Lower Aspartate Aminotransferase Levels Research Articles

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Hepatoprotective Effect of the Ursolic Acid-Oleanolic Acid Mixture Administered Intragastrically in Mice with Liver Damage Induced by Anti-TB Drugs

OBJECTIVE: The hepatoprotective (HPP) effect of the ursolic acid and oleanolic acid (UA/OA) mixture administered intragastrically (i.g.) against the damage caused by antituberculosis drugs (rifampicin/isoniazid/pyrazinamide, -RIF/INH/PZA-) is described. MATERIALS AND METHODS: The UA/OA mixture was obtained from the methanolic extract (MeOH) of _Rosmarinus officinalis_. The assay was performed in male Balb/C mice with hepatic damage induced by RIF/INH/PZA, and, as a positive control, silymarin (SIL) was used. The UA/OA mixture was administered by i.g. at 10 and 20 mg/kg during 60 days. RESULTS: The UA/OA mixture administered at 10 and 20 mg/kg for 60 days favored body weight gain and lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). This effect was similar to positive control (SIL). At the histological level, a slight reduction of steatosis in the group that received the UA/OA mixture at 10 mg/kg was observed with respect to the group with hepatic damage and with the UA/OA group at 20 mg/kg. The UA/OA mixture at 10 mg/kg showed a good HPP effect. CONCLUSIONS: The UA/OA mixture administered i.g. favored body weight gain and lowered levels of hepatic enzymes while reducing steatosis before the damage caused by antituberculosis drugs. The best dose was 10 mg/kg administered over 60 days.

Comparative and Predictive Analysis of Clinical and Metabolic Features of Anorexia Nervosa and Bulimia Nervosa.

Eating disorders have become increasingly prevalent over the years; the age at which they appear has decreased, and they can lead to serious illness or death. Therefore, the number of studies on the matter has increased. Eating disorders like anorexia nervosa (AN) and bulimia nervosa (BN) are affected by many factors including mental illnesses that can have serious physical and psychological consequences. Accordingly, the present study aimed to compare the clinical and metabolic features of patients with AN and BN and identify potential biomarkers for distinguishing between the two disorders. Clinical data of 41 participants who sought treatment for eating disorders between 2012 and 2022, including 29 AN patients and 12 BN patients, were obtained from NPIstanbul Brain Hospital in Istanbul, Turkey. The study included the clinical variables of both outpatient and inpatient treatments. Principal component analysis (PCA) was utilized to gain insights into differentiating AN and BN patients based on clinical characteristics, while machine learning techniques were applied to identify eating disorders. The study found that thyroid hormone levels in patients with AN and BN were influenced by non-thyroidal illness syndrome (NTIS), which could be attributed to various factors, including psychiatric disorders, substance abuse, and medication use. Lipid profile comparisons revealed higher triglyceride levels in the BN group (P<0.05), indicating increased triglyceride synthesis and storage as an energy source. Liver function tests showed lower levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in BN patients (P<0.05), while higher prolactin levels (P<0.05) suggested an altered hypothalamic-pituitary-gonadal axis. Imbalances in minerals such as calcium and magnesium (P<0.05) were observed in individuals with eating disorders. PCA effectively differentiated AN and BN patients based on clinical features, and the Naïve Bayes (NB) model showed promising results in identifying eating disorders. The findings of the study provide important insights into AN and BN patients' clinical features and may help guide future research and treatment strategies for these conditions.

Association between thyroid function and diabetes peripheral neuropathy in euthyroid type 2 diabetes mellitus patients

