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Purpose: Volumetric and health assessment of the liver is crucial to avoid poor post-operative outcomes following liver resection surgery. No current methods allow for concurrent and accurate measurement of both Couinaud segmental volumes for future liver remnant estimation and liver health using non-invasive imaging. In this study, we demonstrate the accuracy and precision of segmental volume measurements using new medical software, Hepatica™. Methods: MRI scans from 48 volunteers from three previous studies were used in this analysis. Measurements obtained from Hepatica™ were compared with OsiriX. Time required per case with each software was also compared. The performance of technicians and experienced radiologists as well as the repeatability and reproducibility were compared using Bland–Altman plots and limits of agreement. Results: High levels of agreement and lower inter-operator variability for liver volume measurements were shown between Hepatica™ and existing methods for liver volumetry (mean Dice score 0.947 ± 0.010). A high consistency between technicians and experienced radiologists using the device for volumetry was shown (± 3.5% of total liver volume) as well as low inter-observer and intra-observer variability. Tight limits of agreement were shown between repeated Couinaud segment volume (+ 3.4% of whole liver), segmental liver fibroinflammation and segmental liver fat measurements in the same participant on the same scanner and between different scanners. An underestimation of whole-liver volume was observed between three non-reference scanners. Conclusion: Hepatica™ produces accurate and precise whole-liver and Couinaud segment volume and liver tissue characteristic measurements. Measurements are consistent between trained technicians and experienced radiologists. [ABSTRACT FROM AUTHOR]

Development of obesity is associated with excessive fat accumulation and oxidative stress along with chronic inflammation. Goji berries (Lycium barbarum) are high in polyphenolic compounds and have anti-inflammatory, anti-oxidant, and hypolipidemic properties that may alleviate the pathogenesis of obesity and related metabolic complications. Thus, the aim of this study was to investigate potential metabolic benefits of GB supplementation against high fat (HF) diet-induced obesity and its comorbidities in HF diet-fed rats (male Sprague–Dawley, n = 8/group, 6 weeks old). We also sought to examine the potential metabolic benefits of fermented GB (FGB) with L. plantarum CB3 and possible distinctions in the degree and/or mechanism of action compared to GB. GB and FGB supplementation suppressed the gene expression of inflammation indices at the local (adipose tissues) and systemic (liver) levels. In addition, GB and FGB supplementation upregulated the gene expression of antioxidant enzymes compared to the HF and/or even low fat (LF) group with more remarkable antioxidant effects by GB supplementation. Also, GB and FGB supplementation protected from HF-induced damages of the liver and dyslipidemia. In conclusion, we demonstrated that GB and FGB supplementation protected from HF-induced metabolic complications primarily by improving hepatic function and corresponding lipid metabolism via their anti-inflammatory and antioxidant properties. To our knowledge, this is the first in vivo study confirming metabolic benefits of GB in a fermented form. Thus, these findings support the potential application of both GB and FGB to ameliorate obesity-associated metabolic abnormalities. [ABSTRACT FROM AUTHOR]

This study tested the possible protective and therapeutic effects of Viscum album extract and probiotics against carbon tetrachloride (CCl4)-induced acute/chronic liver injury. Male Wistar rats were assigned to seven groups: Control, acute CCl4, acute V. album + CCl4, acute V. album + Probiotics + CCl4, chronic CCl4, chronic CCl4 + V. album, and chronic CCl4 + V. album + Probiotics. Acute and chronic liver injuries were induced by 2 mg/kg CCl4 (i.p.) and 1 mg/kg CCl4 (i.p.), respectively. The extract and probiotics were administered daily to related groups. Serum enzyme activities, lipid profile, total protein, albumin, bilirubin, heme oxgenase-1 and 8-hydroxydeoxyguanosine levels were measured. Liver tissue sections stained with Hematoxylin-Eosin. Acute or chronic CCl4-exposure caused to significant changes in concentrations/activities of the measured parameters. The oral administration of extract and probiotics showed protective and therapeutic effects against CCl4-induced liver-injury. The supplementation of intestinal flora by the use of probiotics may enhance the efficacy of orally given therapeutic extracts. [ABSTRACT FROM AUTHOR]

