting the antischistosomal efficacy of the antimonial when a 1:2 APT/penicillamine ratio was used. The findings provide further evidence of the potential usefulness of penicillamine in the antimonial treatment of schistosomiasis. PMID:4543547

  19. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  20. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  1. Small difference in international normalized ratio may yield a significant impact on prioritizing patients listed for liver transplantation.

    PubMed

    Sarvary, E; Seregely, Zs; Fazakas, J; Kovacs, F; Gaal, I; Beko, G; Varga, J; Kobori, L; Nemes, B; Gorog, D; Varga, M; Langer, R M; Monostory, K; Jaray, J; Gerlei, Zs

    2010-01-01

    Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.

  2. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    SciTech Connect

    Kageyama, Ken Yamamoto, Akira Okuma, Tomohisa Hamamoto, Shinichi Takeshita, Toru Sakai, Yukimasa Nishida, Norifumi Matsuoka, Toshiyuki Miki, Yukio

    2013-10-15

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

  3. Evidence-Based Advances in Rabbit Medicine.

    PubMed

    Summa, Noémie M; Brandão, João

    2017-09-01

    Rabbit medicine has been continuously evolving over time with increasing popularity and demand. Tremendous advances have been made in rabbit medicine over the past 5 years, including the use of imaging tools for otitis and dental disease management, the development of laboratory testing for encephalitozoonosis, or determination of prognosis in rabbits. Recent pharmacokinetic studies have been published, providing additional information on commonly used antibiotics and motility-enhancer drugs, as well as benzimidazole toxicosis. This article presents a review of evidence-based advances for liver lobe torsions, thymoma, and dental disease in rabbits and controversial and new future promising areas in rabbit medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Effects of catechin-rich oil palm leaf extract on normal and hypertensive rats' kidney and liver.

    PubMed

    Jaffri, Juliana M; Mohamed, Suhaila; Ahmad, Intan Natasya; Mustapha, Noordin M; Manap, Yazid A; Rohimi, Nordanial

    2011-09-15

    Catechin-rich oil palm (Elaeis guineensis) leaf extract (OPLE) possesses good ex vivo vasodilation, antioxidant and cardiovascular properties. This study evaluated the beneficial or toxic effects of OPLE on the liver and kidneys of normal and hypertensive rats. The OPLE (500mg/kg body weight) were administered orally to normal Wistar Kyoto rats, spontaneously hypertensive rats (SHR) and N-ω-nitro-l-arginine methyl ester (l-NAME)-induced NO-deficient hypertensive rats. The OPLE reduced hypertension in NO-deficient rats, but not in SHR. Hepatocytes or glomeruli injury and oxidative markers were high in hypertensive rats compared to normal rats, and they were reduced (p<0.05) by OPLE supplementation, even when there was no blood pressure reduction. Unlike the hypertensive drug captopril, the OPLE showed no toxicity to normal rats. The dose reported is equivalent 0.5g of catechins/day for humans or 2.5cups of tea. The catechins are from an abundant alternative source for potential use as functional food.

  5. Normal birth weight piglets with impaired preweaning growth utilize alternative metabolic pathways in the liver

    USDA-ARS?s Scientific Manuscript database

    The present study was designed to determine if normal weight pigs that grow poorly during the pre-weaning period have altered hepatic metabolism, as reported for intrauterine growth retarded pigs. Eight pairs of average birth weight pigs (1.57 +/- 0.05 kg) were identified that diverged in weight by...

  6. Therapeutic efficacy of novel microwave-sensitized mPEG-PLGA@ZrO2@(DOX + ILS) drug-loaded microspheres in rabbit VX2 liver tumours.

    PubMed

    Mao, Jingsong; Tang, Shunsong; Hong, Duo; Zhao, Fan; Niu, Meng; Han, Xiangjun; Qi, Ji; Bao, Han; Jiang, Yutian; Fu, Changhui; Long, Dan; Meng, Xianwei; Su, Hongying

    2017-03-09

    The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO2@(DOX + ILS) (mPEG-PLGA@ZrO2@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO2 into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO2@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres in a rabbit VX2 liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.

  7. Effects of grape pomace on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

    PubMed Central

    Choi, Chang-Sook; Chung, Hae-Kyung; Choi, Mi-Kyung

    2010-01-01

    The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing H2O2 that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and

  8. Studies on responsiveness of hepatoma cells to catecholamines. II. Comparison of beta-adrenergic responsiveness of rat ascites hepatoma cells with cultured normal rat liver cells.

    PubMed

    Miyamoto, K; Matsunaga, T; Takemoto, N; Sanae, F; Koshiura, R

    1985-05-01

    The pharmacological properties of beta-adrenoceptors in rat ascites hepatoma cells were compared with those in normal rat liver cells which were cultured for 24 hr after collagenase digestion. Adenylate cyclases in the homogenates of cultured normal rat liver cells and rat ascites hepatoma cells, AH44, AH66, AH109A, AH130 and AH7974, were all activated by isoproterenol or NaF to different degrees. The enzyme in rat liver cells was activated by several beta 2-agonists but those in all hepatoma cells hardly responded. Furthermore, salbutamol, a beta 2-partial agonist, antagonized the cyclase activation by isoproterenol in AH130 cells. The Kact value of isoproterenol for the activation of adenylate cyclase in AH130 cells was smaller than that in rat liver cells. A comparison of the Ki values of beta-antagonists for the inhibition of isoproterenol-stimulated cyclase activity shows that while the Ki values of propranolol and butoxamine in AH130 cells were similar to those in rat liver cells, a significant difference was observed in the values for beta 1-selective antagonists between AH130 cells and rat liver cells. The Ki values of metoprolol and atenolol for AH130 cells were 137- and 90-fold lower, respectively, than for normal rat liver cells. From these findings, it is strongly suggested that beta-adrenoceptors in rat ascites hepatoma cells including AH130 cells have similar properties to the mammalian beta 1-receptor.

  9. Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit.

    PubMed

    Vignozzi, Linda; Filippi, Sandra; Comeglio, Paolo; Cellai, Ilaria; Sarchielli, Erica; Morelli, Annamaria; Rastrelli, Giulia; Maneschi, Elena; Galli, Andrea; Vannelli, Gabriella Barbara; Saad, Farid; Mannucci, Edoardo; Adorini, Luciano; Maggi, Mario

    2014-03-25

    A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with testosterone (T), with the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA), or with the anti-TNFα mAb infliximab. Rabbits fed a regular diet were used as controls. Liver histomorphological and gene expression analysis demonstrated NASH in HFD rabbits. Several genes related to inflammation (including TNFα), activation of stellate cells, fibrosis, and lipid metabolism parameters were negatively associated to maximal acetylcholine (Ach)-induced relaxation in penis. When all these putative liver determinants of penile Ach responsiveness were tested as covariates in a multivariate model, only the association between hepatic TNFα expression and Ach response was confirmed. Accordingly, circulating levels of TNFα were increased 15-fold in HFD rabbits. T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.

  10. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits

    PubMed Central

    Hassan, Anwar S.; Ahmed, Jawad H.; Al-Haroon, Sawsan S.

    2012-01-01

    Objective: To investigate the possibility of hepatoprotective effect of Nigella sativa (NS) in INH-induced hepatotoxicity. Materials and Methods: The experiments were carried out on 24 male rabbits. They were divided into 4 groups (6 each); rabbits in group 1 were treated with INH following a standard protocol to induce hepatotoxicity. Rabbits in group 2 received starch. Group 3 received NS 1 g/kg/day before INH treatment. Group 4 rabbits were treated with NS only. Phenobarbital sodium (IP) was given to induce metabolism of INH. INH and NS were given orally. The experiment continued for 12 days; at day 13, animals were sacrificed. Liver function tests, malondialdehyde (MDA) were estimated in serum and in liver homogenates. Liver histopathological examinations were performed. Results: Histopathological changes of hepatotoxicity were found in all INH-treated rabbits. The histopathological findings were normal in three rabbits treated with NS before INH, very mild in two, and with moderate changes in one rabbit. Serum alanine aminotransferase (S.ALT) was elevated after INH treatment and returned back to the control value when NS was given before INH. Similar pattern of effect was noticed with serum aspartate aminotransferase (S.AST), S. total bilirubin, S. MDA, and Serum alkaline phosphatase.In liver homogenate, AST, ALT, and MDA were increased with INH treatment compared to the control, then decreased with NS treatment given before INH Conclusions: NS has hepatoprotective effects against INH-induced hepatotoxicity in rabbits. NS 1 g/kg proved safe, no adverse effects; no histopathological or biological abnormalities were seen. PMID:23248393

  11. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Dumonde, D. C.

    1963-01-01

    The sera of rabbits injected with rat liver, kidney, heart, muscle, spleen and brain in Freund's complete adjuvant fixed complement with rabbit tissue. This complement-fixing activity was attributed to autoantibodies which were able to fix complement in vitro with the tissue of the rabbit in which they occurred. Absorption, gel diffusion and antibody and antigen titrations indicated that some of the anti-liver, anti-kidney, anti-heart, anti-muscle and anti-brain sera contained organ-specific autoantibody. The sera also contained autoantibody reacting with widely distributed antigen(s), which was relatively labile at 65°. The anti-kidney and anti-brain sera reacted with distinct antigens which were extracted from rabbit kidney and brain with a mixture of chloroform and methanol. The natural autoantibody of Kidd and Friedewald was usually labile at 65° and behaved like a macroglobulin on sucrose gradient centrifugation. Sera taken 1 week after immunization with rat tissue contained heat-labile macroglobulin antibody. However, sera taken 1 month after immunization also contained small molecular weight antibody which was stable at 65°. PMID:13965166

  12. Comparison of the coagulation profile of fatty liver haemorrhagic syndrome-susceptible laying hens and normal laying hens.

    PubMed

    Thomson, A E; Gentry, P A; Squires, E J

    2003-09-01

    1. The rate of thrombin generation in plasma from Fatty Liver Haemorrhagic Syndrome-susceptible laying hens (FLHS, UCD-003) is more rapid than in plasma from age-matched normal Single Comb White Leghorn (SCWL) laying hens. 2. The rate of thrombin generation in plasma was determined by measuring the biological activity of the specific coagulation proteins, Factors V, VII, VIII, IX and X. 3. The higher activity of Factors V, VII and X in FLHS-susceptible laying hens compared with normal SCWL hens remained consistent after plasma lipid concentrations were reduced. 4. Analysis of the fatty acid composition of plasma phospholipids showed that in normal SCWL laying hens phosphatidylethanolamine contained C18:3n3 whereas it contained C20:3n3 in FLHS-susceptible laying hens. 5. The results suggest that alterations in the composition of the phospholipids that are essential cofactors in the biochemical reactions involved in thrombin generation may be a contributing factor in the development of FLHS.

  13. Free 25-hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxyvitamin D levels.

    PubMed Central

    Bikle, D D; Halloran, B P; Gee, E; Ryzen, E; Haddad, J G

    1986-01-01

    We determined the free fraction of 25-dihydroxyvitamin D (25OHD) in the serum of subjects with clinical evidence of liver disease and correlated these measurements to the levels of vitamin D binding protein and albumin. These subjects when compared to normal individuals had lower total 25OHD levels, higher percent free 25OHD levels, but equivalent free 25OHD levels. These subjects also had reduced vitamin D binding protein and albumin concentrations. The total concentration of 25OHD correlated positively with both vitamin D binding protein and albumin, whereas the percent free 25OHD correlated negatively with vitamin D binding protein and albumin. The free 25OHD levels did not correlate with either vitamin D binding protein or albumin. We conclude that total vitamin D metabolite measurements may be misleading in the evaluation of the vitamin D status of patients with liver disease, and recommend that free 25OHD levels also be determined before making a diagnosis of vitamin D deficiency. PMID:3745436

  14. Hypolipidaemic effects of Citrullus colocynthis L. in rabbits.

    PubMed

    Daradka, Haytham; Almasad, Motasem M; Qazan, Walid Sh; El-Banna, Nasser M; Samara, Omar H

    2007-08-15

    Aim of this research to study the effect of Citrullus colocynthis (70% EtOH) extract on lipid profile on Rabbits. The plant extract was orally administered to the atherogenic rabbits (atherogenic diet + cholesterol powder supplement 400 mg/kg/body weight/day dissolved in 5 mL coconut oil) at dose of 1.2 g kg(-1) body weight/day. During the hall period of the experiment blood was collected and serum was analyzed for lipid profile. Animals were sacrificed; the heart and the liver were collected and kept at -20 degrees C until assayed. Biochemical analysis of blood serum and tissue (liver and heart muscle) level were made for cholesterol, Phospholipids and triglycerides. In addition blood serum was analyzed further for HDL-Cholesterol. All the results were statistically analyzed using students t-test. Hypolipidaemic nature of Citrullus colocynthis (70% EtOH) extract was studied in hyperlipidaemic Rabbits. The increased cholesterol levels were brought to normal by administration of Citrullus colocynthis. Serum cholesterol levels dropped from 940.7 to 230.41 (75.55%) and further to 119.2 (87.32%) by the end of the experiment. Similarly, phospholipids and triglycerides levels were observed to be also reduced. The tissues lipids profiles of liver and heart muscle showed similar changes in those noticed in serum lipids. Citrullus colocynthis possesses active hypolipidaemic constituents.

  15. Transmission of Hepatitis E Virus from Rabbits to Cynomolgus Macaques

    PubMed Central

    Liu, Peng; Bu, Qiu-Ning; Han, Jian; Du, Ren-Jie; Lei, Ya-Xin; Ouyang, Yu-Qing; Li, Jie; Zhu, Yong-Hong; Lu, Feng-Min; Zhuang, Hui

    2013-01-01

    The recent discovery of hepatitis E virus (HEV) strains in rabbits in the People’s Republic of China and the United States revealed that rabbits are another noteworthy reservoir of HEV. However, whether HEV from rabbits can infect humans is unclear. To study the zoonotic potential for and pathogenesis of rabbit HEV, we infected 2 cynomolgus macaques and 2 rabbits with an HEV strain from rabbits in China. Typical hepatitis developed in both monkeys; they exhibited elevated liver enzymes, viremia, virus shedding in fecal specimens, and seroconversion. Comparison of the complete genome sequence of HEV passed in the macaques with that of the inoculum showed 99.8% nucleotide identity. Rabbit HEV RNA (positive- and negative-stranded) was detectable in various tissues from the experimentally infected rabbits, indicating that extrahepatic replication may be common. Thus, HEV is transmissible from rabbits to cynomolgus macaques, which suggests that rabbits may be a new source of human HEV infection. PMID:23628346

  16. Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

    PubMed Central

    Burns, S P; Cohen, R D; Iles, R A; Bailey, R A; Desai, M; Germain, J P; Going, T C

    1999-01-01

    The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was abolished during DKA; indeed, gluconeogenesis was most active in the perivenous region. Whereas in normal livers perfused at pH 7.4 the periportal region showed a markedly elevated intracellular pH (pH(i)) compared with the perivenous zone, this distribution of pH(i) was reversed in DKA, with an intermediate distribution in normal livers perfused at pH 6. 8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periportally was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three groups; oxygen uptake was greatly decreased perivenously despite adequate oxygen supply. These findings are consistent with our previous observations of the lobular co-location of high pH(i) and gluconeogenesis, and might offer an explanation of how high gluconeogenic rates can continue in spite of severe systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA. PMID:10493939

  17. Efficacy of garlic extract on hepatic coccidiosis in infected rabbits (Oryctolagus cuniculus): histological and biochemical studies.

    PubMed

    Toulah, Fawzia H; Al-Rawi, Maisaa M

    2007-12-01

    The rabbits were divided into three groups, of 12 rabbits each. G1 was the (non-infected non-treated) as control, G2 was the (infected-non treated), and G3 was the (infected and treated) rabbits. Each rabbit in the infected groups were given (10(3)) sporuleted oocysts of Eimeria stiedae per rabbit after forty five days exactly. Faecal sample of rabbits from each group were examined each day post infection till oocysts appeared in faeces. The treatment was given by using suitable dosage of garlic according to body weight. After 15, 21, 28, & 35 days post-treatment faecal oocysts were output. Biochemical parameters as serum liver function (ALT, AST, GGT & ALP) that denoted the he-patic cells injury. The results showed a significant differences in the mean values of oocysts shedding and their mean number in bile ducts between Gs 2 &3 from the 15th day post infection (PI) (mean +/-SD:40.33 +/- 16.72 & 25.17 +/- .56 respectively) till the experimental end on the 35th day (55.75 +/- 19.79 & 0.94 +/- 1.43 respectively). The histopathological alterations were in liver of G2 at the experimental end. Coccidiosis in G2 induced histopathological alterations in liver tissue, marked cytoplasmic vacuolations in hepatocytes with clear signs of karyolysis, and dilatation of sinusoids with increase in Kupffer cells. Leukocytic infiltration around congested blood vessels was noticed. Efficacy of garlic on E. stiedae in infected Gs was resident. The liver of G3 regained almost normal appearance compared to control.

  18. In vitro and in vivo aphrodisiac properties of Corchorus depressus Linn. on rabbit corpus cavernosum smooth muscle relaxation and sexual behavior of normal male rats.

    PubMed

    Kataria, Sandeep; Kaur, Dilsher; Rao, Shaival Kamalaksha; Khajuria, Ravi K

    2013-06-21

    Corchorus depressus Linn. has been used as an aphrodisiac in traditional Indian medicine to treat male sexual dysfunction and impotency. The petroleum ether, chloroform, ethyl acetate, n-butanol and aqueous fractions of 95% methanol extract of Corchorus depressus were screened initially for their in vitro aphrodisiac activity on rabbit corpus cavernosum smooth muscle. The chloroform fraction (CDC) was found to be the most active and therefore investigated further on general mating behavior, libido and potency of normal male Wistar albino rats in comparison with the standard drug, Sildenafil citrate. Animals were divided into the following groups: Control, SC CDC 100, CDC 200, and CDC 400, who received saline, Sildenafil citrate or the chloroform fraction of Corchorus depressus at doses of 100, 200 or 400mg/kg b.wt., respectively. The route of administration for all the groups was oral dosing, which was once in a day for 45 days. To analyze the mating behavior, female rats with estrus phase were used. The chloroform fraction of methanolic extract of Corchorus depressus significantly reduced ML, IL, PEI and III. There was a significant increase in the MF, IF and EL and serum testosterone levels throughout the study period. The potency test significantly increased erections, quick flips, long flips and total reflex. In vitro aphrodisiac activity was significantly higher in chloroform fraction at a concentration of 25.0mg/ml, which induced 71.4% relaxation. The combined results of the above mentioned models indicate that the chloroform fraction of Corchorus depressus produces a significant increase in sexual activity as exhibited by 25mg/ml in vitro and 400mg/kg in vivo. In comparison with the control, all the drug-treated groups have shown drug-induced effects for a few parameters. In vitro and in vivo studies provide valuable experimental evidence that the chloroform fraction of methanolic extract of Corchorus depressus possesses aphrodisiac property. This study

  19. [Experimental research on the prevention of rabbit postoperative abdominal cavity adhesion with PLGA membrane].

    PubMed

    Pang, Xiubing; Pan, Yongming; Hua, Fei; Sun, Chaoying; Chen, Liang; Chen, Fangming; Zhu, Keyan; Xu, Jianqin; Chen, Minli

    2015-02-01

    The aim of this paper is to explore the prevention of rabbit postoperative abdominal cavity adhesion with poly (lactic-co-glycotic acid) (PLGA) membrane and the mechanism of this prevention function. Sixty-six Japanese white rabbits were randomly divided into normal control group, model control group and PLGA membrane group. The rabbits were treated with multifactor methods to establish the postoperative abdominal cavity adhesion models except for those in the normal control group. PLGA membrane was used to cover the wounds of rabbits in the PLGA membrane group and nothing covered the wounds of rabbits in the model control group. The hematologic parameters, liver and kidney functions and fibrinogen contents were detected at different time. The rabbit were sacrificed 1, 2, 4, 6, 12 weeks after the operations, respectively. The adhesions were graded blindly, and Masson staining and immunohistochemistry methods were used to observe the proliferation of collagen fiber and the expression of transforming growth factor β1 (TGF-β1) on the cecal tissues, respectively. The grade of abdominal cavity adhesion showed that the PLGA membrane-treated group was significant lower than that in the model control group, and it has no influence on liver and kidney function and hematologic parameters. But the fibrinogen content and the number of white blood cell in the PLGA membrane group were significant lower than those of model control group 1 week and 2 weeks after operation, respectively. The density of collagen fiber and optical density of TGF-β1 in the PLGA membrane group were significant lower than those of model control group. The results demonstrated that PLGA membrane could be effective in preventing the abdominal adhesions in rabbits, and it was mostly involved in the reducing of fibrinogen exudation, and inhibited the proliferation of collagen fiber and over-expression of TGF-β1.

