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Sample records for normal rabbit liver

  1. Liver lobe torsion in three adult rabbits.

    PubMed

    Wenger, S; Barrett, E L; Pearson, G R; Sayers, I; Blakey, C; Redrobe, S

    2009-06-01

    This paper describes three cases of liver lobe torsion in rabbits presenting with anorexia, lethargy, jaundice and abdominal pain. This condition was associated with anaemia and elevation of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase. Abnormal radiological findings included hepatomegaly, gas-filled intestinal loops consistent with gastrointestinal ileus and ascites. Ultrasonographic findings included heterogeneous liver parenchyma, free abdominal fluid and reduced bowel motility. Diagnosis was confirmed by histopathological examination of the liver in all three cases. PMID:19527423

  2. Chromate reduction by rabbit liver aldehyde oxidase

    SciTech Connect

    Banks, R.B.; Cooke, R.T. Jr.

    1986-05-29

    Chromate was reduced during the oxidation of 1-methylnicotinamide chlorine by partially purified rabbit liver aldehyde oxidase. In addition to l-methylnicotinamide, several other electron donor substrates for aldehyde oxidase were able to support the enzymatic chromate reduction. The reduction required the presence of both enzyme and the electron donor substrate. The rate of the chromate reduction was retarded by inhibitors or aldehyde oxidase but was not affected by substrates or inhibitors of xanthine oxidase. These results are consistent with the involvement of aldehyde oxidase in the reduction of chromate by rabbit liver cytosolic enzyme preparations.

  3. Carbon tetrachloride-induced liver injury in the rabbit.

    PubMed Central

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J. A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed. Images Fig. 1 Fig. 2 PMID:6309207

  4. Focal lesions in normal liver.

    PubMed

    Semelka, Richard C; Martin, Diego R; Balci, N Cem

    2005-10-01

    A variety of lesions occur in the normal liver. This review will describe the most common benign, malignant, and infectious lesions. Illustration will be made of the magnetic resonance imaging (MRI) appearance of the most common of these. Due to the high accuracy for liver lesion detection and characterization, and the intrinsic safety of the modality, MR should be considered the primary imaging tool to investigate liver diseases. PMID:16174062

  5. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    PubMed Central

    Ibarra, R.; Dazard, J-E.; Sandlers, Y.; Rehman, F.; Abbas, R.; Kombu, R.; Zhang, G-F.; Brunengraber, H.; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT−) to samples from (LG+/LG−) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT−) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined. PMID:24723740

  6. Photodynamic therapy on normal rabbit mandible

    NASA Astrophysics Data System (ADS)

    Fan, Kathleen F.; Hopper, Colin; Speight, Paul M.; Davies, Claire; Bown, Stephen G.

    1995-03-01

    Photodynamic therapy has been proposed as an intra-operative adjunct to surgical resection of tumors invading bone. To assess this, we studied the effects of PDT in normal bone. Forty- four rabbits were sensitized with Photofrin 3 mg/kg, 5-aminolaevulinic acid (ALA) 400 mg/kg, or meso-tetrahydroxyphenylchlorin (mTHPC) 0.3 mg/kg. A mandibular incisor was removed and the socket irradiated with a cylindrical diffusion fiber (630 nm Photofrin and ALA, 650 nm mTHPC, 100 J per treatment). Irradiation was given 1 or 48 hours after Photofrin, 72 hours after mTHPC, whilst 2 doses were given 2.5 and 4 hours after the first fractionated dose of ALA. The socket of the ipsilateral maxillary incisor was used as a nonirradiated control to assess healing without PDT. Other controls assessed healing after irradiation of unsensitized animals. Rabbits were killed 3, 10, and 21 days after treatment. Tooth socket healing appeared to be the same in all groups of animals with evidence of woven bone formation by 10 days. We conclude that PDT is unlikely to have any effect on healing in normal bone, which makes it suitable for treating tumors invading bone.

  7. Electrochemotherapy on liver tumours in rabbits.

    PubMed Central

    Ramirez, L. H.; Orlowski, S.; An, D.; Bindoula, G.; Dzodic, R.; Ardouin, P.; Bognel, C.; Belehradek, J.; Munck, J. N.; Mir, L. M.

    1998-01-01

    Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies. Images Figure 1 Figure 2 PMID:9649121

  8. The role of liver and spleen in the metabolism of intravenously injected fat in rabbits.

    PubMed

    VAN DEN BOSCH, J; EVRARD, E; BILLIAU, A; JOOSSENS, J V; DE SOMER, P

    1961-12-01

    The uptake of intravenously injected coconut oil emulsion by the liver and spleen was investigated by gas-liquid chromatography in normal, triton-injected, and hypercholesterolemic rabbits. The lauric and myristic acids from this emulsion, almost absent in the tissues of normal animals, were used as marked acids. In normal rabbits only the liver took up a quantitatively important fraction of the injected fat. The uptake by the spleen appears to be due to a different mechanism than that of the liver. In rabbits given triton the liver was incapable of taking up large quantities of fat, while the uptake in the spleen was undisturbed. 12 hours after injection the plasma, liver, and spleen of normal animals contained only 14 per cent of the dose. With animals given triton 71 per cent of the injected dose was recovered, most of it in the plasma. Hypercholesterolemic rabbits cleared an injected fat emulsion and took fat into the liver at the same rate as the controls. When triton is injected 6 hours after the administration of the emulsion, the fat taken up in the liver reappears in the plasma. PMID:13924523

  9. Comparison of sympathetic nerve activity normalization procedures in conscious rabbits.

    PubMed

    Burke, Sandra L; Lim, Kyungjoon; Moretti, John-Luis; Head, Geoffrey A

    2016-05-01

    One of the main constraints associated with recording sympathetic nerve activity (SNA) in both humans and experimental animals is that microvolt values reflect characteristics of the recording conditions and limit comparisons between different experimental groups. The nasopharyngeal response has been validated for normalizing renal SNA (RSNA) in conscious rabbits, and in humans muscle SNA is normalized to the maximum burst in the resting period. We compared these two methods of normalization to determine whether either could detect elevated RSNA in hypertensive rabbits compared with normotensive controls. We also tested whether either method eliminated differences based only on different recording conditions by separating RSNA of control (sham) rabbits into two groups with low or high microvolts. Hypertension was induced by 5 wk of renal clipping (2K1C), 3 wk of high-fat diet (HFD), or 3 mo infusion of a low dose of angiotensin (ANG II). Normalization to the nasopharyngeal response revealed RSNA that was 88, 51, and 34% greater in 2K1C, HFD, and ANG II rabbits, respectively, than shams (P < 0.05), but normalization to the maximum burst showed no differences. The RSNA baroreflex followed a similar pattern whether RSNA was expressed in microvolts or normalized. Both methods abolished the difference between low and high microvolt RSNA. These results suggest that maximum burst amplitude is a useful technique for minimizing differences between recording conditions but is unable to detect real differences between groups. We conclude that the nasopharyngeal reflex is the superior method for normalizing sympathetic recordings in conscious rabbits. PMID:26921439

  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. Bile Acid Synthesis in the Isolated, Perfused Rabbit Liver

    PubMed Central

    Mosbach, E. H.; Rothschild, M. A.; Bekersky, I.; Oratz, M.; Mongelli, J.

    1971-01-01

    These experiments were carried out to demonstrate the usefulness of the perfused rabbit liver for studies of bile acid metabolism, and to determine the rate-limiting enzyme of bile acid synthesis. Rabbits were fed a semisynthetic diet, with or without the addition of 1% cholestyramine, under controlled conditions. At the end of 2-5 wk, the livers were removed and perfused for 2.5 hr employing various 14C-labeled precursors to measure de novo cholic acid synthesis. The livers were then analyzed for cholesterol, and the bile collected during the perfusion was analyzed for cholesterol and bile acids. Control bile contained, on the average, 0.34 mg of glycocholate, 7.4 mg of glycodeoxycholate, and 0.06 mg of cholesterol. After cholestyramine treatment of the donor rabbits, the bile contained 3.3 mg of glycocholate, 3.7 mg of glycodeoxycholate, and 0.05 mg of cholesterol. It was assumed that in cholestyramine-treated animals the enterohepatic circulation of the bile acids had been interrupted sufficiently to release the feedback inhibition of the rate-controlling enzyme of bile acid synthesis. Therefore, a given precursor should be incorporated into bile acids at a more rapid rate in livers of cholestyramine-treated animals, provided that the precursor was acted upon by the rate-controlling enzyme. It was found that the incorporation of acetate-14C, mevalonolactone-14C, and cholesterol-14C into cholate was 5-20 times greater in the livers of cholestyramine-treated animals than in the controls. In contrast, there was no difference in the incorporation of 7α-hydroxycholesterol-14C into cholate regardless of dietary pretreatment. It was concluded that given an adequate precursor pool, the 7α-hydroxylation of cholesterol is the rate-limiting step in bile acid formation. PMID:5097576

  12. Effect of fruits of Moringa oleifera on the lipid profile of normal and hypercholesterolaemic rabbits.

    PubMed

    Mehta, Komal; Balaraman, R; Amin, A H; Bafna, P A; Gulati, O D

    2003-06-01

    Rabbits were fed Moringa oleifera (200mg/kg/day, p.o.) or lovastatin (6mg/kg/day, p.o.) in banana pulp along with standard laboratory diet and hypercholesterolaemic diet for 120 days. Moringa oleifera and lovastatin were found to lower the serum cholesterol, phospholipid, triglyceride, VLDL, LDL, cholesterol to phospholipid ratio and atherogenic index, but were found to increase the HDL ratio (HDL/HDL-total cholesterol) as compared to the corresponding control groups. Treatment with M. oleifera or lovastatin in normal rabbits decreased the HDL levels. However, HDL levels were significantly increased or decreased in M. oleifera- or lovastatin-treated hypercholesterolaemic rabbits, respectively. Lovastatin- or M. oleifera-treated hypercholesterolaemic rabbits showed decrease in lipid profile of liver, heart and aorta while similar treatment of normal animals did not produce significant reduction in heart. Moringa oleifera was found to increase the excretion of faecal cholesterol. Thus, the study demonstrates that M. oleifera possesses a hypolipidaemic effect. PMID:12738086

  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. Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution.

    PubMed

    Weeks, C M; Roszak, A W; Erman, M; Kaiser, R; Jörnvall, H; Ghosh, D

    1999-01-01

    The three-dimensional structure of the R form of rabbit liver fructose 1,6-bisphosphatase (Fru-1,6-Pase; E.C. 3.1.3.11) has been determined by a combination of heavy-atom and molecular-replacement methods. A model, which includes 2394 protein atoms and 86 water molecules, has been refined at 2.3 A resolution to a crystallographic R factor of 0.177. The root-mean-square deviations of bond distances and angles from standard geometry are 0.012 A and 1.7 degrees, respectively. This structural result, in conjunction with recently redetermined amino-acid sequence data, unequivocally establishes that the rabbit liver enzyme is not an aberrant bisphosphatase as once believed, but is indeed homologous to other Fru-1,6-Pases. The root-mean-square deviation of the Calpha atoms in the rabbit liver structure from the homologous atoms in the pig kidney structure complexed with the product, fructose 6-phosphate, is 0.7 A. Fru-1,6-Pases are homotetramers, and the rabbit liver protein crystallizes in space group I222 with one monomer in the asymmetric unit. The structure contains a single endogenous Mg2+ ion coordinated by Glu97, Asp118, Asp121 and Glu280 at the site designated metal site 1 in pig kidney Fru-1,6-Pase R-form complexes. In addition, two sulfate ions, which are found at the positions normally occupied by the 6-phosphate group of the substrate, as well as the phosphate of the allosteric inhibitor AMP appear to provide stability. Met177, which has hydrophobic contacts with the adenine moiety of AMP in pig kidney T-form complexes, is replaced by glycine. Binding of a non-hydrolyzable substrate analog, beta-methyl-fructose 1,6-bisphosphate, at the catalytic site is also examined. PMID:10089399

  15. Effect of Pressure on Liver Stiffness During the Development of Liver Fibrosis in Rabbits.

    PubMed

    Tang, Wen Bo; Xu, Qing Hua; Jiao, Zi Yu; Wu, Rong; Song, Qing; Luo, Yu Kun

    2016-01-01

    This study was designed to investigate whether hepatic arterial pressure and portal pressure have an effect on liver stiffness during the development of liver fibrosis. Liver fibrosis was induced in 50 healthy New Zealand white rabbits. Laparotomy was performed to measure liver stiffness, and the portal vein and hepatic artery were successively ligated to repeat the measurements. A significant difference was observed among liver stiffness values measured at different time points (F = 22.82, p < 0.001). Differences between original liver stiffness and liver stiffness measured after portal ligation were positively correlated with portal pressure (r = 0.801, p < 0.001). In animals with grade 4 liver fibrosis, the increase in liver stiffness caused by pressure was greater than that caused by extracellular matrix accumulation (p = 0.002). In conclusion, hepatic arterial pressure and portal pressure have a significant effect on liver stiffness during the development of liver fibrosis. PMID:26497767

  16. 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.

  17. Defining Normal Liver Stiffness Range in a Normal Healthy Chinese Population without Liver Disease

    PubMed Central

    Fung, James; Lee, Cheuk-kwong; Chan, Monica; Seto, Wai-kay; Wong, Danny Ka-ho; Lai, Ching-lung; Yuen, Man-fung

    2013-01-01

    Background For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. Aims To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. Methods This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. Results Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89). The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p<0.001). There was also a decline in median Lliver stiffness in the older age group, from 4.2 kPa in those <25 years to 3.4 kPa for those >55 years (p=0.001). Conclusions The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness. PMID:24386446

  18. Glycosylation of ribonuclease A catalysed by rabbit liver extracts.

    PubMed Central

    Khalkhall, Z; Marshall, R D

    1975-01-01

    Crude extracts of rabbit liver catalyse in vitro the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to bovine pancreatic ribonuclease A. The enzymic activity is contained in rough endoplasmic reticulum. It has an absolute requirement for a bivalent metal ion: Co-2+ greater than Mn-2+ greater than Ni-2+. Mg-2+ is ineffective. There is enzymic activity in the absence of detergent, but increased activity is observed in the presence of Triton X-100. The site of glycosylation of ribonuclease A is asparagine-34, and glycosylation occurs only at this point. These findings agree with the hypothesis that the sequence Asn-X-Thr(Ser) (where X may be one of a number of types of amino acid) is a necessary, but not sufficient, condition for N-acetylglucosaminylation of a protein-bound asparagine residue. PMID:1156375

  19. 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.

  20. The normal microflora of the female rabbit's genital tract.

    PubMed Central

    Jacques, M; Olson, M E; Crichlow, A M; Osborne, A D; Costerton, J W

    1986-01-01

    Microorganisms associated with the vagina, cervix and uterus of rabbits were isolated and identified. The predominant microorganisms isolated from the vaginas and cervices were coagulase-negative staphylococci, micrococci, and nonfermentative bacilli. Coagulase-negative staphylococci were isolated frequently, but in small numbers, from the uteri. The pH of the rabbit vagina was found to be near neutrality. Our data indicate that the genital flora of female rabbits is relatively simple, regarding the number and type of microorganisms. PMID:3756680

  1. Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits.

    PubMed

    Jing, Jin; Liu, Chun; Zhu, Shun-Xing; Jiang, Ying-Mei; Wu, Liu-Cheng; Song, Hong-Yan; Shao, Yi-Xiang

    2016-06-15

    To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000±20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits. PMID:27198796

  2. 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.

  3. 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. PMID:17282574

  4. Kinetic studies on the regulation of rabbit liver pyruvate kinase

    PubMed Central

    Irving, M. G.; Williams, J. F.

    1973-01-01

    Two kinetically distinct forms of pyruvate kinase (EC 2.7.1.40) were isolated from rabbit liver by using differential ammonium sulphate fractionation. The L or liver form, which is allosterically activated by fructose 1,6-diphosphate, was partially purified by DEAE-cellulose chromatography to give a maximum specific activity of 20 units/mg. The L form was allosterically activated by K+ and optimum activity was recorded with 30mm-K+, 4mm-MgADP−, with a MgADP−/ADP2− ratio of 50:1, but inhibition occurred with K+ concentrations in excess of 60mm. No inhibition occurred with either ATP or GTP when excess of Mg2+ was added to counteract chelation by these ligands. Alanine (2.5mm) caused 50% inhibition at low concentrations of phosphoenolpyruvate (0.15mm). The homotropic effector, phosphoenolpyruvate, exhibited a complex allosteric pattern (nH=2.5), and negative co-operative interactions were observed in the presence of low concentrations of this substrate. The degree of this co-operative interaction was pH-dependent, with the Hill coefficient increasing from 1.1 to 3.2 as the pH was raised from 6.5 to 8.0. Fructose 1,6-diphosphate interfered with the activation by univalent ions, markedly decreased the apparent Km for phosphoenolpyruvate from 1.2mm to 0.2mm, and transformed the phosphoenolpyruvate saturation curve into a hyperbola. Concentrations of fructose 1,6-diphosphate in excess of 0.5mm inhibited this stimulated reaction. The M or muscle-type form of the enzyme was not activated by fructose 1,6-diphosphate and gave a maximum specific activity of 0.3 unit/mg. A Michaelis–Menten response was obtained when phosphoenolpyruvate was the variable substrate (Km=0.125mm), and this form was inhibited by ATP, as well as alanine, even in the presence of excess of Mg2+. PMID:4722439

  5. 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.

  6. Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet.

    PubMed

    Kanjilal, Sanjit; Kaki, Shiva Shanker; Rao, Bhamidipati V S K; Sugasini, Dhavamani; Rao, Yalagala Poornachandra; Prasad, Rachapudi B N; Lokesh, Belur R

    2013-01-01

    The hypocholesterolemic effects of two low calorie structured lipids (SL1 and SL2) containing essential fatty acids, prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits. The feeding experiment conducted on rats as well as rabbits, fed on normal and atherogenic diet containing 10% of SL1 and SL2 (experimental) and sunflower oil (control) indicated no adverse effects on growth and food intake. However, the structured lipids beneficially lowered serum and liver lipids, particularly cholesterol, LDL cholesterol, triglycerides and also maintains the essential fatty acid status in serum and liver. The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet. These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups. Therefore the structured lipids, designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets. PMID:23017421

  7. Tissue residues of some sulphonamides in normal and Eimeria stiedai infected rabbits.

    PubMed

    Atta, A H; el-Zeni; Samia, A

    1999-07-01

    Tissue residues of sulphadiazine (SDZ), sulphadimidine (SDD) and sulphquinoxaline (SQ) were studied in healthy and E. stiedai infected rabbits following oral administration of 0.5 g/l drinking water for 5 days. The solid-phase extraction and HPLC was used to determine the concentration of the three sulphonamides in a single tissue sample. SDZ was detected in the liver and kidney in concentrations below the tolerance levels at day 5 and no residues could be detected at day 7 after drug withdrawal. SDD and SQ were detected in all of the tested organs of healthy rabbits up to day 5, where the highest concentration was reported in the liver (0.08 +/- 0.02 and 0.09 +/- 0.02 g/g respectively). In infected rabbits, the three sulphonamides were detected up to day 7 in concentrations higher than the tolerance limits (> 0.1 g/g) in the liver and kidney and lower levels in other tissues. A withdrawal period of 4 days for SDZ and 5 days for SDD and SQ in healthy rabbits and 7 days for SDZ and 8 days for SDD and SQ in E. stiedai infected rabbits is suggested. PMID:10481374

  8. [Isoelectric spectra of liver tissue and blood serum albumin for rabbits of different age].

    PubMed

    Sopkina, D A; Ostolovskiĭ, E M; Ivlev, V N

    1978-01-01

    The isoelectric spectrum of albumin isolated from the liver and blood serum of 30-, 45- and 90-day rabbits was studied. By the method of isoelectric focusing in the boron-borate buffer--mannitol system. It is shown that the liver albumin displays heterogeneity ans is separated into four-five fractions, with pJ 4.8-6.0. Age peculiarities are found for the isoelectric spectrum of this protein. The serum albumin spectrum for rabbits of the studied age groups is characterized by the presence of a homogeneous peak with pJ 5.59, 5.57 and 5.47 corresponding to 30, 45 and 90-day age, respectively. Identity of serum albumin and protein of some liver albumin spectrum components is established by analyzing the pattern of the isoelectric spectrum for a mixture of preparations of 90-day rabbit proteins under comparison. PMID:34911

  9. No virus replication in domestic cats fed with RHDV-infected rabbit livers.

    PubMed

    Zheng, T; Lu, G; Napier, A M; Lockyer, S J

    2003-08-29

    Previous studies have shown that feral cats (Felis catus) from rabbit haemorrhagic disease (RHD) epidemic areas in New Zealand had antibodies against RHD Virus (RHDV) and RHDV RNA was identified by nested RT-PCR from one seropositive feral cat liver. To assess whether RHDV replicates and produces clinical consequences in cats following the consumption of RHDV-infected rabbit, a challenge trial was conducted by feeding cats RHDV-infected rabbit livers. Antibodies against RHDV were detected by immunoassay from sera of cats collected 10 days after the consumption of RHDV-infected livers. Animals fed four times with RHDV-infected livers, had higher antibody titres than animals fed only once. RHDV RNA was detected by nested RT-PCR from mesenteric lymph nodes, tonsil, spleen and liver of cats fed with RHDV-infected livers. RHDV anti-genomic RNA was also detected by nested RT-PCR from mesenteric lymph nodes collected from one animal 2 days after the fourth feed. RHDV was detected by antigen ELISA from cat faeces 1-2 days after the consumption of RHDV-infected livers. Even though a large amount of RHDV has been used, cats did not show any signs of disease. Although abortive RHDV replication could not be ruled out, active RHDV replication was not demonstrated. PMID:12860077

  10. 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

  11. 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.

  12. 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

  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. Relationship between liver disorders and protection against Eimeria stiedai infection in rabbits immunized with soluble antigens from the bile of infected rabbits.

    PubMed

    Hanada, S; Omata, Y; Umemoto, Y; Kobayashi, Y; Furuoka, H; Matsui, T; Maeda, R; Saito, A

    2003-02-13

    Soluble antigens exist in the bile of rabbits infected with Eimeria stiedai (E. stiedai) in the acute phase, and rabbits immunized with the antigens show resistance against the infection. In this study, the liver function of rabbits immunized either with the soluble antigens or PBS were examined following the parasite challenge. Rabbits immunized with PBS shed a number of oocysts and showed an increase in r-glutamyltransferase (GGT) activity and a decrease in blood Indocyanine green (ICG) clearance. However, rabbits immunized with the soluble antigens shed a lower number of oocysts and showed a transient increase of alanine-aminotransferase (ALT) activity on Day 8 post-challenge (p.c.). The blood Indocyanine green clearance of the rabbits showed no change throughout the experiment. By histopathological observation of the liver, a number of merozoites were found in the biliary ducts on Day 8 post-challenge in the non-immunized rabbits. In contrast, a number of lymphocytes and neutrophilic leukocytes assembled around the biliary ducts of the immunized rabbits, but few parasites were found there on Day 8 post-challenge. These results suggest that the soluble antigens stimulate local immune reactions, for example around the biliary ducts, resulting in elimination of the parasite's development. PMID:12531300

  15. 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.

  16. Assessment of QT-prolonging drugs in the isolated normal and failing rabbit hearts.

    PubMed

    Kijtawornrat, Anusak; Sawangkoon, Suwanakiet; Hamlin, Robert L

    2012-01-01

    Lengthening of QTc is the usual signal to indicate torsadogenic potential of a therapeutic agent. The ICH S7B guideline recommends that new chemical entities should be assessed for potential of delayed ventricular repolarization in animal models. The aim of this study was to determine a feasibility of using isolated failing heart rabbit to assess the QT-lengthening drugs in comparison with their effects on isolated normal heart rabbits. Heart failure was induced by ligation of the left anterior descending and descending branch of left circumflex coronary arteries. One month after ligation, all rabbits were anesthetized and the hearts were removed quickly, and they were perfused with the oxygenated Krebs-Henseleit solution to which escalating concentrations of QT-lengthening compounds were added. RR, QT, and QTc(F) were not significantly different, at rest, between failing and normal hearts. During baseline, dP/dtmax was lower and dP/dtmin was higher for failing hearts than for normals. In responses to all three QT-lengthening compounds, RR, QT and QTc(F) lengthened similarly in a dose-response manner in both the failing and normal hearts. Neither the failing nor the normal hearts developed fatal arrhythmias, torsades de pointes. Langendorff preparations of failing hearts are as good as normal isolated hearts and can be use to assess the potential of delayed ventricular repolarization of test articles. PMID:22687985

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

    PubMed

    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

  18. 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

  19. 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

  20. Action of streptokinase on parameters of hemostasis in rabbits with toxic liver damage due to carbon tetrachloride

    SciTech Connect

    Nikandrov, V.N.; Naumovich, S.A.; Votyakov, V.I.

    1987-07-01

    The authors study the specific nature of changes in the parameters of hemostasis in rabbits with experimental toxic liver damage. Streptokinase was injected intravenously. Toxic liver damage was induced by injections of carbon tetrachloride. The parameters studied included acceleration of lysis of the blood clot, increased fibrinolytic activity and thrombin time, lowered level of fibrinogen and antithrombin III.

  1. 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

  2. Immunohistochemical demonstration of fibronectin in the most superficial layer of normal rabbit articular cartilage.

    PubMed Central

    Nishida, K; Inoue, H; Murakami, T

    1995-01-01

    OBJECTIVE--To locate fibronectin ultrastructurally in the most superficial layer of normal articular cartilage of rabbits, in order to clarify its role in joint physiology. METHODS--Articular cartilage was obtained from the femoral condyle of seven normal adult rabbits and prepared by a method that included tannic acid fixation. Polyclonal antibodies against rabbit fibronectin were used in an immunohistochemical electron microscopic study, without any enzymic digestion but with a pre-embedding method for the transmission electron microscopy. RESULTS--The cartilage surface was successfully preserved by tannic acid fixation. The most superficial layer in electron photomicrographs was approximately 200-300 nm thick, cell free, and appeared to have two parallel components: the more superficial lamina and the deeper lamina. Gold labelled fibronectin lined this layer in immunohistochemical electron photomicrographs. CONCLUSIONS--Fibronectin covering the surface of the articular cartilage may have a role in joint lubrication and protection of the cartilage by binding with the collagenous matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a charge barrier in close relationship with the collagen fibrils in the deeper lamina. Significant alteration in these functions may be one of the first causal steps leading to destruction of the articular cartilage. Images PMID:8546534

  3. Catabolism of low density lipoproteins by perfused rabbit livers: cholestyramine promotes receptor-dependent hepatic catabolism of low density lipoproteins.

    PubMed

    Chao, Y S; Yamin, T T; Alberts, A W

    1982-07-01

    Rabbits fed a wheat starch/casein diet develop a marked hypercholesterolemia accompanied by a decrease in the number of EDTA-sensitive binding sites on plasma membrane fractions of the liver for low density lipoproteins (LDL) and beta-migrating very low density lipoproteins [Chao, Y.-S., Yamin, T.-T. & Alberts, A. W. (1982) J. Biol. Chem., in press]. Inclusion of 1% cholestyramine resin in this diet prevents the increase in plasma cholesterol, increases the removal of LDL from plasma, and increases the number of hepatic plasma membrane LDL-binding sites. To determine the functional role of hepatic LDL-binding sites in the catabolism of LDL, we studied the catabolism of (125)I-labeled LDL ((125)I-LDL) by in situ perfused rabbit livers in a recirculating system. The rate of catabolism was measured from the increment of nonprotein-bound radioiodine in the perfusate. The receptor-dependent catabolism of LDL by the liver was calculated from the difference of hepatic catabolism of (125)I-LDL and catabolism of (125)I-labeled cyclohexanedione-modified LDL, which does not bind to LDL receptors. The data show that about 74% of LDL catabolized by perfused livers from chow-fed rabbits is through the receptor-dependent pathway and 26% is through the receptor-independent pathway. In rabbits fed a cholesterol diet, the hepatic catabolism of (125)I-LDL is reduced, and the receptor-dependent catabolism of (125)I-LDL is abolished. In rabbits fed the wheat starch/casein diet, the receptor-dependent catabolism of (125)I-LDL is reduced by 40% when compared with hepatic catabolism in chow-fed rabbits. Perfused livers from rabbits fed the wheat starch/casein diet supplemented with 1% cholestyramine show a 5,4-fold increase of receptor-dependent catabolism of (125)I-LDL when compared with that of livers from rabbits fed the wheat starch/casein diet alone. Thus, these studies demonstrate that the change in the number of rabbit hepatic membrane LDL receptors induced by dietary manipulation

  4. Characterization of mesenchymal stem cells isolated from the rabbit fetal liver.

    PubMed

    Moreno, Rafael; Martínez-González, Itziar; Rosal, Marta; Farwati, Abduljalil; Gratacós, Eduard; Aran, Josep M

    2010-10-01

    Physiological attributes of mesenchymal stem cells (MSCs) including straightforward manipulation, multilineage differentiation, immunoregulation, and tropism for injury settings render them ideal therapeutic agents for tissue repair/regeneration. Nevertheless, further studies in suitable animal models of disease are needed to translate the potential of MSCs into clinical applications. We report here the isolation and preliminary characterization of MSCs from fetal rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic adherence owing to their developmental immaturity. Both cytochemical staining and mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs did express neither major histocompatibility complex (MHC) class I/II nor CD80/CD86, all these immune synapse components were induced upon in vitro culture. Furthermore, fl-MSCs became efficiently transduced for long-term transgene expression with a retroviral vector. Thus, the special biological qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell therapy strategies applied to a variety of rabbit models of injury, such as osteochondral lesions. PMID:20148649

  5. 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

  6. [Histopathological and ultrastructural changes in the liver and their pathogenesis in burns of rabbits].

    PubMed

    Liu, Y S

    1991-12-01

    48 health male rabbits were randomly divided into two groups: a napalm burn group and a healthy control group. The total area of burn was 30% TBSA full-thickness burn. Blood and liver tissue specimens were taken at 2, 6, 12, 24, 48, 72 and 168 hours postburn for quantitative analysis of serum enzymes, protein and histopathological, subcellular examination of the liver. Results indicated that hepatic pathological changes were characterized by an early onset, severity in extent, wide distribution and diversified morphology. Basic pathological changes in the liver included: (1) degeneration and necrosis of the hepatic cells and their transitional changes; (2) infiltration of inflammatory cells in parenchyma and interstices; (3) proliferation and swelling of Kupffer cells with active phagocytosis and subsequent degeneration. The overall course of changes observed in the liver specimens was divided into four phases: (1) congestive and anoxia phase, (2) inflammation phase, (3) degeneration and necrosis phase, (4) repair phase. The causes and pathogenesis of the four phases were analysed and discussed. Three possibilities of their pathogenesis were suggested according to morphological features and the course of the development of focal intracytoplasmic degeneration (FCD) and lytic necrosis (FCLY). PMID:1687451

  7. INFLUENCE OF LIGHT ENVIRONMENT ON THE ORGANIC CONSTITUTION OF NORMAL RABBITS WITH ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT

    PubMed Central

    Brown, Wade H.

    1928-01-01

    The influence of light environment on the organic constitution of normal rabbits was studied by comparing the weights of organs of animals that had been living under cerrtain conditions for long periods of time. It was found that the light environment produced an effect on the physical constitution of the rabbits which was comparable to the effects produced on the functional activity of the same animals. PMID:19869504

  8. Ultrastructural changes in the rabbit liver induced by carbamate insecticide bendiocarb.

    PubMed

    Holovska, Katarina; Almasiova, Viera; Cigankova, Viera

    2014-01-01

    Carbamates (CB) are used as insecticides and some of them have been registered as human drugs. The mechanism of CB poisoning involves reversible inhibition of acetylcholine esterase. In the present study, we investigated changes in liver ultrastructure in rabbits (Oryctolagus cuniculus) which were administered bendiocarb for 3, 10, 20, and 30 days. Rabbits in all experimental groups received capsules of bendiocarb (96% Bendiocarb, Bayer, Germany) per os daily at a dose of 5 mg/kg of body weight, and after day 11 received the same dose every 48 h. The observed changes were only moderate, focal, and the effect on the liver was not uniform. On the third day of the experiment, injured hepatocytes had dilated bile capillaries with reduced microvilli. There were no visible alterations in the intercellular contacts. Nuclei of these cells were irregular in shape. Many hepatocytes showed considerable increase in the number of peroxisomes. On day 10 of the experiment, the number of peroxisomes was reduced. Other changes, such as dilated rough endoplasmic reticulum and proliferation of smooth endoplasmic reticulum were observed on day 20. The number of lipid droplets in hepatocytes gradually increased. Usually they were present in low numbers, but on day 30 of the experiment their number increased significantly. They coalesced and formed a single lipid droplet which changed the shape of the nuclei. The results presented in this study indicate that both short and long-term administration of bendiocarb affects the liver ultrastructure. At the same time we also observed rapid onset of regeneration of the damaged tissue through activation of hepatocytes and oval cells. PMID:24901965

  9. Chemiluminescent responses of alveolar macrophages from normal and Mycobacterium bovis BCG-vaccinated rabbits as a function of age.

    PubMed Central

    Chida, K; Myrvik, Q N; Leake, E S; Gordon, M R; Wood, P H; Ricardo, M J

    1987-01-01

    Luminol-dependent chemiluminescence (CL) responses of alveolar macrophages (AM) from normal and Mycobacterium bovis BCG-vaccinated infant and adult rabbits were compared. AM from 1-, 7-, and 14-day-old normal rabbits exhibited much lower peak CL responses than did AM from 28- and 42-day-old normal animals as well as rabbits 2 to 3 or 5 to 6 months and 1 to 2 years of age. The most striking differences among AM from infant and adult rabbits were noted when AM were obtained from 28-day-old and 5- to 6-month old rabbits 21 days after the rabbits were immunized with 200 micrograms of BCG intravenously. In this case, AM from 5- to 6-month-old animals gave peak counts per minute of 400,000 to 500,000 whereas AM from 28-day-old rabbits vaccinated with BCG (harvested at 49 days of age) gave peak counts per minute of only 40,715 +/- 2,688. These data reveal that AM from neonatal animals are grossly deficient as responders to phorbol myristate acetate-induced CL. This deficiency, which improved with age, is still apparent in AM from 28-day-old animals. The data also reveal that BCG vaccination of 28-day-old animals yields AM that are poor responders to phorbol myristate acetate compared with AM from BCG-vaccinated animals 2 to 3 and 5 to 6 months of age. AM from animals vaccinated with BCG at 28 days of age contained fewer and smaller electron-dense lysosomelike structures than did AM from adult rabbits similarly vaccinated. These findings provide an explanation for the difficulties infants have in developing effective cell-mediated immune responses against intracellular parasites. Images PMID:3553004

  10. The stereochemical configuration of lysobisphosphatidic acid from rat liver, rabbit lung and pig lung.

    PubMed

    Joutti, A; Brotherus, J; Renkonen, O; Laine, R; Fischer, W

    1976-11-19

    Lysobisphosphatidic acid known also as bis(monoacyl-glycerol)phosphate, was isolated from liver of rats treated with Triton WR1339, and from rabbit and pig lung. Alkaline hydrolysates of all these samples of lysobisphosphatidic acid were essentially similar and contained phosphorus, total glycerol, free glycerol, total glycerophosphates, beta-glycerophosphate, total alpha-glycerophosphates, sn-glycero-1-phosphate and sn-glycero-3-phosphate in a molar ratio of 1.0 : 2.0 : 1.0 : 1.0 :0.6 : 0.4 : 0.38 : 0.04. This proves that the backbone of the principal lysobisphosphatidic acid from all three sources has the structure of 1-sn-glycerophospho-1-sn-glycerol. PMID:990300

  11. 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.

  12. Identification of genes transcribed by Pasteurella multocida in rabbit livers through the selective capture of transcribed sequences.

    PubMed

    Guo, Dongchun; Lu, Yan; Zhang, Aiqin; Liu, Jiasen; Yuan, Dongwei; Jiang, Qian; Lin, Huan; Si, Changde; Qu, Liandong

    2012-06-01

    Pasteurella multocida, a Gram-negative nonmotile coccobacillus, is the causative agent of fowl cholera in poultry, hemorrhagic septicemia in cattle, atropic rhinitis in swine, and snuffles in rabbits. The differentially expressed gene profile of P. multocida in infected rabbit livers was identified and compared with that from in vitro culture by selective capture of transcribed sequences. A total of 31 genes were identified, of which 28 encoded enzymes for amino acid biosynthesis and metabolism, intermediary metabolism, and energy metabolism, or proteins for regulatory adaptive responses, general microbial stress response, transport proteins, and secreted proteinases. Three were unknown, novel genes. Five genes representing different categories were chosen randomly and verified by real-time reverse transcriptase-polymerase chain reaction analysis. All were upregulated by P. multocida in infected rabbit livers, with changes ranging from 1.61- to 13.55-fold when compared with in vitro cultures. This study has identified genes of P. multocida that are upregulated during infection of rabbit livers when compared with in vitro growth conditions. The genes will provide a molecular basis for further study of the pathogenesis of P. multocida. PMID:22448890

  13. 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.

  14. 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

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

    PubMed

    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

    2016-06-01

    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 transplant recipients

  16. Radiofrequency Ablation of Rabbit Liver In Vivo: Effect of the Pringle Maneuver on Pathologic Changes in Liver Surrounding the Ablation Zone

    PubMed Central

    Kim, Seung Kwon; Ryu, Jeong-ah; Choi, Dongil; Lee, Won Jae; Lee, Ji Yeon; Lee, Ju Hyun; Sung, Yon Mi; Cho, Eun Yoon; Hong, Seung-Mo; Kim, Jong-Sung

    2004-01-01

    Objective We wished to evaluate the effect of the Pringle maneuver (occlusion of both the hepatic artery and portal vein) on the pathologic changes in the hepatic vessels, bile ducts and liver parenchyma surrounding the ablation zone in rabbit livers. Materials and Methods Radiofrequency (RF) ablation zones were created in the livers of 24 rabbits in vivo by using a 50-W, 480-kHz monopolar RF generator and a 15-gauge expandable electrode with four sharp prongs for 7 mins. The tips of the electrodes were placed in the liver parenchyma near the porta hepatis with the distal 1 cm of their prongs deployed. Radiofrequency ablation was performed in the groups with (n=12 rabbits) and without (n=12 rabbits) the Pringle maneuver. Three animals of each group were sacrificed immediately, three days (the acute phase), seven days (the early subacute phase) and two weeks (the late subacute phase) after RF ablation. The ablation zones were excised and serial pathologic changes in the hepatic vessels, bile ducts and liver parenchyma surrounding the ablation zone were evaluated. Results With the Pringle maneuver, portal vein thrombosis was found in three cases (in the immediate [n=2] and acute phase [n=1]), bile duct dilatation adjacent to the ablation zone was found in one case (in the late subacute phase [n=1]), infarction adjacent to the ablation zone was found in three cases (in the early subacute [n=2] and late subacute [n=1] phases). None of the above changes was found in the livers ablated without the Pringle maneuver. On the microscopic findings, centrilobular congestion, sinusoidal congestion, sinusoidal platelet and neutrophilic adhesion, and hepatocyte vacuolar and ballooning changes in liver ablated with Pringle maneuver showed more significant changes than in those livers ablated without the Pringle maneuver (p < 0.05) Conclusion Radiofrequency ablation with the Pringle maneuver created more severe pathologic changes in the portal vein, bile ducts and liver parenchyma

  17. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    SciTech Connect

    Tsutsui, H.; Tomoike, H.; Nakamura, M. )

    1990-08-01

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using ({sup 14}C)antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of ({sup 14}C)antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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. PMID:20406856

  3. Changes in the blood lipid profile after administration of Ocimum sanctum (Tulsi) leaves in the normal albino rabbits.

    PubMed

    Sarkar, A; Lavania, S C; Pandey, D N; Pant, M C

    1994-10-01

    Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents. PMID:7883302

  4. 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

  5. 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.

  6. Automated Quantification of Tumor Viability in a Rabbit Liver Tumor Model after Chemoembolization Using Infrared Imaging.

    PubMed

    D'inca, Hadrien; Namur, Julien; Ghegediban, Saida Homayra; Wassef, Michel; Pascale, Florentina; Laurent, Alexandre; Manfait, Michel

    2015-07-01

    The rabbit VX2 tumor is a fast-growing carcinoma model commonly used to study new therapeutic devices, such as catheter-based therapies for patients with inoperable hepatocellular carcinoma. The evaluation of tumor viability after such locoregional therapies is essential to directing hepatocellular carcinoma management. We used infrared microspectroscopy for the automatic characterization and quantification of the VX2 liver tumor viability after drug-eluting beads transarterial chemoembolization (DEB-TACE). The protocol consisted of K-means clustering followed by principal component analysis (PCA) and linear discriminant analysis (LDA). The K-means clustering was used to classify the spectra from the infrared images of control or treated tumors and to build a database of many tissue spectra. On the basis of this reference library, the PCA-LDA analysis was used to build a predictive model to identify and quantify automatically tumor viability on unknown tissue sections. For the DEB group, the LDA model determined that the surface of tumor necrosis represented 91.6% ± 8.9% (control group: 33.1% ± 19.6%; Mann-Whitney P = 0.0004) and the viable tumor 2.6% ± 4% (control group: 62.2% ± 15.2%; Mann-Whitney P = 0.0004). Tissue quantification measurements correlated well with tumor necrosis (r = 0.827, P < 0.0001) and viable tumor (r = 0.840, P < 0.0001). Infrared imaging and PCA-LDA analysis could be helpful for easily assessing tumor viability. PMID:25979795

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

    PubMed Central

    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

    Background: 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. Methods: 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). Results: 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). Conclusion: 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

  8. Effects of dietary cholesterol and its oxidation products on pathological lesions and cholesterol and lipid oxidation in the rabbit liver.

    PubMed

    Hur, Sun Jin; Nam, Ki Chang; Min, Byungrok; Du, Min; Seo, Kwon Il; Ahn, Dong Uk

    2014-01-01

    This study was conducted to determine the effects of dietary cholesterol (CHO) and cholesterol oxidation products (COPs) on the induction of pathological lesions in rabbit liver tissues. Liver lesions were induced only when the levels of CHO and COPs in the diet were very high. The amount of CHO measured in the liver increased when dietary CHO was increased; by comparison, dietary COPs affected liver CHO amounts to a lesser extent. The TBARS (thiobarbituric acid reactive substances) value measured for the liver samples also increased when dietary CHO and COP levels were elevated, and the TBARS value was more strongly affected by the amount of COPs in the diet than by the amount of CHO. At 6 and 12 weeks, COP levels were the highest in the group that received 1.2 g CHO + 0.8 g COPs, followed by the 0.5 g CHO + 0.5 g COPs and 1.6 g CHO + 0.4 g COPs groups; the control (0 g) group showed the lowest COP levels among all groups. In this study, we found that not only dietary CHO but also COPs were involved in hypercholesterolemia induced liver lesions when the amount of CHO and COPs was high. PMID:24696857

  9. 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

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

    PubMed

    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; Geschwind, Jean-François

    2016-06-01

    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. For the

  11. Metabolic and structural studies on serum- and liver-glycosaminoglycans in normal and liver-injured rats.

    PubMed

    Gressner, A M; Köster-Eiserfunke, W; Van de Leur, E; Greiling, H

    1980-05-01

    The incorporation of [35S]sulfate into total and specific types of serum glycosaminoglycans was studied in rats with acute, subacute or chronic liver injury (liver cirrhosis), and compared with that of normal rats. The macromolecular (protein-bound) nature of serum glycosaminoglycans in normal and diseased animals was also analysed. The results show a strong increase in rate and extent of [35S]sulfate incorporation into total serum glycosaminoglycans for acutely but a decrease for subacutely and chronically liver damaged rats. The time-course of distribution of label between serum chondroitin sulfate and dermatan sulfate exhibits significant changes in liver-injured animals, in particular a relatively high proportion of dermatan [35S]sulfate in rats with cirrhotic livers. In comparison with serum glycosaminoglycans the labeling profile of glycosaminoglycans in the cirrhotic liver was quite different (heparan sulfate:dermatan sulfate:chondroitin sulfate = 1:0.34:0.09) and changed only insignificantly during a 1 h labeling period. The protein-bound moiety of serum glycosaminoglycans was not affected by liver disease; but the elution profile of chondroitin [35S]sulfate from Dowex 1 X 2 for treated rats was altered, thus indicating a structural modification of its carbohydrate chain. PMID:7430957

  12. Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy.