Post hepatectomy liver failure (PHLF) could occur even though an adequate liver volume is preserved. Liver function is not strictly related to the volume and the necessity to pre-operatively predict the future liver remnant (FLR) function is emerging, together with the wide spreading of techniques, aiming to optimize the FLR. The aim of this study was to systematically review all the available tests, to pre-operatively assess the liver function and to estimate the risk of PHLF. A systematic literature research of Medline, Embase, Scopus was performed in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, to identify all the studies available for pre-operative liver function tests to assess the risk of PHLF and/or complications. From the 1122 references retrieved, 79 were included in the review. Dynamic functional tests, such as indocyanine green test (ICG), could evaluate only global liver function, with no definition of functional capacity of the remnant. Magnetic resonance imaging (MRI) with liver-specific contrast agents enables both liver function and volume evaluation; the absence of ionizing radiation showed a better patient's compliance. Nuclear imaging studies as hepatobiliary scintigraphy (HBS) present the unique ability to allow a precise evaluation of the segmental liver function of the remnant liver. Liver volume could overestimate liver function. Several liver function tests are available to evaluate the risk of PHLF in the pre-operative setting. However, no single test alone could accurately predict PHLF. Pre-operative combination between a dynamic quantitative test, such as ICG, with MRI or HBS, should enable a more complete functional evaluation. Functional tests to predict PHLF should be chosen according to patient's characteristics, disease, and center experience. [ABSTRACT FROM AUTHOR]

Purpose: Octreotide (OCT) has been successfully used for treatment of acromegaly and neuroendocrine tumors for more than 30 years. However, long-term safety of OCT has not been documented in placebo-controlled setting. This present analysis pooled safety data from two similarly-designed, randomized, and placebo-controlled studies to evaluate long-term safety of long-acting OCT (20, 30 mg); targeted post-hoc analyzes focused on cardiac, hepatic, and renal safety.Methods: Two studies (NCT00131144, NCT001308450) were conducted in patients with diabetic retinopathy (OCT20 = 191, OCT30 = 348, placebo = 347). In this analysis, patients were stratified based on baseline glomerular filtration rate. Hepatic, cardiac, and renal adverse events (AEs) were identified by standardized MedDRA queries.Results: Median duration of exposure was >3.5 years. Most common AEs reported with OCT were diarrhea, cholelithiasis, hypoglycemia, nasopharyngitis, and hypertension. Incidence of cardiac events (QT prolongation and arrhythmia) with OCT20 and OCT30 were comparable to placebo (OCT20, RR = 1.11 [95% CI, 0.61-2.03]; OCT30, RR = 1.09 [95% CI, 0.70-1.68]). For ECG findings, changes in QTcF were similar in treatment groups, and outliers did not exceed 480 ms. Incidence of cardiac ischemia was lower with OCT than placebo (OCT20 = 12.6%, OCT30 = 10.6%, placebo = 15.3%). Incidence of liver-related AEs was higher with OCT30 than placebo (RR = 2.04 [95% CI, 1.28-3.26]); incidences were comparable with OCT20 and placebo (RR = 1.50 [95% CI, 0.69-3.25]). Overall incidences of renal AEs were comparable between treatment groups (OCT20 = 5.8%; OCT30 = 6.3%; placebo = 7.2%). Drug-related SAEs were reported more frequently with OCT (OCT20 = 7.9%; OCT30 = 10.1%; placebo = 3.5%); predominantly gallbladder-related, GI-related, and hypoglycemia.Conclusions: The results from these long-term placebo-controlled studies confirm the established safety profile of long-acting OCT, in particular low risk of cardiac, hepatic and renal toxicity in a high-risk population. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L).Methods: This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated.Results: The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P < 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2).Conclusions: In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated. [ABSTRACT FROM AUTHOR]

The objective of this study was to understand the role of liver in modulating remote organ dysfunction during severe acute pancreatitis (SAP). We used sodium taurocholate and endotoxin to induce SAP in the rats and confirmed the development of this condition by measuring serum and ascite levels of the biomarkers of liver and lung damage. Our results showed that expression of tumor necrosis factor (TNF)-α was up-regulated sequentially, first in the gut, then in the liver, and finally in lung. Moreover, the SAP-induced increase in the expressions of TNF-α and IL-6 occurring in gut, liver, and lung was directly related to the increase in time. However, in liver and lung, the transcriptional activity of NF-κB and expression of TNF-α at 4 and 8 h were not increased. The distribution sequence of the pro-inflammatory cytokines to various organs was determined by their detection in the blood from portal vein and inferior vena cava. Although liver received TNF-α during 0.5-8 h of the SAP induction, the release of this cytokine into vena cava was not increased in this period of time. In conclusion, our results suggest that the aggravation of SAP leading to development of MODS exhibited the gut-liver-lung cytokine axis. Furthermore, this study indicates that liver performs both protective and stimulatory activities in the modulation of pro-inflammatory cytokine generation and their distribution to remote organs, such as lungs. [ABSTRACT FROM AUTHOR]

