Hepatic Transaminase Levels Research Articles

Supplementation of the Flavonoid Myricitrin Attenuates the Adverse Metabolic Effects of Long-Term Consumption of a High-Fat Diet in Mice.

The flavonoid myricitrin exhibits various pharmacological and physiological effects. However, studies on the effects of myricitrin on obesity are limited. We hypothesized that dietary myricitrin would attenuate the adiposity and metabolic dysfunction that occur in obesity. To test this hypothesis, mice were randomly fed a high-fat diet (HFD) or HFD supplemented with myricitrin for 16 weeks. Myricitrin significantly reduced white adipose tissue (WAT) mass, adipocyte size, and plasma leptin levels, and also attenuated dyslipidemia. These changes appeared to result from increased energy expenditure and activation of the carnitine acyltransferase (CPT) and β-oxidation in WAT. Expressions of the proinflammatory genes NF-κB, TLR2, MCP1, and TNF-α were also lower in the WAT of myricitrin-supplemented mice. Moreover, myricitrin markedly reduced hepatic triglyceride accumulation and plasma aspartate transaminase levels by increasing CPT activity and reducing fatty acid synthase activity in the liver. Myricitrin-supplemented mice also showed improved glucose tolerance, insulin sensitivity, and decreased hyperinsulinemia, along with decreased levels of circulating resistin. In conclusion, long-term consumption of a myricitrin-supplemented diet may effectively protect against HFD-induced obesity and related metabolic disorders.

Ceftriaxone Therapy of Bacterial Meningitis in Children

Twenty-nine children, age 3 months to 11 years, admitted with the clinical diagnosis of bacterial meningitis to the Department of Child Health, were included in a prospective treatment study of ceftriaxone (RocephinHoffmann- La Roche AG Bas/e, Switzerland). Ceftriaxone was used as the only antibiotic agent in single daily dose of 100 mg/kg body weight given intravenously for a minimum of 10 days. Of these 29 patients, 25 (86.2%) recovered, 3 (10.3%) died and 1 (3.4%) no respond to treatment. Among fatal cases, two patients had subdural empyema and one had a cerebral abscess. The microorganisms isolated from cerebrospinal fluid were: Streptococcus pneumoniae (5), Pseudomonas sp. (4), Proteus sp. (2), Salmonella typhi (1), Escherichia coli (1), Clostridium sp. (1), Pseudomonas aeruginosa (1), Staphylococcus aureus {1), and Streptococcus haemolyticus (1). In 12 patients (41,4%), organisms were not identified. The diagnosis was made based on clinical symptoms, Gram staining, cell count. ~!·tease, and protein in the CSF. In all patients, repeated spinal fluid cultures had no bacterial growth at 24 hours after initation of intravenous therapy. No evidence of clinical important drug toxicity was observed. Three p'Oiients, however, had lightly elevated hepatic transaminase levels, and one patient had rnild neutropenia. These clinical and bacteriological results suggested that ceftriaxone is reasonably safe and effective in the treatment of bacterial meningitis caused by the most common pediatric pathogens in Indonesian children over one month of age.

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study

BackgroundThe duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal...

Inhibiting Extracellular Cathepsin D Reduces Hepatic Steatosis in Sprague⁻Dawley Rats †.

Dietary and lifestyle changes are leading to an increased occurrence of non-alcoholic fatty liver disease (NAFLD). Using a hyperlipidemic murine model for non-alcoholic steatohepatitis (NASH), we have previously demonstrated that the lysosomal protease cathepsin D (CTSD) is involved with lipid dysregulation and inflammation. However, despite identifying CTSD as a major player in NAFLD pathogenesis, the specific role of extracellular CTSD in NAFLD has not yet been investigated. Given that inhibition of intracellular CTSD is highly unfavorable due to its fundamental physiological function, we here investigated the impact of a highly specific and potent small-molecule inhibitor of extracellular CTSD (CTD-002) in the context of NAFLD. Treatment of bone marrow-derived macrophages with CTD-002, and incubation of hepatic HepG2 cells with a conditioned medium derived from CTD-002-treated macrophages, resulted in reduced levels of inflammation and improved cholesterol metabolism. Treatment with CTD-002 improved hepatic steatosis in high fat diet-fed rats. Additionally, plasma levels of insulin and hepatic transaminases were significantly reduced upon CTD-002 administration. Collectively, our findings demonstrate for the first time that modulation of extracellular CTSD can serve as a novel therapeutic modality for NAFLD.