    PubMed

    Yang, S; Tan, T M C; Wee, A; Leow, C K

    2004-01-01

    For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration. PMID:14745500

  13. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.

    PubMed

    Huang, Wendong; Ma, Ke; Zhang, Jun; Qatanani, Mohammed; Cuvillier, James; Liu, Jun; Dong, Bingning; Huang, Xiongfei; Moore, David D

    2006-04-14

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth. PMID:16614213

  14. Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.

    PubMed Central

    Leclerc, G; Gal, D; Takeshita, S; Nikol, S; Weir, L; Isner, J M

    1992-01-01

    The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease. Images PMID:1387886

  15. 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.

  16. 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.

  17. Bile Acid Flux Is Necessary for Normal Liver Regeneration

    PubMed Central

    Naugler, Willscott E.

    2014-01-01

    Background & Aims Many signals governing liver regeneration (LR) following 2/3 partial hepatectomy (PH) are recognized, but the primary signal(s) remains unknown. The aim of the study was to confirm that the remnant liver after PH lacks capacity to secrete the BA pool returning via the enterohepatic ciruculation (EHC), which may in turn stimulate LR. Methods After standard PH, BA flux was documented and BA signaling (Fgf15) and synthesis (Cyp7a) determined by qPCR. Rat biliary fistula (BF) and Asbt knockout mouse models interrupted the EHC prior to PH, and standard assays for LR employed along with complete RNA sequencing. CCl4 intoxication after BF tested the hypothesis in an alternate injury model. Results BA rise in systemic blood immediately following PH, confirming that the remnant liver cannot handle the BA returning via portal circulation. When the BA pool is drained prior to PH in the rat BF model, LR is markedly attenuated, a phenomenon reversed with duodenal BA replacement. Hepatocyte proliferation is similarly attenuated after PH in the Asbt knockout mouse as well as after CCl44 intoxication in rats with BF. Complete RNA sequencing in the rat PH model shows that early c-jun and AP-1 gene expression pathways are down regulated in the absence of BA, coincident with attenuated LR. Conclusions Absent BA return to the liver after PH or CCl4 injury markedly attenuates LR, though hepatocyte proliferation still occurs, inferring that BA flux and signaling are not the sole signals governing LR. Transcriptional networks involving c-jun and AP-1 are involved in the BA-specific effects on hepatocyte proliferation. PMID:24841254

  18. EFFECT ON PERFUSION VALUES OF SAMPLING INTERVAL OF CT PERFUSION ACQUISITIONS IN NEUROENDOCRINE LIVER METASTASES AND NORMAL LIVER

    PubMed Central

    Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.

    2014-01-01

    Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401

  19. Intraprocedural Diffusion-Weighted PROPELLER MRI to Guide Percutaneous Biopsy Needle Placement within Rabbit VX2 Liver Tumors

    PubMed Central

    Deng, Jie; Virmani, Sumeet; Yang, Guang-Yu; Tang, Richard; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

    2010-01-01

    Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) magnetic resonance imaging (MRI) can be used to guide biopsy needle placement during percutaneous interventional procedures to selectively target viable and necrotic tissues within VX2 rabbit liver tumors. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 15 VX2 liver tumors, baseline DWPROPELLER images acquired prior to the interventional procedure were used for apparent diffusion coefficient (ADC) measurements. Next, intraprocedural DW-PROPELLER scans were performed with needle position iteratively adjusted to target viable, necrotic, or intermediate border tissue regions. DW-PROPELLER ADC measurements at the selected needle tip locations were compared with the percentage of tumor necrosis qualitatively assessed at histopathology. Results DW-PROPELLER images demonstrated intratumoral tissue heterogeneity and clearly depicted the needle tip position within viable and necrotic tumor tissues. Mean ADC measurements within the region-of-interest encompassing the needle tip were highly correlated with histopathologic tumor necrotic tissue assessments. Conclusion DW-PROPELLER is an effective method to selectively position the biopsy needle tip within viable and necrotic tumor tissues. The DW-PROPELLER method may offer an important complementary tool for functional guidance during MR-guided percutaneous procedures. PMID:19629976

  20. 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. PMID:26335575

  1. Correlation of Doxorubicin Delivery and Tumor Necrosis after Drug-eluting Bead Transarterial Chemoembolization of Rabbit VX2 Liver Tumors.

    PubMed

    Gaba, Ron C; Emmadi, Rajyasree; Parvinian, Ahmad; Casadaban, Leigh C

    2016-09-01

    Purpose To quantify the correlation between doxorubicin (DOX) delivery and tumor necrosis after drug-eluting bead (DEB) transarterial chemoembolization (TACE). Materials and Methods In this animal care committee-approved study, New Zealand white rabbit VX2 liver tumors were treated transarterially with DOX-loaded 70-150-μm DEBs in five treatment groups with varying drug doses: sham (saline), 0 mg, 12.5 mg, 25 mg, and 37.5 mg. DEB TACE was followed by 3- and 7-day sacrifice, tumor harvest, and sectioning. Drug delivery was assessed by using fluorescence imaging, and tumor necrosis was quantified by means of histologic analysis. Statistical correlation of DOX delivery and tumor necrosis was performed by using the Spearman rank correlation coefficient (ρ). Results Thirty-six VX2 tumors (median diameter, 1.3 cm) in 20 rabbits (median weight, 2.8 kg) underwent successful DEB TACE. Treatment groups included eight, seven, eight, five, and eight tumors of similar size (P > .05). Tumors showed progressively greater DOX extent (sham, 0%; 0 mg, 0%; 12.5 mg, 3%; 25 mg, 20%; and 37.5 mg, 27%) and intensity (sham, 0.4; 0 mg, 1.9; 12.5 mg, 8.5; 25 mg, 9.6; and 37.5 mg, 18.3) and higher median percentage necrosis (sham, 68%; 0 mg, 64%; 12.5 mg, 76%; 25 mg, 78%; and 37.5 mg, 83%) across DOX treatment groups. Correlation of DOX extent (ρ = 0.975, P = .005) and intensity (ρ = 0.900, P = .037) with percentage tumor necrosis was statistically significant. Conclusion Incremental increases in DOX correlate with greater necrosis in rabbit VX2 liver tumors after DEB TACE. This result indicates an essential role for chemotherapy-induced cytotoxicity in TACE effectiveness and supports the use of chemotherapeutic drugs in transarterial therapy. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26967144

  2. The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits

    PubMed Central

    Nammi, Srinivas; Boini, Murthy K; Lodagala, Srinivas D; Behara, Ravindra Babu S

    2003-01-01

    Background The leaf juice or water decoction of Catharanthus roseus L. (Apocyanaceae) is used as a folk medicine for the treatment of diabetes all over the world. In the present investigation, the leaf juice of C. roseus has been evaluated for its hypoglycemic activity in normal and alloxan-induced diabetic rabbits. Methods The blood glucose lowering activity of the leaf juice was studied in normal and alloxan-induced (100 mg/kg, i.v.) diabetic rabbits, after oral administration at doses of 0.5, 0.75 and 1.0 ml/kg body weight. Blood samples were collected from the marginal ear vein before and also at 4, 6, 8, 10, 12, 16, 18, 20 & 24 h after drug administration and blood glucose was analyzed by Nelson-Somogyi's method using a visible spectrophotometer. The data was compared statistically by using Student's t-test. Results The leaf juice of C. roseus produced dose-dependent reduction in blood glucose of both normal and diabetic rabbits and comparable with that of the standard drug, glibenclamide. The results indicate a prolonged action in reduction of blood glucose by C. roseus and the mode of action of the active compound(s) of C. roseus is probably mediated through enhance secretion of insulin from the β-cells of Langerhans or through extrapancreatic mechanism. Conclusions The present study clearly indicated a significant antidiabetic activity with the leaf juice of Catharanthus roseus and supports the traditional usage of the fresh leaves by Ayurvedic physicians for the control of diabetes. PMID:12950994

  3. 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.

  4. Erythrophagocytosis by Liver Macrophages (Kupffer Cells) Promotes Oxidative Stress, Inflammation, and Fibrosis in a Rabbit Model of Steatohepatitis

    PubMed Central

    Otogawa, Kohji; Kinoshita, Kohji; Fujii, Hideki; Sakabe, Masahide; Shiga, Ryoko; Nakatani, Kazuki; Ikeda, Kazuo; Nakajima, Yuji; Ikura, Yoshihiro; Ueda, Makiko; Arakawa, Tetsuo; Hato, Fumihiko; Kawada, Norifumi

    2007-01-01

    Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. Here, we report a molecular aspect of this disease elucidated using rabbits fed a cholesterol-rich high-fat diet and exhibiting insulin resistance. The liver in this model showed steatohepatitis with fibrosis and high mRNA expression for some cytokines, heme oxygenase-1, transforming growth factor-β1, and collagen α1(I). Erythrocytes isolated from the model showed marked fragility and the externalization of phosphatidylserine (PS) on the outer leaflet of the membrane and were frequently engulfed by Kupffer cells/macrophages in the hepatic sinusoids. Expression of milk fat globule-epidermal growth factor (EGF)-factor 8, a PS-binding protein, was augmented in the liver. In culture, RAW 264.7 cells engulfed erythrocytes oxidized by tert-butyl hydroperoxide, a process that was inhibited by anti-milk fat globule-EGF-factor 8 antibody. In addition, PS-positive erythrocytes appeared entrapped in the model liver in ex vivo perfusion experiments. Finally, in specimens from NASH patients, the aggregation of erythrocytes in inflammatory hepatic sinusoids was notable. These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis. PMID:17322381

  5. Glucocorticoids differentially regulate Na-bile acid cotransport in normal and chronically inflamed rabbit ileal villus cells.

    PubMed

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit; Sundaram, Uma

    2010-05-01

    Previous studies have demonstrated that apical Na-bile acid cotransport (ASBT) is inhibited during chronic ileitis by both a decrease in the affinity as well as a decrease in the number of cotransporters. Methylprednisolone (MP), a commonly used treatment for inflammatory bowel disease (IBD, e.g., Crohn's disease), has been shown to reverse the inhibition of several other Na-solute cotransporters during chronic enteritis. However, the effect of MP on ASBT in the chronically inflamed ileum is not known. MP stimulated ASBT in villus cells from the normal rabbit ileum by increasing the cotransporter expression without a change in the affinity of the cotransporter for bile acid. Western blot studies demonstrated an increase in cotransporter expression. MP reversed the inhibition of ASBT in villus cells from the chronically inflamed ileum. Kinetic studies demonstrated that the mechanism of MP-mediated reversal of ASBT inhibition was secondary to a restoration of both affinity as well as cotransporter numbers. Western blot analysis demonstrated restoration of cotransporter numbers after MP treatment of rabbits with chronic ileitis. Thus MP stimulates ASBT in the normal ileum by increasing cotransporter numbers. MP reverses the inhibition of ASBT during chronic ileitis. However, MP restores the diminished affinity as well as cotransporter expression levels during chronic ileitis. Thus MP differentially regulates ASBT in the normal and in the chronically inflamed ileum. PMID:20075140

  6. Glucocorticoids differentially regulate Na-bile acid cotransport in normal and chronically inflamed rabbit ileal villus cells

    PubMed Central

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit

    2010-01-01

    Previous studies have demonstrated that apical Na-bile acid cotransport (ASBT) is inhibited during chronic ileitis by both a decrease in the affinity as well as a decrease in the number of cotransporters. Methylprednisolone (MP), a commonly used treatment for inflammatory bowel disease (IBD, e.g., Crohn's disease), has been shown to reverse the inhibition of several other Na-solute cotransporters during chronic enteritis. However, the effect of MP on ASBT in the chronically inflamed ileum is not known. MP stimulated ASBT in villus cells from the normal rabbit ileum by increasing the cotransporter expression without a change in the affinity of the cotransporter for bile acid. Western blot studies demonstrated an increase in cotransporter expression. MP reversed the inhibition of ASBT in villus cells from the chronically inflamed ileum. Kinetic studies demonstrated that the mechanism of MP-mediated reversal of ASBT inhibition was secondary to a restoration of both affinity as well as cotransporter numbers. Western blot analysis demonstrated restoration of cotransporter numbers after MP treatment of rabbits with chronic ileitis. Thus MP stimulates ASBT in the normal ileum by increasing cotransporter numbers. MP reverses the inhibition of ASBT during chronic ileitis. However, MP restores the diminished affinity as well as cotransporter expression levels during chronic ileitis. Thus MP differentially regulates ASBT in the normal and in the chronically inflamed ileum. PMID:20075140

  7. 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.

  8. Wave-length dependencies of light scattering in normal and cold swollen rabbit corneas and their structural implications*

    PubMed Central

    Farrell, R. A.; McCally, R. L.; Tatham, P. E. R.

    1973-01-01

    1. The studies described herein involve the use of light scattering measurements to characterize the ultrastructural arrangement of the constituent collagen fibrils in rabbit corneal stromas. 2. Theoretical light scattering techniques for calculating the scattering to be expected from the structures revealed by electron micrographs are discussed, and comparison with the experimental light scattering tests the validity of these structures. 3. The wave-length dependence of light transmission and of angular light scattering from normal corneas is in agreement with the short range ordering of collagen fibrils depicted in electron micrographs. 4. The transmission measurements on oedematous rabbit corneas indicate that transmission decreases linearly with the ratio of thickness to normal thickness. 5. The wave-length dependence of transmission through cold swollen corneas indicates that the increased scattering is caused by large inhomogeneities in the ultrastructure. Electron micrographs do, indeed, reveal the presence of such inhomogeneities in the form of large regions completely devoid of fibrils. ImagesPlate 1Plate 2Plate 3 PMID:4754873

  9. METABOLISM OF ALPHA-NAPHTHOFLAVONE BY RAT, MOUSE, RABBIT, AND HAMSTER LIVER MICROSOMES

    EPA Science Inventory

    The metabolism of alpha-naphthoflavone (ANF) was studied in hepatic microsomes from rats, mice, rabbits, and hamsters, species in which ANF exerts its biological activities. The major metabolites produced by all species were ANF-5,6-oxide, ANF-6-phenol, and ANF-7,8-dihydrodiol. M...

  10. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas.

    PubMed

    Paradis, V; Youssef, N; Dargère, D; Bâ, N; Bonvoust, F; Deschatrette, J; Bedossa, P

    2001-03-01

    There is growing evidence that senescent cells accumulate in vivo and are associated with the aging process in parallel with the progressive erosion of telomeres. Because recent data show that telomere shortening is involved in the pathogenesis of liver cirrhosis, we looked for replicative senescence cells in normal livers, chronic hepatitis C, and hepatocellular carcinoma (HCC). Replicative senescent cells were detected on liver tissue cryosections using expression of a specific marker, senescence-associated beta-galactosidase, a cytoplasmic enzyme detected at pH 6. A total of 57 frozen liver samples (15 normal liver, 32 chronic hepatitis C, and 10 HCCs) were studied. Replicative senescence was graded as absent in 56% of cases (32 of 57) and present in 44% (25 of 57). Replicative senescence was considered present in 3 of 15 normal livers (20%), 16 of 32 chronic hepatitis cases (50%), and 6 of 10 HCCs (60%). In the group of nontumoral livers, the presence of senescent cells in liver was associated with older age (P =.03). In the group with chronic hepatitis C, fibrosis stage, but not activity grade, was significantly correlated with the accumulation of replicative senescent cells (P <.001). Finally, beta-Gal staining in nontumoral tissue was strongly correlated with the presence of HCC in the surrounding liver (P <.001). These results suggest that chronic hepatitis C represents a relevant model of accelerated replicative senescence and that accumulation of replicative senescent cells predispose to HCC development. Detection of replicative senescent cells may then serve as a predictive marker of a hepatocellular carcinoma in the surrounding tissue. HUM PATHOL 32:327-332. PMID:11274643

  11. 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

  12. The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor.

    PubMed

    Qian, Kun; Ma, Yingying; Wan, Jiangshan; Geng, Shinan; Li, Han; Fu, Qianwen; Peng, Xiaole; Kan, Xuefeng; Zhou, Guofeng; Liu, Wei; Xiong, Bin; Zhao, Yanbing; Zheng, Chuansheng; Yang, Xiangliang; Xu, HuiBi

    2015-08-28

    Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions. PMID:26079186

  13. Distribution of nitric oxide synthase in normal and cirrhotic human liver

    PubMed Central

    McNaughton, Lance; Puttagunta, Lakshmi; Martinez-Cuesta, Maria Angeles; Kneteman, Norm; Mayers, Irvin; Moqbel, Redwan; Hamid, Qutayba; Radomski, Marek W.

    2002-01-01

    Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α1-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca2+-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca2+-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders. PMID:12482944

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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. PMID:27408922

  20. 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.

  1. Transarterial oily chemoembolization with lidamycin shows potent therapeutic efficacy in VX2 rabbit liver tumor

    PubMed Central

    Zhong, Genshen; Qi, Jinsong; Huo, Shuhua; Xue, Huichao; Xu, Zhishan; Li, Jinsong; Zhou, Yanjun; Wu, Minna; Li, Liang

    2015-01-01

    Transarterial oily chemoembolization (TOCE) is one of the most effective approaches for the treatment of patients with hepatocellular carcinoma (HCC), who are not suitable for surgical therapy. Lidamycin (LDM), a potent antitumor antibiotic, demonstrates good antitumor efficacy in various tumor types, both in vitro and in vivo. In this study, the antitumor efficacy of LDM combined with TOCE against the rabbit VX2 tumor was assessed. A toxicity assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) demonstrated that a combination of LDM with lipiodol did not impair the cytotoxicity of LDM against HepG2 cells in vitro. Using TOCE in rabbit VX2 tumor models, LDM showed a more powerful inhibitory effect against the tumor and lowered the expression levels of proliferating cell nuclear antigen (PCNA), cluster of differentiation 31 (CD31), and vascular endothelial growth factor (VEGF) compared to Adriamycin (ADM); moreover, this improvement was not accompanied by an increase of hepatotoxicity as shown by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. These results suggested that LDM combined with TOCE may be a feasible strategy in HCC therapy in the future. PMID:26543376

  2. 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.

  3. 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

  4. Mean scatterer spacing estimation in normal and thermally coagulated ex vivo bovine liver.

    PubMed

    Rubert, Nicholas; Varghese, Tomy

    2014-04-01

    The liver has been hypothesized to have a unique arrangement of microvasculature that presents as an arrangement of quasiperiodic scatterers to an interrogating ultrasound pulse. The mean scatterer spacing (MSS) of these quasiperiodic scatterers has been proposed as a useful quantitative ultrasound biomarker for characterizing liver tissue. Thermal ablation is an increasingly popular method for treating hepatic tumors, and ultrasonic imaging approaches for delineating the extent of thermal ablation are in high demand. In this work, we examine the distribution of estimated MSS in thermally coagulated bovine liver and normal untreated bovine liver ex vivo. We estimate MSS by detecting local maxima in the spectral coherence function of radio frequency echoes from a clinical transducer, the Siemens VFX 9L4 transducer operating on an S2000 scanner. We find that normal untreated bovine liver was characterized by an MSS of approximately 1.3 mm. We examined regions of interest 12 mm wide laterally, and ranging from 12 mm to 18 mm axially, in 2 mm increments. Over these parameters, the mode of the MSS estimates was between 1.25 and 1.37 mm. On the other hand, estimation of MSS in thermally coagulated liver tissue yields a distribution of MSS estimates whose mode varied between 0.45 and 1.0 mm when examining regions of interest over the same sizes. We demonstrate that the estimated MSS in thermally coagulated liver favors small spacings because the randomly positioned scatterers in this tissue are better modeled as aperiodic scatterers. The submillimeter spacings result from the fact that this was the most probable spacing to be estimated if the discretely sampled spectral coherence function was a uniformly random two-dimensional function. PMID:24554290

  5. Mean Scatterer Spacing Estimation in Normal and Thermally Coagulated Ex Vivo Bovine Liver

    PubMed Central

    Rubert, Nicholas; Varghese, Tomy

    2014-01-01

    The liver has been hypothesized to have a unique arrangement of microvasculature that presents as an arrangement of quasiperiodic scatterers to an interrogating ultrasound pulse. The mean scatterer spacing (MSS) of these quasiperiodic scatterers has been proposed as a useful quantitative ultrasound biomarker for characterizing liver tissue. Thermal ablation is an increasingly popular method for treating hepatic tumors, and ultrasonic imaging approaches for delineating the extent of thermal ablation are in high demand. In this work, we examine the distribution of estimated MSS in thermally coagulated bovine liver and normal untreated bovine liver ex vivo. We estimate MSS by detecting local maxima in the spectral coherence function of radio frequency echoes from a clinical transducer, the Siemens VFX 9L4 transducer operating on an S2000 scanner. We find that normal untreated bovine liver was characterized by an MSS of approximately 1.3 mm. We examined regions of interest 12 mm wide laterally, and ranging from 12 mm to 18 mm axially, in 2 mm increments. Over these parameters, the mode of the MSS estimates was between 1.25 and 1.37 mm. On the other hand, estimation of MSS in thermally coagulated liver tissue yields a distribution of MSS estimates whose mode varied between 0.45 and 1.0 mm when examining regions of interest over the same sizes. We demonstrate that the estimated MSS in thermally coagulated liver favors small spacings because the randomly positioned scatterers in this tissue are better modeled as aperiodic scatterers. The submillimeter spacings result from the fact that this was the most probable spacing to be estimated if the discretely sampled spectral coherence function was a uniformly random two-dimensional function. PMID:24554290

  6. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    NASA Astrophysics Data System (ADS)

    Zhou, Fang; Wei, Huajiang; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; He, Yonghong; Xie, Shusen; Guo, Zhouyi

    2015-02-01

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues.

  7. Histochemical studies of the colonic epithelial glycoproteins of the normal rabbit.

    PubMed

    Reid, P E; Walker, D C; Terpin, T; Owen, D A

    1988-10-01

    Two general classes of glycoproteins have been identified in the colonic epithelial cells of New Zealand white rabbits. Each is associated with an ultrastructurally distinct secretory cell. The first of these classes is found in cells, termed vesiculated columnar cells, characterized by electron-translucent vesicles, a small rough endoplasmic reticulum-Golgi complex and prominent microvilli. The glycoproteins of the vesiculated cells contain abundant O-sulphate ester, sialic acids with ester substituents at positions C-8 or C-9 (or with two or three side chain substituents) and neutral sugars with vicinal diols whose periodate oxidation is prevented by an O-acyl ester substituent(s). The second class of glycoproteins occurs in goblet cells characterized by electron-dense vesicles, an abundant rough endoplasmic reticulum, a well-developed Golgi apparatus and few, if any, microvilli. Goblet cells along the entire length of the crypts contain neutral sugars with periodate-oxidisable vicinal diols and a ferriferricyanide-reactive component. Cells in the upper halves of the crypts also contain components that are sulphated, Schiff-reactive and acid-fast. In the lower halves of the crypts, the goblet cells contain smaller quantities of the above components plus sialic acids, some of which possibly have an O-acyl substituent located at position C-8 or C-9 (or which have two or three side chain O-acyl substituents). It is suggested that the function of the glycoproteins from the vesiculated columnar cells is protective and that from the goblet cells is lubricative. PMID:2464561

  8. [Effect of Fuzheng Huayu recipe on CYP450 isozymes in normal and liver fibrosis rats].

    PubMed

    Zheng, Tian-hui; Liu, Wei; Li, Shu-ping; Yang, Tao; Wang, Chang-hong; Liu, Cheng-hai

    2015-03-01

    To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats. PMID:26226765

  9. Characteristics of liver on magnetic resonance diffusion-weighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

    PubMed Central

    Yuan, You-Hong; Xiao, En-Hua; Liu, Jian-Bin; He, Zhong; Jin, Ke; Ma, Cong; Xiang, Jun; Xiao, Jian-Hua; Chen, Wei-Jian

    2008-01-01

    AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (χ2 = 32.61, P < 0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (χ2 = 21.50, P < 0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually

  10. Transcatheter arterial embolization combined with radiofrequency ablation activates CD8+ T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors

    PubMed Central

    Duan, Xu-Hua; Li, Teng-Fei; Zhou, Guo-Feng; Han, Xin-Wei; Zheng, Chuan-Sheng; Chen, Peng-fei; Feng, Gan-Sheng

    2016-01-01

    Purpose To evaluate the effect of transcatheter arterial embolization (TAE) combined with radiofrequency ablation (RFA) treatment (TAE + RFA) on the expression of heat shock protein 70 (HSP70) in residual tumors and explore the relationship between the HSP70 and CD8+ T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model. Materials and methods Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA) with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8+ T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment. Results TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8+ T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8+ T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012), day 3 (r=0.93, P=0.021), and day 7 (r=0.8934, P=0.034). Conclusion In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8+ T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial therapeutic modality for tumor control and antitumor immune response in this model. PMID:27274279

  11. Effects of cholestyramine on low density lipoprotein binding sites on liver membranes from rabbits with endogenous hypercholesterolemia induced by a wheat starch-casein diet.

    PubMed

    Chao, Y; Yamin, T T; Alberts, A W

    1982-04-10

    Rabbits fed a wheat starch-casein diet develop a marked hypercholesterolemia with a lipoprotein distribution similar to that of humans. Approximately 76% of the total cholesterol is carried in the low density lipoprotein (LDL) fraction (1.006 less than d less than 1.063 g/ml). Inclusion of 1% cholestyramine in the diet prevents the increase in plasma cholesterol. The cholestyramine effect is mediated through an increased fractional catabolic rate of 125I-LDL. In order to determine the potential role of hepatic LDL receptors in the removal of LDL from the plasma, binding of 125I-LDL and 125I-beta-VLDL (beta-migrating very low density lipoproteins) to hepatic membranes prepared from livers of rabbits fed the wheat starch-casein diet with or without cholestyramine supplementation was investigated. Membranes from livers of the cholestyramine-supplemented animals exhibit high levels of specific EDTA-sensitive binding of either of the 125I-labeled lipoproteins. Very little EDTA-sensitive binding occurs on liver membranes from wheat starch-casein-fed rabbits that have not been treated with cholestyramine. These results indicate that the hypercholesterolemia in rabbits associated with the wheat starch-casein diet is wholly or partially the result of a decreased number of specific hepatic LDL receptors and thus a decreased catabolism of plasma cholesterol. The response of the liver to the inclusion in the diet of the bile acid sequestrant, cholestyramine, is to maintain or increase the number of specific LDL binding sites, thus promoting catabolism of plasma cholesterol. PMID:6277940

  12. Inactivation of purified rat liver cytochrome P-450 2B1 and rabbit liver cytochrome P-450 2B4 by N-methylcarbazole.

    PubMed

    Kuemmerle, S C; Shen, T; Hollenberg, P F

    1994-01-01

    Metabolism of N-methylcarbazole by purified rat liver cytochrome P-450 2B1 or rabbit liver P-450 2B4 resulted in the inactivation of these enzymes in a time-dependent, pseudo-first order manner as assayed spectrally by the decrease in the reduced CO spectrum at 450 nm. The inactivation was saturable with respect to the concentration of N-methylcarbazole, and a Ki = 5.2 microM and kINACT = 0.14 min-1 were determined for the inactivation of P-450 2B1. For P-450 2B4 inactivation, the Ki was 23 microM and the kINACT = 0.21 min-1. There was no increase in the reduced CO spectrum at 420 nm accompanying the inactivation, and the slight loss of the P-450 heme prosthetic group, as determined by the spectrum at 418 nm, was not sufficient to account for the loss of the reduced CO spectrum at 450 nm. The metabolism of N-methylcarbazole by P-450 did not result in the formation of a metabolic intermediate complex, which could also be responsible for the loss of cytochrome P-450 activity. Loss of catalytic activity for further substrate metabolism was also observed after preincubation of enzyme with N-methylcarbazole and the loss of catalytic activity correlated with the loss of the reduced CO spectrum. Accompanying the loss of spectrally detectable P-450 2B1 and P-450 2B4 catalytic activity, there was an increase in the NADPH oxidation rate. This increased rate persisted on subsequent addition of NADPH. PMID:8070309

  13. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort

    PubMed Central

    Kälsch, Julia; Bechmann, Lars P.; Heider, Dominik; Best, Jan; Manka, Paul; Kälsch, Hagen; Sowa, Jan-Peter; Moebus, Susanne; Slomiany, Uta; Jöckel, Karl-Heinz; Erbel, Raimund; Gerken, Guido; Canbay, Ali

    2015-01-01

    Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m2 and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals. PMID:26269425

  14. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort.

    PubMed

    Kälsch, Julia; Bechmann, Lars P; Heider, Dominik; Best, Jan; Manka, Paul; Kälsch, Hagen; Sowa, Jan-Peter; Moebus, Susanne; Slomiany, Uta; Jöckel, Karl-Heinz; Erbel, Raimund; Gerken, Guido; Canbay, Ali

    2015-01-01

    Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75 y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m(2) and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals. PMID:26269425

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

    PubMed Central

    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.

  16. 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.

  17. Cell lineage study in the liver using retroviral mediated gene transfer. Evidence against the streaming of hepatocytes in normal liver.

    PubMed Central

    Bralet, M. P.; Branchereau, S.; Brechot, C.; Ferry, N.

    1994-01-01

    The fate of normal hepatocytes in adult rat liver was studied after genetic labeling using the Escherichia coli beta-galactosidase gene coupled to a nuclear localization signal. The marker gene was introduced by direct in vivo retroviral-mediated gene transfer into hepatocytes 24 hours after partial hepatectomy. Analysis of beta-galactosidase expression in the liver at various time after gene transfer revealed that labeled hepatocytes were distributed throughout the entire lobule with a predominance in the periportal and mediolobular regions. Long-term experiments demonstrated that division of hepatocytes did occur as was revealed by the increasing number of beta-galactosidase-positive cells in isolated clusters. There was no evidence for the participation of stem cells in this process. Moreover, we found that after more than 1 year, the pattern of distribution of positive cells within the lobule was not modified. This suggests that hepatocytes do not migrate from the portal space to the perivenous region, as has been previously hypothesized. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8178942

  18. 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. PMID:23021237

  19. 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

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

    PubMed

    Perepelyuk, Maryna; Chin, LiKang; 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

  1. Binding and kinetic data for rabbit liver fructose-1,6-bisphosphatase with Zn2+ as cofactor

    PubMed Central

    Benkovic, Patricia A.; Caperelli, Carol A.; Maine, Margaret De; Benkovic, Stephen J.

    1978-01-01

    Atomic absorption determinations of zinc content were employed to demonstrate the technique to obtain zinc-free rabbit liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11). Reactivation of the apoenzyme by Zn2+ is rapid (within 1 min) and restores up to 96% of the initial specific activity. Gel filtration measurements showed that the enzyme contains four binding sites for zinc per molecule, one per subunit. The dissociation constants for the initial two binding sites are less than 0.1 μM. In the presence of a substrate analog, (α + β) methyl D-fructofuranoside 1,6-bisphosphate, at a level where two analog molecules are bound per phosphatase molecule, a total of eight Zn2+ ions bind at 8 μM Zn2+, revealing the presence of additional binding sites, including the catalytic one. The activity in the presence of Zn2+ is maximal at ca. 8 μM Zn2+, which corresponds to saturation of the four subunit sites plus the catalytic sites in the presence of substrate. At metal ion concentrations less than 10 μM, the order of activation is Zn2+ > Mn2+ > Mg2+. In kinetic assays with two metal cofactors the effect of Zn2+ at concentrations less than 10 μM on either the Mg2+ or the Mn2+ assays is inhibitory owing to the apparent formation of mixed (two different elements) metal ion-enzyme complexes possessing a catalytic activity that is measureable but lower than anticipated if the catalysis by the various metal ions is simply additive. Hence the activation by EDTA of the Mg2+ and Mn2+ assays is explicable in terms of Zn2+ removal, thus eliminating mixed metal species. Collectively these observations suggest that fructose-1,6-bisphosphatase may function in vivo as a Zn2+ metalloprotein. PMID:209458

  2. Effect of low density lipoprotein receptor deficiency on the metabolism of apolipoprotein B-100 in blood plasma. Kinetic studies in normal and Watanabe heritable hyperlipidemic rabbits.

    PubMed Central

    Yamada, N; Shames, D M; Havel, R J

    1987-01-01

    The kinetics of apolipoprotein (apo) B-100 in particles containing apo E (B,E particles) or lacking apo E (B particles) were studied in Watanabe heritable hyperlipidemic (WHHL) rabbits deficient in low density lipoprotein (LDL) receptors, and compared with those of normal rabbits after injection of radioiodinated very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL. In both groups results of kinetic modeling were consistent with the hypothesis that all apo B enters the plasma in VLDL, mainly as B,E particles, followed by delipidation and partial conversion to IDL and LDL, with concomitant conversion of some B,E particles to B particles. In WHHL rabbits, production of VLDL apo B was reduced by 40%, but LDL production was increased threefold. Defective removal of B,E and B particles in all three lipoprotein classes, coupled with preserved processes of delipidation, can account for the observed increases in the concentration of apo B (threefold in VLDL, fivefold in IDL, and twenty-twofold in LDL) in WHHL rabbits. PMID:3611356

  3. Galactosylated poly(ethyleneglycol)-lithocholic Acid selectively kills hepatoma cells, while sparing normal liver cells.

    PubMed

    Gankhuyag, Nomundelger; Singh, Bijay; Maharjan, Sushila; Choi, Yun-Jaie; Cho, Chong-Su; Cho, Myung-Haing

    2015-06-01

    Delivering drugs selectively to cancer cells but not to nearby normal cells is a major obstacle in drug therapy. In this study, lithocholic acid (LCA), a potent anti-cancer drug, is converted to two forms of poly(ethyleneglycol) (PEG) conjugates, viz., PEG-LCA (PL) and lactobionic acid (LBA) conjugated PEG-LCA (LPL). The latter form contains a galactose ligand in LBA to target the hepatocytes. Both forms are self-assembled to form nanoparticle formulation, and they have high potency than LCA to kill HepG2 cancer cells, sparing normal LO2 cells. Besides, LPL has high specificity to mouse liver cells in vivo. Western blot results confirm that the cell death is occurred through apoptosis induced by LPL nanoparticles. In conclusion, the induction of apoptosis and cell death is much more efficient with LPL nanoparticles than LCA molecules. PMID:25657071

  4. Data on differentially expressed microRNAs in the liver between nonalcoholic fatty liver disease and normal Wistar rat using Solexa sequencing.

    PubMed

    Zhang, Deqing; Wang, Yuqian; Ji, Zhibin; Wang, Zhonghua

    2016-09-01

    The dataset includes data from the Solexa sequencing reported in our paper: "Identification and differential expression of microRNAs associated with fat deposition in the liver of Wistar rats with nonalcoholic fatty liver disease" [1]. The data collected include small RNAs and microRNAs in liver tissue from high glucose-induced NAFLD Wistar rats, using normal Wistar rats as their negative controls. 6 small RNA libraries were constructed and the expression profiles were compared between the two groups. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) with the accession number GEO: GSE68411, was generated including the basic analysis. PMID:27331102

  5. Formation of (4R)- and (4S)-4-hydroxyochratoxin A and 10-hydroxyochratoxin A from Ochratoxin A by rabbit liver microsomes.

    PubMed Central

    Størmer, F C; Støren, O; Hansen, C E; Pedersen, J I; Aasen, A J

    1983-01-01

    Three metabolites were formed from ochratoxin A in the presence of rabbit liver microsomal fractions and NADPH. They were isolated by extraction, thin-layer chromatography, and high-pressure liquid chromatography. Two of them were identified as (4R)- and (4S)-4-hydroxyochratoxin A. It is suggested on the basis of mass and nuclear magnetic resonance spectroscopy that the third metabolite is 10-hydroxyochratoxin A. The formation of the metabolites was inhibited by carbon monoxide and metyrapone and was stimulated when microsomes from phenobarbital-treated animals were used. The results suggest that cytochrome P-450 catalyzes the formation of these metabolites. PMID:6859843

  6. Automated segmentation and quantification of liver and spleen from CT images using normalized probabilistic atlases and enhancement estimation

    PubMed Central

    Linguraru, Marius George; Sandberg, Jesse K.; Li, Zhixi; Shah, Furhawn; Summers, Ronald M.

    2010-01-01

    Purpose: To investigate the potential of the normalized probabilistic atlases and computer-aided medical image analysis to automatically segment and quantify livers and spleens for extracting imaging biomarkers (volume and height). Methods: A clinical tool was developed to segment livers and spleen from 257 abdominal contrast-enhanced CT studies. There were 51 normal livers, 44 normal spleens, 128 splenomegaly, 59 hepatomegaly, and 23 partial hepatectomy cases. 20 more contrast-enhanced CT scans from a public site with manual segmentations of mainly pathological livers were used to test the method. Data were acquired on a variety of scanners from different manufacturers and at varying resolution. Probabilistic atlases of livers and spleens were created using manually segmented data from ten noncontrast CT scans (five male and five female). The organ locations were modeled in the physical space and normalized to the position of an anatomical landmark, the xiphoid. The construction and exploitation of liver and spleen atlases enabled the automated quantifications of liver∕spleen volumes and heights (midhepatic liver height and cephalocaudal spleen height) from abdominal CT data. The quantification was improved incrementally by a geodesic active contour, patient specific contrast-enhancement characteristics passed to an adaptive convolution, and correction for shape and location errors. Results: The livers and spleens were robustly segmented from normal and pathological cases. For the liver, the Dice∕Tanimoto volume overlaps were 96.2%∕92.7%, the volume∕height errors were 2.2%∕2.8%, the root-mean-squared error (RMSE) was 2.3 mm, and the average surface distance (ASD) was 1.2 mm. The spleen quantification led to 95.2%∕91% Dice∕Tanimoto overlaps, 3.3%∕1.7% volume∕height errors, 1.1 mm RMSE, and 0.7 ASD. The correlations (R2) with clinical∕manual height measurements were 0.97 and 0.93 for the spleen and liver, respectively (p<0.0001). No significant

  7. Evaluation of hypointense liver lesions during hepatobiliary phase MR imaging in normal and cirrhotic livers: is increasing flip angle reliable?

    PubMed

    Xiao, Yu-dong; Ma, Cong; Liu, Jun; Li, Hua-bing; Zhang, Zi-shu; Zhou, Shun-ke

    2016-01-01

    Gd-EOB-DTPA is a newly developed liver specific magnetic resonance contrast agent, which is widely used for focal liver lesion (FLL) detection and liver function evaluation. However, it has been demonstrated that hepatocytes uptake of Gd-EOB-DTPA obviously decreased in cirrhotic liver, and cirrhotic liver parenchyma may show reduced enhancement in hepatobiliary phase, which would result in decreased liver-to-lesion contrast (LLC) and liver to lesion signal intensity ratio (LLSIR). Therefore, it is important to improve the image quality in cirrhotic liver, as it may alter therapeutic strategy. In this paper, we have shown adjustments of the flip angle (FA) provides a simple step to achieve better image quality for evaluation of FLLs, especially to those patients with severe liver cirrhosis. On the basis of our quantitative analysis, both of the LLC and the LLSIR with high FA protocol were always higher than those of low FA protocol. Additionally, on high FA images, more FLLs were detected, peritumoral invasion was found, boundary of the tumor was more remarkably, and better visualization of bile duct was observed. In conclusion, for the patient with severe liver cirrhosis, increasing FA can obviously improve the image quality, which is helpful for FLLs depiction. PMID:26732462

  8. Association of blood pressure level with nonalcoholic fatty liver disease in nonhypertensive population: Normal is not the new normal.

    PubMed

    Qian, Lin-Yan; Tu, Jian-Fei; Ding, Ya-Hui; Pang, Jie; Che, Xian-Da; Zou, Hai; Huang, Dong-Sheng

    2016-07-01

    The functional crosstalk between nonalcoholic fatty liver disease (NAFLD) and hypertension has been reported by some literatures; however, in nonhypertensive individuals, there is no article describes the characteristic of NAFLD. In this study, we aimed to determine the strength of the association between NAFLD with normal blood pressure (BP) in nonhypertensive individuals. This cross-sectional study was conducted in the sixth Affiliated Hospital of Wenzhou Medical University, from October 2007 to December 2011. In brief, 24,200 subjects were enrolled to participate in the survey. Among those subjects, there were 5305 enrolled subjects, those with filling the diagnostic criteria for NAFLD (21.9%; 4803 males and 502 females). Nonhypertension was identified in 17,403 (71.9%; 8179 males and 9224 females). The PR% of NAFLD for the systolic blood pressure (SBP) in quartiles 1 to 4 was 10.83, 12.55, 20.38, and 19.97. SBP, diastolic blood pressure (DBP), sex, age, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, fasting plasma glucose, uric acid, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol are closely associated with the risk for NAFLD. SBP (odds ratio [OR]: 1.092, 95% confidence interval [CI]: 1.030-1.158; P < 0.05) and DBP (OR: 1.157, 95%CI: 1.094-1.223; P < 0.05) were found to be independent risk factors for NAFLD. Our analysis indicates that BP is significantly associated with NAFLD in nonhypertensive individuals; SBP and DBP are found to be independent risk factors for NAFLD. PMID:27442673

  9. 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

    ...: Premarketing Clinical Evaluation'' (74 FR 38035; July 30, 2009). This guidance explained that drug-induced... 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?''...

  10. Proliferating cell nuclear antigen (PCNA) activity in hepatocellular carcinoma, benign peri-neoplastic and normal liver.

    PubMed

    Mun, Kein-Seong; Cheah, Phaik-Leng; Baharudin, Nurul Bahiyah; Looi, Lai-Meng

    2006-12-01

    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA

  11. A Mechanistic Assessment of the Discordance between Normal Serum Alanine Aminotransferase Levels and Altered Liver Histology in Chronic Hepatitis B

    PubMed Central

    Gong, Xianqiong; Yang, Jiaen; Tang, Jinmo; Gu, Chong; Huang, Lijian; Zheng, Ying; Liang, Huiqing; Wang, Min; Wu, Chuncheng; Chen, Yue; Zhang, Manying; Yu, Zhijian; Mao, Qianguo

    2015-01-01

    To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort. PMID:26230094

  12. Effects of Short Term Exposure of Atrazine on the Liver and Kidney of Normal and Diabetic Rats

    PubMed Central

    Jestadi, Dinesh Babu; Phaniendra, Alugoju; Babji, Undru; Srinu, Thupakula; Shanmuganathan, Bhavatharini

    2014-01-01

    The present study evaluates the effects of short term (15 days) exposure of low dose (300 μg kg−1) of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) on antioxidant status and markers of liver and kidney damage in normal (nondiabetic) and diabetic male Wistar rats. Rats were divided into four groups: Group I as normal control, Group II as atrazine treated, Group III as diabetic control, and Group IV as atrazine treated diabetic rats. Atrazine administration resulted in increased MDA concentration as well as increased activities of SOD, CAT, and GPx in both liver and kidney of atrazine treated and atrazine treated diabetic rats. However, GSH level was decreased in both liver and kidney of atrazine treated and atrazine treated diabetic rats. Atrazine administration led to significant increase in liver damage biomarkers such as AST, ALT, and ALP as well as kidney damage biomarkers such as creatinine and urea in both normal and diabetic rats, but this increase was more pronounced in diabetic rats when compared to normal rats. In conclusion, the results of the present study demonstrate that short term exposure of atrazine at a dose of 300 μg kg−1 could potentially induce oxidative damage in liver and kidney of both normal and diabetic rats. PMID:25349608

  13. Phospholipid Profile of the Stomach and Duodenum of Normal Rabbits Fed with Supplements of Unripe Pawpaw (Carica papaya) and Unripe Plantain (Musa sapientum) Extract

    NASA Astrophysics Data System (ADS)

    Eriyamremu, G. E.; Asagba, S. O.; Osagie, V. E.; Ojeaburu, S. I.; Lolodi, O.