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Gene delivery to primary hepatocytes is an important tool for a number of applications including the study of liver cell biology and pathology, drug screening, and gene therapy. Robust transfection of primary hepatocytes, however, is significantly more difficult to achieve than in cell lines or readily dividing primary cells. In this report, we investigated in vitro gene delivery to both primary rat hepatocytes and Huh7.5.1 cells (a hepatoma cell line) using a number of viral and non-viral methods, including Lipofectamine 2000, FuGene HD, Nucleofection, Magnetofection, and lentiviruses. Our results showed that Lipofectamine 2000 is the most efficient reagent for green fluorescent protein (GFP) gene delivery to primary rat hepatocytes (33.3 ± 1.8% transfection efficiency) with minimal adverse effect on several hepatic functions, such as urea and albumin secretion. The lentiviral vectors used in this study exhibited undetectable gene delivery to primary rat hepatocytes but significant delivery to Huh7.5.1 cells (>80% transfection efficiency). In addition, we demonstrated lentiviral-based and spatially defined delivery of the GFP gene to Huh7.5.1 cells for use in biological microelectromechanical systems. [ABSTRACT FROM AUTHOR]

Purpose: To compare the pharmacokinetic (PK) parameters of a single dose of erlotinib in cancer patients with moderate hepatic impairment (MHI) to those of cancer patients with adequate hepatic function (AHF). Methods: Cancer patients with either AHF or MHI were treated with a single 150 mg dose of erlotinib on day 1 only followed by 96 h of plasma sampling for PK assessment. From day 5, patients were allowed to continue daily erlotinib in a maintenance phase. Non-smoking patients were stratified into an AHF cohort (total bilirubin ≤ upper limit of normal [ULN] and ALT/AST ≤ 1.5 X ULN) or a MHI cohort (Child-Pugh score of 7-9). The frequency of adverse events and laboratory changes were assessed. Results: Thirty-six patients, 21 with AHF and 15 with MHI, received at least one dose of erlotinib. The PK of erlotinib was similar between the two cohorts with a median C of 1.09 versus 0.828 μg/mL and corresponding median AUC 29.3 versus 30.5 μg h/mL for the AHF and MHI cohorts, respectively. Adverse events from erlotinib in cancer patients with MHI were consistent with the known safety profile. Conclusions: The PK and safety profiles of erlotinib in patients with MHI were similar to those with AHF. As a result, a reduced starting dose of erlotinib in patients with MHI is not required and treatment should be guided by patients' tolerability. [ABSTRACT FROM AUTHOR]

Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic steatohepatitis (NASH) is a common histological finding on liver biopsy in morbidly obese patients. The condition, although benign, can progress to cirrhosis and liver failure. We investigated the effect of the duodenal switch (DS) operation on hepatic function and architecture, specifically hepatic steatosis and NASH. Methods: Between November 1999 and June 2004, 697 DS operations were performed for the treatment of morbid obesity. A Tru-Cut needle liver biopsy was routinely performed during the DS operation. Liver function tests were drawn preoperatively for AST and ALT, and again postoperatively at 6, 12 and 18 months and yearly thereafter. Repeat Tru-Cut liver biopsy was performed on all patients (n = 78) who underwent a second intra-abdominal operation for any indication ≥6 months postoperatively. The pathologist evaluated the 2 sets of liver biopsies in a blinded fashion. The hepatic adipose tissue content and the degree of hepatitis were compared in these patients. Results: A transient worsening of the AST (13% of the baseline value, P<.02) and ALT ( 130-160% of the baseline value, P<.0001) levels was found at 6 months after the DS operation. Normal levels were achieved by 12 months postoperatively. A progressive improvement of about 3 grades in severity of NASH and a 60% improvement in hepatic steatosis, were seen by 3 years after the DS operation. Conclusion: DS improves both hepatic steatosis and its resulting inflammation. No detrimental effects on hepatic function were noted after 6 months. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-κB activation, improves altered metabolic and hemodynamic changes and organ dysfunctions caused by endotoxic shock. Design and setting: Prospective, randomized, animal study in a laboratory at a university hospital. Subjects: Twenty- three anesthetized male beagle dogs (10–14 kg). Interventions: Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. A central venous catheter was inserted into the femoral vein, and lactated Ringer's solution (10 ml/kg per hour) was administered throughout the study period. Three groups of animals were studied: (a) the lipopolysaccharide (LPS) group (n=8), which received LPS (250 ng/kg per minute for 2 h); (b) the LPS plus N2733 group (n=8), which received N2733 (30 mg/ kg intravenously and 10 mg/kg hour for 6 h) after the start of LPS; and (c) the N2733 group (n=7), which received N2733 (30 mg/kg intravenously and 10 mg/kg per hour for 6 h). Measurements and results: Changes in hemodynamics, blood gas, gastric intramural pH, and renal and hepatic function were measured for 6 h. Coadministration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension, metabolic acidosis, and gastric mucosal acidosis but did not affect renal or hepatic function. Conclusions: Administration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension and metabolic and gastric mucosal acidosis in an anesthetized canine endotoxic shock model, suggesting its beneficial effect on local blood flow against tissue hypoxia. These findings suggest that blockade of NF-κB activation prevents hypodynamic shock and gastric hypoperfusin in endotoxic shock. [ABSTRACT FROM AUTHOR]

