Altered Liver Function Research Articles

Liver function and serum amylase alterations following laparoscopic and open cholecystectomy and its significance

Background: Gall stone disease is the commonest gastro intestinal disease requiring surgical intervention, laparoscopic cholecystectomy (LC) which has replaced open cholecystectomy (OC). LC has more advantages over OC but has few drawback such as CO2 pneumoperitoneum leading to altered liver functions. The study was done with the aim to compare liver function tests in patients undergoing LC & OC and to compare these values in two groups preoperatively and postoperatively at 24 hrs, 48 hrs, 72 hrs.Methods: A total of 151 patients were admitted with cholelithiasis, out of which 72 patients underwent surgery between January 2018 to January 2019. Patients were selected by block randomization method into 2 groups containing 28 in each (Group 1- OC and Group 2- LC). SGPT, SGOT, LDH, TB, DB, IB, ALP and S. amylase were studied pre-operatively and at intervals of 24 hrs, 48 hrs, 72 hrs postoperatively. Comparison was made between both groups.Results: Pre and postoperatively stage, the level of LFT in Group 1 and Group 2 were similar except IB, which was significantly high in Group 1. At 24 hrs the difference in TB, DB, SGPT and S. amylase were statistically significant (p<0.05) between the groups. At 48 hrs difference between Group 1 and Group 2 in TB, DB, SGOT and SGPT were statistically significant (p<0.05). At 72 hrs difference between Group 1 and Group 2 in only SGPT was statistically significant (p<0.05).Conclusions: Cholecystectomy (OC and LC) lead to transient but reversible significant hepatic enzymes alterations. These alterations are self limited and return to reference values within 10 days of operation. The cause of alteration might be liver tractions, electrocoagulation’s and manipulation of duct.

Altered Expression and Function of Hepatic Transporters in a Rodent Model of Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common form of inherited polycystic kidney disease (PKD) and is a leading cause of kidney failure. Fluid-filled cysts develop in the kidneys of patients with ADPKD, and cysts often form in their liver and other organs. Previous data have shown that bile acids are increased in the liver of polycystic kidney (PCK) rats, a rodent model of PKD; these changes may be associated with alterations in liver transporter expression and function. However, the impact of PKD on hepatic transporters has not been characterized. Therefore, this preclinical study was designed to investigate hepatic transporter expression and function in PCK compared with wild-type (WT) Sprague-Dawley rats. Transporter gene expression was measured by quantitative polymerase chain reaction, and protein levels were quantified by Western blot and liquid chromatography-tandem mass spectroscopy (LC-MS/MS)-based proteomic analysis in rat livers. Transporter function was assessed in isolated perfused livers (IPLs), and biliary and hepatic total glutathione content was measured. Protein expression of Mrp2 and Oatp1a4 was decreased 3.0-fold and 2.9-fold, respectively, in PCK rat livers based on Western blot analysis. Proteomic analysis confirmed a decrease in Mrp2 and a decrease in Oatp1a1 expression (PCK/WT ratios, 0.368 ± 0.098 and 0.563 ± 0.038, respectively; mean ± S.D.). The biliary excretion of 5(6)-carboxy-2',7'-dichlorofluorescein, a substrate of Oatp1a1, Mrp2, and Mrp3, was decreased 28-fold in PCK compared with WT rat IPLs. Total glutathione was significantly reduced in the bile of PCK rats. Differences in hepatic transporter expression and function may contribute to altered disposition of Mrp2 and Oatp substrates in PKD.