    This study reports the effect of unripe pawpaw and/or unripe plantain extracts on the phospholipid profile of the stomach and duodenum of normal rabbits. Supplementation of chow with unripe pawpaw or plantain extract significantly reduced (p< 0.05) the weight gained by rabbits compared with the control. The total phospholipids content in the stomach and duodenum were significantly increased (p< 0.05) in the test groups compared to the control. In the stomach and duodenum, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SGM) were significantly increased (p< 0.05) in the test groups compared to the control. Pawpaw occasioned a decrease in the PE/PC ratio in both tissues as against an increase observed in the SGM/PC ratio. The results presented suggests that unripe pawpaw meal and unripe plantain extract alter the phospholipid profile of the stomach and duodenum in ways which may affect membrane fluidity of these tissues and would have profound effect on the gastro-duodenal mucosa and thus have implication(s) for gastric and duodenal ulcers in rabbits.

  14. 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.

  15. Characterisation of the hepatic progenitor cell compartment in normal liver and in hepatitis: an immunohistochemical comparison between dog and man.

    PubMed

    Ijzer, J; Schotanus, B A; Vander Borght, S; Roskams, T A D; Kisjes, R; Penning, L C; Rothuizen, J; van den Ingh, T S G A M

    2010-06-01

    The liver progenitor cell compartment in the normal canine liver and in spontaneous canine acute (AH) and chronic hepatitis (CH) was morphologically characterised and compared to its human equivalents. Immunohistochemistry was performed for cytokeratin-7 (CK7), human hepatocyte marker (Hep Par 1), multidrug resistance-associated protein-2 (MRP2), and breast cancer resistance protein (BCRP) on paraffin and frozen sections from canine and human tissues. Normal liver showed similar morphology and immunohistochemical reaction of the progenitor cell compartment/canal of Hering in man and dog. In addition, a ductular reaction, comparable in terms of severity, location and immunohistochemical characteristics, was observed in canine and human AH and CH. CK7 was a good marker for canine progenitor cells, including intermediate cells, which were positively identified in cases of AH and CH. In both species, BCRP was expressed in both hepatocytes and bile ducts of the normal liver, and in ductular reaction in AH and CH. MRP2 detected bile canalicular membranes in man and dog. These findings underline the similarities between canine and human liver reaction patterns and may offer mutual advantage for comparative research in human and canine spontaneous liver diseases. PMID:19369099

  16. INFLUENCE OF LIGHT ENVIRONMENT ON THE GROWTH OF HAIR IN NORMAL RABBITS WITH ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT

    PubMed Central

    Brown, Wade H.

    1928-01-01

    In a series of experiments dealing with the influence of light environment on normal rabbits, the growth of hair over shaved areas was used as an index of functional activity. The conditions compared were exposure to neon light, complete exclusion of light, and exposure to diffuse, filtered sunlight of varying intensity. It was found that prolonged existence under these conditions affected the proliferative activity of hair follicles in a manner and to an extent comparable with the effects produced by the same environmental conditions on the growth and nutrition of the animals themselves. PMID:19869471

  17. Pegylated Interferon-α Modulates Liver Concentrations of Activin-A and Its Related Proteins in Normal Wistar Rat

    PubMed Central

    Refaat, Bassem; El-Shemi, Adel Galal; Ashshi, Ahmed Mohamed; Mahamid, Elaf Wael; Al-Qadi, Noha Mohammed

    2015-01-01

    Aims. To measure the expression of activin βA-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-α (Peg-INF-α) and ribavirin (RBV). Materials and Methods. 40 male Wistar rats were divided equally into 4 groups: “control,” “Peg-only” receiving 4 injections of Peg-INF-α (6 µg/rat/week), “RBV-only” receiving ribavirin (4 mg/rat/day) orally, and “Peg & RBV” group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA. Results. Peg-INF-α  ± RBV altered the expression of all candidate molecules in the liver at the gene and protein levels (P < 0.05) and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groups (P < 0.05). There were also significant correlations between serum and liver activin-A and follistatin. Conclusion. Peg-INF-α modulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-α on the production of activins and follistatin by the liver and immune cells. PMID:26236109

  18. 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

  19. 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.

  20. 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

  1. Development and use of a new perfusion technique to study glucose metabolism of the aortic wall in normal and alloxan-diabetic rabbits

    SciTech Connect

    Brown, B.J.M.

    1985-01-01

    This study investigated (1) possible alterations in glucose uptake and utilization in the perfused, normal, and diabetic vascular wall of rabbits and (2) the effects thereon of insulin and exogenous glucose concentration. Part I involved development and characterization of an in vitro perfusion technique that closely reproduced predetermined in vivo conditions of aortic blood flow, arterial blood pressure, heart rate and pulse pressure. The responsiveness of the preparation to vasoactive agents was assessed with concentrations of norepinephrine (NE) from 10/sup -9/ to 10/sup -4/ M. In Part II, the effects of NE-induced tension development on glucose metabolism were determined by perfusion with oxygenated physiological salt solution (PSS) containing 7 mM glucose and tracer amounts of uniformly labeled /sup 14/C-glucose. Aortas from 8 week-diabetic rabbits were perfused under similar conditions employing a NE infusion in the presence or absence of insulin (150 uU/ml) and variable levels of glucose. Effects of NE-induced tension development include an apparent increase (39%) in glucose uptake and a twofold increase in /sup 14/CO/sub 2/ and lactate production. Aortas from diabetic rabbits perfused with PSS containing 7 mM glucose demonstrated marked decreases in glucose uptake (74%), /sup 14/CO/sub 2/ (68%), lactate (30%), total tissue glycogen (75%) and labeled tissue phospholipids (70%). Insulin or elevation of exogenous glucose to 25 mM (diabetic levels) normalized glucose uptake, but had differential effects on the pattern of substrate utilization. The marked alterations of glucose metabolism in the diabetic state may contribute to the functional changes observed in diabetic blood vessels.

  2. 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. PMID:27189963

  3. Cellular localization of type I III and IV procollagen gene transcripts in normal and fibrotic human liver.

    PubMed Central

    Milani, S.; Herbst, H.; Schuppan, D.; Surrenti, C.; Riecken, E. O.; Stein, H.

    1990-01-01

    The authors have determined the cell types producing alpha 1 (I), alpha 2 (I), alpha 1 (III), and alpha 1 (IV) procollagen gene transcripts in adult human liver by in situ hybridization with [35S]-labeled RNA probes. The liver specimens comprised a total of 20 biopsies with normal histology and biopsies with fibrosis or cirrhosis at different clinical stages and of heterogeneous origins. In normal liver, procollagen type I, III, and IV transcripts were detected in stromal and vascular mesenchymal cells of portal tracts and central veins, as well as in some perisinusoidal cells of the lobule. In fibrotic liver, increased levels of these procollagen mRNAs were observed in the same locations, and particularly enhanced in stromal cells of fibrotic septa and portal tracts, as well as in perisinusoidal cells. Expression of alpha 1 (IV) procollagen RNA was additionally found in some vascular endothelial and bile duct epithelial cells. Although previously suggested as the major source of liver collagens, hepatocytes showed no significant procollagen transcript levels in any of our samples. Thus, procollagen synthesis does not appear to be a function of hepatocytes, but rather of mesenchymal, endothelial, and bile duct epithelial cells in adult human liver. These findings may have implications for the development of specifically targeted antifibrotic therapies. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:2372043

  4. 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

  5. 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

  6. 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. PMID:9417868

  7. 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.

  8. Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes

    PubMed Central

    De Angelis, Claudio; Marietti, Milena; Bruno, Mauro; Pellicano, Rinaldo; Rizzetto, Mario

    2015-01-01

    In recent years, the description of isolated bile duct dilatation has been increasingly observed in subjects with normal liver function tests and nonspecific abdominal symptoms, probably due to the widespread use of high-resolution imaging techniques. However, there is scant literature about the evolution of this condition and the impact of endoscopic ultrasound (EUS) in the diagnostic work up. When noninvasive imaging tests (transabdominal ultrasound, computed tomography or magnetic resonance cholangiopancreatography) fail to identify the cause of dilatation and clinical or biochemical alarm signs are absent, the probability of having biliary disease is considered low. In this setting, using EUS, the presence of pathologic findings (choledocholithiasis, strictures, chronic pancreatitis, ampullary or pancreatic tumors, cholangiocarcinoma), not always with a benign course, has been observed. The aim of this review has been to evaluate the prevalence of disease among non-jaundiced patients without signs of cytolysis and/or cholestasis and the assessment of EUS yield. Data point out to a promising role of EUS in the identification of a potential biliary pathology. EUS is a low invasive technique, with high accuracy, that could play a double cost-effective role: identifying pathologic conditions with dismal prognosis, in asymptomatic patients with negative prior imaging tests, and excluding pathologic conditions and further follow-up in healthy subjects. PMID:26191344

  9. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    PubMed Central

    2014-01-01

    Purpose: To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. Methods: This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. Results: CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Conclusion: Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US. PMID:24936491

  10. Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

    PubMed Central

    Park, Hee Sun; Lee, Jeong Min; Kim, Young Il; Woo, Sungmin; Yoon, Jung Hwan; Choi, Jin-Young; Choi, Byung Ihn

    2015-01-01

    Objective To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. Materials and Methods This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. Results P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Conclusion Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent. PMID:26357497

  11. 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

  12. 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

  13. 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. PMID:18819560

  14. Assessment of Safety and Therapeutic Efficacy of Rosa damascena L. and Quercus infectoria on Cardiovascular Performance of Normal and Hyperlipidemic Rabbits: Physiologically Based Approach.

    PubMed

    Joukar, Siyavash; Askarzadeh, Masoumeh; Shahouzehi, Beydolah; Najafipour, Hamid; Fathpour, Hossein

    2013-01-01

    According to the use of Quercus infectoria (QI) and Rosa damascena L. (RD) for therapeutic purposes and lack of adequate information about their cardiovascular effects, we investigated the cardiovascular indices of rabbits which chronically pretreated with these agents. Animal groups were control group (CTL), RD and QI groups with normal chow plus 1.5 g RD and QI extracts, respectively, in each kg of the diet for 45 days; Hyperlipidemic (H) group received high-fat diet for 45 days; H+RD and H+QI groups received high fat diet plus QI and RD extracts, respectively. Blood pressure was greater in H+RD group than CTL, RD, and H groups. Left ventricular developed pressure and left ventricular systolic pressure increased significantly in H+RD group versus CTL and RD groups (P < 0.05 and P < 0.0001, resp.) and in H+QI groups (P < 0.01 versus QI groups). Left ventricular end diastolic pressure (LVEDP) showed significant reduction in H+QI group versus H group. QI attenuated the values of total cholesterol, LDL, TG, and atherogenic indices of plasma when coadministrated with a high-fat diet. The results suggest the antilipidemic and antiatherogenic effects of QI. In addition, the use of RD along with a high-fat diet may increase the risk of hypertension in rabbits. PMID:24163695

  15. Assessment of Safety and Therapeutic Efficacy of Rosa damascena L. and Quercus infectoria on Cardiovascular Performance of Normal and Hyperlipidemic Rabbits: Physiologically Based Approach

    PubMed Central

    Askarzadeh, Masoumeh; Shahouzehi, Beydolah; Najafipour, Hamid; Fathpour, Hossein

    2013-01-01

    According to the use of Quercus infectoria (QI) and Rosa damascena L. (RD) for therapeutic purposes and lack of adequate information about their cardiovascular effects, we investigated the cardiovascular indices of rabbits which chronically pretreated with these agents. Animal groups were control group (CTL), RD and QI groups with normal chow plus 1.5 g RD and QI extracts, respectively, in each kg of the diet for 45 days; Hyperlipidemic (H) group received high-fat diet for 45 days; H+RD and H+QI groups received high fat diet plus QI and RD extracts, respectively. Blood pressure was greater in H+RD group than CTL, RD, and H groups. Left ventricular developed pressure and left ventricular systolic pressure increased significantly in H+RD group versus CTL and RD groups (P < 0.05 and P < 0.0001, resp.) and in H+QI groups (P < 0.01 versus QI groups). Left ventricular end diastolic pressure (LVEDP) showed significant reduction in H+QI group versus H group. QI attenuated the values of total cholesterol, LDL, TG, and atherogenic indices of plasma when coadministrated with a high-fat diet. The results suggest the antilipidemic and antiatherogenic effects of QI. In addition, the use of RD along with a high-fat diet may increase the risk of hypertension in rabbits. PMID:24163695

  16. Sonographic Assessment of the Normal Dimensions of Liver, Spleen, and Kidney in Healthy Children at Tertiary Care Hospital.

    PubMed

    Thapa, N B; Shah, S; Pradhan, A; Rijal, K; Pradhan, A; Basnet, S

    2015-01-01

    Background Ultrasonography is one of the most common imaging modality to measure dimensions of visceral organs in children. However, the normal limit of size of visceral organs according to age and body habitus has not been specified in the standard textbooks. This might result in under detection of organomegaly in pediatrics population. Objective The objective of this study was to determine the normal range of dimensions for the liver, spleen, and kidney in healthy children. Method This is prospective cross-sectional, hospital-based study done at Tertiary-care teaching hospital. Participants included 272 pediatric subjects (152 male and 120 female) with normal physical or sonographic findings who were examined because of problems unrelated to the measured organs. The subjects were one month to 15 year (180 months) old. All measured organs were sonographically normal. Relationships of the dimensions of these organs with sex, age, body weight and height were investigated. Limits of normal dimensions of these organs were defined. Result Normal length of liver, kidneys and spleen were obtained sonographically for 272 children (152 male [55.9%] and 120 female [44.1%]) in the age group from 1 months to 15 (180 months) years. The mean age was 45.78 months (SD, 44.73). The measured dimensions of all these organs showed highest correlation with height and age so the descriptive analysis of the organ dimensions (mean, minimum, and maximum values, SD and 5th and 95th percentiles) were expressed in 10 age groups along with height range of the included children. The mean length of right kidney was shorter than the left kidney length, and the difference was statistically significant (p = 0.001). Conclusion This study provides practical and comprehensive guide to the normal visceral organ dimension in pediatric population. The normal range limit of the liver, spleen, and kidney determined in this study could be used as a reference in daily practice in local radiology clinics

  17. Unusual glycogenic hepatopathy causing abnormal liver enzymes in a morbidly obese adolescent with well-controlled type 2 diabetes: resolved after A1c was normalized by metformin.

    PubMed

    Umpaichitra, Vatcharapan

    2016-08-01

    We report, for the first time, a case of an accumulation of glycogen in the liver causing elevation of liver enzymes in a 15-year-old morbidly obese adolescent male with well-controlled type 2 diabetes. Notably, the patient did not have poorly controlled type 1 diabetes and did not require insulin. After normalization of the A1c with metformin, elevated liver enzymes returned to normal. PMID:27400632

  18. 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

  19. INFLUENCE OF LIGHT ENVIRONMENT ON THE GROWTH AND NUTRITION OF NORMAL RABBITS WITH ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT

    PubMed Central

    Brown, Wade H.

    1928-01-01

    The influence of light environment on the growth and nutrition of normal rabbits was studied by comparing the weight curves of animals living under different environmental conditions for periods of 4 to 8 months and the effects of change from one environment to another. Prolonged exposure to neon light was compared with confinement in the dark and exposure to diffuse, filtered sunlight of varying intensity. The results of the experiments showed that growth and nutrition were greatly affected by the light environment in which the animals lived. The effects produced by a given environment varied with the color or breed of the animal and appeared to be out of proportion to the differences in the intensity of the light or the energy represented. PMID:19869470

  20. 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. PMID:25619362

  1. 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

  2. Molecular cloning of the canine c-Met/HGF receptor and its expression in normal and regenerated liver.

    PubMed

    Neo, Sakurako; Kansaku, Norio; Furuichi, Mitsuru; Watanabe, Masashi; Hisamatsu, Sin; Ohno, Koichi; Hisasue, Masaharu; Tsuchiya, Ryo; Yamada, Takatsugu

    2005-05-01

    The c-Met proto-oncogene is the receptor for hepatocyte growth factor (HGF), which is a member of the tyrosine kinase family. Activation of the HGF/c-Met signal pathway leads to cell proliferation, motility, regeneration, and morphogenesis. In this study, the complete nucleotide sequence of complementary DNA (cDNA) of canine c-Met was cloned, and its distribution was determined in tissues. The canine c-Met cDNA clone had an open reading frame of 4419 bp that encoded a putative polypeptide of 1383 amino acids. The c-Met mRNA was expressed in a variety of canine tissues including peripheral blood mononuclear cells (PBMC), bone marrow, liver, kidney, lung, stomach, uterus, testis, thymus, lymph node, small intestine, colon, adrenal gland, thyroid gland, heart, muscle, skin, pancreas, ovary, prostate, spleen, fat, cerebrum, and cerebellum. In addition, the c-Met mRNA expression in normal and regenerated liver was examined. The levels of the mRNA increased 2-fold in regenerated liver compared to that found in normal liver, indicating that c-Met is involved in various functions including remodeling of canine hepatocytes. PMID:15942139

  3. Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.

    PubMed Central

    Markov, G G; Dessev, G N; Russev, G C; Tsanev, R G

    1975-01-01

    1. The effect of gamma-irradiation (4000rd) on the synthesis of ribosomal (pre-rRNA) and heterogeneous nuclear RNA (pre-mRNA) in normal and in regenerating rat liver was studied by using 40 min labelling with [6(-14)C]orotic acid. 2. Partial hepatectomy caused a sharp transient increase in the specific radioactivity of the endogenous low-molecular-weight RNA precursors in the livers of both normal and irradiated rats. Irradiation of intact animals did not affect the pool. 3. Irradiation enhanced the synthesis of pre-rRNA for at least 12h. The synthesis of pre-mRNA was also enhanced, but only in the first 3h after irradiation. 4. Partial hepatectomy strongly stimulated the synthesis of both pre-rRNA and pre-mRNA. 5. The synthesis of pre-rRNA was enhanced also in regenerating liver of animals irradiated before or after the operation. The conclusion can be drawn that the early increase in the synthesis of ribosomal RNA is a non-specific cellular response to different injuring factors. 6. The only case where irradiation caused an early inhibition of RNA synthesis was that of pre-mRNA in regenerating liver. This supports the hypothesis that ionizing radiation does not suppress the transcription per se but affects the mechanisms of activation of new genes (cellular programming). PMID:1147904

  4. Hepatic retinoid stores are required for normal liver regeneration[S

    PubMed Central

    Shmarakov, Igor O.; Jiang, Hongfeng; Yang, Kryscilla Jian Zhang; Goldberg, Ira J.; Blaner, William S.

    2013-01-01

    Preliminary studies of liver regeneration induced by partial hepatectomy (PHE) identified a substantial depletion of hepatic retinoid stores, by greater than 70%, in regenerating livers of wild-type C57Bl/6J mice. To understand this, we compared responses of wild-type and lecithin:retinol acyltransferase (Lrat)-deficient mice, which totally lack hepatic retinoid stores, to PHE. The Lrat-deficient livers showed delayed regeneration in the first 24 h after PHE. At 12 h after PHE, we observed significantly less mRNA expression for growth factors and cytokines implicated in regulating the priming phase of liver regeneration, specifically for Hgf and Tgfα, but not Tgfβ. Compared with wild-type mice, the changes in mRNA levels for p21 and cyclins E1, B1, and A2 mRNAs and for hepatocellular BrdU incorporation and mitoses were delayed (i.e., shifted to later times) in regenerating Lrat−/− livers. Concentrations of all-trans-retinoic acid were significantly lower in the livers of Lrat−/− mice following PHE, and this was accompanied by diminished expression of known retinoid-responsive genes. At later times after PHE, the rate of liver weight restoration for Lrat−/− mice was parallel to that of wild-type mice, although additional biochemical differences were observed. Thus, hepatic retinoid stores are required for maintaining expression of signaling molecules that regulate cell proliferation and differentiation immediately after hepatic injury, accounting for the delayed restoration of liver mass in Lrat−/− mice. PMID:23349206

  5. High-throughput and rapid quantification of lipids by nanoflow UPLC-ESI-MS/MS: application to the hepatic lipids of rabbits with nonalcoholic fatty liver disease.

    PubMed

    Byeon, Seul Kee; Lee, Jong Cheol; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

    2016-07-01

    A rapid and high-throughput quantification method (approximately 300 lipids within 20 min) was established using nanoflow ultrahigh-pressure liquid chromatography-tandem mass spectrometry (nUPLC-ESI-MS/MS) with selective reaction monitoring (SRM) and applied to the quantitative profiling of the hepatic lipids of rabbits with different metabolic conditions that stimulate the development of nonalcoholic fatty liver disease (NAFLD). Among the metabolic conditions of rabbits in this study [inflammation (I), high-cholesterol diet (HC), and high-cholesterol diet combined with inflammation (HCI)], significant perturbation in hepatic lipidome (>3-fold and p < 0.01) was observed in the HC and HCI groups, while no single lipid showed a significant change in group I. In addition, this study revealed a dramatic increase (>2-fold) in relatively high-abundant monohexosylceramides (MHCs), sphingomyelins (SMs), and triacylglycerols (TGs) in both the HC and HCI groups, especially in MHCs as all 11 MHCs increased by larger than 3- to 12-fold. As the levels of the relatively high-abundant lipids in the above classes increased, the total lipidome level of each class increased significantly by approximately 2-fold to 5-fold. Other classes of lipids also generally increased, which was likely induced by the increase in mitogenic and nonapoptotic MHCs and SMs, as they promote cell proliferation. On the other hand, a slight decrease in the level of apoptotic ceramides (Cers) was observed, which agreed with the general increase in total lipid level. As distinct changes in hepatic lipidome were observed from HC groups, this suggests that HC or HCI is highly associated with NAFLD but not inflammation alone itself. Graphical Abstract Schematic of lipidomic analysis from hepatic tissue using nanoflow LC-ESI-MS/MS and nUPLC-ESI-MS/MS. PMID:27178550

  6. 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.

  7. Rate and rhythm dependency of propagation from normal myocardium to a Ba++, K+-induced slow response zone in rabbit left atrium.

    PubMed

    Masuda, M O; de Carvalho, A P

    1982-03-01

    Strips of rabbit atrium 2-3 mm wide and 10-12 mm long were used to study how normal propagating action potentials excite a region where slow responses are the only form of electrical activity. One end of the preparation was bathed in normal Tyrode's solution. The rest was exposed to Tyrode's solution with high K+ (12.7 mM) and Ba++ (1 mM) (TKBa solution). The normal end was electrically stimulated and activity was monitored extra- and intracellularly (3 M KCl microelectrodes) as it propagated into the TKBa-treated region. We observed that the slow response could be elicited optimally by the normal action potential only within a limited range of stimulation frequencies (from around 0.3 to 1 Hz). At higher frequencies, progressive "fatigue" of slow response was observed. At frequencies lower than this range, normal action potentials were unable to stimulate slow response. To clarify the mechanism under this behavior, slow responses were directly elicited by electrical stimulation of strips wholly bathed in TKBa. Rate dependency of slow response excitability was again observed. Conclusions are: slow response excitability is enhanced transiently at each stimulation; the enhanced excitability state subsides very slowly and may take as long as 10 seconds to disappear; the enhanced state is cumulative from cycle to cycle so that excitability increases with increasing frequencies of stimulation above 0.1 Hz; and high frequency block due to fatigue and block due to excitability depression at low frequency delimit an optimal frequency window for slow response excitation and conduction. PMID:7060236

  8. Pathology of congenital syphilis in rabbits.

    PubMed Central

    Froberg, M K; Fitzgerald, T J; Hamilton, T R; Hamilton, B; Zarabi, M

    1993-01-01

    We have developed a model for congenital syphilis in the rabbit. This report provides additional information on newborn tissue pathology in animals that were infected in utero. A total of 35 pregnancies were evaluated, each containing 6 to 12 newborns. In the infected group, the mortality was approximately 50%; of the live newborns, half appeared normal and half were hyperreflexic, weak, and runty. Gross pathology in the sickly newborns was quite prevalent and involved enlarged spleens with isolated spots of necrosis; enlarged livers that were overtly congested and hemorrhagic and had numerous granular, white spots; and brains with hemorrhage in the occipital area. Histopathology was apparent in different tissues. Lymphocytes, plasma cells, and vacuolated macrophages were prominent in livers, spleens, brains, and bones. A few actively motile treponemes were visualized by dark-field microscopy within extracts of spleen and within cerebrospinal fluid. Low numbers of treponemes were also demonstrated in sections of brain and liver by using the Warthin-Starry silver stain technique. Blood hematocrits were decreased, and extramedullary hematopoiesis was prominent within spleens and livers; this is consistent with anemia. This rabbit model exhibits many of the same pathologic features commonly found in human congenital syphilis. Images PMID:8406873

  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. 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.

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

    PubMed Central

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

    1982-01-01

    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. PMID:7138735

  12. 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.

  13. 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. PMID:27321377

  14. 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

  15. ChIP-seq in steatohepatitis and normal liver tissue identifies candidate disease mechanisms related to progression to cancer

    PubMed Central

    2013-01-01

    Background Steatohepatitis occurs in alcoholic liver disease and may progress to liver cirrhosis and hepatocellular carcinoma. Its molecular pathogenesis is to a large degree unknown. Histone modifications play a key role in transcriptional regulations as marks for silencing and activation of gene expression and as marks for functional elements. Many transcription factors (TFs) are crucial for the control of the genes involved in metabolism, and abnormality in their function may lead to disease. Methods We performed ChIP-seq of the histone modifications H3K4me1, H3K4me3 and H3K27ac and a candidate transcription factor (USF1) in liver tissue from patients with steatohepatitis and normal livers and correlated results to mRNA-expression and genotypes. Results We found several regions that are differentially enriched for histone modifications between disease and normal tissue, and qRT-PCR results indicated that the expression of the tested genes strongly correlated with differential enrichment of histone modifications but is independent of USF1 enrichment. By gene ontology analysis of differentially modified genes we found many disease associated genes, some of which had previously been implicated in the etiology of steatohepatitis. Importantly, the genes associated to the strongest histone peaks in the patient were over-represented in cancer specific pathways suggesting that the tissue was on a path to develop to cancer, a common complication to the disease. We also found several novel SNPs and GWAS catalogue SNPs that are candidates to be functional and therefore needs further study. Conclusion In summary we find that analysis of chromatin features in tissue samples provides insight into disease mechanisms. PMID:24206787

  16. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Mechanism of coumarin action: sensitivity of vitamin K metabolizing enzymes of normal and warfarin-resistant rat liver.

    PubMed

    Hildebrandt, E F; Suttie, J W

    1982-05-11

    The in vitro effects of two coumarin anticoagulants, warfarin and difenacoum, on rat liver microsomal vitamin K dependent carboxylase, vitamin K epoxidase, vitamin K epoxide reductase, and cytosolic vitamin K reductase (DT-diaphorase) from the livers of normal and a warfarin-resistant strain of rats have been determined. Millimolar concentrations of both coumarins are required to inhibit the carboxylase and epoxidase activities in both strains of rats. Sensitivity of DT-diaphorase to coumarin inhibition differs when a soluble or liposomal-associated substrate is used, but the diaphorases isolated from both strains of rats have comparable sensitivity. The anticoagulant difenacoum is an effective rodenticide in the warfarin-resistant strain of rats, and the only enzyme studied from warfarin-resistant rat liver that demonstrated a significant differential inhibition by the two coumarins used was the vitamin K epoxide reductase. This enzyme also showed the greatest sensitivity to coumarin inhibition among the enzymes studied. These results support the hypothesis that the physiologically important site of action of coumarin anticoagulants is the vitamin K epoxide reductase. PMID:6807339

  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. 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

  4. Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein†

    PubMed Central

    Chang, Benny Hung-Junn; Li, Lan; Paul, Antoni; Taniguchi, Susumu; Nannegari, Vijayalakshmi; Heird, William C.; Chan, Lawrence

    2006-01-01

    Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp−/− cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments. PMID:16428458

  5. 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. PMID:20692471

  6. Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels

    PubMed Central

    Luo, Yu-qi; Ma, Xiao-jing; Hao, Ya-ping; Pan, Xiao-ping; Xu, Yi-ting; Xiong, Qin; Bao, Yu-qian; Jia, Wei-ping

    2015-01-01

    Aim: Osteocalcin is involved in the progression of nonalcoholic fatty liver disease (NAFLD) in animal models and humans. In this study we investigated the relationship between serum osteocalcin levels and NAFLD in postmenopausal Chinese women. Methods: A total of 733 postmenopausal women (age range: 41–78 years) with normal blood glucose levels were enrolled in this cross-sectional study. Women taking lipid-lowering or anti-hypertensive drugs were excluded. Serum osteocalcin levels were assessed using an electrochemiluminescence immunoassay. The degree of NAFLD progression for each subject was assessed through ultrasonography. The fatty liver index (FLI) of each subject was calculated to quantify the degree of liver steatosis. Results: The median level of serum osteocalcin for all subjects enrolled was 21.99 ng/mL (interquartile range: 17.84–26.55 ng/mL). Subjects with NAFLD had significantly lower serum osteocalcin levels (18.39 ng/mL; range: 16.03–23.64 ng/mL) compared with those without NAFLD (22.31 ng/mL; range: 18.55–27.06 ng/mL; P<0.01). Serum osteocalcin levels decreased with incre¬mental changes in the FLI value divided by the quartile (P-value for trend<0.01). The serum osteocalcin levels showed a negative correlation with the FLI values, even after adjusting for confounding factors (standardized β=−0.124; P<0.01). Binary logistic regression analysis identified an individual's serum osteocalcin level as an independent risk factor for NAFLD (odds ratio: 0.951; 95% confidence interval: 0.911–0.992; P=0.02). Conclusion: Serum osteocalcin levels are inversely correlated with NAFLD in postmenopausal Chinese women with normal blood glucose levels. PMID:26567728

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. 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. PMID:24486698

  9. Tissue distribution of subcutaneously administered aluminum chloride in weanling rabbits

    SciTech Connect

    Du Val, G.; Grubb, B.R.; Bentley, P.J.

    1986-01-01

    The purpose of the investigation was to determine blood and tissue levels of aluminum (Al) in normal young rabbits. Furthermore, tissue distribution and accumulation of Al were determined as related to blood concentration in Al-dosed rabbits. The levels of Al accumulated were determined in different tissues of growing rabbits after continuous subcutaneous administration of Al chloride (3.78 mg/d) for 28 d. No signs of toxicity were apparent from comparisons of hematocrit or weight gain between control and Al-dosed rabbits. The largest concentration of the Al was observed in bone, which was also found to have the highest levels in the control rabbit tissues. Following bone, the experimental animals showed the greatest increase of Al levels in kidney cortex, kidney medulla, liver, testes, skeletal muscle, heart, brain white matter, and brain hippocampus, in that order. No significant difference was found in brain grey matter between control and experimental animals. As the brain tissue of the Al-treated animals had the lowest Al level of the tissues measured, it appears that there is a partial blood-brain barrier to entry of Al.

  10. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  11. Mitochondrial DNA and nuclear DNA from normal rat liver have a common sequence.

    PubMed Central

    Hadler, H I; Dimitrijevic, B; Mahalingam, R

    1983-01-01

    Although Pst I does not cut the circular mitochondrial genome of the rat, BamHI generates from this genome two unequal fragments of DNA. Each of these fragments was cloned in pBR322. Nuclear DNA was digested from rat liver singly or doubly with Pst I and BamHI, and it was demonstrated that nuclear DNA shared a common sequence with the larger mitochondrial DNA BamHI fragment. The cloned larger mitochondrial DNA fragment was further subdivided with HindIII into four pieces that were labeled and then used to probe the double-digested nuclear DNA. The hybridization data showed that the common sequence is less than 3 kilobase pairs long and lies within the part of the mitochondrial genome containing the D-loop and a portion of the rRNA genes. It therefore appears that, as in lower eukaryotes, there are shared sequences between the nuclear and mitochondrial genomes in mammals. Images PMID:6579536

  12. Mitochondrial DNA, RNA and protein synthesis in normal, hypothyroid and mildly hyperthyroid rat liver during cold exposure.

    PubMed

    Goglia, F; Liverini, G; Lanni, A; Barletta, A

    1988-02-01

    We have examined in isolated liver mitochondria the effect of cold exposure on DNA, RNA and protein synthesis in normal, hypothyroid and mildly hyperthyroid rats. In normal rats DNA polymerase activity increased from the first day of cold exposure remaining high up to the fifteenth day. RNA polymerase and protein synthesis were stimulated from the fifth day of cold exposure, maintaining a high level up to the fifteenth day. These activities were related to serum triiodothyronine (T3) levels. Indeed propylthiouracil (PTU) administration to cold-exposed rats drastically depressed the above activities, whereas T3 administration to PTU-treated cold-exposed rats restored them to about the values prevalent in normal cold-exposed rats. The translation products analyzed by gel electrophoresis showed that different effects may be exerted by T3 depending on whether its circulating levels are physiologically or pharmacologically modified. These findings suggest that T3 may be involved in the regulation of the acclimation process by acting, presumably with a permissive role, on those activities which determine a modification of the mitochondrial morphometric features and an increase in mitochondria number and turnover. PMID:2451625

  13. The morphologic characteristics of intercellular junctions between normal human liver cells and cells from patients with extrahepatic cholestasis.

    PubMed Central

    Robenek, H.; Herwig, J.; Themann, H.

    1980-01-01

    In freeze-fracture replicas the bile canaliculi of normal human livers showed a lumen of rather constant size with parallel margins. The zonula occludens consists of a complex anastomosing network of intramembranous ridges on the P face and complementary grooves of the E face of the plasmalemma of liver parenchymal cells. The zonula occludens is usually composed of three to five ridges running parallel to the lumen of the bile canaliculus that are surrounded by a looser meshwork of variable orientation. All tight junctions observed in control replicas appeared as continuous barriers without any disruptions. Extrahepatic cholestasis produced considerable morphologic alterations in the canaliculi and tight junctions. The lumen of the canliculi enlarged, and the microvilli disappeared. Side branches, irregularities, and outpouchings of the canalicular membrane extending into the cytoplasm of the hepatocytes were frequently observed. The complexity of the branching pattern and the number of strands in the zonulae occludentes changed extensively. Junctional strands away from their usual pericanalicular location were present on the lateral surface of the plasma membrane. The altered zonulae occludents contain regions in which the strands had a fragmented appearance or were completely absent. These discontinuities in the junctional meshwork provide a direct pathway between the lumen of the bile canaliculus and the intercellular space. They strongly suggest a leakage of the canaliculosinusoidal barrier. Of further interest is the diffuse aggregation of the usually randomly distributed intramembranous particles of the P face of the plasmalemma. The aggregates consist of 10-50 individual particles. Concomitantly, the desmosomes appeared to be more numerous than normally. The number and structure of gap junctions remained unaffected. The results of this investigation are discussed in relation to those obtained after experimental bile duct ligation in rats. Images Figure 8

  14. Multiple forms of cytochrome P-450 purified from liver microsomes of phenobarbital- and 3-methylcholanthrene-pretreated rabbits. II. Spectral properties.

    PubMed

    Hashimoto-Yutsudo, C; Imai, Y; Sato, R

    1980-08-01

    The spectral properties of multiple forms of cytochrome P-450 purified or partially purified from liver microsomes of phenobarbital (PB)- and 3-methylcholanthrene (MC)-treated rabbits have been studied. Both optical absorption and EPR studies have shown that the oxidized forms of P-450(1), P-450(2) (from PB-treated animals), and P-450(3) (from MC-treated animals) are in the low spin state, having a Soret absorption peak at 417-418 nm. Oxidized P-448(1) (from both PB- and MC-treated animals), on the other hand, shows a Soret peak at 393 nm and a weak band at 646 nm. This and EPR evidence indicate that P-448(1) contains heme which is predominantly in the high spin state, though EPR studies at low temperature indicate the presence of a small amount of low spin ferric heme. The presence of tightly bound MC in P-448(1) purified from MM-treated animals is reflected by characteristic absorption peaks in the ultraviolet region, but this does not affect the absorption spectra in the Soret and visible regions. Emulgen 913, a nonionic detergent, causes the conversion of oxidized P-448(1) from the high to the low spin state, as evidenced by optical absorption and EPR results; bound MC inhibits this conversion in a noncompetitive way. Binding of ethyl isocyanide to reduced P-450(1) and P-448(1) results in the appearance of two Soret peaks in the 430 and 455 nm regions, the relative intensities of which are dependent on pH. At any pH the 455 nm peak of P-448(1) is always higher than that of P-450(1). Benzphetamine and aniline, added to oxidized P-450(1), cause Type I and Type II spectral changes, respectively, but the magnitudes of the changes are small in both cases. The Soret peak of oxidized P-448(1) at 393 nm is completely shifted to 420 nm on addition of aniline, resulting in a reverse Type I spectral change; acetanilide causes the conversion of the Soret peak to the low spin state to only a slight extent. The conversions caused by aniline and acetanilide are both inhibited

  15. Characterization of the cadmium complex of peptide 49-61: a putative nucleation center for cadmium-induced folding in rabbit liver metallothionein IIA.

    PubMed

    Muñoz, A; Laib, F; Petering, D H; Shaw, C F

    1999-08-01

    The synthetic peptide fragment containing residues 49-61 of rabbit liver metallothionein II (MT-II) (Ac-Ile-Cys-Lys-Gly-Ala-Ser-Asp-Lys-Cys-Ser-Cys-Cys-Ala-COOH), which includes the only sequential four cysteines bound to the same metal ion in Cd7MT, forms a stable, monomeric Cd-peptide complex with 1:1 stoichiometry (Cd:peptide) via Cd-thiolate interactions. This represents the first synthesis of a single metal-binding site of MT independent of the domains. The 111Cd NMR chemical shift at 716 ppm indicates that the 111Cd2+ in the metal site is terminally coordinated to four side-chain thiolates of the cysteine residues. The pH of half dissociation for this Cd-peptide derivative, approximately 3.3, demonstrates an affinity similar to that for Cd7MT. Molecular mechanics calculations show that the thermodynamically most stable folding for this isolated Cd2+ center has the same counterclockwise chirality (lambda or S) observed in the native holo-protein. These properties are consistent with its proposed role as a nucleation center for cadmium-induced protein folding. However, the kinetic reactivity of the CdS4 structure toward 5,5'-dithiobis(5-nitrobenzoate) (DTNB) and EDTA is greatly increased compared to the complete cluster (a-domain or holo-protein). The rate law for the reaction with DTNB is rate = (k(uf) + k(1,f) + k(2,f) [DTNB])[peptide], where k(uf) = 0.15 s(-1), k(1,f)= 2.59x10(-3) s(-1), and k(2,f) = 0.88 M(-1) s(-1). The ultrafast step (uf), observable only by stopped-flow measurement, is unprecedented for mammalian (M7MT) and crustacean (M6MT) holo-proteins or the isolated domains. The accommodation of other metal ions by the peptide indicates a rich coordination chemistry, including stoichiometries of M-peptide for Hg2+, Cd2+, and Zn2+, M2-peptide for Hg2+ and Au+, and (Et3PAu)2-peptide. PMID:10555583

  16. 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.

  17. Protective Effect of Egyptian Propolis against Rabbit Pasteurellosis

    PubMed Central

    Nassar, Somia A.; Mohamed, Amira H.; 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

  18. The effect of about one third craniectomy on the cerebrospinal fluid flow rate as estimated by radionuclide cisternography in normal rabbits.