Omega-3 fatty acids are protective in hepatic ischemia reperfusion injury in the absence of GPR120 signaling

BackgroundA single dose of IV fish oil (FO) before hepatic ischemia reperfusion injury (HIRI) increases hepatocyte proliferation and reduces necrosis in wild type (WT) mice. It has been suggested that the GPR120 receptor on Kupffer cells mediates FO's ability to reduce HIRI. The purpose of this study was to determine whether GPR120 is required for FO to reduce HIRI. MethodsSixty-four (n = 8/group) adult male WT (C57BL/6) and GPR120 knockout (KO) mice received IV FO (1 g/kg) or saline 1 h prior to HIRI or sham operation. Mice were euthanized 24 h postoperatively for analysis of hepatic histology, NFκB activity, and serum alanine transaminase (ALT) levels. ResultsFO pretreated livers had less necrosis after HIRI than saline pretreated livers in both WT (mean ± SEM 25.9 ± 7.3% less, P = 0.007) and KO (36.6 ± 7.3% less, P < 0.0001) mice. There was no significant difference in percent necrosis between WT-FO and KO-FO groups. Sham groups demonstrated minimal necrosis (0–1.9%). Mean [95% CI] ALT after HIRI was significantly higher (P = 0.04) in WT-Saline mice (1604 U/L [751–3427]) compared to WT-FO (321 U/L [150–686]) but was not significantly higher in KO-Saline mice compared to KO-FO. There were no differences in ALT between WT-FO and KO-FO mice who underwent HIRI or between groups who underwent sham surgery. There were no differences in NFκB or IKKβ activation among groups as measured by Western blot analysis. ConclusionsIV FO pretreatment was able to reduce HIRI in GPR120 KO mice, suggesting the hepatoprotective effects of FO are not mediated by GPR120 alone.

Serelaxin (recombinant human relaxin-2) treatment affects the endogenous synthesis of long chain poly-unsaturated fatty acids and induces substantial alterations of lipidome and metabolome profiles in rat cardiac tissue

Background and Purpose: Recombinant human relaxin-2, serelaxin, is being proved as a novel drug with therapeutic efficacy in some cardiovascular diseases, especially heart failure, a disease whose physiopathology and course are firmly correlated with important alterations in cardiac metabolism. The aim of our present work was to investigate changes in the cardiac metabolome following relaxin-2 treatment.Experimental Approach: Sprague-Dawley rats were treated with human recombinant relaxin-2 using osmotic minipumps at a dose of 0.4 mg/kg/day for 2 weeks. Body composition was measured with a nuclear magnetic resonance imaging system seven days after surgery and on the final day of the experiment. The last two days of treatment, respiratory quotient, locomotor activity and energy expenditure were measured with a calorimetric system. The plasma levels of relaxin-2, total cholesterol, high- and low- density lipoproteins (HDL, LDL), triglycerides and the hepatic enzymes glutamic-pyruvic transaminase (GTP) and gamma-glutamyltransferase (GGT) levels were analyzed. The metabolic profiling of both atria from relaxin-2-treated and control rats was carried out using two separate ultra-high performance liquid chromatography (UHPLC)-Time of Flight-MS based platforms analyzing methanol and chloroform/methanol extracts combined with a UHPLC-single quadrupole-MS based platform used to analyze aminoacids and with a methanol/water extract platform that covered polar metabolites. Identified ion features in the methanol extract platform included fatty acids, acyl carnitines, bile acids, monoacylglycerophospholipids, monoetherglycerophospholipids, free sphingoid bases, and oxidized fatty acids. The chloroform / methanol extract platform provided coverage over glycerolipids, cholesterol esters, sphingolipids, diacylglycerophospholipids, and acyl-ether-glycerophospholipids. Gene expression levels of the adipokines adiponectin, leptin and nesfatin-1 in visceral adipose tissue and cardiac gene expression levels of key enzymes of desaturation and elongation of n-6 and n-3 PUFAs were assessed by Real Time-PCR.Key Results: Twenty-eight metabolites out of three hundred sixty-two were significantly altered by human relaxin-2. These included fifteen glycerophospholipids: three phosphatidylethanolamines (PE) and twelve phosphatidylcholines (PC); eight sphingolipids: three ceramides (Cer) and five sphingomyelins (SM); and also five aminoacids and one carboxylic acid. Interestingly, the majority of changes correspond to lipid classes, twelve of them polyunsaturated diacylglycerophosphatidylcholines with long acyl chains, containing mainly docosahexaenoic acid (22:6) and arachidonic acid (20:4). Atrial levels of Elovl5 (Elongation of very long chain fatty acids protein 5), Fads1 (Δ5-fatty acid desaturase) and Fads2 (Δ6-fatty acid desaturase), key enzymes of elongation and desaturation of n-6 and n-3 PUFAs like arachidonic acid and DHA, respectively, were significantly increased by relaxin-2 treatment. Atrial tissues from rats treated with relaxin-2 showed a significant increase in the mRNA levels of Srebf1, a transcription factor that activates the gene expression of Elovl5, Fads1 and Fads2.The treatment with relaxin-2 significantly decreased the visceral fat mRNA expression levels of adiponectin, leptin and nesfatin-1, adipokines known to exert an important influence on the regulation of cardiovascular function.Conclusion and Implications: Serelaxin (human recombinant relaxin-2) treatment induces significant changes in cardiac major components of the membrane lipid bilayer such as glycerophospholipids and sphingolipids, known to have structural roles but also very relevant regulatory effects in cardiac function. Serelaxin induced also modifications in several aminoacids of high influence in cardiac energy metabolism regulation. Our results highlight the need to further understand the role of relaxin-2 in the regulation of cardiac energy metabolism, in the context of the therapeutic strategies for the treatment of cardiometabolic pathologies as heart failure.