  20. Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet.

    PubMed

    Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L

    2014-03-01

    Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development

  1. Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model.

    PubMed

    Guehring, Thorsten; Unglaub, Frank; Lorenz, Helga; Omlor, Georg; Wilke, Hans-Joachim; Kroeber, Markus W

    2006-05-01

    Intervertebral disc (IVD) pressure measurement is an appropriate method for characterizing spinal loading conditions. However, there is no human or animal model that provides sufficient IVD pressure data. The aim of our study was to establish physiological pressure values in the rabbit lumbar spine and to determine whether temporary external disc compression and distraction were associated with pressure changes. Measurements were done using a microstructure-based fibreoptic sensor. Data were collected in five control rabbits (N, measurement lying prone at segment L3/4 at day 28), five rabbits with 28 days of axial compression (C, measurement at day 28) and three rabbits with 28 days of axial compression and following 28 days of axial distraction (D, measurement at day 56). Disc compression and distraction was verified by disc height in lateral radiographs. The controls (N) showed a level-related range between 0.25 MPa-0.45 MPa. The IVD pressure was highest at level L3/4 (0.42 MPa; range 0.38-0.45) with a decrease in both cranial and caudal adjacent segments. The result for C was a significant decrease in IVD pressure (0.31 MPa) when compared with controls (P=0.009). D showed slightly higher median IVD pressure (0.32 MPa) compared to C, but significantly lower levels when compared with N (P=0.037). Our results indicate a high range of physiological IVD pressure at different levels of the lumbar rabbit spine. Temporary disc compression reduces pressure when compared with controls. These data support the hypothesis that temporary external compression leads to moderate disc degeneration as a result of degradation of water-binding disc matrix or affected active pumping mechanisms of nutrients into the disc. A stabilization of IVD pressure in discs treated with temporary distraction was observed.

  2. Ultrasonography and Low-field Magnetic Resonance Imaging of the Common Calcanean Tendon in a Rabbit Model for Tendinopathy Research: a Descriptive Study of Normal Anatomy.

    PubMed

    Skalec, A; Przyborowska-Zhalniarovich, P; Janus, I; Kirstein, K; Mieszkowska, M; Adamiak, Z; Chrószcz, A; Janeczek, M

    2016-09-01

    In spite of recent advances in treatment protocols, tendinopathies continue to challenge orthopaedists and surgeons. Due to the complexity of both tendon injuries and the healing processes, animal models are essential for addressing fundamental questions in tendinopathy research. Diagnostic imaging could contribute to the evaluation of animal models, thus providing information, which could be translated to human tendinopathies. The objective of our study was to evaluate in situ appearance of the rabbit common calcanean tendon with ultrasonography and magnetic resonance imaging. Additionally, we sought to assess and compare the feasibility and usefulness of these techniques in a rabbit model while focusing on the imaging of the particular structures involved in calcaneal tendon disorders. Eight California rabbits were used for post-mortem sonographic and low-field magnetic resonance examination. Morphometry was performed on longitudinal sonograms and sagittal MRI scans. The craniocaudal diameter of the tendon was measured at four points of interest. Ultrasonography and magnetic resonance provided good visualisation of the tendon origin, the paratenon and the pre-Achilles fat pad. Magnetic resonance images presented in more detail the structure of the calcaneal insertion. Both modalities failed to visualise the individual components of the common calcanean tendon and the bursa of the calcaneal tendon. Statistical analysis of measurements obtained showed that the craniocaudal diameter of the common calcanean tendon in a rabbit increases significantly with a growing length from the calcaneal tuber. Both magnetic resonance and ultrasonography are feasible, and should be considered complementary, not alternative imaging techniques in a rabbit common calcanean tendon model.

  3. Ginkgo biloba extract inhibits the development of experimental atherosclerosis in rabbits.

    PubMed

    Wójcicki, J; Samochowiec, L; Juźwiak, S; Gonet, B; Syryński, W; Barcew-Wiszniewska, B; Roźewicka, L; Tustanowski, S; Ceglecka, M; Juzyszyn, Z; Myśliwlec, Z; Kałdonska, M; Górnik, W; Kadłubowska, D

    1994-06-01

    Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + standardized. Ginkgo biloba extract (GB), and (4) HFD + rutin (as a well known substance it was used for comparison of pure single flavonol diglycoside activity with total extract). The experiment lasted 12 weeks. The most pronounced reduction in lipid metabolism disturbances and in the severity of plaque formation occurred after the GB had been administered. Lipid content in serum, liver homogenate and liver microsomes was depressed. HDL-cholesterol concentration was increased. Diminution of the malondialdehyde level in plasma was accompanied by an increase in the concentration of ascorbate free radicals in the liver in vitro. Testosterone concentrations in serum were normalized whilst the cytochrome P-450 content in liver microsomes was increased. Surface area of the lipid deposits at 12 weeks measured planimetrically averaged 85.5 % in HFD-fed animals vs 54.7 % in GB-treated rabbits. Quite distinct superiority of GB in antiatherosclerotic activity, as compared with rutin, was shown. These findings suggest that GB, in addition to lowering serum lipid level and possessing antioxidant properties in rabbits on an experimental diet, also affects metabolic processes in the liver and may modify lipid deposition in major arteries. Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  4. Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury

    PubMed Central

    Perepelyuk, Maryna; Terajima, Masahiko; Wang, Andrew Y.; Georges, Penelope C.; Janmey, Paul A.; Yamauchi, Mitsuo

    2013-01-01

    Liver fibrosis is characterized by excessive deposition of extracellular matrix proteins by myofibroblasts derived from hepatic stellate cells and portal fibroblasts. Activation of these precursors to myofibroblasts requires matrix stiffness, which results in part from increased collagen cross-linking mediated by lysyl oxidase (LOX) family proteins. The aims of this study were to characterize the mechanical changes of early fibrosis, to identify the cells responsible for LOX production in early injury, and to determine which cells in normal liver produce collagens and elastins, which serve as substrates for LOXs early after injury. Hepatocytes and liver nonparenchymal cells were isolated from normal and early-injured liver and examined immediately for expression of LOXs and matrix proteins. We found that stellate cells and portal fibroblasts were the major cellular sources of fibrillar collagens and LOXs in normal liver and early after injury (1 day after bile duct ligation and 2 and 7 days after CCl4 injury). Activity assays using stellate cells and portal fibroblasts in culture demonstrated significant increases in LOX family enzymatic activity as cells became myofibroblastic. LOX family-mediated deoxypyridinoline and pyridinoline cross-links increased after CCl4-mediated injury. There was a significant association between liver stiffness (as quantified by the shear storage modulus G′) and deoxypyridinoline levels; increased deoxypyridinoline levels were also coincident with significantly increased elastic resistance to large strain deformations, consistent with increased cross-linking of the extracellular matrix. These data suggest a model in which the liver is primed to respond quickly to injury, activating potential mechanical feed-forward mechanisms. PMID:23328207

  5. Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

    PubMed Central

    Ma, Hongxia; Zheng, Lin; Liu, Yunbo; Zhao, Chenyan; Harrison, Tim J.; Ma, Yuyuan; Sun, Shuhua; Zhang, Jingang; Wang, Youchun

    2010-01-01

    Background A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77–79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. Methods Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination. Findings Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation. Conclusions These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis. PMID:20161794

  6. Elevated Liver Enzymes

    MedlinePlus

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  7. Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease

    PubMed Central

    Nishioka, K.; Levin, A. G.; Simons, M. J.

    1975-01-01

    The relative sensitivities of counterimmunoelectrophoresis (CIE) and haemagglutination assays for the detection of hepatitis B surface antigen (HBsAg) and antibodies (anti-HBs) were compared. Twelve scientists from ten countries in Asia, Africa and the Pacific region participated in the study. The participants provided serum samples from 15 953 subjects comprising patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), as well as blood donors and other normal individuals. For the detection of HBsAg in a reference panel serum, immune adherence haemagglutination (IAHA) was slightly more sensitive than passive haemagglutination inhibition (PHI); CIE was the least sensitive. Mean HBsAg frequencies in patients with acute hepatitis, chronic hepatitis, cirrhosis, and HCC were significantly higher than in healthy controls. Passive haemagglutination (PHA) was more sensitive than CIE for the detection of anti-HBs. The frequency of anti-HBs in patients with HCC was significantly lower than that in the other groups. Mean anti-HBs frequencies in patients with acute hepatitis, chronic hepatitis, and cirrhosis were not significantly different from that in normal subjects. Subtyping of HBsAg was performed by PHI. Among asymptomatic carriers the predominant HBsAg subtype in northeast Asia was adr.In India, ayw predominated in carriers, with the demarcation between adr and ayw occurring west of Burma. In West Africa the only subtype detected was ayw, but in East Africa the majority subtype was adw. The r subtype was found only in Asian populations east of India and in Western Pacific populations. In Papua New Guinea all four subtypes were identified. With one possible exception, the subtypes of HBsAg-positive patients with liver disease reflected the predominant type in each geographic location. PMID:1084799

  8. Opposite effects of sleep deprivation on the continuous reaction times in patients with liver cirrhosis and normal persons.

    PubMed

    Lauridsen, Mette Munk; Frøjk, Jesper; de Muckadell, Ove B Schaffalitzky; Vilstrup, Hendrik

    2014-09-01

    The continuous reaction times (CRT) method describes arousal functions. Reaction time instability in a patient with liver disease indicates covert hepatic encephalopathy (cHE). The effects of sleep deprivation are unknown although cirrhosis patients frequently suffer from sleep disorders. The aim of this study was to determine if sleep deprivation influences the CRT test. Eighteen cirrhosis patients and 27 healthy persons were tested when rested and after one night's sleep deprivation. The patients filled out validated sleep quality questionnaires. Seven patients (38%) had unstable reaction times (a CRTindex < 1.9) compatible with cHE. In these patients, the wakefulness improved or normalized their reaction speed and CRTindex (p = 0.01). There was no change in the other patients' reaction speed or stability. Seven patients (38%) reported poor sleep that was not related to their CRT tests before or after the sleep deprivation. In the healthy participants, the sleep deprivation slowed their reaction times by 11% (p < 0.0001) and in 7 persons (25%) destabilized them. The acute sleep deprivation normalized or improved the reaction time stability of the patients with a CRTindex below 1.9 and had no effect in the patients with a CRTindex above 1.9. There was no relation between reported sleep quality and reaction time results. Thus, in cirrhosis patients, sleep disturbances do not lead to 'falsely' slowed and unstable reaction times. In contrast, the acute sleep deprivation slowed and destabilized the reaction times of the healthy participants. This may have negative consequences for decision-making.

  9. Disorders of the Reproductive Tract of Rabbits.

    PubMed

    Harcourt-Brown, Frances Margaret

    2017-05-01

    Disorders of the reproductive tract are common in rabbits. Conditions are different in rabbits that are farmed for their meat or fur and those that are kept as pets. Farmed rabbits suffer from infections and diseases associated with pregnancy. Congenital abnormalities are more likely to be recognized and treated in pet rabbits. Pet rabbits suffer from age-related changes to their genital tract (hyperplasia, neoplasia, or hernias). Neutering is an important part of prevention and treatment of reproductive disorders. Knowledge of normal male and female reproductive anatomy is essential to prevent complications. These are described and illustrated. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  10. Changes in Normal Liver and Spleen Volume after Radioembolization with {sup 90}Y-Resin Microspheres in Metastatic Breast Cancer Patients: Findings and Clinical Significance

    SciTech Connect

    Paprottka, Philipp M. Schmidt, G. P.; Trumm, C. G.; Hoffmann, R. T.; Reiser, M. F.; Jakobs, T. F.

    2011-10-15

    Purpose: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. Methods: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. Results: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. Conclusions: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

  11. Protective effect of Egyptian propolis against rabbit pasteurellosis.

    PubMed

    Nassar, Somia A; Mohamed, Amira H; Soufy, Hamdy; Nasr, Soad M

    2013-01-01

    The present study was conducted to study the protective effect of ethanolic extract of propolis given subcutaneously (S/C) either alone or in combination with inactivated formalized Pasteurella multocida (P. multocida) vaccine in rabbits challenged with virulent P. multocida strain. Twenty-eight New-Zealand rabbits, 6-8 weeks old and not vaccinated against pasteurellosis, were randomly divided into four equal groups. Group (1) was kept as nonvaccinated control. Group (2) was injected S/C with propolis. Group (3) was vaccinated (S/C) with P. multocida vaccine only. Group (4) was injected with vaccine mixed with propolis as adjuvant. Groups (2, 3, and 4) received the same doses of propolis and vaccine after 4 weeks as a booster dose. The experiment continued for six weeks during which clinical signs, body weight, and mortality rate were recorded. Blood samples were collected every 2 weeks of treatment for evaluating the erythrogram and biochemical parameters. At the end of six weeks, all groups were subjected to challenge with a virulent strain of P. multocida. Two weeks later, tissue specimens were collected from different organs for histopathological investigation. Results showed that before challenge all rabbits of different groups were apparently healthy and had good appetite. After challenge, control group (1) showed acute form of the disease, 100% mortality rate, and severe histopathological changes. Rabbits of groups (2 and 3) showed less severe clinical signs, mortality rate, and histopathological changes than control. Rabbits of group (4) were apparently healthy with normal histological picture. In conclusion, an ethanolic extract of propolis injected alone or combined with formalized inactivated P. multocida vaccine improved general health conditions, liver and kidney functions in addition to reduction of the severity of adverse clinical signs, mortality rates, and histopathological changes associated with challenge of rabbits with P. multocida strain.

  12. A strategy for quantitative bioanalysis of non-polar neutral compounds by liquid chromatography/electrospray ionization tandem mass spectrometry: determination of TS-962, a novel acyl-CoA:cholesterol acyltransferase inhibitor, in rabbit aorta and liver tissues.

    PubMed

    Yamaguchi, J; Matsuno, Y; Hachiuma, K; Ogawa, N; Higuchi, S

    2001-01-01

    A strategy for the sensitive and reliable quantitative determination of non-polar neutral compounds in biological matrices by liquid chromatography/electrospray ionization tandem mass spectrometry is described in the context of assay development for TS-962, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in rabbit aorta and liver tissues. The electrospray ionization (ESI) mass spectrum of this compound with a mobile phase of water/acetonitrile did not give abundant [M + H]+ ions, but did give alkali metal cation adducts such as [M + Na]+, [M + CH3CN + Na]+ and [M + K]+ ions. The cationized species are acknowledged as unsuitable precursor ions for selected reaction monitoring (SRM) for various reasons, such as difficulty in obtaining characteristic product ions in low-energy collision-induced dissociation, and irreproducibility of the adduct-ion intensities. To overcome this problem, a solution of 3.4 mM trifluoroacetic acid in 2-propanol was added to the mobile phase as a postcolumn additive, resulting in a decrease of the undesirable adduct formation and significant enhancement of [M + H]+ ion intensity. An attempt was then made to prevent the matrix effect by employing a column-switching system, which allowed direct injection of a large volume of 2-propanolic tissue homogenate (950 microL) followed by sufficient clean-up, separation, and ESI-SRM on-line. This enabled development of a sensitive and reliable assay method for TS-962 in rabbit aorta and liver tissues in the concentration range of 5-500 ng/g wet tissue using a 25-mg aliquot of tissue sample. Application of this method to the determination of aortic TS-962 levels at 24 h after repeated oral administration of this compound (3 mg/kg) once a day for 12 weeks to 1% cholesterol-fed rabbits is also presented. Results showed that TS-962 is well distributed to both the thoracic and abdominal aorta tissues, at levels higher than the 50% inhibitory concentration value of this compound for

  13. Studies on adenosine triphosphate transphosphorylases. Human isoenzymes of adenylate kinase: isolation and physicochemical comparison of the crystalline human ATP-AMP transphosphorylases from muscle and liver.

    PubMed

    Kuby, S A; Fleming, G; Frischat, A; Cress, M C; Hamada, M

    1983-02-10

    Procedures are described for the isolation, in crystalline form, of the adenylate kinases from autopsy samples of human muscle and from human liver. Weight average molecular weights were determined by sedimentation equilibrium to be 22,000 (+/- 700) and 25,450 (+/- 160) for the human muscle and liver isoenzymes, respectively. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, their molecular weights were estimated to be 21,700 and 26,500 for the muscle and liver enzymes, respectively. Both isoenzymes are accordingly monomeric proteins in their native state. Amino acid analyses are reported here for the normal human liver, calf liver, and rabbit liver adenylate kinases and compared with the normal human muscle, calf muscle, and rabbit muscle myokinases. The liver types as a group and the muscle types as a group show a great deal of homology, but some distinct differences are evident between the liver and muscle enzyme groups, especially in the number of residues of His, Pro, half-cystine, and the presence of tryptophan in the liver enzymes. The normal human liver adenylate kinase, as isolated in this report, has proved to be similar in its properties, if not identical, to the adenylate kinase isolated directly from human liver mitochondria (Hamada, M., Sumida, M., Okuda, H., Watanabe, T., Nojima, M., and Kuby, S. A. (1982) J. Biol. Chem. 257, 13120-13128). Therefore, the liver-type adenylate kinase may be considered a mitochondrial type.

  14. Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients

    PubMed Central

    Wang, Rui; Zhang, Ming-Guang; Luo, Ou; He, Liu; Li, Jia-Xin; Tang, Yun-Jing; Luo, Yan-Li; Zhou, Min; Tang, Li; Zhang, Zong-Xia; Wu, Hao; Chen, Xin-Zu

    2015-01-01

    Abstract A prospective randomized, controlled, single-blinded trial to compare the effectiveness and safety of heparin saline (HS) to those of normal saline (NS) as flushing and locking solutions for peripheral venous catheter (PVC) in decompensated liver cirrhosis (DLC) patients. Patients with DLC at our institution between April 2012 and March 2013 were enrolled after obtaining informed consent. The patients were randomly allocated into 2 groups: the NS group received preservative-free 0.9% sodium chloride as the flushing and locking solution, while the HS group received HS (50 U/mL). PVC-related events and the duration of PVC maintenance were compared between the 2 groups. Moreover, the preinfusion and postinfusion levels of prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet (PLT) were also compared. A total of 32 and 36 DLC patients in the NS (125 PVCs) and HS (65 PVCs) groups, respectively, were analyzed. Baseline characteristics, including gender, age, Child–Pugh grade, PVC type and administration of anticoagulant, and irritant agents, were comparable between the 2 groups (P > 0.05). The maintenance times of the HS and NS groups were 80.27 ± 26.47 and 84.19 ± 29.32 hours, respectively (P = 0.397). Removal of PVC for abnormal reasons occurred in 30.7% and 22.4% of patients in the HS and NS groups (P = 0.208). The PVC occlusion rates were 6.2% and 5.6% in the HS and NS groups, respectively (OR = 1.11, 95% CI 0.31–3.92). The PT, APTT, and PLT levels were comparable between the 2 groups both before and after infusion (P > 0.05). Incremental analyses showed that Child–Pugh grade C might be a risk factor for the suppression of PLT in the HS group. We consider NS to be as effective as and safer than conventional HS for flushing and locking PVC in decompensated liver cirrhosis patients. PMID:26252305

  15. Focal liver lesions: SPIO-, gadolinium-, and ferucarbotran-enhanced dynamic T1-weighted and delayed T2-weighted MR imaging in rabbits.

