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PubMed1996

Graft function and outcome of older (> or = 60 years) donor livers.

Livers from donors > or = 60 years of age are often considered inadequate for transplantation by many centers. With waiting times exceeding 1 year in our region, we have aggressively used livers from this donor age group. Between 1990 and 1994, 209 patients received 223 liver grafts at our institution. Of these, 29 (13%) were from donors > or = 60 years of age (group A) and 194 (87%) were from donors < 60 years of age (group B). The two groups were matched for recipient diagnosis and severity of disease. Group A and B donors had similar liver, renal, and hematologic studies prior to donation. Weight, sex, race and vasopressor requirement were also similar. Postoperative alanine aminotransferase, aspartate aminotransferase,and prothrombin time were not significantly different over the first 10 postoperative days. Group A grafts were significantly more cholestatic than group B grafts on postoperative days 6-10. The retransplantation rate for primary graft nonfunction was not significantly different from group A (6.7%) and group B (3.4%; P=0.04). Patient and graft survival rates at 1 year were 58.6 % and 44.8% for group A and 79.2% and 74.5% for group B (P<0.001 for both). Four of 12 deaths in the first year in group A were completely unrelated to graft function. If these are excluded, patient and graft survival rates were 68% and 52%, which are better but still significantly less than in group B. Initial graft function of older donor livers are similar to that of the matched younger group. However, patient and graft survival rates were significantly worse for the older donors, even when corrected for unrelated deaths. Livers should not be discarded based on age alone without inspection and/or biopsy to rule out significant steatosis. Prompt retransplantation for primary graft nonfunction of older donors are generally more cholestatic than those from the younger donor age group; however, many of them function quite well. At the present time, given the inability to identify donor variables associated with decreased recipient survival, we recommend cautious use of older liver grafts in healthier recipients.

Adult↗
PubMed1996

Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2.

We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism of caffeine using mice lacking its expression (CYP1A2 -/-). The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice. The clearance was concomitantly eight times slower. No parameter that could affect the pharmacokinetics differed between CYP1A2-/-and wild-type mice such as creatinine for kidney function; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2EI, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially 1-methylxanthine and I-methylurate) were also found in the urines of the CYP1A2-/-animals, although at 40% of the level found in wild-type mice. These data indicate that the clearance of caffeine in wild-type mice is primarily determined by CYP1A2.

Animals↗
PubMed2006

Rebiopsy in patients with untreated hepatitis C: a useful procedure.

BACKGROUND: The progression of fibrosis in the early stages of chronic hepatitis C virus is variable, and the ideal interval to perform a new biopsy in untreated patients is still unknown. AIMS: We evaluated the histologic progression of patients with untreated hepatitis C virus with two liver biopsies and correlated disease progression with demographic, epidemiologic, biochemical, and histologic variables. PATIENTS AND METHODS: Untreated hepatitis C virus-infected patients with two liver biopsies at a minimum interval of 1 year were studied. Gender, age, parenteral risk factors, duration of infection, alcohol intake, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and histologic findings were analyzed. RESULTS: Fifty-five patients were included. The first biopsy showed low grades of fibrosis and periportal necroinflammatory activity in 93%. A second biopsy was performed after 39 +/- 14 months; 40% of patients showed a progression of fibrosis and/or periportal necroinflammation. Comparison between groups with and without histologic worsening revealed no differences in demographic, epidemiologic, biochemical, or histologic data. CONCLUSIONS: Histologic worsening occurred in 40% of untreated patients after 3.2 years. No factor could be established at the first biopsy to predict which patients are at risk of progression. Thus, histologic reassessment between 3 and 5 years seems to be the only approach to document disease progression and establish treatment indication.

Adolescent↗
PubMed2004

Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion.

BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.

Acid-Base Equilibrium↗
PubMed2004

Noninvasive evaluation of graft steatosis in living donor liver transplantation.

BACKGROUND: Hepatic steatosis affects graft function as well as postoperative recovery of donors in living donor liver transplantation. Liver macrovesicular steatosis in living donors was assessed using quantitative X-ray computed tomography (CT) analysis and histological examination of intraoperative liver biopsy. METHODS: A total of 266 living donors with complete pretransplant CT data and intraoperative "time 0" biopsy were included in the study. Liver biopsy specimen obtained during donor operation was examined for macrovesicular steatosis and was classified as none; mild (<30%); moderate (30%-60%); or severe (>60%). Liver-to-spleen CT attenuation values ratio (L/S ratio) on noncontrast-CT was evaluated for its usefulness as an index of hepatic steatosis in comparison with other parameters including body mass index (BMI) and serum liver function tests (gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, cholinesterase, and total cholesterol) using receiver operating characteristic (ROC) analysis. RESULTS.: Histological grade of macrovesicular steatosis was none in 198 patients (74.4%), mild in 50 (18.8%), moderate in 15 (5.7%), and severe in 3 (1.1%). The median L/S ratios for the respective histological grades were 1.20 (range: 1.00-1.46), 1.12 (0.83-1.37), 1.01 (0.74-1.21), and 0.90 (0.70-0.99) (P<0.0001). The ROC curve for L/S ratio was located closest to the upper left corner, and the area under the curve of L/S ratio was significantly larger than that of any other preoperative variables. CONCLUSION: L/S ratio calculated from preoperative CT can be a useful tool to discriminate hepatic macrovesicular steatosis. Based on the present results, the optimal cut-off value for L/S ratio to exclude more than moderate steatosis would be 1.1.

Adult↗
PubMed2006

Curcumin has potent liver preservation properties in an isolated perfusion model.

BACKGROUND: Curcumin has profound antioxidant and anti-inflammatory properties. This research assessed the effect of curcumin on liver preservation. METHODS: Sprague-Dawley rat livers were flushed with different preservation solutions [Euro-Collins solution (EC), phosphate buffer saline (PBS), University of Wisconsin solution (UW)] with or without curcumin (25-200 microM) and stored at 4 degrees C for 24-48 hours. Livers were then perfused for 120 minutes via the portal vein with oxygenated Krebs-Henseleit bicarbonate buffer solution at a pressure of 18 cm H2O in a perfusion apparatus. The livers in the normal (NL) group were flushed with EC, PBS, or UW, then immediately perfused (zero preservation time). RESULTS: We found that curcumin at 100 microM concentration had the optimal preservation characteristics. Portal flow rates and bile production were significantly higher and liver enzymes (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) were significantly lower in the EC+C livers and PBS+C livers than in the EC or PBS with optimum concentration of 100 microM of curcumin. Comparing UW+C vs. UW livers, at 24 hours there was no difference in these parameters; however, at 36 hours and 48 hours, portal flow rates and bile production were significantly higher in UW+C livers. CONCLUSIONS: We found that curcumin has inherent organ preservation quality as it enhanced liver preservation in PBS. In addition, curcumin enhanced the preservation quality of EC and UW solutions, thereby extending the preservation time while maintaining the organ quality.

Animals↗
PubMed1991

Evaluation of fasting and postprandial total serum bile acid concentration in dogs with hepatobiliary disorders.

The fasting and 2 h postprandial total serum bile acid concentrations (FSBA and PSBA), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin (Total), and retention of bromosulphthalein were determined in a group of dogs with various hepatobiliary disorders as well as in a group of dogs with other diseases than hepatobiliary disorders. Although FSBA and PSBA were generally elevated in cases of hepatobiliary disorders, no distinction between different disease groups could be made based solely on FSBA and PSBA. FSBA and PSBA were found to be relatively sensitive and specific parameters compared to the other hepatic tests. PSBA tended to be superior to the other parameters investigated in terms of sensitivity, specificity, positive predictive value, and negative predictive value.

Animals↗
PubMed1991

Evaluation of triflupromazine as a sedative in camels (Camelus dromedarius).

Effects of administration of triflupromazine were evaluated in 11 adult domesticated camels (Camelus dromedarius) weighing 403 +/- 29.5 kg (Mean +/- SE). Six camels were used to evaluate sedative properties of the drug and its effects on haematological and blood biochemical parameters. In the remaining 5 camels, effects on haemodynamics, acid base status and blood gases were studied. In all the animals triflupromazine was administered intramuscularly in the gluteal region at the rate of 2 mg/kg. Camels voluntarily sat down 48.9 +/- 5.4 min after administration of the drug but stood up again if disturbed. Drowsiness, drooping of lower lip and salivation were evident. The animals stood on their own and started walking with ataxia after 159 +/- 7 min and recovered completely from the effect of drug within 259 +/- 23 min. The drug caused a significant tachycardia and a moderate hypotension. The decrease in central venous pressure was also significant. Rectal temperature, respiratory rate, acid base status, blood gases, haemoglobin concentration, packed cell volume, total erythrocyte count, total leucocyte count, differential leukocyte count, blood urea nitrogen, plasma alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, blood glucose and plasma concentrations of sodium, potassium, chloride and inorganic phosphate were not significantly affected by triflupromazine.

Animals↗
PubMed2006

Prognostic significance of common preoperative laboratory variables in clear cell renal cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of common preoperative laboratory variables evaluated before surgery for clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: We retrospectively analysed the records of 355 patients who had surgery for clear cell RCC, assessing: clinical factors, including preoperative laboratory measurements, i.e. haemoglobin level, leukocyte count, platelet count, erythrocyte sedimentation rate (ESR), serum calcium, alkaline phosphatase (ALP), albumin, bilirubin, alanine aminotransferase, aspartate aminotransferase, and red blood cells in urine; and pathological factors, with the survival rates after surgery. RESULTS: The presence of metastasis, tumour stage and tumour size, with the ESR and ALP before surgery, were identified as significant prognostic factors for progression-free survival in a multivariate analysis. The same factors were significant independent factors for disease-specific survival, except for ESR and ALP, which were nearly statistically significant. When limited to non-metastatic tumours only, the multivariate analysis showed that ESR and ALP, with tumour stage, grade, size and necrosis, were independent prognostic factors for disease-specific survival. CONCLUSIONS: Along with traditionally accepted prognostic factors, these results suggest that common laboratory variables assessed before surgery, e.g. ESR and ALP, might also be useful in assessing the prognosis for patients with non-metastatic clear cell RCC. Including various laboratory variables in prognostic algorithms for RCC should be considered after further validation in RCCs of various histological subtypes and stages.

Adult↗
PubMed2006

Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.

Animals↗
PubMed2004

Insulin resistance in chronic hepatitis C.

Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients. 15 patients and nine healthy controls without any known condition that may affect IR were enrolled to the study. Chronic hepatitis C was diagnosed by liver biopsy (hepatic activity index was also determined in 10 patients) and appropriate viral and biochemical tests. Eight patients were given interferon therapy, which had been stopped for at least 3 months before the study. Euglycaemic hyperinsulinemic clamp technique was performed as previously described and peripheral glucose utilisation rate, M value, was calculated in mg/kg/min by infusion of 40 IU/m2/min regular insulin. M value of the control group was significantly higher than that of chronic hepatitis C patients (M = 5.1+/-1 vs. 3.7+/-1; p = 0.004), which was consistent with IR in the patient group. There was no significant correlation between the M value and alanine aminotransferase, aspartate aminotransferase and hepatic activity index (p = 0.621, 0.549, 0.479, respectively). Our results suggest that IR is present in chronic hepatitis C patients; it is not directly related to hepatic injury, moreover, it may be associated with some component(s) inherent to hepatitis C virus.

Blood Glucose↗
PubMed2005

Development of an HSV-tk transgenic mouse model for study of liver damage.

The herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system that selectively depletes cells expressing HSV-tk upon treatment with GCV has provided a valuable tool for developing a new animal model expressing the desired tissue damage. In this paper, an HSV-tk vector with an albumin promoter/enhancer was constructed. Based on the favourable killing effect on Hep-G2 cells by the recombinant construct, the HSV-tk transgenic mouse strains were developed. One strain of the TK transgenic mouse (TK5) was studied intensively. Integration of the target gene was confirmed primarily by PCR. Fluorescence in situ hybridization following G-banding analysis demonstrated that the insertion site was located at 2F1-G3. The hepatocyte-specific transcription and expression of HSV-tkwas verified by reverse transcription (RT)-PCR as well as by immunohistochemical staining. When two second-generation mice (TK5-F1 and TK5-F2) were injected with GCV, the pathogenic alterations in the liver were readily identified, including the appearance of vaculation in the hepatocytes with inflammatory infiltration in the liver, and diffuse proliferation of hepatocytes. In addition, the blood test demonstrates a significant increase of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. In conclusion, the transgenic mouse model with hepatocyte-specific expressed HSV-tk developed hepatitis with administration of GCV, had morphological and clinical chemical characteristics indicative of hepatocellular disease and should be useful for the the study of inducible liver-specific diseases.

Animals↗
PubMed2006

Protective effect of dietary curcumin and capsaicin on induced oxidation of low-density lipoprotein, iron-induced hepatotoxicity and carrageenan-induced inflammation in experimental rats.

The beneficial influence of dietary curcumin, capsaicin and their combination on the susceptibility of low-density lipoprotein (LDL) to oxidation was examined in an animal study. Individually, both dietary curcumin and capsaicin significantly inhibited the in vivo iron-induced LDL oxidation, as well as copper-induced oxidation of LDL in vitro. The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that of individual compounds. This protective influence of spice principles was also indicated by the relative anodic electrophoretic mobility of oxidized LDL on agarose gel. In another study, rats injected with iron showed hepatic toxicity as measured by an increase in lipid peroxides and elevated serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. Dietary curcumin, capsaicin and their combination reduced the activities of these enzymes, and lowered the liver lipid peroxide level, indicating amelioration of the severity of iron-induced hepatotoxicity. In yet another study, a comparison of the extent of carrageenan-induced paw inflammation showed that both dietary curcumin and capsaicin moderately lowered inflammation, while the spice principles in combination were more effective. Dietary curcumin and capsaicin significantly decreased the activity of 5'-lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles. Results suggest that dietary curcumin and capsaicin individually are protective to LDL oxidation both in vivo and in vitro, to iron-induced hepatotoxicity and to carrageenan-induced inflammation. This beneficial effect was higher when the two compounds were fed in combination.

Animals↗
PubMed1992

Serum biochemical values of rusa deer (Cervus timorensis russa) in New Caledonia.

Blood samples were collected from 91 rusa deer (Cervus timorensis russa), immediately after being shot. Serum mean biochemical values from shot deer are presented for blood urea nitrogen, creatinine, creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, albumin, calcium, and phosphorus. Mean total protein and albumin increased with age. There was an age-associated increase of gamma globulins. Mean creatine kinase activity and creatinine, albumin and phosphorus concentrations were higher in stags than in hinds. Pregnant hinds had lower mean creatine kinase activity and phosphorus and higher mean alanine aminotransferase and total protein than non-pregnant hinds. Mean calcium concentration increased when deer were agitated before bleeding.

Aging↗
PubMed1996

Hematology and clinical chemistry values of normal and euthymic hairless adult male Dunkin-Hartley guinea pigs (Cavia porcellus).

Hematology and serum chemistry measurements were performed on blood specimens from 12 male Dunkin-Hartley hairless guinea pigs Crl:IAF(HA)BR and 10 haired Dunkin-Hartley male guinea pigs Crl:(HA)BR. Significantly higher activities of alanine aminotransferase, aspartate aminotransferase, amylase, and creatine kinase were observed in the hairless guinea pigs as compared to the haired strain. Alkaline phosphatase activity was found to be lower in the hairless guinea pig. The hairless guinea pigs were found to have serum urea concentrations approximately 46% higher than the normal guinea pig strain. The erythrocytic mean cell volume of the hairless strain was found to be smaller, with a greater hemoglobin content. Hairless guinea pigs were found to have approximately 40% fewer leukocytes with a reversed lymphocyte:neutrophil ratio compared to the haired guinea pigs which had much higher lymphocyte counts.

Journal Article↗
PubMed2002

Clinical chemistry of companion avian species: a review.

Birds have evolved alternate physiologic strategies to contend with dehydration, starvation, malnutrition, and reproduction. Basic anatomic and functional differences between birds and mammals impact clinical chemistry values and their evaluation. Interpretation of the results of standard biochemical analyses, including BUN, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma glutamyltransferase, bilirubin, ammonia, alkaline phosphatase, cholesterol, bile acids, glucose, albumin, globulins, calcium, phosphorus, prealbumin (transthyretin), fibrinogen, iron, and ferritin, is reviewed and discussed in relation to these physiological differences. The use and interpretation of alternative analytes appropriate for avian species, such as uric acid, biliverdin, glutamate dehydrogenase, and galactose clearance, also are reviewed. Normal avian urine and appropriate use of urinalysis, an integral part of laboratory diagnosis in mammalian species that frequently is omitted from avian diagnostic protocols, is discussed.

Animals↗
PubMed2006

Fatal hepatic sarcocystosis in a puppy with eosinophilia and eosinophilic peritoneal effusion.

A 3-month-old male Golden Retriever puppy was evaluated for lethargy and fever of 2-days duration. Results of a CBC and biochemical profile revealed marked eosinophilia (6.3 X 10(3)/microL; reference interval 0.1-1.2 X 10(3)/microL), moderate thrombocytopenia, and increased activities of alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Hepatomegaly and peritoneal effusion were found using abdominal ultrasound. Peritoneal fluid analysis revealed eosinophilic inflammation (23,000 nucleated cells/microL with 88% eosinophils). Despite supportive treatment the puppy's condition deteriorated rapidly; euthanasia was requested, and a necropsy performed. Microscopically, there was marked necrosuppurative and eosinophilic hepatitis with vasculitis. Numerous hepatocytes contained protozoal organisms suspected to be Toxoplasma gondii or Neospora caninum. However, serum was negative for both T gondii and N caninum antibodies; polymerase chain reaction assay on hepatic tissue was negative for both organisms; and immunohistochemical evaluation of hepatic tissue using serum raised against T gondii, N caninum, and Sarcocystis neurona also was negative. Schizont morphology suggested that merozoites replicated by endopolygeny, forming rosettes around a central residual body. Transmission electron microscopy revealed that merozoites lacked rhoptries. These findings were consistent with a diagnosis of Sarcocystis canis, an apicomplexan parasite with an unknown life cycle.

Animals↗
PubMed2002

Effects of long-term creatine supplementation on liver and kidney functions in American college football players.

The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function. Twenty-three members of an NCAA Division II American football team (ages = 19-24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20 g (mean SD = 13.9 5.8 g) for 0.25 to 5.6 years (2.9 1.8 years). Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups. Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant. Therefore, it appears that oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.

Administration, Oral↗