Evaluation of the effects of Ocimum basilicum essential oil in Nile tilapia diet: growth, biochemical, intestinal enzymes, haematology, lysozyme and antimicrobial challenges

Due to the intensification of tilapiculture, problems attributed to health of fish stocks have become more frequent. The objective of the present study was to evaluate growth, physiological responses and survival of Nile tilapia juveniles fed a diet containing the essential oil of Ocimum basilicum (EOOB) and infected by Aeromomas hydrophila. Five diets (in quadruplicates) were evaluated with increasing levels of EOOB (0.0 - control; 0.25; 0.5; 1.0 and 2.0 kg diet−1). On day 45, three fish from each tank were sampled and blood, intestine and liver samples were taken. On day 46, nine fish from each tank were infected with A. hydrophila followed by a 15-day period of observation. An addition of 2.0 mL EOOB in the diet improved the growth performance and increased haematological variables and activity of intestinal enzymes. Higher concentrations of EOOB in the diet reduced plasma triglycerides and glucose and hepatic glycogen and alanine aminotransferase (ALT) levels and increased plasma total proteins and ALT levels and lysozyme post-infection activity. The survival of fish after A. hydrophila infection was not influenced by the addition of EOOB in the diet. The use of 1.0 mL EOOB kg diet−1 seems to be more suitable than 2.0 mL EOOB kg diet−1 since the latter may be related to liver damage.

Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: A randomized, double-blind and placebo-controlled clinical trial

Ethnopharmacological evidenceNigella sativa (N. sativa) seeds are used in the Iranian traditional medicine for the treatment of liver diseases. Aim of studyTo study the efficacy and safety of N. sativa seed oil in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). Materials and methodsSixty patients received 2.5 mL fully standardized N. sativa seed oil every 12 h and 60 other patients received placebo for 3 months. At the baseline and endpoint, hepatic steatosis ultrasound grade and blood levels of triglycerides, LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), ALT (alanine aminotransferase), AST (aspartate aminotransferase), blood urea nitrogen, creatinine and complete blood cell count as well as body mass index were determined in the oil and placebo groups and compared. ResultsGrade of hepatic steatosis was significantly reduced in the oil group compared to the placebo group (P = 0.004). Mean ± standard deviation of changes of variables in the oil and placebo groups were respectively 32.6 ± 16.6 and 14.2 ± 19.7% for ALT (P < 0/001), 29.4 ± 16.3 and 12.3 ± 16.8% for AST (P < 0.001), 10 ± 13.9 and 0.22 ± 18.2% for triglycerides (P = 0.001), 14.1 ± 9.8 and 9.2 ± 11.1% for LDL-C (P = 0.01), 9.5 ± 7.7 and 4.8 ± 6.5% for HDL-C (P = 0.001). However, the oil did not significantly affect the other outcome variables compared to the placebo (all P > 0.05). No adverse effect was observed. ConclusionsThe N. sativa seed oil seems to be safe and improve liver steatosis and injury and blood levels of triglycerides, LDL-C and HDL-C in the NAFLD patients.