    PubMed

    Schnorr, Jörg; Wagner, Susanne; Abramjuk, Claudia; Drees, Randi; Schink, Tania; Schellenberger, Eyk A; Pilgrimm, Herbert; Hamm, Bernd; Taupitz, Matthias

    2006-07-01

    To compare a superparamagnetic iron oxide (SPIO), VSOP-C184, with a gadopentetate dimeglumine with regard to signal-enhancing effects on T1-weighted dynamic magnetic resonance (MR) images and with another SPIO contrast medium with regard to signal-reducing effects on delayed T2-weighted MR images. All experiments were approved by the responsible Animal Care Committee. Twenty rabbits (five for each contrast agent and dose) implanted with VX-2 carcinoma were imaged at 1.5 T. VSOP-C184 at 0.015 and 0.025 mmol Fe/kg was compared with gadopentetate dimeglumine at 0.15 mmol Gd/kg and ferucarbotran at 0.015 mmol Fe/kg. The imaging protocol comprised a T1-weighted dynamic gradient-echo (GRE) MR before injection and at 6-second intervals for up to 42 seconds after injection and a T2-weighted turbo spin-echo MR before and 5 minutes after injection. Images were evaluated quantitatively, and contrast media were compared by using nonparametric analysis of variance. At dynamic T1-weighted GRE MR imaging with 0.015-mmol Fe/kg VSOP-C184, 0.025-mmol Fe/kg VSOP-C184, gadopentetate dimeglumine, and ferucarbotran, the median peak contrast-to-noise ratio (CNR) was 20.7 (25th percentile, 16.3; 75th percentile, 22.6), 24.2 (25th percentile, 19.3; 75th percentile, 28.5), 16.4 (25th percentile, 13.7; 75th percentile, 20.3), and 14.0 (25th percentile, 11.4; 75th percentile, 16.8), respectively. Both doses of VSOP-C184 yielded significantly higher CNR (P < .05) than the other two agents. At T2-weighted turbo spin-echo imaging with 0.015-mmol Fe/kg VSOP-C184, 0.025-mmol Fe/kg VSOP-C184, gadopentetate dimeglumine, and ferucarbotran, the median CNR was 15.0 (25th percentile, 13.4; 75th percentile, 21.3), 15.7 (25th percentile, 14.5; 75th percentile, 19.8), 11.3 (25th percentile, 8.2; 75th percentile, 12.2), and 15.7 (25th percentile, 12.5; 75th percentile, 22.4), respectively. There was no significant difference between VSOP-C184 and ferucarbotran; both had a significantly higher CNR than did

  16. Oculoscopy in Rabbits and Rodents.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  17. Intraorgan differences of blood flow, oxygen supply and glycogen content in the multilobular liver of normal and hemorrhagic rats.

    PubMed

    Metzger, H P; Schywalsky, M

    1992-02-01

    In order to characterize intraorgan differences in blood supply of the rat liver, hepatic blood flow (HBF), surface oxygen tension (sPO2) and glycogen content of the largest and smallest lobi have been determined for normal and hemorrhagic rats (N = 68) in ketamin-xylazine anesthesia. 1. Mean HBF +/- SD of lobus sinister measured 1.07 +/- 0.23 ml/g min (n = 119 determinations, N = 9 rats); HBF of lob. caudatus dexter showed a left-shifted histogram (mean value = 0.77 ml/g.min, median = 0.72 ml/g.min, modul = 0.63 ml/g.min, p less than 0.005). 2. Mean sPO2 +/- SD of lob. sin. measured 23 +/- 6.8 mm Hg (n = 168, N = 16). The histograms of lob. caudat. dext. and sin. were left-shifted (mean value of l.c.d. = 9 mm Hg, median = 4 mm Hg, modul = 0 mm Hg, mean value of l.c.s. = 16 mm Hg, median = 17 mm Hg, modul = 0 mm Hg). Under hemorrhage sPO2 became almost zero in 91% of the measurements. 3. In response to an arterial bolus of fluorescence stained gamma-globulins, spreading of the dye showed a pronounced front and marked periportal area within lob. sin., while an irregular convective front and a much smaller area were detected within both of the lobi caudati. Under hemorrhage, intersinusoidal staining and undefined, irregular contours were observed within all lobes. 4. Compared with lob. sin. preferential glycogen depletion and partial centrilobular necrosis were detected within both of the lob. caudati while under hemorrhage the glycogen stores were empty and severe group necroses have been observed especially within the small lobi. From the data it is concluded that in comparison to lob. sin. an insufficient supply and pronounced vulnerability against hepatic ischemia exists within the small lobi caudati.

  18. Cytotoxicity mechanism of α-MMC in normal liver cells through LRP1 mediated endocytosis and JNK activation.

    PubMed

    Wang, Ling; Shen, Fubing; Zhang, Min; He, Qianchuan; Zhao, Hui; Yu, Xiaoping; Yang, Shuxia; Liu, Yang; Deng, Nianhua; Zheng, Juecun; Zhu, Lixia; Liu, Xiaolan

    2016-05-16

    Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein isolated from Momordica charantia, is a potential drug candidate with strong anti-tumor activity. However, α-MMC has a severe hepatotoxicity when applied in vivo, which may greatly hinders its use in clinic in the future. The biological mechanism of hepatotoxicity induced by α-MMC is largely unknown, especially the mechanism by which α-MMC enters the hepatocytes. In this study, we investigated α-MMC-induced cytotoxicity in normal liver L02 cell line as well as the mechanism underlying it. As expected, α-MMC is more toxic in L02 cells than in various normal cells from other organs. The cytotoxic effect of α-MMC on L02 cells is found to be mediated through cell apoptosis as detected by flow cytometry and fluorescence microscopy. Importantly, α-MMC was shown to bind to a specific receptor on cell membrane, as the density of the cell membrane receptor is closely related to both the amount of α-MMC endocytosed and the cytotoxicity in different cell lines. By using LRP1 competitive inhibitor α2-M or siRNA targeting LRP1, we further identified that LRP1 protein served as the membrane receptor for α-MMC. Both α2-M and siRNA targeting LRP1 can significantly inhibit α-MMC's endocytosis as well as its cytotoxicity in L02 cells. In addition, it was found that α-MMC can activate the JNK signalling pathways via LRP1 in L02 cells. As JNK activation often leads to cell apoptosis, the activation of JNK may play an important role in α-MMC-induced cytotoxicity. To our knowledge, this is the first report showing that LRP1 mediates the cytotoxicity of α-MMC through (1) endocytosis and induced apoptosis and (2) the activation of the JNK pathway. Our findings shed light on the fundamental mechanism of hepatotoxicity of α-MMC and offer reference to understand its mechanism of lymphocytotoxicity and neurotoxicity.

  19. Reassessment of sst(5) somatostatin receptor expression in normal and neoplastic human tissues using the novel rabbit monoclonal antibody UMB-4.

    PubMed

    Lupp, Amelie; Hunder, Anna; Petrich, Aline; Nagel, Falko; Doll, Christian; Schulz, Stefan

    2011-01-01

    The frequent overexpression of somatostatin receptors (sst) in neuroendocrine tumors provides the molecular basis for the diagnostic and therapeutic application of stable somatostatin analogs. Whereas octreotide acts mainly via the sst(2) receptor, the novel pan-somatostatin analog pasireotide exhibits particular high affinity for the sst(5) receptor. To determine whether a patient is a candidate for octreotide or pasireotide therapy, it is important to evaluate the somatostatin receptor status. However, so far highly specific rabbit monoclonal antibodies have been developed for the sst(2) receptor only (clone UMB-1). Here, we have extensively characterized a novel rabbit monoclonal antibody for the human sst(5) receptor (clone UMB-4). In a comparative immunohistochemical study, the expression of sst(5) and sst(2) receptors was assessed using UMB-4 and UMB-1, respectively. Western blot experiments unequivocally demonstrated that UMB-4 selectively detected its cognate sst(5) receptor and did not cross-react with other proteins present in crude tissue homogenates. UMB-4 yielded a highly effective immunostaining of distinct cell populations in formalin-fixed, paraffin-embedded human tissues with a predominance of plasma membrane staining. In the pituitary, sst(5) was present on all growth hormone (GH)- and adrenocorticotropin hormone (ACTH)-producing cells whereas sst(2) was only observed on a subpopulation of GH-positive cells. Consequently, sst(5) was detectable on the majority of GH and ACTH adenomas. In contrast, sst(2) was only seen on GH but not on ACTH adenomas. The rabbit monoclonal antibodies UMB-4 and UMB-1 will facilitate the assessment of the somatostatin receptor status of human tumors during routine histopathological examinations. Copyright © 2011 S. Karger AG, Basel.

  20. Biorhythms of activities of liver and blood dehydrogenases and changes in body weight of the rats feeding normal diet or excess of sugar substitutes.

    PubMed

    Petrovich, Yu A; Volozhin, A I; Zubtsov, V A; Kichenko, S M

    2007-12-01

    Biorhythms with higher levels of activity of sorbitol dehydrogenase and lactate dehydrogenase in blood plasma, specific activity of sorbitol dehydrogenase, lactate dehydrogenase, and malate dehydrogenase in the liver, and body weight of rats were more pronounced in the spring-summer period than in the autumn-winter period. These specific features were revealed in animals feeding a normal diet or food with 54 and 27% sugar substitute sorbitol. However, specific activity of glucose-6-phosphate dehydrogenase in the liver was higher in the autumn-winter period. Activity of sorbitol dehydrogenase in blood plasma increased by tens of times due to induction of sorbitol synthesis (substrate) in the liver. Sugar substitute xylitol is structurally similar to sorbitol, but is not the substrate for sorbitol dehydrogenase. However, the effect of xylitol on activities of lactate dehydrogenase, malate dehydrogenase, and glucose-6-phosphate dehydrogenase in the spring-summer period was similar to that of sorbitol.

  1. [The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory].

    PubMed

    Pang, Jing-yao; Bai, Zhao-fang; Niu, Ming; Tu, Can; Ma, Zhi-jie; Zhao, Yan-ling; Zhao, Kui-jun; You, Yun; Wang, Jia-bo; Xiao, Xiao-he

    2015-08-01

    The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of

  2. Effect of chlorpromazine on lipid metabolism in aortas from cholesterol-fed rabbits and normal rats, in vitro: inhibition of sterol esterification and modification of phospholipid synthesis

    SciTech Connect

    Bell, F.P.

    1983-06-01

    Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in isolated arterial microsomes and in intact arterial tissue from the rat and cholesterol-fed rabbit in vitro. In isolated rabbit arterial microsomes, CPZ resulted in a concentration-dependent inhibition of ACAT with 50% inhibition of (1-14C)oleoylCoA incorporation into (14C)cholesteryl esters occurring at 0.1 mM CPZ. CPZ also effectively inhibited the incorporation of (14C)oleate into triglycerides without affecting incorporation into diglycerides. Additionally, CPZ altered the pattern of arterial phospholipids synthesized from (1-14C)oleate. Incorporation into phosphatidylcholine was depressed while incorporation into phosphatidylinositol was increased. Since diglyceride synthesis appeared to be unaffected by CPZ, a redirection of phosphatidic acid into the CDP-diglyceride pathway of glycerolipid synthesis does not adequately account for the effect of CPZ on arterial phospholipid and triglyceride synthesis in these experiments.

  3. Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13 HEPAVIH cohort study.

    PubMed

    Carrieri, M Patrizia; Lions, Caroline; Sogni, Philippe; Winnock, Maria; Roux, Perrine; Mora, Marion; Bonnard, Philippe; Salmon, Dominique; Dabis, François; Spire, Bruno

    2014-01-01

    We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Normal and retrograde perfusion to probe the zonal distribution of sulfation and glucuronidation activities of harmol in the perfused rat liver preparation.

    PubMed

    Pang, K S; Koster, H; Halsema, I C; Scholtens, E; Mulder, G J; Stillwell, R N

    1983-03-01

    The role of zonal distributions of metabolic activities (sulfation and glucuronidation) in the liver on the kinetics of harmol conjugation was investigated. A computer simulation approach was adopted to better understand the effects of distributions of these conjugation activities in competition for a common drug substrate. Several distributions of the sulfation and glucuronidation systems were defined with respect to the flow path of blood; the conjugation activities along the flow path were in turn translated as time elapsed after entry of the substrate via blood into the organ. Realistic values of Km and Vmax for the sulfation and glucuronidation systems were assigned in the simulations. Directional flow, namely, normal vs. retrograde delivery of substrate was used as an additional variable. When the "center" of distribution of the sulfation system was anterior to that for glucuronidation, the steady-state hepatic extraction ratio of harmol (E) would increase, whereas the ratio of the steady-state rates of formation of harmol sulfate to harmol glucuronide (S/G ratio) would decrease when harmol was presented in a reversed direction (via retrograde perfusion), as compared with normal directional flow to the liver. The converse was true for an anterior distribution of the glucuronidation system; E would decrease, whereas S/G would increase with retrograde perfusion. To evaluate such zonal differences experimentally, perfusion studies were conducted in livers of male Wistar rats. A constant concentration of harmol (50 microM) was delivered under constant hepatic flow rate (10 ml/min/liver) by normal and retrograde perfusions to the same rat liver preparation. The steady-state hepatic E was higher (P less than .005) during retrograde perfusion than during normal perfusion, whereas the S/G ratio was significantly decreased (P less than .0005). The observations suggest an intercellular difference in the distribution of the two conjugating systems and are consistent

  5. Histopathological and biochemical effects of intraoperative interstitial radiofrequency-induced hyperthermia and intraoperative electron radiation, alone and in combination, on normal canine liver tissue

    SciTech Connect

    Williford, K.J.

    1988-01-01

    Acute and chronic histopathologic and biochemical effects on normal canine liver tissue from a single intraoperative application of heat and radiation, heat alone, and radiation alone have been evaluated in 54 adult mongrel dogs. The tolerance of normal canine liver tissue to single doses of intraoperative radiation therapy (IORT) was evaluated at doses of 5, 10, 20, 30, and 40 Gy. In addition, intraoperative interstitial hyperthermia (43{degree}C, 60 minutes, 500 kHz) was applied alone and in combination with a single intraoperative dose of 30 Gy from an 18 MeV electron beam. Blood flow at the center of the implantation site before, during and after hyperthermia treatments was also evaluated.

  6. Modulation of ornithine decarboxylase activity in the normal and regenerating rat liver by various doses of the peptide morphogen of Hydra

    SciTech Connect

    Yarygin, K.N.; Kazimirskii, A.N.; Kositskii, G.I.; Rubina, A.Yu.; Vinogradov, V.A.; Pylaev, A.S.

    1986-11-01

    In this investigation, changes in ornithine decarboxylase (ODC) activity were studied in the normal and regenerating liver of rats receiving injections of various doses of Hydra peptide morphogen (HPM). Activity of ODC was determined by a radioisotope method based on liberation of /sup 14/CO/sub 2/ from L-(1-/sup 14/C)-ornithine. The results indicate in the author's opinion that HPM may have a role in the regulation of anabolic processes and, in particular, of regenerative processes in mammals.

  7. SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis.

    PubMed

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

  8. SPF Rabbits Infected with Rabbit Hepatitis E Virus Isolate Experimentally Showing the Chronicity of Hepatitis

    PubMed Central

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits. PMID:24937350

  9. Sonographic assessment of the normal limits and percentile curves of liver, spleen, and kidney dimensions in healthy school-aged children.

    PubMed

    Safak, Alp Alper; Simsek, Enver; Bahcebasi, Talat

    2005-10-01

    The purpose of this study was to determine the normal standards of liver, spleen, and kidney dimensions and the relationship of each with sex, age, body weight, height, body mass index, and body surface area in healthy school-aged children. Seven hundred twelve healthy school-aged children (7-15 years) in 2 neighboring cities, including rural areas and city centers, were evaluated prospectively. Sex, age, weight, height, body mass index, and body surface area were determined for each case. Organ dimensions were measured 3 times, and the mean values were recorded. All measured organs had a normal position, shape, and echo texture. The children were separated into 5 groups according to body weight. There were no significant differences in organ dimensions with respect to sex (P > .05). The mean right kidney length was shorter than the left kidney length, and the difference was significant (P = .009). Body weight showed the best correlation with liver, spleen, and kidney dimensions. The results were also supported by the variance and covariance of the correlation coefficients. The normal limits of the liver, spleen, and kidneys are important parameters during a sonographic examination. This study revealed that organ dimensions showed the best correlation with body weight. To our knowledge, in clinical practice there are no pediatric organ dimension percentile graphs for interpretation of sonographic examinations. We hope this study contributes to daily practice in radiology clinics.

  10. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    SciTech Connect

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Mishto, Michele; Santoro, Aurelia; Fiorentino, Michelangelo; Capri, Miriam; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio

    2010-06-25

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  11. HEREDITARY ACHONDROPLASIA IN THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1945-01-01

    Pathological observations on hereditary achondroplasia in the rabbit have been described. At autopsy, the chief features of interest are: reduced size with disproportionately shortened extremities and large head, cutaneous and subcutaneous edema of variable degree and distribution, small shortened bones with a cartilaginous appearance and texture, immature teeth, and cleft palate in one-fourth the cases; blood-stained fluid in the thoracic and abdominal cavities; a comparatively small heart pointing to the right of the midline, a very large firm thymus, a large pale soft spleen, a large swollen liver with red mottling, and a stomach distended with thin greenish mucus but no milk. The mean relative weights of all organs in terms of the net body weight were larger than those of normal new-born litter mates. The mean actual weights of the kidneys, the brain, and especially the spleen and the thymus were also larger than their respective normal values, those of the heart, liver, and adrenals were slightly smaller, while that of the pituitary was the same. Histologically, all endochondral cartilages show marked abnormalities of differentiation with pronounced deficiency of ossification. Calcification of membranous bones is likewise deficient. The histological abnormalities of the long bones are very similar to, if not identical with, those characteristic of human fetal chondrodystrophy, the creeper fowl condition, the "bull-dog" calf, and achondroplasia of the dog. No histological evidence was found in any organ which would suggest a basis for a responsible causal agent of the abnormality. Minor to marked vascular dilatation and congestion and edema is a variable feature but is fairly widely distributed. The changes in the thyroid indicate an active gland. The cellular pattern of the pituitary is characterized by some increase in basophilic cells. The lymphoid elements of the spleen are more or less depleted. The hemopoietic tissue in the spleen and liver is reduced in

  12. Liver Immunology

    PubMed Central

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  13. Iron in spleen and liver: Some cases of normal tissues and tissues from patients with hematological malignancies

    NASA Astrophysics Data System (ADS)

    Alenkina, Irina V.; Oshtrakh, Michael I.; Felner, Israel; Vinogradov, Alexander V.; Konstantinova, Tatiana S.; Semionkin, Vladimir A.

    2016-10-01

    Iron deposits in spleen and liver tissues obtained from several healthy people and patients with mantle cell lymphoma, acute myeloid leukemia and primary myelofibrosis were studied using Mössbauer spectroscopy and magnetization measurements. The results obtained demonstrated differences in the iron content in tissues as well as some variations in the ferrihydrite-like iron core structure in the iron storage proteins in these tissues. The presence of tiny amount of magnetite and paramagnetic component in spleen and liver tissue was also detected in different quantities in the studied tissues.

  14. INFECTIOUS MYXOMATOSIS (SANARELLI) IN PREGNANT RABBITS

    PubMed Central

    Sprunt, Douglas H.

    1932-01-01

    Pregnancy in rabbits alters the reactivity of the tissues to the virus of infectious myxomatosis. The livers of pregnant animals with the myxoma have a central acidophilic necrosis. Secondary lesions in the lungs are much more numerous and larger in the pregnant than in the non-gravid animals. In like manner the lesions in the spleen are more extensive in the pregnant rabbit. On the other hand the skin lesions of the pregnant animal are decreased in size. PMID:19870088

  15. Unexplained common bile duct dilatation with normal serum liver enzymes: diagnostic yield of endoscopic ultrasound and follow-up of this condition.

    PubMed

    Bruno, Mauro; Brizzi, Rosario F; Mezzabotta, Lavinia; Carucci, Patrizia; Elia, Chiara; Gaia, Silvia; Mengozzi, Giulio; Romito, Alessandrina V; Eloubeidi, Mohamad A; Rizzetto, Mario; De Angelis, Claudio

    2014-09-01

    There is scant literature about common bile duct (CBD) dilatation with normal liver function tests (LFTs). The aims of this study were to assess the diagnostic yield of endoscopic ultrasound (EUS) in patients with CBD dilatation, normal LFTs, and prior inconclusive imaging tests, and to assess the natural history of these subjects. We retrospectively reviewed our EUS database for patients referred for evaluation of CBD dilatation, normal LFTs, and prior inconclusive imaging. We excluded patients with a prior endoscopic retrograde cholangiopancreatography or a history of biliary obstruction, pancreatitis, or jaundice. Follow-up data were retrieved from medical records or by calling the general practitioners, referring specialists, patients, or their closest relatives. A total of 57 patients were enrolled. The mean CBD diameter was 12.5±3.6 mm. The majority of patients (50.8%) were asymptomatic. Abnormal EUS findings were recorded in 12 (21%) subjects: 6 patients had a periampullary diverticulum, 2 had ampullary adenoma, 2 had signs of chronic pancreatitis, 1 had a cancer of the pancreatic head, and 1 had a 7 mm CBD stone. Neither age, sex, prior cholecystectomy, clinical presentation, CBD diameter, nor a dilated main pancreatic duct were predictors of abnormal EUS findings. None of the patients complained of biliary symptoms or showed abnormal LFTs on long-term follow-up. CBD dilatation with normal liver chemistry is not always a benign condition. Even when prior imaging tests are negative, EUS may allow to diagnose conditions overlooked by standard diagnostic imaging.