Beta-oxidation is the most important pathway to provide energy for the liver. Our recent findings indicated that radiolabeled medium chain fatty acid analogs could be used as radiopharmaceuticals in the liver, allowing us to monitor alterations in energy metabolism on the cellular level. In the present study, pharmacokinetical analysis of a radioiodmated medium chain fatty acid analog, p-[123I] iodophenylenanthic acid ([123I]IPEA), was carried out in normal and hepatitis model rats to investigate the index for the measurement of beta-oxidation activity in hepatocytes. The rate constant for metabolism of [123I]IPEA in the liver showed a strong correlation with the ATP level, which was determined as an indicator of beta-oxidation activity in hepatocytes. The radioactivity profile in the liver after [123I]IPEA administration provided important information regarding hepatic viability, and the metabolic rate constant of [123I]IPEA calculated by a pharmacokinetic method was a useful criterion for hepatic diagnosis based on hepatic cellular energy metabolism. [ABSTRACT FROM AUTHOR]

In order to investigate whether the size of the caudate lobe of the cirrhotic liver is related to the hepatic functional reserve, the morphometric analysis of the caudate lobe was preformed retrospectively using computed tomography in 106 consecutive patients of whom 67 had compensated (group 1), and 39 uncompensated (group 2) liver cirrhosis. In 51 patients, hepatic measurements were repeated in follow-up. Age- and gender-matched controls were studied. The size of the caudate lobe and the ratio of the caudate to right lobe were correlated with liver function. The caudate lobe was larger in the study patients than in the controls, and larger in group 1 than in group 2 (P<0.01). The caudate to right lobe ratios were also greater in the study patients especially in group 1 (P<0.01). In follow-up, the regression coefficient for the caudate to right lobe ratio was positive in group 1 and negative in group 2 (P<0.05). Even though the caudate lobe of patients with uncompensated liver cirrhosis was larger than that of the controls, patients with compensated liver cirrhosis had a larger caudate lobe and higher caudate to right lobe ratio compared to the patients with uncompensated liver cirrhosis. The caudate lobe may have played an important role in maintaining proper liver function in these patients. [ABSTRACT FROM AUTHOR]

Objective: To determine whether plasma volume determined by the indocyanine green (ICG) dilution method (PV-ICG) is equally accurate independently of its disappearance rate from plasma in the critically ill.Design: Retrospective clinical investigation.Setting: Intensive care unit of a university teaching hospital.Patients and Methods: 192 adult patients were initially enrolled. The PV-ICG and the initial distribution volume of glucose (IDVG) were calculated utilizing a one-compartment model by simultaneous administration of ICG 25 mg and glucose 5 g on the first day of measurement in each patient. Twenty-one patients were excluded from the study because of a higher PV-ICG/IDVG ratio (> 0.45) indicating apparent overestimation of the PV-ICG associated with the generalized protein capillary leakage. The remaining 171 patients were divided into four groups according to the magnitude of their disappearance rate of ICG from plasma (Ke-ICG).Results: Convergence was assumed consistently in each ICG or glucose decay curve, even in the lower Ke-ICG less than 0.10/min. The relationship between the two volumes was not statistically different among groups.Conclusions: The results suggest that the measurement of the PV-ICG can be equally accurate independently of its disappearance rate from plasma unless there is generalized protein capillary leakage. [ABSTRACT FROM AUTHOR]

In our series of 12 patients with unresectable primary liver cancers, hepatic function changes after hepatic artery ligation (HAL) have been investigated. Significant elevation of SGPT, SGOT and LDH were observed on the one hand, and only slight or no derangement in AKP, γ-GT, 5'-NT and bilirubin was noted on the other hand. Factors influencing hepatic function changes after HAL are discussed. The importance of high postoperative oxygen saturation of portal vein blood in maintaining a stable oxygen consumption of hepatocytes is stressed. [ABSTRACT FROM AUTHOR]