Previous studies disclosed that a high thyroid stimulating hormone level is an independent risk factor for diabetes peripheral neuropathy (DPN) in subclinical hypothyroidism (SCH) patients with type 2 diabetes mellitus (T2DM). However, whether thyroid metabolism has an effect on DPN in euthyroid T2DM patients remains unknown. The aim of this study was to identify the association between thyroid function and DPN in euthyroid T2DM patients. A set of 580 euthyroid T2DM patients was enrolled in the current study and stratified into DPN and Non-DPN groups. Mann–Whitney U test was performed to analyze the continuous variables of biochemical and thyroid metabolism indicators, and the Chi-square test was used to compare the categorical variables. Spearman correlation analysis was performed to analyze the relationship between clinical indicators and free thyroxine (FT4). By using the logistic regression analysis, the prevalence of DPN in different thyroid function indicators were evaluated. T2DM patients with DPN had obviously lower levels of aspartate aminotransferase (AST), alpha-hydroxybutyric dehydrogenase (α-HBDH), superoxide dismutase (SOD), calcium (Ca), creatinine (Cr), uric acid (UA), retinol binding protein (RBP), total protein (TP), albumin (ALB), alanine aminotransferase (ALT) and FT4 than the T2DM patients without DPN (P < 0.05). FT4 was associated with TP, prealbumin (PA), ALB, SOD, anion gap (AG), Ca, chlorine (Cl), UA, RBP, apoprotein A (Apo A), apoprotein B (Apo B), apoprotein E (Apo E), and total cholesterol (TC). According to the FT4 quartile, participants were sequentially divided into four groups to compare the prevalence of DPN between each group. The data suggested that the prevalence of DPN in these four groups was 53.79%, 53.28%, 54.97%, 38.10%, respectively. Moreover, compared with quartile 4, patients in quartile 1, 2, 3 all had a significantly higher risk of DPN (P = 0.007, P = 0.011, P = 0.004). The level of FT4 was negatively correlated with the prevalence of DPN in euthyroid T2DM patients.

Detrimental Effect of Tannin on Growth Performance, Visceras Weight and Blood Biochemistry in Broiler Chickens Reared Under Tropical Area.

Restriction of antibiotic growth promoters (AGP) in Indonesia reduces broiler production due to bacterial diseases. Some poultry farmers have attempted to replace AGP with phytogenic compounds, such as tannin as an in-feed additive. Therefore, this study was carried out to investigate the effects of tannin administration on the productionperformance, viscera weight, and lipoprotein levels of tropically-raised broiler chickens. Cobb Strain broiler chicks aged one day were used in an experiment with a completely random design, three treatments, and four replicate pens, each containing nine birds. Three dietary treatments were assigned to the birds: basal diet (negative control), basal diet+0.03% Zn Bacitracyn (positive control), and basal diet+0.05% tannin for the starter phase of 1-21 days and the grower phase of 22-42 days, respectively. Tannin supplementation significantly increased the feed conversion ratio in all phases relative to the control group. Tannin supplementation in the diet significantly reduced daily feed intake during the grower phase, final body weight, carcass weight, intestine weight, liver weight, and total visceral weight, compared to the control group. Tannin had lower levels of aspartate aminotransferase but higher levels of low-density lipoprotein and alanine aminotransferase. Tannin addition in broiler diets might not improve growth performance and health. Therefore, it is not suggested as a substitute for AGPs in broiler diets.

Abstract 13538: Associations Between Circulating Liver Enzymes and Platelet Reactivity

Introduction: The liver plays an essential role in thrombopoiesis and coagulation, and circulating liver enzymes are associated with altered platelet counts. However, the role of liver enzymes in the modulation of platelet reactivity remains unclear. Methods: A total of 3,429 Framingham Heart Study participants were included in this study. Platelet reactivity to 8 agonists, including adenosine diphosphate (ADP), thromboxane A 2 mimetic (U46619) and arachidonic acid (AA), was measured using light transmission aggregometry (LTA), Multiplate impedance aggregometry and Optimul aggregometry. Platelet counts and platelet-red blood cell aggregates were enumerated using flow cytometry. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Associations of platelet reactivity phenotypes with liver circulating liver enzyme levels analyzed using linear mixed-effects models and adjusted for sex, age, relatedness, smoking, aspirin-, and statin-use. To correct for multiple testing, a Bonferroni-correction threshold of P&lt;0.0011 was used to account for multiple comparisons. Results: Higher ALT levels were associated with platelet disaggregation in LTA to ADP (β=0.056, SE=0.02, P=3.54E-04), and with decreased platelet reactivity in response to U46619 in Optimul (EC 50 : β=0.064, SE=0.019, P=7.65E-04). Interestingly, higher AST levels were associated with decreased platelet counts (β=-0.082, SE=0.019, P=1.04E-05), platelet reactivity to U46619 (β=-0.069, SE=0.018, P=1.04E-04) and AA (β=-0.047, SE=0.013, P=3.12E-04), and circulating platelet-red blood cell aggregates (β=-0.062, SE=0.018, P=9.54E-04). Conclusion: Our findings suggest that ALT levels could alter primary platelet aggregation. AST may indirectly modulate platelet counts. In addition, lower AST levels may contribute to platelet hyperresponsiveness. Lastly, ALT and AST levels may have antagonistic effects on the formation of platelet and red blood cell aggregates, which may indirectly influence platelet margination within vessels. Additional studies are underway to examine whether liver fat, a marker of fibrosis associated with cardiovascular disease, is also associated with altered platelet function.