  16. Efficacy of diclazuril in the prevention and cure of intestinal and hepatic coccidiosis in rabbits.

    PubMed

    Vanparijs, O; Hermans, L; van der Flaes, L; Marsboom, R

    1989-07-15

    The efficacy of diclazuril against intestinal and hepatic coccidiosis was studied in artificially infected rabbits. Prophylaxis against intestinal coccidiosis was evaluated using a mixed infection of Eimeria intestinalis, Eimeria magna and Eimeria perforans. Continuous medication in the feed at 1 p.p.m. was 100% effective in reducing oocyst output and faecal scores, and weight gain and feed efficiency were normal. Hepatic coccidiosis induced by Eimeria stiedai was prevented at 0.5 and 1 p.p.m. as shown by negative oocyst counts, normal liver weight, absence of liver lesions, and normal body-weight gain and feed efficiency. Medication at 1 p.p.m. for 7 consecutive days during the prepatent phase of hepatic coccidiosis resulted in large reductions in oocyst counts and lesion scores with a normal liver weight and growth performance. Diclazuril at 1 p.p.m. in the feed prevented both intestinal and hepatic coccidiosis in rabbits and can be advocated for safe mass medication.

  17. Management of Bleeding in Post-liver Disease, Surgery and Biopsy in Patients With High Uncorrected International Normalized Ratio With Prothrombin Complex Concentrate: An Iranian Experience.

    PubMed

    Parand, Alireza; Honar, Naser; Aflaki, Khashayar; Imanieh, Mohammad Hadi; Haghighat, Mahmood; Cohan, Nader; Haghpanah, Sezaneh; Marietta, Marco; Serati, Zahra; Haghbin, Saeedeh; Karimi, Mehran

    2013-12-01

    To evaluate the efficacy of prothrombin complex concentrate (PCC) in the management of bleeding in patients with liver disease and patients undergoing surgery or biopsy who had a high uncorrected international normalized ratio (INR). In this study, we examined an Iranian sample and investigated the efficacy of PCC to manage bleeding in patients with liver disease and also patients with high uncorrected INR who were scheduled for surgery or biopsy. A total of 25 patients including 16 patients with post-liver disease bleeding (group 1) and 9 patients with high uncorrected INR who were scheduled for surgery or biopsy (group 2) were enrolled. All patients were treated with 25 IU/kg PCC, and efficacy was defined as any reduction in or cessation of bleeding episodes and correction of INR before surgery or biopsy. The patients were also evaluated for any adverse effects. INR decreased significantly in both groups of patients, with no bleeding episodes during or after the study in group 1 and during or after surgery/biopsy in group 2. All patients tolerated the therapy well without any significant adverse effects. The efficacy of PCC therapy was satisfactory in this study. PCC therapy in patients with liver disease and patients undergoing surgery or biopsy seems to be effective and safe, and may be a good treatment strategy for these patients, if fresh frozen plasma or vitamin K are not effective.

  18. (99m)Tc sulfur colloid and (99m)Tc mebrofenin hepatobiliary functional liver imaging in normal and diabetic rats.

    PubMed

    Al-Saeedi, Fatma; Loutfi, Issa

    2011-01-01

    To use (99m)Tc sulfur colloid ((99m)Tc-SC) and (99m)Tc mebrofenin ((99m)Tc-BrIDA) to study liver function in normal and diabetic rats. Radionuclide imaging was performed on 2 groups of rats, using (99m)Tc-SC for one group and (99m)Tc-BrIDA for the other (20 rats per group) before and after induction of diabetes mellitus (DM) using streptozotocin administration (55 mg/kg i.p.). Dynamic acquisition was obtained for 1 h after the injection of 37 MBq of radiotracer. For the (99m)Tc-SC group, organ/tissue uptake was determined by drawing regions of interest (ROI) over the heart, liver, spleen and also the whole body (WB). The ratio of the ROI of each organ to the WB ROI was calculated. For (99m)Tc-BrIDA, ratios of cumulative count rates in liver, liver parenchyma, biliary tree and abdomen ROI to a WB ROI were also calculated. Statistical analysis was performed to compare the ratios of organ/tissue uptake to WB uptake before and after DM induction using the paired t test. (99m)Tc-SC uptake ratios (means ±SD) showed a lower liver-to-WB uptake ratio (0.75 ± 0.05) in the rats after DM induction compared to baseline (0.81 ± 0.06), while the cardiac blood pool showed higher uptake ratios in the rats after DM induction (p = 0.026). For (99m)Tc-BrIDA, there was no significant difference in radiotracer uptake ratios obtained from the rats before and after DM induction (p = 0.41). Using functional liver imaging, there was a statistically significant decrease in the liver phagocytic/reticuloendothelial system function after DM induction, as evidenced by decreased (99m)Tc-SC liver uptake and increased blood pool compared to prediabetes, while the hepatobiliary function remained unchanged after DM induction using (99m)Tc-BrIDA imaging. Copyright © 2011 S. Karger AG, Basel.

  19. Fat and protein from olive oil-fried sardines interact to normalize serum lipoproteins and reduce liver lipids in hypercholesterolemic rats.

    PubMed

    Sánchez-Muniz, Francisco J; García-Linares, M Carmen; García-Arias, M Trinidad; Bastida, Sara; Viejo, Jesús

    2003-07-01

    Fatty fish consumption has been recommended due to its high (n-3) PUFA content. However, an effect of its protein on serum lipids and lipoproteins has also been suggested. The present study was designed to determine the acceptability of diets containing sardines fried in olive oil or the fat extracted from those sardines and the normalization of serum lipids and lipoproteins, the hepatic lipid profile, and the fatty acid composition of the liver of growing Wistar rats fed these diets after dietary loading of cholesterol. Hypercholesterolemia was induced for 3 wk by feeding rats a casein/olive oil/cholesterol diet. Rats were then switched for 2 wk to cholesterol-free purified diets containing casein plus olive oil (CO), sardines fried in olive oil (S) and casein plus the fat extracted from sardines fried in olive oil (CSF). The S and CSF diets were well accepted by the rats. Withdrawal of dietary cholesterol markedly reduced (P < 0.05) serum cholesterol level in all of the groups, but the S group had the greatest decrease and the CO group the smallest decrease. The S group had a more normal lipoprotein profile, in which HDL was the major lipid carrier, whereas rats of the CO group still had beta-VLDL particles. CSF-fed rats had an intermediate profile. Liver fat and total, free and esterified cholesterol levels were lower (P < 0,05) in the S group than in the other two groups. The S and CSF diets increased (P < 0.05) the (n-3) PUFA content in hepatic triacylglyceride, cholesterol ester and phospholipid fractions. The liver fatty acid profile of the S group was more normalized than those of the other two groups. These findings suggest that the inclusion in the diet of whole sardines fried in olive oil normalizes cholesterol metabolism in hypercholesterolemic rats more quickly than consumption of their extracted fat.

  20. Dithiothreitol abrogates the effect of arsenic trioxide on normal rat liver mitochondria and human hepatocellular carcinoma cells

    SciTech Connect

    Paul, Manash K. Kumar, Rajinder; Mukhopadhyay, Anup K.

    2008-01-15

    Arsenic trioxide (ATO) is a known environmental toxicant and a potent chemotherapeutic agent. Significant correlation has been reported between consumption of arsenic-contaminated water and occurrence of liver cancer; moreover, ATO-treated leukemia patients also suffers from liver toxicity. Hence, modulation of ATO action may help to prevent populations suffering from arsenic toxicity as well as help reduce the drug-related side effects. Dithiothreitol (DTT) is a well-known dithiol agent reported to modulate the action of ATO. Controversial reports exist regarding the effect of DTT on ATO-induced apoptosis in leukemia cells. To the best of our knowledge, no report illustrates the modulatory effect of DTT on ATO-induced liver toxicity, the prime target for arsenic. Mitochondria serve as the doorway to apoptosis and have been implicated in ATO-induced cell death. Hence, we attempted to study the modulatory effect of DTT on ATO-induced dysfunction of mammalian liver mitochondria and human hepatocellular carcinoma cell line (Hep3B). We, for the first time, report that ATO produces complex I-mediated electron transfer inhibition, reactive oxygen species (ROS) generation, respiration inhibition, and ATO-induced ROS-mediated mitochondrial permeability transition (MPT) opening. DTT at low concentration (100 {mu}M and less) prevents the effect of ATO-induced complex I-malfunctions. DTT protects mitochondria from ATO-mediated opening of MPT and membrane potential depolarization. DTT also prevented ATO-induced Hep3B cell death. Thus, at low concentrations DTT abrogates the effect of ATO on rat liver mitochondria and Hep3B cell line. Therefore, the present result suggests, that use of low concentration of dithiols as food supplement may prevent arsenic toxicity in affected population.

  1. Liver transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100090.htm Liver transplant - series—Normal anatomy To use the sharing ... to slide 5 out of 5 Overview The liver is in the right upper abdomen. The liver ...

  2. Studies on responsiveness of hepatoma cells to catecholamines. III. Difference between the receptor-adenylate cyclase regulating systems in AH130 cells and cultured normal rat liver cells.

    PubMed

    Sanae, F; Matsunaga, T; Miyamoto, K; Koshiura, R

    1986-10-01

    The responsiveness to three beta-adrenergic agonists, isoproterenol (IPN), epinephrine (Epi) and norepinephrine (NE) in AH13O cells was examined compared with that in normal rat liver cells which were cultured for 24 hr after collagenase digestion. As regards to the activation of adenylate cyclase in the cell homogenates, the relative affinity of the three agonists was in order of IPN greater than NE greater than Epi in AH130 cells and IPN greater than Epi greater than NE in cultured normal liver cells. While the efficacies of the three agonists were similar in cultured liver cells, those of NE and Epi were markedly lower than that of IPN in AH13O cells and were increased to the similar level of IPN by pretreatment with phentolamine, but not with prazosin. Clonidine inhibited the activation of adenylate cyclase by IPN in AH13O cells. When cells were preincubated with islet-activating protein (IAP), the activity of adenylate cyclase in the presence or absence of agonist in both cell lines increased. In IAP-treated AH13O cells, the efficacies of NE and Epi became close to that of IPN. Adenylate cyclase in IAP-treated AH13O cells was activated by GTP in a dose-dependent manner, but that in IAP-treated cultured liver cells was not. In the presence of IPN, biphasic (activatory and inhibitory) effects of GTP on the cyclase were observed, and the inhibitory phase was eliminated by the IAP-treatment in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Hepatosteatosis and hepatic insulin resistance are blunted by argirein, an anti-inflammatory agent, through normalizing endoplasmic reticulum stress and apoptosis in diabetic liver.

    PubMed

    Shi, Fang-Hong; Wu, You; Dai, De-Zai; Cong, Xiao-Dong; Zhang, Yu-Mao; Dai, Yin

    2013-06-01

    Insulin resistance represents a mechanism underlying defect metabolism of carbohydrate and lipid linked to inflammatory reactions in diabetic liver. We hypothesized that the changes may be secondary to endoplasmic reticulum (ER) stress, which could be alleviated by either argirein or valsartan. Hepatosteatosis in diabetic liver was induced in rats fed with a high-fat diet (HFD) for 12 weeks combined with a single low dose of streptozotocin (STZ 35 mg/kg, ip). Interventions (mg/kg/d, po)with either argirein (50, 100 and 200) or valsartan (12) were conducted in the last 4 weeks. In diabetic liver fat was significantly accumulated in association with elevated hepatic glucose, serum insulin and homeostasis model assessment of insulin resistance value. Downregulated glucose transporter 4, insulin receptor substrate-1 and leptin receptor (P < 0.01) were found relative to normal, where DNA ladder, downregulated B cell lymphoma/leukemia-2, upregulated B cell lymphoma/leukemia-2 Associated X protein and upregulated ER stress chaperones such as Bip/GRP78 (also known as Binding Protein, BiP), PKR-like ER kinase (PERK), p-PERK/PERK and C/EBP homologous protein were significant. These abnormalities were significantly ameliorated by argirein and valsartan. Hepatosteatosis induced by HFD/low STZ manifests insulin resistance and apoptosis, linked to an entity of low-grade inflammation due to activated ER stress sensors. With anti-inflammatory activity either argirein or valsartan blunts hepatosteatosis through normalizing ER stress and apoptosis in the diabetic liver. © 2013 Royal Pharmaceutical Society.

  4. Quantification of choline concentration following liver cell apoptosis using 1H magnetic resonance spectroscopy.

    PubMed

    Shen, Zhi-Wei; Cao, Zhen; You, Ke-Zeng; Yang, Zhong-Xian; Xiao, Ye-Yu; Cheng, Xiao-Fang; Chen, Yao-Wen; Wu, Ren-Hua

    2012-03-14

    To evaluate the feasibility of quantifying liver choline concentrations in both normal and apoptotic rabbit livers in vivo, using 1H magnetic resonance spectroscopy (1H-MRS). 1H-MRS was performed in 18 rabbits using a 1.5T GE MR system with an eight-channel head/neck receiving coil. Fifteen rabbits were injected with sodium selenite at a dose of 10 μmol/kg to induce the liver cell apoptosis. Point-resolved spectroscopy sequence-localized spectra were obtained from 10 livers once before and once 24 h after sodium selenite injection in vivo. T1 and T2 relaxation time of water and choline was measured separately in the livers of three healthy rabbits and three selenite-treated rabbits. Hematoxylin and eosin and dUTP-biotin nick end labeling (TUNEL) staining was used to detect and confirm apoptosis. Choline peak areas were measured relative to unsuppressed water using LCModel. Relaxation attenuation was corrected using the average of T1 and T2 relaxation time. The choline concentration was quantified using a formula, which was tested by a phantom with a known concentration. Apoptosis of hepatic cells was confirmed by TUNEL assay. In phantom experiment, the choline concentration (3.01 mmol/L), measured by 1H-MRS, was in good agreement with the actual concentration (3 mmol/L). The average T1 and T2 relaxation time of choline was 612 ± 15 ms and 74 ± 4 ms in the control group and 670 ± 27 ms and 78 ± 5 ms in apoptotic livers in vivo, respectively. Choline was quantified in 10 rabbits, once before and once after the injection with sodium selenite. The choline concentration decreased from 14.5 ± 7.57 mmol/L before sodium selenite injection to 10.8 ± 6.58 mmol/L (mean ± SD, n = 10) after treatment (Z = -2.395, P < 0.05, two-sample paired Wilcoxon test). 1H-MRS can be used to quantify liver choline in vivo using unsuppressed water as an internal reference. Decreased liver choline concentrations are found in sodium selenite-treated rabbits undergoing liver cell

  5. Phospholamban Overexpression in Transgenic Rabbits

    PubMed Central

    Pattison, J. Scott; Waggoner, Jason R.; James, Jeanne; Martin, Lisa; Gulick, James; Osinska, Hanna; Klevitsky, Raisa; Kranias, Evangelia G.; Robbins, Jeffrey

    2008-01-01

    There has been considerable interest in pursuing phospholamban as a putative therapeutic target for overcoming depressed calcium handling in human heart failure. Studies predominantly done in mice have shown that phospholamban is a key regulator of sarcoplasmic reticulum calcium cycling and cardiac function. However, mice differ significantly from humans in how they regulate calcium, whereas rabbits better recapitulate human cardiac function and calcium handling. To investigate phospholamban’s role in the rabbit heart, transgenic rabbits that overexpressed wild-type phospholamban in the ventricular cardiomyocytes and slow-twitch skeletal muscles were generated. Rabbits expressing high levels of phospholamban were not viable due to severe skeletal muscle wasting, the onset of cardiac pathology and early death. A viable transgenic line exhibited a 30% increase in PLN protein levels in the heart. These animals showed isolated foci of cardiac pathology, but cardiac function as well as the response to β-adrenergic stimulation were normal. SR-calcium uptake measurements showed that the transgenic hearts had the expected reduced affinity for calcium. The data show that phospholamban-overexpressing transgenic rabbits differ markedly in phenotype from analogous transgenic mice in that rabbits are quite sensitive to alterations in phospholamban levels. Exceeding a relatively narrow window of phospholamban expression results in significant morbidity and early death. PMID:17882530

  6. Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe.

    PubMed

    O'Rourke, Ann P; Lazebnik, Mariya; Bertram, John M; Converse, Mark C; Hagness, Susan C; Webster, John G; Mahvi, David M

    2007-08-07

    Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

  7. Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents.

    PubMed Central

    Lundberg, I; Håkansson, M

    1985-01-01

    The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods. PMID:2864077

  8. Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance.

    PubMed

    Borel, A L; Nazare, J A; Smith, J; Aschner, P; Barter, P; Van Gaal, L; Eng Tan, C; Wittchen, H U; Matsuzawa, Y; Kadowaki, T; Ross, R; Brulle-Wohlhueter, C; Alméras, N; Haffner, S M; Balkau, B; Després, J P

    2015-03-01

    To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D). Multicenter, international observational study: cross-sectional analysis. Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation. Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15-1.74), women: OR 1.62 (1.29-2.04)), iIGT (men: OR 1.59 (1.15-2.01), women: OR 1.30 (0.96-1.76)), IFG+IGT (men: OR 1.64 (1.27-2.13), women: OR 1.83 (1.36-2.48)) and nT2D (men: OR 1.80 (1.35-2.42), women: OR 1.73 (1.25-2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12-1.90), women: OR 1.81 (1.41-2.35)), IFG+IGT (men: OR 1.42 (1.14-1.77), women: OR 1.74 (1.35-2.26)) and nT2D (men: OR 1.77 (1.40-2.27), women: OR 2.38 (1.81-3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45-0.88)). Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women.

  9. Prevalence and pathological study on rabbit hepatic coccidiosis in Taiwan.

    PubMed

    Wang, J S; Tsai, S F

    1991-10-01

    Five breeds of rabbits, which included the New Zealand, Californian, Spot, Rex and Angora rabbit, were found from a survey of 1,152 rabbits in Taiwan. The prevalence of coccidia in young rabbits (weaning-2 months old) was 95% to 100%. Adult female rabbits usually acted as carriers within the farm and transmitted the parasite to young rabbits, which caused severe infection with clinical signs and even death. Parasitism of hepatic coccidia (Eimeria stiedai) in the rabbit led to severe mortality. Numerous and scattered white nodules about 0.1 to 0.5 cm in diameter were seen on the liver surface and dark greenish mucoid exudate was found in intestinal lumen. Histopathologic lesions included hyperplasia of the bile duct epithelium with different developmental stages of coccidia within. Oocysts could be seen in the lumen, and granuloma tissues encircle the bile duct with infiltration of inflammatory cells. The other organs were not infected.

  10. Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment.

    PubMed

    Ligabue, Matteo; Lucchetti, Dario; Catone, Tiziana; Fabrizi, Laura; Marvasi, Luigi; Zaghini, Anna; Coni, Ettore

    2005-11-01

    Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.

  11. Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

    PubMed

    Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

    2015-11-01

    Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase

  12. Coexisting bicuspid aortic and pulmonary valves with normally related great vessels diagnosed by live/real time three-dimensional transesophageal echocardiography.

    PubMed

    Kemaloğlu Öz, Tuğba; Karadeniz, Fatma Özpamuk; Gundlapalli, Hareesh; Erer, Betul; Sharma, Rohit K; Ahmed, Mustafa; Nanda, Navin C; Yıldırım, Aydın; Orhan, Gökçen; Öz, Ayhan; Eren, Mehmet

    2014-02-01

    Coexistence of bicuspid aortic and pulmonary valves in the same patient is a very rare entity identified mainly during surgery and postmortem. To the best of our knowledge, only one case has been diagnosed by two-dimensional echocardiography in a newborn with malposition of the great arteries but no images were presented. Here, we are reporting the first case of bicuspid pulmonary and aortic valves diagnosed by live/real time three-dimensional transesophageal echocardiography in an adult with normally related great arteries. © 2014, Wiley Periodicals, Inc.