Methylsulfonylmethane for treatment of low back pain: A safety analysis of a randomized, controlled trial

ObjectiveTo ensure that 16 weeks of methylsulfonylmethane (MSM) does not cause adverse effects in patients with the musculoskeletal disorders of osteoarthritis and back pain. DesignWe carried out a subgroup analysis on data from a randomized, double-blind, placebo-controlled trial, “The use of Methylsulfonylmethane (MSM) in the treatment of low back pain,” to determine the safety of taking 6 g daily of MSM (OptiMSM®, Bergstrom Nutrition). We monitored metabolic parameters to determine whether MSM altered hematologic, liver or kidney function. We also monitored physiologic parameters of blood pressure and weight. SettingFamily Medicine Residency, Mike O’Callaghan Military Medical Center. Main outcome measuresMetabolic parameters as measured by hematologic function - white blood cells (WBC), platelets, hemoglobin (Hb), glucose; liver function as measured by - total bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Physiologic parameters as measured by weight, diastolic (DBP) and systolic blood pressure (SBP); kidney function as measured by creatinine. ResultsAnalysis of outcome measures showed no significant difference between MSM and placebo (p < 0.05) safety values. ConclusionMSM has no effects on WBC, platelets, Hb, total bilirubin, AST, ALT, creatinine weight, DBP, or SBP in this study.

Cinnamomum cassia exhibits antileishmanial activity against Leishmania donovani infection in vitro and in vivo.

BackgroundThere is a pressing need for drug discovery against visceral leishmaniasis, a life-threatening protozoal infection, as the available chemotherapy is antiquated and not bereft of side effects. Plants as alternate drug resources has rewarded mankind in the past and aimed in this direction, we investigated the antileishmanial potential of Cinnamomum cassia.MethodologyDichloromethane, ethanolic and aqueous fractions of C. cassia bark, prepared by sequential extraction, were appraised for their anti-promastigote activity along with apoptosis-inducing potential. The most potent, C. cassia dichloromethane fraction (CBD) was evaluated for anti-amastigote efficacy in infected macrophages and nitric oxide (NO) production studied. The in vivo antileishmanial efficacy was assessed in L. donovani infected BALB/c mice and hamsters and various correlates of host protective immunity ascertained. Toxicity profile of CBD was investigated in vitro against peritoneal macrophages and in vivo via alterations in liver and kidney functions. The plant secondary metabolites present in CBD were identified by gas chromatography-mass spectroscopy (GC-MS).Principal findingsCBD displayed significant anti-promastigote activity with 50% inhibitory concentration (IC50) of 33.6 μg ml-1 that was mediated via apoptosis. This was evidenced by mitochondrial membrane depolarization, increased proportion of cells in sub-G0-G1 phase, ROS production, PS externalization and DNA fragmentation (TUNEL assay). CBD also inhibited intracellular amastigote proliferation (IC50 14.06 μg ml-1) independent of NO production. The in vivo protection achieved was 80.91% (liver) and 82.92% (spleen) in mice and 75.61% (liver) and 78.93% (spleen) in hamsters indicating its profound therapeutic efficacy. CBD exhibited direct antileishmanial activity, as it did not specifically induce a T helper type (Th)-1-polarized mileu in cured hosts. This was evidenced by insignificant modulation of NO production, lymphoproliferation, DTH (delayed type hypersensitivity), serum IgG2a and IgG1 levels and production of Th2 cytokines (IL-4 and IL-10) along with restoration of pro-inflammatory Th1 cytokines (INF-γ, IL-12p70) to the normal range. CBD was devoid of any toxicity in vitro as well as in vivo. The chemical constituents, cinnamaldehyde and its derivatives present in CBD may have imparted the observed antileishmanial effect.ConclusionsOur study highlights the profound antileishmanial efficacy of C. cassia bark DCM fraction and merits its further exploration as a source of safe and effective antieishmanial compounds.

Altered development of fetal liver perfusion in pregnancies with pregestational diabetes.

BackgroundPregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control.MethodsIn a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24–36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed.ResultsThe umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C.ConclusionsIn spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition

Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B=520.895; p=0.010), digestive anatomy type 3 (B=75.612; p=0.025), citrulline level (B=3.428; p=0.040), parenteral olive oil intake (B=-0.570; p=0.043), and oral intake (B=182.227; p=0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.

Avian Liver: The Forgotten Organ.