    PubMed

    Karacalioglu, Alper O; Erdogan, Ersin; Duz, Bulent; Kilic, Selim; Ayan, Asli; Ozguven, Mehmet A

    2011-01-01

    Since, the effect of a large cranial defect on the cerebrospinal fluid (CSF) flow rate is still not clear, this study was designed to evaluate the effect of craniectomy in rabbits by using a radionuclide technique, under in vivo physiologic conditions. Eleven male New Zealand white rabbits were examined. After the injection of technetium-99m-diethylene-triaminepenta-acetic acid into the fourth ventricle of each rabbit, dynamic acquisition for 60 min (1 min per frame) was performed pre-op followed by about one third craniectomy to each animal. Injection of the radiopharmaceutical and the imaging steps were repeated at 24 h (post-op 24 h) and at 7 days (post-op 7 d) after craniectomy. The region of interest (ROI) was drawn around the injection site and a time activity curve was generated. Slopes of each curve were calculated to detect the flow rate of the radiopharmaceutical from the injection site during 60 min. Besides, the count decreased ratio (ROIcounts of the last frame ROI counts of the first frame X100) was calculated. Our results showed that the pre-op values of the slope of the time-activity curve and the count decreased ratio were decreased 24 h and 7 d post-op but statistically significant was only the difference between the above values pre-op and 7 d post-op (P=0.04, P=0.01 respectively). In conclusion, the data of the present study indicate that the CSF flow rate in rabbits decreased 7 d after one third craniectomy. PMID:21512663

  19. Pathogenesis of Herpesvirus sylvilagus infection in cottontail rabbits.

    PubMed

    Hesselton, R M; Yang, W C; Medveczky, P; Sullivan, J L

    1988-12-01

    Experimental infection with Herpesvirus sylvilagus produces clinical and histopathologic changes in its natural host, the cottontail rabbit (Sylvilagus floridanus), similar to those observed in humans acutely infected with Epstein-Barr virus (EBV). Twenty-seven seronegative cottontail rabbits were infected with Herpesvirus sylvilagus and all developed antibodies within 10 days. Neutralizing antibody was detected as early as 7 days after infection. Virus was isolated from blood mononuclear cells, spleen, bone marrow, thymus, lymph nodes, kidneys, lung, and liver as early as 3 days after infection. Infected animals showed leucocytosis, monocytosis, and lymphocytosis with the appearance of atypical lymphocytes. Peripheral blood abnormalities peaked at 10-14 days after infection, and returned to normal by 28 days after infection, with the exception of atypical lymphocytosis that persisted in some animals for more than 2 years after experimental infection. More severe histopathologic changes were seen in virus-infected juvenile rabbits than adult rabbits; these changes included viral myocarditis, interstitial pneumonia, and lymphocytic myositis. Reactive hyperplasia and subsequent lymphocytic depletion of spleen and lymph nodes were reminiscent of that seen in virus-associated hemophagocytosis syndrome. Prominent lymphoid hyperplasia of many nonlymphoid organs, most notably the kidney and lungs, was observed. The development of these lymphoproliferative lesions and other lymphoid changes during H. sylvilagus infection suggest that this system may be a model to study similar lesions induced by EBV infection in humans. PMID:2849303

  20. Intracranial volume in craniosynostotic rabbits.

    PubMed

    Mooney, M P; Burrows, A M; Wigginton, W; Singhal, V K; Losken, H W; Smith, T D; Dechant, J; Towbin, A; Cooper, G M; Towbin, R; Siegel, M I

    1998-05-01

    Although craniosynostosis alters brain growth direction resulting in compensatory changes in the neurocranium, it has been suggested that such compensations occur with little reduction in intracranial volume (ICV). This hypothesis was tested in a rabbit model with nonsyndromic, familial coronal suture synostosis. Cross-sectional three-dimensional computed tomographic head scans were obtained from 79 rabbits (25 normal, 28 with delayed-onset synostosis, and 26 with early-onset synostosis) at 25, 42, and 126 days of age. Intracranial contents were reconstructed and indirect ICV was calculated. Results revealed that by 25 days of age the intracranial contents from early-onset synostosed rabbit skulls showed rostral (anterior) constrictions and a "beaten copper" morphology in the parietal and temporal regions compared with the other two groups. These deformities increased in severity with age. Quantitatively, ICV was significantly reduced (P < 0.05) by 7% in rabbits with early-onset synostosis compared with both control rabbits and rabbits with delayed-onset synostosis at 25 days of age. By 126 days of age, ICV in rabbits with synostosis was significantly reduced (p < 0.05) by 11% in early-onset synostosis and by 8% in delayed-onset synostosis compared with normal rabbits. Results suggest that in rabbits with uncorrected craniosynostosis, compensatory changes in the neurocranium were not adequate to allow normal expansion of the neurocapsular matrix. Further research is needed to determine if ICV reduction is correlated with cerebral atrophy or cerebral spinal fluid (i.e., ventricular or subarachnoid) space compression in this model. PMID:9693554

  1. 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

  2. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    PubMed

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. PMID:22024496

  3. Distribution of lactoferrin and 60/65 kDa heat shock protein in normal and inflamed human intestine and liver.

    PubMed Central

    Peen, E; Eneström, S; Skogh, T

    1996-01-01

    Immunisation against the mycobacterial heat shock protein (hsp-65) has been proposed to lead to production of autoantibodies against human lactoferrin. Such antibodies occur in ulcerative colitis and in primary sclerosing cholangitis. This study analysed the distribution of hsp-65 and lactoferrin in biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis and studied whether immunisation against mycobacterial hsp-65 resulted in production of antilactoferrin antibodies and vice versa. Polyclonal rabbit antihuman lactoferrin and monoclonal mouse anti-hsp-65 (ML30) were used for immunohistochemistry on biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis. Rats were immunised against human lactoferrin and mycobacterial hsp-65 respectively. Antibody measurements were done by enzyme immunosorbent assays. It was found that lactoferrin and hsp-60/65 were not codistributed. Lactoferrin was found on vascular endothelium and in nonparenchymal liver cells both in inflamed and uninflamed tissues, but only in the hepatocytes of inflamed liver. ML30 reactivity was not inhibited by antilactoferrin antibodies. Rat anti-hsp-65 serum had no detectable antilactoferrin antibodies. In conclusion, antilactoferrin antibodies probably do not arise by immunisation against mycobacterial hsp-65. Both nonparenchymal cells and hepatocytes probably participate in clearance of lactoferrin. Endothelial exposure of lactoferrin may have pathogenic implications in diseases with antilactoferrin autoantibodies. Images Figure 1 Figure 2 PMID:8566841

  4. Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

    PubMed Central

    Biermann, Jürgen; Wu, Kezhong; Odening, Katja E.; Asbach, Stefan; Koren, Gideon; Peng, Xuwen; Zehender, Manfred; Bode, Christoph; Brunner, Michael

    2010-01-01

    Transgenic rabbits expressing loss-of-function pore mutants of the human gene KCNQ1 (KvLQT1-Y315S) have a Long QT-Syndrome 1 (LQT1) phenotype. We evaluated for the first time the effect of nicorandil, an opener of ATP-sensitive potassium channels, and of isoproterenol on cardiac action potential duration and heart rate dependent dispersion of repolarisation in transgenic LQT1 rabbits. In vivo LQT1 and littermate control were subjected to transvenous electrophysiological studies; in vitro monophasic action potentials were recorded from explanted Langendorff-perfused hearts. In vivo ventricular effective refractory periods (VERP) at the right ventricular base were significantly prolonged in LQT1 as compared to littermate control, resulting in a more pronounced VERP dispersion in LQT1. This difference in VERP dispersion between LQT1 and littermate control disappeared after infusion of nicorandil. In vitro, mean action potential durations (APD75 and APD90) of LQT1 were significantly prolonged compared to littermate control at baseline. Nicorandil decreased APD75 and APD90 in LQT1 and littermate control at all stimulated heart rates. After adding nicorandil, the APD90 at all hearts rates and the APD75 at high heart rates were no longer different. Dispersion of repolarisation (ΔAPD75 and ΔAPD90) was heart rate dependently decreased after nicorandil at all tested stimulation cycle lengths only in LQT1. We demonstrated phenotypic differences of LQT1 and littermate control in vivo and in vitro. Nicorandil 20 μmol/l improved repolarisation abnormalities and heterogeneities in transgenic LQT1 rabbits. PMID:20959120

  5. 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. PMID:27262837

  6. [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

  7. 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.

  8. Comparable TNF-alpha, IFN-gamma and GM-CSF production by purified normal marrow CD3 cells in response to horse anti-lymphocyte and rabbit antithymocyte globulin.

    PubMed

    Piaggio, G; Podestá, M; Pitto, A; Pittaluga, G B; Isaza, A; Benvenuto, F; Bruno, B; Bacigalupo, A

    1998-04-01

    In vitro priming of T cell with horse antilymphocyte globulin (HALG) results in cytokine release, and this has been associated with its clinical efficacy in patients with severe aplastic anaemia (SAA). Rabbit antithymocyte globulin (RATG) has been studied less extensively. In this study we compare the in vitro priming effect of HALG and RATG on purified normal marrow T cells: end-points of the study were 1) levels of TNF-alpha (TNF-alpha), IFN-gamma (IFN-gamma) GM-CSF in T cell supernatants, and 2) effect of T cell supernatants on colony formation with or without exogenous GM-CSF TNF-alpha, IFN-gamma and GM-CSF levels were comparable for HALG, RATG and phytohaemagglutinin (PHA). T cell supernatants showed comparable enhancement of colony formation in the presence of recombinant human GM-CSF (rhGM-CSF) and supported colony forming unit granulomacrophage (CFU-GM) growth in the absence of growth factor. This study shows that horse and rabbit derived ALG/ATG and PHA have a comparable in vitro priming effect on T cells: both agents should probably be tested for their clinical efficacy in SAA patients. PMID:9579877

  9. Transgenic rabbits with lymphocytic leukemia induced by the c-myc oncogene fused with the immunoglobulin heavy chain enhancer.

    PubMed Central

    Knight, K L; Spieker-Polet, H; Kazdin, D S; Oi, V T

    1988-01-01

    Transgenic rabbits with the rabbit c-myc oncogene fused with the rabbit immunoglobulin heavy chain enhancer region (E mu) DNA were developed by microinjecting pronuclei of single cell zygotes with the gene construct and implanting the microinjected eggs into pseudopregnant females. At age 17-20 days, 3 of 21 offspring born to seven females were found to have peripheral blood leukocyte counts of greater than 100,000 per mm3. Histology analyses showed extensive lymphocytic infiltration in the liver and kidney, indicating that these rabbits had a malignant lymphocytic leukemia. Genomic DNA analyses of thymus and peripheral blood lymphocytes revealed that the leukemic rabbits were transgenic and that both immunoglobulin heavy and kappa light chain genes were rearranged in the leukemic cells; thus, the leukemic cells are of B-cell lineage. One to four heavy and light chain gene rearrangements were observed, suggesting that the B-cell tumors were oligoclonal. Stable tissue culture cell lines from the bone marrow and peripheral blood of one of the transgenic rabbits have been developed. The development of B-cell leukemias in rabbits with the E mu-myc transgene contrasts with the development of B-cell lymphomas in mice carrying a similar transgene. The lymphomas in mice develop in adults and are monoclonal in origin. The leukemias in rabbits develop in juveniles, less than 3 weeks after birth, and appear oligoclonal in origin. The leukemias seem to develop in rabbit at a specific stage of development, and we suggest that a normal developmental signal may be involved in the oncogenesis. Images PMID:2834733

  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. Quantitative analysis of real-time tissue elastography for evaluation of liver fibrosis

    PubMed Central

    Shi, Ying; Wang, Xing-Hua; Zhang, Huan-Hu; Zhang, Hai-Qing; Tu, Ji-Zheng; Wei, Kun; Li, Juan; Liu, Xiao-Li

    2014-01-01

    The present study aimed to investigate the feasibility of quantitative analysis of liver fibrosis using real-time tissue elastography (RTE) and its pathological and molecule biological basis. Methods: Fifty-four New Zealand rabbits were subcutaneously injected with thioacetamide (TAA) to induce liver fibrosis as the model group, and another eight New Zealand rabbits served as the normal control group. Four rabbits were randomly taken every two weeks for real-time tissue elastography (RTE) and quantitative analysis of tissue diffusion. The obtained twelve characteristic quantities included relative mean value (MEAN), standard deviation (SD), blue area % (% AREA), complexity (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT), entropy (ENT), inverse different moment (IDM), angular secon moment (ASM), correlation (CORR) and liver fibrosis index (LF Index). Rabbits were executed and liver tissues were taken for pathological staging of liver fibrosis (grouped by pathological stage into S0 group, S1 group, S2 group, S3 group and S4 group). In addition, the collagen I (Col I) and collagen III (Col III) expression levels in liver tissue were detected by Western blot. Results: Except for KURT, there were significant differences among the other eleven characteristic quantities (P < 0.05). LF Index, Col I and Col III expression levels showed a rising trend with increased pathological staging of liver fibrosis, presenting a positive correlation with the pathological staging of liver fibrosis (r = 0.718, r = 0.693, r = 0.611, P < 0.05). Conclusion: RTE quantitative analysis is expected for noninvasive evaluation of the pathological staging of liver fibrosis. PMID:24955175

  12. Diffuse fatty metamorphosis of a large, well-differentiated hepatocellular carcinoma originating in the normal liver: a case report and literature review.

    PubMed

    Komiyama, Satoshi; Okazaki, Hiroshi; Nakao, Satoshi; Nishigori, Shuhei; Terada, Masahiro; Hamanaka, Jun; Miura, Yuki; Oka, Hiroyuki; Suzaki, Fumio; Tanaka, Katsuaki

    2015-10-01

    Fatty changes are frequently observed in small, well-differentiated hepatocellular carcinomas (HCCs), but are rarely observed in large (over 30 mm in diameter) lesions. Here, we report a 76-year-old man who developed a large (58 mm in diameter), well-differentiated HCC with diffuse extensive fatty changes in the right lobe of the liver. He had no history of alcohol abuse, obesity, or hepatitis B or C infection, and no autoantibodies, but he did have type 2 diabetes. The serum alpha-fetoprotein level was within the normal range, and ultrasonography showed a round hyperechoic lesion. Dynamic contrast-enhanced computed tomography revealed a tumor with inhomogeneous low attenuation in the arterial, portal, and venous phases, mimicking an angiomyolipoma. The patient underwent central bisegmentectomy of the liver, and the histological diagnosis was well-differentiated HCC with diffuse extensive fatty changes. The surrounding non-cancerous area was normal. A review of the published literature found six published cases of large, well-differentiated HCC with extensive fatty changes. Unlike the patients in most previous reports, our patient did not have any underlying liver disease and had no history of alcohol abuse. PMID:26416601

  13. Outbreak of rabbit hemorrhagic disease in domestic lagomorphs.

    PubMed

    Campagnolo, Enzo R; Ernst, Mark J; Berninger, Mary L; Gregg, Douglas A; Shumaker, Thomas J; Boghossian, Aida M

    2003-10-15

    Rabbit hemorrhagic disease (RHD) was diagnosed in domestic lagomorphs on a rabbit farm in Illinois. Clinical signs of RHD in affected rabbits included signs of depression, anorexia, fever, paddling, convulsions, and sudden death. Findings of necropsies and histologic evaluations of specimens of liver and spleen were indicative of RHD. In liver specimens obtained from dead rabbits, RHD viral antigen was detected via hemagglutination assay and viral antigen-detection ELISA. The source of the outbreak was traced to a rabbitry in Utah. As the disease spread, the outbreak involved rabbits in various regions of the United States; > 4,800 rabbits were euthanatized and buried as a result of the depopulation effort in several states. The economic impact of the disease can be considerable; if the disease is suspected, it is imperative that the appropriate state or federal veterinarian's office be contacted immediately. PMID:14584745

  14. The amino acid sequence of the peptide containing the thiol group of creatine kinase from normal and dystrophic chicken breast muscle. Comparison of some of the immunological properties of the antibodies developed in rabbits against these enzymes

    PubMed Central

    Roy, Buddha P.

    1974-01-01

    The major 14C-labelled peptides from creatine kinase from normal and dystrophic chicken muscle obtained by carboxymethylating the reactive thiol groups with iodo[2-14C]acetic acid and digestion with trypsin were purified by ion-exchange chromatography on Dowex-50 (X2) and by paper electrophoresis. The chromatographic characteristics of the 14C-labelled peptides, their electrophoretic mobilities at pH6.5, and their amino acid compositions were identical for the two enzymes. The sequence of amino acids around the essential thiol groups of creatine kinase from normal and dystrophic chicken muscle was shown to be Ile-Leu-Thr-CmCys-Pro-Ser-Asn-Leu-Gly-Thr-Gly-Leu-Arg (CmCys, carboxymethylcysteine). This sequence is almost identical with that for the creatine kinases in human and ox muscle and bovine brain and is very similar to that of arginine kinase from lobster muscle. Antibodies to the enzymes were raised in rabbits and their reaction with the creatine kinase from normal and dystrophic muscles in interfacial, immunodiffusion and immunoelectrophoretic experiments was studied. The cross-reaction between normal muscle creatine kinase and antisera against the dystrophic muscle enzyme (or vice versa) observed by immunodiffusion and by immunoelectrophoretic experiments further suggests that the enzymes from normal and dystrophic chicken muscle are similar in structure. The results of the present study, the identical amino acid sequence of the peptides containing the reactive thiol group from both the normal and dystrophic chicken muscle enzymes and the immunological similarities of the two enzymes are in accord with the similarity of the two enzymes observed by Roy et al. (1970). ImagesPLATE 1 PMID:4219281

  15. Expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in the normal and cirrhotic human liver.

    PubMed Central

    Couvelard, A.; Scoazec, J. Y.; Feldmann, G.

    1993-01-01

    We compared the expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in normal human liver, in which the endothelial lining of hepatic sinusoids is discontinuous and devoid of basement membrane, and in cirrhosis, during which sinusoids might undergo a process of capillarization and acquire a continuous lining and a typical basement membrane. In normal liver, sinusoidal endothelial cells displayed a very restricted repertory of cell-adhesion molecules: the intercellular adhesion molecules PECAM-1 and CD34 were undetectable and only two integrins, alpha 1 beta 1 and alpha 5 beta 1, were present, whereas the laminin receptors alpha 6 beta 1 and alpha 2 beta 1 were undetectable and the beta 3 integrins were faintly expressed. In capillarized sinusoids, sinusoidal endothelial cells displayed striking changes in their repertory of cell-adhesion molecules, including the expression of PECAM-1 protein and messenger RNAs and the induction of the laminin receptors alpha 6 beta 1 and alpha 2 beta 1. Such changes co-localized with subendothelial laminin deposits. In conclusion, normal sinusoidal endothelial cells express a distinctive set of cell-adhesion molecules, adapted to their structural and microenvironmental characteristics, and this repertory is dramatically modified during sinusoidal capillarization, possibly as a consequence of the concomitant matrix changes. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8362973

  16. Accumulation of sup 125 I-factor XI in atheroma of rabbit with hereditary hyperlipidemia (WHHL-rabbit)

    SciTech Connect

    Komiyama, Y.; Masuda, M.; Murakami, T.; Nishikado, H.; Egawa, H.; Nishimura, T.; Morii, S.; Murata, K. )

    1989-10-01

    We have studied the turnover and accumulation of rabbit factor XI (F.XI) in atherosclerotic lesion in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit) to reveal the participation of blood coagulation in atherosclerotic lesion. Rabbit F.XI was iodinated and administered intravenously to WHHL rabbits and Japanese white rabbits. The turnover of {sup 125}I-rabbit F.XI was significantly faster in WHHL rabbits (T1/2 = 2.84 +/- 0.44 days) than in normal rabbits (T1/2 = 4.44 +/- 0.42 days). The thoracic aorta of WHHL rabbit was strongly labelled with {sup 125}I-rabbit F.XI, in sections obtained after 5 days by en-face autoradiography, whereas no radioactivity was detected in normal aorta. By an immunohistochemical study of WHHL rabbit aorta, we confirmed that many F.XI- and fibrin-related compounds existed in the atheroma, whereas albumin did not in these area. These results suggest that the activation of F.XI proceeds on the atherosclerotic lesions of WHHL rabbits.

  17. Pre-existing Epithelial Diversity in Normal Human Livers: A Tissue-tethered Cytometric Analysis in Portal/Periportal Epithelial Cells

    PubMed Central

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

    2012-01-01

    Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BEC). 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 pre-existing 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 pre-existed 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. scatter plots) 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. Results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bi-potential 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. Conclusion Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable pre-existent hybrid epithelial diversity in normal human liver. This computationally-enabled tissue analysis approach offers much broader potential beyond the results presented here. PMID:23150208

  18. 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. PMID:27605807

  19. Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

    SciTech Connect

    Overturf, M.L.; Smith, S.A.; Hewett-Emmett, D.; Loose-Mitchell, D.S.; Soma, M.R.; Gotto, A.M. Jr.; Morrisett, J.D. )

    1989-02-01

    A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more {sup 125}I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group.

  20. 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

  1. An investigation of the pharmacological response to vitamin K1 in the rabbit.

    PubMed Central

    Winn, M. J.; Cholerton, S.; Park, B. K.

    1988-01-01

    1. The relationship between pharmacological response and disposition of a dose of vitamin K1 (10 mgkg-1, i.v.) in normal rabbits and in rabbits treated with the coumarin anticoagulant brodifacoum, has been studied. 2. High performance liquid chromatography (h.p.l.c.) with electrochemical detection (EC) was used to determine concentrations of vitamin K1 in plasma, whole liver homogenate, and liver microsomes. 3. After intravenous administration of vitamin K1, plasma concentrations of the vitamin declined in a tri-exponential fashion. There were no differences between the two groups over the first 24 h of the experiment. However, between 24 h and the end of the study, plasma concentrations of vitamin K1 in the presence of brodifacoum were significantly (P less than or equal to 0.05) below those of vehicle-treated rabbits. 4. Seventy-two hours after administration of vitamin K1, plasma concentrations of the vitamin were not different from normal. 5. Three hours after administration of vitamin K1, the concentrations of the vitamin in whole liver were 46.6 +/- 4.3 micrograms g-1 in the presence of brodifacoum, and 32.8 +/- 6.4 micrograms g-1 in the absence of brodifacoum; and were significantly (P less than or equal to 0.05) greater than normal (127.7 +/- 44.3 ng g-1). Likewise, microsomal concentrations of vitamin K1 (4.00 +/- 2.38 micrograms mg-1 protein, and 2.65 +/- 1.01 micrograms mg-1 protein, in the presence and absence of brodifacoum, respectively) were significantly (P less than or equal to 0.01) greater than normal (16.0 +/- 3.5 ng mg-1 protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207975

  2. 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

  3. Influence of N,N-dimethylaniline on the association of phenobarbital-induced cytochrome P-450 and NADPH-cytochrome c(P-450) reductase in a reconstituted rabbit liver microsomal enzyme system.

    PubMed

    Hlavica, P; Golly, I; Wolf, J

    1987-09-01

    N,N-Dimethylaniline when added to reaction mixtures provokes deviation from Michaelis-Menten law of the interaction kinetics of NADPH-cytochrome c(P-450) reductase (NADPH:ferrihaemoprotein oxidoreductase, EC 1.6.2.4) with highly purified phenobarbital-induced rabbit liver microsomal cytochrome P-450 (P-450LM2). This phenomenon is not associated with the low-to-high spin transition in the iron-coordination sphere of the haemoprotein, as elicited by the arylamine. Substrate-triggered departure from linearity of the kinetics is abolished by inclusion into the assay media of p-chloromercuribenzoate, hinting at a vital role in the process of thiols. Similarly, the parabolic progress curve (nH = 1.7) is transformed to a straight line (nH = 1.01) when the N-terminal reductase-binding domain in the P-450LM2 molecule is selectively blocked through covalent attachment of fluorescein isothiocyanate (FITC); such a modification does not alter the affinity of the haemoprotein for the amine substrate. Steady-state fluorescence polarization measurements reveal that N,N-dimethylaniline perturbs the motional properties of the fluorophore-bearing reductase-binding region, suggesting the induction of a conformational change. Summarizing these results, the data possibly indicate N,N-dimethylaniline-induced cooperativity in the association of reductase with P-450LM2. PMID:3113486

  4. Age- and Gender Dependent Liver Fat Content in a Healthy Normal BMI Population as Quantified by Fat-Water Separating DIXON MR Imaging

    PubMed Central

    Ulbrich, Erika J.; Fischer, Michael A.; Manoliu, Andrei; Marcon, Magda; Luechinger, Roger; Nanz, Daniel; Reiner, Caecilia S.

    2015-01-01

    Objectives To establish age- and sex-dependent values of magnetic resonance (MR) liver fat-signal fraction (FSF) in healthy volunteers with normal body-mass index (BMI). Methods 2-point mDIXON sequences (repetition time/echo time, 4.2msec/1.2msec, 3.1msec) at 3.0 Tesla MR were acquired in 80 healthy volunteers with normal BMI (18.2 to 25.7 kg/m2) between 20 and 62 years (10 men/10 women per decade). FSF was measured in 5 liver segments (segment II, III, VI, VII, VIII) based on mean signal intensities in regions of interest placed on mDIXON-based water and fat images. Multivariate general linear models were used to test for significant differences between BMI-corrected FSF among age subgroups. Pearson and Spearman correlations between FSF and several body measures were calculated. Results Mean FSF (%) ± standard deviations significantly differed between women (3.91 ± 1.10) and men (4.69 ± 1.38) and varied with age for women/men (p-value: 0.002/0.027): 3.05 ± 0.49/3.74 ± 0.60 (age group 20–29), 3.75 ± 0.66/4.99 ± 1.30 (30–39), 4.76 ± 1.16/5.25 ± 1.97 (40–49) and 4.09 ± 1.26/4.79 ± 0.93 (50–62). FSF differences among age subgroups were significant for women only (p = 0.003). Conclusions MR-based liver fat content is higher in men and peaks in the fifth decade for both genders. PMID:26554709

  5. Enhancing HOTAIR/MiR-10b Drives Normal Liver Stem Cells Toward a Tendency to Malignant Transformation Through Inducing Epithelial- to-Mesenchymal Transition.

    PubMed

    Ye, Ping; Wang, Tao; Liu, Wei-Hui; Li, Xiu-Chuan; Tang, Li-Jun; Tian, Fu-Zhou

    2015-08-01

    Previously, other groups and our team consistently have demonstrated that the possible origination of liver cancer stem cells (LCSCs) is the malignant transformation from liver normal stem cells (LNSCs). However, this complex and multi-step process is far from clear due to the accumulation of various gene dysregulations. Because non-coding RNAs (ncRNAs) could regulate multiple genes, a family of genes, and even whole chromosomes, this study further investigated the effect of dysregulated short ncRNA microRNA-10b and long ncRNA HOX transcript antisense RNA (HOTAIR) between LNSCs and LCSCs on phenotype reversion. To clarify the role of ncRNA in malignant transformation of LNSCs, we used lentivirus transduction to enhance the miR-10b and HOTAIR expression levels in our previously isolated rat LNSCs. The malignant abilities of proliferation, invasiveness, and tumorigenesis were observed and compared in cells before and after ncRNAs enhancement. After microRNA-10b and HOTAIR were enhanced separately, several cancer stem cell (CSC)-like traits appeared in these LNSCs, including in vitro-enhanced proliferative capacity, expression of putative LCSC markers, progressive invasive ability, and even in vivo aggravation into and taking the place of normal liver tissue. Furthermore, strengthened expression of these ncRNAs partially degraded E-cadherin in LNSCs, which is one of the classic markers in epithelial-to-mesenchymal transition (EMT). HOTAIR or miR-10b enhanced in LNSCs may drive the LNSCs to a tendency toward malignant transformation. This study partially uncovers the mechanism by which miR-10b or HOTAIR promotes malignant transformation of LNSCs through down-regulating E-cadherin and inducing EMT. PMID:25708830

  6. Liver Panel

    MedlinePlus

    ... liver; the best test for detecting hepatitis Alkaline phosphatase (ALP) – an enzyme related to the bile ducts ... only moderately elevated or close to normal. Alkaline phosphatase (ALP) ALP may be significantly increased with obstructed ...

  7. Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease

    PubMed Central

    Zhu, Gui-Qi; Braddock, Martin; Zhang, Dong-Chu; Shi, Ke-Qing; Song, Dan; Zheng, Ming-Hua

    2016-01-01

    Objectives Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD. Methods A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference. Results The prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD. Conclusions Increased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors. PMID:26735337

  8. Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

    PubMed Central

    Zhu, Pei-Li; Pan, Si-Yuan; Zhou, Shu-Feng; Zhang, Yi; Wang, Xiao-Yan; Sun, Nan; Chu, Zhu-Sheng; Yu, Zhi-Ling; Ko, Kam-Ming

    2015-01-01

    Background Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice. Methods Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%−9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured. Results Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF

  9. Stannous chloride induces alterations in enzyme activities, lipid peroxidation and histopathology in male rabbit: antioxidant role of vitamin C.

    PubMed

    El-Demerdash, F M; Yousef, M I; Zoheir, Malak A

    2005-12-01

    Stannous chloride (SnCl2) is widely used in daily human life to conserve soft drinks, in food manufacturing and biocidal preparations. It had genotoxicity, immunotoxicity, neurotoxicity and oxidative stress. Therefore, the present experiment was carried out to determine the effectiveness of l-ascorbic acid (AA) in alleviating the toxicity of SnCl2 on some enzyme activities and oxidative damage in male New Zealand white rabbits. Six rabbits per group were assigned to 1 of 4 treatment groups: 0 mg AA and 0 mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20 mg SnCl2/kg BW (1/500 LD50); 20 mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Liver and kidney specimens were processed for histopathologic studies. Results obtained showed that SnCl2 significantly (P < 0.05) induced free radicals in rabbit liver, testes, kidney, lung, brain and heart. While, the activity of glutathione S-transferase (GST) and the level of sulfhydryl groups (SH-group) were decreased (P < 0.05) in all tested organs except brain and heart. Aspartate aminotransferase (AST) activity was increased (P < 0.05) in liver and decreased in testes, but alanine aminotransferase (ALT) did not change. The activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) were decreased (P < 0.05) in liver, testes, kidney and lung. Also, the activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma of rabbits treated with SnCl2 compared to control group. Histopathologic studies showed marked changes in hepatocytes as well as proliferation of duct epithelium, dilatation and congestion of blood vessels as well as mononuclear inflammatory infiltrate. The kidney were also severely affected by SnCl2 the Bowman's space was increased, with infiltration of renal parenchyma by mononuclear inflammatory infiltrate and changes in cells lining convoluted tubule. Ascorbic acid alone significantly decreased the levels of free radicals

  10. 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

  11. 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. PMID:2927083

  12. Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

    PubMed

    Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

    2003-05-01

    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

  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. PMID:23474012

  14. 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

  15. Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

    PubMed Central

    Oniki, Kentaro; Saruwatari, Junji; Izuka, Tomoko; Kajiwara, Ayami; Morita, Kazunori; Sakata, Misaki; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

    2015-01-01

    In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11–8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction. PMID:26200108

  16. 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. PMID:23642871

  17. 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

  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. 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

  20. 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. PMID:26960981

  1. 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. J. Med. Virol. 88:681-685, 2016. © 2015 Wiley Periodicals, Inc. PMID:26334930

  2. Hypocholesterolemic and Antiatherosclerotic Potential of Basella alba Leaf Extract in Hypercholesterolemia-Induced Rabbits.

    PubMed

    Baskaran, Gunasekaran; Salvamani, Shamala; Azlan, Azrina; Ahmad, Siti Aqlima; Yeap, Swee Keong; Shukor, Mohd Yunus

    2015-01-01

    Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis. PMID:26697097

  3. Hypocholesterolemic and Antiatherosclerotic Potential of Basella alba Leaf Extract in Hypercholesterolemia-Induced Rabbits

    PubMed Central

    Baskaran, Gunasekaran; Salvamani, Shamala; Azlan, Azrina; Ahmad, Siti Aqlima; Yeap, Swee Keong; Shukor, Mohd Yunus

    2015-01-01

    Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis. PMID:26697097

  4. 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.

  5. Autoimmunity in Experimental Trypanosoma congolense Infections of Rabbits 1

    PubMed Central

    Mansfield, John M.; Kreier, Julius P.

    1972-01-01

    Autoimmunity in rabbits with experimental Trypanosoma congolense infections was investigated. Complement-fixing (CF) and precipitating autoantibodies to normal allogeneic and autologous tissues were found in the sera of all infected rabbits tested; the titers of CF autoantibody occurring during infection were significantly higher than normally occurring titers of autoantibody in pre-infection serum samples. Autoantibody did not cross-react with trypanosome antigens, and Wassermann antibody was not detected in normal or infected rabbit sera. Passive transfer of autoantibody to normal rabbits did not produce observable pathology or death. Physicochemical methods of analysis revealed that the autoantibody was exclusively of the immunoglobulin M class. That cell-mediated autoimmunity to normal tissue antigens did not occur during T. congolense infections was shown by histological analyses, skin tests, migration inhibitory factor, and skin reactive factor tests. Images PMID:4629248

  6. The effects of fermented wheat powder (Lisosan G) on the blood lipids and oxidative status of healthy rabbits.

    PubMed

    Pozzo, Luisa; Vizzarri, Francesco; Ciardi, Marco; Nardoia, Maria; Palazzo, Marisa; Casamassima, Donato; Longo, Vincenzo

    2015-10-01

    A number of studies have shown that whole grain products have strong antioxidant effects. Lisosan G, a powder produced from the fermentation of Triticum aestivum, has shown hepatoprotective effects. The aim of this paper was to evaluate the effects of Lisosan G on the serum lipid profile and oxidative status of healthy rabbits. Forty rabbits were fed either a normal diet or a diet containing 10 g, 20 g or 30 g Lisosan G/kg of feed for 60 days. The supplementation of Lisosan G did not cause any alteration of the aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin or creatinine concentrations, but caused a reduction in triglycerides, in low density lipoprotein (LDL) cholesterol, and an increase in high density lipoprotein (HDL) cholesterol. The antioxidant activity of Lisosan G has been confirmed on the basis of the reduction in the blood reactive oxygen metabolites (ROMs) and in the level of the thiobarbituric acid reactive substances (TBARS) together with increased vitamin A and E concentrations in the blood. Moreover, Lisosan G also caused the induction of antioxidant enzymes in the liver and kidney of the treated rabbits. This study has shown the ability of Lisosan G to improve the lipid profile and antioxidant status of the blood in healthy rabbits. PMID:26188178

  7. Heparin Saline Versus Normal Saline for Flushing and Locking Peripheral Venous Catheters in Decompensated Liver Cirrhosis Patients: A Randomized Controlled Trial.

    PubMed

    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

    2015-08-01

    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

  8. 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.

  9. 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

  10. Cysticercosis in laboratory rabbits.

    PubMed

    Owiny, J R

    2001-03-01

    There are no data on the current incidence of Taenia pisiformis in laboratory rabbits. Two cases of cysticercosis most likely due to T. pisiformis in laboratory rabbits (intermediate host) are presented. Both rabbits had no contact with dogs (final host); their caretakers did not work with dogs, and these caretakers changed into facility scrubs and wore gloves when working with the rabbits. Rabbit 1 may have been infected after being fed hay at our facility. In light of the life cycle of the parasite and the history of rabbit 2, it potentially could have been infected prior to arrival at our facility. There have been only three cases of tapeworm cysts in rabbits in our facility (average daily census, 250) during the last 10 years (incidence, < 1%). This report indicates that although cysticercosis is rare in laboratory rabbits, one should always be aware of such incidental findings. Although it may not produce overt illness in the rabbit, hepatic migration could adversely affect the outcome of some experimental procedures PMID:11300689

  11. Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: Do they differ from obese or overweight non-alcoholic fatty liver disease?

    PubMed Central

    Kumar, Ramesh; Rastogi, Archana; Sharma, Manoj Kumar; Bhatia, Vikram; Garg, Hitendra; Bihari, Chhagan; Sarin, Shiv Kumar

    2013-01-01

    Background: Obesity is an important risk factor for non-alcoholic fatty liver disease (NAFLD); however, NAFLD does occur in lean subjects. This study was aimed to evaluate the magnitude, clinical, pathological, and metabolic profiles of NAFLD in normal body mass index (BMI) subjects (defined as lean NAFLD) in comparison to overweight or obese NAFLD and lean healthy control. Materials and Methods: 336 subjects (205 consecutive NAFLD, and 131 healthy controls) were studied. Results: Among 205 NAFLD patients, 27 (13.2%) were lean, while 141 (68.8%) and 37 (18%) patients were obese and overweight, respectively. The lean NAFLD compared to obese NAFLD had significantly lesser degree of fasting hyperinsulinemia (P < 0.001), homeostasis model assessment insulin resistance (HOMA-IR, P < 0.001), and lower prevalence of diabetes mellitus (P = 0.01) and metabolic syndrome (P < 0.001). The profiles of serum lipids were similar between all 3 BMI categories, and 89% of lean NAFLD were dyslipidemic. Compared to obese subjects, patients with lean NAFLD had less hepatic necro-inflammation (P = 0.05) and fibrosis (P < 0.001). However, the proportion of steatohepatitis and advanced fibrosis were similar between all BMI categories. The profiles of overweight NAFLD were similar to those of lean NAFLD, except for higher HOMA-IR, uric acids and male gender in overweight group. Despite being lean, the mean BMI of lean NAFLD were still higher than unselected lean healthy controls (P = 0.02). Conclusions: Lean NAFLD patients have less severe disease, minor, or no insulin resistance, but are frequently dyslipidemic and have BMI higher than lean healthy control. PMID:23961483

  12. 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

  13. 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

  14. Development and implementation of a stereoselective normal-phase liquid chromatography-tandem mass spectrometry method for the determination of intrinsic metabolic clearance in human liver microsomes.

    PubMed

    Zhang, Yingru; Caporuscio, Christian; Dai, Jun; Witkusa, Michael; Rose, Anne; Santella, Joseph; D'Arienzo, Celia; Wang-Iverson, David B; Tymiak, Adrienne A

    2008-11-01

    The stereoselective determination of stereoisomers in biological samples provides vital information on stereospecific metabolism and pharmacokinetic profiles of the drugs. Despite the unique advantage and the great success of normal-phase (NP) HPLC for the separations of drug stereoisomers using polysaccharide-type chiral stationary phases (CSPs), the technique is rarely applied to quantitative HPLC-MS-MS bioanalysis. This is, at least in part, due to the incompatibility between the usual mobile phase (n-hexane or n-heptane) in normal-phase HPLC and the MS ionization sources which poses a potential detonation hazard. An environmentally friendly and nonflammable alternative solvent, ethoxynonafluorobutane (ENFB), was reported previously to potentially provide an ideal solution for combining the powers of stereoselective NP chromatographic separation and MS-MS detection. In this study, a stereoselective NP-HPLC-MS-MS method was developed using ENFB to quantify a pair of Bristol Myers Squibb (BMS) proprietary drug stereoisomers and their ketone metabolite for an in vitro study, which demonstrated, for the first time, the practical applicability and utility of ENFB for bioanalysis in pharmaceutical industry. The effects of different organic modifiers and temperature, as well as the comparison between ENFB and the usual solvent, heptane, for the separation, are discussed. The resolution of the stereoisomers was achieved using 63% of 3:1 mixture of ethanol and methanol with 37% ENFB on a Chiralpak AD-H column at 50 degrees C. High sensitivity was obtained using the MS-MS detection in the positive ion atmospheric pressure chemical ionization (APCI) mode. The lower limit of quantitation (LLOQ) for the first stereoisomer and the ketone metabolite was 5 ng/mL, and was 10 ng/mL for the second isomer in the human liver microsome-potassium phosphate buffer matrix. The linear dynamic range of 5-1000 ng/mL for both isomers and 10-1000 ng/mL for the metabolite were demonstrated

  15. Astroviruses in Rabbits

    PubMed Central

    Moschidou, Paschalina; Pinto, Pierfrancesco; Catella, Cristiana; Desario, Constantina; Larocca, Vittorio; Circella, Elena; Bànyai, Krisztian; Lavazza, Antonio; Magistrali, Chiara; Decaro, Nicola; Buonavoglia, Canio

    2011-01-01

    By screening rabbits with enterocolitis or enteritis complex and asymptomatic rabbits, we identified a novel astrovirus. The virus was distantly related (19.3%–23.7% aa identity) in the capsid precursor to other mammalian astroviruses within the Mamastrovirus genus. By using real-time reverse transcription PCR, with specific primers and probes and targeting a conserved stretch in open reading frame 1b, we found rabbit astrovirus in 10 (43%) of 23 samples from animals with enteric disease and in 25 (18%) of 139 samples from asymptomatic animals in Italy during 2005–2008. The mean and median titers in the positive animals were 102× and 103× greater, respectively, in the symptomatic animals than in the asymptomatic animals. These findings support the idea that rabbit astroviruses should be included in the diagnostic algorithm of rabbit enteric disease and animal experiments to increase information obtained about their epidemiology and potential pathogenic role. PMID:22172457

  16. Nitrosylation of rabbit ferrous heme-hemopexin.

    PubMed

    Fasano, Mauro; Bocedi, Alessio; Mattu, Marco; Coletta, Massimo; Ascenzi, Paolo

    2004-10-01

    Hemopexin (HPX) serves as a trap for toxic plasma heme, ensuring its complete clearance by transportation to the liver. Moreover, HPX-heme has been postulated to play a key role in the homeostasis of nitric oxide (NO). Here, the thermodynamics for NO binding to rabbit ferrous HPX-heme as well as the EPR and optical absorption spectroscopic properties of rabbit ferrous nitrosylated HPX-heme (HPX-heme-NO) are reported. The value of the dissociation equilibrium constant for NO binding to rabbit ferrous HPX-heme (i.e., H) is (1.4+/-0.2)x10(-7) M, at pH 7.0 and 10.0 degrees C; the value of H is unaffected by sodium chloride. At pH 7.0, rabbit ferrous HPX-heme-NO is a six-coordinate heme-iron species, characterized by an X-band EPR spectrum with an axial geometry and by epsilon=146 mM(-1) cm(-1) at 419 nm. At pH 4.0, rabbit ferrous HPX-heme-NO is a five-coordinate heme-iron species, characterized by an X-band EPR spectrum with three-line splitting centered at 334 mT and by epsilon=74 mM(-1) cm(-1) at 387 nm. The p K(a) value of the reversible pH-induced six- to five-coordinate spectroscopic transition is 4.8+/-0.1 in the absence of sodium chloride and 4.3+/-0.1 in the presence of 1.5x10(-1) M sodium chloride. This result is in agreement with the effect of sodium chloride on rabbit HPX-heme stability. The present data have been analyzed in parallel with those of a related heme model compound and heme-protein systems. PMID:15378409

  17. Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model.

    PubMed

    Chen, Jeane; White, Sarah B; Harris, Kathleen R; Li, Weiguo; Yap, Jonathan W T; Kim, Dong-Hyun; Lewandowski, Robert J; Shea, Lonnie D; Larson, Andrew C

    2015-08-01

    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 h. 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

  18. 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

  19. Effect of anaesthesia on insulin-induced hypoglycemia in rabbits.

    PubMed

    Haynes, F J; Cheema-Dhadli, S; Halperin, R M; Zettle, R; Robinson, L; Halperin, M L

    1988-12-01

    The aim of this study was to determine how anaesthetized rabbits survive much longer than awake rabbits after receiving an insulin overdose. Insulin appeared to act in both groups of rabbits because there was a prompt fall in circulating glucose, free fatty acids, and beta-hydroxybutyrate concentrations. Carbohydrate appeared to be the principal energy source for anaesthetized rabbits because their respiratory quotient approached unity. Although the fall in glycemia was similar in both groups of rabbits, the circulating lactate concentration rose only in the anaesthetized group. This rise in lactate in the initial 60 min after insulin was given could account for most of the fall in glycemia if the source of lactate was the glucose pool. The decline in hepatic glycogen was close to 100 mumol/g liver; this would account for about one-third of the total energy turnover and close to one-half of the measured glucose appearance in these anaesthetized rabbits. As judged from the rate of oxygen consumption, muscle glycogen seemed to supply two-thirds of the fuel to be oxidized in these rabbits. However, only one-third of the lactate released from muscle was first converted to glucose and the remainder was oxidized directly to CO2. Although insulin provided the metabolic setting for a rapid rate of glucose oxidation, this rate appeared to be diminished when the overall rate of oxygen consumption was lower during anaesthesia. PMID:3067835

  20. 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. PMID:27147250

  1. A rabbit ear model for cold stress testing.

    PubMed

    Smith, T L; Gordon, S; Holden, M B; Smith, B P; Russell, G B; Koman, L A

    1994-01-01

    A rabbit ear model resembling the human digit was studied to determine the vascular response of the rabbit ear to a cold stress. Following moderate cooling (10 minutes at 5 degrees - 8 degrees C), auricular blood flow and cutaneous perfusion were reduced. This decrease was reversed by 30 minutes of warming. The response in the rabbit ear to cold stress is similar to that of normal human digits. The similarities between the control of the circulation in human digits and rabbit ears may result from the similarities in digital and auricular vascular receptors and receptor subtypes. Verification of the rabbit model provides an experimental method for obtaining important data regarding digital pathophysiology and the treatment of cold intolerance. Further study with this model will provide clinically relevant information regarding the pathophysiology of digital thermoregulatory abnormalities. PMID:7830538

  2. 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. PMID:26973070

  3. Vitamin D plasma binding protein. Turnover and fate in the rabbit.

    PubMed Central

    Haddad, J G; Fraser, D R; Lawson, D E

    1981-01-01

    The metabolic disposition of the plasma binding protein (DBP) for vitamin D and its metabolites was studied in adult rabbits. Apo-DBP was purified from rabbit plasma and enzymatically labeled with radioiodine. The radioiodine-labeled protein retained its ability to bind vitamin D sterols and its physicochemical properties. When 125I-labeled DBP and 131I-labeled rabbit albumin were simultaneously injected intravenously, the 125I was cleared from plasma at a faster rate (t 1/2 = 1.7 d) than 131I (t 1/2 = 5 d) and 125I was present in excess of 131I in kidney, liver, skeletal muscle, heart, lung, intestine, testis, and bone 1 h after injection. In contrast to DBP, 25(OH)D3 was cleared more slowly (t 1/2 = 10.7 d). Compared to albumin, DBP radioactivity appeared earlier and in greater quantity in the urine of catheterized rabbits. Gel filtration analyses of plasma revealed most of the 125I to elute in the position of DBP, with only small amounts in the less than 1,000-dalton region. In contrast, almost all of the urine 125I eluted in this small molecular weight fraction. The molar ratio of DBP to 25(OH)D3 in normal rabbit plasma was 138/1. The extravascular pool of DBP was calculated to be 1.5-2.4 times larger than the intravascular DBP pool, and the molar replacement rate of DBP was 1,350-fold higher than that of 25(OH)D3. The plasma disappearance curves of holo-DBP, prepared either by saturating with 25(OH)D3 or by covalently linking 3 beta-bromoacetoxy-25(OH)D3, were very similar to that of apo-DBP. Neuraminidase treatment of DBP did not alter its plasma survival. These studies indicate that DBP or DBP-25(OH)D3 complex is removed from plasma by a variety of tissues, that the DBP moiety is degraded during this process, and that a significant recirculation of 25(OH)D3 probably occurs. The molar excess of DBP to 25(OH)D3 in plasma, and the relatively rapid turnover of DBP indicate that a high capacity, high affinity, and dynamic transport mechanism for vitamin D sterols

  4. Liver Cancer

    MedlinePlus

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  5. Liver scan

    MedlinePlus

    ... hyperplasia or adenoma of the liver Abscess Budd-Chiari syndrome Infection Liver disease (such as cirrhosis or ... Amebic liver abscess Cirrhosis Hepatic vein obstruction (Budd-Chiari) Hepatitis Liver cancer - hepatocellular carcinoma Liver disease Splenic ...