  13. Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases

    PubMed Central

    Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

    2015-01-01

    Abstract Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66–0.84) for at least moderate inflammation and 0.82 (95% CI 0.75–0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate

  14. Study on impression smears of hepatic coccidiosis in rabbits.

    PubMed

    Sivajothi, S; Reddy, B Sudhakara; Rayulu, V C

    2016-09-01

    Hepatic coccidiosis is a contagious and lethal disease condition in rabbits. The disease was recorded in six rabbits suffering with watery diarrhoea. Clinically, affected rabbits showed decreased growth rate, anorexia, debilitation, diarrhea and rough hair coat. Examination of the faecal samples revealed the presence of unsporulated oocysts of Eimeria spp. After sporulation Eimeria stiedae oocysts were identified. Postmortem examination revealed hepatomegaly with presence of discrete yellowish-white nodules on the surface of the liver. Impression smears from the liver revealed the presence of numerous developmental stages of E. stiedae corresponding with the stage of the liver lesion and also represent the histological changes of the liver. Rabbits were treated with a combination of sulphaquinoxaline and diaveridine for five days.

  15. Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

    PubMed

    Mao, Jingjing; Zhao, Yue; She, Ruiping; Cao, Binbin; Xiao, Peng; Wu, Qiaoxing; Guo, Zhaojie; Ma, Longhuan; Soomro, Majid Hussain

    2014-01-01

    Rabbit hepatitis E virus (HEV) is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

  16. Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization.

    PubMed

    Courtaut, Flavie; Derangère, Valentin; Chevriaux, Angélique; Ladoire, Sylvain; Cotte, Alexia K; Arnould, Laurent; Boidot, Romain; Rialland, Mickaël; Ghiringhelli, François; Rébé, Cédric

    2015-09-29

    Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXRβ and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXRβ, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXRβ could be a promising target in cancer therapy.

  17. Human liver nucleolar antigens.

    PubMed

    Busch, R K; Busch, H

    1981-10-01

    In an extension of previous studies on the antigens in rat liver nucleoli (R. K. Busch, R. C. Reddy, D. H. Henning, and H. Busch, Proc. Soc. Exp. Biol. Med. 160, 185 (1979); R. K. Busch and H. Busch, Tumori 63, 347 (1977); F. M. Davis, R. K. Busch, L. C. Yeoman, and H. Busch, Cancer Res. 38, 1906 (1978), rabbit antibodies were elicited to human liver nucleoli isolated by the sucrose--Mg2+ method (10). Fluorescent nucleoli were found in liver cryostat sections treated with rabbit anti-human liver nucleolar antibodies followed by fluorescein-conjugated goat anti-rabbit antibodies. In HeLa cells, fluorescence was distributed throughout the nucleus and in a nuclear network but was not localized to the nucleolus. In placental cryostat sections, an overall nuclear fluorescence was observed with some localization to nucleoli. Immunodiffusion analysis revealed two immunoprecipitin bands which appeared to be liver specific. Other immunoprecipitin bands were common to liver, placenta, and HeLa nuclear extracts. Rocket immunoelectrophoresis revealed two liver-specific antigens, one migrating to the cathode and the other to the anode Other rockets exhibited identity to antigens of other nuclear extracts. These results demonstrate the presence of human liver nucleolar-specific antigens which were not found in the HeLa and placental cells.

  18. Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens.

    PubMed

    Matthaei, Markus; Kerr, Peter J; Read, Andrew J; Hick, Paul; Haboury, Stephanie; Wright, John D; Strive, Tanja

    2014-06-09

    Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. We quantified RHDV replication and shedding in 4-5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4-5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important role in RHDV field epidemiology, in

  19. Is liver perfusion CT reproducible? A study on intra- and interobserver agreement of normal hepatic haemodynamic parameters obtained with two different software packages.

    PubMed

    Bretas, Elisa Almeida Sathler; Torres, Ulysses S; Torres, Lucas Rios; Bekhor, Daniel; Saito Filho, Celso Fernando; Racy, Douglas Jorge; Faggioni, Lorenzo; D'Ippolito, Giuseppe

    2017-10-01

    To evaluate the agreement between the measurements of perfusion CT parameters in normal livers by using two different software packages. This retrospective study was based on 78 liver perfusion CT examinations acquired for detecting suspected liver metastasis. Patients with any morphological or functional hepatic abnormalities were excluded. The final analysis included 37 patients (59.7 ± 14.9 y). Two readers (1 and 2) independently measured perfusion parameters using different software packages from two major manufacturers (A and B). Arterial perfusion (AP) and portal perfusion (PP) were determined using the dual-input vascular one-compartmental model. Inter-reader agreement for each package and intrareader agreement between both packages were assessed with intraclass correlation coefficients (ICC) and Bland-Altman statistics. Inter-reader agreement was substantial for AP using software A (ICC = 0.82) and B (ICC = 0.85-0.86), fair for PP using software A (ICC = 0.44) and fair to moderate for PP using software B (ICC = 0.56-0.77). Intrareader agreement between software A and B ranged from slight to moderate (ICC = 0.32-0.62) for readers 1 and 2 considering the AP parameters, and from fair to moderate (ICC = 0.40-0.69) for readers 1 and 2 considering the PP parameters. At best there was only moderate agreement between both software packages, resulting in some uncertainty and suboptimal reproducibility. Advances in knowledge: Software-dependent factors may contribute to variance in perfusion measurements, demanding further technical improvements. AP measurements seem to be the most reproducible parameter to be adopted when evaluating liver perfusion CT.

  20. Gd-EOB-DTPA-enhanced MRI T1 mapping for assessment of liver function in rabbit fibrosis model: comparison of hepatobiliary phase images obtained at 10 and 20 min.

    PubMed

    Zhou, Zhi-Peng; Long, Li-Ling; Huang, Li-Juan; Yang, Teng-Fei; Huang, Zhong-Kui

    2017-04-01

    To compare hepatobiliary phase (HBP) images obtained at 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for assessment of liver function in rabbit fibrosis model on 3.0 T MR imaging. 34 animals were separated into three groups: 5 for a control group, 14 for a mild fibrosis group, and 15 for a severe fibrosis group based on pathological proof. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at 10 and 20 min after Gd-EOB-DTPA enhancement. Indocyanine green retention rates at 15 min (ICG R15) were performed for all animals. T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all groups. T1rt on 10 min HBP and 20 min HBP showed significant difference (p < 0.05) among all groups. T1rt and rrT1rt in three groups showed no-significant difference (p > 0.05) between 10 min HBP and 20 min HBP. T1rt on both 10 and 20 min HBP showed significant correlation with ICG R15 (p < 0.05); rrT1rt on both 10 min HBP and 20 min HBP showed significant inverse correlation with ICG R15 (p < 0.05). Comparing 10 min HBP and 20 min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10 min HBP T1 mapping is feasible for quantitatively assessing liver function.

  1. Liver transplantation☆

    PubMed Central

    Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

    2007-01-01

    Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

  2. RABBIT POX

    PubMed Central

    Rosahn, Paul D.; Hu, Ch'uan-K'uei

    1935-01-01

    Observations on an epidemic of rabbit pox occurring in an isolated animal room during the winter of 1933–34 are reported. The clinical manifestations, consisting of a generalized papular eruption involving the skin and mucous membranes, together with blepharitis, ophthalmia, nasal discharge and lymphadenopathy were essentially similar to those noted in a pox epidemic of the previous year. This was true in general also of the pathological findings except that vacuolization, local necrosis and vesicle formation were seen in the epidermis, while in the previous year the microscopic pathology in the skin was confined to the corium. Evidence was presented indicating that the infection can be transmitted through the medium of a personal carrier, and that transmission in this manner can occur during the incubation period or before a definite diagnosis is possible. The findings also demonstrated that the etiological agents responsible for the disease reported here and that of the previous year were immunologically related, and that the immunity in recovered animals effectively persisted during the entire period for which data are available, 9 to 12 months. It appeared also that young animals suckling an immune doe were more refractory to the development of the lesions of rabbit pox than were the young of susceptible does. PMID:19870418

  3. Suitability of boron carriers for BNCT: accumulation of boron in malignant and normal liver cells after treatment with BPA, BSH and BA.

    PubMed

    Chou, F I; Chung, H P; Liu, H M; Chi, C W; Lui, W Y

    2009-07-01

    Hepatocellular carcinoma remains widely prevalent in tropical Africa and south-east Asia. At present, there are no effective treatments for hepatoma and its prognosis is extremely poor unless the tumor was diagnosed in an early stage and resected before metastasis. Therefore, boron neutron capture therapy (BNCT) may provide an alternative therapy for treatment of hepatocellular carcinoma. In this study, the intracellular concentrations of L-boronophenylalanine (BPA), sodium borocaptate (BSH) and boric acid (BA) were examined in human hepatoma HepG2 and liver Clone 9 cell cultures. With the use of 25 microgB/mL media of BPA, BSH and BA, the intracellular uptake of boron in HepG2 and Clone 9 cells was compared. The suitability of BPA, BSH and BA were further evaluated on the basis of organ-specific boron distribution in normal rat tissues. BPA, BSH and BA were administered via intraperitoneal injection into rats with corresponding boron concentrations of 7, 25, and 25mg/kg body weight, respectively. The accumulation rates of BPA, BSH and BA in HepG2 cells were higher than that of Clone 9 cells. Boron concentration in BPA, BSH and BA treated HepG2 cells were 1.8, 1.5, and 1.6-fold of Clone 9 cells at 4h, respectively. In both HepG2 and Clone 9 cells, although the concentration of boron in BPA-treated cells exceeded that in BA-treated ones, however, cells treated with BPA had similar surviving fraction as those treated with BA after neutron irradiation. The accumulation ratios of boron in liver, pancreas and kidney to boron in blood were 0.83, 4.16 and 2.47, respectively, in BPA treated rats, and 0.75, 0.35 and 2.89, respectively, in BSH treated rats at 3h after treatment. However, boron does not appear to accumulate specifically in soft tissues in BA treated rats. For in situ BNCT of hepatoma, normal organs with high boron concentration and adjacent to liver may be damaged in neutron irradiation. BPA showed high retention in pancreas and may not be a good drug for

  4. Structural changes in rabbit oral epithelium caused by zinc deficiency.

    PubMed

    Joseph, C E; Ashrafi, S H; Waterhouse, J P

    1981-01-01

    We report the successful establishment of zinc deficiency in rabbits by dietary means. The soybean protein of a standard rabbit diet was replaced by egg albumin. Weanling, New Zealand white rabbits, were fed a low zinc diet containing 1.5 microgram Zn/g of diet. Zinc-deficient rabbits showed stunted growth, weight loss, altered posture, partial alopecia and crusting of skin. Structural alterations in oral epithelium of the zinc-deficient rabbits included in the tongue flattened filiform papillae showing parakeratosis, in the cheek parakeratosis of the normally nonkeratinized epithelium and hyperplasia of the lip epidermis.

  5. A FILTERABLE VIRUS INFECTION OF RABBITS

    PubMed Central

    Andrewes, C. H.; Miller, C. Philip

    1924-01-01

    1. In two, and possibly four, of six transmission series of rabbits inoculated in the beginning with the blood of apparently normal rabbits a virus was recovered having the same properties as that recovered from series originally inoculated with material from rheumatic fever patients. The virus was immunologically identical with Rivers-Tillett Virus III and with that obtained from the rheumatic fever series. In conducting the control series precautions were taken to prevent infection of rabbit stock from known sources of the virus. 2. Treating rabbits with benzene does not appreciably increase their susceptibility to infection with the virus. 3. The virus is probably a parasite of the domestic rabbit but up to the present time the natural course of the infection in that animal is unknown. PMID:19868959

  6. Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits.

    PubMed

    Choe, S C; Kim, H S; Jeong, T S; Bok, S H; Park, Y B

    2001-12-01

    Naringin, a bioflavonoid found in citrus fruit peel, is known to have an antioxidative effect, but its effect on atherosclerosis has not been studied. This study evaluated the effect of naringin on blood lipid levels and aortic fatty streaks, and its action mechanism in hypercholesterolemic rabbits. Male New Zealand white rabbits were fed a 0.25% cholesterol diet and divided into an untreated group (n = 4), a naringin-treated group (n = 5; 500 mg/kg per day), and a lovastatin-treated group (n = 5; 20 mg/kg per day). After 8 weeks, blood was sampled and analyzed biochemically. Aorta and liver were harvested and examined histologically. Cholesterol level in rabbits fed the 0.25% cholesterol diet reached 17 times normal and decreased in the rabbits fed naringin and lovastatin, whose effects were not statistically significant (p > 0.05). However, both naringin and lovastatin effectively decreased the area of fatty streak in thoracic aorta on macroscopic analysis (p < 0.05) and significantly reduced subintimal foam cell infiltration on microscopic morphometry (p < 0.05). These foam cells were macrophages on immunohistochemical analysis. Naringin treatment inhibited hypercholesterolemia-induced intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells. Hypercholesterolemia caused fatty liver and elevation of liver enzymes, which was prevented by naringin but not by lovastatin. Naringin significantly reduced fatty streak formation and neointimal macrophage infiltration and also inhibited the expression of ICAM-1 in endothelial cells, suggesting that suppression of ICAM-1 contributed to the antiatherogenic effect. Naringin, unlike lovastatin, has a hepatoprotective action.

  7. Factors Predicting HBsAg Seroclearance and Alanine Transaminase Elevation in HBeAg-Negative Hepatitis B Virus-Infected Patients with Persistently Normal Liver Function

    PubMed Central

    Chien, Tai-Long; Wang, Jing-Houng; Kee, Kwong-Ming; Chen, Chien-Hung; Hung, Chao-Hung; Lu, Sheng-Nan

    2016-01-01

    Background A certain proportion of hepatitis B virus (HBV)-infected patients with persistently normal alanine transaminase (ALT) levels have significant fibrosis. Using liver stiffness measurements (Fibroscan®) and laboratory data, including serum ALT, quantitative HBsAg (qHBsAg), and HBV DNA, we attempted to predict the natural histories of these patients. Methods Non-cirrhotic HBeAg-negative chronic hepatitis B patients with persistently normal ALT were followed up prospectively with the end points of HBsAg seroclearance and ALT elevation above the upper limit of normal. The factors that were predictive of the end points were identified. Results A total of 235 patients with an average age of 48.1 +/- 10.7 years were followed up for 7 years. Eight patients (3.4%) lost HBsAg, and 15 patients (6.4%) experienced ALT elevation. The overall cumulative HBsAg seroclearances were 0.4%, 1.3% and 2.3% at years 1, 3 and 5, respectively. Regarding HBsAg seroclearance, the qHBsAg (< 30 IU/ml) cutoff resulted in a hazard ratio (HR) of 19.6 with a 95% confidence interval (CI) of 2.2–166.7 (P = 0.008). The baseline ALT level (odd ratio (OR) 1.075, 95% CI 1.020–1.132, P = 0.006) and a qHBsAg above 1000 IU/ml (3.7, 1.1–12.4, P = 0.032) were associated with ALT elevation. Limited to men, the baseline liver stiffness (1.6, 1.0–2.5, P = 0.031) and a qHBsAg above 1000 IU/ml (10.4, 2.1–52.4, P = 0.004) were factors that were independently associated with ALT elevation. Conclusion A low qHBsAg level predicted HBsAg clearance. Baseline ALT and a qHBsAg above 1000 IU/ml were independent predictive factors for ALT elevation. Among the men, the independent predictive factors for ALT elevation were qHBsAg and liver stiffness. PMID:27935953

  8. Sitagliptin prevents the development of metabolic and hormonal disturbances, increased β-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats.

    PubMed

    Maiztegui, Bárbara; Borelli, María I; Madrid, Viviana G; Del Zotto, Héctor; Raschia, María A; Francini, Flavio; Massa, María L; Flores, Luis E; Rebolledo, Oscar R; Gagliardino, Juan J

    2011-01-01

    The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3 weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2 mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight, intraperitoneally). Water and food intake, oral glucose tolerance, plasma glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration, HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-β (HOMA for β-cell function) and liver triacylglycerol content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triacylglycerol content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus these compounds, useful in treating Type 2 diabetes, would also prevent/delay the progression of early metabolic and tissue markers of this disease.

  9. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    PubMed Central

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics. PMID:25544897

  10. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits.

    PubMed

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of "Pachkutta," a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.

  11. Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

    PubMed Central

    Hunt, C. E.; Duncan, L. A.

    1985-01-01

    Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model

  12. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits.

    PubMed

    Badimon, J J; Badimon, L; Galvez, A; Dische, R; Fuster, V

    1989-03-01

    The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels.

  13. Risk of zoonotic transmission of HEV from rabbits.

    PubMed

    Lhomme, Sébastien; Dubois, Martine; Abravanel, Florence; Top, Sokunthea; Bertagnoli, Stéphane; Guerin, Jean-Luc; Izopet, Jacques

    2013-10-01

    Hepatitis E virus strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. Further issues remain to be clarified, including whether the genotype of rabbit HEV differs from human and swine HEV genotype 3 and whether rabbit HEV can infect human and other animals. HEV was found in farmed rabbits in several geographic areas of China, in USA and more recently in France. The prevalence of antibodies against HEV was 36%, 57% and 55% in rabbits from Virginia (USA), Gansu Province and Beijing (China), respectively. HEV RNA was detected in 16.5% of serum samples from farmed rabbits in Virginia, 7.5% in Gansu Province and 7.0% in Beijing. HEV RNA was detected in 7% of bile samples from farmed rabbits and in 23% of liver samples from wild rabbits in France. The full-length genomic sequences analysis indicates that all the rabbit strains belong to the same clade. Nucleotide sequences were 72.2-78.2% identical to HEV genotypes 1-4. Comparison with HEV sequences of human strains circulating in France and reference sequences identified a human strain closely related to rabbit HEV. A 93-nucleotide insertion in the X domain of the ORF1 of the human strain and in all the rabbit HEV strains was found. Moreover, the ability of rabbit HEV to cause cross-species infection in a pig model has recently been demonstrated. Rabbit HEV can replicate efficiently in human cell lines. Collectively, these data support the possibility of zoonotic transmission of HEV from rabbits.

  14. Increased visceral adiposity with normal weight is associated with the prevalence of non-alcoholic fatty liver disease in Japanese patients with type 2 diabetes.

    PubMed

    Bouchi, Ryotaro; Takeuchi, Takato; Akihisa, Momoko; Ohara, Norihiko; Nakano, Yujiro; Nishitani, Rie; Murakami, Masanori; Fukuda, Tatsuya; Fujita, Masamichi; Minami, Isao; Mihara, Masatomo; Yoshimoto, Takanobu; Ogawa, Yoshihiro

    2016-07-01

    To investigate the impact of increased visceral adiposity with normal weight (OB[-]VA[+]) on the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes. This was a cross-sectional study of 140 Japanese patients with type 2 diabetes (mean age 65 ± 11 year; 44.6% women). Visceral fat area (VFA; cm(2) ) and liver attenuation index (LAI) were assessed by abdominal computed tomography. The patients were divided into four groups by VFA and body mass index (BMI; kg/m(2) ) as follows: BMI <25 kg/m(2) and VFA <100 cm(2) (OB[-]VA[-]), BMI ≥25 kg/m(2) and VFA <100 cm(2) (OB[+]VA[-]), BMI <25 kg/m(2) and VFA ≥100 cm(2) (OB[-]VA[+]), and BMI ≥25 kg/m(2) and VFA ≥100 cm(2) (OB[+]VA[+]). Multivariate linear regression and logistic regression analysis were carried out to determine the impact of OB(-)VA(+) on LAI. In the present study, 25.0% were OB(-)VA(+) patients, where the LAI levels were lower (1.09 ± 0.22) than those in OB(-)VA(-) patients (1.23 ± 0.15), and were equivalent to those in OB(+)VA(+) patients (1.03 ± 0.26). In multivariate linear regression analysis, OB(-)VA(+) was independently associated with LAI (standardized β-0.212, P = 0.014). In multivariate logistic regression analysis, OB(-)VA(+) was a significant predictor of LAI <0.9 (odds ratio 5.88, 95% confidence interval 1.03-33.52, P = 0.046). The present study provides evidence that increased visceral adiposity with normal weight is a strong predictor for the prevalence of non-alcoholic fatty liver disease in Japanese patients with type 2 diabetes. © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  15. Transmission electron microscopic observations on ultrastructural alterations in Schistosoma mansoni adult worms recovered from C57BL/6 mice treated with radiation-attenuated vaccine and/or praziquantel in addition to passive immunization with normal and vaccinated rabbit sera against infection.