Clinical features of children with coronavirus disease 2019 Delta variant infection after vaccination with inactivated SARS-CoV-2 vaccine

To study the clinical features of children with coronavirus disease 2019 (COVID-19) Delta variant infection vaccinated or not vaccinated with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. A total of 11 children with COVID-19 Delta variant infection who were vaccinated with inactivated SARS-CoV-2 vaccine and were hospitalized in the designated hospital in Henan Province, China, from November 3 to December 17, 2021 were enrolled as the vaccinated group. Thirty-one children with COVID-19 Delta variant infection who were not vaccinated and were hospitalized during the same period were enrolled as the unvaccinated group. A retrospective analysis was performed on their epidemiological data, clinical features, and laboratory examination results. There was no significant difference in gender composition and disease classification between the two groups (P>0.05), and there was also no significant difference in the incidence rates of the clinical symptoms such as cough, expectoration, and fever between the two groups (P>0.05). No significant difference was found between the two groups in leukocyte count, lymphocyte percentage, alanine aminotransferase, and serum creatinine (P>0.05). Compared with the unvaccinated group, the vaccinated group had significantly lower levels of aspartate aminotransferase, lactate dehydrogenase, and creatine kinase-MB (P<0.05). There was no significant difference between the two groups in the proportion of children with elevated C-reactive protein or procalcitonin and the levels of peripheral blood cytokines (P>0.05). The vaccinated group had significantly lower counts of B lymphocytes and total T lymphocytes (CD3+) than the unvaccinated group (P<0.05). Compared with the unvaccinated group, the vaccinated group had a significantly higher positive rate of IgG on admission and at week 2 of the course of disease (P<0.05), as well as a significantly higher Ct value of nucleic acid at weeks 1 and 2 of the course of disease (P<0.05). Vaccination with inactivated SARS-CoV-2 vaccine may reduce myocardial injury caused by SARS-CoV-2 Delta variant. For children with SARS-CoV-2 Delta variant infection after the vaccination, more attention should be paid to their immune function.

Effect of Nonalcoholic Fatty Liver Disease (NAFLD) on COVID-19: A Single-Center Study of 3983 Patients With Review of Literature.

