Γ-glutamyltransferase Levels Research Articles

Newborn with Lethargy, Jaundice, and Coagulopathy.

Laboratory results include the following: white blood cell count, 21,600/μL (21.6 × 109/L; reference range, 9,000-30,000/μL [9-30 × 109/L]); hemoglobin, 18.2 g/dL (182 g/L; reference range, 14.0-24.0 g/dL [140-240 g/L]); platelet count, 111 × 103/μL (111 × 109/L; reference range, 150-450 × 103/μL [150-450 × 109/L]); blood type, B+; direct antiglobulin test, negative; and reticulocyte count, 4% (reference range, 3%-7%). Comprehensive metabolic panel is significant for hyponatremia, with a sodium level of 132 mEq/L (132 mmol/L; reference range, 135-145 mEq/L [135-145 mmol/L]). Liver enzyme levels are normal (alanine aminotransferase, 41 U/L [0.68 μkat/L]; aspartate aminotransferase, 86 U/L [1.44 μkat/L]), as are total protein (5.4 g/dL [54 g/L]) and albumin (3.0 g/dL [30 g/L]) levels. Repeated bilirubin level is 12.4 mg/dL (212 µmol/L) at 14 hours after birth, with an elevated direct bilirubin level of 2.9 mg/dL (49.6 µmol/L). Direct or conjugated hyperbilirubinemia is defined as a direct bilirubin level greater than 2 mg/dL (34.2 mmol/L) or more than 20% of total bilirubin. γ-Glutamyl transferase level is normal. Coagulation studies show an elevated prothrombin time of 23.4 seconds (reference range, 11-17 seconds), with an international normalized ratio of 2.1 (reference range, 0.9-1.3); activated partial thromboplastin level is 49.5 seconds (reference range, 30-60 seconds). Fibrinogen level is decreased at 70 mg/dL (0.70 g/L) (reference range, 230-450 mg/dL [230-450 g/L]). Lactate level is 24.3 mg/dL (2.7 mmol/L; reference range, 2.0-26.9 mg/dL [0.22-2.98 mmol/L]). Ammonia level is 96.6 µg/dL (69 μmol/L; reference range, 89.6-149.9 µg/dL [64-107 μmol/L]). Cerebrospinal fluid studies are unremarkable. Magnetic resonance imaging (MRI) of the brain and echocardiography are normal. Ultrasonography of the abdomen shows diffuse hepatic echogenicity. Blood and cerebrospinal fluid cultures are negative. Further testing reveals the diagnosis.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver.

Background and Objectives: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). Materials and Methods: Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included. The demographic and clinical data, radiological results and histopathological findings were reviewed and summarized. Results: We analyzed 36 patients comprising 6 PHL patients and 30 SHL patients. The median age at diagnosis tended to be younger in PHL than in SHL (59 vs. 63 years old, p = 0.349). Both entities had a small male predominance. The PHL patients tended to have higher levels of aspartate aminotransferase, alanine transaminase and serum albumin and lower levels of alkaline phosphatase, total bilirubin, γ-glutamyl transferase and lactate dehydrogenase compared with SHL, but there was no significant difference. Multiple mass lesions were the most common radiological finding in both groups. Diffuse large B-cell lymphoma was the predominant subtype in both groups (67% in PHL and 40% in SHL). The PHL patients had a longer median survival than the SHL patients (not reached vs. 3 months, p = 0.003). Conclusions: Although there was no significant difference between PHL and SHL in clinical, laboratory and radiological features, the SHL patients had very poor outcomes with a median survival time of 3 months. Effective therapies are urgently required for these patients.

Prediction and validation of nonalcoholic fatty liver disease by fatty liver index in a Japanese population.