    PubMed

    El-Shabasy, Eman A; Reda, Enayat S; Abdeen, Sherif H; Said, Ashraf E; Ouhtit, Allal

    2015-04-01

    Although the current treatment of schistosomiasis relies largely on praziquantel (PZQ), it has not been successful in significantly reducing the overall rate of disease cases, one of the suggested reasons being the inevitable resistance to PZQ. Previous studies showed that radiation-attenuated vaccine provides protection against Schistosoma mansoni in a host of various species. In the present study, we evaluated the effect of various vaccination strategies in C57BL/6 mice, including single or multiple vaccination strategy, subcurative dose (20 mg/kg) of PZQ, and a combination of single vaccination with subcurative dose of PZQ. Treatment either with subcurative dose of PZQ or with a single vaccination of attenuated cercariae (500 per mouse), caused significant reduction in total worm burden, hepatic, and intestinal ova counts of 43.03, 73.2, and 59.5 and 37.97, 52.02, and 26.3%, respectively. Furthermore, tegumental changes were observed. In multiple vaccinated group, there was an extensive lysis in tegumental layers. High deformations in gastrodermis, testis cells, vitelline cells, and oocytes were recorded. Also, this study is to explore the role of humoral immunity using highly resistant rabbits that had been exposed to three immunizations with ultraviolet (UV)-irradiated cercariae (8000 per rabbit in each immunization), and their sera were tested for their ability to transfer protection. The reduction in challenge worm burden had reached 32.76-43.64% when compared with recipients of normal serum or no serum. The reduction in hepatic and intestinal ova counts reached to 74.4 and 71.08% in group immunized with vaccinated rabbit sera. Swelling and extensive lysis of tegumental layers, gastrodermis lumen, spermatocytes, and deformation of oocytes were recorded with more severity than that recorded in normal rabbit sera group. Our findings recorded that multiple vaccination strategy is the most effective strategy then passive transfer of vaccinated rabbit. This gives

  16. Biotransformation of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) by a Rabbit Liver Cytochrome P450: Insight into the Mechanism of RDX Biodegradation by Rhodococcus sp. Strain DN22

    PubMed Central

    Bhushan, Bharat; Trott, Sandra; Spain, Jim C.; Halasz, Annamaria; Paquet, Louise; Hawari, Jalal

    2003-01-01

    A unique metabolite with a molecular mass of 119 Da (C2H5N3O3) accumulated during biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Rhodococcus sp. strain DN22 (D. Fournier, A. Halasz, J. C. Spain, P. Fiurasek, and J. Hawari, Appl. Environ. Microbiol. 68:166-172, 2002). The structure of the molecule and the reactions that led to its synthesis were not known. In the present study, we produced and purified the unknown metabolite by biotransformation of RDX with Rhodococcus sp. strain DN22 and identified the molecule as 4-nitro-2,4-diazabutanal using nuclear magnetic resonance and elemental analyses. Furthermore, we tested the hypothesis that a cytochrome P450 enzyme was responsible for RDX biotransformation by strain DN22. A cytochrome P450 2B4 from rabbit liver catalyzed a very similar biotransformation of RDX to 4-nitro-2,4-diazabutanal. Both the cytochrome P450 2B4 and intact cells of Rhodococcus sp. strain DN22 catalyzed the release of two nitrite ions from each reacted RDX molecule. A comparative study of cytochrome P450 2B4 and Rhodococcus sp. strain DN22 revealed substantial similarities in the product distribution and inhibition by cytochrome P450 inhibitors. The experimental evidence led us to propose that cytochrome P450 2B4 can catalyze two single electron transfers to RDX, thereby causing double denitration, which leads to spontaneous hydrolytic ring cleavage and decomposition to produce 4-nitro-2,4-diazabutanal. Our results provide strong evidence that a cytochrome P450 enzyme is the key enzyme responsible for RDX biotransformation by Rhodococcus sp. strain DN22. PMID:12620815

  17. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-04-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

  19. Assessment of a Novel Vaccine Against Rabbit Hemorrhagic Disease Virus in Young Rabbits.

    PubMed

    Pacho, Sonsoles; Dahdouh, Elias; Merino, Javier; Suárez, Monica

    2016-12-01

    Rabbit hemorrhagic disease virus (RHDVb) is the new variant of the classical RHDV, a virulent pathogen responsible for an acute disease in young rabbits. The virus invades internal organs, especially the liver, spleen, kidneys, and gut; prevents coagulation; and causes liver necrosis. This eventually leads to quick death of the animal because of hemorrhage. In this study, we evaluated the effects of a new vaccine against RHDVb in rabbits at a young age, after experimental infection using four different viral isolates. Our findings show that the vaccine had a protective effect with survival rates reaching 80-100% against the different isolates. These results suggest that this vaccine, when applied to young animals, is an effective tool to protect against the disease caused by RHDVb in rabbitries.

  20. The expression and concentration of CD40 ligand in normal pregnancy, preeclampsia, and hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome.

    PubMed

    Azzam, Hanan A G; Abousamra, Nashwa K; Goda, Hossam; El-Shouky, Reda; El-Gilany, Abdel-Hady

    2013-01-01

    Preeclampsia has been associated with increased platelet activation detected before disease onset. Inappropriate activation of platelets may be involved in pathogenesis in preeclampsia by promoting coagulation and thrombosis and also as a mediator of inflammation. The exaggerated platelet activation and inflammation leading to endothelial damage in preeclampsia can be explained by the CD40-CD40 ligand (CD40L) system. Expression of CD40L on platelets was determined by whole-blood flow cytometry, and serum levels of soluble CD40L (sCD40L) were measured by enzyme-linked immunosorbent assay in 11 women with mild preeclampsia, 11 women with severe preeclampsia, and six women with hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome compared with 13 normotensive pregnant women as a control group. The platelet surface expression of CD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with normal pregnancy group (P = 0.001; P ≤ 0.001; P = 0.003, respectively), with no significant difference being found between women with mild preeclampsia compared with HELLP and severe preeclampsia compared with HELLP (P = 0.2; P = 0.8, respectively). The serum concentration of sCD40L was significantly higher in women with mild and severe preeclampsia and HELLP compared with the normal pregnancy group (P = 0.001; P ≤ 0.001; P = 0.022, respectively), with no significant difference being found between women with mild compared with severe preeclampsia or HELLP and severe preeclampsia compared with HELLP (P = 0.7; P = 0.6; P = 0.6, respectively). In conclusion, the higher expression and concentration of CD40L in women with preeclampsia and HELLP syndrome compared with normal pregnant women may indicate an exaggerated activation of platelets and endothelial cells in the disorder.

  1. Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets.

    PubMed

    Zhang, Hao; Li, Yue; Hou, Xiang; Zhang, Lili; Wang, Tian

    2016-05-01

    We previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets' biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

  2. Successful treatment of sebaceous adenitis in a rabbit with ciclosporin and triglycerides.

    PubMed

    Jassies-van der Lee, Annette; van Zeeland, Yvonne; Kik, Marja; Schoemaker, Nico

    2009-02-01

    A 4-year-old rabbit was presented with a chronic exfoliative dermatitis and patchy alopecia. General physical examination revealed no abnormalities. Skin scrapings and fungal culture were negative. A blood sample was obtained for a complete blood cell count and biochemical profile, and yielded results that were within normal limits. Radiographic examination of the thorax excluded the presence of a thymoma. Histopathology of the skin showed orthokeratotic hyperkeratosis, absence of sebaceous glands and mural lymphocytic folliculitis, consistent with sebaceous adenitis. Oral treatment was started with ciclosporin dissolved in a medium-chain triglyceride solution (Miglyol 812), combined with essential fatty acids and topical propylene glycol sprays. Within 2 months of treatment, complete regression of skin lesions and regrowth of hair was observed. Serum chemistry values including kidney and liver function tests remained within reference range during the course of treatment. Histopathological examination of control biopsies of the skin showed presence of normal sebaceous glands and active hair follicles. Treatment was changed to a different pharmaceutical formulation of ciclosporin without Miglyol and deterioration of clinical signs was noticed. Using pure Miglyol 812, however, resulted in a gradual improvement of 60%. A nearly complete response was again observed after re-administration of the combination ciclosporin/Miglyol. It is hypothesized that sebaceous adenitis in the rabbit is most likely due to an autoimmune reaction directed at the sebaceous glands and a defect in lipid metabolism. The outcome indicates that a combination of ciclosporin and Miglyol 812 is a promising new treatment for sebaceous adenitis in rabbits.

  3. Mix-breeding with HEV-infected swine induced inapparent HEV infection in SPF rabbits.

    PubMed

    Liu, Lin; Wang, Lin; Xia, Junke; Zhang, Yulin; Zeng, Hang; Liu, Peng; Zou, Qinghua; Wang, Ling; Zhuang, Hui

    2016-04-01

    Studies have shown that swine HEV (sHEV) and rabbit HEV (rHEV) can experimentally infect rabbits and swine, respectively. However, no published data have documented isolating sHEV strains from rabbits in natural environment so far. To clarify the possibility of natural cross-species transmission of sHEV to rabbits, the pigs with HEV infection were farmed along with SPF rabbits in the same enclosed space. Five of 10 rabbits had seroconversion for anti-HEV antibody from the third week after mix-breeding. However, HEV RNA remained undetectable in feces, serum, liver and bile of the ten rabbits; and no obvious elevation of ALT was observed. The results possibly suggested that sHEV might lead to an inapparent infection of SPF rabbits by fecal-oral route. © 2015 Wiley Periodicals, Inc.

  4. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  5. Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits.

    PubMed

    Habibuddin, Mohammed; Daghriri, Hassan Ali; Humaira, Touseef; Al Qahtani, Mohammed Saeed; Hefzi, Ali Al Hasan

    2008-05-08

    People of Asir region of Saudi Arabia chew Caralluma sinaica (CS) to lower glucose level. To establish its utility in diabetes mellitus we have under taken this study. The effect of CS on streptozotocin (STZ)-induced diabetic model as well as effect on oral glucose tolerance test were studied. The extract was shown to have positive test for possessing following chemical constituents like phenolic alkaloids, glycosides, flavonoids, coumarins, steroids and tannins. Administration of CS in different doses (50, 100, 150 and 200mg/kg, p.o.) to normal animals caused significant (P<0.01) decrease in glucose level. Prior administration of either CS (100mg/kg, p.o.) or glibenclamide (GB) (5mg/kg, p.o.) blocked the rise of glucose caused by the streptozotocin. Antidiabetic activity of CS was compared with clinically available drug GB. Administration of CS (100mg/kg, p.o.) to diabetic rabbits for 30 days has been shown to decrease plasma glucose level to almost normal level (P<0.001). Liver and kidney weight expressed as percentage of body weight significantly (P<0.05; P<0.01) increased in diabetic rabbits versus normal control (CNT). CS significantly (P<0.05) reversed the increasing weight of liver caused by STZ but not GB. STZ induced lowering of glycogen content of liver and muscle was reversed by both CS and GB. STZ induced a significant (P<0.001) increase in renal glycogen content this was almost normalized by CS (P<0.001) whereas GB significantly decreased (P<0.002) glycogen content. In oral glucose tolerance test administration of glucose increased plasma glucose level significantly in the diabetic control over the 2-h period. Compared to diabetic control plasma glucose levels in rabbits given CS or GB were significantly lower at all the time points that blood was sampled after oral glucose load. Comparing with the GB treatment blood glucose lowering effect was more pronounced for diabetic rabbits given CS. All these effects could explain the basis for use of this

  6. Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects.

    PubMed Central

    Taylor, R; Magnusson, I; Rothman, D L; Cline, G W; Caumo, A; Cobelli, C; Shulman, G I

    1996-01-01

    Despite extensive recent studies, understanding of the normal postprandial processes underlying immediate storage of substrate and maintenance of glucose homeostasis in humans after a mixed meal has been incomplete. The present study applied 13C nuclear magnetic resonance spectroscopy to measure sequential changes in hepatic glycogen concentration, a novel tracer approach to measure postprandial suppression of hepatic glucose output, and acetaminophen to trace the pathways of hepatic glycogen synthesis to elucidate the homeostatic adaptation to the fed state in healthy human subjects. After the liquid mixed meal, liver glycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 min, falling rapidly thereafter (0.26 mmol/liter per min). The mean increment at peak represented net glycogen synthesis of 28.3 +/- 3.7 g (approximately 19% of meal carbohydrate content). The contribution of the direct pathway to overall glycogen synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively. Hepatic glucose output was completely suppressed within 30 min of the meal. It increased steadily from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per min then rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min). This pattern of change mirrored precisely the plasma glucagon/insulin ratio. These data provide for the first time a comprehensive picture of normal carbohydrate metabolism in humans after ingestion of a mixed meal. PMID:8550823

  7. Variant rabbit hemorrhagic disease virus in young rabbits, Spain.

    PubMed

    Dalton, Kevin P; Nicieza, Inés; Balseiro, Ana; Muguerza, María A; Rosell, Joan M; Casais, Rosa; Álvarez, Ángel L; Parra, Francisco

    2012-12-01

    Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.

  8. Radiosensitivity of hepatoma cell lines and human normal liver cell lines exposed in vitro to carbon ions and argon ions at the HIRFL

    NASA Astrophysics Data System (ADS)

    Jing, Xigang; Li, Wenjian; Wang, Zhuanzi; Wei, Wei; Guo, Chuanling; Lu, Dong; Yang, Jianshe

    2009-05-01

    Human hepatoma (SMMC-7721) and normal liver (L02) cells were irradiated with γ-rays, 12C 6+ and 36Ar 18+ ion beams at the Heavy Ion Research Facility in Lanzhou (HIRFL). By using the Calyculin-A induced premature chromosome condensation technique, chromatid-type breaks and isochromatid-type breaks were scored separately. Tumor cells irradiated with heavy ions produced a majority of isochromatid break, while chromatid breaks were dominant when cells were exposed to γ-rays. The relative biological effectiveness (RBE) for irradiation-induced chromatid breaks were 3.6 for L02 and 3.5 for SMMC-7721 cell lines at the LET peak of 96 keVμm -112C 6+ ions, and 2.9 for both of the two cell lines of 512 keVμm -136Ar 18+ ions. It suggested that the RBE of isochromatid-type breaks was pretty high when high-LET radiations were induced. Thus we concluded that the high production of isochromatid-type breaks, induced by the densely ionizing track structure, could be regarded as a signature of high-LET radiation exposure.

  9. Combination of high-intensity focused ultrasound irradiation and hydroxyapatite nanoparticle injection to injure normal goat liver tissue in vivo without costal bone incision.

    PubMed

    Liu, L; Xiao, Z; Xiao, Y; Wang, Z; Li, F; Li, M; Peng, X

    2014-10-20

    The aims of this study were to evaluate the in vivo safety of intravenous nano-hydroxyapatite (nano-HA), to explore how nano-HA might influence the effects of high-intensity focused ultrasound (HIFU) on normal liver tissue, and to investigate whether intravenous nano-HA could enhance HIFU for hepatocellular carcinoma ablation in a goat model. The present study, for the first time, indicated that the delivery of abundant nano-HA into the body over short periods of time could be assembled by the hepatic reticuloendothelial system, subsequently leading to a rapid rise of ultrasound-induced overheating, and ultimately resulting in enlargement of the coagulation necrotic area for ablated hepatocellular carcinoma in goats both in vivo and ex vivo. On the other hand, therapeutic doses of nano-HA were much lower than the lethal dose, and consequently presented transient and mild abnormalities of hepatic enzymes and renal function during the first 24 h after nano-HA injection. These results suggested that the combined application of nano-HA and HIFU is potentially a more effective alternative option compared to surgery for hepatocellular carcinoma local ablation in a safe and feasible manner.

  10. Exposure to a commercial glyphosate formulation (Roundup®) alters normal gill and liver histology and affects male sexual activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes).

    PubMed

    Hued, Andrea Cecilia; Oberhofer, Sabrina; de los Ángeles Bistoni, María

    2012-01-01

    Roundup is the most popular commercial glyphosate formulation applied in the cultivation of genetically modified glyphosate-resistant crops. The aim of this study was to evaluate the histological lesions of the neotropical native fish, Jenynsia multidentata, in response to acute and subchronic exposure to Roundup and to determine if subchronic exposure to the herbicide causes changes in male sexual activity of individuals exposed to a sublethal concentration (0.5 mg/l) for 7 and 28 days. The estimated 96-h LC50 was 19.02 mg/l for both male and female fish. Gill and liver histological lesions were evaluated through histopathological indices allowing quantification of the histological damages in fish exposed to different concentrations of the herbicide. Roundup induced different histological alterations in a concentration-dependent manner. In subchronic-exposure tests, Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide. It is expected that in natural environments contaminated with Roundup, both general health condition and reproductive success of J. multidenatata could be seriously affected.

  11. Hepatoprotective and toxicological studies of Salvia bucharica methanolic extract in rabbits.

    PubMed

    Ahmad, Mansoor; Muhammed, Shafi; Mehjabeen, -; Jahan, Noor

    2014-11-01

    Most of the species of genus Salvia are famous for having medicinal properties due to their chemical constituents. Salvia bucharica (Lamiacea) is found in Balochistan near Quetta in Hannaurak and Kalat. It is used in traditional system of medicine and claims to cure liver ailments. In current study crude methanolic extract (CME) of Salvia bucharica was obtained from the leaves and tested for hepatoprotective activity and possible toxicity in rabbits. Liver toxicity was induced in rabbits by administration of carbon tetra chloride (CCl4) and evaluated by biochemical tests and histopathology of tissues. In this study rabbits were divided in to 3 groups (5 rabbit in each group). Rabbits of group I (control) were administered only vehicle (0.9% sodium chloride) orally. Rabbits of group II were given CCl4 and group III were treated with CCl4 and S. bucharica CME orally. For hepatoprotective effect serum enzyme level and total protein level were calculated. Histopathology of liver sections of rabbits was also carried out to observe protective effect. Biochemical, hematological and histoptahological parameters were studied on rabbits for toxicological studies. S. bucharica CME showed significant liver protection with reduction in total bilirubin, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT). And decrease in Albumin and globulin. In toxicological studies, biochemical and histoptahological parameters showed no significant toxicity in liver, heart and kidneys. It is concluded that S. bucharica CME showed hepatoprotective effects with nontoxic profile.

  12. Wildlife of southern forests habitat & management (Chapter 15): Rabbits

    Treesearch

    James G. Dickson

    2003-01-01

    Rabbits, or lagomorphs, resemble rodents. But unlike rodents they have relatively large hind legs, large ears, a short fluffy tail, and 2 sets of upper incisors. Like rodents their incisors grow continually. They can either walk or hop, and are fleet and elusive when evading predators. They normally are silent but are capable of several different vocalizations. Rabbits...

  13. Liver Failure in Pregnancy.

    PubMed

    Bacak, Stephen J; Thornburg, Loralei L

    2016-01-01

    Acute liver failure is a rare but life-threatening medical emergency in pregnancy whose true incidence remains unknown. Many cases of acute liver failure are caused by pregnancy-related conditions such as acute fatty liver of pregnancy and HELLP syndrome. However, acute deterioration in liver function can also be caused by drug overdose, viral infections, and an exacerbation of underlying chronic liver disease. This article provides an overview of the normal liver changes that occur during pregnancy, and summarizes the most common conditions and general management strategies of liver failure during pregnancy.

  14. Comparative analysis of genome sequences of the Th2 cytokine region of rabbit (Oryctolagus cuniculus) with those of nine different species

    PubMed Central

    Gertz, E. Michael; Agarwala, Richa; Mage, Rose G.; Schäffer, Alejandro A.

    2012-01-01

    The regions encoding the coordinately regulated Th2 cytokines IL5, IL4 and IL13 are located on chromosomes 5 of man and 11 of mouse. They have been intensively studied because these interleukins have protective roles in helminth infections, but may lead to detrimental effects such as allergy, asthma, and fibrosis in lung and liver. We added to previous studies by comparing sequences of syntenic regions on chromosome 3 of the rabbit (Oryctolagus cuniculus) genome OryCun 2.0 assembly from a tuberculosis-susceptible strain, with the corresponding region of ENCODE ENm002 from a normal rabbit as well as with 9 other mammalian species. We searched for rabbit transcription factor binding sites in putative promoter and other non-coding regions of IL5, RAD50, IL13 and IL4. Although we identified several differences between the two donor rabbits in coding and non-coding regions of potential functional significance, confirmation awaits additional sequencing of other rabbits. PMID:23239928

  15. LIVER INJURY, LIVER PROTECTION, AND SULFUR METABOLISM

    PubMed Central

    Miller, L. L.; Whipple, G. H.