The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase A inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase A inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidation was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quinacrine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome P content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase A are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis, possibly due to an inadequate plasma concentration of the drug in some patients. In order to improve therapeutic results the influence of liver function on the plasma levels of mebendazole was investigated during long term therapy. Plasma mebendazole concentrations measured before the morning dose (trough values) showed a highly significant, negative correlation both with the aminopyrine breath test (ABT; r=−0.78, n=14, p<0.001) and the second exponential component of bromsulphthalein elimination (BSP- k; r=−0.74, n=12, p<0.01). These relationships also applied over longer than a single day, since trough and peak mebendazole levels observed over an interval of 6 months before and after testing liver function were equally well correlated with ABT and BSP-k. The daily dosage and other liver function tests seemed to be of minor importance in determining the plasma levels. It was concluded that the microsomal function of the liver and/or cholestasis might be important determinants of plasma mebendazole levels. The results of the study imply that higher and more effective mebendazole concentrations might be achieved by inhibition of the drug metabolizing capacity of the liver rather than by increasing the dose of mebendazole. [ABSTRACT FROM AUTHOR]

Quantiative measurement is required to define the severity of chronic liver disease and the effects of therapy on its complications. This paper presents a method of such assessment based on measurement of hepatocyte function, liver volume, functional liver blood flow, portal perfusion and cardiac output. Data are presented on 54 patients evaluated prior to, and one year after DSRS for variceal bleeding. Preoperative testing showed that alcoholics (n=24) had significantly (p<0.05) larger liver and smaller spleen volumes than nonalcoholic cirrhotics (n=22) and patients with portal vein thrombosis (n=8), but that the other parameters were not significantly different by etiologies. At one year after DSRS: all groups showed a significant (p<0.01) reduction of 41 per cent in spleen size: liver volume was significantly (p<0.05) reduced in cirrhotics: there was a significantly (p<0.01) greater loss of portal perfusion in alcoholic cirrhosis: liver blood flow showd a significant (p<0.05) rise in alcoholics when compared to nonalcoholics and portal vein thrombosis patients: cardiac output ros in alcoholic cirrhosis: hepatocyte function was not significantly different in any group. This study shows that in patients all doing well clinically one year after DSRS, there are markedly different hemodynamic responses. Further studies on cirrhosis aimed at improving therapy for its complications should include some objective, quentitative assessment, first to define the study population, and second to measure the effect of the therapy. [ABSTRACT FROM AUTHOR]

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p<0.05) and 19.7% of dose (p<0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r=0.971) but not to ALT activity in plasma at 1 h (r=0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT. [ABSTRACT FROM AUTHOR]

The aim of the proposed work was to analyze the toxicity of oxidized carbon nanotubes (CNTox), functionalized by doxorubicin (CNT-Dox) and fluorescein (CNT-FITC) on cell and organism level. The cytotoxic effect of CNTox, CNT-Dox, and CNT-FITC was analyzed on tumor cells in vitro (2-D, 3-D cultures) and on Balb2/c mice model in vivo. As a result, it was demonstrated the possibility of doxorubicin immobilization on the surface of CNT and controlled release of doxorubicin (Dox) from the surface of CNT. Dox immobilization coincident with decreasing cytotoxic effect CNT-Dox compared with free Dox. Breakdown of peptide bonds with CNT surface led to the release of doxorubicin and dose-dependent enhancement of the cytotoxic effect of CNTs and Dox. The combined cytotoxic effect from CNTs, Dox, and trypsin on the survival of tumor cells was shown. At the organism level, it was investigated the effect of the obtained nanostructures on the state of hepatic enzymatic system, the protein metabolism, and cell blood composition of the experimental animals. CNTox influence in vivo model was statistically the same as control. CNT-Dox demonstrated lower total organism toxic effect compared to the pure doxorubicin. Deviations in the cell blood composition indicated a general toxic effect of CNT-Dox, but it was more moderate compared with of pure doxorubicin. From the data obtained, we concluded that binding CNTs with doxorubicin allows reducing toxicity of the doxorubicin on the general biochemical indicators of blood and violations in the blood cells composition in vivo. At the same time, the combined effect of CNTs and doxorubicin after drug release allowed us to achieve greater efficacy in suppressing tumor growth in vitro. [ABSTRACT FROM AUTHOR]