  6. 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.

  7. Novel bocaparvoviruses in rabbits.

    PubMed

    Lanave, G; Martella, V; Farkas, S L; Marton, S; Fehér, E; Bodnar, L; Lavazza, A; Decaro, N; Buonavoglia, C; Bányai, K

    2015-11-01

    Bocaparvovirus is a newly established genus within the family Parvoviridae and has been identified as a possible cause of enteric, respiratory, reproductive/neonatal and neurological disease in humans and several animal species. In this study, metagenomic analysis was used to identify and characterise a novel bocaparvovirus in the faeces of rabbits with enteric disease. To assess the prevalence of the novel virus, rectal swabs and faecal samples obtained from rabbits with and without diarrhoea were screened with a specific PCR assay. The complete genome sequence of the novel parvovirus was reconstructed. The virus was distantly related to other bocaparvoviruses; the three ORFs shared 53%, 53% and 50% nucleotide identity, respectively, to homologous genes of porcine bocaparvoviruses. The virus was detected in 8/29 (28%) and 16/95 (17%) samples of rabbits with and without diarrhoea, respectively. Sequencing of the capsid protein fragment targeted by the diagnostic PCR identified two distinct bocaparvovirus populations/sub-types, with 91.7-94.5% nucleotide identity to each other. Including these novel parvoviruses in diagnostic algorithms of rabbit diseases might help inform their potential pathogenic role and impact on rabbit production and the virological profiles of laboratory rabbits. PMID:26383859

  8. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B

    SciTech Connect

    Thompson, A.R. Puget Sound Blood Center, Seattle, WA ); Darlington, G. ); Armentano, D.; Woo, S.L.C.

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. The authors report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently {gamma}-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  9. [Dietotherapy children with liver diseases].

    PubMed

    Pavlovskaia, E V; Strokova, T V; Topil'skaia, N V; Isakova, V A

    2009-01-01

    In children with liver diseases disorders of the nutritional status appear more quickly and delay normal growth and development. Administration of the nutritional support based on nosological and syndromal approaches lets provide optimal conditions for normalization of the liver functions, improves efficiency of therapy and prognosis of the disease. The article contents modern recommendations on the organization of nutrition in children with different liver diseases, correction of metabolic disorders during complications of liver pathology. PMID:20120964

  10. Viral diseases of the rabbit.

    PubMed

    Krogstad, Aric P; Simpson, Janet E; Korte, Scott W

    2005-01-01

    Viral disease in the rabbit is encountered infrequently by the clinical practitioner; however, several viral diseases were reported to occur in this species. Viral diseases that are described in the rabbit primarily may affect the integument, gastrointestinal tract or, central nervous system or maybe multi-systemic in nature. Rabbit viral diseases range from oral papillomatosis, with benign clinical signs, to rabbit hemorrhagic disease and myxomatosis, which may result in significant clinical disease and mortality. The wild rabbit may serve as a reservoir for disease transmission for many of these viral agents. In general, treatment of viral disease in the rabbit is supportive in nature. PMID:15585192

  11. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  12. Cysticercus fasciolaris infection induced oxidative stress and apoptosis in rat liver: a strategy for host-parasite cross talk.

    PubMed

    Giri, Bikash Ranjan; Roy, Bishnupada

    2016-07-01

    Parasitic helminths have developed various strategies to induce or inhibit apoptosis in the cells of their host, thereby modulating the host's immune response and aiding dissemination to the host. Cysticercus fasciolaris, the larval form of Taenia taeniaeformis, parasitized different intermediate hosts like rats, rabbits, etc. and is cosmopolitan in distribution. In the present study, we have investigated host-parasite interactions and the resulting effect of C. fasciolaris in the liver of rat. Histology of the infected livers showed dilation and damages of hepatic cells near the parasite. Infected liver cells showed an increase in DNA fragmentation and chromatin condensation compared to the normal liver. Acridine orange and ethidium bromide dual staining revealed the presence of apoptotic cells in the infected liver. The decline in the mitochondrial membrane potential in the infected liver suggested that the observed apoptosis is mitochondria mediated. Occurrence of an elevated level of active executioner caspases 3/7 in the infected rat liver further confirms the occurrence of apoptosis. Different antioxidant enzymes were also evaluated and revealed a notable decline in the level of glutathione and glutathione-S-transferase activity leading to the augmented generation of reactive oxygen species. Results of the present study revealed that C. fasciolaris infection leads to apoptosis in the liver of rats which may be a surviving strategy for the parasitic larvae. PMID:26987645

  13. A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. II. Intracranial contents, intracranial volume, and intracranial pressure.

    PubMed

    Mooney, M P; Siegel, M I; Burrows, A M; Smith, T D; Losken, H W; Dechant, J; Cooper, G; Fellows-Mayle, W; Kapucu, M R; Kapucu, L O

    1998-06-01

    This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis, and this second part presents neuropathological findings and age-related changes in intracranial volume (ICV) and intracranial pressure (ICP) in 106 normal rabbits and 56 craniosynostotic rabbits from this colony. Brain morphology and anteroposterior length were described in 44 rabbit fetuses and perinates (27 normal; 17 synostosed). Middle meningeal artery patterns were qualitatively assessed from 2-D PCC MRI VENC scans and endocranial tracings from 15, 126-day-old rabbits (8 normal, 7 rabbits with unicoronal synostosis). Brain metabolism was evaluated by assessing 18F-FDG uptake with high-resolution PET scanning in 7, 25-day-old rabbits (3 normal, 4 with unicoronal or bicoronal synostosis). Intracranial contents and ICV were assessed using 3-D CT scanning of the skulls of 30 rabbits (20 normal,10 with unicoronal synostosis) at 42 and 126 days of age. Serial ICP data were collected from 66 rabbits (49 normal; 17 with unicoronal synostosis) at 25 and 42 days of age. ICP was assessed in the epidural space using a Codman NeuroMonitor microsensor transducer. Results revealed that cerebral cortex morphology was similar between normal and synostosed fetuses around the time of synostosis. Significantly (P<0.05) decreased A-P cerebral hemisphere growth rates and asymmetrical cortical remodeling were noted with increasing age in synostotic rabbits. In addition, rabbits with unicoronal suture synostosis exhibited asymmetrical middle meningeal artery patterns, decreased and asymmetrical brain metabolism, a "beaten-copper" intracranial appearance, significantly (P<0.05) decreased ICV, and significantly (P<0.01) elevated ICP compared with normal control rabbits. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light

  14. Influence of prednisolone on antipyrine and chloramphenicol disposition in rabbits.

    PubMed

    Shukla, V K; Garg, S K; Mathur, V S

    1984-01-01

    A study was conducted to see the effect of 15- and 30-day corticosteroid therapy (prednisolone 0.25 mg/kg/day) on the metabolism of antipyrine and chloramphenicol in rabbits. Antipyrine and chloramphenicol were given to rabbits orally at doses of 20 and 50 mg/kg, respectively on days 0, 15 and 30 of prednisolone therapy. The half-life of antipyrine and chloramphenicol were significantly reduced (p less than 0.05) after 15 and 30 days of the corticosteroid therapy. It is concluded that this effect might be due to the induction of liver microsomal enzymes. PMID:6473505

  15. Percutaneous Ultrasound Guided Implantation of VX2 for Creation of a Rabbit Hepatic Tumor Model

    PubMed Central

    White, Sarah B.; Chen, Jeane; Gordon, Andrew C.; Harris, Kathleen R.; Nicolai, Jodi R.; West, Derek L.; Larson, Andrew C.

    2015-01-01

    Creation of a VX2 tumor model has traditionally required a laparotomy and surgical implantation of tumor fragments. Open surgical procedures are invasive and require long procedure times and recovery that can result in post-operative morbidity and mortality. The purpose of this study is to report the results of a percutaneous ultrasound guided method for creation of a VX2 model in rabbit livers. A total of 27 New Zealand white rabbits underwent a percutaneous ultrasound guided approach, where a VX2 tumor fragment was implanted in the liver. Magnetic resonance imaging was used to assess for tumor growth and necropsy was performed to determine rates of tract seeding and metastatic disease. Ultrasound guided tumor implantation was successful in all 27 rabbits. One rabbit died 2 days following the implantation procedure. Two rabbits had no tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26 (92%) rabbits. During the follow-up period, tract seeding was seen in 8% of rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous ultrasound guided tumor implantation safely provides reliable tumor growth for establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract seeding, compared to previously reported methods. PMID:25853660

  16. Improved Hepatocyte Engraftment After Portal Vein Occlusion in LDL Receptor-Deficient WHHL Rabbits and Lentiviral-Mediated Phenotypic Correction In Vitro.

    PubMed

    Goulinet-Mainot, Sylvie; Tranchart, Hadrien; Groyer-Picard, Marie-Thérèse; Lainas, Panagiotis; Saloum Diop, Papa; Holopherne, Delphine; Gonin, Patrick; Benihoud, Karim; Ba, Nathalie; Gauthier, Olivier; Franco, Dominique; Guettier, Catherine; Pariente, Danièle; Weber, Anne; Dagher, Ibrahim; Huy Nguyen, Tuan

    2012-02-01

    Innovative cell-based therapies are considered as alternatives to liver transplantation. Recent progress in lentivirus-mediated hepatocyte transduction has renewed interest in cell therapy for the treatment of inherited liver diseases. However, hepatocyte transplantation is still hampered by inefficient hepatocyte engraftment. We previously showed that partial portal vein embolization (PVE) improved hepatocyte engraftment in a nonhuman primate model. We developed here an ex vivo approach based on PVE and lentiviral-mediated transduction of hepatocytes from normal (New Zealand White, NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits: the large animal model of familial hypercholesterolemia type IIa (FH). FH is a life-threatening human inherited autosomal disease caused by a mutation in the low-density lipoprotein receptor (LDLR) gene, which leads to severe hypercholesterolemia and premature coronary heart disease. Rabbit hepatocytes were isolated from the resected left liver lobe, and the portal branches of the median lobes were embolized with Histoacryl® glue under radiologic guidance. NZW and WHHL hepatocytes were each labeled with Hoechst dye or transduced with lentivirus expressing GFP under the control of a liver-specific promoter (mTTR, a modified murine transthyretin promoter) and were then immediately transplanted back into donor animals. In our conditions, 65-70% of the NZW and WHHL hepatocytes were transduced. Liver repopulation after transplantation with the Hoechst-labeled hepatocytes was 3.5 ± 2%. It was 1.4 ± 0.6% after transplantation with either the transduced NZW hepatocytes or the transduced WHHL hepatocytes, which was close to that obtained with Hoechst-labeled cells, given the mean transduction efficacy. Transgene expression persisted for at least 8 weeks posttransplantation. Transduction of WHHL hepatocytes with an LDLR-encoding vector resulted in phenotypic correction in vitro as assessed by internalization of fluorescent LDL ligands

  17. Improved Hepatocyte Engraftment After Portal Vein Occlusion in LDL Receptor-Deficient WHHL Rabbits and Lentiviral-Mediated Phenotypic Correction In Vitro

    PubMed Central

    Goulinet-Mainot, Sylvie; Tranchart, Hadrien; Groyer-Picard, Marie-Thérèse; Lainas, Panagiotis; Saloum Diop, Papa; Holopherne, Delphine; Gonin, Patrick; Benihoud, Karim; Ba, Nathalie; Gauthier, Olivier; Franco, Dominique; Guettier, Catherine; Pariente, Danièle; Weber, Anne; Dagher, Ibrahim; Huy Nguyen, Tuan

    2012-01-01

    Innovative cell-based therapies are considered as alternatives to liver transplantation. Recent progress in lentivirus-mediated hepatocyte transduction has renewed interest in cell therapy for the treatment of inherited liver diseases. However, hepatocyte transplantation is still hampered by inefficient hepatocyte engraftment. We previously showed that partial portal vein embolization (PVE) improved hepatocyte engraftment in a nonhuman primate model. We developed here an ex vivo approach based on PVE and lentiviral-mediated transduction of hepatocytes from normal (New Zealand White, NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits: the large animal model of familial hypercholesterolemia type IIa (FH). FH is a life-threatening human inherited autosomal disease caused by a mutation in the low-density lipoprotein receptor (LDLR) gene, which leads to severe hypercholesterolemia and premature coronary heart disease. Rabbit hepatocytes were isolated from the resected left liver lobe, and the portal branches of the median lobes were embolized with Histoacryl® glue under radiologic guidance. NZW and WHHL hepatocytes were each labeled with Hoechst dye or transduced with lentivirus expressing GFP under the control of a liver-specific promoter (mTTR, a modified murine transthyretin promoter) and were then immediately transplanted back into donor animals. In our conditions, 65–70% of the NZW and WHHL hepatocytes were transduced. Liver repopulation after transplantation with the Hoechst-labeled hepatocytes was 3.5 ± 2%. It was 1.4 ± 0.6% after transplantation with either the transduced NZW hepatocytes or the transduced WHHL hepatocytes, which was close to that obtained with Hoechst-labeled cells, given the mean transduction efficacy. Transgene expression persisted for at least 8 weeks posttransplantation. Transduction of WHHL hepatocytes with an LDLR-encoding vector resulted in phenotypic correction in vitro as assessed by internalization of fluorescent LDL

  18. FXR and liver carcinogenesis

    PubMed Central

    Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

    2015-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

  19. T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

    NASA Astrophysics Data System (ADS)

    Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

    2016-05-01

    Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the

  20. T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues.

    PubMed

    Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

    2016-05-01

    Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent. PMID:27113247

  1. Liver angioscintigraphy: clinical applications.

    PubMed

    Dragoteanu, Mircea; Cotul, Sabin O; Pîgleşan, Cecilia; Tamaş, Stefan

    2004-03-01

    Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients. PMID:15054528

  2. Nonpathogenicity of antiintestinal antibody in the rabbit.

    PubMed Central

    Rabin, B. S.; Rogers, S. J.

    1976-01-01

    Rabbits were immunized with intestinal extract prepared from rabbits, guinea pigs, and germ-free rats. The resultant serum antibody response to intestinal antigen was determined by gel precipitation and direct tissue immunofluorescence. Forty-eight hours prior to sacrifice of each immunized animal, a portion of the duodenum, ileum, and colon were traumatized to bring circulating antibody into contact with the tissue. Sections for histology and direct immunofluorescence were taken from the area of trauma, just adjacent to the area, and 10 cm from it. The humoral immune response, the presence of tissue bound immunoglobulin, and tissue histology were compared. The area of trauma in normal and immunized animals showed the same histologic changes. In each animal, tissue just adjacent to the area of trauma and 10 cm from it were histologically identical. The pathologic alterations in the immunized animals were similar to those associated with malabsorption in man. Direct immunofluorescence of the intestinal tissue revealed bound immunoglobulin in histologically normal and abnormal tissue. Precipitating antibody to intestine was present in the serum of rabbits with normal and abnormal histology. Thus, antiintestinal antibody as dected by precipitation in gel and direct tissue immunofluorescence does not appear to be a factor in the pathogenesis of this model of immunologically induced histologic changes in the intestine. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 PMID:1266943

  3. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile

    PubMed Central

    Gu, Lei; Zhang, Guo-Fang; Kombu, Rajan S.; Allen, Frederick; Kutz, Gerd; Brewer, Wolf-Ulrich; Roe, Charles R.

    2010-01-01

    The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Am J Physiol Endocrinol Metab 291: E860–E866, 2006) that the intravenous infusion of triheptanoin increases lipolysis traced by the turnover of glycerol. In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate ± glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous Ra but not oleate endogenous Ra. Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate β-oxidation and C5-ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders. PMID:19903863

  4. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile.

    PubMed

    Gu, Lei; Zhang, Guo-Fang; Kombu, Rajan S; Allen, Frederick; Kutz, Gerd; Brewer, Wolf-Ulrich; Roe, Charles R; Brunengraber, Henri

    2010-02-01

    The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Am J Physiol Endocrinol Metab 291: E860-E866, 2006) that the intravenous infusion of triheptanoin increases lipolysis traced by the turnover of glycerol. In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate +/- glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous R(a) but not oleate endogenous R(a). Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate beta-oxidation and C(5)-ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders. PMID:19903863

  5. Liver Facts

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Liver Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ...

  6. Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver

    PubMed Central

    Hug, George; Schubert, William K.; Chuck, Gail

    1969-01-01

    Low activity of phosphorylase and increased concentration of glycogen were found in liver tissue from five children with asymptomatic hepatomegaly. In vitro activation of liver phosphorylase in these patients occurred at the rate of 10% or less of normal. Elimination of the defect by the addition of kinase that activates phosphorylase demonstrated the integrity of the phosphorylase enzyme and the deficient activity of dephophophosphorylase kinase. On the average, 60% of the phosphorylase enzyme of normal human liver was in the active form. Phosphorylase kinase of rabbit muscle activated phosphorylase of normal human liver to a final value that was significantly higher than the one obtained in the absence of muscle phosphorylase kinase. The ultrastructural examination of hepatic tissue from the five patients revealed increased amounts of glycogen. There was scarcity of endoplasmic reticulum. There was intercellular glycogen in continuity with the glycogen of the hepatocytes through breaks in their circumference. Lipid droplets with lucid areas in the form of needles and plates contained aggregates of glycogen. There were numerous lysosomes, some containing glycogen. Large vacuoles filled with glycogen and surrounded by a membrane were seen occasionally. The vacuoles might reflect the lysosomal pathway of glycogen degradation, since there was apparent fusion of such autophagic vacuoles with small vesicles resembling primary lysosomes. Images PMID:5774108

  7. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models

    PubMed Central

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y. Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  8. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models.

    PubMed

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  9. The Cutaneous Rabbit Revisited

    ERIC Educational Resources Information Center

    Flach, Rudiger; Haggard, Patrick

    2006-01-01

    In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE…

  10. Effects of Khaya senegalensis leaves on performance, carcass traits, hemtological and biochemical parameters in rabbits

    PubMed Central

    Abdel-Wareth, A. A. A.; Hammad, Seddik; Ahmed, Hassan

    2014-01-01

    One of the challenges facing farmers today is to ensure adequate integration of natural resources into animal feeds. The aim of the present study is to evaluate the effects of Khaya senegalensis (KS) leaves on the performance of growing male rabbits, carcass traits and biochemical as well as hematological parameters. Thirty New Zealand White male growing rabbits were randomly divided into 3 groups (10 rabbits per group). Group I (control) received standard rabbit diet. Rabbits in group II and group III were fed standard rabbit diet supplemented with 35 % and 65 % KS leaves, respectively. All rabbits were fed daily for 25 days. The performance parameters and carcass criteria, including daily body weight gain, final body weight, and the percentage of dressing, were increased in rabbits fed 35 % KS when compared to the control group. Kidney and liver weight ratios increased significantly in group II but dropped in group III. Furthermore, liver enzymes - alanine aminotransferase and aspartate transaminase and kidney function parameters - urea, and creatinine - increased in both group II (significant P<0.05) and in group III (significant P<0.01) when compared to the control group. Moreover, KS leaves induced a significant increase (P<0.05) in the total white blood cell count, the percentage of granulocytes and the platelet count; whereas, the percentage of lymphocytes, red blood cell count, hemoglobin content, mean corpuscular hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration were not statistically significantly changed. This study demonstrates that the performance parameters and carcass traits are improved by the replacement of rabbit's diet with KS leaves. However, KS leaves may adversely affect liver and kidney function in a dose-dependent manner. Therefore, further studies are required to elucidate the maximum tolerable and toxic, as well as lethal doses, and to isolate the pharmacologically active components from KS leaves. PMID

  11. Clinical biochemical aspects of glutaminase toxicity in rabbits and Rhesus monkeys.

    PubMed Central

    Hambleton, P.; Benbough, J. E.; Baskerville, A.; Harris-Smith, P. W.

    1980-01-01

    Treatment with a chemically modified glutaminase was lethal to rabbits and Rhesus monkeys at all but the lowest doses. Changes in the serum levels of triglycerides, glucose, creatinine, urea, cholesterol and protein and in the activities of some serum enzymes were the probable result of the development of lesions in liver, kidney and intestine observed at necropsy. Treatment with unmodified glutaminase induced similar changes in rabbits but not in Rhesus monkeys. PMID:6775664

  12. Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

    PubMed Central

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  13. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits.

    PubMed

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  14. BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

    PubMed Central

    Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi, Marco Martins; Caetano, Edie Benedito

    2015-01-01

    Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers. PMID:27022549

  15. Phase separation of X-irradiated lenses of rabbit

    SciTech Connect

    Clark, J.I.; Giblin, F.J.; Reddy, V.N.; Benedek, G.B.

    1982-02-01

    The phase separation temperature (Tcat) was studied as a function of time (age) after the administration of a single dose of radiation (2000 rad), which induces cataract in the rabbit lens. In the normal unirradiated lens, Tcat decreases linearly with age at a rate (DTcat/dt) approximately 2.2 degrees/week. In the irradiated lens, Tcat initially decreases with age much less than the normal lens, then rises sharply with age at the time of the appearance of opacity in the living rabbit eye. We suggest that the phase separation temperature may serve as a sensitive and early indicator of cataractogenic processes in the lens.

  16. Liver involvement in systemic infection

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2014-01-01

    The liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. In particular, hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. In this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. In most patients with systemic infections, treatment for the invading microbes is enough to normalize the liver function tests. However, some patients may show severe liver injury or fulminant hepatic failure, requiring intensive treatment of the liver. PMID:25276279

  17. T1, T2, and relative proton density at 0. 35 T for spleen, liver, adipose tissue, and vertebral body: normal values

    SciTech Connect

    Nyman, R.; Ericsson, A.; Hemmingsson, A.; Jung, B.; Sperber, G.; Thuomas, K.A.

    1986-12-01

    An MRI installation (Magnetom, Siemens, software version B1 of NUMARIS) working at 0.35 T was used to estimate T1, T2, and relative proton density in the spleen, liver, adipose tissue, and vertebral body in 14 healthy volunteers. Two double-echo sequences were applied for all subjects: TR = 500 ms, TE1 = 35 and TE2 = 70 ms; and TR = 1600 ms, TE1 = 35 and TE2 = 70 ms. The images were sampled in regions of interest and appropriate relaxation expressions fitted to the ROI data yielding relaxation parameters and relative proton densities. Relaxation expressions, included in standard software (Siemens), were compared to more elaborate functions, developed in parallel to this study. The latter were found more appropriate, especially for high T1 values, and gave the following mean values for the four tissues (estimated uncertainty of mean in parentheses) T1 (ms) 915(36), 428(5), 261(7), and 501(11); T2 (ms) 79.7(8.8), 51.0(0.2), 59.8(1.0), and 64.7(0.8); and corresponding relative proton density (rho, arbitrary units) 2088(136), 2182(10), 2915(49), and 2136(21). The uncertainty in the values was estimated in the fitting procedure and does not include systematic errors. The relative noise in the ROIs was about 9% and the reproducibility of the ROI mean values about 8%.

  18. Mitigative action of mono isoamyl 2, 3-dimercaptosuccinate (MiADMS) against cadmium-induced damage in cultured rat normal liver cells

    PubMed Central

    Odewumi, Caroline O.; Buggs, Rebecca; Badisa, Veera L.D.; Latinwo, Lekan M.; Badisa, Ramesh B.; Ikediobi, Christopher O.; Darling-Reed, Selina F.; Owens, Marcia A.

    2012-01-01

    Cadmium is non-essential, carcinogenic and multitarget pollutant in the environment. Monoisoamyl 2, 3-dimercaptosuccinate (MiADMS) is an ester of dimercaptosuccinicacid that acts as an antioxidant and chelator. Therefore, the mitigative action of MiADMS on viability, morphology, antioxidative enzymes and cell cycle were studied on rat liver cells treated with cadmium chloride (CdCl2). The cells were treated with 150 μM CdCl2 alone or cotreated with 300 μM MiADMS (concurrently, 2 h or 4 h post CdCl2 treatment) for 24 h. The viability of cells treated with CdCl2 alone was decreased in comparison to the control cells. Cotreatment with MiADMS resulted in an increase in cell viability in comparison to the CdCl2 alone treated cells. The CdCl2 treatment altered the morphological shape of the cells, while cotreatment with MiADMS restored the shape. Antioxidative enzymes activities were decreased in the cells treated with CdCl2 alone, while MiADMS cotreatment resulted in an increase in enzyme activities. The CdCl2 arrested the cells in S phase of the cell cycle. Cotreatment with MiADMS alleviated cell cycle arrest by shifting to G1 phase. These results clearly show the mitigative action of MiADMS on CdCl2 toxicity and may suggest that MiADMS can be used as an antidote against cadmium. PMID:21911053

  19. Dietary cholesterol modulates the excitability of rabbit hippocampal CA1 pyramidal neurons

    PubMed Central

    Wang, Desheng; Schreurs, Bernard G.

    2010-01-01

    Previous work has shown high dietary cholesterol can affect learning and memory including rabbit eyeblink conditioning and this effect may be due to increased membrane cholesterol and enhanced hippocampal amyloid beta production. This study investigated whether dietary cholesterol modulates rabbit hippocampal CA1 neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2% cholesterol or normal chow for 8 weeks revealed changes including decreased after-hyperpolarization amplitudes (AHPs) – an index of membrane excitability shown to be important for rabbit eyeblink conditioning. This index was reversed by adding copper to drinking water – a dietary manipulation that can retard rabbit eyeblink conditioning. Evidence of cholesterol effects on membrane excitability was provided by application of methyl-β-cyclodextrin, a compound that reduces membrane cholesterol, which increased the excitability of hippocampal CA1 neurons. PMID:20639007

  20. Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits

    PubMed Central

    Yan, Peng; Yang, Xiaohong; Yang, Xiaoyu; Zheng, Weidong; Tan, Yunbing

    2014-01-01

    Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9–10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation. PMID:25206785

  1. Liver Wellness

    MedlinePlus

    ... to liver wellness. • There are more than 100 liver diseases. • Liver disease is one of the top 10 causes of ... out of every 10 Americans is affected by liver disease. • Some liver diseases such as hepatitis A, hepatitis ...

  2. Insights into the antiatherogenic molecular mechanisms of andrographolide against Porphyromonas gingivalis-induced atherosclerosis in rabbits.

    PubMed

    Al Batran, Rami; Al-Bayaty, Fouad; Al-Obaidi, Mazen M Jamil; Ashrafi, Amer

    2014-12-01

    Atherosclerosis is the commonest and most important vascular disease. Andrographolide (AND) is the main bioactive component of the medicinal plant Andrographis paniculata and is used in traditional medicine. This study was aimed to evaluate the antiatherogenic effect of AND against atherosclerosis induced by Porphyromonas gingivalis in White New Zealand rabbits. Thirty rabbits were divided into five groups as follows: G1, normal group; G2-5, were orally challenged with P. gingivalis five times a week over 12 weeks; G2, atherogenic control group; G3, standard group treated with atorvastatin (AV) 5 mg/kg; and G4 and G5, treatment groups treated with AND 10 and 20 mg/kg, respectively over 12 weeks. Serums were subjected to antioxidant enzymatic and anti-inflammatory activities, and the aorta was subjected to histological analyses. Groups treated with AND showed a significant reversal of liver and renal biochemical changes, compared with the atherogenic control group. In the same groups, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) levels in serum were significantly increased (P < 0.05), and lipid peroxidation (malondialdehyde (MDA)) levels were significantly decreased (P < 0.05), respectively. Furthermore, treated groups with AV and AND showed significant decrease in the level of VCAM-1 and ICAM-1 compared with the atherogenic control group. In aortic homogenate, the level of nitrotyrosine was significantly increased, while the level of MCP1 was significantly decreased in AV and AND groups compared with the atherogenic control group. In addition, staining the aorta with Sudan IV showed a reduction in intimal thickening plaque in AV and AND groups compared with the atherogenic control group. AND has showed an antiatherogenic property as well as the capability to reduce lipid, liver, and kidney biomarkers in atherogenic serum that prevents atherosclerosis complications caused by P. gingivalis. PMID:25172523

  3. Terahertz spectroscopic imaging of a rabbit VX2 hepatoma model

    NASA Astrophysics Data System (ADS)

    Park, Jae Yeon; Choi, Hyuck Jae; Cho, Kyoung-Sik; Kim, Kyu-Rae; Son, Joo-Hiuk

    2011-03-01

    Terahertz (THz) spectroscopic imaging technique was applied to classify the tumor region in the rabbit liver with VX2 hepatocellular carcinoma. Within the measurement range of 0.1-2 THz, the average reflectance values for all tumor samples were more than 4% higher than those for healthy cells, and the terahertz measurements correlated well with histological analysis results. This study on paraffin-embedded tissues showed the alteration of cell density and protein content in tumors, excluding the effect of water.

  4. Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin-induced diabetic albino rats

    PubMed Central

    Oche, Okpe; Sani, Ibrahim; Chilaka, Njoku Godwin; Samuel, Ndidi Uche; Samuel, Atabo

    2014-01-01

    Objective To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. Methods A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. Results The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control. Conclusion This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat. PMID:25182283

  5. Rabbit care and husbandry.

    PubMed

    Bradley, Teresa

    2004-05-01

    This article provides information for the veterinary staff to be better prepared to care for the special needs of rabbit patients as they are presented in increased frequency for veterinary care. Housing, nutrition,restraint, and recognizing illness are covered in detail. Descriptions of techniques for blood collection, oral medication administration, and injection sites are included. Preventive care recommendations for examinations from first visit to geriatric visits are outlined as well as indications for spaying and neutering. Also provided are lists that will aid the veterinary staff in providing instructions when the appointment is made, recommendations for boarding, surgical, and anesthetic considerations and clinical signs that are associated with pain in rabbits. PMID:15145392

  6. Rabbits killing birds revisited.

    PubMed

    Zhang, Jimin; Fan, Meng; Kuang, Yang

    2006-09-01

    We formulate and study a three-species population model consisting of an endemic prey (bird), an alien prey (rabbit) and an alien predator (cat). Our model overcomes several model construction problems in existing models. Moreover, our model generates richer, more reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rabbit or the cat when the bird is endangered. We confirm the existence of the hyperpredation phenomenon, which is a big potential threat to most endemic prey. Specifically, we show that, in an endemic prey-alien prey-alien predator system, eradication of introduced predators such as the cat alone is not always the best solution to protect endemic insular prey since predator control may fail to protect the indigenous prey when the control of the introduced prey is not carried out simultaneously. PMID:16529776

  7. Measurement of Tear Production in English Angora and Dutch Rabbits

    PubMed Central

    Rajaei, Seyed Mehdi; Rafiee, Siamak Mashhady; Ghaffari, Masoud Selk; Masouleh, Mohammad N; Jamshidian, Mahmoud

    2016-01-01

    The purpose of this study was to establish normal values for tear production tests in different breeds of domestic rabbits. Healthy adult rabbits (n = 60; 120 eyes) of 2 different breeds (English angora and Dutch; n = 15 of each sex and breed) were used in this study. Tear production was measured by using the 1-min Schirmer tear test (STT), phenol red thread test (PRTT), and endodontic absorbent paper point tear test (EAPTT). In addition, horizontal palpebral fissure length was evaluated as a measure of ocular adnexal dimensions. Tear production (mean ± 1 SD) in English angora rabbits was 5.4 ± 1.6 mm/min according to the STT, 25.0 ± 2.7 mm in 15 s for the PRTT, and 18.8 ± 2.1 mm/min by the EAPTT; in Dutch rabbits, these values were 4.6 ± 1.2 mm/min, 23.6 ± 2.3 mm in 15 s, and 16.9 ± 1.7 mm/min, respectively. Only the EAPTT revealed a significant difference in tear production between English Angora and Dutch rabbits. These results provide reference values for tear production in English Angora and Dutch rabbits according to 3 different quantitative tear film assessment methods. PMID:27025815

  8. Liver Transplant

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  9. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  10. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  11. Liver biopsy

    MedlinePlus

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  12. Recombinant Rabbit Leukemia Inhibitory Factor and Rabbit Embryonic Fibroblasts Support the Derivation and Maintenance of Rabbit Embryonic Stem Cells

    PubMed Central

    Xue, Fei; Ma, Yinghong; Chen, Y. Eugene; Zhang, Jifeng; Lin, Tzu-An; Chen, Chien-Hong; Lin, Wei-Wen; Roach, Marsha; Ju, Jyh-Cherng; Yang, Lan; Du, Fuliang

    2012-01-01

    Abstract The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2×3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs. PMID:22775411

  13. Biodegradable fixation of rabbit osteotomies.

    PubMed

    Vainionpää, S; Vihtonen, K; Mero, M; Pätiälä, H; Rokkanen, P; Kilpikari, J; Törmälä, P

    1986-06-01

    Osteotomies of the tibial diaphysis were operatively fixed with biodegradable implants in 44 rabbits. Polyglycolic acid (PGA)/polylactic acid (PLA) copolymer implants reinforced with 7 per cent carbon fibre and overlaid with gold were used in 24 rabbits. Poly-beta-hydroxy butyric acid (PHBA) with carbon fibre reinforcement and gold surfacing were used in 20 rabbits. No external support was used. Unsatisfactory results were achieved with the PGA/PLA copolymer implants. Better results were achieved in 15 out of 20 rabbits whose osteotomies were fixed with carbon fibre-reinforced PHBA implants. PMID:3739665

  14. Experimental ulcerative herpetic keratitis. II. Influence of topical corticosteroid in immunised rabbits.

    PubMed Central

    Carter, C A; Easty, D L; Walker, S R

    1981-01-01

    Since the great majority of patients possess immune response to herpes simplex virus (HSV), the influence of a topical anti-inflammatory corticosteroid (0.1% clobetasone butyrate) on ulcerative herpetic keratitis was studied in rabbits with a previous HSV skin infection (immunised) and compared with that in normal rabbits. Corticosteroid treatment had a much greater ulceration-exacerbating effect in immunised than in normal animals. On day 7 the mean area of ulceration in immunised rabbits were 3 times greater in treated eyes. 0.01% clobetasone butyrate treatment had less effect on immunised rabbits; 0.001% had no effect. It is concluded that the immunised rabbit provides a useful experimental model for studying the relationship between concentration of topical anti-inflammatory agents and enhancement of herpetic ulceration. PMID:7260009

  15. Interferometric phase-contrast X-ray CT imaging of VX2 rabbit cancer at 35keV X-ray energy

    SciTech Connect

    Takeda, Tohoru; Wu Jin; Tsuchiya, Yoshinori; Lwin, Thet-Thet; Itai, Yuji; Yoneyama, Akio; Hyodo, Kazuyuki

    2004-05-12

    Imaging of large objects at 17.7-keV low x-ray energy causes huge x-ray exposure to the objects even using interferometric phase-contrast x-ray CT (PCCT). Thus, we tried to obtain PCCT images at high x-ray energy of 35keV and examined the image quality using a formalin-fixed VX2 rabbit cancer specimen with 15-mm in diameter. The PCCT system consisted of an asymmetrically cut silicon (220) crystal, a monolithic x-ray interferometer, a phase-shifter, an object cell and an x-ray CCD camera. The PCCT at 35 keV clearly visualized various inner structures of VX2 rabbit cancer such as necrosis, cancer, the surrounding tumor vessels, and normal liver tissue. Besides, image-contrast was not degraded significantly. These results suggest that the PCCT at 35 KeV is sufficient to clearly depict the histopathological morphology of VX2 rabbit cancer specimen.

  16. Liver lipid composition and intravenous, intraperitoneal, and enteral administration of intralipid.

    PubMed

    Morán Penco, J M; Maciá Botejara, E; Salas Martinez, J; Mahedero Ruiz, G; Climent Mata, V; Saenz de Santamaria, J; Vinagre Velasco, L M

    1994-01-01

    We studied the variations arising in plasma and liver lipids after intravenous (i.v.), intraperitoneal (IP), and intragastric (IG) administration of a fat overdose on the order of 4 g.kg-1 body wt.day-1 in the form of Intralipid (ITL) 20% to 33 New Zealand rabbits for 15 days. The control group was submitted for surgery but did not receive an ITL supplement. The results show weight gain in all animals and normal liver enzyme values. There was an increase in plasma lipids in groups supplemented by the parenteral route (i.v. and IP), and fatty acids showed a similar distribution, in terms of percentages, to that for ITL. In liver tissue, there was an increase in the fractions related to ethanolamine and a decrease in phospholipids of choline and serine. In the i.v. group, neutral lipids predominated compared with other groups. The livers of all supplemented animals (i.v., IP, and IG) showed a higher content of stearic and linoleic acid and a reduction in oleic acid. Study with optical microscopy showed a microvacuolization affecting the three areas of the hepatic acini in the i.v. group, seen with electron microscopy as vacuoles lacking membranes and surrounded by mitochondria. In conclusion, there is an increase in hepatic steatosis in parenteral groups and a greater deposit of neutral lipids in the i.v. group, related to the administration route, without biochemical signs of liver dysfunction. PMID:8199419

  17. Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading

    PubMed Central

    Huisman, Elise S; Andersson, Gustav; Scott, Alexander; Reno, Carol R; Hart, David A; Thornton, Gail M

    2014-01-01

    The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon. PMID:24571598

  18. Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading.

    PubMed

    Huisman, Elise S; Andersson, Gustav; Scott, Alexander; Reno, Carol R; Hart, David A; Thornton, Gail M

    2014-05-01

    The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon. PMID:24571598

  19. Acute liver failure and liver transplantation.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  20. Safety of Microbubbles and Transcranial Ultrasound in Rabbits

    NASA Astrophysics Data System (ADS)

    Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

    2007-05-01

    The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

  1. Serotonin (5-hydroxytryptamine) glucuronidation in vitro: assay development, human liver microsome activities and species differences.

    PubMed

    Krishnaswamy, S; Duan, S X; Von Moltke, L L; Greenblatt, D J; Sudmeier, J L; Bachovchin, W W; Court, M H

    2003-02-01

    1. The main purpose was to develop a high-performance liquid chromatography (HPLC)-based method to assay serotonin glucuronidation activity using liver microsomal fractions. Application of this method was then demonstrated by determining serotonin UDP-glucuronosyltransferase (UGT) enzyme kinetics using human liver microsomes and recombinant human UGT1A6. Interspecies differences were also evaluated using liver microsomes from 10 different mammalian species. 2. Incubation of liver microsomes with serotonin, UDP-glucuronic acid and magnesium resulted in the formation of a single product peak using HPLC with fluorescence and ultraviolet absorbance detection. This peak was confirmed as serotonin glucuronide based on sensitivity to beta-glucuronidase and by obtaining the expected mass of 352 with positive-ion mass spectrometry. 3. Following a preparative HPLC isolation, the structure of this metabolite was established as serotonin-5-O-glucuronide by (1)H-NMR spectroscopy. 4. Enzyme kinetic studies showed apparent K(m) and V(max) of 8.8 +/- 0.3 mM and 43.4 +/- 0.4 nmoles min(-1) mg(-1) protein, respectively, for human liver microsomes, and 5.9 +/- 0.2 mM and 15.8 +/- 0.2 nmoles min(-1) mg(-1), respectively, for recombinant UGT1A6. 5. The order of serotonin-UGT activities in animal liver microsomes was rat > mouse > human > cow > pig > horse > dog > rabbit > monkey > ferret. Cat livers showed no serotonin-UGT activity. Heterozygous and homozygous mutant Gunn rat livers had 40 and 13%, respectively, of the activity of the normal Wistar rat, indicating a significant contribution by a rat UGT1A isoform to serotonin glucuronidation. 6. This assay provides a novel sensitive and specific technique for the measurement of serotonin-UGT activity in vitro. PMID:12623759

  2. Pathogenicity of rotavirus in rabbits.

    PubMed Central

    Thouless, M E; DiGiacomo, R F; Deeb, B J; Howard, H

    1988-01-01

    The role of rotavirus in diarrheal disease of rabbits was investigated, and a model for human rotavirus infection was established. Orogastric inoculation of 8- and 12-week-old New Zealand White rabbits with a rabbit strain of rotavirus (L:ALA:84) resulted in fecal shedding of virus for 6 to 8 days from 2 to 5 days after inoculation. Most rabbits exhibited diarrhea, coincident with the onset of viral shedding, which persisted for 2 to 4 days. Diarrhea was characterized by soft or fluid stools and fecal staining of the perineum. Inoculation of 3-week-old rabbits resulted in a briefer period of viral shedding and diarrhea of a milder nature. Histopathologic examination during the period of viral shedding revealed a mild, nonsuppurative enteritis. Inoculated rabbits exhibited antibodies in serum to rotavirus by enzyme-linked immunosorbent assay. Sham-inoculated or uninoculated rabbits maintained in the same cage or the same room with inoculated rabbits acquired rotavirus infection. The mild diarrheal disease which resulted with a rotavirus isolate from severe field cases suggests that cofactors were involved. Images PMID:2838507

  3. Neuromuscular lesions in restrained rabbits.

    PubMed

    Mendlowski, B

    1975-01-01

    Ten of 16 rabbits restrained 6 h daily for 35 days developed focal to diffuse degeneration of the sciatic nerves. Very small necrotic areas also were found in the skeletal muscles of seven of 16 rabbits, but the muscle lesions did not correlate with the nerve changes. PMID:180647

  4. Normal faults, normal friction?

    NASA Astrophysics Data System (ADS)

    Collettini, Cristiano; Sibson, Richard H.

    2001-10-01

    Debate continues as to whether normal faults may be seismically active at very low dips (δ < 30°) in the upper continental crust. An updated compilation of dip estimates (n = 25) has been prepared from focal mechanisms of shallow, intracontinental, normal-slip earthquakes (M > 5.5; slip vector raking 90° ± 30° in the fault plane) where the rupture plane is unambiguously discriminated. The dip distribution for these moderate-to-large normal fault ruptures extends from 65° > δ > 30°, corresponding to a range, 25° < θr < 60°, for the reactivation angle between the fault and inferred vertical σ1. In a comparable data set previously obtained for reverse fault ruptures (n = 33), the active dip distribution is 10° < δ = θr < 60°. For vertical and horizontal σ1 trajectories within extensional and compressional tectonic regimes, respectively, dip-slip reactivation is thus restricted to faults oriented at θr ≤ 60° to inferred σ1. Apparent lockup at θr ≈ 60° in each dip distribution and a dominant 30° ± 5° peak in the reverse fault dip distribution, are both consistent with a friction coefficient μs ≈ 0.6, toward the bottom of Byerlee's experimental range, though localized fluid overpressuring may be needed for reactivation of less favorably oriented faults.

  5. Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

    PubMed Central

    Hoang, Joseph K.; Yang, Hwai-I; Le, An; Nguyen, Nghia H.; Lin, Derek; Vu, Vinh D.; Chaung, Kevin; Nguyen, Vincent; Trinh, Huy N.; Li, Jiayi; Zhang, Jian Q.; Chen, Chien-Jen; Nguyen, Mindie H.