    1942-01-01

    Protein-depleted dogs are very susceptible to injurious agents—in particular, chloroform. Methionine given shortly before chloroform anesthesia will give complete protection against chloroform. Methionine (or cysteine plus choline) given 3 or 4 hours after chloroform anesthesia will give significant protection against the liver injury of chloroform anesthesia. Methionine given more than 4 hours after chloroform anesthesia gives no protection against liver injury. Choline alone given before chloroform gives no protection against liver injury. The protein-depleted dogs have livers which are deficient in both nitrogen and sulfur, but sulfur is depleted more than is the nitrogen. The N/S ratio therefore rises. Methionine or cystine feeding promptly makes up this liver sulfur deficit. Viable liver cells are necessary for this uptake of sulfur. Livers of fetuses in utero or of newborn pups tolerate a chloroform anesthesia which will cause fatal liver injury in adults. The nitrogen and sulfur values of these fetus or pup livers are within the high normal values for adults. Blood-forming cells are present in the fetus or pup livers during this period. When these blood islands are eliminated during the 3rd or 4th week of life, the liver then becomes normally susceptible to chloroform liver injury. Methionine or methionine-rich protein digests (e.g. casein) or various proteins by mouth or by vein should prove useful to protect the liver against certain types of injury and to aid in organ repair. PMID:19871248

  16. Liver transplant

    MedlinePlus

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  17. Receptor activity on some mesenchymal cells in CNS of normal rabbits. Indications of the monocytic origin of intracerebral perivascular cells, epiplexus cells and mononuclear phagocytes in the subarachnoid space.

    PubMed

    Oehmichen, M

    1976-01-01

    The surface receptor activity for various cell types within rabbit CNS was investigated. Sheep red blood cells (E) used as markers were washed, sensitized with the IgG-fraction of E-antibodies (EA) or additionally coated with complement (EAC) and incubated with CNS cells. The inhibitory effect produced by the addition of soluble IgG was investigated. Incubation (1 h) with red cells was undertaken in three ways: 1. Rabbit leptomeninx was stripped and incubated. 2. Rabbits were killed, the brain was perfused with warm buffer and red cell complexes were then injected intracerebrally, intrathecally and intraventricularly into the perfused brains. 3. E, EA and EAC were injected intracerebrally, intrathecally and intra-ventricularly into living rabbits. Using these methods, receptor sites for IgG and complement of mononuclear cells from the subarachnoid space, epiplexus cells and perivascular cells from intracerebral vessels could be demonstrated. In other areas of the body, these receptors have been demonstrated using similar methods only on cells from the monocyte-macrophage series. The common derivation of these three cell types from the monocytes as well as their comparable function within the immune response is discussed.

  18. Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-12-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  19. Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens

    PubMed Central

    2014-01-01

    Background Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. Methods We quantified RHDV replication and shedding in 4–5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Results Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4–5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Conclusions Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important

  20. The association between content of the elements S, Cl, K, Fe, Cu, Zn and Br in normal and cirrhotic liver tissue from Danes and Greenlandic Inuit examined by dual hierarchical clustering analysis.

    PubMed

    Laursen, Jens; Milman, Nils; Pind, Niels; Pedersen, Henrik; Mulvad, Gert

    2014-01-01

    Meta-analysis of previous studies evaluating associations between content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue samples. Normal liver samples from 45 Greenlandic Inuit, median age 60 years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27 Danes, median age 71 years. Element content was measured using X-ray fluorescence spectrometry. Dual hierarchical clustering analysis, creating a dual dendrogram, one clustering element contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure. One dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age. The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant associations with any other element. In contrast to simple statistical methods, which analyses content of elements separately one by one, dual hierarchical clustering analysis incorporates all elements at the same time and can be used to examine the linkage and interplay between multiple elements in tissue samples. Copyright © 2013 Elsevier GmbH. All rights reserved.

  1. Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients.

    PubMed

    Zhang, Lianshan; Liang, Libin; Tong, Tong; Qin, Yuguo; Xu, Yanping; Tong, Xinglong

    2016-10-01

    Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice. Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients. Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet + ATP group. ATP supplementation (40 mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60 mg twice a day for 1 week. Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p < 0.01). ATP treatment significantly decreased serum TG level (p < 0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p < 0.05) and pathological gradation of ballooning degeneration in hepatocytes (p < 0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p < 0.01), but other lipid parameters had no significant change. Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.

  2. Effects of dietary Corinthian currants (Vitis vinifera L., var. Apyrena) on atherosclerosis and plasma phenolic compounds during prolonged hypercholesterolemia in New Zealand White rabbits.

    PubMed

    Yanni, Amalia E; Efthymiou, Vissarion; Lelovas, Pavlos; Agrogiannis, George; Kostomitsopoulos, Nikolaos; Karathanos, Vaios T

    2015-03-01

    Corinthian currants are a rich source of phenolic compounds, which are known to exert beneficial effects on cardiovascular disease. The hypothesis tested is whether dietary supplementation with currants attenuates atherosclerosis and affects plasma phenolics during prolonged hypercholesterolemia in rabbits. Thirty New Zealand White rabbits were fed one of four diets (normal and supplemented with 10% currants, with 0.5% cholesterol, and with 0.5% cholesterol plus 10% currants) for eight weeks. Plasma lipids, glucose and hepatic enzymes were determined. Individual phenolic compounds were identified and quantified in plasma during the dietary intervention. At the end of the study, histological examinations of aorta and liver were performed. The high-cholesterol diet resulted in hypercholesterolemia and oxidative stress, increased aspartate aminotransferase (AST) activity and induced aortic and hepatic lesion formation. Corinthian currant supplementation attenuated atherosclerotic lesions, maintained AST within the normal range and reduced oxidative stress without affecting glucose concentrations. The p-OH-benzoic and p-OH-phenylacetic acids predominated at high concentrations in plasma and remained almost constant during the study in the group that received the normal rabbit chow and the groups given food with added cholesterol either alone or supplemented with currants. Currant supplementation to the normal diet resulted in the reduced absorption of phenolic compounds, as revealed by the measurement of their plasma metabolites, suggesting a regulatory mechanism at the gut level under normal conditions.

  3. Common procedures in rabbits.

    PubMed

    Graham, Jennifer

    2006-05-01

    Rabbits are popular companion animals that present to veterinary clinics for routine and emergency care. Clinics equipped for treat-ing dogs and cats may be easily adapted to accommodate rabbits. This article reviews common procedures performed by the clinician specific to rabbits. Topics include handling and restraint, triage and patient assessment, sample collection, and supportive care techniques. Miscellaneous procedures, including anesthetic delivery, nasolacrimal duct flushing, and ear cleaning, are also discussed.

  4. Experimental study on the fine structure of chicken liver parenchyme with special references to extrasinusoidal macrophages and sinusoidal blood cells. Part 2. Sinusoidal blood cells in normal and India ink perfused livers.

    PubMed

    Ohata, M; Ito, T

    1986-06-01

    Leucocytes and thrombocytes in the chicken liver sinusoids were observed under normal conditions and after intravenous India ink perfusion. The monocytes exhibited conspicuous phagocytic activity. At 30 min or earlier and 4 hr after the perfusion, they ingested considerable amounts of the carbon particles, which were deposited in small vacuoles and/or lysosomes. In this study we revealed two transitional forms of the monocyte changing into the Kupffer cell. In one transitional form, which already at 15 min after the perfusion stored considerable amounts of the particles, the ectoplasmic layer was partly differentiated and projected many pseudopodia into the sinusoid. At 48 hr after the perfusion, the other transitional form was attached by its wide basal surface to the endothelial linig and projected well-developed pseudopodia into the sinusoid like the Kupffer cell without, however, storing the carbon particles. These findings are thought to suggest the transformation of the monocytes into the Kupffer cells. Thus we came to the assumption that the Kupffer cells might be replenished: by self-proliferation; by the macrophages from the hepatic parenchyme into the sinusoid; or by transformation from the monocytes circulating into the sinusoid (the "triple origin" as opposed to the "dual origin" of the Kupffer cell). In the earliest stage after India ink perfusion, the thrombocytes exhibited the most striking reaction comparable to the Kupffer cells toward which they were assembled. The India ink particles were taken up into the "surface connected canalicular system" (SCS), which thickened and made vacuolar expansions as the amount of the particles was increased. At 4 hr after perfusion, the particles disappeared from the majority of the thrombocytes, leaving an empty SCS. The India ink particle uptake and storage by the thrombocyte were thought to be temporary phenomena, different from the true phagocytosis of the macrophages.

  5. Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples

    PubMed Central

    Edavana, Vineetha Koroth; Penney, Rosalind B; Yao- Borengasser, Aiwei; Starlard-Davenport, Athena; Dhakal, Ishwori B; Kadlubar, Susan

    2015-01-01

    Anastrozole is an aromatase inhibitor (AI) used as adjuvant therapy for breast cancer. Anastrozole is subject to direct glucuronidation catalyzed by UDP-glucuronosyltransferase1A4 (UGT1A4). Interindividual variability in anastrozole glucuronidation may be affected by UGT1A4 SNPs. Interplay between drug metabolizing genes such as UGT1A4 and transporter genes may also be affected by genetic variability. Thus, we hypothesize that genetic variability in MRPs could influence anastrozole glucuronidation. The correlation between UGT1A4 and MRP2 or MRP3 transporter gene expressions and the correlation between MRP2 or MRP3 mRNA and anastrozole glucuronidation were analyzed in normal human liver samples. MRP2 and MRP3 mRNA levels were significantly correlated with UGT1A4 mRNA, with anastrozole glucuronidation and with each other (p<0.05). The data also demonstrated that MRP2 SNPs are positively correlated with MRP2 mRNA expression, while there was no association between MRP3 SNPs from this study and MRP3 expression. Significant correlations (p<0.05) between certain MRP2 SNPs (3972C>T, 2366C>T and −24C>T) and anastrozole glucuronidation were observed. There were no observed correlations between MRP3 SNPs and anastrozole glucuronidation. MRP2 polymorphisms have been identified as playing a role in the disposition of other drugs, and the data presented here indicate for the first time that MRP2 SNPs could influence anastrozole metabolism and contribute to interindividual variation in treatment responses. PMID:26985457

  6. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    PubMed

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  7. Normalization of nano-sized TiO2-induced clastogenicity, genotoxicity and mutagenicity by chlorophyllin administration in mice brain, liver, and bone marrow cells.

    PubMed

    El-Ghor, Akmal A; Noshy, Magda M; Galal, Ahmad; Mohamed, Hanan Ramadan H

    2014-11-01

    The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.

  8. Besnoitia oryctofelisi n. sp. (Protozoa: Apicomplexa) from domestic rabbits.

    PubMed

    Dubey, J P; Sreekumar, C; Lindsay, D S; Hill, D; Rosenthal, B M; Venturini, L; Venturini, M C; Greiner, E C

    2003-06-01

    A species of Besnoitia from naturally infected rabbits from Argentina was propagated experimentally in mice, gerbils, rabbits, cats, and cell cultures. Cats fed tissue cysts from rabbits shed oocysts with a prepatent period of nine to 13 days. Sporulated oocysts were infective to gerbils, rabbits, outbred Swiss Webster and interferon gamma gene knockout mice. Bradyzoites were infective orally to gerbils and cats. Tachyzoites were successfully cultivated and maintained in vitro in bovine monocytes and African green monkey kidney cells. Schizonts were seen in the lamina propria of the small intestine of cats fed tissue cysts; the largest ones measured 52 x 45 microm. Schizonts were also present in mesenteric lymph nodes, livers, and other extra-intestinal organs of cats fed tissue cysts. Oocysts were 10-14 x 10-13 microm in size. This rabbit-derived species of Besnoitia resembled B. darlingi of the North American opossum, Didelphis virginiana with an opossum-cat cycle, but it was not transmissible to D. virginiana, and B. darlingi of opossums was not transmissible to rabbits. Based on biological, serological, antigenic, and molecular differences between the rabbit and the opossum Besnoitia, a new name, B. oryctofelisi is proposed for the parasite from domestic rabbits from Argentina.

  9. INFECTIOUS PAPILLOMATOSIS OF RABBITS

    PubMed Central

    Shope, Richard E.; Hurst, E. Weston

    1933-01-01

    A papilloma has been observed in wild cottontail rabbits and has been found to be transmissible to both wild and domestic rabbits. The clinical and pathological pictures of the condition have been described. It has been found that the causative agent is readily filtrable through Berkefeld but not regularly through Seitz filters, that it stores well in glycerol, that it is still active after heating to 67°C. for 30 minutes, but not after heating to 70°C., and that it exhibits a marked tropism for cutaneous epithelium. The activities and properties of the papilloma-producing agent warrant its classification as a filtrable virus. Rabbits carrying experimentally produced papillomata are partially or completely immune to reinfection and, furthermore, their sera partially or completely neutralize the causative virus. The disease is transmissible in series through wild rabbits and virus of wild rabbit origin is readily transmissible to domestic rabbits, producing in this species papillomata identical in appearance with those found in wild rabbits. However, the condition is not transmissible in series through domestic rabbits. The possible significance of this observation has been discussed. The virus of infectious papillomatosis is not related immunologically to either the virus of infectious fibroma or to that of infectious myxoma of rabbits. PMID:19870219

  10. Pathologic Findings in Rabbit Models of Hereditary Hypertriglyceridemia and Hereditary Postprandial Hypertriglyceridemia

    PubMed Central

    Mitsuguchi, Yoko; Ito, Tsunekata; Ohwada, Kazuo

    2008-01-01

    In recent years, the association between hyperlipidemia and the development of arteriosclerosis has been addressed in several studies. Rabbit models of hypertriglyceridemia (TGH) and postprandial hypertriglyceridemia (PHT) have been developed at the authors' institute. TGH rabbits manifest pathology similar to that of humans with TGH, such as xanthoma, in addition to atherosclerosis of arterioles. Furthermore, PHT rabbits show visceral obesity, insulin resistance, and impaired glucose tolerance, with pathologic features similar to those of the metabolic syndrome assumed to be the cause of human ischemic heart disease. This study was designed to investigate the histopathologic features of TGH and PHT rabbits. TGH rabbits showed advanced aortic atherosclerosis, accompanied by intimal thickening of coronary and renal arteries, fatty liver changes, and xanthoma. PHT rabbits demonstrated aortic intimal thickening and hepatic fatty degeneration. The results of this study suggest that TGH and PHT rabbits are useful animal models for studying human hyperlipidemia and metabolic syndrome and the cardiovascular diseases that result from these conditions. PMID:19004373

  11. Experimental transmission of rabbit haemorrhagic disease virus (RHDV) from rabbit to wild mice (Mus spretus and Apodemus sylvaticus) under laboratory conditions.

    PubMed

    Rocha, Gregorio; Alda, Fernando; Pagés, Albert; Merchán, Tomás

    2017-01-01

    Rabbit haemorrhagic disease (RHD) is a highly lethal and contagious viral disease that produces haemorrhagic lesions in liver and lungs of domestic and wild rabbits (Oryctolagus cuniculus). This study investigates the transmission of RHDV from infected rabbits to mice, based on the detection of viral RNA. Sixteen wild mice (Mus spretus, n=12 and Apodemus sylvaticus, n=4) were put in contact with nine rabbits inoculated with RHDV. No mice died following exposure to RHDV-infected rabbits or developed macroscopic haemorrhagic lesions. On the fourth day of contact, RHDV was detected by RT-PCR in the faeces of three of the four mice killed and in the livers of two of them. Three days after contact period with the inoculated rabbits (7th day of the experiment), RHDV was detected by RT-PCR in 100% (n=4) of the faeces and 50% (n=2) of the livers of euthanized animals. Ten days after contact period (14th day of the experiment), RHDV was not detected in the faeces or liver from any of the mice euthanized. However, 64days after contact period, RHDV was detected in the faeces of one mouse (1 of 4). We demonstrate cross-species transmission of RHDV-RNA from rabbit to rodent and the capability of RHDV-RNA to persist in mice for at least 10days after contact, and potentially up to two months, although viral replication within the rodent and/or infectivity was not evaluated in the present study.

  12. Rabbits' eye globe sonographic biometry.

    PubMed

    Toni, Maria Carolina; Meirelles, Adriana Érica Wilkes Burton; Gava, Fábio Nelson; Camacho, Aparecido Antônio; Laus, José Luiz; Canola, Júlio Carlos

    2010-11-01

    To measure intraocular structures in New Zealand White breed rabbits (Oryctolagus cuniculus Linnaeus, 1758) using A-mode and B-mode ultrasound with a 20 MHz transducer. In this study, the eyes of 15 rabbits were evaluated for determination of intraocular measurements using an ophthalmic ultrasound unit able to operate in both A and B-modes. The distances from the cornea to the anterior capsule of the lens (D1), from the anterior capsule of the lens to the posterior capsule of the lens (D2), from the posterior capsule of the lens to the retina (D3) and the complete length of the eye, which corresponds to the distance from the cornea to the retina (D4) were taken. The mean values obtained were 2.70 mm (± 0.22 mm) for D1, 7.32 mm (± 0.40 mm) for D2, 7.10 mm (± 0.45 mm) for D3 and 17.12 mm (± 0.41 mm) for D4. Statistical analyses using the Student's t-test showed that there were no differences between the eyes. The study was feasible without the need of pharmacological restraint and yielded normal mean values for ocular sonographic biometry in rabbits. © 2010 American College of Veterinary Ophthalmologists.

  13. Regulatory T cells are decreased in acute RHDV lethal infection of adult rabbits.

    PubMed

    Teixeira, Luzia; Marques, Raquel M; Aguas, Artur P; Ferreira, Paula G

    2012-08-15

    Rabbit hemorrhagic disease virus (RHDV) is the etiologic agent of rabbit hemorrhagic disease (RHD), an acute lethal infection that kills 90% of adult rabbits due to severe acute liver inflammation. Interestingly, young rabbits are naturally resistant to RHDV infection. Here, we have compared naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) between young and adult rabbits after infection by RHDV. The number and frequency of Tregs was decreased in the spleen of adult rabbits 24h after the RHDV infection; this was in contrast with the unchanged number and frequency of splenic Tregs found in young rabbits after the same infection. Also, serum levels of IL-10 and TGF-β were enhanced in the infected adult rabbits whereas no alteration was observed in infected young rabbits. However, this increase is accompanied by a burst of pro-inflammatory cytokines, but seems not able to prevent the death of the animals with severe acute liver inflammation in few days after infection. Since Tregs downregulate inflammation, we conclude that their decrease may contribute to the natural susceptibility of adult rabbits to RHDV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Clinical value of blood glucose measurement in pet rabbits.

    PubMed

    Harcourt-Brown, F M; Harcourt-Brown, S F

    2012-06-30

    Blood glucose was measured with a portable glucose meter in 907 rabbits, including 238 clinically healthy ones. Blood glucose concentrations ranged from 1.2 to 30.1 mmol/l. Diabetes mellitus was not encountered. No significant effect of sex or sedation was found. Hypoglycaemia was seen in 16 rabbits including one with an insulinoma. There was a significant relationship between blood glucose, food intake, signs of stress and severity of clinical disease. Rabbits showing signs of stress had higher blood glucose than rabbits with no signs and rabbits that were totally anorexic had higher blood glucose values than those that were eating normally or those with reduced food intake. Severe hyperglycaemia (>20 mmol/l) was associated with conditions with a poor prognosis. Rabbits with confirmed intestinal obstruction had a mean blood glucose of 24.7 mmol/l (n=18). This was significantly higher than the rabbits with confirmed gut stasis, which had a mean value of 8.5 mmol/l (n=51). The conclusion of the study was that blood glucose is a measurable parameter that can be used to assess the severity of a rabbit's condition and help to differentiate between gut stasis and intestinal obstruction in rabbits that are anorexic.

  15. Liver Transplant

    MedlinePlus

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about ... resource. www.paulcox.com.au Why is the liver important? The liver is the second largest organ ...

  16. Microenvironment of liver regeneration in liver cancer.

    PubMed

    Li, Han-Min; Ye, Zhi-Hua

    2017-07-01

    The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of "tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment" can regulate "the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration"; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.

  17. Characterization of cell-cycle progression and growth of WB-F344 normal rat liver epithelial cells following gamma-ray exposure.