Fatty liver index (FLI) calculated by using body mass index (BMI), waist circumference and levels of γ-glutamyl transferase and triglycerides is a non-invasive predictor of nonalcoholic fatty liver disease (NAFLD). The original study in Italy showed that the cutoff level for prediction of NAFLD was FLI ≥60. However, the sex difference in FLI was not taken into consideration, and it is unclear whether the cutoff value can be applied to other races. We investigated the cutoff value of FLI for prediction of NAFLD determined by abdominal ultrasonography using receiver operating characteristic curve analyses in 14,471 Japanese subjects (men/women: 9,240/5,231; mean age: 48 ± 9 years). There was a significant interaction between sex and FLI for detection of NAFLD (p < 0.001). The cutoff values of FLI in men and women were 35.1 (area under the curve [AUC]: 0.82) and 15.6 (AUC: 0.91), respectively. When the subjects were divided by the absence and presence of obesity (BMI ≥25), there was a significant interaction between FLI and obesity for detection of NAFLD in women (p < 0.001) but not in men (p = 0.679). The cutoff values of FLI in non-obese/obese men and women were 22.6/52.6 and 11.2/33.2, respectively. In conclusion, the cutoff value of FLI for prediction of NAFLD in Japanese individuals was lower than that in the original study, and there is a significant sex difference. The simple and useful cutoff values in Japanese men and women are FLI ≥35 (non-obese/obese: 23/53) and FLI ≥16 (non-obese/obese: 11/33), respectively.

Development of a Prognostic Nomogram in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Following Trans-Arterial Chemoembolization with Drug-Eluting Beads.

ObjectiveTo develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE).MethodsThis retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed.ResultsTumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79–0.97) in the training cohort and 0.87 (95% CI, 0.75–0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application.ConclusionWe developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.

Molecular Prevalence of Equine Parvovirus-Hepatitis in the Sera of Clinically Healthy Horses in South Korea.

Equine parvovirus-hepatitis (EqPV-H) causes equine hepatitis. The prevalence of EqPV-H in healthy horses has been reported in the United States, China, Germany, and Austria. The present study determined the prevalence of EqPV-H in the sera of clinically healthy horses in South Korea to identify the potential factors for infection and examine the genetic diversity of EqPV-H DNA sequences through comparison with foreign strains. Serum samples collected from 321 horses were tested for EqPV-H using non-structural protein 1 (NS1)-specific polymerase chain reaction. The associations of EqPV-H infection with sex, age, aspartate aminotransferase and γ-glutamyl transferase levels, and race performance were analyzed. Fourteen samples tested positive for EqPV-H (4.4%, 14/321), and EqPV-H infection was associated with sex (p = 0.006) and performance (p = 0.049). In both EqPV-H-positive and control horses, liver-specific biochemical analytes were within the normal ranges. Phylogenetic analyses based on the partial sequences of EqPV-H NS1 revealed that the Korean EqPV-H isolates shared approximately 98.7–100% similarity. Of these, 11 Korean isolates shared high similarity with strains from the United States, Germany, and China, and the remaining three strains were distinct in phylogenetic analyses. The present study describes the current molecular prevalence, potential risk factors, and genetic diversity of Korean EqPV-H.

CT Image Features under Reconstruction Algorithm in Analysis of the Effect of Probiotics Combined with Ursodeoxycholic Acid in Treatment of Intrahepatic Cholestasis of Pregnancy.

This research was to explore the adoption value of computed tomography (CT) images based on adaptive statistical iterative reconstruction (ASIR) algorithm in the evaluation of probiotics combined with ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy (ICP). A total of 82 patients with ICP were selected as the research subjects and they were randomly rolled into experimental group (380 mg probiotics enteric-soluble capsule twice a day, combined with 90 mg ursodeoxycholic acid soft capsule three times a day) and control group (90 mg ursodeoxycholic acid soft capsule three times a day), with 41 cases in each. The treatment course was four months. The ASIR algorithm was constructed and applied to the CT image analysis and diagnosis of ICP patients. The effects of filtering back projection (FBP) reconstruction and ASIR algorithm on CT image quality, denoising degree, and artifacts of ICP patients were compared. Moreover, blood indicator levels of ICP patients before and after treatment were assessed. The results showed that the SD values of liver and gallbladder (20.77 Hu and 27.58 Hu) in the reconstructed image of the ASIR algorithm were significantly lower than those of the FBP algorithm (40.58 Hu and 45.63 Hu) (P < 0.05). The SNR values of the liver and gallbladder (3.68 and 2.05) of the reconstructed image were significantly higher than those of the FBP algorithm (1.91 and 1.19) (P < 0.05). The overall image quality after ASIR reconstruction (3.92 points) was significantly better than that of the FBP algorithm (2.36 points), and the image noise score (3.21 points) reconstructed by the FBP algorithm was higher than that by the ASIR algorithm (1.83 points). The artifact score of FBP reconstructed image (4.47 points) was greatly higher than that of ASIR algorithm (2.26 points) (P < 0.05). Before treatment, there was no remarkable difference in the indexes between the two groups of patients (P > 0.05). After treatment, the γ-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP) levels (327.55 U/L and 778.15 μmol/L) of the experimental group of ICP patients were higher than those of the control group (248.63 U/L and 668.43 μmol/L), with substantial difference between the two groups (P < 0.05). The blood ammonia (BA) level (151.09 μmol/L) of the experimental group was lower than that of the control group (178.46 μmol/L), and the difference between the two groups was remarkable (P < 0.05). To sum up, the CT image denoising degree based on ASIR algorithm was high, with few artifacts and good overall quality. Probiotics combined with ursodeoxycholic acid in the treatment of ICP can effectively improve the liver function and intestinal flora of patients, which was of great significance in the clinical diagnosis and treatment of the disease.