The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity.

Fumonisin B1 (FB1), a congener of fumonisins produced by Fusarium species, is the most abundant and most toxicologically active fumonisin. FB1 causes severe mycotoxicosis in animals, including nephrotoxicity, hepatotoxicity, and disruption of the intestinal barrier. However, mechanisms associated with FB1 toxicity are still unclear. Preliminary studies have highlighted the role of liver X receptors (LXRs) during FB1 exposure. LXRs belong to the nuclear receptor family and control the expression of genes involved in cholesterol and lipid homeostasis. In this context, the toxicity of FB1 was compared in female wild-type (LXR+/+) and LXRα,β double knockout (LXR-/-) mice in the absence or presence of FB1 (10mg/kg body weight/day) for 28days. Exposure to FB1 supplemented in the mice's drinking water resulted in more pronounced hepatotoxicity in LXR-/- mice compared to LXR+/+ mice, as indicated by hepatic transaminase levels (ALT, AST) and hepatic inflammatory and fibrotic lesions. Next, the effect of FB1 exposure on the liver transcriptome was investigated. FB1 exposure led to a specific transcriptional response in LXR-/- mice that included altered cholesterol and bile acid homeostasis. ELISA showed that these effects were associated with an elevated FB1 concentration in the plasma of LXR-/- mice, suggesting that LXRs participate in intestinal absorption and/or clearance of the toxin. In summary, this study demonstrates an important role of LXRs in protecting the liver against FB1-induced toxicity, suggesting an alternative mechanism not related to the inhibition of sphingolipid synthesis for mycotoxin toxicity.

Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia

Background and aimsHeterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased cardiovascular disease risk. Despite multiple LDL-C–lowering therapies, many HeFH patients do not reach LDL-C targets. Mipomersen, an antisense oligonucleotide against apolipoprotein B (apoB), might further lower LDL-C in HeFH patients. We assessed the efficacy and safety of two mipomersen dosing regimens in HeFH patients and explored whether thrice-weekly dosing improves the benefit-risk profile. MethodsIn this double-blind trial, HeFH patients (LDL-C >160 mg/dL) on maximal tolerated LDL-lowering therapy were randomized to mipomersen 200 mg once weekly (n = 104), mipomersen 70 mg thrice weekly (n = 102), or placebo in matching frequency (n = 103) for 60 weeks. Main outcomes were LDL-C, apoB, and lipoprotein(a) levels after 60 weeks of treatment. ResultsMipomersen 200 mg once weekly and mipomersen 70 mg thrice weekly significantly lowered LDL-C compared with placebo by 21.0% and 18.8%, respectively, and apoB by 22.1% and 21.7% (all p < 0.001). Lipoprotein(a) was significantly lowered by 27.7% (p < 0.001) with thrice-weekly dosing. Injection-site reactions and flu-like symptoms led to discontinuation in 21.2% (200 mg), 17.6% (70 mg), and 5.8% (placebo) of participants. Alanine transaminase was elevated (≥3× upper limit of normal at least once) in 21.2%, 21.6%, and 1.0% of subjects, respectively. ConclusionsMipomersen 200 mg once weekly and 70 mg thrice weekly are effective in lowering apoB-containing lipoproteins in HeFH patients. This is counterbalanced by limited tolerability and increased hepatic transaminase levels in about 21% of patients. The thrice-weekly dosing regimen was associated with lower frequency of flu-like symptoms, which might help avert discontinuation in some patients, but otherwise had no major benefits.