    2016-01-01

    Abstract For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores. A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively. After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels. PMID:27495067

  6. Renal handling of guanidino compounds in rat and rabbit.

    PubMed

    Levillain, O; Marescau, B; De Deyn, P P

    1997-03-01

    1. Guanidino compounds (GCs) have been quantified in different mammalian tissues such as brain, liver, muscle and kidney. The high anatomical heterogeneity of the kidney suggests that GCs could be unevenly distributed along the corticopapillary axis of the kidney in different species. 2. This study was designed to quantify twelve GCs in the different zones of rat and rabbit kidney. The kidneys were sliced and pieces of seven definite zones were weighed and homogenized for further GC extraction. GCs were determined by liquid chromatography. 3. The results indicate that: (1) GCs were unevenly distributed along rat and rabbit kidney; (2) qualitative and quantitative studies proved that each GC shows a particular distribution pattern along the corticopapillary axis for a given species; (3) in rats, alpha-keto-delta-guanidinovaleric acid, guanidinosuccinic acid, creatinine (CTN), methylguanidine and to a lesser extent gamma-guanidinobutyric acid increased steeply along the inner medulla in parallel to urea, whereas in rabbits, most of the GCs reached a plateau in the inner medulla and remained constant at this level; (4) gamma-guanidinobutyric acid was specifically found in the rat kidney; (5) argininic acid was higher in rabbit compared with rat kidney; (6) significantly higher levels of homoarginine were found in all zones of the rat kidney compared with the rabbit kidney. 4. The results suggest that: (1) GCs are mostly localized within the nephron segments; (2) an accumulation of GCs in the inner medulla might be explained either by a recycling process or by an intracellular storage as has been reported for urea, amino acids and organic osmolytes; (3) some GCs might be synthesized in nephron segments as reported for arginine (Arg) and guanidinoacetic acid (GAA); (4) several metabolic pathways of the GCs seemed to differ between rat and rabbit; (5) except for creatine, CTN, Arg and GAA, it seems unlikely that GCs might significantly increase the intracellular

  7. Renal handling of guanidino compounds in rat and rabbit.

    PubMed Central

    Levillain, O; Marescau, B; De Deyn, P P

    1997-01-01

    1. Guanidino compounds (GCs) have been quantified in different mammalian tissues such as brain, liver, muscle and kidney. The high anatomical heterogeneity of the kidney suggests that GCs could be unevenly distributed along the corticopapillary axis of the kidney in different species. 2. This study was designed to quantify twelve GCs in the different zones of rat and rabbit kidney. The kidneys were sliced and pieces of seven definite zones were weighed and homogenized for further GC extraction. GCs were determined by liquid chromatography. 3. The results indicate that: (1) GCs were unevenly distributed along rat and rabbit kidney; (2) qualitative and quantitative studies proved that each GC shows a particular distribution pattern along the corticopapillary axis for a given species; (3) in rats, alpha-keto-delta-guanidinovaleric acid, guanidinosuccinic acid, creatinine (CTN), methylguanidine and to a lesser extent gamma-guanidinobutyric acid increased steeply along the inner medulla in parallel to urea, whereas in rabbits, most of the GCs reached a plateau in the inner medulla and remained constant at this level; (4) gamma-guanidinobutyric acid was specifically found in the rat kidney; (5) argininic acid was higher in rabbit compared with rat kidney; (6) significantly higher levels of homoarginine were found in all zones of the rat kidney compared with the rabbit kidney. 4. The results suggest that: (1) GCs are mostly localized within the nephron segments; (2) an accumulation of GCs in the inner medulla might be explained either by a recycling process or by an intracellular storage as has been reported for urea, amino acids and organic osmolytes; (3) some GCs might be synthesized in nephron segments as reported for arginine (Arg) and guanidinoacetic acid (GAA); (4) several metabolic pathways of the GCs seemed to differ between rat and rabbit; (5) except for creatine, CTN, Arg and GAA, it seems unlikely that GCs might significantly increase the intracellular

  8. Subacute oral toxicity of endosulfan in male new zealand white rabbits.

    PubMed

    Hatipoglu, F S; Gulay, M S; Balic, A; Yildiz-Gulay, O; Volkan, S

    2008-01-01

    ABSTRACT The present study was conducted using 6 to 8 month old New Zealand white male rabbits (nine rabbits per treatment group). Daily gavages of 3, 1.5, 0.75, or 0 mg endosulfan/kg BW in corn oil resulted in the death of five (55%), three (33%), zero (0%), and zero (0%) rabbits, respectively, in 30 days. All rabbits were monitored for any observable toxic symptoms throughout the experimental period (30 d) and they also were weighed weekly to monitor body weight gain. All deaths occurred within the first 3 weeks and nervous symptoms were observed only for a few minutes before death. Alterations recorded in hematological parameters within the groups (hemoglobin, packed cell volume, and total erythrocyte count) were due to endosulfan exposure. Serum alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels were significantly elevated in the 3 mg/kg dose group. Gross post-mortem and histopathological changes in various organs (lung, liver, kidney, and testes) of rabbits treated with endosulfan were observed with typical organochlorine dose-dependent signs of toxicity. Although some animals appeared to adjust to relatively high daily doses of endosulfan for 30 days, biochemical and histological evidence indicated varied liver and kidney damage relative to dosage administered to these animals. The current subacute (30 day) study suggested a NOAEL of 0.75 mg endosulfan/kg in New Zealand white rabbits. PMID:20020928

  9. Effects of prostaglandin on experimental bone malignancy and on scintigrams of bone and marrow. [Rabbits

    SciTech Connect

    Otsuka, N.; Ito, Y.; Nagai, K.; Terashima, H.; Yanagimoto, S.; Muranaka, A.

    1981-05-01

    The correlation between prostaglandin E (PgE) and scintigrams of bone (Tc-99m MDP) and bone marrow (Tc-99m SC) was investigated in normal and VX-2-bearing rabbits. PgE in plasma of normal rabbits was 486.2. In rabbits with VX-2 transplanted into femoral muscles, PgE was in the normal range unless the tumor invaded bone. PgE was not increase significantly in rabbits when the tumor was transplanted into the marrow cavity. When tumor invaded bone, PgE increassed markedly (to 1335). Elevation of PgE did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group did not higher than in the untreated group. Indomethacin may suppress the local acceleration of calcium metabolism.

  10. The quantitation of C6 in rabbit and human sera

    PubMed Central

    Tedesco, F.; Lachmann, P. J.

    1971-01-01

    C6 quantitation was carried out in rabbit and human sera by the single radial immunodiffusion technique. The C6 content of the rabbit and human sera used as standards was estimated by precipitin analysis, using an anti-C6 antiserum labelled with 125I. The mean C6 level in normal human serum was 11 μg/ml, whereas in normal rabbit serum it was 35 μg/ml. Sera from forty rabbits heterozygous for C6 deficiency were found to have a mean concentration of C6 of 14 μg/ml. The C6 level was estimated in sera from patients with various immunological disorders and found to be significantly higher in the sera from patients with rheumatoid arthritis and normal in the sera from patients with SLE, glomerulonephritis, nephrotic syndrome and myeloma. C6 haemolytic assays were found to correlate well with the antigenic assays only in fresh sera. In various circumstances this correlation breaks down, presumably because of C6 inactivator. This inactivator, in contrast to C3-inactivator, appears to be bound to antigen–antibody complement complexes. ImagesFig. 2Fig. 3 PMID:4998970

  11. Towards liver-directed gene therapy: retrovirus-mediated gene transfer into human hepatocytes.

    PubMed

    Grossman, M; Raper, S E; Wilson, J M

    1991-11-01

    Liver-directed gene therapy is being considered in the treatment of inherited metabolic diseases. One approach we are considering is the transplantation of autologous hepatocytes that have been genetically modified with recombinant retroviruses ex vivo. We describe, in this report, techniques for isolating human hepatocytes and efficiently transducing recombinant genes into primary cultures. Hepatocytes were isolated from tissue of four different donors, plated in primary culture, and exposed to recombinant retroviruses expressing either the LacZ reporter gene or the cDNA for rabbit LDL receptor. The efficiency of gene transfer under optimal conditions, as determined by Southern blot analysis, varied from a maximum of one proviral copy per cell to a minimum of 0.1 proviral copy per cell. Cytochemical assays were used to detect expression of the recombinant derived proteins, E. coli beta-galactosidase and rabbit LDL receptor. Hepatocytes transduced with the LDL receptor gene expressed levels of receptor protein that exceeded the normal endogenous levels. The ability to isolate and genetically modify human hepatocytes, as described in this report, is an important step towards the development of liver-directed gene therapies in humans. PMID:1767337

  12. A rabbit model of non-typhoidal Salmonella bacteremia

    PubMed Central

    Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M.; McLeod, Charles G.; Levine, Myron M.; Rothman, Richard E.; Gaydos, Charlotte A.; DeTolla, Louis J.

    2014-01-01

    Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. PMID:25033732

  13. The submicrosomal distribution of hepatic uridine diphosphate glucuronyltransferases in the rabbit

    PubMed Central

    Gram, Theodore E.; Hansen, Alfred R.; Fouts, James R.

    1968-01-01

    1. Rabbit liver microsomes were subfractionated into rough- and smooth-surfaced types, and glucuronyltransferase activity in each microsomal subfraction was determined with p-nitrophenol, o-aminophenol and phenolphthalein as substrates. The glucuronyltransferase activity measured with p-nitrophenol and o-aminophenol as substrates was localized predominantly in rough-surfaced microsomes. Glucuronyltransferase measured with phenolphthalein as substrate was equally present in rough- and smooth-surfaced microsomes. 2. Phenobarbital pretreatment of rabbits did not stimulate any of the glucuronyltransferase activities measured in either rough- or smooth-surfaced microsomes. 3. Preincubation of rabbit liver microsomes for 30–60min. at 37° under oxygen did not cause any loss of glucuronyltransferase activity. Such preincubation caused either no change or increased enzyme activity in both submicrosomal fractions. The relative distribution of transferase activity in rough- and smooth-surfaced microsomes was not affected by preincubation. PMID:5639914

  14. Tyzzer's Disease of Rabbits: Isolation and Propagation of Bacillus piliformis (Tyzzer) in Embryonated Eggs

    PubMed Central

    Ganaway, James R.; Allen, Anton M.; Moore, Thomas D.

    1971-01-01

    Bacillus piliformis (Tyzzer) was isolated from the liver of rabbits with Tyzzer's disease and serially passaged in embryonated hens' eggs. Weanling rabbits given the 32nd egg passage developed lesions typical of Tyzzer's disease and died. B. piliformis was reisolated from the liver of these rabbits in embryonated eggs. Outside the host cell, the motile vegetative phase appeared to be unstable, and no means was found to preserve its viability; the results of titrations were believed to be dependent upon the resistant stage or spore. The spore withstood repeated freeze and thaw and was resistant to heat treatment of 56 C for 1 hr but not 80 C for 0.5 hr. None of several antibacterial substances tested in embryonated eggs was completely inhibitory; B. piliformis was resistant to sulfamethazine and chloramphenicol. The taxonomic position of this pleomorphic, gram-negative, sporeforming, pathogenic bacterium which appears to grow only in certain cells of several species remains unresolved. Images PMID:16557992

  15. Factors affecting the seroprevalence of lagovirus infection in wild rabbits (Oryctolagus cuniculus) in Southern Spain.

    PubMed

    García-Bocanegra, Ignacio; Astorga, Rafael J; Napp, Sebastián; Huerta, Belén; Carbonero, Alfonso; Perea, Anselmo; Arenas, Antonio

    2011-07-01

    Cross-sectional studies were carried out on wild rabbit (Oryctolagus cuniculus) populations in Southern Spain to assess the prevalence of lagovirus infection and to identify potentially associated risk factors. A total of 619 blood and 487 liver samples from wild rabbits were collected from seven hunting areas with different Mediterranean ecosystems. Logistic regression analysis was used to assess associations between seropositivity and an extensive set of variables. The seroprevalence was 29.2% (95% CI: 25.6-32.8) and lagoviruses were not detected in liver samples. Logistic regression indicated that seropositivity to lagoviruses was associated with seropositivity to myxomatosis, wild rabbit density, the existence of artificial feeding sites, mean maximum monthly temperatures of 20-30 °C, and annual accumulated rainfall of >600 mm. PMID:20643566

  16. Neurological Assessment Scores in Rabbit Embolic Stroke Models

    PubMed Central

    Brown, Aliza; Woods, Sean; Skinner, Robert; Hatton, Jeff; Lowery, John; Roberson, Paula; Hennings, Leah; Culp, William C

    2013-01-01

    Background: Neurological outcomes and behavioral assessments are widely used in animal models of stroke, but assessments in rabbit models are not fully validated. The wryneck model of neurological assessment scores (NAS) was compared to percent infarct volume (%IV) values (infarct volume is a proven clinical indicator of stroke severity) and arterial occlusion localization in three rabbit angiographic stroke models. Hypothesis: NAS values will correlate with percent infarct volume values. Methods: Anesthetized New Zealand White rabbits (N=131, 4-5 kg) received internal carotid artery emboli by angiographic catheter introduced into the femoral artery and occlusions were characterized. Rabbits were evaluated at 24 hours post embolism using the NAS test of 0 (normal) to 10 (death). Deficit criteria included neck twist, righting reflex, extension reflex in hind paw and forepaw, and posture. Brain sections stained with triphenyltetrazolium chloride (TTC) were analyzed for %IV. Volume of the infarct was measured and calculated as a percent of the total brain volume. Results: The aggregate correlation for NAS values vs. %IV values was R=0.61, p<0.0001, a strong positive relationship, while correlations of the NAS components ranged from R=0.28-0.46. Occlusionsof the posterior cerebral artery vs. the middle cerebral artery alone produced significantly greater deficit scores at p<0.0001. Conclusions: These positive results validate the NAS system in the rabbit angiographic embolic stroke model. PMID:24265650

  17. In vivo laser-induced breakdown in the rabbit eye

    NASA Astrophysics Data System (ADS)

    Cain, Clarence P.; DiCarlo, Cheryl D.; Kennedy, Paul K.; Noojin, Gary D.; Amnotte, Rodney E.; Roach, William P.

    1995-05-01

    Threshold measurements for femtosecond laser pulsewidths have been made for retinal minimum visible lesions (MVLs) in Dutch Belted rabbit and rhesus monkey eyes. Laser-induced breakdown (LIB) thresholds in biological materials including vitreous, normal saline, tap water, and ultrapure water have been measured and reported using an artificial eye. We have recorded on video the first LIB causing bubble formation in any eye in vivo using albino rabbit eyes (New Zealand white) with 120- femtosecond (fs) pulses and pulse energies as low as 5 microjoules ((mu) J). These bubbles were clearly formed anterior to the retina within the vitreous humor and, with 60 (mu) J of energy, they lasted for several seconds before disappearing and leaving no apparent damage to the retina. We believe this to be true LIB because of the lack of pigmentation or melanin granules within the albino rabbit eye (thus no absorptive elements) and because of the extremely high peak powers within the 5-(mu) J, 120-fs laser pulse. These high peak powers produce self-focusing of the pulse within the vitreous. The bubble formation at the breakdown site acts as a limiting mechanism for energy transmission and may explain why high-energy femotsecond pulses at energies up to 100 (mu) J sometimes do not cause severe damage in the pigmented rabbit eye. This fact may also explain why it is so difficult to produce hemorrhagic lesions in either the rabbit or primate eye with 100-fs laser pulses.

  18. Intra-arterial delivery of triolein emulsion increases vascular permeability in skeletal muscles of rabbits

    PubMed Central

    Kim, Hak Jin; Kim, Yong Woo; Lee, In Sook; Song, Jong Woon; Jeong, Yeon Joo; Choi, Seon Hee; Choi, Kyung Un; Suh, Kuen Tak; Cho, Byung Mann

    2009-01-01

    Background To test the hypothesis that triolein emulsion will increase vascular permeability of skeletal muscle. Methods Triolein emulsion was infused into the superficial femoral artery in rabbits (triolein group, n = 12). As a control, saline was infused (saline group, n = 18). Pre- and post-contrast T1-weighted MR images were obtained two hours after infusion. The MR images were qualitatively and quantitatively evaluated by assessing the contrast enhancement of the ipsilateral muscles. Histologic examination was performed in all rabbits. Results The ipsilateral muscles of the rabbits in the triolein group showed contrast enhancement, as opposed to in the ipsilateral muscles of the rabbits in the saline group. The contrast enhancement of the lesions was statistically significant (p < 0.001). Histologic findings showed that most examination areas of the triolein and saline groups had a normal appearance. Conclusion Rabbit thigh muscle revealed significantly increased vascular permeability with triolein emulsion; this was clearly demonstrated on the postcontrast MR images. PMID:19604410

  19. Prevalence of Lawsonia intracellularis, Salmonella spp. and Eimeria spp. in healthy and diarrheic pet rabbits.

    PubMed

    Lim, Jeong Ju; Kim, Dong Hyeok; Lee, Jin Ju; Kim, Dae Geun; Kim, Sang Hun; Min, Wongi; Chang, Hong Hee; Rhee, Man Hee; Kim, Suk

    2012-02-01

    A total of 170 fresh fecal samples (healthy; n=137, diarrheic; n=33) were collected from pet rabbits. By using PCR and formol-ether concentration method, a total 13/137 healthy rabbit feces were positive for L. intracellularis, 6/137 for Salmonella, and 13/137 for Eimeria. On the other hand, a total 17/33 diarrheic rabbit fecal samples were positive for L. intracellularis, 10/33 for Salmonella, and 21/33 for Eimeria. From these results, more than 20% of clinically normal and 97% of diarrheic rabbits were positive for single or concurrent infection of three pathogens. To the best of our knowledge, this is the first report to describe the prevalence of the microorganisms L. intracellularis, Salmonella and Eimeria in pet rabbits. PMID:21959895

  20. The Alpha-1A Adrenergic Receptor in the Rabbit Heart

    PubMed Central

    Myagmar, Bat-Erdene; Swigart, Philip M.; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  1. The Alpha-1A Adrenergic Receptor in the Rabbit Heart.

    PubMed

    Thomas, R Croft; Cowley, Patrick M; Singh, Abhishek; Myagmar, Bat-Erdene; Swigart, Philip M; Baker, Anthony J; Simpson, Paul C

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  2. In vitro glutathione conjugation of methyl iodide in rat, rabbit, and human blood and tissues.

    PubMed

    Poet, Torka S; Wu, Hong; Corley, Richard A; Thrall, Karla D

    2009-05-01

    Methyl iodide (MeI) is an intermediate in the manufacture of some pesticides and pharmaceuticals, and is under review for US registration as a non-ozone depleting alternative for methyl bromide for pre-plant soil fumigation. MeI is primarily metabolized via conjugation with glutathione (GSH), with further metabolism to S-methyl cysteine and methanethiol. To facilitate extrapolations of animal pharmacokinetic data to humans, rate constants for the GSH metabolism of MeI were determined in cytosols prepared from the liver and kidneys of rats, human donors, female rabbits, and rabbit fetuses, from rabbit olfactory and respiratory epithelium, and from rabbit and rat blood using a headspace vial equilibration technique and two-compartment mathematical model. MeI was metabolized in liver and kidney from adults of all three species, but metabolism was not detectable in fetal rabbit kidney. Maximal metabolic rates (V(max)) were similar in liver from rat and human donors (approximately 40 and 47 nmol/min/mg, respectively) whereas the V(max) rates in kidney cytosols varied approximately three-fold between the three species. No difference was observed in the loss of MeI from active and inactive whole blood from either rats or rabbits. The metabolism in olfactory and respiratory epithelial cytosol had Michaelis-Menten constant (K(m)) values that were several times higher than for any other tissue, suggesting essentially first-order metabolism in the nose. The metabolism of MeI in human liver cytosol prepared from five individual donors indicated two potential populations, one high affinity/low capacity and one with a lower affinity but higher capacity. PMID:19519152

  3. Radiographic liver size in Pekingese dogs versus other dog breeds.

    PubMed

    Choi, Jihye; Keh, Seoyeon; Kim, Hyunwook; Kim, Junyoung; Yoon, Junghee

    2013-01-01

    Differential diagnoses for canine liver disease are commonly based on radiographic estimates of liver size, however little has been published on breed variations. Aims of this study were to describe normal radiographic liver size in Pekingese dogs and to compare normal measurements for this breed with other dog breeds and Pekingese dogs with liver disease. Liver measurements were compared for clinically normal Pekingese (n = 61), normal non-Pekingese brachycephalic (n = 45), normal nonbrachycephalic (n = 71), and Pekingese breed dogs with liver disease (n = 22). For each dog, body weight, liver length, T11 vertebral length, thoracic depth, and thoracic width were measured on right lateral and ventrodorsal abdominal radiographs. Liver volume was calculated using a formula and ratios of liver length/T11 vertebral length and liver volume/body weight ratio were determined. Normal Pekingese dogs had a significantly smaller liver volume/body weight ratio (16.73 ± 5.67, P < 0.05) than normal non-Pekingese brachycephalic breed dogs (19.54 ± 5.03) and normal nonbrachycephalic breed dogs (18.72 ± 6.52). The liver length/T11 vertebral length ratio in normal Pekingese (4.64 ± 0.65) was significantly smaller than normal non-Pekingese brachycephalic breed dogs (5.16 ± 0.74) and normal nonbrachycephalic breed dogs (5.40 ± 0.74). Ratios of liver volume/body weight and liver length/T11 vertebral length in normal Pekingese were significantly different from Pekingese with liver diseases (P < 0.05). Findings supported our hypothesis that Pekingese dogs have a smaller normal radiographic liver size than other breeds. We recommend using 4.64× the length of the T11 vertebra as a radiographic criterion for normal liver length in Pekingese dogs. PMID:23094756

  4. Liver transplant

    MedlinePlus

    ... series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  5. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun ...

  6. Liver biopsy

    MedlinePlus

    ... Test is Performed The biopsy helps diagnose many liver diseases . The procedure also helps assess the stage (early, advanced) of liver disease. This is especially important in hepatitis C infection. ...

  7. Liver Diseases

    MedlinePlus

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  8. Characterization of cDNA clones encoding rabbit and human serum paraoxonase: The mature protein retains its signal sequence

    SciTech Connect

    Hassett, C.; Richter, R.J.; Humbert, R.; Omiecinski, C.J.; Furlong, C.E. ); Chapline, C.; Crabb, J.W. )

    1991-10-22

    Serum paraoxonase hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. High serum paraoxonase levels appear to protect against the neurotoxic effects of organophosphorus substrates of this enzyme. The amino acid sequence accounting for 42% of rabbit paraoxonase was determined. From these data, two oligonucleotide probes were synthesized and used to screen a rabbit liver cDNA library. Human paraoxonase clones were isolated from a liver cDNA library by using the rabbit cDNA as a hybridization probe. Inserts from three of the longest clones were sequenced, and one full-length clone contained an open reading frame encoding 355 amino acids, four less than the rabbit paraoxonase protein. Amino-terminal sequences derived from purified rabbit and human paraoxonase proteins suggested that the signal sequence is retained, with the exception of the initiator methionine residue. Characterization of the rabbit and human paraoxonase cDNA clones confirms that the signal sequences are not processed, except for the N-terminal methionine residue. The rabbit and human cDNA clones demonstrate striking nucleotide and deduced amino acid similarities (greater than 85%), suggesting an important metabolic role and constraints on the evolution of this protein.

  9. The cottontail rabbits of Virginia

    USGS Publications Warehouse

    Llewellyn, L.M.; Handley, C.O.

    1945-01-01

    Five races of cottontail rabbits belonging to three species occur in Virginia. One of them, the Mearns cottontail (Sylvilagus floridanus mearnsi), is reported here for the first time. It occurs in six southwestern counties of the state, while the eastern cottontail (S. f. mallurus) occurs in the remainder of the state with the exception of Smith and Fishermans islands off the eastern coast of Cape Charles, where it is replaced by Hitchens cottontail (S. f. hitchensi). The New England cottontail (S. transitionalis) is found on the higher mountain peaks, above 3000 feet, and the swamp rabbit (S. palustris) occurs in the Dismal Swamp region of southeastern Virginia.....The height of the breeding season for the eastern cottontail in Virginia is March and April, but breeding continues through the entire year except in December and January. The average litter size based on embryo counts was 4.7. The sex ratio of 234 specimens from all parts of the state, taken mostly in the December to February period, was 53 males to 47 females. That of a group of 145 rabbits live-trapped at Blacksburg during February and Marchwas 58 males to 42 females. The figures show that males are more active than females during the winter months, and therefore are more easily taken then....In transplanting cottontails from one section of the state to another, it is recommended that only cottontails of the same race as those originally present in the region being restocked be released there....Tularemia is not a common disease among rabbits in Virginia, but the rabbit ticks are often carriers of the disease and may transmit it to rabbits. Rabbit ticks are also found to be carriers of Rocky Mountain fever and American Q. fever. After the ticks drop off the rabbits to hibernate in the ground, which is likely to occur during mid-winter in Virginia, there is relatively little danger of humans contracting tularemia by contact with rabbits. Present laws in Virginia which prohibit rabbit hunting until the

  10. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease. PMID:23628170

  11. Pediatric liver transplantation

    PubMed Central

    Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

  12. Liver Biopsy

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is ... Points to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that ...

  13. Liver Biopsy

    MedlinePlus

    ... PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is a ... to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that involves ...

  14. Hematological assessment in pet rabbits: blood sample collection and blood cell identification.

    PubMed

    Moore, David M; Zimmerman, Kurt; Smith, Stephen A

    2015-01-01

    Pet rabbits are presented to veterinary clinics for routine care and treatment of clinical diseases. In addition to obtaining clinical history, additional diagnostic testing may be required, including hematological assessments. This article describes common blood collection methods, including venipuncture sites, volume of blood that can be safely collected, and handling of the blood. Hematological parameters for normal rabbits are provided for comparison with in-house or commercial test results. A description of the morphology of rabbit leukocytes is provided to assist in performing a differential count. Differential diagnoses are provided for abnormal values identified in the hemogram. PMID:25421022

  15. Properdin Levels in the Sera of Rabbits Exposed to a Silica Dust Cloud

    PubMed Central

    MacNab, Gwen M.; Webster, Ian

    1962-01-01

    The properdin levels in the sera of rabbits exposed to a silica dust cloud for 19 weeks were investigated. The results show a decline in the properdin titres of the experimental animals up to the sixth week of exposure. After the fourteenth week of dusting, it was observed that the properdin levels of the rabbits were restored to normal. The significance of these findings is discussed. PMID:14468041

  16. Topical Application of Naltrexone Facilitates Reepithelialization of the Cornea in Diabetic Rabbits

    PubMed Central

    Sassani, Joseph W.; Carroll, Melissa A.; McLaughlin, Patricia J.

    2009-01-01

    Delayed corneal re-epithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standarized corneal abrasions in diabetic (alloxan-induced) New Zealand white rabbits (glucose levels). NTX at a concentration of 10−4 M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled type 1 diabetic (DB), insulin-controlled type 1 diabetic (DB-IN), or nondiabetic (Normal) rabbits. Wound healing was monitored, and noninvasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal re-epithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 hr following surgery. At 72 hr, DB NTX rabbits had residual defects that were 64%–82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9–37% smaller than DB-IN rabbits receiving SV, and 6–40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy. PMID:19853024

  17. Rabbit model of rotavirus infection.

    PubMed Central

    Conner, M E; Estes, M K; Graham, D Y

    1988-01-01

    A new small animal model was developed to study parameters of rotavirus infections, including the active immune response. Seronegative New Zealand White rabbits (neonatal to 4 months old) were inoculated orally with cultivatable rabbit rotavirus strains Ala, C11, and R2 and with the heterologous simian strain SA11. The course of infection was evaluated by clinical findings, virus isolation (plaque assay and enzyme-linked immunosorbent assay), and serologic response. All four strains of virus were capable of infecting rabbits as determined by isolation of infectious virus from intestinal contents or fecal samples, by seroconversion, or by a combination of these methods. The responses differed depending on the virus strain used for inoculation. Rabbits remained susceptible to primary infection to at least 16 weeks of age (upper limit examined). Virus excretion in intestinal contents was detected from 6 h to 7 days postinoculation. RNA electropherotypes of inocula and viruses isolated from rabbits were the same in all samples tested. Transmission of Ala virus and R2 virus but not SA11 virus from inoculated animals to uninoculated controls also occurred. In a challenge experiment with Ala virus, 74- and 90-day-old rabbits were rechallenged with Ala 5 weeks after a primary infection with Ala. Virus was excreted in feces from 2 to 8 days after the primary infection but was not excreted after challenge. These results indicate that the rabbit provides an ideal model to investigate both the primary and secondary active immune responses to rotavirus infections and to evaluate candidate vaccines. Images PMID:2833612

  18. Impairment of cingulothalamic learning-related neuronal coding in rabbits exposed to cocaine in utero: general and sex-specific effects.

    PubMed

    Taylor, C L; Freeman, J H; Holt, W; Gabriel, M

    1999-02-01

    Neuronal activity was recorded in the cingulate cortex and the limbic thalamus in Dutch-belted rabbits (Oryctolagus cuniculus) exposed to cocaine (8 mg/kg/day i.v.) or saline in utero during acquisition and reversal learning of a discriminative avoidance response. Anterior cingulate cortical excitatory training-induced activity (TIA) was attenuated in cocaine-exposed female rabbits during acquisition and reversal learning, but only during reversal learning in male rabbits. Posterior cingulate cortical excitatory TIA was lessened in cocaine-exposed rabbits during acquisition, whereas discrimination between the positive and negative cues was enhanced. Neuronal firing was attenuated in the anterior ventral thalamus in cocaine-exposed rabbits during acquisition and reversal learning. Behavioral learning was normal in cocaine-exposed rabbits. Other data suggest that rabbits exposed to cocaine in utero exhibit a learning deficit when trained with nonsalient cues. PMID:10197907

  19. Drug binding affinities and potencies are best described by a log-normal distribution and use of geometric means

    SciTech Connect

    Stanisic, D.; Hancock, A.A.; Kyncl, J.J.; Lin, C.T.; Bush, E.N.

    1986-03-05

    (-)-Norepinephrine (NE) is used as an internal standard in their in vitro adrenergic assays, and the concentration of NE which produces a half-maximal inhibition of specific radioligand binding (affinity; K/sub I/), or half-maximal contractile response (potency; ED/sub 50/) has been measured numerous times. The goodness-of-fit test for normality was performed on both normal (Gaussian) or log /sub 10/-normal frequency histograms of these data using the SAS Univariate procedure. Specific binding of /sup 3/H-prazosin to rat liver (..cap alpha../sub 1/-), /sup 3/H rauwolscine to rat cortex (..cap alpha../sub 2/-) and /sup 3/H-dihydroalprenolol to rat ventricle (..beta../sub 1/-) or rat lung (..beta../sub 2/-receptors) was inhibited by NE; the distributions of NE K/sub I/'s at all these sites were skewed to the right, with highly significant (p < 0.01) deviations from normality. However, these data were better described by log-normal distributions. Similar results were obtained with ED/sub 50/'s of NE in isolated rabbit aorta (..cap alpha../sub 1/), phenoxybenzamine-treated dog saphenous vein (..cap alpha../sub 2/) and guinea pig atrium (..beta../sub 1/). The vasorelaxant potency of atrial natriuretic hormone in histamine-contracted rabbit aorta also was better described by a log-normal distribution, indicating that log-normalcy is probably a general phenomenon of drug-receptor interactions. Because data of this type appear to be log-normally distributed, geometric means should be used in parametric statistical analyses.

  20. Carbaryl distribution in rabbit tissues and body fluids.

    PubMed

    Malvisi, J; Zaghini, A; Stracciari, G L

    1992-12-01

    After single po administration of 14C-naphthylcarbamate, liquid scintillation assays evaluated the distribution of carbaryl in rabbit serum, liver, kidneys, small and large intestine, spleen, heart, muscles of the thigh and lungs and its excretion in urine and feces at 2, 4, 6 and 8 h after dosing. At 2 and 8 h radioactivity was not observed in spleen, heart, muscle and lungs, while all other tissues had increased values up to 6 h. The main excretory pathway of carbaryl was the kidneys. PMID:1287968

  1. Angiogenesis dependent characteristics of tumor observed on rabbit VX2 hepatic carcinoma

    PubMed Central

    Guan, Liming

    2015-01-01

    Objective: To evaluate angiogenesis dependent characteristics of carcinoma proliferation, metastasis and to found if there is tumor vascularity architecture defect. Methods: 36 rabbits were random divided into 2 groups: Experimental group: 18 rabbits liver were implanted with VX2 tumor by surgery operation; Control group: 18 experimental rabbits performed the same surgery operation without tumor implantation, the course of tumor growth and blood vessel invasion was observed by autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau’s histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEA I); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy. SPSS 19.0 software was used for the statistical analyses of the data. Results: The tumor grew acceleration after tumor angiogenesis, volume of original tumors was correlated with vascular caliber. The central tumor found necrosis without enough blood supply while tumor grew rapidly after tumor angiogenesis. The tumor infiltrated into liver blood sinus, blood vessels in hepatic interstitial tissue, the liver capsular vein and important organs metastasis such as lungs, kidneys, abdominal cavity caused rabbits died. The average vascular density count of 18 experimental rabbits under 400 times light microscope were 43.17 ± 8.68/vessels/High Power Field; Tumor vascular diameter all within 200 μm. Vascular elastic fiber staining presented tumor blood vessels internal, external elastic plate intact, vascular endothelial cells organelles of tumor were integrity without endothelial cells architecture defect found by pathologic observation. Conclusion: Proliferation and metastasis of rabbit VX2 hepatic carcinoma was correlated with tumor angiogenesis and no tumor

  2. Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis

    PubMed Central

    Shikhman, A; Amiel, D; D'Lima, D; Hwang, S; Hu, C; Xu, A; Hashimoto, S; Kobayashi, K; Sasho, T; Lotz, M

    2005-01-01

    Objective: To examine the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimental osteoarthritis (OA). Methods: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). In the first study, rabbits (six in each group) received intramuscular injections of GlcNAc or normal saline three times a week starting 1 week postoperatively. In the second study, rabbits (eight in each group) were injected intra-articularly with GlcNAc (either once or twice a week) or normal saline. In the third study, rabbits (seven in each group) were injected intra-articularly twice a week with either GlcNAc, hyaluronan, or normal saline. Animals were killed 8 weeks after ACLT for macroscopic and histological assessment of the knee joints. Results: Intramuscular administration of GlcNAc in rabbits with experimental knee OA did not show chondroprotective effects but showed mild anti-inflammatory activity. In contrast, intra-articular administration of GlcNAc twice a week reduced cartilage degradation. Additionally, intra-articular GlcNAc also suppressed synovitis. Once a week intra-articular injections of GlcNAc did not demonstrate therapeutic efficacy. The chondroprotective efficacy of GlcNAc was better than that of viscosupplementation treatment with hyaluronan. Conclusion: Intra-articular GlcNAc has chondroprotective and anti-inflammatory activity in experimental OA. PMID:15608304

  3. PATHOGENESIS AND IMMUNE RESPONSES OF FRANCISELLA TULARENSIS STRAINS IN WILD-CAUGHT COTTONTAIL RABBITS (SYLVILAGUS SPP.).

    PubMed

    Brown, Vienna R; Adney, Danielle R; Bielefeldt-Ohmann, Helle; Gordy, Paul W; Felix, Todd A; Olea-Popelka, Francisco J; Bowen, Richard A

    2015-07-01

    Francisella tularensis is a highly virulent, zoonotic bacterium that causes significant natural disease and is of concern as an organism for bioterrorism. Serologic testing of wildlife is frequently used to monitor spatial patterns of infection and to quantify exposure. Cottontail rabbits (Sylvilagus spp.) are a natural reservoir for F. tularensis in the US, although very little work has been done experimentally to determine how these animals respond to infection; thus, information gathered from field samples can be difficult to interpret. We characterized clinical disease, bacteremia, pathology, and antibody kinetics of North American cottontail rabbits experimentally infected with five strains of F. tularensis. Rabbits were infected with four field strains, including MA00-2987 (type A1b), WY96-3418 (type A2), KY99-3387, and OR96-0246 (type B), and with SchuS4 (type A1a), a widely used, virulent laboratory strain. Infection with the different strains of the bacterium resulted in varied patterns of clinical disease, gross pathology, and histopathology. Each of the type A strains were highly virulent, with rabbits succumbing to infection 3-13 d after infection. At necropsy, numerous microabscesses were observed in the livers and spleens of most rabbits, associated with high bacterial organ burdens. In contrast, most rabbits infected with type B strains developed mild fever and became lethargic, but the disease was infrequently lethal. Those rabbits infected with type B strains that survived past 14 d developed a robust humoral immune response, and F. tularensis was not isolated from liver, spleen, or lung of those animals. Understanding F. tularensis infection in a natural reservoir species can guide serosurveillance and generate new insights into environmental maintenance of this pathogen. PMID:25984770

  4. Catabolism of circulating enzymes: plasma clearance, endocytosis, and breakdown of lactate dehydrogenase-1 in rabbits.

    PubMed

    Smit, M J; Beekhuis, H; Duursma, A M; Bouma, J M; Gruber, M

    1988-12-01

    Lactate dehydrogenase-1 (EC 1.1.1.27), intravenously injected into rabbits, was cleared with first-order kinetics (half-life 27 min), until at least 80% of the injected activity had disappeared from plasma. Radioactivity from injected 125I-labeled enzyme disappeared at this same rate. Trichloroacetic-acid-soluble breakdown products started to appear in the circulation shortly after injection of the labeled enzyme. Body scans of the rabbits for 80 min after injection of 131I-labeled enzyme revealed rapid accumulation of label in the liver, peaking 10-20 min after injection. Subsequently, activity in the liver declined and radioactivity (probably labeled breakdown products of low molecular mass) steadily accumulated in the bladder. Tissue fractionation of liver, 19 min after injection of labeled enzyme, indicated that the radioactivity was present both in endosomes and in lysosomes, suggesting uptake by endocytosis, followed by breakdown in the lysosomes. Measurements of radioactivity in liver and plasma suggest that the liver is responsible for the breakdown of at least 75% of the injected enzyme. Radioautography of tissue sections of liver and spleen showed accumulated radioactivity in sinusoidal liver cells and red pulpa, respectively. These results are very similar to those for lactate dehydrogenase-5, creatine kinase MM, and several other enzymes that we have previously studied in rats. PMID:3197286

  5. Malignant mesenchymal tumors in two white-tailed jack rabbits (Lepus townsendii).

    PubMed

    Jardine, Claire; Wobeser, Gary A; Simko, Elemir

    2004-10-01

    Two white-tailed jack rabbits (Lepus townsendii) with proliferative lesions in their internal organs were submitted to the Canadian Cooperative Wildlife Health Centre (Saskatoon, Saskatchewan, Canada) for necropsy because of concern that dogs that had contact with the hares might have been exposed to an infectious disease. In both hares, the primary diagnosis was neoplasia. One hare had metastatic leiomyosarcoma and uterine fibroma, the other had metastatic mesenchymal tumors involving the liver and mesentery. These cases represent the only reports of malignant mesenchymal tumors in white-tailed jack rabbits that we have found in the literature. PMID:15650095

  6. Evaluation of the Safe Ischemic Time of Clamping During Intermittent Pringles Maneuver in Rabbits

    PubMed Central

    Kolahdoozan, Mohsen; Behdad, Akbar; Hosseinpour, Mehrdad; Behdad, Samin; Rezaei, Mohammad Taghi

    2015-01-01

    Background: The liver is the most commonly injured organ in blunt abdominal trauma. Although major hepatic bleeding may be partially controlled with portal triade clamping (the Pringle’s maneuver), continuous prolonged clamping results in liver ischemia. Objectives: The purpose of this study was to determine the safe time of Pringle maneuver based on pathologic changes of liver in rabbit models. Materials and Methods: In an experimental study, 20 New-Zealand white rabbits were selected. In laparotomy, a blunt dissector was passed through the foramen of Winslow and the hepato-duodenal ligament encircled with an umbilical tape. En masse Pringle maneuver was performed using atraumatic flexible clamps. Rabbits were divided into four groups based on Pringle maneuver time (30 minutes, 45 minutes, 60 minutes, and 75 minutes). A hepatic biopsy was performed at the beginning of operation. The degree of tissue injury was evaluated using blood markers. Results: There were five rabbits in each group. At the end of 60 minutes ischemia, only minor alterations were observed in pathological specimens. At the end of 75 minutes, hepatocyte damage and necrosis were observed. The serum levels of alanine aminotransferase (Group A: P = 0.02; Group B: P = 0.01; Group C: P = 0.0002; Group D: P = 0.01) and Aspartate aminotransferase (Group A: P = 0.03; Group B: P = 0.002; Group C: P = 0.0004; Group D: P = 0.0003) were significantly increased post-operatively. The maximum level was in the first day after operation. Conclusions: Continuous portal triade clamping (the Pringle maneuver) during liver ischemia (30 and 45 minutes) in rabbits resulted in no ischemic change. Increasing time of clamping to 30 minutes was safe in intermittent Pringle maneuver. PMID:26848477

  7. Vascularization of the ureter after experimental ureterolysis in rabbits.

    PubMed

    Sirca, A; Dekleva, A; Kordas, I

    1978-03-01

    The left ureter was isolated and its nutritive arteries interrupted in 43 rabbits. The blood flow in the isolated and in the control ureters was estimated intravitally by measuring the temperature in the wall of the ureters, and postmortally by counting the capillaries injected with India ink. The vascularization of the isolated ureter was lowered at 3 days after surgery and returned to normal values at 14 days. PMID:640805

  8. Teratology studies in the rabbit.

    PubMed

    Allais, Linda; Reynaud, Lucie

    2013-01-01

    The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compounds, including vaccines (see Chapters 1-7).Its availability, practicality in housing and in mating as well as its large size makes the rabbit the preferred choice as a non-rodent species. The study protocols are essentially similar to those established for the rat (Chapter 9), with some particularities. The study designs are well defined in guidelines and are relatively standardized between testing laboratories across the world.As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations. PMID:23138902

  9. Differential Fault Analysis of Rabbit

    NASA Astrophysics Data System (ADS)

    Kircanski, Aleksandar; Youssef, Amr M.

    Rabbit is a high speed scalable stream cipher with 128-bit key and a 64-bit initialization vector. It has passed all three stages of the ECRYPT stream cipher project and is a member of eSTREAM software portfolio. In this paper, we present a practical fault analysis attack on Rabbit. The fault model in which we analyze the cipher is the one in which the attacker is assumed to be able to fault a random bit of the internal state of the cipher but cannot control the exact location of injected faults. Our attack requires around 128 - 256 faults, precomputed table of size 241.6 bytes and recovers the complete internal state of Rabbit in about 238 steps.

  10. European Rabbits as Reservoir for Coxiella burnetii

    PubMed Central

    González-Barrio, David; Maio, Elisa; Vieira-Pinto, Madalena

    2015-01-01

    We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii. PMID:25988670

  11. Raising rabbits in a moving visual environment: an attempt to modify directional sensitivity in the retina

    PubMed Central

    Daw, N. W.; Wyatt, H. J.