Diarrhea duration and performance outcomes of pre-weaned dairy calves supplemented with bacteriophage

This study aimed to evaluate lytic bacteriophage supplementation in pre-weaned dairy calves on disease occurrence, performance, and biochemical parameters. Two hundred Holstein × Gyr crossbred female calves were divided into two groups: CON, no supplementation; and PHAGE, bacteriophage supplementation (1 g·d−1) from day 3 until day 70 of life. Calves were monitored daily for age of first diarrheal episode and its duration. Fecal samples were cultured for bacterial isolation and PCR was performed to identify Escherichia coli virulence genes and to confirm Salmonella spp. Performance outcomes were evaluated up to 80 d of age. Blood samples were collected to determine serum levels of total proteins, albumin, cholesterol, γ-glutamyl transferase, and urea. PHAGE group had fewer days with diarrhea (PHAGE: 4.68 d, CON: 6.61 d; P = 0.03). Fecal samples of three animals in PHAGE and nine in CON were positive for E. coli after PCR tests. Average daily gain of PHAGE was higher up to 80 d of life (P &lt; 0.05). PHAGE mean was lower for albumin and higher for urea (P = 0.004 and P &lt; 0.001, respectively). Phage therapy during the pre-weaned period reduced the duration of neonatal diarrhea, providing greater weight gain for calves.

Сучасний підхід до діагностики серцево-судинних розладів у новонароджених із груп перинатального ризику в неонатальний період

З метою удосконалення та систематизування підходу до діагностики серцево-судинних розладів у новонароджених шляхом комплексної оцінки допплерехокардіографічних параметрів, біохімічних маркерів (рівень лактатдегідрогенази, γ-глутамілтрансферази) та поліморфними варіантами С786Т у гені ендотеліальної синтази оксиду азоту (еNOS), T58C у гені мітохондріальної супероксиддисмутази (MnSOD2) та Ser49Gly в гені β1-адренорецептора (ADRB1) обстежені 133 новонароджені, із них 73 з групи перинатального ризику (І група) та 60 здорових доношених новонароджених (ІІ група). За результатами обстеження, бівентрикулярна дисфункція встановлена в 19,1 % дітей І групи, серед яких у 4 (5,5 %) обстежених встановлена систоло-діастолічна, у 10 (13,6 %) новонароджених — діастолічна дисфункція шлуночків серця. У 12 (20,0 %) передчасно народжених дітей та в 4 (30,7 %) новонароджених із затримкою внутрішньоутробного розвитку встановлено гіпокінетичний тип центральної гемодинаміки, що супроводжувалося підвищеними рівнями лактатдегідрогенази і γ-глутамілтрансферази в сироватці крові та змінами діастолічного наповнення шлуночків серця. Встановлена наявність асоціації між генотипом СС поліморфізму гена еNOS та скоротливою здатністю міокарда лівого шлуночка, інтегральною функцією лівого шлуночка за індексом Теї у передчасно народжених дітей із групи перинатального ризику, носіїв алелі С за поліморфізмом гена MnSOD2 та з легеневою гіпертензією, в неонатальний період. Наявність генотипу GG поліморфізму гена ADRB1 можна вважати предиктором розвитку гіпокінетичного режиму центральної гемодинаміки.