Simple SummaryThe liver is a multi-purpose organ, with involvement in bile secretion, and lipid, carbohydrate and protein metabolism, as well as a number of other metabolic functions. This organ can adapt easily to changes in feed and the environment. Being at the centre of a number of digestive, metabolic and productive activities, it is essential to have a better understanding of this organ and the factors affecting liver functionality.Despite having huge responsibilities in avian species, published reports on the influence of dietary factors and other possible constraints on the size, development and function of liver are limited. Consideration of the factors that could influence and alter liver function is therefore of critical relevance. In the current review, aspects of liver structure and function, and the influence of feed restriction, anti-nutritional factors, structural components and feed additives on liver are discussed. Effects of feed technology techniques such as thermal treatment and pelleting, feed particle size and whole grain feeding on the liver are also reviewed. A discussion of lipogenesis and lipid storage in poultry is presented to provide a better understanding and to differentiate the normal pathways of lipid metabolism from abnormal (i.e., disordered) pathways. The liver is the main site of fat synthesis in poultry, but under certain conditions, excessive fat can accumulate in the liver and cause problems. Factors contributing to the fatty liver syndrome are also examined.

Ameliorative effect of zinc oxide nanoparticles against potassium bromate-mediated toxicity in Swiss albino rats.

Potassium bromate (PB) is a commonly used food additive, a prominent water disinfection by-product, and a class IIB carcinogen. It exerts a various degree of toxicity depending on its dose and exposure duration consumed with food and water in the living organisms. The present investigation aims to demonstrate the protective efficacy of zinc oxide nanoparticles (ZnO NPs) derived from Ochradenus arabicus (OA) leaf extract by green technology in PB-challenged Swiss albino rats. The rodents were randomly distributed, under the lab-standardized treatment strategy, into the following six treatment groups: control (group I), PB alone (group II), ZnO alone (group III), ZnO NP alone (group IV), PB + ZnO (group V), and PB + ZnO NPs (group VI). The rats were sacrificed after completion of the treatment, and their blood and liver samples were collected for further analysis. Group II showed extensive toxic effects with altered liver function markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, glutathione-S-transferase, and thioredoxin reductase) and compromised redox status (SOD, CAT, GR, GPx, GSH, MDA, and total carbonyl content). The histopathological analysis and comet assay further supported the biochemical results of the same group. Besides, group III also showed moderate toxicity evidenced by an alteration in most of the studied parameters while group IV demonstrated mild toxicity after biochemical analysis indicating the excellent biocompatibility of the NPs. However, group VI exhibited attenuation of the PB-induced toxic insults to a significant level as compared to group II, whereas group V failed to show similar improvement in the studied parameters. All these findings entail that the ZnO NPs prepared by green synthesis have significant ameliorative property against PB-induced toxicity in vivo. Moreover, administration of the NPs improved the overall health of the treated animals profoundly. Hence, these NPs have significant therapeutic potential against the toxic effects of PB and similar compounds in vivo, and they are suitable to be used at the clinical and industrial levels.

Noninvasive Evaluation of Liver Function in Morbidly Obese Patients.

Background More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. Methods In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic capacity of cytochrome P450 1A2). Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score (NAS). NASH clinical score was additionally calculated from laboratory and clinical parameters. Results Median liver function capacity was 286 (IQR = 141) μg/kg/h. 27% of patients were histologically categorized as definite NASH, 39% as borderline, and 34% as not NASH. A significant correlation was observed between liver function capacity and NAS (r = −0.492; p < 0.001). The sensitivity and specificity of the LiMAx® test to distinguish between definite NASH and not NASH were 85.2% and 82.9% (AUROC 0.859), respectively. According to the NASH clinical scoring system, 14% were classified as low risk, 31% as intermediate, 26% as high, and 29% as very high risk. Liver function capacity is also significantly correlated with the NASH clinical scoring system (r = −0.411; p < 0.001). Conclusions Obese patients show a diminished liver function capacity, especially those suffering from type 2 diabetes. The liver function capacity correlates with histological and clinical scoring systems. The LiMAx® test may be a valuable tool for noninvasive screening for NASH in obese patients.