    1974-01-01

    1. Rabbits were raised inside drums with vertical stripes painted on the inside. The rabbits were held stationary while the drum rotated continually around them: rotation was always in the same direction for any one animal. Rabbits in one litter were put in the drum for 15 min/day from 10-15 days after birth to about 60 days after birth, with the drum rotating to the right. Rabbits in another litter were put in for 15 min/day with the drum moving left. Rabbits in three other litters were put in for 2-3 hr/day with the drum moving right. All rabbits were kept in the dark when not in the drum. 2. Optokinetic nystagmus was measured by photographing eye movements during drum rotation at various stages of development. The response to rotation in both directions was measured in a few adult animals. Only small differences were found in the adult animals between optokinetic nystagmus in response to a drum moving right compared to a drum moving left. 3. Recordings were made from ganglion cells in the retina and their receptive fields were mapped. A total of 607 cells from deprived rabbits were analysed. The percentages of on-centre and off-centre centre-surround types, on-off directionally sensitive types, and on-directionally sensitive types were not significantly different from normal. 4. The percentages of directionally sensitive cells responding in the anterior, posterior, superior and inferior directions were normal. The fall-off in sensitivity for these cells with change in direction from the preferred direction was normal. 5. A few orientation sensitive cells were found responding to horizontally oriented bars. 6. We conclude that this selective deprivation of rabbits had little effect on the optokinetic response and no effect on the organization of the retina. PMID:4421344

  12. Urinary obstruction reduces glomerulogenesis in the developing kidney: a model in the rabbit.

    PubMed

    McVary, K T; Maizels, M

    1989-08-01

    To study the effect of unilateral ureteral obstruction upon the development of the kidney a fetal rabbit model was developed. A total of 27 rabbits underwent ureteral ligation in utero (24 days after conception) and 34 underwent ureteral ligation at term (30 days after conception). Two rabbits undergoing in utero ureteral ligation underwent decompression at term. Fetal development was evaluated by glomerular counts of mid sagittal sections of the kidney and compared to that of 67 normal rabbits, 43 littermates of rabbits undergoing surgery, 12 rabbits with missed ligation of the ureter and 4 whose ureters were ligated after the period of nephrogenesis had ended (57 days after conception). In the normal rabbit term occurred at 31 days after conception but nephrogenesis continued until 48 days when the cortical glomerular count reached approximately 650. Ligation of the ureter at 24 days led to a rapid decrease in cortical glomerular counts in the obstructed kidney but glomeruli developing within the nephrogenic cap were more resistant to the effects of the obstruction. Glomerular counts in the nonobstructed kidney were similar to those of littermates. Ligation of the ureter at 30 days produced similar findings. All operated fetuses and their littermates showed glomerular counts less than that of normal animals of the same age. In the 2 fetuses who underwent ureteral ligation at 24 days after conception and decompression at 30 days after conception sacrifice at 42 days after conception revealed that glomerular counts that had been reduced by 95 per cent by the obstruction showed 80 per cent recovery after decompression. It appears that renal development can be quantified by glomerular counts in the rabbit. Obstruction during fetal development reduces these counts while in a limited sample decompression of the obstructed kidney partially restores them. This model appears to be suitable for the study of the effects of fetal surgery upon renal function. PMID:2746793

  13. Nutritional requirements and diet choices of the pygmy rabbit (Brachylagus idahoensis): a sagebrush specialist.

    PubMed

    Shipley, Lisa A; Davila, Tara B; Thines, Nicole J; Elias, Becky A

    2006-11-01

    Sagebrush (Artemisia tridentata) comprises up to 99% of the winter and 50% of the summer diets of pygmy rabbits (Brachylagus idahoensis). Few animals specialize on such plants as sagebrush, which contain high levels of plant chemicals that can be toxic. We investigated the nutritional requirements of pygmy rabbits and their ability and propensity to consume sagebrush alone and as part of a mixed diet. We compared diet choices of pygmy rabbits with that of a generalist forager, the eastern cottontail (Sylvilagus floridanus). Pygmy rabbits had a moderately low nitrogen requirement (306.5 mg N/kg(0.75)/d), but a relatively high energy requirement, needing 750.8 kJ digestible energy/kg(0.75)/d to maintain their body mass while residing in small cages. They digested fiber in pelleted diets similarly to other small hindgut fermenters, but both cottontails and pygmy rabbits digested the fiber in sagebrush better than expected based on its indigestible acid detergent lignin content. Pygmy rabbits consumed more sagebrush than cottontails, regardless of the amount and nutritional quality of supplemental pellets provided. When consuming sagebrush alone, they ate barely enough to meet their energy requirements, whereas cottontails ate only enough sagebrush to meet 67% of theirs. Both rabbit species ate more sagebrush as the quality and quantity of supplemental pellets declined, and more greenhouse-grown sagebrush than sagebrush grown outside. Urine was more acidic when consuming sagebrush than when consuming pellets, indicating detoxification by the liver. Pygmy rabbits do not require sagebrush to survive, but seem to tolerate terpenes and other plant chemicals in sagebrush better than cottontails do. PMID:17082988

  14. A pandemic strain of calicivirus threatens rabbit industries in the Americas.

    PubMed

    McIntosh, Michael T; Behan, Shawn C; Mohamed, Fawzi M; Lu, Zhiqiang; Moran, Karen E; Burrage, Thomas G; Neilan, John G; Ward, Gordon B; Botti, Giuliana; Capucci, Lorenzo; Metwally, Samia A

    2007-01-01

    Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) - a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat. PMID:17910765

  15. A pandemic strain of calicivirus threatens rabbit industries in the Americas

    PubMed Central

    McIntosh, Michael T; Behan, Shawn C; Mohamed, Fawzi M; Lu, Zhiqiang; Moran, Karen E; Burrage, Thomas G; Neilan, John G; Ward, Gordon B; Botti, Giuliana; Capucci, Lorenzo; Metwally, Samia A

    2007-01-01

    Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) – a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat. PMID:17910765

  16. Agglutination of Staphylococcus aureus by Rabbit Sera

    PubMed Central

    Forsgren, Arne; Forsum, Urban

    1972-01-01

    Of 137 Staphylococcus aureus strains, 87 agglutinated in normal rabbit serum. The agglutination was shown to be caused by the Fc-part of immunoglobulin G (IgG). F(ab1)2-fragments of IgG and immunoglobulin M (IgM) in corresponding concentrations were unreactive. The agglutinating strains had a high or moderate content of protein A. Strains with a low content of protein A and protein A-negative mutants did not agglutinate. The importance of the reaction between the Fc part of IgG and protein A for serotyping of S. aureus is demonstrated. Two alternative methods for serotyping S. aureus are suggested, using either F(ab1)2 fragments of IgG or intact IgM. Images PMID:4564678

  17. Cytotoxicity of Rabbit Blood for Listeria monocytogenes

    PubMed Central

    Shultz, Leonard D.; Wilder, M. S.

    1971-01-01

    Our studies reveal that normal rabbit blood contains a potent bactericidin active against Listeria monocytogenes. The factor is present in greatest amounts in fresh undiluted serum but is absent in platelet extracts. A correlation was observed between the virulence of Listeria strains and their relative ability to survive in serum. The bactericidal titers obtained for plasma and plasma serum indicate that clotting must occur for optimum expression of antilisterial activity. The lethal action is not elevated after immunization with viable Listeria nor does it appear to depend on heat-labile components of complement. The active factor was removed from serum by filtration through a cellulose asbestos filter pad and further purified by carboxymethyl cellulose chromatography. Iron significantly diminishes serum lethality and completely abolishes the action of the purified component. The listericidal factor resembles β-lysin but may be a distinct part of a multiple system of similar bactericidins. PMID:5005312

  18. Osteoblastic Osteosarcoma in a Rabbit

    PubMed Central

    Ishikawa, Megumi; Kondo, Hirotaka; Onuma, Mamoru; Shibuya, Hisashi; Sato, Tsuneo

    2012-01-01

    An osteosarcoma developed in the tarsal joint region involving the distal tibia of a domestic rabbit (Oryctolagus cuniculus). Micrometastases were present in the lungs. Histologically the tumor was composed of ovoid to short-spindle cells with abundant giant cells, producing irregular islands of osteoids. The tumor cells were immunopositive with antiosteocalcin monoclonal antibody, consistent with their derivation from osteoblasts. According to review of 10 published cases, productive osteoblasic osteosarcoma is the most common bone tumor in rabbits, with half of all cases developing in the skull or facial bones. PMID:22546918

  19. Association between macroscopic appearance of liver lesions and liver histology in dogs with splenic hemangiosarcoma: 79 cases (2004-2009).

    PubMed

    Clendaniel, Daphne C; Sivacolundhu, Ramesh K; Sorenmo, Karin U; Donovan, Taryn A; Turner, Avenelle; Arteaga, Theresa; Bergman, Philip J

    2014-01-01

    Medical records for 79 dogs with confirmed splenic hemangiosarcoma (HSA) following splenectomy were reviewed for information regarding either the presence or absence of macroscopic liver lesions and the histopathological characteristics of the liver. Only 29 of 58 dogs (50%) with grossly abnormal livers had HSA metastasis. No dogs with grossly normal livers had metastasis detected on liver pathology. Gross lesions in the liver such as multiple nodules, dark-colored nodules, and active bleeding nodules were highly associated with malignancy. For the dogs in this study, performing biopsy in a grossly normal liver was a low-yield procedure in dogs with splenic HSA. PMID:25001171

  20. A comparative analysis of liver transcriptome suggests divergent liver function among human, mouse and rat.

    PubMed

    Yu, Yao; Ping, Jie; Chen, Hui; Jiao, Longxian; Zheng, Siyuan; Han, Ze-Guang; Hao, Pei; Huang, Jian

    2010-11-01

    The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function, we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. Our results show that 17396 genes are expressed in the human liver. 238 genes were identified as liver enrichment genes, involved in the functions of immune response and metabolic processes, from the MPSS and EST datasets. A comparative analysis of liver transcriptomes was performed in humans, mice and rats with microarray datasets shows that the expression profile of homologous genes remains significantly different between mouse/rat and human, suggesting a functional variance and regulation bias of genes expressed in the livers. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease. PMID:20800674

  1. Experimental infection of young rabbits with a rabbit enteric coronavirus.

    PubMed Central

    Descôteaux, J P; Lussier, G

    1990-01-01

    The clinical signs and lesions caused by the rabbit enteric coronavirus (RECV) were studied in young rabbits orally inoculated with a suspension containing RECV particles. The inoculated animals were observed daily for evidence of diarrhea. Fecal samples and specimens from the small intestine and from the gut associated lymphoid tissue (GALT) were collected from 2 h to 29 days postinoculation (PI) and processed for immune electron microscopy (IEM) and light microscopy. Coronavirus particles were detected in the cecal contents of most inoculated animals from 6 h to 29 days PI. Lesions were first observed 6 h PI and were characterized by a loss of the brush border of mature enterocytes located at the tips of intestinal villi and by necrosis of these cells. At 48 h PI, short intestinal villi and hypertrophic crypts were noted. In the GALT, complete necrosis of the M cells as well as necrosis of the enterocytes lining the villi above the lymphoid follicules with hypertrophy of the corresponding crypts were observed in all the animals. Five inoculated rabbits had diarrhea three days PI. The presence of RECV particles in the feces of the sick animals and the microscopic lesions observed in the small intestine suggested that the virus was responsible for the clinical signs. A few inoculated rabbits remained free of diarrhea. Fecal material collected at postmortem examination contained RECV particles. The results suggest that the virus could also produce a subclinical infection. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2174299

  2. The Effect of Irreversible Electroporation on the Femur: Experimental Study in a Rabbit Model

    PubMed Central

    Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    Irreversible electroporation (IRE) is a novel ablation method that has been tested in humans with lung, prostate, kidney, liver, lymph node and presacral cancers. As a new non-thermal treatment, the use of IRE to ablate tumors in the musculoskeletal system might reduce the incidence of fractures. We aimed to determine the ablation threshold of cortical bone and to evaluate the medium- and long-term healing process and mechanical properties of the femur in a rabbit model post-IRE ablation. The ablation threshold of cortical bone was between 1090 V/cm and 1310 V/cm (120 pulses). IRE-ablated femurs displayed no detectable fracture but did exhibit signs of recovery, including osteoblast regeneration, angiogenesis and bone remodeling. In the ablation area, revascularization appeared at 4 weeks post-IRE. Osteogenic activity peaked 8 weeks post-IRE and remained high at 12 weeks. The mechanical strength decreased briefly 4 weeks post-IRE but returned to normal levels within 8 weeks. Our experiment revealed that IRE ablation preserved the structural integrity of the bone cortex, and the ablated bone was able to regenerate rapidly. IRE may hold unique promise for in situ bone tissue ablation because rapid revascularization and active osteogenesis in the IRE ablation area are possible. PMID:26655843

  3. The Effect of Irreversible Electroporation on the Femur: Experimental Study in a Rabbit Model.

    PubMed

    Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    Irreversible electroporation (IRE) is a novel ablation method that has been tested in humans with lung, prostate, kidney, liver, lymph node and presacral cancers. As a new non-thermal treatment, the use of IRE to ablate tumors in the musculoskeletal system might reduce the incidence of fractures. We aimed to determine the ablation threshold of cortical bone and to evaluate the medium- and long-term healing process and mechanical properties of the femur in a rabbit model post-IRE ablation. The ablation threshold of cortical bone was between 1090 V/cm and 1310 V/cm (120 pulses). IRE-ablated femurs displayed no detectable fracture but did exhibit signs of recovery, including osteoblast regeneration, angiogenesis and bone remodeling. In the ablation area, revascularization appeared at 4 weeks post-IRE. Osteogenic activity peaked 8 weeks post-IRE and remained high at 12 weeks. The mechanical strength decreased briefly 4 weeks post-IRE but returned to normal levels within 8 weeks. Our experiment revealed that IRE ablation preserved the structural integrity of the bone cortex, and the ablated bone was able to regenerate rapidly. IRE may hold unique promise for in situ bone tissue ablation because rapid revascularization and active osteogenesis in the IRE ablation area are possible. PMID:26655843

  4. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

  5. Real-time PCR assay for the detection of picoplankton DNA distribution in the tissues of drowned rabbits.

    PubMed

    Uchigasaki, Seisaku; Tie, Jian; Haseba, Takeshi; Cui, Fanlai; Ohno, Youkichi; Isobe, Eiji; Isahai, Isamu; Tsutsumi, Hirofumi

    2016-05-01

    The detection of plankton DNA is one of the important methods for the diagnosis of drowning from postmortem tissues. This study investigated the quantities of picoplankton (Cyanobacteria) DNA in the lung, liver, kidney tissues and blood of drowned and non-drowned rabbits, and the sensitivity of detection of picoplankton DNA by polymerase chain reaction (PCR) detect for the diagnosis of death from drowning. For this purpose, the DNA of the 16S ribosomal RNA gene of picoplankton was quantitatively assayed from the tissues of drowned and non-drowned rabbits immersed in water after death. Each of the liver, kidney and lung tissues and blood were obtained from drowned and non-drowned rabbits. Picoplankton DNA in the tissues was extracted using the DNeasy® Blood & Tissue kit to determine the yield of picoplankton DNA from each tissue. TaqMan real-time PCR was performed for quantitative analysis of picoplankton DNA. Target DNA was detected in the liver, kidney and lung samples obtained from the drowned rabbits, while no picoplankton DNA was detected in the non-drowned rabbit tissues (except in lung samples). The results verified that direct PCR for the detection of picoplankton DNA is useful for the diagnosis of drowning. Although we observed seasonal changes in the quantity of picoplankton in river water, we were able to detect DNA from various organs of drowned bodies during the season when picoplankton were not the most abundant. PMID:27161920

  6. Amino acids fail to prevent halothane depression of albumin synthesis: studies in the isolated perfused rat liver.

    PubMed

    Kruskal, J B; Franks, J J; Kirsch, R E

    1991-01-01

    Halothane (1.3 MAC) and ethanol (0.4%) depress albumin synthesis in isolated perfused rat livers (IPRLs). Addition of amino acids prevents depression by ethanol. We have examined the effects of amino acids on albumin synthesis by IPRLs exposed to halothane. Seventeen livers were perfused with a mixture of rat erythrocytes and rabbit plasma. Five were exposed to oxygen/carbon dioxide alone and 12 to oxygen/carbon dioxide with 1.5% halothane. A mixture of 10 essential amino acids was added to the perfusate of six of the halothane-exposed livers to a concentration approximately 10 times the normal rat plasma level. Perfusate concentrations of newly synthesized albumin were measured by radial immunodiffusion, and the rate of synthesis for the 4.25-h study period was calculated. The mean +/- SEM albumin synthetic rate (mg/h per 300-g rat) in the control group (12.13 +/- 1.36) was significantly greater than in the group receiving halothane alone (6.98 +/- 0.92). Amino acid treatment failed to prevent halothane depression of albumin synthesis (8.68 +/- 0.84). Thus, although amino acids block ethanol depression of albumin synthesis, we could show no such effect in rat livers exposed to halothane. PMID:1984365

  7. Effect of syphilitic rabbit sera taken at different periods after infection on treponemal motility, treponemal attachment to mammalian cells in vitro, and treponemal infection in rabbits.

    PubMed

    Wong, G H; Steiner, B; Graves, S

    1983-08-01

    The time course of antibody synthesis during syphilis was studied in experimentally infected rabbits. A rapid antibody response was seen; the rabbits became positive in both the rapid plasma reagin (RPR) test and Treponema pallidum haemagglutination assay (TPHA) by nine days after infection. Treponemal immobilising antibodies were also seen as early as nine days after infection. Antibody inhibition of treponemal attachment to baby rabbit genital organ (BRGO) cells in culture occurred with immune sera taken 30 days after infection but not earlier. When T pallidum was mixed with immune syphilitic rabbit sera taken at different stages of the infection and used to infect normal rabbits the rabbits became partially resistant to T pallidum only when the treponemes were mixed with sera taken at least 30 days after syphilitic infection. This appearance correlated well with the development of antibodies which blocked attachment of T pallidum to host cells. These antibodies may be involved in the resistance to reinfection which develops in syphilis as the disease progresses. PMID:6347332

  8. Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits

    PubMed Central

    Zubairi, Maysaa B.; Ahmed, Jawad H.; Al-Haroon, Sawsan S.

    2014-01-01

    Objectives: To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity. Materials and Methods: Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed. Results: Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments. Conclusion: Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection. PMID:25538338

  9. Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits.

    PubMed

    Sethi, Jyoti; Yadav, Mridul; Sood, Sushma; Dahiya, Kiran; Singh, Veena

    2010-10-01

    Fresh leaves of Ocimum Sanctum (OS) were used to study its effect on male reproductive function (sperm count and reproductive hormones) in male albino rabbits. Animals in the test group received supplementation of 2 g of fresh leaves of OS per rabbit for 30 days, while the control group was maintained on normal diet for the same duration. Sperm count and hormonal estimation [testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH)] were done in serum samples of both groups and compared. A significant decrease was noted in the sperm count in test group rabbits. Serum testosterone levels showed marked increase while FSH and LH levels were significantly reduced in OS-treated rabbits. The results suggest the potential use of OS as an effective male contraceptive agent. PMID:21455446

  10. Cell-mediated Immunity to Human Tamm-Horsfall Glycoprotein in Autoimmune Liver Disease with Renal Tubular Acidosis

    PubMed Central

    Tsantoulas, D. C.; McFarlane, I. G.; Portmann, B.; Eddleston, A. L. W. F.; Williams, Roger

    1974-01-01

    Cell-mediated immune responses to Tamm-Horsfall glycoprotein isolated from human urine were investigated using the leucocyte migration test. Abnormal responses were found in 91% of patients with active chronic hepatitis or primary biliary cirrhosis with an associated renal tubular acidosis (R.T.A.) but in only 19% of those without R.T.A. In nearly all of a group of patients without autoimmune liver disease and in a control group of normal subjects results were within normal limits. In addition, using an immunofluorescent technique with rabbit antibody to human Tamm-Horsfall glycoprotein, it was possible to show the presence in human liver cell membrane of material reacting immunologically as Tamm-Horsfall. These findings suggest that the development of an immune response to this glycoprotein, initiated by release of cross-reacting antigens from damaged hepatocytes, could be the mechanism underlying the occurrence of R.T.A. in some patients with autoimmune liver disease. ImagesFIG. 3 PMID:4611578

  11. Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model.

    PubMed

    Hu, Jiafen; Cladel, Nancy; Peng, Xuwen; Balogh, Karla; Christensen, Neil D

    2008-02-01

    Cottontail rabbit papillomavirus (CRPV)/rabbit model is widely used to study pathogenesis of papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol 2006;177(11):8037-45]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPVE1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic rabbits, respectively, by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic rabbits from both genetic backgrounds but not in the control-vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software. PMID:18187239

  12. Histopathological features of Capillaria hepatica infection in laboratory rabbits.

    PubMed

    Mowat, Vasanthi; Turton, John; Stewart, Jacqui; Lui, Kai Chiu; Pilling, Andrew M

    2009-08-01

    Capillaria hepatica is a nematode parasite of wild rodents and other mammals. Adult worms inhabit the liver. Recently, during the necropsy examination of a group of 160 rabbits from a commercial supplier, firm pale or cystic areas (1-5 mm) were noted on the liver in thirteen animals. On further investigation, these animals were found to be infected with C. hepatica. The histopathological features of the infection in the rabbit are described for the first time and diagnostic features recorded. Lesions were identified predominantly in portal tracts consisting of dilated bile ducts with luminal debris, peribiliary inflammatory cell infiltrates, and fibrosis. Large granulomas (macrogranulomas) were evident in portal areas and involved the bile ducts. Macrogranulomas contained collections of characteristic C. hepatica eggs, macrophages, eosinophils, and lymphocytes. Small granulomas (microgranulomas), characterized by epithelioid macrophages surrounded by lymphocytes and eosinophils, were also identified. C. hepatica eggs were also observed in the lumina of the bile ducts and gall bladder. No adult C. hepatica worms were identified. Oocysts of Eimeria stiedae were also evident in the biliary epithelium in some animals. The unique characteristics of the C. hepatica life cycle are described, and the differential diagnosis of hepatic capillariasis is discussed. PMID:19581239

  13. Fate of transgenic deoxyribonucleic acid fragments in digesta and tissues of rabbits fed genetically modified soybean meal.

    PubMed

    Morera, P; Basiricò, L; Ronchi, B; Bernabucci, U

    2016-03-01

    Numerous animal feeding studies have investigated the presence of DNA from transgenic plants in tissues from different animal species, but the data reported are sometimes controversial. The aim of this study was to investigate the presence of transgenic DNA (tDNA) in the digesta and tissues of a meat rabbit breed fed genetically modified (GM) soybean meal. Fifteen male New Zealand White rabbits were used for the experimental trial. Ten rabbits (treated group [TG]) were fed a mixed feed containing 10% GM soybean meal and 5 rabbits (control group [CG]) received a mixed feed containing conventional soybean meal, both from weaning (28 d of age) to slaughter (80 ± 3 d). Samples of blood, liver, kidney, heart, stomach, intestine (jejunum), lateral quadricep muscle, longissimus muscle, and perirenal adipose tissue were collected to assess the possible DNA transfer from GM feed to animal tissues. Samples of stomach contents and feces were also taken to study the degradability of ingested tDNA from feed in the digestive tract of rabbit. Moreover, samples of hair were collected to determine the possible environmental contamination from feed powders present on the farm. The DNA extraction was performed using specific genomic DNA kits. All samples were monitored, by using real-time PCR, for oligonucleotide primers and probes specific for the transgenic Roundup Ready soybean 40-3-2 and for the endogenous () gene. As an internal control of rabbit tissues, the presence of the () gene was used. In this study, no fragments of tDNA were detectable in tissue DNA samples of rabbits except in the extracted DNA from stomach digesta, feces, and hair of rabbits fed with GM soybean. Similar results were found for the reference gene, whereas the presence of the gene was detected in all rabbit tissues. The lack of tDNA of soybean in rabbit tissues represents an important result, which demonstrates that meat from rabbits fed a diet containing GM feed is as that derived from rabbits fed

  14. Liver bioengineering

    PubMed Central

    Caralt, Mireia; Velasco, Enrique; Lanas, Angel; Baptista, Pedro M

    2014-01-01

    Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. PMID:25102189

  15. Na+ transport by rabbit urinary bladder, a tight epithelium.

    PubMed

    Lewis, S A; Diamond, J M

    1976-08-27

    By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially

  16. Reversibility of cadmium-induced health effects in rabbits

    SciTech Connect

    Nomiyama, K.; Nomiyama, H.

    1984-03-01

    Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 ..mu..g Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects. 31 references, 4 figures.

  17. [Effect of GABA receptor agonist phenibut on behavior and respiration of rabbits in the negative emotional situation].

    PubMed

    Ziablitseva, E A; Pavlova, I V

    2007-01-01

    The influence of systemic injection of GABA-receptor agonist--phenibut (40 mg/kg, s/c) on open field behavior, behavioral reactivity and changes in respiratory parameters after exposure of negative emotional stimuli was studied in three rabbit groups differentiated by locomotor activity in open field (active, passive and medium-active animals). The injection of phenibut results in decrease of rabbits horizontal locomotor activity and some components of research behavior in open field and also decrease of behavioral reactivity on emotional stimuli. At the same time the probability of both an active orienting exploratory or defensive reactions and passive reactions (freezing) were decreased. The influence of phenibut depended on typological features of rabbits: the most potent effect occurred upon behavior of active rabbits, less on passive animals and practically none on medium-active rabbits. The phenibut injection results in increase of duration of inhalation during exposure to emotional stimuli, whereas it decreased in normal. PMID:17944107

  18. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  19. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  20. Benign Liver Tumors

    MedlinePlus

    ... Search: Your Liver Liver Health and Wellness Recipes Liver Disease Information Patients & Families Caregiver's FAQ Become an Organ ... 2013 Liver Awareness Month Personal Story - David Roncori Liver Disease - The Big Picture 13 Ways to a Healthy ...

  1. Bisphenol A exposure induces metabolic disorders and enhances atherosclerosis in hyperlipidemic rabbits.

    PubMed

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2015-09-01

    Bisphenol A (BPA) is an artificial environmental endocrine disrupter. Excess exposure to BPA may induce many disorders in the metabolism and cardiovascular system. However, the underlying toxicological mechanisms remain largely unknown. In this study, we administered genetically hyperlipidemic Watanabe heritable hyperlipidemic (WHHL-MI) rabbits (male, 14 week old), which have more common features with humans than the mouse and rat especially in the metabolism and cardiovascular system, with BPA at 40 mg kg(-1)  day(-1) for 8 weeks by gavage and compared their plasma lipids, glucose and insulin response with those of the vehicle group. All of the rabbits were sacrificed, and their pancreas, liver, adipose tissue, heart and aorta were analyzed using histological and morphometric methods. Furthermore, we treated human hepatoma HepG2 cells and human umbilical cord vein endothelial cells (HUVECs), with different doses of BPA based on the serum BPA levels in the WHHL rabbits for 6 h to investigate the possible molecular mechanisms. Our results showed that BPA-treated rabbits showed insulin resistance, prominent adipose accumulation and hepatic steatosis. Additionally, BPA exposure also caused myocardial injury and enhanced the development of atherosclerosis in the aortic arch with increased macrophage number (86%) and advanced lesion areas (69%). Increased expression of inflammatory genes found in the liver of BPA-treated rabbits along with the up-regulation of ER stress, lipid and glucose homeostasis and inflammatory genes in the cultured HepG2 cells and HUVECs suggest that BPA may induce metabolic disorders and enhance atherosclerosis through regulating above molecular pathways in the liver and endothelium. PMID:25619500

  2. Enhanced thromboxane synthesis in atria from infarcted rabbit hearts

    SciTech Connect

    Dunkel, C.G.; Evers, A.S.; Needleman, P.

    1986-03-05

    The authors have previously shown that left ventricular myocardial infarction (MI) results in enhanced thromboxane (Tx) synthesis in response to n-formylmethionyl-leucyl-phenylalanine (fMLP). To anatomically localize this response, cardiac atria and ventricles were removed from normal rabbits and rabbits subjected 4 days previously to MI. Atria were placed in a tissue bath, ventricles were perfused with buffer via the vasculature and both preparations were challenged with fMLP. TxB/sub 2/ in the bath media or ventricular effluent was measured by specific RIA. Atria from normal and infarcted hearts produced similar basal levels of Tx. Following fMLP stimulation, atria from infarcted hearts produced 10X more Tx than normal atria. Ventricles from normal and infarcted hearts produced no Tx basally and only small quantities with fMLP stimulation. Incubation of microsomes prepared from the various chambers of the heart with (/sup 14/-C) arachidonate showed that Tx synthetic capacity in both normal and infarcted hearts resides almost exclusively in the right cardiac atria. These results show that cardiac Tx synthesis is largely an atrial phenomenon and that left ventricular myocardial infarction results in enhanced fMLP-stimulated Tx synthesis.

  3. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  4. Liver transplant

    MedlinePlus

    Risks for any anesthesia are: Problems breathing Reactions to medications Risks for any surgery are: Bleeding Heart attack or stroke Infection Liver transplant surgery and management after surgery carry major risks. There is ...

  5. The effect of MRI contrast agents on hepatic and splenic uptake in the rabbit during (99m) Tc-MDP bone scintigraphy.

    PubMed

    Qiu, Lin; Tang, Yuhui; Chen, Yue; Huang, Zhanwen; Zhu, Yan; Zhang, Li; Cai, Liang; Wan, Qiang; Feng, Yue

    2015-01-01

    The objective of this study was to investigate the effects of Omniscan® and Magnevist® on (99m) Tc-MDP uptake in rabbits during (99m) Tc-MDP bone scintigraphy. In Experiment Group 1, 30 healthy adult rabbits were randomized into six subgroups (n = 5); each subgroup experienced a different time interval between injections (30 min, 60 min, 120 min, 240 min, 360 min, 24 h). All six subgroups were injected first with Omniscan®, then with (99m) Tc-MDP. After 7 days, the same six subgroups were injected with normal saline followed by (99m) Tc-MDP at the same time intervals. In Experiment Group 2, 20 healthy adult rabbits were allocated randomly to four subgroups (n = 5); each subgroup experienced a different time interval between injections (30 min, 60 min, 120 min, 240 min). All four subgroups were injected first with Magnevist®, then with (99m) Tc-MDP. After 7 days, the same four subgroups were injected with normal saline followed by (99m) Tc-MDP. In all experiments, whole-body skeletal imaging was performed. Liver, spleen, and background were delineated to determine the target-to-background (T/B) ratio. Diffusely increased intake of the imaging agent was seen in the liver and spleen when the injection-time interval between Omniscan® and (99m) Tc-MDP varied from 30 min to 240 min and when the time interval between Magnevist® and (99m) Tc-MDP was 30 min-60 min. The imaging findings are consistent with the results of L/B and S/B ratios in each experiment group. Both Omniscan® and Magnevist® have an effect on (99m) Tc-MDP uptake during bone scanning; the main effect is diffusely increased hepatic and splenic activity. PMID:26036779

  6. Rabbit Ileal Loop Response to Strains of Clostridium perfringens1

    PubMed Central

    Duncan, Charles L.; Sugiyama, H.; Strong, Dorothy H.

    1968-01-01

    The ligated loop of the rabbit intestine was investigated as a possible experimental model for the study of Clostridium perfringens food poisoning. The method of preparation of the challenge inoculum was important in determining whether a given strain would provoke a response. When cultures were grown for 4 hr at 37 C in Skim Milk (Difco), 14 of 29 type A strains isolated from food-poisoning outbreaks consistently produced exudation of fluid and consequent dilation of the ileal segments. In contrast, 15 of the 18 strains derived from other sources failed to elicit a response. By use of different inoculum preparations, nearly all strains could be made to give at least an occasional positive loop reaction. Diarrhea was not obtained in rabbits by intraluminal injection into the normal ileum or by per os administration of the cultures. Lecithinase, purified and in concentrated culture supernatant fractions, failed to produce a response in the isolated ileal loops. Images PMID:4297020

  7. Infrared laser welding of the rabbit cornea in vivo

    NASA Astrophysics Data System (ADS)

    Williams, John M.; Burstein, Neal L.; Nowicki, Michael J.; Zietkiewicz, Christopher J.; Jeffers, William Q.

    1995-05-01

    The hydrogen fluoride laser has been used to successfully weld corneal tissue in vivo. Previous experiments have demonstrate the success of producing watertight welds in both porcine and human cadaver corneas. Wound bursting strengths of up to three times normal intraocular pressure have been reported. In this study, an in vivo model was utilized, specifically the rabbit cornea. Twelve New Zealand white rabbits, received a 7 mm, full thickness, linear corneal incision in one eye, and stay sutures were placed. Six of the wounds were welded with a semiconductor infrared laser, and six eyes served as controls. At two and four weeks, both histologic and tensiometric studies were performed. There was a trend toward increasing wound strength when the two and four week specimens were compared. Corneal welding may prove to be an adjunct to current suturing techniques in humans. Procedures requiring the closure of corneal incisions such as cataract extraction or penetrating keratoplasty may benefit from this technique.

  8. Experimental infection of eastern cottontail rabbits Sylvilagus floridanus) with infectious bovine rhinotracheitis virus.

    PubMed

    Lupton, H W; Reed, D E

    1979-09-01

    Experimental infection of eastern cottontail rabbits (Sylvilagus floridanus) with infectious bovine rhinotracheitis virus caused acute keratoconjunctivitis and a fatal systemic infection. The clinical syndrome was characterized initially by blepharospasm and ocular discharge. The rabbits were markedly depressed on post-exposure day (PED) 5 and were dead or moribund on PED 6. The virus was readily recovered from liver and adrenal gland tissue on PED 6 and from conjunctival swabs on PED 1 to 6. Histopathologic studies revealed a few necrotic foci in the liver and multiple focal to diffuse necrosis of the adrenal glands. Viral isolation and immunofluorescence tests were used to demonstrate a direct association between infectious bovine rhinotracheitis viral antigens and the lesions. PMID:230773

  9. [Liver intervention].

    PubMed

    Oi, H

    2000-12-01

    Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID:11197832

  10. Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression

    PubMed Central

    Yang, Dongshan; Song, Jun; Zhang, Jifeng; Xu, Jie; Zhu, Tianqing; Wang, Zhong; Lai, Liangxue; Chen, Y. Eugene

    2016-01-01

    The laboratory rabbit has been a valuable model system for human disease studies. To make the rabbit model more amendable to targeted gene knockin and stable gene over-expression, we identified a rabbit orthologue of the mouse Rosa26 locus through genomic sequence homology analysis. Real-time PCR and 5′ RACE and 3′ RACE experiments revealed that this locus encodes two transcript variants of a long noncoding RNA (lncRNA) (rbRosaV1 and rbRosaV2). Both variants are expressed ubiquitously and stably in different tissues. We next targeted the rabbit Rosa26 (rbRosa26) locus using CRISPR/Cas9 and produced two lines of knock-in rabbits (rbRosa26-EGFP, and rbRosa26-Cre-reporter). In both lines, all the founders and their offspring appear healthy and reproduce normally. In F1 generation animals, the rbRosa26-EGFP rabbits express EGFP, and the rbRosa26-Cre-reporter rabbits express tdTomato ubiquitously in all the tissues examined. Furthermore, disruption of rbRosa26 locus does not adversely impact the animal health and reproduction. Therefore, our work establishes rbRosa26 as a safe harbor suitable for nuclease mediated gene targeting. The addition of rbRosa26 to the tool box of transgenic research is expected to allow diverse genetic manipulations, including gain-of function, conditional knock out and lineage-tracing studies in rabbits. PMID:27117226

  11. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

    PubMed Central

    Wan Ahmad Kamal, Wan Syazli Rodzaia; Noor, Norizal Mohd; Abdullah, Shafie

    2013-01-01

    Background Ischemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published. Methods Sixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed. Results The results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups. Conclusions In conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts. PMID:24286040

  12. Herpesvirus sylvilagus in cottontail rabbits: evidence of shedding but not transplacental transmission.

    PubMed

    Spieker, J O; Yuill, T M

    1977-01-01

    Herpesvirus sylvilagus was inoculated into five cottontail rabbits (Sylvilagus floridanus) at various stages of pregnancy; they subsequently had litters in the laboratory. Three other cottontails chronically infected with the virus were bred and bore young in large outdoor pens. Thirty-four living neonates and dead fetuses were weighed, measured and aseptically necropsied. A total of 31 liver, spleen and kidney samples, 16 lymph node, 28 heart and 10 brain samples were collected and processed for inoculation into rabbit kidney cell cultures to attempt virus isolation. Virus was not detected in the 147 tissue samples tested. Pre-conception viremias ranged from 10-21 plaque-forming units per 0.5 ml. Virus isolation was attempted from 26 oral and lacrymal, 23 genital, nine urine and fecal, and four milk and male ejaculate samples from eight infected rabbits. Virus was recovered from two salivary samples from the same rabbit. Triamcinolone acetonide administered daily for four days to five rabbits did not stimulate excretion of virus. PMID:190423

  13. A novel rabbit model for studying RPE transplantation

    PubMed Central

    Cong, Lidan; Sun, Dawei; Zhang, Zhongyu; Jiao, Wanqiu; Rizzolo, Lawrence J.; Peng, Shaomin

    2008-01-01

    Purpose The goal of this project is to develop a model of retinal pigment epithelium (RPE) transplantation that permits extensive and reliable analysis of the transplants. Methods Cultures of newborn rabbit RPE were evaluated by morphology, electrophysiology and the expression of zonula occludens-1, cytokeratin and a melanocyte marker (S-100). Cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) were transplanted into the subretinal space of rabbits using a 30 gauge needle without making a conjunctival flap or sclerotomy. The transplants were examined by fundus photography, confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT) and angiography. At two months the retina was examined histochemically. Results A one minute incubation at 37°C with 20μM CFDA-SE did not affect morphology or the expression of marker proteins. In co-culture, the labeled cells integrated into monolayers that developed a normal transepithelial electrical resistance of 400-450 Ωcm2. Dye was not transferred from labeled to non-labeled RPE cells. Transplanted RPE was detectable for at least 2 months. Angiography demonstrated an intact blood retinal barrier. The normal morphology of the retina and lack of debris in the subretinal space, suggested the transplanted RPE was functional. Conclusions Primary cultures of newborn rabbit RPE were highly differentiated even when labeled with CFDA-SE. Labeled cells could be followed long-term in vitro and in vivo. This model can examine how culture and transplantation protocols affect the reformation of a functional RPE monolayer. The similar size of rabbit and human eyes will facilitate the translation of these protocols to the bedside. PMID:18502985

  14. Hypocholesterolemic activity of nut shell extract of Semecarpus anacardium (Bhilawa) in cholesterol fed rabbits.

    PubMed

    Sharma, A; Mathur, R; Dixit, V P

    1995-06-01

    Administration of S. anacardium nut shell extract to cholesterol fed rabbits resulted in a significant reduction in serum cholesterol (-73.3%) and serum LDL-Chol. (-80%). The extract feeding also prevented the accumulation of cholesterol/triglycerides in liver, heart muscle and aorta and caused a regression of plaques (75.3-83.5%). These results indicate that S. anacardium is hypocholesterolemic in action and prevents cholesterol induced atheroma. Possible mechanism of action is discussed. PMID:7590951

  15. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD)

    PubMed Central

    2014-01-01

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection. PMID:24490832

  16. Ionophore antibiotic (narasin) poisoning in rabbits.

    PubMed

    Salles, M S; Lombardo de Barros, C S; Barros, S S

    1994-10-01

    Outbreaks of narasin poisoning in rabbits from several commercial rabbit-raising farms in the state of Parana, Brazil, are reported. Approximately 5,000/35,000 rabbits died after having consumed a pelleted ration to which poultry ration premix had been added. Clinical signs included apathy, anorexia, muscle weakness, impaired walking, diarrhea, respiratory distress, and opistothonus. Gross findings were not remarkable, but varying degrees of degeneration, necrosis and regeneration of skeletal muscles were consistent histopathological features in affected rabbits. Myocardial changes were mild or absent. Thirty ppm of narasin were detected in the ration fed the rabbits. The disease was experimentally reproduced by feeding the suspected ration and by administering narasin po to rabbits. PMID:7839570

  17. Enteropathogenic Escherichia coli Prevalence in Laboratory Rabbits

    PubMed Central

    Swennes, Alton G.; Buckley, Ellen M.; Madden, Carolyn M.; Byrd, Charles P.; Donocoff, Rachel S.; Rodriguez, Loretta; Parry, Nicola M. A.; Fox, James G.

    2013-01-01

    Rabbit-origin enteropathogenic E. coli (EPEC) causes substantial diarrhea-associated morbidity and has zoonotic potential. A culture-based survey was undertaken to ascertain its prevalence. EPEC was isolated from 6/141 (4.3%) commercially-acquired laboratory rabbits. Three of these did not have diarrhea or EPEC-typical intestinal lesions; they instead had background plasmacytic intestinal inflammation. Asymptomatically infected rabbits may function as EPEC reservoirs. PMID:23391439

  18. The thermal dependence of Na+ flux in isolated liver cells from ectotherms and endotherms.

    PubMed

    Else, Paul L

    2016-07-15

    The thermal dependence (0-40°C) of Na(+) flux in isolated liver cells of three endotherms (mice, rat and rabbit) was compared with that of ectotherms in the form of a thermally tolerant amphibian (cane toad), a cold-water fish (rainbow trout) and a thermophilic reptile (lizard). Mammals were found to share similar high rates of Na(+) flux (3.0-3.7 nmol Na(+) mg(-1) protein min(-1)) at their normal body temperatures (36-39°C). These Na(+) flux rates were significantly greater (P<0.0004-0.0001) than those of the ectotherms, which shared similar low rates of Na(+) flux (0.7-1.3 nmol Na(+) mg(-1) protein min(-1)) at their very different normal acclimated body temperatures (15°C for trout, 25°C for toad and 37°C for the lizard species). Trout, which possess highly unsaturated membranes (similar to those of mammals), showed a Na(+) flux with high thermal sensitivity at low temperatures similar to that found in mammals at higher temperatures. The thermal sensitivity of toad Na(+) flux was significantly less (P<0.05-0.01) than that of rat and rabbit. Trout Na(+) flux did not increase with increasing temperature much above 20°C, whereas all other species measured increased their Na(+) flux with increasing temperature up to 40°C. In conclusion, at normal operating body temperatures, the rate of Na(+) flux is much lower in ectotherms. PMID:27207635

  19. Effect of chocolate and Propolfenol on rabbit spermatogenesis and sperm quality following bacterial lipopolysaccharide treatment.

    PubMed

    Collodel, Giulia; Moretti, Elena; Del Vecchio, Maria Teresa; Biagi, Marco; Cardinali, Raffaella; Mazzi, Lucia; Brecchia, Gabriele; Maranesi, Margherita; Manca, Daniela; Castellini, Cesare

    2014-08-01

    The aims of the study were to evaluate the effects of chocolate and propolis-enriched diets on rabbit spermatogenesis, sperm motility, and ultrastructure following bacterial lipopolysaccharide (LPS) treatment. Thirty-two New Zealand White rabbits were divided into four groups. The LPS-Propolfenol(®) group received propolis (500 mg/kg/day) in their diet for 15 days, while the LPS-chocolate group was fed 70% cacao chocolate (1 g/1 kg/day) for the same period. Following the diet treatments, rabbits in the LPS-Propolfenol(®) and LPS-chocolate groups, and an LPS group received a single intraperitoneal dose of 50 μg/kg LPS, and the control group received only saline. Kinematic sperm traits were evaluated with a computer assisted sperm analyzer (CASA) system, and ultrastructural characteristics were examined by transmission electron microscopy (TEM). Testicular and epididymal tissues were observed by light microscopy and TEM and multiplex real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect and quantify toll-like receptor-4 (TLR-4) gene expression. The values of the analyzed semen parameters of rabbits treated with LPS-Propolfenol(®) and LPS-chocolate did not show any variations compared with the control group, but they were lower in rabbits treated only with LPS. Alterations observed in the testicular tissue of LPS treated-rabbits were not detected in specimens from the LPS-chocolate and LPS-Propolfenol(®) groups, which showed normal spermatogenesis. The TLR-4 mRNA expression was similar in controls, in LPS treated, and in LPS-chocolate groups, but it was significantly (p < 0.01) decreased in LPS-Propolfenol(®) rabbits. In conclusion, a chocolate and propolis-enriched diet showed a protective effect on the spermatogenetic process of buck rabbits following LPS treatment. PMID:24785944

  20. Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

    PubMed Central

    Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy; Trichel, Anita; Ortiz, Luis A.; Cole, Kelly Stefano; Barry, Eileen

    2011-01-01

    Background Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. PMID:21931798

  1. Multi-institutional Quantitative Evaluation and Clinical Validation of Smart Probabilistic Image Contouring Engine (SPICE) Autosegmentation of Target Structures and Normal Tissues on Computer Tomography Images in the Head and Neck, Thorax, Liver, and Male Pelvis Areas

    SciTech Connect

    Zhu, Mingyao; Bzdusek, Karl; Brink, Carsten; Eriksen, Jesper Grau; Hansen, Olfred; Jensen, Helle Anita; Gay, Hiram A.; Thorstad, Wade; Widder, Joachim; Brouwer, Charlotte L.; Steenbakkers, Roel J.H.M.; Vanhauten, Hubertus A.M.; Cao, Jeffrey Q.; McBrayne, Gail; Patel, Salil H.; Cannon, Donald M.; Hardcastle, Nicholas; Tomé, Wolfgang A.; Guckenberg, Matthias; Parikh, Parag J.