    PubMed

    Gerashchenko, Bogdan I; Azzam, Edouard I; Howell, Roger W

    2004-10-01

    Apparently normal rat liver epithelial cells (WB-F344) have been widely used in studies pertaining to carcinogenesis. Ionizing radiation, a well known carcinogen, is known to perturb cell-cycle progression in a dose-dependent manner, thereby causing delay in cell proliferation. However, for WB-F344 cells, there is a paucity of such data, which are of substantial importance in understanding their radiation response. Here, the distribution of phases in the cell-cycle and the proliferation ability of WB-F344 cells are characterized at various time points after the cells have been irradiated with different doses of gamma-rays. After WB-F344 cells reached 100% confluence, they were trypsinized and suspended at 3.5 x 10(5) cells/ml in culture medium. Cells were irradiated in suspension with (137)Cs gamma-rays at doses from 1-10 Gy. After irradiation, 1 x 10(5) cells were plated into 60 x 15-mm culture dishes and incubated at 37 degrees C, with 2% CO(2) and 98% air. At 12, 24, 36, 48, and 60 h postirradiation, cells were harvested, counted, and subjected to flow cytometric cell-cycle analysis. Growth curves of WB-F344 cells irradiated with gamma-rays started to separate at 36 h postirradiation. By 60 h postirradiation, the growth curves for each of the 10 absorbed doses were distinctly separated. Drastic redistributions of control and irradiated cells within G(0)/G(1)-, S-, and G(2)/M-phases of the cell cycle were observed during the first 36 h of cell growth. At each time point postirradiation, cell-cycle phase profiles of irradiated cells were altered in a dose-dependent manner. In general, there was a strong correlation between the percentage of G(2)/M-phase cells and absorbed dose, with the exception of 24 h postirradiation. The percentage of G(2)/M-phase cells increased as a function of time postirradiation, suggestive of delays in the passage of cells through the G(2) cell-cycle checkpoint. This work provides a general description of cell cycle redistribution and

  18. Metabolism of hydroanthracenones in rabbits

    PubMed Central

    Robertson, J. S.; Dunstan, P. J.

    1972-01-01

    1. The metabolism of 1-oxo-octahydro- and 2- and 9-oxoperhydro-anthracenes was investigated in rabbits. All compounds increased the urinary glucuronide content. 2. The 1-oxo and 2-oxo compounds were reduced to the corresponding alcohols whereas the 9-oxo compound was hydroxylated. 3. The reduction in vitro of these compounds and related ketones was investigated with three different enzyme systems (liver alcohol dehydrogenase, hydroxy steroid dehydrogenase, aromatic aldehyde–ketone reductase) in an attempt to explain the results in vivo. 4. Successful reduction of many ketones with aromatic aldehyde–ketone reductase suggests that the kidney may be of importance in the reduction in vivo of certain cyclic carbonyl compounds. PMID:5073736

  19. Poly(lactide-co-glycolide) Microspheres for MRI-Monitored Delivery of Sorafenib in a Rabbit VX2 model

    PubMed Central

    Chen, Jeane; White, Sarah B.; Harris, Kathleen R.; Li, Weiguo; Yap, Jonathan WT; Kim, Dong-Hyun; Lewandowski, Robert J.; Shea, Lonnie D.; Larson, Andrew C.

    2015-01-01

    Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 hours. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors. PMID:26022791

  20. Determination of hepatic galactose elimination capacity using 2-[18F]fluoro-2-deoxy-D-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

    PubMed Central

    SØRENSEN, MICHAEL

    2011-01-01

    Objective A PET method is developed for non-invasive measurement of regional metabolic liver function using the galactose analog 2-[18F]fluoro-2-deoxy-D-galactose, FDGal. The aim of the present study was to determine the reproducibility of the method in pigs before translating it to human studies. Material and methods Five anesthetized pigs were studied twice within an interval of three days. A dynamic PET recording was performed with an injection of 100 MBq FDGal. Non-radioactive galactose was administered throughout the PET recordings to achieve near-saturated elimination kinetics. Arterial blood samples were collected for determination of blood concentrations of FDGal and galactose (cgal). Net metabolic clearance of FDGal, KFDGal, was calculated from linear representation of data. The approximate maximal hepatic removal rate, Vmax, of galactose (mmol/l tissue/min) was calculated as KFDGal cgal. The estimates from Day 1 and Day 2 were compared and the coefficient of variation, COV, of the estimates calculated. Functional heterogeneity in normal pig liver was evaluated as COV of the tissue concentration of radioactivity during quasi steady-state metabolism. Results There was no significant difference between Vmax from Day 1 and Day 2 (p = 0.38), and the reproducibility was good with a COV of 14% for the whole liver. In normal pig liver tissue, mean COV after an injection of FDGal was on average 15.6% with no day-to-day variation (p = 0.7). Conclusions The novel FDGal PET method for determination of hepatic metabolic function has a good reproducibility and is promising for future human studies of regional liver function. PMID:20695723

  1. Liver intravoxel incoherent motion (IVIM) magnetic resonance imaging: a comprehensive review of published data on normal values and applications for fibrosis and tumor evaluation

    PubMed Central

    Li, Yáo T.; Cercueil, Jean-Pierre; Yuan, Jing; Chen, Weitian; Loffroy, Romaric

    2017-01-01

    A comprehensive literature review was performed on liver intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) technique and its applications. Heterogeneous data have been reported. IVIM parameters are magnetic field strength dependent to a mild extent. A lower Dslow (D) value at 3 T than at 1.5 T and higher perfusion fraction (PF) value at 3 T than at 1.5 T were noted. An increased number of b values are associated with increased IVIM parameter measurement accuracy. With the current status of art, IVIM technique is not yet capable of detecting early stage liver fibrosis and diagnosing liver fibrosis grades, nor can it differentiate liver tumors. Though IVIM parameters show promise for tumor treatment monitoring, till now how PF and Dfast (D*) add diagnostic value to Dslow or apparent diffusion coefficient (ADC) remains unclear. This paper shows the state-of-art IVIM MR technique is still not able to offer reliable measurement for liver. More works on the measurement robustness are warranted as they are essential to justify follow-up clinical studies on patients. PMID:28275560

  2. PSITTACOSIS : III. EXPERIMENTALLY INDUCED INFECTIONS IN RABBITS AND GUINEA PIGS.

    PubMed

    Rivers, T M; Berry, G P

    1931-06-30

    1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely. 2. Serial passages of the virus through rabbits and guinea pigs do not cause the active agent to lose its pathogenicity for parrots and mice. 3. The chief clinical evidences of infection in rabbits and guinea pigs following intracranial inoculation of the virus are fever and loss of weight. The pathological changes are characterized by a mild meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively immune. 5. Two strains of virus, human and parrot, were found to be immunologically similar. 6. No evidence was obtained to show that human convalescent serum possesses an appreciable amount of neutralizing substances.

  3. Reevaluation of lipolytic activity of growth hormone in rabbit adipocytes.

    PubMed

    Barenton, B; Batifol, V; Combarnous, Y; Dulor, J P; Durand, P; Vezinhet, A

    1984-07-18

    The lipolytic activities of porcine pituitary fractions and purified growth hormone (GH) from human (h), porcine (p), ovine (o) and rabbit (Rb) origin as well as ovine placental lactogen (oPL), were compared to that of ACTH on rabbit adipocytes. All the GH preparations and oPL were equivalent in inhibiting the binding of labelled oGH to liver plasma membranes from pregnant rabbits. ACTH, and to a lesser extent porcine pituitary fractions and hGH, stimulated free fatty acid production by isolated adipocytes. The sensitivity of the adipocytes to these factors was increased when adenosine deaminase was added to the incubation medium. But, RbGH, pGH, oGH and oPL had no effect. We conclude that GH is not directly involved in the control of lipolysis in rabbit adipocytes and that the effect of hGH is rather due to a contamination of this preparation by other pituitary factors.

  4. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands.

    PubMed

    Burt, Sara A; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H M

    2016-09-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates. Dutch rabbits are unlikely to be a zoonotic source.

  5. Rabbit orthopedic surgery.

    PubMed

    Rich, Gregory A

    2002-01-01

    Orthopedic surgery in rabbits poses several unique parameters for the veterinary surgeon. It is imperative for the veterinarian to be knowledgeable about the anatomic features of the surgical repair site and to become familiar with a rabbit's pain and discomfort often associated with orthopedic injuries. Handling the perioperative and postoperative pain and potential GI disturbances are crucial for a successful outcome of the surgical case. This article is designed to help the veterinary surgeon prepare for the orthopedic surgical procedure and the peripheral physiologic needs of the rabbit from presentation through recovery.

  6. 18F-FDG PET/CT qualitative and quantitative evaluation in neurofibromatosis type 1 patients for detection of malignant transformation: comparison of early to delayed imaging with and without liver activity normalization.

    PubMed

    Chirindel, Alin; Chaudhry, Muhammad; Blakeley, Jaishri O; Wahl, Richard

    2015-03-01

    (18)F-FDG PET/CT has shown increased accuracy, compared with morphologic imaging, in differentiating malignant peripheral nerve sheath tumors (MPNSTs) from benign neurofibromas (BNFs) in patients with neurofibromatosis type 1 (NF1). Delayed (18)F-FDG PET imaging typically enhances malignant tumor to background. Our goal was to compare the effectiveness of early (1-h) and delayed (4-h) (18)F-FDG PET/CT imaging in differentiating MPNSTs from BNFs in patients with NF1, with and without liver activity normalization. NF1 patients presenting new symptoms or enlarging lesions were clinically evaluated with early and delayed (18)F-FDG PET/CT imaging. SULmax (maximum standardized uptake value derived for lean body) and SULmax/liver (lesion uptake adjusted to mean liver activity) were obtained for all sites identified with abnormal metabolic activity. Qualitative and quantitative evaluations, including receiver-operating-characteristic (ROC) comparison of early and delayed imaging sessions, were performed. Histopathology and clinical follow-up (1-9 y) were considered as a gold standard. Forty-one NF1 patients with early and delayed (18)F-FDG PET/CT scans were identified, and 93 lesions were retrospectively analyzed, representing 24 MPNSTs (all histologically confirmed) and 69 BNFs (26 histologically confirmed). Qualitative evaluation on early imaging showed sensitivity, specificity, positive predictive value, and negative predictive value for separating MPNSTs from BNFs of 91%, 84%, 67%, and 96% versus 91%, 81%, 63%, and 96%, respectively, on 4-h delayed imaging. The mean SULmax was significantly higher for MPNSTs than BNFs on both early scans (6.5 vs. 2.0, P < 0.01) and delayed imaging (8.3 vs. 2.3, P < 0.02). However, SULmax overlap between benign and malignant lesions persisted even after normalization to mean liver activity. ROC-derived best SULmax cutoffs were 3.2 on early (area under the curve, 0.973) and 4.1 on delayed scans (area under the curve, 0.978). ROC analysis

  7. Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France.

    PubMed

    Izopet, Jacques; Dubois, Martine; Bertagnoli, Stéphane; Lhomme, Sébastien; Marchandeau, Stéphane; Boucher, Samuel; Kamar, Nassim; Abravanel, Florence; Guérin, Jean-Luc

    2012-08-01

    Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains' genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007-2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%-78.2% identical to HEV genotypes 1-4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.

  8. Use of allicin as feed additive to enhance vaccination capacity of Clostridium perfringens toxoid in rabbits.

    PubMed

    Abu El Hammed, Waleed; Soufy, Hamdy; El-Shemy, Ahmed; Nasr, Soad M; Dessouky, Mohamed I

    2016-04-12

    The present study assessed the efficacy of Clostridium perfringens (C. perfringens) toxoid and/or allicin - as feed additive - in rabbits for preventing or minimizing the severity of infection with locally isolated strain of C. perfringens type A. Serum biochemical, immunological and pathological investigations were also done. One hundred rabbits of 6 weeks of age were divided into five equal groups (G1-G5). G1 were kept as normal control. G2 was allocated for C. perfringens type A infection. G3 was vaccinated with C. perfringens toxoid at zero time and then with a booster dose at the 3rd week of the experimental period. G4 was treated with allicin 20% added to the ration (200mg/kg ration) all over the experimental period. G5 was vaccinated with C. perfringens toxoid at the zero time then with a booster dose at the 3rd week of the experiment period, and treated with allicin 20% from the zero time till the end of the experiment. At the 4th week, G2, G3, G4 and G5 were challenged orally (5 ml) and subcutaneously (2 ml) with 24h cooked meat broth containing 1 × 10(7) colony-forming units/ml of C. perfringens type A strain. Blood and tissue samples were collected from all groups po st-vaccination then post-challenge for biochemical analysis, serum neutralization test and histopathological examinations. Results revealed that rabbits treated with both allicin and toxoid vaccine demonstrated high level of antitoxin titre post-challenge, improved liver and kidney functions, and reduced morbidity and mortality rates and the severity of histopathological changes associated with challenge of rabbits with C. perfringens type A strain. In conclusion, vaccination of rabbits with C. perfringens toxoid combined with allicin 20% gave better protection, enhanced immune response and had no adverse effects on the general health conditions against C. perfringens type A infection compared to rabbits vaccinated with C. perfringens toxoid only.

  9. [Hemoperfusion alleviated paraquat-induced kidney inflammation injury of rabbit].

    PubMed

    Zhi, Shaoce; Wu, Dong; Li, Lingwen; Hong, Guangliang; Li, Mengfang; Wu, Bin; Lu, Zhongqiu

    2015-09-01

    To investigate the effect of hemoperfusion on paraquat-Induced kidney inflammation injury of rabbit and the mechanism of it. 60 male rabbits were randomly divided into 4 groups, the normal control group (n=6, the rabbits were given NS by gavage) , blank control group (n=18, he rabbits were given 2 hours hemoperfusion once within 1 hour after given NS by gavage), paraquat poisoning group (n=18, the rabbits were given 50 mg/kg 20% paraquat solution by gavage) , hemoperfusion treatment group (n=18, the rabbits were given 2 hours hemoperfusion once within 1 hour after 20% paraquat solution espoused). The last 3 groups were divided into 3 observation time groups (1, 3, 7 day), contained 6 rabbits each group. On days 1, 3, 7 all groups rabbits were anesthetized and sacrificed, and their kidney tissues collected. The levels of NF-κB mRNA by RT-PCR, and the expression of NF-κB protein was measured by Western blotting,The expression levels of TNF-α, IL-6, iNOS measured by chemical colorimetric method to to observe inflammatory injury. Compared with the normal control group rabbits, there were no changes in the TNF-α, IL-6, iNOS, NF-κB mRNA and protein of blank control group (P>0.05), while the expression of TNF-α, IL-6, NF-κB mRNA and protein in the kidney tissue of PQ group and were significantly increased (P<0.05). The pathological results of kidney tissues were no abnormalities onnormal control group and blank control group. HP significantly increase resistance to PQ-induced inflammation injury in the rabbit kidney and exert a protective effect on PQ-induced kidney injury.

  10. RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are infectious in rabbits.

    PubMed

    Cossaboom, Caitlin M; Huang, Yao-Wei; Yugo, Danielle M; Kenney, Scott P; Piñeyro, Pablo; Matzinger, Shannon R; Heffron, C Lynn; Pierson, F William; Meng, Xiang-Jin

    2014-11-07

    Hepatitis E virus (HEV), the causative agent of hepatitis E, is a single-stranded positive-sense RNA virus belonging to the family Hepeviridae. At least four genotypes of the family infect humans: genotypes 1 and 2 are transmitted to humans through contaminated water, while genotypes 3 and 4 are zoonotic and have animal reservoirs. A novel strain of HEV recently identified in rabbits is a distant member of genotype 3, and thus poses a potential risk of zoonotic transmission to humans. The objective of this study was to construct and characterize an infectious cDNA clone of the rabbit HEV. Two full-length cDNA clones of rabbit HEV, pT7g-rabHEV and pT7-rabHEV, were constructed and their infectivity was tested by in vitro transfection of Huh7 human liver cells and by direct intrahepatic inoculation of rabbits with capped RNA transcripts. Results showed that positive signal for rabbit HEV protein was detected by an immunofluorescence assay with a HEV-specific antibody in Huh7 human liver cells transfected with capped RNA transcripts from the two full-length cDNA clones. Rabbits intrahepatically inoculated with capped RNA transcripts from each of the two clones developed active HEV infection as evidenced by seroconversion to anti-HEV antibodies, and detection of rabbit HEV RNA in sera and feces of inoculated animals. The availability of a rabbit HEV infectious cDNA clone now affords us the ability to delineate the mechanism of HEV replication and cross-species infection in a small animal model.

  11. Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

    PubMed

    Keswani, Sundeep G; Balaji, Swathi; Katz, Anna B; King, Alice; Omar, Khaled; Habli, Mounira; Klanke, Charles; Crombleholme, Timothy M

    2015-03-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight. Laparotomy was performed on New Zealand White rabbits on day 21 of 30 days of gestation and litters were divided into five groups: Control (first position)+phosphate-buffered saline (PBS), control+Ad-IGF-1, runt (third position)+PBS, runt+Ad-IGF-1, and runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal-fetal placenta interface (n=12) 48 hr after gene therapy. There was minimal gene transfer detected in the pups or maternal organs. At term, compared with the normally grown first-position control, the runted third-position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intraplacental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intraplacental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of nonviral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of

  12. The Coadministration of Unoxidized and Oxidized Desi Ghee Ameliorates the Toxic Effects of Thermally Oxidized Ghee in Rabbits

    PubMed Central

    Uddin, Islam

    2017-01-01

    Desi Ghee was thermally oxidized at 160°C for 9 h and characterized for peroxide value (PV), free fatty acid (FFA), thiobarbituric acid reactive substances (TBARS), radical scavenging activity (RSA), and fatty acid and cholesterol composition using GC-MS. Oxidized (OG) and normal ghee (NG) were fed to rabbits in different doses. Blood was collected for hematology and biochemical analyses after 7 and 14 days. The oxidation of desi ghee increased the PV, FFA, and TBARS values and showed a decline in the RSA values. GC-MS revealed that desi ghee was rich in saturated fatty acids (55.9 g/100 g) and significant amounts of oleic acid (26.2 g/100 g). The OG significantly decreased the body weight, which was normalized by the coadministration of NG. Serum lipid profile showed a dose dependent increase in total cholesterol, triglycerides, and low density lipoproteins (LDL) and decrease in RBCs count, hematocrit, glucose, and hemoglobin concentration with OG feeding. These parameters were normalized by coadministration of NG. Liver histopathology of OG fed groups showed bile duct dilation and necrotic changes, while normal architecture showed in NG groups, compared to control. These results indicate that NG has no significant effect on rabbits comparing with OG and that it was beneficial when coadministered with oxidized ghee. PMID:28299204

  13. Oil well rabbit

    SciTech Connect

    Yerian, H.W.

    1983-10-18

    A well rabbit is described which has a high gas seal capacity as well as resistance to wear and structural failure. The rabbit comprises a one-piece elongated generally cylindrical body having external circumferential gas-sealing grooves spaced along its length and a set of helically oriented slots at its lower end. The circumferential grooves, which work collectively in the manner of a labyrinth seal, are undercut in a way to deflect escaping gas streams and promote turbulence to enhance their gas-sealing capability. The undercut profile and relative spacing of the grooves leaves a large surface area between the grooves for distributing radial forces and thereby decreasing the wear rate of the rabbit. The helically oriented slots convert energy of upward escaping gas into rotational energy in the rabbit. (3 claims.

  14. SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.

    PubMed

    Zhang, Yanfei; Guo, Wei; Wen, Yadan; Xiong, Qinghui; Liu, Hongrui; Wu, Jian; Zou, Yunzeng; Zhu, Yizhun

    2012-09-01

    To investigate SCM-198 (also known as "leonurine"), a compound in Herba leonuri, as well as its effect on the progression of atherosclerosis in hypercholesterolemic rabbits and underlying mechanisms. Thirty New Zealand male White rabbits (5 groups, n = 6) were fed either a normal diet or a high-cholesterol diet (1%). The rabbits on the high-cholesterol diet received treatments of low, moderate, and high doses of SCM-198 and placebo concurrently. Eight weeks later, the animals underwent ultrasonographic imaging. They were then sacrificed for further pathological and molecular biological analysis. SCM-198-treated rabbits showed a significant alleviation in the development of atherosclerosis in a dose-dependent manner. The lesions were smaller after the SCM-198 treatments. In addition, the elasticity of the arteries and hemodynamic status improved, accompanied with a decrease in smooth muscle cell migration and, macrophage infiltration, as well as the expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the aortas. Marginal changes in the lipid parameters were found in the SCM-198-treated rabbits, with high-density lipid cholesterol (HDL-C) elevation and triglyceride (TG) reduction at the high dose. SCM-198 treatment dose-dependently reduced levels of serum soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the mRNA levels of VCAM-1, IL-6, TNF-α, monocyte chemoattractant protein-1 (MCP-1), iNOS and MMP-9 in the aorta. In addition, SCM-198 also dose-dependently increased the total antioxidant capacities and in parallel decreased the lipid peroxidation levels in the serum and liver. The antioxidant effects of SCM-198 were implicated by the enhanced activities of catalase (CAT), superoxi