Paternal Programming of Liver Function and Lipid Profile Induced by a Paternal Pre-Conceptional Unhealthy Diet: Potential Association with Altered Gut Microbiome Composition

Background/Aims: Paternal exposure to adverse environmental conditions can act on offspring’s phenotype and influence offspring’s later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring’s (F2) liver function and gut microbiome composition. Methods: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). Results: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. Conclusion: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.

Uric Acid and Its Correlation with Various Metabolic Parameters: A Population-Based Study.

Introduction:Uric acid, apparently an inert waste product, was found to have association with various metabolic disorders. The data regarding prevalence of serum uric acid (SUA) abnormalities and its correlation with other anthropo-metabolic parameters, however, are scanty.Materials and Methods:In all, 405 participants from a rural area were investigated for various metabolic parameters including uric acid. SUA level was evaluated for having any correlation with other anthropometric and metabolic disorders like obesity, dyslipidemia, metabolic syndrome (MetS), hypertension, calcium and vitamin D abnormalities, liver function, and glycemic alterations. Lean MetS is defined as those having waist criteria below the region specific waist criteria and even then satisfying the definition of MetS as per the National Cholesterol Education Program (NCEP) ATP-III (Adult Treatment Panel) criteria.Results:The mean uric acid was 4.2 mg/dL (±1.35), with 4.9 mg/dL (±1.28) for males and 3.7 mg/dL (±1.14) for females. Thirteen of 405 people (3.2%) found to have uric acid level of more than 7.0 mg/dL, and eight people out of 405 (2.0%) had hypouricemia. SUA showed correlation with age, blood pressure, and the anthropometric parameters for obesity, for example, weight, body mass index, waist circumference, waist hip ratio, waist height ratio, fasting insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. However, fasting glucose, calcium, phosphate, 25-hydroxy vitamin D3, and iPTH did not show any correlation with the SUA level. Compared to the healthy population, SUA level was elevated in MetS as defined by International Diabetes Federation (IDF) criteria. However, the SUA in healthy population was not significantly different from the Lean MetS, and SUA of Lean MetS was not significantly different from Obese MetS.Conclusion:SUA is elevated in MetS compared to the normal population. However, SUA in Lean MetS is not different from Obese MetS.

Effect of quercetin on oxidative stress and liver function in beta-thalassemia major patients receiving desferrioxamine: A double-blind randomized clinical trial.

Background:Blood transfusion therapy is lifesaving for beta-thalassemia major patients, yet it indirectly causes complications such as oxidative stress and liver dysfunction. In the present study, we investigated the effect of quercetin supplementation on oxidative stress and liver function in beta-thalassemia major patients.Materials and Methods:In this double-blind clinical trial, 84 beta-thalassemia patients who received desferrioxamine (DFO) were randomly assigned to two groups; the treatment group received 500 mg quercetin tablet daily for 12 weeks, and the control group received placebo. In addition to demographic and anthropometric assessment, malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were biochemically assessed to detect the effect of quercetin on oxidative stress and liver function, respectively. The data were analyzed using SPSS 21. P < 0.05 was considered statistically significant.Results:Before adjusting for confounding variables, within-group comparison showed that quercetin supplementation reduced ALT (P < 0.001) and TAC (P < 0.001) significantly. Between-group comparison using analysis of covariance analysis though showed that quercetin could significantly reduce ALT (P = 0.002), but there was an insignificant increase in SOD and TAC, and insignificant decrease in GPx, MDA, AST, and ALP (P > 0.05).Conclusion:According to our results, consumption of 500 mg quercetin supplement daily for 3 months along with DFO treatment might be able to alter liver function, but not the oxidative stress in beta-thalassemia major patients.