Neonatal Hyperbilirubinemia and Cholestasis.

Neonatal Hyperbilirubinemia and Cholestasis.

Abdominal and gastrointestinal manifestations in COVID-19 patients: Is imaging useful?

Coronavirus disease 2019 (COVID-19) can be considered a systemic disease with a specific tropism for the vascular system, in which the alterations of the microcirculation have an important pathogenetic role. The lungs are the main organ involved in COVID-19, and severe progressive respiratory failure is the leading cause of death in the affected patients; however, many other organs can be involved with variable clinical manifestations. Concerning abdominal manifestations, the gastrointestinal tract and the hepatobiliary system are mainly affected, although the pancreas, urinary tract and spleen may also be involved. The most common gastrointestinal symptoms are loss of appetite, followed by nausea and vomiting, diarrhea and abdominal pain. Gastrointestinal imaging findings include bowel wall thickening, sometimes associated with hyperemia and mesenteric thickening, fluid-filled segments of the large bowel and rarely intestinal pneumatosis and ischemia. Hepatic involvement manifests as an increase in the enzymatic levels of alanine aminotransferase, aspartate aminotransferase, serum bilirubin and γ-glutamyl transferase with clinical manifestations in most cases mild and transient. The most frequent radiological features are hepatic steatosis, biliary sludge and gallstones. Edematous acute pancreatitis, kidney infarct and acute kidney injury from acute tubular necrosis have been described more rarely in COVID-19. Lastly, splenic involvement is characterized by splenomegaly and by the development of solitary or multifocal splenic infarcts with classic wedge-shaped or even rounded morphology, with irregular or smooth profiles. In summary, the abdominal radiological findings of COVID-19 are nonspecific and with poor pathological correlation reported in the literature. Ultrasound and particularly computed tomography with multiphasic acquisition are the diagnostic methods mainly utilized in COVID-19 patients with abdominal clinical symptoms and signs. Although radiological signs are not specific of abdominal and gastrointestinal involvement, the diagnostic imaging modalities and in particular computed tomography are helpful for the clinician in the management, evaluation of the severity and evolution of the COVID-19 patients.

Expression and clinical significance of interleukin-16 in patients with primary biliary cholangitis

Objective: To investigate the expressional condition of interleukin-16 (IL-16) in the liver and serum of patients with primary biliary cholangitis (PBC). Methods: Liver biopsies samples were collected from 70 cases and 10 healthy controls, and serum samples were collected from 62 cases and 87 healthy controls. The expression of IL-16 in liver was detected by immunohistochemistry, and the serum level of IL-16 was determined by enzyme-linked immunosorbent assay. The correlation between the expression level of IL-16 and the severity of disease was determined by correlation analysis with clinical biomarker. The t-test was used for normally distributed data. Wilcoxon signed rank sum test was used for non-normally distributed data. Results: The expression level of IL-16 in the liver of PBC patients was significantly higher than that in the healthy control group (P = 0.002 5), and it was mainly expressed in infiltrating lymphocytes in the portal area. Correlation analysis showed that the level of IL-16 in liver tissue was positively correlated with the degree of liver inflammation (r = 0.36, P = 0.002). In addition, the serum IL-16 level of PBC patients were significantly higher than that of healthy people (P = 0.000 5), and serum IL-16 level was correlated with the level of cholestasis biomarker γ-glutamyltransferase (r = 0.31, P = 0.03). Conclusion: The expression level of IL-16 is significantly increased in liver and serum of PBC patients, and it is positively correlated with the severity of the disease, suggesting that IL-16 may be used as a biomarker to assess the severity of the disease.

Hepatocyte-derived canine familiaris-microRNAs as serum biomarkers of hepatic steatosis or fibrosis as implicated in the pathogenesis of canine cholecystolithiasis.