BackgroundThe presence of metabolic syndrome (MS) is associated with increased disease severity in patients with coronavirus disease 2019 (COVID-19). Non-alcoholic fatty liver disease (NAFLD) associated with or without MS may be related to increased morbidity and mortality in COVID-19, but large Indian studies are lacking. The present study was carried out to assess the impact of NAFLD on the clinical outcomes in patients with COVID-19 infection.MethodsAll patients with COVID-19 hospitalized at a tertiary care hospital in eastern India from April 4 to December 31, 2020, were included in the study. Patients who underwent non-contrast CT (NCCT) chest were evaluated for the presence of hepatic steatosis based on a validated criterion liver attenuation (HU) value lower than the spleen, absolute liver attenuation lower than 40 HU, and liver to spleen attenuation ratio less than 1. Patients were divided into two groups, those with or without fatty liver. Baseline characteristics including age, sex, liver function tests, and outcomes including duration of hospital stay and mortality were compared.ResultsA total of 6003 COVID-19-positive patients were admitted during the study period. Of these patients, 214 children (<18 years) with COVID-19 infection were excluded. One hundred and eight patients with a history of significant ethanol abuse were excluded from the analysis. NCCT scan was not done in 1698 patients. Finally, 3983 patients were included in the study. They were divided into two groups depending on the presence or absence of NAFLD. Of the 3983 patients, 814 (20.4%) had NAFLD. Overall in-hospital mortality among the study group was 6.4%. The mortality rate among patients with NAFLD was 6.7% while that in patients without fatty liver was 6% (P=0.381). Similarly, the mean duration of hospital stay was also comparable between both the groups (10.63±7.2days vs 10.65±6.6 days;P=0.66). Prevalence of NAFLD was similar in survivors and non-survivors; 759 of 2981 patients (25.4%) and 55 of 188 patients 29.2% (P=0.381), respectively. On univariate analysis, male sex, older age, elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) along with low serum albumin and low absolute eosinophil counts (AEC) were associated with higher mortality. However, on multivariate analysis, only older age, male sex, and low albumin levels were associated with higher mortality. Surprisingly, a sub-group analysis showed that females without NAFLD were at a higher risk of mortality than those with fatty liver (4.9% vs 12.3%; P=0.006). Similarly, patients with lower AST levels had higher mortality compared to patients with significantly elevated AST levels (more than two times the upper limit of normal (ULN)), irrespective of the presence of fatty liver.ConclusionsThe prevalence of fatty liver in severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infected patients is similar to the general population in India, the presence of which is not a predictor of severe disease. However, mortality is higher in males and elderly patients.

A Novel Predictive Model in Recognizing Severe COVID-19 and Multiorgan Injuries: Platelet-to-CRP Ratio

Aims In view of the emerging virus variations and pandemic worldwide, it is urgent to explore effective models predicting disease severity. Methods We aimed to investigate whether platelet-to-CRP ratio (PC ratio) could predict the severity of COVID-19 and multi-organ injuries. Patients who complained of pulmonary or gastrointestinal symptoms were enrolled after confirmation of SARS-CoV-2 infection via qRT-PCR. Those who complained of gastrointestinal symptoms were defined as having initial gastrointestinal involvement. Chest computed tomography (CT) was then performed to classify the patients into mild, moderate, and severe pneumonia groups according to the interim management guideline. qRT-PCR was also performed on stool to discern those discharging virus through the gastrointestinal tract. Logistic regression models were applied to analyze the association between PC ratio and severity of pneumonia, risk of initial gastrointestinal involvement, and multi-organ injuries. Results When compared to the bottom tertile of PC ratio, the adjusted odds ratio was −0.51, p < 0.001 and −0.53, p < 0.001 in moderate and severe pneumonia, respectively. Furthermore, the adjusted odds ratio for initial gastrointestinal involvement was 0.18 (82% lower) when compared to the bottom tertile of PC ratio, p=0.005. The area under ROC on moderate-to-severe pneumonia and initial gastrointestinal involvement was 0.836 (95% CI: 0.742, 0.930, p < 0.001) and 0.721 (95% CI: 0.604, 0.839, p=0.002), respectively. The upper tertiles of PC ratio showed lower levels of aspartate aminotransferase (p=0.016) and lactic dehydrogenase (p < 0.001). Conclusions Platelet-to-CRP ratio could act as an effective model in recognizing severe COVID-19 and multi-organ injuries.

The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys

Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function.

Aspartate aminotransferase and cardiovascular disease—a narrative review

: This narrative review summarized the existing knowledge on the association between aspartate aminotransferase (AST) and cardiovascular disease (CVD). AST plays a key role in the metabolism of amino acids, maintenance of NAD+/NADH ratio in cells, Krebs cycle activity, synthesis of purine/pyrimidine bases, urea and protein synthesis and gluconeogenesis. In humans, AST exists as two genetically and immunologically distinct isoenzymes: cytoplasmic AST and mitochondrial AST and both forms are found in circulation. AST activity is widely distributed across human tissues with the highest activity found in heart, liver, skeletal muscle, kidney and brain. An elevated AST activity may reflect tissue damage (plasma membrane disruption or apoptosis), plasma membrane bleb formation, increased tissue expression and macroenzymes (complexes of AST with plasma proteins). Serum AST activity is increased in patients with acute myocardial infarction in proportion with the extent of myocardial necrosis. Epidemiological evidence suggests the existence of an association between AST activity and CVD or mortality with positive, inverse or U (or J)-shaped association patterns. An elevated AST level not occurring in the setting of inflammatory liver disease may signify an increased cardiovascular risk related to nonalcoholic fatty liver disease (NAFLD), cardiometabolic risk factors (metabolic syndrome, abdominal obesity, insulin resistance and diabetes), chronic alcoholism and structural heart disease (myocardial infarction or congestive heart failure). A positive association between AST and CVD is more common in epidemiological studies in Asian population. Low AST levels may reflect increased cardiovascular risk related to vitamin B6 deficiency, advanced chronic kidney or liver diseases and inflammatory diseases. High and low AST levels have clinical meaning and both of them should be analyzed.

IL-33 ameliorates liver injury and inflammation in Poly I:C and Concanavalin-A induced acute hepatitis

The IL-33/ST2 axis is known to be involved in liver pathologies and IL-33 is over-expressed in mouse hepatitis models. We aimed to investigate the proposed protective effect of IL-33 in murine fulminant hepatitis induced by a Toll like receptor 3 (TLR3) viral mimetic, Poly I:C or by Concanavalin-A (ConA). The Balb/C mice were administered intravenously with ConA (15 mg/kg) or Poly I:C (30 μg/mouse) to induce acute hepatitis along with vehicle control. The recombinant mouse IL-33 (rIL-33) was injected (0.2 μg/mouse) to mice 2 h prior to ConA or Poly I:C injection to check its hepato-protective effects. The gross lesions, level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), histopathology (H&E staining) and levels of IFNγ and TNFα were measured by ELISA. The gross pathological liver injury induced by Poly I:C or ConA was reduced by rIL-33 administration in mice. The levels of AST and ALT were significantly (P ≤ 0.05) higher in mice challenged with Poly I:C or ConA in comparison to control mice. The rIL-33 pre-treated mice in both Poly I:C and ConA challenge groups showed significantly (P ≤ 0.05) lower levels of AST and ALT, and decreased liver injury (parenchymal and per-vascular necrotic areas) in histological liver sections. The soluble levels of TNFα and IFNγ were significantly (P ≤ 0.05) raised in Poly I:C or ConA challenged mice than control mice. The levels of TNFα and IFNγ were significantly reduced (P ≤ 0.05) in rIL-33 pre-treated mice. In conclusion, the exogenous IL-33 administration mitigated liver injury and inflammation (decreased levels of IFNγ and TNFα) in Poly I:C and ConA-induced acute hepatitis in mice.

High TNF-α and/or p38MAPK expression predicts a favourable prognosis in patients with T1N0M0 hepatocellular carcinoma: An immunohistochemical study.

Tumour necrosis factor α (TNF-α) and p38 mitogen-activated protein kinase (p38MAPK) serve an important role in regulating tumour cell apoptosis. However, a limited number of studies have investigated the predictive value of both TNF-α and p38MAPK in hepatocellular carcinoma (HCC). An integrated bioinformatics analysis was initially performed using two datasets available from the Oncomine™ database to determine the association between TNF-α and/or p38MAPK expression and prognosis of patients with HCC. Subsequently, TNF-α and p38MAPK expression in tissue samples from 83 patients with HCC classified as T1N0M0, using the Tumour-Node-Metastasis (TNM) staging system, was investigated using immunohistochemistry. The associations between clinicopathological characteristics and different TNF-α and p38MAPK expression levels in HCC were investigated using the χ2 test. Kaplan-Meier and Cox univariate/multivariate survival analyses were performed to explore the predictive significance of TNF-α and/or p38MAPK expression in patients with HCC. Using the Oncomine™ database, it was revealed that TNF-α and/or p38MAPK expression was not significantly associated with overall survival (OS) or disease-free survival (DFS) rates; however, TNF-α and p38MAPK expression levels were positively associated (P<0.05), and high p38MAPK expression was significantly associated with low aspartate aminotransferase levels (P<0.05). Compared with low expression levels of TNF-α and p38MAPK together, high expression of TNF-α alone, p38MAPK alone and TNF-α and p38MAPK together were significantly associated with improved OS and DFS rates (P<0.05). Additionally, multivariate Cox regression models suggested that high expression levels of TNF-α alone, p38MAPK alone, or TNF-α and p38MAPK together in the HCC microenvironment were independent predictive factors for OS and DFS rates (P<0.05). Patients with T1N0M0 HCC with high TNF-α and/or p38MAPK expression had a significantly lower risk of recurrence and mortality compared with patients with low TNF-α and p38MAPK expression. Consequently, TNF-α and p38MAPK could serve as predictive biomarkers or potential therapeutic targets for T1N0M0 HCC treatment.

A preliminary study on efficacy of rupatadine for the treatment of acute dengue infection

Currently there are no specific treatments available for acute dengue infection. We considered that rupatadine, a platelet-activating factor receptor inhibitor, might modulate dengue-associated vascular leak. The effects of rupatadine were assessed in vitro, and in a dengue model, which showed that rupatadine significantly reduced endothelial permeability by dengue sera in vitro, and significantly inhibited the increased haematocrit in dengue-infected mice with dose-dependency. We conducted a randomised, placebo-controlled trial in 183 adult patients in Sri Lanka with acute dengue, which showed that rupatadine up to 40 mg daily appeared safe and well-tolerated with similar proportions of adverse events with rupatadine and placebo. Although the primary end-point of a significant reduction in fluid leakage (development of pleural effusions or ascites) was not met, post-hoc analyses revealed small but significant differences in several parameters on individual illness days - higher platelet counts and lower aspartate-aminotransferase levels on day 7 in the rupatadine group compared to the placebo group, and smaller effusions on day 8 in the subgroup of patients with pleural effusions. However, due to the small sample size and range of recruitment time, the potential beneficial effects of rupatadine require further evaluation in large studies focused on recruitment during the early febrile phase.

Association of modified Nordic diet with cardiovascular risk factors among type 2 diabetes patients: a cross-sectional study.

Introduction: Cardiovascular disease (CVD) is one of the most important causes of mortality. Healthy diets can decrease CVDs and other chronic diseases especially in patients with type 2 diabetes. In this study, we investigate association between adherence to the modified Nordic diet and cardiovascular risk factors among patients with type 2 diabetes. Methods: This cross-sectional study was conducted among 339 type 2 diabetic patients. Anthropometric indices, blood pressure, and biochemical tests were evaluated. A validated and reliable semi-quantitative food frequency questionnaire (FFQ) was used to assess dietary intake. Nordic diet scores were calculated based on median intakes of six food groups. Results: Body mass index (BMI) was higher among participants who were in the lowest tertile of adherence to the Nordic diet (P=0.006). There was a significant association between socioeconomic status (SES) and adherence to the Nordic diet (P<0.0001). Participants who were in the top category of adherence to the diet had significantly lower levels of aspartate aminotransferase (AST) (P<0.0001). There was a significant inverse association between adherence to the Nordic diet and low density lipoprotein (LDL) levels (odds ratio [OR]=0.29 95% CI: 0.09, 0.91, P=0.025), high systolic blood pressure (SBP) levels (OR=0.35 95% CI=0.17-0.74, P=0.015), and risk of obesity (OR=0.25 95% CI: 0.10, 0.63, P=0.03). Conclusion: Results suggest that adherence to the Nordic diet is associated with reductions in the prevalence of obesity, LDL levels and blood pressure among type 2 diabetic patients. However, additional studies are needed to confirm these findings.

Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9–18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials.

The effect of curcumin derivatives on the nuclear factor-κB expression in mice with hepatic fibrosis

Objective To investigate the therapeutic effects and mechanisms of curcumin derivatives C66 treatment on hepatic fibrosis. Methods Thirty three C57BL/6J mice were randomly divided into 3 groups: normal control group, model control group and curcumin derivatives C66 treatment group. Nine mice in normal control group were fed with water and food. Hepatic fibrosis model was induced in 24 mice by intraperitoneal injection of 40% carbon tetrachloride at a dose of 4 mL/kg for the first time, followed by 2 mL/kg twice a week for 6 weeks. At week 6, 6 mice were randomly selected to perform pathological examination to evaluate whether the hepatic fibrosis were successfully induced. Mice with hepatic fibrosis were randomized into model control group and curcumin derivatives C66 treatment group with 9 mice in each group. From week 6 on, mice in the treatment group were lavaged with curcumin derivatives C66 at a dosage of 10 mg·/(kg·d). The rest mice were administered with equivalent dosage of 0.5% carboxymethylcellulose sodium. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver hydroxyproline (Hyp) contents were detected, and the semi-quantitative analysis of liver fibrosis was performed by pathological examination in hepatic tissue by hematoxylin and eosin (HE) and Masson staining. The expressions of collagen Ⅰ, α-smooth muscle actin (α-SMA) mRNA and collagen Ⅰ, α-SMA, nuclear factor-kappa B p65 (NF-κB p65), inhibitor kappa B alpha (IκBα) protein in each group were detected by quantitative real-time polymerase chain reaction (RT-PCR) and Western blot. Data were analyzed with one-way ANOVA analysis. Results The serum levels of ALT and AST in model control group, C66 treatment group and normal control group were (202.71±19.66) U/L, (233.42±23.97) U/L; (102.00±11.04) U/L, (120.87±13.83)U/L; (36.66±6.37) U/L and (43.33±8.08)U/L, respectively. The differences between model and normal control group were both significant (t=23.96 and 22.39, respectively; both P<0.05). The C66 treatment group showed significantly lower levels of serum ALT and AST in contrast with model control group (t =11.56 and 10.52, respectively; both P<0.05). Compared to the model control group, hepatic Hyp contents in normal control group and C66 treatment group were significantly different (t=17.50, P<0.05; t=11.45, P<0.05). Collagen Ⅰand α-SMA mRNA expressions in C66 treatment group were remarkably lower in contrast with that in model control group (t=7.23 and 7.95, respectively; both P<0.05). Protein levels of Collagen Ⅰ, α-SMA and NF-κB p65 decreased in C66 treatment group, while IκBα increased significantly (all P<0.05). Conclusion The application of C66 can contribute to the regression of liver fibrosis and the mechanism may rely on the regulation of NF-κB expression. Key words: Liver cirrhosis; Curcumin derivative; NF-kappa B; IκBα; C57BL/6J mice

Association of aspartate aminotransferase with mortality in hemodialysis patients.

Liver disease is a common comorbid condition in maintenance hemodialysis (MHD) patients and may be associated with poor survival. The relationship between aspartate aminotransferase (AST) and survival has not yet been addressed in these patients. We hypothesized that higher AST level is associated with higher death risk in MHD patients. A 5-year (January 2007-December 2011) cohort of 109 718 MHD patients was studied in the USA in dialysis clinics where AST was measured in at least 50% of all outpatients in the baseline calendar quarter. Survival models were adjusted for demographic variables, and available clinical and laboratory surrogates of malnutrition-inflammation complex, and cubic survival splines were plotted. A linear association existed between baseline serum AST levels and mortality. Increasing AST of >20 IU/L was incrementally and almost linearly associated with higher death risk at all levels of adjustment. In fully adjusted models, AST levels of ≥40 IU/L were associated with the highest risk of mortality (hazard ratio: 1.46, 95% CI: 1.38-1.54). Low AST levels (<15 IU/L) were associated with increased death risk only in fully adjusted models examining hepatitis C virus-positive patients. Higher AST level of >20 IU/L is incrementally associated with higher mortality in MHD patients whereas AST in the 15-20 IU/L range is associated with the greatest survival. These findings suggest that the assessment of liver function and improving liver disease may confer survival benefit to MHD patients.

비타민 C 투여는 간 부분절제술에 의한 간 재생을 촉진 시킴

비타민 C는 신진대사에 연관되어 있으며 특히 항산화 기능을 가지고 있다. 본 연구에서는 생체에서 비타민 C를 합성할 수 없는 SMP 30 녹아웃 마우스에 간 절제술을 시행하여 간 재생에서 비타민 C의 역할을 관찰하였다. 간 절제술은 마우스 중간엽 및 좌엽을 제거한 부분절제술을 수행하였다. 마우스는 간 절제술 후 비타민 C를 투여한 군(KV)와 비타민 C를 투여하지 않는 군(KO)로 나누어서 비타민 C의 효과를 관찰하였다. 결과 비타민 C를 투여한 KV 마우스의 간 회복이 투여하지 않는 KO 마우스에 비해 촉진되었다. KV 마우스의 혈액에서 관찰된 간소상 지표인 아스파르타산 아미노전달효소 및 간 손상 정도가 KO 마우스에 비해 낮게 관찰되었다. KV 마우스에서는 HGF와 c-Met에 의해서 TGF-베타 수용체 신호전달계가 활성화되고 세포주기 조절인자인 cyclin D1과 PCNA의 발현이 빠르게 증가되었다. 반면 KO 마우스에서는 활성화 되지 않았다. 또한 ERK와 GSK-3&#x3B2; 단백질의 활성화가 관찰되었으며 세포분열 간세포들의 유의적인 증가가 관찰되었다. 그리고 KV 마우스에서는 혈중 알부민의 농도가 높은 것으로 확인되었다. 따라서 본 실험결과는 SMP 30 결핍 마우스에서 비타민 C 투여는 간 재생시스템의 활성화와 이에 따른 빠른 회복을 초래한다. The capacity for liver regeneration involves a variety of nutritional factors. Vitamin C has multiple metabolic and antioxidant functions. In this study, we investigated the role of vitamin C in liver regeneration following hepatectomy in senescence marker protein (SMP)-30 knockout (KO) mice. Partial hepatectomy was performed by resecting the median and left lateral lobes of mice. Vitamin C accelerated liver recovery in SMP30 KO mice treated with vitamin C (KV). The livers of the KV mice exhibited lower levels of aspartate aminotransferase and lower injury than those of the KO mice. Increased type II transforming growth factor-&#x3B2; receptor (TGF-&#x3B2;RII)-mediated regeneration signaling was accompanied by HGF and cMet in the KV but not the KO mice. Consistent with this, the expression of cell cycle regulatory proteins, including cyclin D1 and proliferating cell nuclear antigen (PCNA), increased rapidly in the KV mice. Enhanced activation of ERK and GSK-3&#x3B2; proteins and a significantly increased number of binuclear hepatocytes were also detected in the livers of the KV mice. Moreover, the KV mice synthesized the highest levels of albumin. These data suggest that treating SMP30 knockout mice with vitamin C resulted in earlier recovery and liver regeneration by activation of the regeneration system.

Omega-3 Fatty Acids Therapy in Children with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

To evaluate the efficacy and safety of omega-3 fatty acid supplementation in children with nonalcoholic fatty liver disease (NAFLD). Overweight/obese children with NAFLD (n = 76; median age, 13 years; IQR, 11.1-15.2 years) were eligible to participate in the study. The diagnosis of NAFLD was based on elevated alanine aminotransferase (ALT) to ≥ 30% of the upper limit of normal (ULN) and liver hyperechogenicity on ultrasound. Patients were randomized to receive omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid, 450-1300 mg/day) or placebo (omega-6 sunflower oil). The primary outcome was the number of patients who demonstrated decreased ALT activity by ≥ 0.3 times the ULN. Secondary outcomes included alterations in liver function tests, liver hyperechogenicity, insulin resistance, and other metabolic markers after 6 months of intervention. Out of 76 enrolled patients, 64 completed the trial and were analyzed. After 6 months, we found no significant differences between the omega-3 and placebo groups in the number of patients with decreased ALT by ≥ 0.3 times the ULN (24 vs 23) or in median (IQR) ALT activity (48.5 [31-62] U/L vs 39 [27-55] U/L), liver hyperechogenicity, insulin resistance, or serum lipid levels. However, patients in the omega-3 group had lower levels of aspartate aminotransferase (28 [25-36] U/L vs 39 [27-55] U/L; P = .04) and gamma-glutamyl transpeptidase (26 [17.5-36.5] U/L vs 35 [22-52] U/L; P = .04), and significantly higher levels of adiponectin. Omega-3 fatty acid supplementation did not increase the number of patients with decreased ALT levels and it did not affect liver steatosis on ultrasound, but it improved aspartate aminotransferase and gamma-glutamyl transpeptidase levels in children with NAFLD compared with placebo. Registered with ClinicalTrials.gov: NCT01547910.