Sub-chronic oral propylene glycol administration sustained normal liver function and histology: A suitable alternative vehicle for hydrophobic test-compounds

Background: An undocumented controversy exists on the suitability/unsuitability of propylene glycol as a solvent or vehicle for hydrophobic test-compounds in animal experimentation(s). This is partly due to the paucity of evidence that aims to probe its histological effects beyond Hematoxylin and Eosin assessment. Objective: To determine the potential suitability/unsuitability of oral propylene glycol as a vehicle for hydrophobic test-compounds by assessing its histological and biochemical effects in female Wistar rats. Methods: The study recruited 10 Wistar rats which were divided into two groups of five rats each as follows: Group 1 received distilled water (2 ml/kg, po) for four consecutive weeks while group 2 received propylene glycol (2 ml/kg, po) for the same period of time. Results: Propylene glycol caused no alteration in liver function as indicated by the plasma levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and hepatic total protein level when both groups were compared (p &gt; 0.05). No significant difference between both groups was also recorded in the oxidative stress status (glutathione and catalase) of their liver homogenates. Histological examinations using Hematoxylin and Eosin (H&amp;E) (general histoarchitecture) as well as special stains such as Gordon and Sweet (reticular fiber formation), Masson’s trichrome (collagen fibers), and periodic acid-Schiff (glycogen content) did not reveal any feature of pathology. Quantification analyses of their liver sections, using image J, further revealed no significant difference (p &gt; 0.05) in their histoarchitectural features. Conclusion: Propylene glycol is a suitable alternative vehicle for hydrophobic test-compounds in experimental studies, as its sub-chronic administration sustained normal liver function and histology

Identification of Piecemeal Degranulation and Vesicular Transport of MBP-1 in Liver-Infiltrating Mouse Eosinophils During Acute Experimental Schistosoma mansoni Infection.

Eosinophils have been long associated with helminthic infections, although their functions in these diseases remain unclear. During schistosomiasis caused by the trematode Schistosoma mansoni, eosinophils are specifically recruited and migrate to sites of granulomatous responses where they degranulate. However, little is known about the mechanisms of eosinophil secretion during this disease. Here, we investigated the degranulation patterns, including the cellular mechanisms of major basic protein-1 (MBP-1) release, from inflammatory eosinophils in a mouse model of S. mansoni infection (acute phase). Fragments of the liver, a major target organ of this disease, were processed for histologic analyses (whole slide imaging), conventional transmission electron microscopy (TEM), and immunonanogold EM using a pre-embedding approach for precise localization of major basic protein 1 (MBP-1), a typical cationic protein stored pre-synthesized in eosinophil secretory (specific) granules. A well-characterized granulomatous inflammatory response with a high number of infiltrating eosinophils surrounding S. mansoni eggs was observed in the livers of infected mice. Moreover, significant elevations in the levels of plasma Th2 cytokines (IL-4, IL-13, and IL-10) and serum enzymes (alanine aminotransferase and aspartate aminotransferase) reflecting altered liver function were detected in response to the infection. TEM quantitative analyses revealed that while 19.1% of eosinophils were intact, most of them showed distinct degranulation processes: cytolysis (13.0%), classical and/or compound exocytosis identified by granule fusions (1.5%), and mainly piecemeal degranulation (PMD) (66.4%), which is mediated by vesicular trafficking. Immunonanogold EM showed a consistent labeling for MBP-1 associated with secretory granules. Most MBP-1-positive granules had PMD features (79.0 ± 4.8%). MBP-1 was also present extracellularly and on vesicles distributed in the cytoplasm and attached to/surrounding the surface of emptying granules. Our data demonstrated that liver-infiltrating mouse eosinophils are able to degranulate through different secretory processes during acute experimental S. mansoni infections with PMD being the predominant mechanism of eosinophil secretion. This means that a selective secretion of MBP-1 is occurring. Moreover, our study demonstrates, for the first time, a vesicular trafficking of MBP-1 within mouse eosinophils elicited by a helminth infection. Vesicle-mediated secretion of MBP-1 may be relevant for the rapid release of small concentrations of MBP-1 under cell activation.

Identification of changes in serum analytes and possible metabolic pathways associated with canine obesity-related metabolic dysfunction

The main objective of this study was to identify analytes that could change and that could help to clarify the metabolic and physiopathological changes related to canine obesity-related metabolic dysfunction (ORMD). For this, serum from 35 overweight/obese dogs, with and without ORMD, was submitted to a comprehensive panel of biochemistry analysis, a gel-free tandem mass tag isobaric label-based proteomic analysis, and, finally, selected proteins were used as a starting point for creating a protein interaction network.Dogs with ORMD showed significantly higher serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (ALP), Ca, total proteins, albumin, total cholesterol, triglycerides, glucose, and butyrylcholinesterase (BChE) activity in comparison with dogs without ORMD. Proteomic analysis revealed that 23 proteins related to lipid metabolism, the complement factor system, cellular adhesion and functionality, inflammation, and coagulation were altered in dogs with ORMD. Finally, the obtained protein interaction network highlighted that the central term of this network was the negative regulation of the immune response. These data suggest that canine ORMD is associated with changes in analytes that reflect altered lipid metabolism, and liver and immune function impairment and suggests the potential for a prothrombotic state and lung function alterations.

The changes and prognostic value of liver function in young adults with severe burn: A retrospective observational study.

To analyze the changes in liver functions and the relationship between alterations in liver function and mortality risk in young adults with third-degree burn wounds on over 90% of the total body surface area (TBSA).A total of 23 fatally burned factory workers in an inflammable dust explosion and fire were enrolled from 2 intensive care units. Clinical data, particularly the laboratory tests for liver function, were retrospectively analyzed and compared between the survivor and non-survivor groups.Compared to survivors, non-survivors had significantly higher total bilirubin (TBIL), glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase, alkaline phosphatase, prothrombin time, and activated partial thromboplastin time (APTT) at the terminal point of this study (P <.05). In addition, the peak values of TBIL, GPT, and longer APTT were higher in non-survivors than in survivors during hospital course, and the peak values of TBIL was one of major prognostic factors for mortality risk. Furthermore, at the first 2 weeks, the cumulative survival rates were significantly lower in patients with liver dysfunction than those without liver dysfunction (P <.01).Our findings show that the great changes in liver function occurred in first 2 weeks after severe burns. Liver dysfunction may have an effect on clinical outcomes of post-burn. Measures to protect liver function and prevent from deterioration could be beneficial in improvement survival rate, especially during the first 2 weeks.

Effect of hydration with Ringer's solution submitted to magnetic field in an experimental model of hepatic ischemia-reperfusion injury in rats

Purpose: To evaluate the effect of hydration with Ringer's solution submitted to magnetic field in experimental model of hepatic ischemia/reperfusion in rats. Methods: Wistar rats weighing 389.58±46.88g were randomly allocated into 2 groups: control group (n = 6) - Hepatic ischemia/reperfusion and hydration with Ringer's solution; and test group (n = 6) - Hepatic ischemia/reperfusion and hydration with Ringer submitted to magnetic field of 20 mT during 2 hours. After anesthesia with ketamine 70 mg/kg and xylazine 7 mg/kg i.p., the animals were weighed and operated by aseptic technique. The ischemia of the median and left liver lobes was induced for 30 minutes using a vascular clip. Then, i.v. hydration with 3 ml of Ringer in the control group, and 3 ml of magnetized Ringer’s solution in the test group. After 24 hours, blood sample and fragment of the left liver lobe were collected for the determination of AST, ALT, ALP and albumin levels, and histopathological examination. Results: There was no significant difference in comparison of the rats weight loss, biochemical measurements and histopathological scores between the groups (p&gt;0.05). Conclusion: The hydration with Ringer's solution submitted to magnetic field after hepatic ischemia/reperfusion in rats did not alter liver function tests neither histopathological scores, comparing with the control group.

Assessment of chemokine and cytokine signatures in patients with dengue infection: A hospital-based study in Kolkata, India

Dengue fever is an acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations. Descriptions of the role of circulating immune modulators such as cytokines or chemokines in dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from West Bengal, eastern India, with respect to clinical profile and pro-inflammatory and inflammatory cytokines. We evaluated the profile of both inflammatory and anti-inflammatory cytokines (IFNγ, IL6, IL10, IL12 and TGFβ) and chemokines (IL8, CXCL9, CXCL10 and RANTES) in 100 hospitalized NS1/IgM confirmed Dengue patients during the epidemic in West Bengal during 2017. Additionally, all necessary blood investigations of the study subjects were performed. The patients mostly hailed from Kolkata, followed by Nadia, 24 Parganas (North and South), Murshidabad and Midnapore. The most common presentations apart from fever and bodyache were gastrointestinal symptoms. An elevated levels of cytokines IL6 and IL10 chemokine IL8 and CXCL10 along with decreased RANTES were found in the patients with Severe Dengue as compared to mild forms of dengue (p < 0.0001) during 3–6 days of infections. A significant association was obtained between most of cytokine and increased SGPT, haematocrit, albumin and decreased platelet count, whereas a negative correlation with the level of RANTES to haematocrit (r=-0.220 with p = 0.029) was found in severe dengue cases with altered liver function parameters. This is the first study demonstrating cytokine and chemokine association with dengue severity from the eastern part of India. Taken together, this study demonstrated that the altered expression levels of IL6, IL10, IL8, CXCL10 and RANTES had significant associations with dengue severity parameters.

γ-Oryzanol supplementation modifies the inflammatory and oxidative response in fulminant hepatic failure in mice

The lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced hepatotoxicity is a classical model to elucidate the mechanisms and explore potential therapeutic drugs for fulminant hepatic failure (FHF). γ-Oryzanol (γ-ORY) has been showed to possess both antioxidant and anti-inflammatory properties in several pathological models. However, it remains unclear whether γ-ORY could protect against LPS/D-GalN-induced hepatotoxicity. Thus, the aim of the current study was to evaluate the effects of γ-ORY supplementation (for 7 consecutive days) in LPS/D-GalN-induced FHF in mice. One hour after the last supplementation with γ-ORY, the animals received LPS/D-GalN (50 and 500 mg/kg, respectively; i.p.). Twenty-four hours after LPS/D-GalN administration, biochemical assays were performed. LPS/D-GalN administration caused severe histological damage in the liver, such as vascular congestion and megalocytosis, as well as elicited hepatic failure. LPS/D-GalN treatment also caused alterations in liver function, increased levels of oxidative stress and inflammatory markers. In contrast, γ-ORY supplementation protected against histological, oxidative and inflammatory alterations induced by LPS/D-GalN exposure. Collectively, our data supports the notion that both oxidative stress and inflammatory responses are two key pathogenic factors that contribute to LPS/D-GaIN-mediated FHF. Due to its antioxidant and anti-inflammatory actions, our study indicates γ-ORY as a putative pharmacological option to prevent LPS/D-GalN-induced hepatotoxicity.

Periodontitis causes abnormalities in the liver of rats.

Periodontitis not only causes injury to the periodontium, but also damages other tissues such as: articulate, renal, cardiac, and hepatic. The objective of this study was to investigate periodontitis induced alterations in liver function and structure using an experimental model. Twenty female rats (Rattus norvegicus) were allocated into two groups: control and periodontitis. Gingival bleeding index and oxidative stress parameters and specific circulating biomarkers were measured. Immunohistochemistry was carried out using alkaline phosphatase (AlkP) staining of the liver. Hepatic tissues, cytokines, and lipid contents were measured. Histopathologic evaluation of the liver was carried out using light and electron microscopy. Liver histopathologic and immunohistochemistry assessment showed increase in steatosis score, and presence of binucleate hepatocytes and positive cells for AlkP in periodontitis versus control group. Ultrastructural evaluation showed significant increase in size and number of lipid droplets (LD), distance between the cisterns of rough endoplasmic reticulum (RER), mitochondria size, foamy cytoplasm, and glycogen accumulation in the liver of the periodontitis group compared with the control group. In addition, plasma levels of AlkP, high-density lipoprotein (HDL), triglycerides, and total cholesterol were also changed. Experimental periodontitis caused immunohistochemistry, histopathologic, ultrastructural, oxidative, and biochemical changes in the liver of rats.