    2013-11-15

    Purpose: Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE). Methods and Materials: CT images of 125 treated patients (32 head and neck [HN], 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients. Results: The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients. Conclusions: Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility.

  2. Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms.

    PubMed Central

    Folkesson, H G; Matthay, M A; Hébert, C A; Broaddus, V C

    1995-01-01

    Acid aspiration lung injury may be mediated primarily by neutrophils recruited to the lung by acid-induced cytokines. We hypothesized that a major acid-induced cytokine was IL-8 and that a neutralizing anti-rabbit-IL-8 monoclonal antibody (ARIL8.2) would attenuate acid-induced lung injury in rabbits. Hydrochloric acid (pH = 1.5 in 1/3 normal saline) or 1/3 normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 or 24 h. In acid-instilled rabbits without the anti-IL-8 monoclonal antibody, severe lung injury developed in the first 6 h; in the long-term experiments, all rabbits died with lung injury between 12 and 14 h. In acid-instilled rabbits given the anti-IL-8 monoclonal antibody (2 mg/kg, intravenously) either as pretreatment (5 min before the acid) or as treatment (1 h after the acid), acid-induced abnormalities in oxygenation and extravascular lung water were prevented and extravascular protein accumulation was reduced by 70%; in the long-term experiments, anti-IL-8 treatment similarly protected lung function throughout the 24-h period. The anti-IL-8 monoclonal antibody also significantly reduced air space neutrophil counts and IL-8 concentrations. This study establishes IL-8 as a critical cytokine for the development of acid-induced lung injury. Neutralization of IL-8 may provide the first useful therapy for this clinically important form of acute lung injury. Images PMID:7615779

  3. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

    Helling, Gunnel; Wahlin, Staffan; Smedberg, Marie; Pettersson, Linn; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

    2016-01-01

    Background Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations. Methods Four different groups of patients were studies; chronic liver failure (n = 40), acute on chronic liver failure (n = 20), acute fulminant liver failure (n = 20), and post-hepatectomy liver failure (n = 20). Child-Pugh and Model for End-stage Liver Disease (MELD) scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion. Results All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100), severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong. Conclusion Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure. PMID:26938452

  4. Studies on the hydrogenation of the progestagen dienogest in vivo and in vitro in the female rabbit.

    PubMed

    Hobe, G; Schön, R; Hajek, M; Undisz, K; Härtl, A

    1998-01-01

    The biotransformation of the progestagen dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-4,9-estradien-3-one) was studied in vivo in female rabbits and in vitro by liver homogenates from female rabbits and rats. In vivo, in the female rabbit, 3H-dienogest was the subject of an extensive biotransformation. A significant difference between the composition of the urinary and biliary metabolite patterns of dienogest was found. While in the urinary metabolite pattern more polar metabolites dominated, in bile of animals with a bile fistula, a dienogest metabolite of medium polarity was prevalent. This main metabolite of dienogest was identified by MS, 1H- and 13C-NMR spectroscopy and CD measurement of an enzymatic dehydrogenation product as the tetrahydro metabolite 17 alpha-cyanomethyl-5 alpha-estr-9-en-3 beta,17 beta-diol. Thus, in vivo, the 4,9-dien-3-oxo-19-norsteroid dienogest is hydrogenated to a 5 alpha H-9-en metabolite. In vitro, however, 3H-dienogest was only poorly transformed by liver homogenates from both species, whereas 3H-levonorgestrel and 3H-3-keto-desogestrel were converted partially by liver homogenates from female rabbits and completely by liver homogenates from female rats. The principal biotransformation reactions of levonorgestrel and 3-ketodesogestrel were the reduction of the 3-oxo group to 3-OH and the 5 beta- and 5 alpha-hydrogenation of the 4-double bond by homogenates of female rabbit liver and female rat liver, respectively. A dihydro metabolite of dienogest, in which the 3-oxo group had been reduced to 3-OH, was isolated in small amounts from the incubation with rabbit liver homogenate. The data indicate that the enzymatic hydrogenation of the 4-double bond of the 4,9-dien-3-oxo steroid dienogest is inhibited in vitro. The hindered hydrogenation reaction in vitro has to be seen in association with the 9-double bond in the steroid molecule. PMID:9654645

  5. [Restrictive ventricular septal defect in a dwarf rabbit].

    PubMed

    Hildebrandt, N; Leuser, C; Miltz, D; Henrich, E; Schneider, M

    2016-01-01

    A 9-week-old intact female dwarf rabbit was presented for evaluation of a heart murmur. Physical examination revealed a grade IV/VI systolic heart murmur with the maximal intensity over the right heart base. Evidence for a left-sided cardiomegaly was present on lateral and dorsoventral radiographs. An electrocardiogram was recorded in right lateral recumbency, which revealed a sinus tachycardia with a heart rate of 360 beats/minute. Echocardiography showed normal dimensions for the atria and ventricles. Two-dimensional echocardiography confirmed the presence of a perimembranous ventricular septal defect (VSD) with a diameter of 0.8 mm. Identification of the VSD was possible from a right (long and short axes) and a left parasternal window. Peak flow velocity of the systolic left to right shunt was 5.2 m/s. Additionally, a relative pulmonic stenosis (peak flow in the pulmonary artery of 1.02 m/s, pulsed-wave Doppler) was present. According to these findings, the VSD was classified as restrictive. At this time point, medical treatment was unnecessary. The re-examination after 7 weeks revealed unchanged morphological and haemodynamic findings. The VSD in this dwarf rabbit displayed both in the physical and echocardiographic examinations typical features as seen in dogs and cats as well as in one New Zealand white rabbit. PMID:26763583

  6. Anatomical variation of arterial supply to the rabbit spleen

    PubMed Central

    IKEGAMI, Reona; TANIMOTO, Yoshimasa; KISHIMOTO, Miori; SHIBATA, Hideshi

    2015-01-01

    The rabbit, which is widely used as an experimental animal and is also popular as a companion animal, has a flat and elongated spleen with the longitudinal hilus running along its visceral surface. The spleen receives via the hilus an arterial supply that is essential for splenic nutrition and normal functioning. However, the distribution and variation of the arteries to the spleen have not been studied in detail. This study investigated anatomical variations of splenic arterial supply in 33 New Zealand White rabbits with a colored latex injection into arteries. We also examined whether the length of the spleen correlated with the number of the splenic branches of the splenic artery. The splenic artery always arose as the first independent branch of the celiac artery and ran along the splenic hilus to usually provide 6 (range, 3 to 10) splenic branches to the spleen. There was a moderate correlation (R=0.6) between the number of splenic branches and the longitudinal length of the spleen. The splenic branches often arose as a trunk or trunks in common with short gastric arteries. The number of common trunk(s) was usually 1 (range, 0 to 4). The data showed that the pattern and number of arterial branches to the spleen varied according to the individual animal, suggesting that such variations should be considered when performing experimental and veterinary surgical treatments in rabbits. PMID:26369291

  7. Electrophysiological Effects of Dexmedetomidine on Sinoatrial Nodes of Rabbits

    PubMed Central

    Pan, Xia; Zhang, Zhen; Huang, Ya-Yi; Zhao, Jing; Wang, Long

    2015-01-01

    Background The purpose of this study was to investigate the electrophysiological effects of dexmedetomidine on pacemaker cells in sinoatrial nodes of rabbits. Methods Healthy rabbits were anesthetized intravenously with sodium pentobarbital, and the hearts were quickly dissected and mounted in a tissue bath. Machine-pulled glass capillary microelectrodes which were connected to a high input impedance amplifier and impaled in dominant pacemaker cells. Thereafter, an intracellular microelectrode technique was used to record action potential. Results The amplitude of action potential, velocity of diastolic (phase 4) depolarization, and rate of pacemaker firing in normal pacemaker cells in sinoatrial node were decreased by use of dexmedetomidine (0.5 ng/ml, 5 ng/ml, 50 ng/ml) in a concentration-dependent manner. Pretreatment with yohimbine (1 μM), did not alter the effects of dexmedetomidine (5 ng/ml) on sinoatrial node pacemaker cells. Pretreatment with CsCl (2 mmol/L), dexmedetomidine (5 ng/ml) decreased the amplitude of action potential, but had no significant effect on other parameters of action potential. Conclusions Dexmedetomidine exerts inhibitory electrophysiological effects on pacemaker cells in sinoatrial nodes of rabbits in a concentration-dependent manner, which may not be mediated by alpha 2-adrenoreceptor. PMID:27122920

  8. Collagenolytic activity is produced by rabbit ligaments and tendon

    SciTech Connect

    Harper, J.; Amiel, D.; Harper, E.

    1986-05-01

    The authors examined the patellar tendon (PT), anterior cruciate ligament (ACL) and medial collateral ligament (MCL) from normal rabbits for collagenase activity. All three connective tissues contain large amounts of collagen and the catabolism of this structural protein is important to their integrity. The authors cultured each tissue in serum free medium for 14 days. Collagenase was produced by all three connective tissues after a lag period of up to 7 days, as detected by the /sup 14/C-glycine peptide-release assay. Culture media that did not express enzyme the authors found to contain inhibitory activity. The collagenases and inhibitors from each tissue have been quantitated and characterized. After 9 days the collagenase activity for the rabbit periarticular tissues was 6.1 (PT), 4.4 (MCL) and 8.6 (ACL) units per milligram of secreted protein. The cleavage site of all three collagenases was found to be similar to that observed for rabbit skin collagenase, and generation of reaction products TC/sup A/ and TC/sup B/ was demonstrated by collagenases from PT, MCL and ACL. These results suggest that the metabolism of ligaments and tendon is regulated by the production of zymogen, active collagenase and inhibitor, similar to other connective tissues. The role of these components in joint injury and joint diseases is currently being investigated.

  9. Increased fragility of pulmonary capillaries in newborn rabbit.

    PubMed

    Fu, Zhenxing; Heldt, Gregory P; West, John B

    2003-05-01

    The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We perfusion fixed the lungs from nine anesthetized newborn rabbits at capillary transmural pressures (P(tm)) of 5 +/- 5, 10 +/- 5, and 15 +/- 5 cmH(2)O. Normal microscopic appearances were seen at P(tm) values of 5 +/- 5 and 10 +/- 5 cmH(2)O, but massive airway edema was observed in lungs perfused at a P(tm) of 15 +/- 5 cmH(2)O. Consistent with this, no disruptions of the alveolar epithelium were observed at P(tm) values of 5 +/- 5 cmH(2)O, but mean values of 0.11 and 1.22 breaks/mm epithelium were found at P(tm) of 10 +/- 5 and 15 +/- 5 cmH(2)O, respectively (P < 0.05 for 5 +/- 5 vs. 15 +/- 5 cmH(2)O). These pressures are in striking contrast to those in the adult rabbit in which, by a similar procedure, a P(tm) of 52.5 cmH(2)O, is required before stress failure is consistently seen. We conclude that stress failure of pulmonary capillaries in newborn rabbit lungs can occur at P(tm) values of less than one-third of those that are required in adult lungs. PMID:12676761

  10. Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

    PubMed

    Vasilaki, Fotini; Tsitsimpikou, Christina; Tsarouhas, Konstantinos; Germanakis, Ioannis; Tzardi, Marias; Kavvalakis, Matthaios; Ozcagli, Eren; Kouretas, Dimitrios; Tsatsakis, Aristidis M

    2016-01-22

    Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period. PMID:26541207

  11. Multivariate normality

    NASA Technical Reports Server (NTRS)

    Crutcher, H. L.; Falls, L. W.

    1976-01-01

    Sets of experimentally determined or routinely observed data provide information about the past, present and, hopefully, future sets of similarly produced data. An infinite set of statistical models exists which may be used to describe the data sets. The normal distribution is one model. If it serves at all, it serves well. If a data set, or a transformation of the set, representative of a larger population can be described by the normal distribution, then valid statistical inferences can be drawn. There are several tests which may be applied to a data set to determine whether the univariate normal model adequately describes the set. The chi-square test based on Pearson's work in the late nineteenth and early twentieth centuries is often used. Like all tests, it has some weaknesses which are discussed in elementary texts. Extension of the chi-square test to the multivariate normal model is provided. Tables and graphs permit easier application of the test in the higher dimensions. Several examples, using recorded data, illustrate the procedures. Tests of maximum absolute differences, mean sum of squares of residuals, runs and changes of sign are included in these tests. Dimensions one through five with selected sample sizes 11 to 101 are used to illustrate the statistical tests developed.

  12. Liver failure in total artificial heart therapy

    PubMed Central

    Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero

    2016-01-01

    Background Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. Methods A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Results Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. Conclusions TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality. PMID:27499942

  13. The Influence of α-Lipoic Acid and Garlic Administration on Biomarkers of Oxidative Stress and Inflammation in Rabbits Exposed to Oxidized Nutrition Oils

    PubMed Central

    Zalejska-Fiolka, Jolanta; Wielkoszyński, Tomasz; Rokicki, Wojciech; Dąbrowska, Natalia; Strzelczyk, Joanna Katarzyna; Kasperczyk, Aleksandra; Owczarek, Aleksander; Błaszczyk, Urszula; Kasperczyk, Sławomir; Stawiarska-Pięta, Barbara; Birkner, Ewa; Gamian, Andrzej

    2015-01-01

    We hypothesized that addition of substances with antioxidant activity could decrease the concentrations of biomarkers of oxidative stress and inflammatory process, thus inhibiting nonalcoholic steatohepatitis development. We investigated the influence of α-lipoic acid (ALA) and garlic administration on the development of adverse changes in rabbit liver and serum under oxidative stress conditions induced with HFD from oxidized oils. We determined 8-hydroxy-2′-deoxyguanosine (8OHdG) and malondialdehyde (MDA) in liver homogenates, total oxidant status (TOS), lipid peroxides (LOO) and tumor necrosis factor alpha (TNFα) in blood serum, and TNFα and IL-1α genes expression in liver. The results indicate that the intake of dietary ALA and garlic was significantly associated with decreases of 8OHdG and MDA levels in rabbits' liver tissue as well as TOS and LOO levels in rabbits' serum. Similarly, TNFα and IL-1α gene expressions were suppressed due to ALA and garlic supplementation. The histopathological analysis confirmed that HFD results in liver disorder leading to steatosis. This adverse effect of HFD was ameliorated by the supplementation of ALA and garlic. The obtained results indicate a beneficial effect of ALA and garlic administration by reducing the oxidative stress intensity and the levels of some proinflammatory cytokines in rabbits fed HFD. PMID:26634212

  14. Management of Hepatitis E Virus (HEV) Zoonotic Transmission: Protection of Rabbits against HEV Challenge following Immunization with HEV 239 Vaccine

    PubMed Central

    Liu, Peng; Du, Ren jie; Wang, Ling; Han, Jian; Liu, Lin; Zhang, Yu lin; Xia, Jun ke; Lu, Feng min; Zhuang, Hui

    2014-01-01

    Hepatitis E virus (HEV) constitutes a significant health burden worldwide, with an estimated approximately 33% of the world’s population exposed to the pathogen. The recent licensed HEV 239 vaccine in China showed excellent protective efficacy against HEV of genotypes 1 and 4 in the general population and pregnant women. Because hepatitis E is a zoonosis, it is also necessary to ascertain whether this vaccine can serve to manage animal sources of human HEV infection. To test the efficacy of the HEV 239 vaccine in protecting animal reservoirs of HEV against HEV infection, twelve specific-pathogen-free (SPF) rabbits were divided randomly into two groups of 6 animals and inoculated intramuscularly with HEV 239 and placebo (PBS). All animals were challenged intravenously with swine HEV of genotype 4 or rabbit HEV seven weeks after the initial immunization. The course of infection was monitored for 10 weeks by serum ALT levels, duration of viremia and fecal virus excretion and HEV antibody responses. All rabbits immunized with HEV 239 developed high titers of anti-HEV and no signs of HEV infection were observed throughout the experiment, while rabbits inoculated with PBS developed viral hepatitis following challenge, with liver enzyme elevations, viremia, and fecal virus shedding. Our data indicated that the HEV 239 vaccine is highly immunogenic for rabbits and that it can completely protect rabbits against homologous and heterologous HEV infections. These findings could facilitate the prevention of food-borne sporadic HEV infection in both developing and industrialized countries. PMID:24498149

  15. Necrotizing granulomatous inflammation of the liver.

    PubMed

    Chou, Chung Kuao; Chou, Shih-Cheng

    2016-09-01

    A 73-year-old patient with necrotizing granulomatous inflammation of the liver is presented. The computed tomography demonstrated 2 hypodense tumors with progressive enhancement in the liver. They became nearly isodense to the normal hepatic parenchyma on the delayed phase. PMID:27594940

  16. A microangiographic study of the effect of hyperthermia on the rabbit bladder

    NASA Technical Reports Server (NTRS)

    Hietala, S. O.; Howells, R.; Hazra, I. A.

    1978-01-01

    A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

  17. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  18. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  19. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  20. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  1. Liver transplant - series (image)

    MedlinePlus

    The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

  2. Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h.

    PubMed

    Maskell, Peter D; Albeishy, Mohammed; De Paoli, Giorgia; Wilson, Nathan E; Seetohul, L Nitin

    2016-03-01

    The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 % error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible. PMID:25863436

  3. Myocardial kinetics of hexakis (trimethylphosphite) technetium-99m (I) chloride (Tc-TMP) in rats, rabbits, dogs, cats and pigs

    SciTech Connect

    Robbins, M.S.; Adams, M.D.

    1984-01-01

    Tc-TMP is readily taken up by the myocardium following intravenous administration to rats and dogs. In order to assess its potential as a myocardial perfusion imaging agent, the biodistribution and pharmacokinetics of Tc-TMP were evaluated following intravenous administration to rats, rabbits, dogs, cats and miniature pigs. Rats and rabbits were killed at several time points within a 24 hr period after treatment and tissue samples were assayed for radioactivity. In rats, estimated heart, liver and lung half-lives were 14.4 hr, 24 min and 40 min, respectively. In rabbits, 0.6% dose/g was observed in the heart at 30 min. Corresponding heart/blood, heart/liver and heart/lung ratios were 39.1, 10.7 and 5.1. Gamma camera imaging experiments were conducted in rabbits, dogs, cats and pigs over a 1-2 hr period following administration of Tc-TMP. All species exhibited myocardial uptake resulting in sustained visualization, although myocardial image intensity was less pronounced in the pig compared to the other species. Regions of interest were selected over the heart, liver and background, and time-activity curves were generated. Minimal myocardial clearance was observed in all species during the imaging time course. Hepatic activity was rapidly cleared in rabbits and pigs (t1/2 < 1.0 hr) resulting in improved heart/liver ratios at later time intervals. The myocardial accumulation and retention of Tc-TMP, demonstrated in five species, supports clinical evaluation as a myocardial imaging agent.

  4. Effect of maternal ethanol intake on fetal rabbit gastrointestinal development.

    PubMed

    Guo, W; Gregg, J P; Fonkalsrud, E W

    1994-08-01

    Maternal ingestion of alcohol is believed to be one factor that greatly influences the development of intrauterine growth retardation (IUGR) and postnatal growth failure. The present study was undertaken to determine whether maternally ingested alcohol adversely affects fetal growth and intestinal mucosal function. Five time-mated New Zealand white rabbit does were given ethanol intravenously (ETH group) (30% vol/vol; 1.0 g/kg/d) on gestational days (GD) 15 through 29 (term, 31 days). Two other rabbits received the same dose of ethanol. Maternal, fetal, and amniotic fluid alcohol levels were measured on GD 24. Four control rabbits (SH group) received normal saline (25 mL, intravenously). At term, the animals were delivered by cesarean section and killed. Seventeen of the 42 ETH fetuses survived the study period (43%); all 24 SH fetuses survived. On GD 24, within 60 minutes after maternal ethanol infusion, the fetal blood alcohol concentration (BAC) increased to 153 +/- 1.97 mg/dL (v maternal, 179 +/- 1.75 mg/dL); the amniotic ethanol level increased to 46 +/- 1.32 mg/dL. Birth weight was lower in the ETH group (46.88 +/- 2.21 g) than in the SH group (55.78 +/- 1.80 g) (P < .01). Disaccharidase activity, an indicator of intestinal mucosal function, showed that lactase activity (per milligram of protein) was significantly lower in ETH fetuses (2.60 x 10(-2) +/- 0.22 UE/mg) than in SH fetuses (3.50 x 10(-2) +/- 0.25 UE/mg) (P = .01); maltase activity and protein content were not affected significantly. This report provides the first description of the adverse effects of maternal alcohol ingestion on the small intestinal mucosal function of the fetal rabbit. PMID:7965501

  5. Viral skin diseases of the rabbit.

    PubMed

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. PMID:24018033

  6. Rabbit models for continuous curvilinear capsulorhexis instruction

    PubMed Central

    Ruggiero, Jason; Keller, Christopher; Porco, Travis; Naseri, Ayman; Sretavan, David W.

    2012-01-01

    PURPOSE To develop a rabbit model for continuous curvilinear capsulorhexis (CCC) instruction. SETTING University of California San Francisco, San Francisco, California, USA. DESIGN Experimental study. METHODS Isolated rabbit lenses were immersed in 2% to 8% paraformaldehyde (PFA) fixative from 15 minutes to 6 hours. Rabbit eyes were treated by substituting aqueous with 2% to 4% PFA for 30 minutes to 6 hours, followed by washes with a balanced salt solution. Treated lenses and eyes were held in purpose-designed holders using vacuum. A panel of 6 cataract surgeons with 5 to 15 years of experience performed CCC on treated lenses and eyes and responded to a questionnaire regarding the utility of these models for resident teaching using a 5-item Likert scale. RESULTS The expert panel found that rabbit lenses treated with increasing amounts of fixative simulated CCC on human lens capsules from the third to the seventh decade of life. The panel also found fixative-treated rabbit eyes to simulate some of the experience of CCC within the human anterior chamber but noted a shallower anterior chamber depth, variation in pupil size, and corneal clouding under some treatment conditions. CONCLUSIONS Experienced cataract surgeons who performed CCC on these rabbit models strongly agreed that isolated rabbit lenses treated with fixative provide a realistic simulation of CCC in human patients and that both models were useful tools for capsulorhexis instruction. Results indicate that rabbit lenses treated with 8% PFA for 15 minutes is a model with good fidelity for CCC training. PMID:22727296

  7. Heterogeneity of collagens in rabbit cornea: type III collagen

    SciTech Connect

    Cintron, C.; Hong, B.S.; Covington, H.I.; Macarak, E.J.

    1988-05-01

    Whole neonate rabbit corneas and adult corneas containing 2-week-old scars were incubated in the presence of (/sup 14/C) glycine. Radiolabeled collagen extracted from the corneas and scar tissue were analyzed by sodium dodecylsulfate/polyacrylamide gel electrophoresis and fluorography to determine the types and relative quantity of collagen polypeptides present and synthesized by these tissues. In addition to other collagen types, type III was found in both neonate cornea and scar tissue from adult cornea, albeit in relatively small quantities. Type III collagen in normal cornea was associated with the residue after pepsin digestion and formic acid extraction of the tissue, and the same type of collagen was extracted from scar tissue after similar treatment. Type III collagen-specific monoclonal antibody bound to developing normal corneas and healing adult tissue sections, as determined by immunofluorescence. Antibody binding was localized to the endothelium and growing Descemet's membrane in fetal and neonate corneas, and restricted to the most posterior region of the corneal scar tissue. Although monoclonal antibody to keratan sulfate, used as a marker for stromal fibroblasts, bound to most of the scar tissue, the antibody failed to bind to the posterior scar tissue positive for type III collagen. We conclude that endothelial cells from fetal and neonate rabbit cornea and endothelium-derived fibroblasts from healing wounds of adult cornea synthesize and deposit type III collagen. Moreover, this collagen appears to be incorporated into the growing Descemet's membrane of normal corneas and narrow posterior portion of the scar tissue.

  8. A rabbit model of human familial, nonsyndromic unicoronal suture synostosis. I. Synostotic onset, pathology, and sutural growth patterns.

    PubMed

    Mooney, M P; Siegel, M I; Burrows, A M; Smith, T D; Losken, H W; Dechant, J; Cooper, G; Kapucu, M R

    1998-06-01

    Poswillo has stated, "The more severe anomalies of the calvaria, such as plagiocephaly, Crouzon [syndrome], and Apert syndrome still defy explanation, in the absence of an appropriate animal system to study" (p. 207). This two-part study reviews data from a recently developed colony of New Zealand white rabbits with familial, nonsyndromic unilateral coronal suture synostosis. Part 1 presents pathological findings and compensatory sutural growth data from 109 normal rabbits and 82 craniosynostotic rabbits from this colony. Synostotic foci, onset, and progression were described in the calvariae from 102 staged (fetal days 21, 25, 27, 33; term = 30 days) fetuses (39 normal, 63 synostosed). Calvarial suture growth patterns from 10 to 126 days of age were assessed from serial radiographs obtained from 89 rabbits (70 normal rabbits and 19 rabbits with unicoronal suture synostosis) with amalgam bone marker implants. Perinatal results revealed that by fetal day 25 the synostotic focal point in synostotic rabbits consistently originated from the endocortical surface of the calvaria in the middle of the coronal suture at a presumed high-tension, interdigitating zone. Histological analysis revealed hyperostotic osteogenic fronts on the affected side compared with the unaffected side. Postnatal sutural growth data revealed a predictable pattern of plagiocephaly (contralateral coronal sutures growing more than ipsilateral sutures and ipsilateral frontonasal and anterior lambdoidal sutures growing more than contralateral sutures), which resulted in early cranial vault deformities and a double "S" shape torquing towards the affected side. The advantages and disadvantages of these rabbits as a model for human familial, nonsyndromic unicoronal suture synostosis are discussed, especially in light of recent cytokine and genetic findings from human craniosynostotic studies. PMID:9694335

  9. Thermal cataract formation in rabbits

    SciTech Connect

    Kramar, P.; Harris, C.; Guy, A.W.

    1987-01-01

    Intraocularly circulating hot water was used to produce cataracts in nine eyes of seven rabbits by maintaining their retrolental temperatures between 43 degrees C and 45 degrees C. A rapid rate of heating (1.3 degrees C/min) plus a sharp temperature gradient across the eye may have been contributing factors in the consistent production of cataracts at these temperatures. Biomicroscopy and light microscopy showed lens changes similar to those associated with acute exposure to microwave radiation. These findings support the assumption that microwave cataractogenesis is due to the local production of elevated temperatures.

  10. Histopathological alterations after a growth promoter boldenone injection in rabbits.

    PubMed

    Tousson, Ehab

    2016-02-01

    Boldenone (BOL) is a derivative of the testosterone that has dual effects on humans, both directly and indirectly; directly as injection to build muscles and indirectly as through consuming meat of animals that where treated with BOL. However, the action of these steroids on different body organs structures is still unclear; therefore, the aim of the present study was to investigate the effect of the intramuscular injection of BOL undecylenate on the different organ structures. A total of 10 adult New Zealand rabbits were divided into two main groups, the first group was the control group, which includes animals that were injected intramuscularly with olive oil and the second group included animals that received two intramuscular injections of 5 mg/kg body weight BOL dissected after 6 weeks. Our results showed that intramuscular injection of rabbits with BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the hepatocytes radially arranged cords with multifocal hepatocellular vacuolations in the liver, glomerulus mass reduction with multifocal glomerular injury in the kidney, disturbances of the cycle of spermatogenesis in the testes. In conclusion, using BOL, while preparing for a young bodybuilding contest, may cause an alteration in the histological structure of most of the body organs; these findings suggested that especially young people who misuse anablic androgenic steroids should be careful if they want to use such steroids to enhance their strength and endurance. PMID:24097356

  11. Visualisation of liver tumours using hand-held real-time strain imaging: results of animal experiments

    PubMed Central

    Melodelima, D; Chenot, J; Souchon, R; Rivoire, M; Chapelon, J-Y

    2012-01-01

    Objective Surgical resection is the only curative option for colorectal hepatic metastases. Intra-operative localisation of these metastases during hepatic resection is performed by intra-operative B-mode imaging and palpation. Because liver metastases are stiffer than normal tissues, elastography may be a useful complement to B-mode imaging. This paper reports quantitative measures of the image quality attained during intra-operative real-time elastographic visualisation of liver metastasis. Methods VX2 tumours were implanted in the liver of eight rabbits and were scanned in vivo. Measurements of the tumour dimensions obtained via elastography were compared with those obtained using B-mode imaging and with gross pathology. Results Measurements of tumour diameters were similar when obtained by intra-operative elastography and pathological measurement methods (mean difference±standard deviation, 0.1±0.9 mm). The contrast between tumours and normal tissues was significantly higher (p<0.05) in elastograms (26±10 dB contrast) than in sonograms (1±1 dB contrast). Sensitivity and specificity for detecting tumours using intra-operative elastography were 100% and 88%, respectively, and positive and negative predictive values were 89% and 100%, respectively. In two cases elastograms were able to detect a tumour that was ambiguous in B-mode images. Conclusion Combined hand-held B-mode/strain imaging may provide additional information that is relevant for detection of liver metastases that may be missed by standard B-mode imaging alone, such as small and/or isoechoic tumours. PMID:22253340

  12. Survival of rabid rabbits after intrathecal immunization.

    PubMed

    Kesdangsakonwut, Sawang; Sunden, Yuji; Aoshima, Keisuke; Iwaki, Yoshimi; Okumura, Masahiro; Sawa, Hirofumi; Umemura, Takashi

    2014-06-01

    Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4-8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8-12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11-18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies. PMID:24397792

  13. Survival of rabid rabbits after intrathecal immunization

    PubMed Central

    Kesdangsakonwut, Sawang; Sunden, Yuji; Aoshima, Keisuke; Iwaki, Yoshimi; Okumura, Masahiro; Sawa, Hirofumi; Umemura, Takashi

    2014-01-01

    Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4–8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8–12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11–18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies. PMID:24397792

  14. Rabbit β-glucuronidase. Subcellular distribution and immunochemical properties

    PubMed Central

    Dean, Roger T.

    1974-01-01

    1. The subcellular distribution of β-glucuronidase and other hydrolases in rabbit liver was investigated. β-Glucuronidase was found in both microsomal and lysosomal fractions. 2. Multiple forms of β-glucuronidase were present in extracts of microsomal and lysosomal fractions. All forms were common to both fractions. 3. A specific antiserum against β-glucuronidase was raised, and characterized by immunoprecipitation and affinity-chromatography procedures. 4. The immunological identity of the multiple forms in the pure β-glucuronidase preparation, and the immunological identity of the β-glucuronidase complement of lysosomal extracts with that of microsomal extracts, were demonstrated by means of the antiserum. The presence of inactive enzyme in various enzyme preparations was shown. ImagesPLATE 1 PMID:4215419

  15. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function

    PubMed Central

    Nilsson, Henrik; Karlgren, Silja; Blomqvist, Lennart; Jonas, Eduard

    2015-01-01

    Background Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. Methods In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. Results Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median −3.5% (−9.3–3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (−0.7–2.5%)]. Discussion The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved. PMID:25297934

  16. Particular RNA fragments as promoters of leukocyte and platelet formation in rabbits.

    PubMed

    Beljanski, M; Plawecki, M

    1979-01-01

    Under well-defined conditions, ribosomal RNA from Escherichia coli is fragmented by pancreatic ribonuclease, leading to the appearance of particular RNA fragments. Some of these fragments act as primers for in vitro replication of DNA extracted from blood-cell and platelet-forming tissues. In experimental rabbits they restore in a rapid and harmless way normal circulating leukocyte and platelet levels when these have been drastically decreased by various chemotherapeutic agents mainly used in anticancer therapy. Imbalance between polynuclear and lymphocyte count provoked in rabbits by cyclophosphamide can be rapidly corrected by treating the animal with active RNA fragments. PMID:381069

  17. Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

    2005-01-01

    In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. 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. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

  18. Nutritional Status and Liver Transplantation

    PubMed Central

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2012-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as ‘metabolic syndrome’, may play a negative role on the overall survival of liver transplant patients. In this report we

  19. Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

    PubMed Central

    Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

    2015-01-01

    Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

  20. Behavioral fever in newborn rabbits

    NASA Technical Reports Server (NTRS)

    Satinoff, E.; Mcewen, G. N., Jr.; Williams, B. A.

    1976-01-01

    New Zealand white rabbit pups aged 12 to 72 hr were divided into three groups and given an intraperitoneal injection of Pseudomonas polysaccharide, a saline vehicle alone, and no treatment, respectively. The animals injected with pyrogen and maintained at an ambient temperature of 32 C for 2 hr did not develop fever. When placed in a thermally graded alleyway, the animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline. Further stay at selected positions for 5 min caused a considerable increase in the rectal temperature of the pyrogen-injected pups but not that of controls. The results support the hypothesis that newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen if the opportunity for thermoregulatory behavior is present. No fever develops if the pups must rely solely on internal thermoregulatory mechanisms. The behavioral system for producing a fever is mature at birth, but an adequate system of internal reflexes does not appear to develop for some days.

  1. Radiocolloid liver imaging in hepatic steatosis

    SciTech Connect

    Lisbona, R.; Rush, C.L.; Derbekyan, V.; Novales-Diaz, J.A.

    1986-03-01

    In a review of 60 patients with fatty infiltration of the liver documented by Xe-133 imaging, 43% had normal radiocolloid liver images, and 57% had abnormal images with various combinations of hepatomegaly, mottling, splenomegaly, and splenic shift of radioactivity. None, however, showed focal defects. Fatty infiltrates do not simulate mass lesions on the radiocolloid study of the liver, and an area of photon deficiency in the presence of hepatic steatosis points to an additional pathologic process. The interpretation of the radiocolloid liver image is unhindered by fatty infiltration when searching for discrete space-occupying lesions.

  2. Normalizing Rejection.

    PubMed

    Conn, Vicki S; Zerwic, Julie; Jefferson, Urmeka; Anderson, Cindy M; Killion, Cheryl M; Smith, Carol E; Cohen, Marlene Z; Fahrenwald, Nancy L; Herrick, Linda; Topp, Robert; Benefield, Lazelle E; Loya, Julio

    2016-02-01

    Getting turned down for grant funding or having a manuscript rejected is an uncomfortable but not unusual occurrence during the course of a nurse researcher's professional life. Rejection can evoke an emotional response akin to the grieving process that can slow or even undermine productivity. Only by "normalizing" rejection, that is, by accepting it as an integral part of the scientific process, can researchers more quickly overcome negative emotions and instead use rejection to refine and advance their scientific programs. This article provides practical advice for coming to emotional terms with rejection and delineates methods for working constructively to address reviewer comments. PMID:26041785

  3. Relationships between variable time, percentage of food restriction and liver histology: which alternative is the best for non-alcoholic fatty liver disease (NAFLD) prevention?

    PubMed

    Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Sedlacek, Radislav

    2016-10-01

    The objective of this study was to analyse the hepatic effects of food restriction in an experimental rabbit model. The study comprised 105 rabbits divided into 6 groups. The two control groups were fed ad libitum (ADL) during the entire experiment (C1 and C2). The experimental groups were restricted between 42-49 days of age, where the rabbits received 50g (R1) or 65g (R2) of food per rabbit per day. Others were restricted between 35-42 days of age, where the rabbits received 50g (R3) or 65g (R4) of food per rabbit per day. For liver analysis, 5 rabbits per group were slaughtered at the ages of 49, 56, 63, 70 days from the R1, R2 groups and at 42, 49, 70 days from the R3, R4 groups. All animals from the C1 and C2 groups developed steatosis with inflammation. Animals from the R1 and R2 groups developed steatosis without inflammation while in the R3 and R4 groups steatosis was not visible. In C1 and C2 groups we observed mostly fatty deposit accumulations while in the R1, R2, R3 and R4 groups, more PAS-positive material accumulations were visible. Liver steatosis correlated with inflammation development and interstitial tissue growth. These results can be used in clinical praxis as signs of NAFLD progression. Early food restriction had intense effects on liver morphology and it seems promising that similar approaches could be applied as preventive treatment for NAFLD development. PMID:26916089

  4. Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits

    PubMed Central

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Ameyaw, Elvis Ofori; Asiamah, Emmanuel Akomanin

    2016-01-01

    AIM To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. METHODS Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators. PMID:27162723

  5. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  6. BESNOITIA ORYCTOFELISI N. SP. (PROTOZOA: APICOMPLEXA) FROM DOMESTIC RABBITS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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,...

  7. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  8. Characterization of PICM-19H porcine liver stem cell line for potential use in a bioartificial liver

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A hepatocyte cell line is needed as the biological component of a bioartificial liver (BAL). One candidate is the PICM-19 pig liver stem cell line. These cells have many normal hepatocyte functions often lacking in tumor-derived liver cell lines. The study characterized a PICM-19 derivative cell ...

  9. Dihydrotestosterone decreases beta-adrenergic receptor binding in the fetal rabbit lung

    SciTech Connect

    Moawad, A.H.; River, L.P.; River, J.M.

    1988-07-01

    Tritium-labeled dihydroalprenolol was used to quantify the beta-adrenergic receptor sites in day 30 fetal rabbit lung tissue. Each of the fetuses of New Zealand White rabbits on day 28 of gestation was injected with dihydrotestosterone (2.0 micrograms) in one horn of the uterus and 10% ethanol in normal saline (the solvent) in the contralateral one. The animals were sacrificed 48 hours later and the fetal lung tissue was assayed. Dihydrotestosterone decreased the beta-adrenergic receptor site number in the treatment group compared with the control group (86 versus 111 fmol/mg protein, p less than 0.05 by paired t-test). In the presence of dihydrotestosterone, beta-adrenergic receptor binding is inhibited in the preterm fetal rabbit. This effect may be implicated in the beta-adrenergic mediation of phospholipid synthesis and/or release by fetal alveolar cells.

  10. Effects of dichloroacetate in spinal stroke in the rabbit.

    PubMed

    Barsan, W G; Hedges, J R; Syverud, S A; Dronen, S C; Dimlich, R V

    1987-08-31

    High levels of brain lactate may contribute to cellular death and dysfunction in acute cerebral ischemia. Although sodium dichloroacetate (DCA) has been shown to lower brain lactate in incomplete cerebral ischemia, functional outcome has not been assessed with DCA. We examined the effects of DCA treatment on functional neurologic outcome using a previously developed model for "spinal stroke" in the rabbit. Thirty male New Zealand white rabbits weighing 1.3-2.8 kg were studied. After anesthesia with 15-40 mg/kg pentobarbital IV, a laparotomy was performed and the aorta exposed. A metal clamp was placed on the aorta just distal to the left renal artery for 20 minutes and then removed. The abdominal wound was closed in two layers. Animals then received either 2cc normal saline (n = 15) or 300 mg/kg DCA in 2cc normal saline (n = 15) over 10 minutes. The animals were returned to their cages when awake and were examined at 24 hours, 48 hours, and 72 hours for neurologic assessment. The exams were performed by a blinded examiner who was unaware of the treatment given. A three point ambulatory score (0 = can't walk, 1 = walk but not hop, 2 = hopping) and a two point activity score (0 = inactive, 1 = active) were used. At 24 hours, 67% of the DCA-treated animals were actively moving about compared to only 27% of the controls (P = 0.03; Fisher Exact Test). Ten of fifteen control animals were unable to walk, while only five of fifteen DCA-treated animals were unable to walk (P = 0.07). Sixty percent of the DCA animals were able to hop compared to 27% of controls (P = 0.06). These results suggest that DCA can reduce morbidity from spinal cord ischemia in the rabbit. PMID:3613862

  11. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    PubMed

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  12. CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection

    PubMed Central

    Kumar, Parveen; Kumar, Rakesh; Manuja, Balvinder Kumar; Singha, Harisankar; Sharma, Anshu; Virmani, Nitin; Yadav, Suresh Chandra; Manuja, Anju

    2015-01-01

    CpG oligodeoxynucleotides (CpG-ODN) stimulate immune cells from a wide spectrum of mammalian species. Class C CpG-ODN is relatively stable and has the combined immune effects of both A and B classes of CpG-ODN. Trypanosoma evansi produces the state of immuno-suppression in the infected hosts. The current chemotherapeutic agents against this parasite are limited in number and usually associated with severe side effects. The present work aimed to determine the immunostimulatory effects of CpG-ODN class C in T. evansi infected rabbits. Rabbits inoculated with CpG C and challenged with T. evansi resulted in delayed onset of clinical signs with reduced severity in comparison to that of T. evansi infected rabbits. The treatment also enhanced humoral immune responses. Histopathological findings in liver and spleen revealed enhancement of mononuclear cell infiltration and secondary B cell follicles. These results demonstrate that CpG-ODN class C, has immunostimulatory properties in rabbit model of trypanosomosis. The use of booster doses or sustained delivery of CpG-ODN will further elucidate the prolonged CpG-ODN generated immune responses. PMID:26039713

  13. Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

    PubMed Central

    Liang, Xin-Mei; Tang, Guang-Yu; Cheng, Ying-Sheng; Zhou, Bi

    2009-01-01

    AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma. PMID:19418587

  14. [Aortic expression of monocyte chemotactic protein-1 (MCP-1) gene in rabbits with experimental atherosclerosis].

    PubMed

    Sekalska, Beata

    2003-01-01

    The theory of Ross describes atherosclerosis as a process induced by inflammatory reactions involving cytokines, cell adhesion molecules, and chemokines. The latter have been identified as the principal mediator of cell recruitment into the vascular wall when accumulating monocytes become a source of foam cells. The most potent monocyte attractant among known chemokines is the monocyte chemotactic protein-1 (MCP-1). This protein is synthesized in vivo by cells of the vascular wall and its expression is largely controlled by NF-kB nuclear transcription factor. The importance of inflammation for the induction and progression of atherosclerosis suggests that anti-inflammatory drugs could be a useful modality in this condition. The present work was undertaken to: 1) adapt the RT-PCR technique to measurements of MCP-1 gene expression in rabbit aorta, 2) assess MCP-1 gene expression in rabbit aorta during atherosclerosis induced with a cholesterol-rich diet, 3) evaluate the effect of ibuprofen on MCP-1 gene expression in rabbit aorta during atherosclerosis induced with a cholesterol-rich diet. The study was done in 72 rabbits assigned to eight even groups on the basis of body weight and starting cholesterol and triglyceride concentrations in serum. All rabbits were fed a standard chow. In some groups, the diet was supplemented with cholesterol and/or ibuprofen. Two months later rabbits in four groups, i.e. control (K2), control with ibuprofen (IK2), cholesterol-rich (M2) and cholesterol-rich with ibuprofen (IM2) were weighed and blood was sampled for measurements of cholesterol and triglyceride concentrations in serum. The liver, heart, kidneys and adrenals were collected at autopsy and weighed. Additionally, a fragment of the ascending aorta was obtained for RT-PCR. The extent of atherosclerosis in aorta was determined using planimetry. Another month later this procedure was repeated for the remaining groups K3, IK3, M3 and IM3. RT-PCR was applied to measure MCP-1 gene

  15. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamm