1,377 results on '"hepatic function"'
Search Results
52. Influence of Carbon Nanotubes and Its Derivatives on Tumor Cells In Vitro and Biochemical Parameters, Cellular Blood Composition In Vivo
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Olena M. Perepelytsina, Andriy P. Ugnivenko, Alexey V. Dobrydnev, Olga N. Bakalinska, Andrii I. Marynin, and Mychailo V. Sydorenko
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Multi-walled carbon nanotubes ,Nanotoxicity ,Multicellular tumor spheroids ,Doxorubicin ,Hepatic function ,Cell blood composition ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Abstract 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.
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- 2018
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53. Metabolic responses to dietary carbohydrate/lipids ratios in neotropical hybrid catfish (♂Pseudoplatystoma corruscans×♀Pseudoplatystoma fasciatum)
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DANIEL OKAMURA, RODRIGO FORTES-SILVA, RENAN R. PAULINO, FELIPE G. DE ARAÚJO, DIEGO V. DA COSTA, RAQUEL T. PEREIRA, and PRISCILA V. ROSA
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enzymes activity ,hepatic function ,intermediary metabolism ,hybrid catfish ,Surubim ,Science - Abstract
Abstract: The purpose of this study was to assess the effect of different carbohydrate and lipid (CHO/L) ratios on the performance and energy metabolism of hybrid catfish (♂Pseudoplatystoma corruscans × ♀ Pseudoplatystoma fasciatum). One hundred and sixty-eight fish (104.9±16.5 g BW) were distributed into 24 100-L tanks. The experiment was performed using a randomised block design with four CHO/L ratios (0.45, 1.00, 1.66 and 2.85) and six replications. Growth performance, protein content, glucose and triglycerides in plasma, muscle and liver, and the hepatic activity of the malic and glucose-6-phosphate dehydrogenase (G6PD) enzymes were measured after 60 feeding days. No significant differences were observed in growth performance, protein and triglycerides of plasma and muscle, hepatic protein or malic enzyme activity. CHO/L: 2.85 provided the highest plasma and liver glucose, while CHO/L: 0.45 showed high liver triglycerides. A linear effect was found for the hepatic activity of G6PD and dietary starch levels (R2=0.93). The hepatic activity of G6PD was greater in CHO/L=2.85 than for CHO/L: 0.45. In conclusion, the limit of dietary starch inclusion and lipids were 15% and 9.00%, respectively (CHO/L: 1.66), and this level did not affect the energy metabolism of the juvenile hybrid catfish.
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- 2019
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54. 3D Hepatic Organoid-Based Advancements in LIVER Tissue Engineering
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Amit Panwar, Prativa Das, and Lay Poh Tan
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liver tissue engineering ,hepatic organoids ,hepatic function ,hepatocytes ,3D culture ,Technology ,Biology (General) ,QH301-705.5 - Abstract
Liver-associated diseases and tissue engineering approaches based on in vitro culture of functional Primary human hepatocytes (PHH) had been restricted by the rapid de-differentiation in 2D culture conditions which restricted their usability. It was proven that cells growing in 3D format can better mimic the in vivo microenvironment, and thus help in maintaining metabolic activity, phenotypic properties, and longevity of the in vitro cultures. Again, the culture method and type of cell population are also recognized as important parameters for functional maintenance of primary hepatocytes. Hepatic organoids formed by self-assembly of hepatic cells are microtissues, and were able to show long-term in vitro maintenance of hepato-specific characteristics. Thus, hepatic organoids were recognized as an effective tool for screening potential cures and modeling liver diseases effectively. The current review summarizes the importance of 3D hepatic organoid culture over other conventional 2D and 3D culture models and its applicability in Liver tissue engineering.
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- 2021
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55. Correlation of bile acids and aspartate-aminotransferase with outcomes in cholestasis of pregnancy.
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Juusela, A.L., Cordero, L., Gimovsky, M., and Nazir, M.
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PREGNANCY outcomes , *BILE acids , *ASPARTATE aminotransferase , *AMNIOTIC liquid , *PREMATURE labor - Abstract
OBJECTIVE: To identify laboratory data that correlates with poor perinatal outcomes. METHODS: A retrospective chart review of women with intrahepatic cholestasis of pregnancy (ICP), admitted for delivery between January 1, 2013 and December 31, 2017, was performed. Chi-square, student's t-test, and ANOVA statistical analysis was performed. The receiver-operator characteristic curves were plotted for the prediction of each category of perinatal outcome and the areas under the curves were determined. All p-values were two-sided, and p < 0.05 was considered statistically significant. RESULTS: Analysis of the 61 ICP cases showed no occurrence of the intrauterine fetal demise (IUFD), stillbirth, abruption, or neonatal demise. ROC curve analysis revealed a statistically significant correlation between bile acid and AST levels and perinatal outcomes. A bile acid (BA) level equal to or greater than 37μmol/L strongly predicted spontaneous preterm labor in women affected by ICP with a sensitivity of 100% and specificity of 60.70% (p = 0.002). A BA level equal to or greater than 42μmol/L strongly predicted meconium-stained amniotic fluid with a sensitivity of 85.70% and specificity of 66.70% (p = 0.006). AST levels equal to or greater than 62 IU/L strongly predicted NICU admission with a sensitivity of 81.30% and specificity of 62.20% (p = 0.002). AST levels equal to or greater than 75 IU/L strongly predicted hyperbilirubinemia in the neonates with a sensitivity of 87.50% and specificity of 69.80% (p = 0.001). CONCLUSIONS: There is a statistically significant correlation between elevated BA and elevated AST levels and adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]
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- 2020
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56. Relationship between myocardial enzyme levels, hepatic function and metabolic acidosis in children with rotavirus infection diarrhea.
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Na-ying Zuo, Yuan-da Zhang, Qing-wei Dong, and Li-po Han
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ROTAVIRUS diseases , *ACIDOSIS , *DIARRHEA , *CREATINE kinase , *COLLOIDAL gold - Abstract
Objective: To investigate the relationship between myocardial enzymes, liver function and metabolic acidosis in children with rotavirus infection diarrhea. Methods: The data of 70 children with infectious diarrhea treated in Baoding Children’s Hospital, China, from October 2017 to April 2018 were retrospectively studied. The antigen of rotavirus in feces was positive by colloidal gold method. According to the clinical features of biochemical indicators and mental status, the patients were divided into four groups, an acidosis-free group, a mild acidosis group, a moderate acidosis group and a severe acidosis group, in line with acidosis severity. In addition to detecting the hepatic functions of the pediatric patients in the four groups, including aspartate aminotransferase (AST), alanine aminotransfer (ALT) levels, and myocardial enzyme levels (e.g., creatine kinase, or CK, and creatine kinase isoenzyme, or CK-MB), the relationships of hepatic function, myocardial enzyme levels and acidosis severity of the patients with infectious diarrhea caused by rotavirus infection were also analyzed. Results: There was no significant difference in sex and age among the four groups (P>0.05). However, there was a significant difference in the frequency of diarrhea and vomiting (p<0.05). In addition, there were significant differences in creatine kinase, CK-MB, AST and ALT levels in children with metabolic acidosis of different severities. Conclusion: With the aggravation of metabolic acidosis, infectious diarrhea caused by rotavirus is characterized by the aggravation of hepatic function and myocardial cells. [ABSTRACT FROM AUTHOR]
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- 2020
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57. Effect of ursodeoxycholic acid on liver markers: A systematic review and meta‐analysis of randomized placebo‐controlled clinical trials.
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Simental‐Mendía, Mario, Sánchez‐García, Adriana, and Simental‐Mendía, Luis E.
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URSODEOXYCHOLIC acid , *CLINICAL trials , *GAMMA-glutamyltransferase , *META-analysis , *ALANINE aminotransferase , *LIVER function tests , *GLUTATHIONE transferase - Abstract
Aim: The objective of this meta‐analysis was to evaluate the effect of ursodeoxycholic acid (UDCA) therapy on serum liver function tests. Methods: PubMed, Web of Science, Scopus and Google Scholar databases were searched to identify randomized placebo‐controlled trials assessing the impact of UDCA on hepatic parameters. Meta‐analysis was conducted using a random‐effects model and sensitivity analysis through the leave‐one‐out method in the Review Manager statistical software version 5.3. Results: After UDCA treatment, meta‐analysis revealed a significant reduction of alanine aminotransferase (weighted mean difference [WMD]: –15.28 U/L, 95% confidence interval [CI]: −23.42, −7.15, P = 0.0002, I2 = 97%), aspartate aminotransferase (WMD: –16.13 U/L, 95% CI: −23.84, −8.42, P < 0.0001, I2 = 97%), gamma‐glutamyl transferase (WMD: –23.29 U/L, 95% CI: −33.97, −12.61, P < 0.0001, I2 = 97%), alkaline phosphatase (WMD: –93.80 U/L, 95% CI: −126.36, −61.25, P < 0.0001, I2 = 95%) and bilirubin (WMD: –0.18 U/L, 95% CI: −0.35, −0.01, P = 0.04, I2 = 93%), but not significant changes in albumin levels (WMD: 0.10 U/L, 95% CI: −0.05, 0.24, P = 0.18, I2 = 80%). Conclusion: The results of the present meta‐analysis suggest a hepatoprotective effect of UDCA by reducing serum liver parameters. [ABSTRACT FROM AUTHOR]
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- 2020
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58. L-glutamine ameliorates adipose-hepatic dysmetabolism in OC-treated female rats.
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Olaniyi, Kehinde Samuel and Olatunji, Lawrence Aderemi
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GLUCOSE-6-phosphate dehydrogenase , *XANTHINE oxidase , *BODY weight , *ORAL contraceptives , *DISTILLED water - Abstract
Adipose dysfunction and inflammation with or without hepatic def ects underlie metabolic obesity. Glutamine (GLU) improves glucoregulation and metabolic indices but its effects on adipose function and hepatic lipid deposition in estrogen-progestin oral contraceptive (EPOC) users are unknown. Therefore, we hypo thesized that GLUT supplementation would protect against adipose dysfunction and e xcess hepatic lipid influx and deposition in EPOC-treated animals by suppressing ade nosine deaminase/xanthine oxidase (ADA/XO) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense. Female Wistar rats weighing 150-180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six r ats/group). The groups received vehicle (distilled water, p.o.), GLUT (1 g/kg), EPOC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and EPOC plus GLUT, respectively, daily for 8 weeks. Results showed that the administration of EPOC caused glucose dysregulation and increased triglyceride-glucose index and visceral adiposity, but the body weight and liver weight were not affected. However, EPOC significantly d ecreased adipose lipid, G6PD and glutathione and increased glycogen synthesis, A DA, XO, uric acid, lipid peroxidation, lactate production and gamma-glutamyl transferase activity (GGT). On the other hand, EPOC increased hepatic lipid, ADA, XO, uric aci d, lipid peroxidation and lactate production and decreased glycogen synthesis, G6PD a nd glutathione. Nevertheless, supplementation with glutamine attenuated these alterations. Collectively, the present results indicate that EPOC causes metabolically ind uced obesity which is associated with adipose dysfunction and hepatic metabolic distu rbance. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA/XO activity and enhancement of G6PD-dependent antioxidant defense. [ABSTRACT FROM AUTHOR]
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- 2020
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59. Dietary supplementation of autolysed yeast enhances growth, liver functionality and intestinal morphology in African catfish.
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Adeoye, Ayodeji A., Obasa, Sam O., Fawole, Femi J., Wan, Alex H. L., and Davies, Simon J.
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CATFISHES , *ALANINE aminotransferase , *YEAST , *CLARIAS gariepinus , *MORPHOLOGY - Abstract
A feeding trial was conducted to evaluate the potential of dietary supplementation of autolysed brewer's yeast (AY) on African catfish. The catfish (22.5 ± 1.15 g/fish, 20 fish 33 L/tank) were fed with either of diets (390 g/kg crude protein, 140 g/kg lipid) supplemented with 0, 3, 6 or 10 g/kg AY (n = 3). After 49 days of feeding, the final body weight and metabolic growth rate of the catfish fed 3 g/kg AY (3‐AY) diet were higher than those fed the control diet (p <.05). The lowest level (p <.05) of alanine transaminase was detected in the blood of the catfish fed 3‐AY diet. The mid‐intestinal histology of the catfish revealed no significant difference (p >.05) in intestinal perimeter ratio. However, an elevated (p <.05) abundance of goblet cells and intraepithelial leucocytes were found in the intestine of catfish fed 3, 6 and 10 g/kg AY diets, with the highest level of abundance recorded in the mid‐intestine of the catfish fed 3‐AY diet. The results suggest that dietary 3 g/kg autolysed brewer's yeast supplementation improves growth performance of African catfish without deleterious effect on liver functionality and gut morphology. [ABSTRACT FROM AUTHOR]
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- 2020
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60. 肾移植术后患者血液他克莫司代谢率(C0/D 值) 对肝肾功能的影响研究.
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魏菁菁, 王冬梅, 胡 俊, and 丁进亚
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BLOOD proteins ,KIDNEY transplantation ,BLOOD sampling ,METABOLISM ,IMMUNOASSAY - Abstract
Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2020
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61. Acetaminophen‐induced hepatotoxicity of cultured hepatocytes depends on timing of isolation from light‐cycle controlled mice.
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Moriya, Koji, Tamai, Miho, Koga, Takumi, Tanaka, Toshiaki, and Tagawa, Yoh‐ichi
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LIVER cells , *HEPATOTOXICOLOGY , *TOXICITY testing , *CIRCADIAN rhythms , *DRUG metabolism , *DRUG development , *DRUG toxicity - Abstract
Most physiological changes follow a daily cycle in animals because their circadian rhythm is adjusted to and synchronized with sunlight. In particular, the circadian rhythm affects liver functions, including pharmacokinetics and metabolism. The influence of circadian rhythm has not been included in hepatotoxicity assays used in drug discovery and development. In this study, the contribution of circadian rhythm was investigated in acetaminophen‐induced hepatotoxicity in mice and primary cultured hepatocytes. Hepatotoxicity was induced via the intraperitoneal administration of acetaminophen to a greater extent at night than during the day in mice. The sensitivity of acetaminophen‐induced hepatotoxicity was consistent with the expression levels of acetaminophen‐metabolizing enzyme and circadian genes. The host‐derived circadian rhythm was still evident in the primary cultured hepatocytes within a day after their isolation from the liver. Primary cultured hepatocytes isolated at night were significantly more sensitive to acetaminophen than those isolated during the day. The sensitivity toward acetaminophen‐induced hepatotoxicity depended on the circadian rhythm of the expression of acetaminophen‐metabolizing genes and intracellular glutathione levels in primary cultured hepatocytes. These results obtained from cultured cells correspond to those in mice, suggesting that the timing of hepatocyte isolation is important when investigating drug metabolism and toxicity tests in culture. [ABSTRACT FROM AUTHOR]
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- 2020
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62. Impact of Comorbidity on Treatment Decision Making and Outcomes
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Lee, Jae Jin, Extermann, Martine, and Koczwara, Bogda, editor
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- 2016
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63. Investigation of Serum Markers of Hepatic Fibrosis in Equids.
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Potier, Julie F.N., Durham, Andy E., Modi, Raakesh, Rosenberg, William, and Dash, Sophie A.
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• Hepatic fibrosis is a good prognostic indicator in cases of hepatopathies in equids. • Hepatic fibrosis (HF) monitoring can help assess response to treatment. • Serum hyaluronic acid and a novel liver fibrosis score correlated with HF in equids. • Procollagen III N-terminal peptide was also correlated with HF in horses and ponies. Liver disease is common in equine practice, and treatment and prognosis are dependent on histopathologic examination of biopsies. Liver biopsy is invasive and expensive which restricts its use. Serum markers are used to predict hepatic fibrosis in humans. This study aimed to investigate the enhanced liver fibrosis (ELF) test, based on serum Hyaluronic Acid (HA), procollagen III N-terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) to detect hepatic fibrosis in equids. Four groups were included; two with increased serum concentrations of liver-derived enzymes and a liver biopsy (group H; 10 horses and ponies and group D; 10 donkeys) and two without any evidence of liver disease (group HC; 10 horses and ponies and group DC; 10 donkeys). All samples were analyzed for concentrations of HA, PIINP, and TIMP-1. Given the failure to detect TIMP-1 in most subjects, a novel eELF (equid ELF) score was calculated, based on HA and PIIINP. HA and PIIINP concentrations and the eELF score, were compared with determined hepatic fibrosis. HA, PIIINP, and eELF were significantly greater in horses and ponies with a histopathologic fibrosis score ≥ 2 compared with those < 2. A similar observation was found with donkeys for HA and eELF. A significant correlation was found between fibrosis score and HA, PIIINP, and eELF for horses and ponies, and between fibrosis score and HA and eELF in donkeys. Serum HA and the eELF score might be useful serum markers to predict and monitor hepatic fibrosis in horses, ponies, and donkeys. [ABSTRACT FROM AUTHOR]
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- 2023
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64. Liver tests and outcomes in heart failure with reduced ejection fraction
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Carly Adamson, Lorna M. Cowan, Rudolf A. de Boer, Mirta Diez, Jarosław Drożdż, Andre Dukát, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Charlotta E.A. Ljungman, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Daniel Lindholm, Olof Bengtsson, David W. Boulton, Peter J. Greasley, Anna Maria Langkilde, Mikaela Sjöstrand, Scott D. Solomon, John J.V. McMurray, Pardeep S. Jhund, and Cardiovascular Centre (CVC)
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DAPAGLIFLOZIN ,EMPAGLIFLOZIN ,Stroke Volume ,Heart failure ,SGLT2 inhibitor ,Bilirubin ,Hepatic function ,Dapagliflozin ,Ventricular Function, Left ,Liver ,Alkaline phosphatase ,Humans ,FUNCTION ABNORMALITIES ,Cardiology and Cardiovascular Medicine - Abstract
Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium–glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. Methods and results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37–2.17], p < 0.001; and 1.52 [1.12–2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. Conclusion: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.
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- 2022
65. Lipid-Free Parenteral Nutrition Is Associated with an Increased Risk of Hepatic Dysfunction in Surgical Critically Ill Patients: A Retrospective Observational Study
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Shih-Chi Wu, Te-An Chen, I-Ju Tsai, Yu-Chun Wang, Han-Tsung Cheng, Chia-Wei Tzeng, Chia-Hao Hsu, and Chih-Hsin Muo
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hepatic function ,intravenous fat emulsion ,parenteral nutrition ,trauma/acute care surgery ,surgical critically ill ,Medicine - Abstract
To evaluate the effects of lipid-free parenteral nutrition (PN) and various intravenous fat emulsions (IVFEs) on hepatic function in surgical critically ill trauma/acute care surgery patients. We retrospectively reviewed trauma/acute care surgery patients without admission hepatic disorder that received PN. The PN groups include lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish-oil contained PN. We excluded patients with (1) age 6.0 mg/dL. The demographics, severity score, comorbidities, blood stream infection, and mortality were collected for analyses. The major outcome is hepatic function. We also performed analyses stratified by separated lipid doses (g/kg/day). A total of 249 patients were enrolled. There were no demographic differences among groups. The lipid-free PN group had a higher incidence of hepatic dysfunction and mortality. Compared to the lipid-free group, the other three IVFEs had significantly lower risks of hepatic dysfunction, while the olive oil-based group had a significantly lower risk of 30 and 90-day mortality. After being stratified by separating lipid doses, the soybean oils showed a decreasing trend of hepatic dysfunction and mortality with increased dosage. Fish oil >0.05 g/kg/day was associated with lower hepatic dysfunction incidences. Our findings suggest that, when compared to IVFEs, surgical critically ill patients with trauma/acute care surgery that received lipid-free PN are associated with an increased risk of hepatic dysfunction. In addition, the olive oil-based group had a significantly lower risk of mortality, while fish oil >0.05 g/kg/day was associated with lower incidences of hepatic dysfunction; however, further studies are warranted.
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- 2021
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66. Modeling Colorectal Cancer-Induced Liver Portal Vein Microthrombus on a Hepatic Lobule Chip.
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Du X, Zou R, Du K, Huang D, Miao C, Qiu B, Ding W, and Li C
- Abstract
Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.
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- 2023
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67. Alterations of Gut Microbiota in Cholestatic Infants and Their Correlation With Hepatic Function
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Cheng Guo, Yinhu Li, Peipei Wang, Yingchao Li, Chuangzhao Qiu, Muxia Li, Daxi Wang, Ruiqin Zhao, Dongfang Li, Ye Wang, Shuaicheng Li, Wenkui Dai, and Lin Zhang
- Subjects
infantile cholestasis ,16S rRNA ,hepatic function ,bacterial biomarkers ,co-abundance network ,Microbiology ,QR1-502 - Abstract
Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis. The diversity in the bacterial community was significantly lower in the IC group than that in the H group (P = 0.013). After determining the top 10 abundant genera of microbes in the IC and H groups, we found that 13 of them were differentially enriched, including Bifidobacterium, Bacteroides, Streptococcus, Enterococcus, and Staphylococcus. As compared with the H group, the IC group had a more complex GM co-occurrence network featured by three core nodes: Phyllobacterium, Ruminococcus, and Anaerostipes. In addition, the positive correlation between Faecalibacterium and Erysipelatoclostridium (r = 0.689, P = 0.000, FDR = 0.009) was not observed in the IC patients. Using the GM composition, the cholestatic patients can be distinguished from healthy infants with high accuracy [areas under receiver operating curve (AUC) > 0.97], wherein Rothia, Eggerthella, Phyllobacterium, and Blautia are identified as valuable biomarkers. Using KEGG annotation, we identified 32 functional categories with significant difference in enrichment of the GM of IC patients, including IC-enriched functional categories that were related to lipid metabolism, biodegradation and metabolism of xenobiotics, and various diseases. In contrast, the number of functions associated with amino acid metabolism, nucleotide metabolism, and vitamins metabolism was reduced in the IC patients. We also identified significant correlation between GM composition and indicators of hepatic function. Megasphaera positively correlated with total bilirubin (r = 0.455, P = 0.002) and direct bilirubin (r = 0.441, P = 0.003), whereas γ-glutamyl transpeptidase was positively associated with Parasutterella (r = 0.466, P = 0.002) and negatively related to Streptococcus (r = -0.450, P = 0.003). This study describes the GM characteristics in the cholestatic infants, illustrates the association between the GM components and the hepatic function, and provides a solid theoretical basis for GM intervention for the treatment of infantile cholestasis.
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- 2018
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68. Physicochemical and pharmacodynamic evaluation of pioglitazone binary systems with hydrophilic carriers.
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Ibrahim, Mohamed Abbas, Abou El Ela1, Amal El Sayeh F., Al-Rasheed, Nouf Mohamed, and Al-Amin, Maha Abdelrahman
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STREPTOZOTOCIN ,GLYCEMIC control ,X-ray powder diffraction ,BLOOD sugar ,DRUG solubility ,DIFFERENTIAL scanning calorimetry - Abstract
Pioglitazone (PGZ) is an antidiabetic agent belongs to thiazolidinediones. Binary systems of PGZ in the matrices of kollicoat IR (KL) and gelucire (GL) at different weight ratios were prepared by kneading and co-evaporation methods, respectively. The drug solid dispersions were characterized in terms of in vitro dissolution studies, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). The effects of PGZ-KL (1:4) solid dispersion on the body weight, blood glucose, renal and hepatic functions of the diabetic rats were evaluated. Enhanced drug dissolution was observed in the case of PGZ-KL binary systems depending on the drug to polymer weight ratio. A reduction of 39.7, 32.7 and 26.6% for diabetic control, PGZ untreated and PGZ-KL (1:4), respectively, was recorded after 2 weeks. PGZ-KL (1:4) solid dispersion also showed significantly lower glucose blood level (p < 0.05) compared to the diabetic control group along the period of experiment. The level of ALT was highly significantly decreased in the animal group treated with PGZ-KL solid dispersion (p < 0.001). However, treatment of diabetic rats with either PGZ-KL or PGZ untreated significantly reduced the level of creatinine compared to the diabetic control and the difference between them was non-significant. [ABSTRACT FROM AUTHOR]
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- 2019
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69. Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions—Multicenter analysis.
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Hiraoka, Atsushi, Kumada, Takashi, Atsukawa, Masanori, Hirooka, Masashi, Tsuji, Kunihiko, Ishikawa, Toru, Takaguchi, Koichi, Kariyama, Kazuya, Itobayashi, Ei, Tajiri, Kazuto, Shimada, Noritomo, Shibata, Hiroshi, Ochi, Hironori, Tada, Toshifumi, Toyoda, Hidenori, Nouso, Kazuhiro, Tsutsui, Akemi, Nagano, Takuya, Itokawa, Norio, and Hayama, Korenobu
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HEPATOCELLULAR carcinoma , *APPETITE loss , *BODY mass index - Abstract
Background/aim: We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of patients. Materials/methods: One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. Results: Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without (P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m2, P < 0.001), while patients with a hand‐foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without (P = 0.007). Conclusion: Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases. [ABSTRACT FROM AUTHOR]
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- 2019
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70. Engineering molecularly mobile polyrotaxane surfaces with heparin‐binding EGF‐like growth factors for improving hepatocyte functions.
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Arisaka, Yoshinori and Yui, Nobuhiko
- Abstract
Hepatocytes in vitro may be useful for treating various types of liver diseases, but these cells immediately lose their functions. Here, we designed sulfonated‐polyrotaxane (PRX) surfaces with immobilized heparin binding‐epidermal growth factor‐like growth factors (HB‐EGFs) for improving hepatic functions. Sulfonated‐PRX triblock copolymers, composed of sulfopropyl ether‐modified α‐cyclodextrins (α‐CDs) threaded onto a poly(ethylene glycol) (PEG) chain as a PRX segment and poly(benzyl methacrylate) at both terminals of the PEG as anchoring segments, were coated onto polystyrene surfaces by a drop cast method. The sulfonated‐PRX surfaces with a small number of threading α‐CDs induced cytoplasmic localization of yes‐associated proteins in HepG2 cells. Moreover, immobilization of HB‐EGFs onto the sulfonated‐PRX surfaces with a small number of threading α‐CDs promoted hepatic functions, including albumin secretion and gene expression. These results suggest that the combination of modulating the mobility of PRXs and immobilizing growth factors is effective for improving hepatic functions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1080–1085, 2019. [ABSTRACT FROM AUTHOR]
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- 2019
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71. Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users.
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Mello, Sueli Moreira, Soubhia, Paula Christiane, Silveira, Gabriela, Lanaro, Rafael, Corrêa-Neto, Nelson Francisco, Linardi, Alessandra, and Costa, José Luiz
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AYAHUASCA , *BEVERAGE consumption , *LIVER function tests , *DIMETHYLTRYPTAMINE , *ALKALOIDS , *AYAHUASCA ceremony - Abstract
Ayahuasca is a beverage obtained from decoctions of the liana Banisteriopsis caapi plus the shrub Psychotria viridis. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The ritualistic use of ayahuasca is becoming a global phenomenon. Most members of ayahuasca churches consume this beverage throughout their life, and many reports have discussed the therapeutic potential of this beverage. Ayahuasca is consumed orally, and the liver, as the major organ for the metabolism and detoxification of xenobiotics absorbed from the alimentary tract, may be susceptible to injury by compounds present in the ayahuasca decoction. In this study, we evaluated biochemical parameters related to hepatic damage in the serum of 22 volunteers who consumed ayahuasca twice a month or more for at least one year. There was no significant alteration in the following parameters: alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and gamma glutamyl transferase. These findings indicate that chronic ayahuasca consumption in a religious context apparently does not affect hepatic function. [ABSTRACT FROM AUTHOR]
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- 2019
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72. Changes of body immunity and inflammatory response in HIV/HCV co-infected patients.
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Dong, Yuhong, Zhi, Xiaoli, and Lei, Guo
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- *
ALANINE aminotransferase , *INVERSE relationships (Mathematics) , *NECROSIS - Abstract
Changes of body immunity and inflammatory response in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients were investigated. Eighty HIV/HCV infected patients admitted to Qingdao No. 6 People's Hospital from August 2015 to December 2017 were selected and divided into two groups according to whether they were complicated with HCV infection or not (n=40 per group). The changes of the related humoral immune indexes, the related cellular immune indexes, the related indexes of hepatic function, the related indexes of inflammatory response in the two groups were compared, and the correlations of high-sensitivity C-reactive protein (hs-CRP) level with alanine aminotransferase (ALT) level, immunoglobulin G (IgG) level and cluster of differentiation 4+ (CD4+) level in the observation group were analyzed. The levels of related humoral immune indexes [immunoglobulin G (IgG), IgA and IgM levels], the related cellular immune indexes (CD4+ and CD8+) in the observation group were lower than those in the control group (P<0.05), and the CD4+/CD8+ ratio in the observation group was lower than that in the control group (P<0.05). The levels of indexes of hepatic function [ALT, aspartate aminotransferase (AST) and total bilirubin] in the observation group were significantly higher than those in the control group (P<0.05). The levels of hs-CRP, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in the observation group were significantly higher than those in the control group (P<0.05). There were positive correlations of hs-CRP level with ALT level and IgG level in the observation group (P<0.05). There was a negative correlation between hs-CRP level and CD4+ level in the observation group (P<0.05). The humoral and cellular immune functions of the HIV/HCV co-infected patients are significantly limited, their hepatic function is significantly impaired and the levels of inflammatory cytokines are markedly increased. The level of hs-CRP is positively correlated with hepatic function and humoral immune function and negatively correlated with cellular immune function. [ABSTRACT FROM AUTHOR]
- Published
- 2019
73. Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.
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Ni, Jia-Yan, Fang, Zhu-Ting, An, Chao, Sun, Hong-Liang, Huang, Zhi-Mei, Zhang, Tian-Qi, Jiang, Xiong-Ying, Chen, Yao-Ting, Xu, Lin-Feng, and Huang, Jin-Hua
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- 2019
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74. Effect of baseline renal and hepatic function on the incidence of adverse drug events: the Japan Adverse Drug Events study.
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Takahashi, Yuri, Sakuma, Mio, Murayama, Hiroki, and Morimoto, Takeshi
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Background: The impact of renal and hepatic dysfunction on the morbidity and mortality of inpatients with adverse drug events (ADEs) is uncertain in daily clinical practice. The objective of this study was to investigate the effect of renal and hepatic function on ADEs and inpatients' morbidity and mortality. Methods: The Japan Adverse Drug Events (JADE) study was a prospective cohort study carried out at three tertiary-care teaching hospitals in Japan. Participants were consecutive inpatients (n=3459) aged 15 years or older. We evaluated the effect of renal and hepatic function on the occurrence of ADEs, and assessed how they affected length of hospital stay (LOS) and in-hospital mortality. We used the estimated glomerular filtration rate to quantify renal function and categorized patients into three groups (normal, ≥60 mL/min/1.73 mm; moderate, ≥30 and <60 mL/min/1.73 mm; severe, <30 mL/min/1.73 mm). We defined patients as having hepatic dysfunction when at least one data point (total bilirubin, aspartate aminotransferase, alanine aminotransferase, or gamma glutamyltransferase) was beyond a cutoff value. Results: We analyzed the laboratory data of 2508 patients. There was a significant difference in the occurrence of ADEs among the three GFR categories (normal, 20%; moderate, 26%; severe, 22%; p=0.02). More ADEs occurred in patients with hepatic dysfunction (25% vs. 20%, p=0.01). LOS was significantly longer in those with ADEs stratified either by renal or by hepatic dysfunction (p<0.0001). ADEs were independently associated with in-hospital mortality, adjusting for renal and hepatic function (p<0.0001). Conclusions: Inpatients' organ dysfunction increased ADEs, and ADEs were associated with both LOS and in-hospital mortality independently, irrespective of renal and hepatic function. [ABSTRACT FROM AUTHOR]
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- 2018
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75. Alterations of Gut Microbiota in Cholestatic Infants and Their Correlation With Hepatic Function.
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Guo, Cheng, Li, Yinhu, Wang, Peipei, Li, Yingchao, Qiu, Chuangzhao, Li, Muxia, Wang, Daxi, Zhao, Ruiqin, Li, Dongfang, Wang, Ye, Li, Shuaicheng, Dai, Wenkui, and Zhang, Lin
- Abstract
Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis. The diversity in the bacterial community was significantly lower in the IC group than that in the H group (P = 0.013). After determining the top 10 abundant genera of microbes in the IC and H groups, we found that 13 of them were differentially enriched, including Bifidobacterium, Bacteroides, Streptococcus, Enterococcus , and Staphylococcus. As compared with the H group, the IC group had a more complex GM co-occurrence network featured by three core nodes: Phyllobacterium, Ruminococcus , and Anaerostipes. In addition, the positive correlation between Faecalibacterium and Erysipelatoclostridium (r = 0.689, P = 0.000, FDR = 0.009) was not observed in the IC patients. Using the GM composition, the cholestatic patients can be distinguished from healthy infants with high accuracy [areas under receiver operating curve (AUC) > 0.97], wherein Rothia, Eggerthella, Phyllobacterium , and Blautia are identified as valuable biomarkers. Using KEGG annotation, we identified 32 functional categories with significant difference in enrichment of the GM of IC patients, including IC-enriched functional categories that were related to lipid metabolism, biodegradation and metabolism of xenobiotics, and various diseases. In contrast, the number of functions associated with amino acid metabolism, nucleotide metabolism, and vitamins metabolism was reduced in the IC patients. We also identified significant correlation between GM composition and indicators of hepatic function. Megasphaera positively correlated with total bilirubin (r = 0.455, P = 0.002) and direct bilirubin (r = 0.441, P = 0.003), whereas γ-glutamyl transpeptidase was positively associated with Parasutterella (r = 0.466, P = 0.002) and negatively related to Streptococcus (r = -0.450, P = 0.003). This study describes the GM characteristics in the cholestatic infants, illustrates the association between the GM components and the hepatic function, and provides a solid theoretical basis for GM intervention for the treatment of infantile cholestasis. [ABSTRACT FROM AUTHOR]
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- 2018
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76. Effects of Cassava Juice (Manihot esculenta Crantz) on Renal and Hepatic Function and Motor Impairments in Male Rats
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Eduardo Rivadeneyra-Domínguez, José Eduardo Pérez-Pérez, Alma Vázquez-Luna, Rafael Díaz-Sobac, and Juan Francisco Rodríguez-Landa
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cassava juice ,renal function ,hepatic function ,motor incoordination ,neurotoxic ,hepatoxicity ,Medicine - Abstract
Cassava (Manihot esculenta Crantz) is a plant that contains neurotoxins such as linamarin and lotaustraline. Its long-term consumption is associated with neuronal damage and contributes to the development of motor impairment in humans and rats. We investigated the effects of the consumption of cassava juice on renal and hepatic function and motor impairments in male rats. The rats received the vehicle, non-toxic and toxic doses of cassava juice, or linamarin as a pharmacological control, over 35 consecutive days. The effects were evaluated in an open field test, rotarod, and swim test. The toxic cassava dose and linamarin resulted in motor impairments in the rotarod and swim test from day 7 of treatment. The toxic cassava dose and linamarin increased the parameters that indicate renal and hepatic damage, with the exception of total protein and albumin levels. Behavioral variables that show motor incoordination (i.e., latency to fall in the rotarod) were negatively correlated with biochemical parameters of renal and kidney damage, whereas spin behavior was positively correlated. Our data indicate that chronic oral consumption of cassava juice caused renal and hepatic damage that was correlated with motor coordination impairment in rats, similarly to their principal neurotoxic compound, linamarin.
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- 2020
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77. Lonicera caerulea berry extract attenuates lipopolysaccharide induced inflammation in BRL-3A cells: Oxidative stress, energy metabolism, hepatic function
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Yuehua Wang, Bin Li, Yan Ma, Xiyao Wang, Xiuyan Zhang, Qi Zhang, and Xianjun Meng
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Lonicera caerulea berry ,Oxidative stress ,Energy metabolism ,Hepatic function ,Pro-inflammatory factors ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Lonicera caerulea fruit is a polyphenol-rich berry. The protective effects of L. caerulea berry extract before and after in vitro digestion on hepatitis were investigated using lipopolysaccharide-induced BRL-3A cell model in this study. The results demonstrated that both undigested extract and digested extract pre-treatment observably inhibited oxidative stress, as evidenced by the reduction in the production of reactive oxygen species, malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyls; significantly maintained energy metabolism and cellular structure, which were verified by the suppression of decline in the activities of ATP synthetase, cytochrome c oxidase and succinate dehydrogenase, and changes in histological structure; markedly modulated hepatic function by attenuating the enhancement in aspartate aminotransferase and alanine aminotransferase activities and the decrease in acetylcholine esterase activity; and remarkably attenuated the production of pro-inflammatory factors such as interleukin-1beta and interleukin-6. Taken together, the application of L. caerulea berry extract protects liver against the damage caused by lipopolysaccharide.
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- 2016
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78. Long‐term hepatic function of patients with compensated cirrhosis following successful direct‐acting antiviral treatment for hepatitis C virus infection
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Nobuyuki Yamashita, Aritsune Ooho, Shinji Shimoda, Hideyuki Nomura, Chie Morita, Jun Hayashi, Yasunori Ichiki, Eiji Kajiwara, Eiichi Ogawa, Koichi Azuma, Toshimasa Koyanagi, Takeaki Satoh, Makoto Nakamuta, Kimihiko Yanagita, Naoki Yamashita, Masami Kuniyoshi, Kazuhiro Takahashi, Akira Kawano, Kazufumi Dohmen, Norihiro Furusyo, Masaki Kato, and Rie Sugimoto
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Hepatitis C virus ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Cohort Studies ,Hepatic function ,Internal medicine ,medicine ,Humans ,Decompensation ,Stage (cooking) ,Aged ,Hepatology ,business.industry ,medicine.disease ,Hepatitis C ,Confidence interval ,Treatment Outcome ,Cohort ,Female ,business ,Cohort study - Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long-term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. METHODS This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon-free DAA treatment before September 2016. The impact of treatment on long-term hepatic function was followed for at least 4 years after the end of treatment, and the progression to decompensation was evaluated. RESULTS The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin-bilirubin (ALBI) grade 2b. During a short-term follow-up 1 year after the end of treatment, FIB-4 index and ALBI score significantly improved. The achievement rates of FIB-4
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- 2021
79. Molecular Mechanism of Changes in Gene Expression of Cytosolic Cu/Zn SOD, Lipid Peroxidation and Hepatic Function Impairments during Experimental Fluorosis
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A. Shashi and Sukanya Thakur
- Subjects
Hepatic function ,Lipid peroxidation ,Cytosol ,chemistry.chemical_compound ,Biochemistry ,Chemistry ,Gene expression ,Molecular mechanism - Abstract
Background: Long term intake of high amount of fluoride leads to fluorosis causing metabolic, functional and structural damages affecting many tissues and organs including dental and skeletal manifestations. The liver is the most susceptible organ to fluoride toxicity because of its active and major role in digestion and detoxification. Aim: The present study aims to elucidate the effects of sodium fluoride on hepatic function biomarkers, lipid peroxidation and gene expression of Cu/Zn SOD in albino rats. Materials and Methods: Wistar albino rats were randomly assigned to three groups. The control rats were given 1 ml deionized water orally for 40 days. Groups II and III were administered 300 and 600 mg NaF/kg b.w. /day for the same period. Animals were sacrificed under anaesthesia, liver tissue was excised and used for biochemical and molecular analysis. The level of fluoride and lipid peroxidation (MDA) as well as reduced glutathione (GSH) content was determined. The activities of cytosolic copper/zinc superoxide dismutase (Cu/Zn SOD), aminotransferases (ALT and AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in the hepatic tissue were determined. The analysis of gene expression of Cu/Zn SOD in the liver was determined using Real-time PCR. Results: The results revealed significantly (P
- Published
- 2021
80. The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart
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C.J. Majoor, Eelko Hak, Bart L. Rottier, J.E. Möhlmann, Onno W. Akkerman, H Vd Vaart, Daan J Touw, Johannes G. M. Burgerhof, A M Akkerman-Nijland, Gerard H. Koppelman, Microbes in Health and Disease (MHD), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), PharmacoTherapy, -Epidemiology and -Economics, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), and Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,drug safety ,Renal function ,Azithromycin ,Kidney Function Tests ,Gastroenterology ,Cystic fibrosis ,THERAPY ,Hepatic function ,Cohort Studies ,Electrocardiography ,Young Adult ,Maintenance therapy ,Liver Function Tests ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,cardiovascular diseases ,Netherlands ,Retrospective Studies ,azithromycin ,Adult patients ,business.industry ,General Medicine ,bacterial infections and mycoses ,medicine.disease ,PROLONGATION ,Anti-Bacterial Agents ,Long QT Syndrome ,MAINTENANCE ,cardiovascular system ,Female ,Long term safety ,business ,Biomarkers ,medicine.drug - Abstract
Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation. Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively. Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed. Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication.
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- 2021
81. Changes in the expression of α-tocopherol-related genes in liver and mammary gland biopsy specimens of peripartum dairy cows.
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Haga, S., Miyaji, M., Nakano, M., Ishizaki, H., Matsuyama, H., Katoh, K., and Roh, S.G.
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VITAMIN E , *DAIRY cattle , *MILK yield , *CATTLE breeding , *MAMMARY glands - Abstract
Blood α-tocopherol (α-Toc) concentrations decline gradually throughout the prepartum period, reaching the nadir after calving in dairy cows. The 6 α-Toc–related molecules [α-Toc transfer protein (TTPA); afamin; scavenger receptor class B, Type I; ATP-binding cassette transporter A1; tocopherol-associated protein (SEC14L2); and cytochrome P450 family 4, subfamily F, polypeptide 2 (CYP4F2)] are expressed in liver and other peripheral tissues. These molecules could regulate α-Toc transport, blood concentrations, and metabolism of α-Toc. Therefore, the aim of this study was to evaluate the changes in the expression of α-Toc–related genes in liver and mammary gland tissues of dairy cows around calving, which have remained elusive until now. In experiment (Exp.) 1, 28 multiparous Holstein cows were used (from −5 to 6 wk relative to parturition) to monitor the changes in dietary α-Toc intake, blood concentrations of α-Toc, and lipoproteins; in Exp. 2, 7 peripartum Holstein cows were used (from −4 to 4 wk relative to parturition) for liver tissue biopsy; and in Exp. 3, 10 peripartum Holstein cows were used (from −8 to 6 wk relative to parturition) to carry out the mammary gland tissue biopsy and milk sampling. In Exp. 1, the serum α-Toc concentrations declined gradually with decreasing amount of α-Toc intake and plasma high-density lipoprotein concentrations toward calving time. However, in the early lactation period after calving, serum α-Toc concentrations remained at a lower concentration despite the recovery of α-Toc intake and plasma high-density lipoprotein concentrations. In Exp. 2, just after calving, the TTPA, SEC14L2, afamin, and albumin mRNA expression levels in the liver were temporarily downregulated, and the hepatic mRNA levels of endoplasmic reticulum stressinduced unfolded protein response markers and acutephase response marker increased at calving. In Exp. 3, the concentrations of α-Toc in colostrum were greater than those in precolostrum (samples were collected at wk −1 relative to parturition) and mature milk. The expression of TTPA, SEC14L2, and CYP4F2 mRNA in bovine mammary gland tissue was detected. However, TTPA and SEC14L2 mRNA expressions showed the opposite trends: the expression levels of TTPA mRNA peaked whereas SEC14L2 mRNA reached a nadir at calving. These results indicate that the expression of α-Toc–related genes involved in specific α-Toc transfer and metabolism in the liver and mammary gland are altered during calving. Moreover, these changes might be associated with the maintenance of lower serum α-Toc concentrations after calving. [ABSTRACT FROM AUTHOR]
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- 2018
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82. Long-term safety of long-acting octreotide in patients with diabetic retinopathy: results of pooled data from 2 randomized, double-blind, placebo-controlled phase 3 studies.
- Author
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Pivonello, Rosario, Muscogiuri, Giovanna, Holder, Geoffrey, Paul, Michaela, Sarp, Severine, Lesogor, Anastasia, Jordaan, Pierre, Eisinger, Johannes, and Colao, Annamaria
- Abstract
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]
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- 2018
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83. RISKS OF LEPTOSPIROSIS LINKED TO LIVING AND WORKING ENVIRONMENTS.
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Manciuc, Doina Carmen, Iordan, Ioana Florina, Adavidoaiei, Anca Maria, and Largu, Maria Alexandra
- Abstract
Although considered a rare disease, endemic to low-income regions and unsanitary environments, leptospirosis is still encountered in some parts of Romania, in both rural and urban environments. Its specific pathways of transmission caused it to be a threat to people working with animals, pest control, farmers or those whose jobs place them in the presence of waters, sewers or in flooded areas. This paper investigates the occurrence and effects of leptospirosis by analyzing 17 cases of infection occurring between 2013 and 2015 in Iasi, Romania. The retrospective study revealed that 82% of leptospirosis cases were determined by serovars of Leptospira spp. known to be transmitted in a professional context or coming from household animals or rodents. These zooantroponosis lead to health risks and renal, hepatic and meningeal damage, which determined a high number of admission days as well as higher costs for care. Prevention of the disease includes non-exposure to risk factors, assuming protecting actions, immunization, chemoprophylaxis in several combinations, as well as education for proper environmental and body hygiene. [ABSTRACT FROM AUTHOR]
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- 2018
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84. Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials.
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Seko, Yuya, Sumida, Yoshio, Sasaki, Kazuyo, Itoh, Yoshito, Iijima, Hiroaki, Hashimoto, Toshio, Ishii, Shinichi, and Inagaki, Nobuya
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CANAGLIFLOZIN , *HYPOGLYCEMIC agents , *SODIUM metabolism inhibitors , *TYPE 2 diabetes , *DYSLIPIDEMIA - Abstract
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]- Published
- 2018
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85. Pharmacokinetics of the antimicrobial drug Sulfanilamide is altered in a preclinical model of vascular calcification.
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Brandoni, Anabel and Torres, Adriana Mónica
- Abstract
In vascular smooth muscle, calcium overload is linked to advancing age. The pharmacokinetics of Sulfanilamide (SA), a compound with antibacterial properties, was evaluated in a preclinical model of vascular calcification. SA was used since it is useful to study possible modifications in the renal and hepatic management of drugs. Vascular calcification was induced by administration of a single high dose of vitamin D3 to rats (treated group) 10 days before the experiments. A parallel control group was processed. The decrease of renal blood flow due to calcification of the renal arteries explains, at least in part, the decrease in the renal clearance of SA observed in treated rats. The liver metabolic function increased in treated rats as demonstrated by increases in plasma appearance rate of acetylated-Sulfanilamide (ASA), hepatic ASA content and hepatic N-acetyltransferase activity. The decrease in renal excretion of SA was not completely compensated by the hepatic metabolism increase, since the elimination rate of SA from the central compartment (K1-0) decreased in the treated group. In summary, in this experimental model with sustained arterial calcinosis induced by a single high dose of vitamin D3 10 days before the experiments, the pharmacokinetics of an aminobenzenesulfonamide is modified, at least in part, by the increase in the activity of hepatic N-acetyltransferase and the decrease in renal blood flow. This study emphasizes the importance of considering the presence of vascular calcification when a drug dose scheme is performed, in order to optimize pharmacotherapeutic results. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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86. How clinicians may use tests of hepatic function now and in the future
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Paul Y. Kwo and T. Tara Ghaziani
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Liver surgery ,Carcinoma, Hepatocellular ,business.industry ,Liver Diseases ,Liver Neoplasms ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,MEDLINE ,General Medicine ,Bioinformatics ,medicine.disease ,End Stage Liver Disease ,Translational Research, Biomedical ,Hepatic function ,Postoperative Complications ,Text mining ,Liver ,Liver Function Tests ,Physiology (medical) ,Carcinoma ,Humans ,Medicine ,business - Published
- 2021
87. Evaluation of Body Weight, Serum Lipid Profile, Glucose Homeostasis, Oxidative Stress and Hepatic Function in Healthy Mice Fed With Zinc Sulphate Supplementation
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Sayema Arefin, Abdur Rahman Ripon, Dipty Rani Bhowmik, Mohammad Tohidul Amin, Atiqur Rahman, and Mohammad Salim Hossain
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medicine.medical_specialty ,medicine.diagnostic_test ,Chemistry ,Pharmaceutical Science ,chemistry.chemical_element ,Zinc ,medicine.disease_cause ,Body weight ,Hepatic function ,Endocrinology ,Internal medicine ,medicine ,Glucose homeostasis ,Pharmacology (medical) ,Lipid profile ,Oxidative stress - Abstract
The present research study was designed to evaluate the effect of zinc supplementation on body weight, serum triglyceride, cholesterol, glucose homeostasis, oxidative stress, and hepatic function in mice. Mice were treated with zinc sulphate at an equivalent weight of 6.5 mg/kg-body weight elemental zinc for four weeks. Bodyweight, serum glucose, triglyceride, cholesterol, serum MDA, nitric oxide, vitamin C, and hepatic enzymes level were determined at the end of the study period. Data from this study showed that supplementation with zinc in mice maintained a balanced blood glucose homeostasis throughout the experimental period. Moreover, treatment with zinc showed a significant (p
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- 2021
88. Body Mass Index and HbA1c Are Associated with Renal and Hepatic Function
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Imam Nafi Yana Saputra, Falah Faniyah, and Yoga Mulia Pratama
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medicine.medical_specialty ,Creatinine ,Kidney ,Waist ,business.industry ,medicine.disease ,Circumference ,Gastroenterology ,Hepatic function ,chemistry.chemical_compound ,Blood pressure ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Diabetes mellitus ,General Earth and Planetary Sciences ,Medicine ,business ,Body mass index ,General Environmental Science - Abstract
Hypertension and diabetes may have implications for damage to other organs such as the kidneys and liver which are evaluated by serum creatinine and ALT, respectively. This study aims to delineate the association between body mass index and hbA1c with renal and hepatic function, respectively. This is a cross-sectional study involving 32 subjects. The research subjects consisted of diabetics and hypertension who were registered in the Muhammadiyah Primary Health Care, Kebanaran, Purwokerto. It was found that in diabetics, there were significant results between serum creatinine and HbA1c values (p
- Published
- 2021
89. Pharmacokinetics and safety of lefamulin after single intravenous dose administration in subjects with impaired‐hepatic function
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Thomas Marbury, Steven P Gelone, Cathie Leister, Wolfgang W Wicha, James Ermer, James A. Dowell, and Jared L. Crandon
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0301 basic medicine ,medicine.medical_specialty ,Metabolite ,030106 microbiology ,Cmax ,030204 cardiovascular system & hematology ,Gastroenterology ,Hepatic function ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Polycyclic Compounds ,Pharmacology (medical) ,Volume of distribution ,business.industry ,Liver Diseases ,Hepatic impairment ,Bacterial pneumonia ,medicine.disease ,chemistry ,Thioglycolates ,Administration, Intravenous ,Diterpenes ,Geometric mean ,business - Abstract
Study objective Lefamulin is a novel pleuromutilin recently approved by the FDA for the treatment of community-acquired bacterial pneumonia. Given that lefamulin is primarily metabolized by CYP450 Phase-1 reactions, this study evaluated the pharmacokinetics of IV lefamulin in subjects with various degrees of hepatic impairment as compared with matched healthy subjects. Design Open-label, Phase 1 clinical pharmacokinetic study SETTING: Research Study Center PATIENTS: Twenty-seven subjects; comprised of 11 individuals with normal hepatic function and eight each with moderate or severe hepatic impairment were included, as classified by Child-Pugh scores. Measurements and main result Subjects were administered a single dose of IV lefamulin 150 mg over 1 hour. Plasma was collected for 48 hours and analyzed for lefamulin and its major metabolite, BC-8041, concentrations in addition to assessing lefamulin plasma protein binding. Pharmacokinetics were evaluated by noncompartmental analysis. Pharmacokinetic parameters were compared using least square geometric mean ratios. Lefamulin was well tolerated in all hepatic function groups. Statistical analyses revealed reductions in Cmax and increases in renal clearance for Moderate and Severe groups, as well as, increased volume of distribution for the Severe group. Lefamulin plasma AUC mean (SD) was similar across groups at 7615 (1554), 8233 (2286), and 8938 (1640) h·ng/mL for Normal, Moderate, and Severe groups, respectively, despite decreased clearance observed primarily during terminal elimination phases. Decreased plasma protein binding was seen in hepatically-impaired versus normal subjects. Conclusion Lefamulin was generally well tolerated. Differences in lefamulin and BC-8041 pharmacokinetics were small, relative to the overall variability, and any changes appear to be compensated by increases in renal clearance and decreased protein binding.
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- 2021
90. Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification
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Issei Saeki, Takuya Iwamoto, Taro Takami, Tatsuro Nishimura, Ryo Sasaki, Takashi Matsuda, Tsuyoshi Ishikawa, Isao Hidaka, and Isao Sakaida
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Child-Pugh score ,hepatic function ,030204 cardiovascular system & hematology ,Gastroenterology ,Hypersplenism ,Group B ,Hepatic function ,03 medical and health sciences ,Hepatic Artery ,0302 clinical medicine ,Partial splenic embolization ,Internal medicine ,medicine.artery ,polycyclic compounds ,Internal Medicine ,medicine ,Humans ,hepatic arterial buffer response ,Arterial hemodynamics ,Common hepatic artery ,business.industry ,partial splenic embolization ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Embolization, Therapeutic ,digestive system diseases ,CHILD-PUGH CLASSIFICATION ,Splenic infarction ,Original Article ,030211 gastroenterology & hepatology ,business - Abstract
Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray's Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.
- Published
- 2021
91. Biochemical and Hematological Indexes of Liver Dysfunction in Horses.
- Author
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Satué, Katiuska, Fazio, Esterina, Medica, Pietro, Miguel, Laura, and Gardón, Juan Carlos
- Abstract
• Biochemical and hematological indexes of liver dysfunction in the horse are considered in this review. • Biochemical and/or hematological changes of various magnitude are indexes of liver dysfunction depending on causes. • Some hematochemical data can be used as prognostic indicators of loss liver function in the horse. • Periodic hematochemical analysis can help monitor the progression of the liver function loss. In the present review, the authors, based on the multiple functions performed by the liver, analyze the multiple biochemical and hematological changes as an expression of altered liver function in the horse. The liver performs important metabolic functions related to the synthesis, degradation, and excretion of various substances. Modification of these functions can be evaluated and diagnosed by determining serum concentrations of several serum analytes, including enzymes and other endogenous substances. Hepatocellular enzymes, such as sorbitol dehydrogenase-SDH and glutamate dehydrogenase-GLDH, are released following hepatocellular necrosis. Hepatobiliary enzymes, such as γ-glutamyl transferase-GGT, increase in response to necrosis, cholestasis, and other alterations in bile conducts. Serum concentrations of mainly endogenous and exogenous substances that the liver should synthesize or eliminate, such as proteins (albumin and globulins), bile acids, urea, glucose, total and direct bilirubin, and coagulation factors, and fibrinogen should be included in the liver function test profile. The interpretation of laboratory tests of liver function will allow the diagnosis of functional loss of the organ. Some of the analytes considered provide information on the prognosis of liver disease. This review will provide an accurate and objective interpretation of the common biochemical and hematological tests in use in the diagnosis of equine hepatic disease patients, aiding still further the veterinary activity on the applied equine clinical cases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
92. Liver tests and outcomes in heart failure with reduced ejection fraction:findings from DAPA-HF
- Author
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Adamson, Carly, Cowan, Lorna M., de Boer, Rudolf A., Diez, Mirta, Drożdż, Jarosław, Dukát, Andre, Inzucchi, Silvio E., Køber, Lars, Kosiborod, Mikhail N., Ljungman, Charlotta E.A., Martinez, Felipe A., Ponikowski, Piotr, Sabatine, Marc S., Lindholm, Daniel, Bengtsson, Olof, Boulton, David W., Greasley, Peter J., Langkilde, Anna Maria, Sjöstrand, Mikaela, Solomon, Scott D., McMurray, John J.V., Jhund, Pardeep S., Adamson, Carly, Cowan, Lorna M., de Boer, Rudolf A., Diez, Mirta, Drożdż, Jarosław, Dukát, Andre, Inzucchi, Silvio E., Køber, Lars, Kosiborod, Mikhail N., Ljungman, Charlotta E.A., Martinez, Felipe A., Ponikowski, Piotr, Sabatine, Marc S., Lindholm, Daniel, Bengtsson, Olof, Boulton, David W., Greasley, Peter J., Langkilde, Anna Maria, Sjöstrand, Mikaela, Solomon, Scott D., McMurray, John J.V., and Jhund, Pardeep S.
- Abstract
Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium–glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. Methods and results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37–2.17], p < 0.001; and 1.52 [1.12–2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. Conclusion: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.
- Published
- 2022
93. Severe hypertransaminasemia during mild SARS‐CoV‐2 infection: A pediatric case report and literature review
- Author
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Bianca Lattanzi, Gaia Martelli, Alessandro Volpini, Salvatore Cazzato, and Alessandra Palpacelli
- Subjects
Liver injury ,Pediatrics ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Case Report ,Case presentation ,medicine.disease ,SARS‐CoV‐2 ,RJ1-570 ,Acute illness ,Hepatic function ,Pathogenesis ,Transaminasemia ,Liver ,COVID‐19 ,Pediatrics, Perinatology and Child Health ,medicine ,business ,Children - Abstract
Introduction Liver injury during SARS‐CoV‐2 infection has a multifactorial pathogenesis and it is frequent in pediatric cases. Case presentation We report a case with severe hypertransaminasemia associated with mild SARS‐CoV‐2 infection. Conclusion This highlights the potential need of hepatic function evaluation during acute illness and follow‐up even in non‐critically ill children with COVID‐19., Liver injury during SARS‐CoV‐2 infection has a multifactorial pathogenesis. We describe a pediatric case with severe increase of serum aminotransferases in the course of mild SARS‐Cov‐2 infection.
- Published
- 2021
94. A PK/PD model of saxagliptin: to simulate its pharmacokinetics and pharmacodynamics in healthy adults and patients with impaired hepatic function
- Author
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Feng Miao, Lu Shi, Wenyan Sun, Yang Liu, and Guopeng Wang
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Hepatic function ,chemistry.chemical_compound ,Pharmacokinetics ,chemistry ,business.industry ,Pharmaceutical Science ,Medicine ,Pharmacology ,Saxagliptin ,business ,PK/PD models - Published
- 2021
95. Assembly and Disassembly of the Micropatterned Collagen Sheets Containing Cells for Location-Based Cellular Function Analysis
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Hee-Hoon Kim, Won-Il Jeong, Je-Kyun Park, Jaejung Son, and Jun Hee Lee
- Subjects
Chemistry ,Oxygen gradient ,010401 analytical chemistry ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Hepatic function ,Function analysis ,Liver tissue ,Hepatic stellate cell ,Biophysics ,Electrical and Electronic Engineering ,0210 nano-technology ,Drug toxicity ,Biotechnology ,Micropatterning - Abstract
The liver has complex microenvironments, where parenchymal hepatocytes and non-parenchymal cells coexist. Hepatocytes exhibit different metabolic functions depending on their location by the oxygen gradient and the transcriptional changes of genes, which is called liver zonation. Three-dimensional (3D) liver tissue engineering has reproduced the complex microenvironments, but there is a limitation in analyzing them by location. In this study, a novel 3D tissue-level hepatic cell culture platform is developed via stacking the manipulable collagen sheets to spatially analyze the reconstructed metabolic zonation. The controlled assembly of the sheets containing hepatocytes and endothelial cells, respectively, creates a 3D co-culture environment that improves hepatic function. In addition, the sheet micropatterning can be used to control the accessibility of oxygen and nutrients in the stacked sheets. The disassembly of the stacked sheets enables a layer-by-layer analysis and allows us to confirm the metabolic zonation qualitatively. A demonstration of acetaminophen-induced liver injury using the stacked sheets shows the improved drug sensitivity by co-culture and chemical induction and presents the quantitative results of the different cellular responses to the drug by layers according to metabolic zonation. Therefore, this platform is expected to be used for an in-depth analysis of drug toxicity in complex tissues via spatial analysis.
- Published
- 2021
96. Dynamic and Continuous Monitoring of Renal and Hepatic Functions with Exogenous Markers
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Achilefu, Samuel, Dorshow, Richard B., de Meijere, Armin, editor, Kessler, Horst, editor, Ley, Steven V., editor, Thiem, Joachim, editor, Vögtle, Fritz, editor, Houk, K. N., editor, Lehn, Jean-Marie, editor, Schreiber, Stuart L., editor, Trost, Barry M., editor, Yamamoto, Hisashi, editor, and Krause, Werner, editor
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- 2002
- Full Text
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97. Pharmacokinetics of Gepotidacin in Subjects With Normal Hepatic Function and Hepatic Impairment
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Richard A. Preston, Mohammad Hossain, Yu Tao, Aline Barth, Etienne Dumont, Thomas Marbury, and Courtney Tiffany
- Subjects
safety ,Adult ,Male ,Gepotidacin ,medicine.medical_specialty ,Saliva ,Adolescent ,gepotidacin ,Pharmaceutical Science ,Original Manuscript ,Urine ,030226 pharmacology & pharmacy ,Gastroenterology ,Severity of Illness Index ,Hepatic function ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,Dosing ,Aged ,Aged, 80 and over ,business.industry ,Acenaphthenes ,Hepatic impairment ,Liver Diseases ,liver failure ,Articles ,Middle Aged ,Anti-Bacterial Agents ,Tolerability ,030220 oncology & carcinogenesis ,Area Under Curve ,Female ,business ,pharmacokinetics ,Heterocyclic Compounds, 3-Ring ,Half-Life - Abstract
Gepotidacin is a novel triazaacenaphthylene bacterial topoisomerase inhibitor. This phase 1 nonrandomized, open‐label, multicenter, 2‐part study evaluated the pharmacokinetics, safety, and tolerability of oral gepotidacin 1500 mg in 3 different hepatic settings (normal, moderate impairment, and severe impairment). Gepotidacin was safe and generally tolerated in all subjects. Compared to subjects with normal hepatic function, gepotidacin plasma area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) and maximum concentration significantly increased by 1.7‐ and 1.9‐fold, respectively, in severe hepatic impairment; increases in moderate impairment were not statistically significant. No significant effect was observed for gepotidacin plasma elimination half‐life (geometric mean range, 8.2–9.1 hours) across hepatic groups. Renal clearance increased in moderate (16%) and severe (52%) hepatic impairment vs normal. The mean fraction of gepotidacin dose excreted in urine increased with increasing hepatic impairment (normal, 7.5%; moderate, 11.2%; and severe, 19.9%). Urine gepotidacin concentrations remained high for 12 hours in all hepatic groups after dosing. Saliva gepotidacin concentrations displayed a linear relationship with plasma concentrations (R2 = 0.76). The ratio of saliva AUC to unbound plasma AUC and elimination half‐life were not affected by hepatic impairment. These data indicate that gepotidacin dose adjustment is not required in mild to moderate hepatic impairment; severe hepatic impairment may require increases in dosing interval or dose reduction.
- Published
- 2021
98. Effects of modified ultrafiltration on postoperative hepatic and renal function of pediatric patients with congenital cyanotic/non-cyanotic heart defect who underwent open heart surgery: Retrospective study
- Author
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Zeynep Eyileten, Deniz Bozdogan, Adnan Uysalel, and Mustafa Şirlak
- Subjects
medicine.medical_specialty ,business.industry ,Cardiopulmonary bypass time ,Hasta ,Heart defect ,modified ultrafiltration,cardiopulmonary bypass,pediatric open heart surgery ,Cardiac surgery ,Surgery ,law.invention ,Hepatic function ,Health Care Sciences and Services ,law ,modifiye ultrafiltrasyon,kardiyopulmoner baypas,pediatrik açık kalp cerrahisi ,Modified ultrafiltration ,Cardiopulmonary bypass ,General Earth and Planetary Sciences ,Medicine ,DIURETIC USAGE ,Sağlık Bilimleri ve Hizmetleri ,business ,General Environmental Science - Abstract
Amaç: Pediatrik kardiyopulmoner baypas total vücut sıvında ve damar geçirgenliğinde artmaya neden olur. Dokular aralarına sızan bu sıvı organ fonksiyonlarında bozulmalara neden olmaktadır. Modifiye ultrafiltrasyon çocuklarda kardiyopulmoner baypasa bağlı oluşan toplam vücut sıvı artışının neden olduğu organ fonksiyon bozukluklarını önlemek amacıyla geliştirilmiştir. Bu çalışmada amacımız konjenital kalp hastalığı nedeni ile kardiyopulmoner baypas kullanılarak opere edilen siyanotik ve siyanotik olmayan çocuklarda MUF kullanımının karaciğer ve böbrek fonksiyonları üzerine etkisiniaraştırmaktı.Gereç ve Yöntemler: Ocak 2009 ile ağustos 2011 yılları arasında Ankara Üniversitesi Tıp Fakültesi Kalp ve damar cerrahisi kliniğinde opere edilen modifiye ultrafiltrasyon kullanılan (grup 1) n:63, kullanılmayan (grup 2) n:31 toplam 93 hasta çalışmaya dahil edildi. Daha önceden bilinen operasyon ve organ fonksiyon bozukluğu olan, acil şartlarda operasyona alınan, sistemik ve otoimmün hastalığı olan ve kompleks kardiyak anomali nedeni ile parsiyel düzeltme yapılan hastalar çalışmaya dahil edilmedi. Organ fonksiyonlarının değerlendirilmesi amacıyla operasyon öncesinde ve sonrasında kan örnekleri alındı. Hastalar operasyon sonrası ilk 8 ve 24.saat idrar miktarı, drenaj miktarı, diüretik kullanımı, inotrop kullanımı, kan ve kan ürünü kullanımı, diyaliz ihtiyacı ve mortalite açısından retrospektif olarak incelendi.Bulgular: Preoperatif verileri ve operasyon verileri açısından gruplar benzerdi. Grup 1 için kreatinin düzeyinin operasyon sonrasında yüzde değişim oranı %56,5, grup 2 için %25,8 olarak hesaplandı. Vücut yüzey alanına göre univaryant analizde anlamlı olarak bulundu. (p:0,0310,05). Sonuç: Pediatrik açık kalp cerrahisinde modifiye ultrafiltrasyonun kullanımının böbrek yetmezliği gelişimini azalttığı ve karaciğer fonksiyonlarını koruduğunu düşünmekteyiz., Aim: Increased total body water and capillary permeabilty in pediatric cardiopulmonary bypass can cause organ disfunction. Modified ulltrafiltration is developed for decrease total body water and attenuate organ disfunction. The purpose of this study, is to investigate retrospective effects of modified ultrafiltration on postoperative hepatic and renal functions of pediatric patients with congenital siyanotic/nonsiyanotic heart defect who underwent open heart surgery.Material and methods: In this study, we assessed 93 children who underwent pediatric cardiac surgery with cardiopulmonary bypass from January 2009 to August 2011.Patients were divided into two groups. Group 1 (n=62) patiens, to whom modified ultrafiltration was performed, compared with 31control patients (group 2). Patients who had redo cardiac surgery, preoperative organ disfunction, otoimmune disease, genetic disorders, shunt and emergency operations were excluded. Pre and postoperative biochemical parameters, postoperative urine output, chest tube drenaige, diüretic usage, blood and blood product transfusion, dialysis requirement and mortality were compared.Results: Age, weight, body surface area, congenital defect type and number, preoperative and intraoperative blood samples measurement, cross clamp time, cardiopulmonary bypass time were similar between 2 groups (p>0,05).The difference in percent increase in creatinine leves of 2 group was statistically significant When these changes were re-evaluated according to the body surface area by univariate analysis(p0,05) Conclusion: Hemodynamic, pulmonary, hematologic and immunologic effects of modified ultrafiltration are well known. Although our study group was not big enough to get a conclusion, we believe that modified ultrafiltration can be an effective method in preservation of renal and hepatic function of the patients who underwent total reconstructive congenital heart surgery.
- Published
- 2020
99. Atividade do extrato de lichia (Litchi chinensis Sonn.) sobre os parâmetros bioquímicos e histológicos de ratos diabéticos
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Gustavo de Almeida Xavier, Gérsika Bitencourt Santos, Ródney André de Melo, Everton Charles Ferreira dos Santos, Bruno Cesar Correa Salles, Ana Claudia Frota Machado de Melo Lopes, Flávia de Fátima Brasil, Gustavo Henrique Bortolozzo Correa, Fábio Martins da Costa, and Marcela Rezende Pieroni
- Subjects
0106 biological sciences ,medicine.medical_specialty ,Cholesterol ,business.industry ,04 agricultural and veterinary sciences ,General Medicine ,medicine.disease ,01 natural sciences ,Hepatic function ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Diabetes mellitus ,040103 agronomy & agriculture ,medicine ,0401 agriculture, forestry, and fisheries ,Pulp (tooth) ,Pancreas ,business ,010606 plant biology & botany - Abstract
Diabetes mellitus (DM) é uma doença crônica não transmissível caracterizada como o aumento da glicose, devido às disfunções do metabolismo dos carboidratos, lipídios e proteínas. Aliado com o avanço da ciência os frutos e seus subprodutos tem sido considerados promotores da saúde. Neste estudo foi avaliado o efeito anti-hiperglicêmico do extrato hidroetanólico da casca e polpa dos frutos de Litchi chinensis (lichia) em ratos diabéticos. Foram utilizados ratos wistar (250 a 300 g) com DM induzido por aloxana 130 mg/kg. Os animais foram tratados com 300 mg/kg de extratos de Litchi chinensis, durante 75 dias, por gavagem. Foram avaliados a glicemia e os biomarcadores, como os triglicérides, colesterol, função renal e hepática. Tecidos como fígado, rins, coração e pâncreas foram retirados para análise histológica. Os ratos diabéticos tratados com a casca de Litchi chinensis apresentaram uma redução significativa na glicemia em jejum, quando comparados aos ratos não tratados. Além dessa ação benéfica, os ratos tratados tanto com a casca quanto com a polpa, obtiveram redução dos níveis de lipídeos, reduzindo as taxas de triglicerídeos e colesterol. Portanto, Litchi chinensis mostrou seu benefício nos efeitos hipoglicemiantes e hipolipemiantes, tendo potencial terapêutico na prevenção e no tratamento das complicações do diabetes mellitus.
- Published
- 2020
100. EFFECT OF REMOTE ISCHEMIC PRECONDITIONING ON HEPATIC FUNCTION AFTER CO2 PNEUMOPERITONEUM
- Author
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Aldo Cunha Medeiros, Keyla Borges Ferreira Rocha, Ítalo Medeiros Azevedo, and Joyce Freitas
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine.disease ,Gastroenterology ,Hepatic function ,Pneumoperitoneum ,Co2 pneumoperitoneum ,Laparotomy ,Liver tissue ,Internal medicine ,medicine ,Alkaline phosphatase ,Ischemic preconditioning ,Liver function ,business - Abstract
Objective: This study aimed to examine whether remote ischemic preconditioning can influence the effects of pneumoperitoneum with CO2 on the function and structure of the liver of rodents. Methods: Three groups of 6 Wistar rats each were used. 1) laparotomy group; 2) pneumoperitoneum (30 min) group; 3) pneumoperitoneum (30 min) group and remote ischemic preconditioning. Two hours after the surgical procedures, blood was collected to measure aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Euthanasia was performed with an overdose of thiopental (100 mg/kg i.p.). Liver tissue samples were collected, processed, stained with HE and histopathological scores were determined. Values expressed as mean±standard deviation were analyzed by the Fischer and Tukey's tests, with significance p 0,05). Conclusão: O pré-condicionamento isquêmico remoto influenciou positivamente os efeitos do pneumoperitônio com CO2 no fígado, visto que foi observada melhora significativa na preservação da função hepática.
- Published
- 2020
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