Hepatic cholesterol accumulation in small breed dogs is a leading risk factor for hepatic fatty changes, gallbladder hypomotility, and cholelith development, which, if not discovered early, could lead to life-threatening choledocholithiasis and acute pancreatitis. This study proposed to assess the use of hepatocyte-derived canine familiaris (cfa)-microRNAs (miRNA-122, -34a, and -21) as new diagnostic serum biomarkers of liver steatosis or fibrosis, for which both processes have been implicated in canine cholecystolithiasis. Forty client-owned dogs diagnosed with cholecystolithiasis and hepatic steatosis (C+HS) or fibrosis (C+HF) based on ultrasonographic, biochemical, and histopathologic findings, and 20 healthy dogs used as controls were included in the study. Serum cfa-miRNA expression was determined using a real-time polymerase chain reaction assay. Serum cfa-miRNA-122 and -34a expression was significantly upregulated in the C+HS (P<.001) and C+HF (P<.01) groups compared with the control group and showed a positive correlation with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), and triglycerides (TG) levels in the C+HS group. Cfa-miRNA-122 and -34a expression discriminated the diseased groups from the control group betterthan traditional serum-derived liver biomarkers, as evidenced by areas under the receiver operating characteristic (AUC-ROC) curve of 0.99 and 0.97 for cfa-miRNA-122 expression in the C+HS and C+HF groups, and 1.0 and 0.96 for cfa-miRNA-34a in the C+HS and C+HF groups, respectively. Cfa-miRNA-21 expression was upregulated only in the C+HF group compared with the C+HS (P<.01) and control (P<.001) groups and showed a positive correlation with serum ALT, AST, TBIL, ALP, and GGT and negative correlation with serum TC and TG levels. Cfa-miRNA-21 expression could also differentiate the C+HF group from the control and C+HS groups with a diagnostic performance superior to that of the conventional serum biochemical variables as evidenced by AUCs of 1.0 and 0.98, respectively. Serum cfa-miRNA-122, -34a, and -21 expression was significantly upregulated in dogs with cholecystolithiasis with hepatic steatosis or fibrosis compared with control dogs. These miRNAs could serve as novel biomarkers for hepatic steatosis or fibrosis, which have been implicated in the pathogenesis of cholecystolithiasis.

Endoscopic Biliary Decompression by Dual Stents in Elderly Patients with Acute Cholangitis of Severe Type Due to Choledocholithiasis.

Background/Aims: Both endoscopic nasobiliary drainage (ENBD) and a plastic stent placement have some limitations in biliary decompression of elderly patients with acute cholangitis of severe type (ACST) due to choledocholithiasis. Dual stent placement may improve bile drainage without obvious discomfort. Here, we evaluated its advantages in the biliary decompression of elderly patients with ACST. Materials and Methods: A total of 257 elderly patients (≥65 years) with ACST had undergone urgent endoscopic decompression by nasobiliary catheter (ENBD group), single plastic stent (single-stent group), or dual plastic stents (dual-stent group). The data of the three groups was compared retrospectively. Results: The demographic data of the patients in the three groups were comparable. After endoscopic decompression, the serum total bilirubin and γ-glutamyl transferase levels in the dual-stent group were decreased faster than that in the single-stent group (P < .05). The abdominal pain in the dual-stent group was dramatically slighter than that in the ENBD group (P < .05). Compared with two other groups, the acute physiology and chronic health evaluation II scores were decreased dramatically quicker (P < .05) and the length of intensive care unit stay was significantly shorter (P < .05) in the dual-stent group. In the second endoscopic retrograde cholangiopancreatography, the rate of complete stone clearance in the dual-stent group was significantly higher than that in the ENBD group (P < .05). Conclusions: Dual-stent placement might be a better choice for elderly patients with ACST due to choledocholithiasis in comparison with ENBD or a single-stent placement.

Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies

BackgroundChlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears. ObjectiveThe present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo. MethodsDocking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits. ResultThe in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5–30 μg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks. ConclusionThe findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications.

Fructose Intake Impairs the Synergistic Vasomotor Manifestation of Nitric Oxide and Hydrogen Sulfide in Rat Aorta.

In this study, we evaluated the effect of eight weeks of administration of 10% fructose solution to adult Wistar Kyoto (WKY) rats on systolic blood pressure (SBP), plasma and biometric parameters, vasoactive properties of the thoracic aorta (TA), NO synthase (NOS) activity, and the expression of enzymes producing NO and H2S. Eight weeks of fructose administration did not affect SBP, glycaemia, or the plasma levels of total cholesterol or low-density and high-density lipoprotein; however, it significantly increased the plasma levels of γ-glutamyl transferase and alanine transaminase. Chronic fructose intake deteriorated endothelium-dependent vasorelaxation (EDVR) and increased the sensitivity of adrenergic receptors to noradrenaline. Acute NOS inhibition evoked a reduction in EDVR that was similar between groups; however, it increased adrenergic contraction more in fructose-fed rats. CSE inhibition decreased EDVR in WKY but not in fructose-fed rats. The application of a H2S scavenger evoked a reduction in the EDVR in WKY rats and normalized the sensitivity of adrenergic receptors in rats treated with fructose. Fructose intake did not change NOS activity but reduced the expression of eNOS and CBS in the TA and CSE and CBS in the left ventricle. Based on our results, we could assume that the impaired vascular function induced by increased fructose intake was probably not directly associated with a decreased production of NO, but rather with impairment of the NO–H2S interaction and its manifestation in vasoactive responses.

Genetic Regulation of Biomarkers as Stress Proxies in Dairy Cows

Stress in livestock reduces productivity and is a welfare concern. At a physiological level, stress is associated with the activation of inflammatory responses and increased levels of harmful reactive oxygen species. Biomarkers that are indicative of stress could facilitate the identification of more stress-resilient animals. We examined twenty-one metabolic, immune response, and liver function biomarkers that have been associated with stress in 416 Italian Simmental and 436 Italian Holstein cows which were genotyped for 150K SNPs. Single-SNP and haplotype-based genome-wide association studies were carried out to assess whether the variation in the levels in these biomarkers is under genetic control and to identify the genomic loci involved. Significant associations were found for the plasma levels of ceruloplasmin (Bos taurus chromosome 1—BTA1), paraoxonase (BTA4) and γ-glutamyl transferase (BTA17) in the individual breed analysis that coincided with the position of the genes coding for these proteins, suggesting that their expression is under cis-regulation. A meta-analysis of both breeds identified additional significant associations with paraoxonase on BTA 16 and 26. Finding genetic associations with variations in the levels of these biomarkers suggests that the selection for high or low levels of expression could be achieved rapidly. Whether the level of expression of the biomarkers correlates with the response to stressful situations has yet to be determined.

Protective role of All Trans Retinoic Acid on B16F10 melanoma cell line metastasis in C57BL/6 mice by enhancing RAR- β protein and homeostasis maintenance

ABSTRACT Lung cancer is the leading cancer according to the World Health Organization (WHO), resulting in highest death rate worldwide due to the high level of metastasis. Hence, the drugs that protect from metastasis either as an adjuvant or a primary therapeutic agent may help to reduce the death rate. In this study, All Trans Retinoic Acid (ATRA) was tested for its action against metastatic lodging of B16F10 melanoma cells in the lung and liver of the C57BL/6 mouse model. Serum, lung and liver were evaluated biochemically for the cancer associated changes. Metastatic cancer development was confirmed by tumor nodule formation and histopathological analysis. RAR-β protein expression was analyzed by immunohistochemistry and histopathology. ATRA treated mice showed a percentage of inhibition on metastatic tumor growth in lung and liver and a corresponding protection against pathological changes in these organs. Cholesterol and γ-Glutamyl Transferase (GGT) levels found in cancer induced mice were reduced in the ATRA treated group. As compared to the normal group, lung tissue from cell line induced cancer control group had less RAR-β protein expression while the ATRA treated group showed enhanced RAR-β protein expression. This indicates that the anti-metastasis effects of ATRA might have shown the induction of RAR-β expression and subsequent molecular signaling pathways to regulate the homeostasis of biochemical changes. This study demonstrated the capability of ATRA to prevent the establishment of metastasis by the melanoma cell line into the lung and liver of experimental mice.

Deleterious Variants in ABCC12 are Detected in Idiopathic Chronic Cholestasis and Cause Intrahepatic Bile Duct Loss in Model Organisms

The etiology of cholestasis remains unknown in many children. We surveyed the genome of children with chronic cholestasis for variants in genes not previously associated with liver disease and validated their biological relevance in zebrafish and murine models. Whole-exome (n= 4) and candidate gene sequencing (n= 89) was completed on 93 children with cholestasis and normal serum γ-glutamyl transferase (GGT) levels without pathogenic variants in genes known to cause low GGT cholestasis such as ABCB11 or ATP8B1. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 genome editing was used to induce frameshift pathogenic variants in the candidate gene in zebrafish and mice. In a 1-year-old female patient with normal GGT cholestasis and bile duct paucity, we identified a homozygous truncating pathogenic variant (c.198delA, p.Gly67Alafs∗6) in the ABCC12 gene (NM_033226). Five additional rare ABCC12 variants, including a pathogenic one, were detected in our cohort. ABCC12 encodes multidrug resistance-associated protein 9 (MRP9) that belongs to the adenosine 5'-triphosphate-binding cassette transporter C family with unknown function and no previous implication in liver disease. Immunohistochemistry and Western blotting revealed conserved MRP9 protein expression in the bile ducts in human, mouse, and zebrafish. Zebrafish abcc12-null mutants were prone to cholangiocyte apoptosis, which caused progressive bile duct loss during the juvenile stage. MRP9-deficient mice had fewer well-formed interlobular bile ducts and higher serum alkaline phosphatase levels compared with wild-type mice. They exhibited aggravated cholangiocyte apoptosis, hyperbilirubinemia, and liver fibrosis upon cholic acid challenge. Our work connects MRP9 with bile duct homeostasis and cholestatic liver disease for the first time. It identifies a potential therapeutic target to attenuate bile acid-induced cholangiocyte injury.

An Uncommon Lesion of the Liver

Question: A 32-year-old man with a positive history of hepatitis B infection for 15 years was admitted to our hospital because of abnormal liver function tests results, including the elevated levels of alanine aminotransferase (97 U/L; normal range, 7–40 U/L), aspartate aminotransferase (146 U/L; reference range, 13–35 U/L) and γ-glutamyl transferase (233 U/L, reference range, 7–45 U/L). A blood cell count showed an elevated eosinophil cell count (1.87 × 109/L, reference range, 0.02×109–0.52 × 109/L).

Dynamic monitoring of serum liver function indexes in patients with COVID-19.

BACKGROUNDSome patients with the novel 2019 coronavirus disease (COVID-19) display elevated liver enzymes. Some antiviral drugs that can be used against COVID-19 are associated with a risk of hepatotoxicity.AIMTo analyze the clinical significance of the dynamic monitoring of the liver function of patients with COVID-19. METHODSThis was a retrospective study of patients diagnosed with COVID-19 in January and February 2020 at the Department of Infection, Shantou Central Hospital. The exclusion criteria for all patients were: (1) History of chronic liver disease; (2) History of kidney disease; (3) History of coronary heart disease; (4) History of malignancy; or (5) History of diabetes. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase, and total bilirubin of patients with COVID-19 were measured on days 1, 3, 7 and 14 after admission, and compared to non-COVID-19 patents.RESULTSTwelve patients with COVID-19 (seven men and five women) and twelve controls (eight men and four women) were included. There were one, two, and nine patients with severe, mild, and moderate COVID-19, respectively. There were no differences in age and sex between the two groups (both P > 0.05). No significant differences were found in albumin, ALT, AST, γ-glutamyltransferase, or total bilirubin between the controls and the patients with COVID-19 on day 1 of hospitalization (all P > 0.05). Serum albumin showed a decreasing trend from days 0 to 7 of hospitalization, reaching the lowest level on day 7. Total bilirubin was higher on day 3 than on day 7. ALT, AST, and γ-glutamyltransferase did not change significantly over time. The severe patient was observed to have ALT levels of 67 U/L and AST levels of 75 U/L on day 7, ALT of 71 U/L and AST of 35 U/L on day 14, and ALT of 210 U/L and AST of 123 U/L on day 21.CONCLUSIONChanges in serum liver function indicators are not obvious in the early stage of COVID-19, but clinically significant changes might be observed in severe COVID-19.