Chlordecone potentiates auto-immune hepatitis and promotes brain entry of MHV3 during viral hepatitis in mouse models

Chlordecone is an organochlorine used in the 1970’s as a pesticide in banana plantations. It has a long half-life in the soil and can potentially contaminate humans and animals through food. Chlordecone targets, and mainly accumulates in, the liver, leading to hepatomegaly and neurological signs in mammals. Chlordecone does not cause liver injuries or any inflammation by itself at low doses, but it can potentiate the hepatotoxic effects of other chemicals and drugs. We studied the impact of chlordecone on the progression of acute hepatitis in mouse models of co-exposure to chlordecone with Concanavalin A or murine hepatitis virus type 3. We examined the progression of these two types of hepatitis by measuring hepatic transaminase levels in the serum and inflammatory cells in the liver, liver histological studies. Amplified tremors presented in the MHV3- chlordecone mouse model had led us to study the expression of specific genes in the brain. We show that chlordecone amplifies the auto-immune hepatitis induced by Concanavalin A by increasing the number of liver NKT cells, which are involved in liver damage. Chlordecone also accelerated the death of mice infected by murine hepatitis virus and enhanced the entry of the virus into the cervical spinal cord in infected mice, leading to considerable neurological damage. In conclusion, chlordecone potentiates both the Concanavalin A-induced hepatitis and brain damage caused by an hepatotropic/neurotropic virus.

Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment.

ObjectiveThe mechanism of liver injury with low-dose methotrexate (MTX) is incompletely understood. This study was designed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and liver injury during MTX treatment for rheumatoid arthritis (RA).MethodsBetween October 2014 and May 2015, we enrolled all MTX users for RA and monitored participant serum hepatic transaminase levels for 1 year. All patients had normal transaminase levels before the first MTX prescription. Using diagnostic criteria for non-alcoholic steatohepatitis (NASH), we performed histological analyses for patients presenting persistent transaminitis, defined as elevations of hepatic transaminases in four of six determinations during the follow-up period. Possible risk factors for persistent transaminitis were also examined.ResultsWe followed 846 RA patients with a mean cumulative MTX dose of 2.48 g and identified 51 patients presenting persistent transaminitis. According to multivariate logistic regression analysis, obesity (odds ratio [OR] 3.23, p < 0.001), type 2 diabetes (OR 3.52, p = 0.001), hypercholesterolemia (OR 2.56, p = 0.004), and hyperuricemia (OR 3.52, p = 0.019), which are recognized as risk factors for NAFLD, were independently associated with a risk of persistent transaminitis. Among patients with persistent transaminitis, 42 showed fatty liver at ultrasonography. These patients had no evidence of alcoholic fatty liver, chronic viral hepatitis, autoimmune liver diseases, or hereditary liver diseases. Biopsy specimens were obtained from 32 patients, and we found that a NASH-like pattern was the most prevalent histological abnormality. There was no significant impact of MTX dose and duration on the histological severity.ConclusionRisk factors and histological findings are similar between NAFLD/NASH and liver injury during low-dose MTX treatment for RA, which suggests a strong association between both entities. NAFLD/NASH may be an underlying condition causing persistent transaminitis in MTX-treated RA patients. The results of this study illustrate the need for monitoring liver injury in RA patients with NAFLD risk factors during MTX treatment.

Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin‑induced model of liver injury.

Oxaliplatin is a core chemotherapeutic agent used for the treatment of colorectal liver metastasis; however, liver injury caused by oxaliplatin increases the risk of peri-operative morbidity and mortality. Magnesium isoglycyrrhizinate (MgiG) is a magnesium salt of 18-α glycyrrhizic acid stereo-isomer that has demonstrated liver-protective effects against toxins and hepatitis. In the present study, the liver-protective effect of MgiG against oxaliplatin-induced hepatic injury was examined in vitro and in vivo. The results demonstrated that MgiG had a protective effect against oxaliplatin-induced liver injury, as evidenced by the alleviation of hepatic pathological damage and transaminase levels. The protective effect of MgiG was demonstrated to be correlated with inhibition of oxidative stress, the interleukin-6 pathway and the coagulation system. Altogether, the present findings suggested that MgiG may have potential value in the clinical prevention and treatment of oxaliplatin-induced liver injury.

Inclusions vertes dans les polynucléaires neutrophiles et les monocytes : à propos de deux cas

This study reports a rare cytological observation: the presence of green turquoise cytoplasmic inclusions in neutrophils and monocytes on a blood smear. These inclusions were transiently observed in two patients admitted in intensive care unit for a septic shock complicated by a multivisceral failure leading to patient death. Their presence was concomitant with increased hepatic transaminase levels associated to a severe liver necrosis. Such green inclusions have rarely been reported to date and have been observed in similar clinical contexts with a high risk of mortality. These unusual inclusions, in various number in leukocytes, should not be confused with Döhle bodies and cytologists must be aware about it.

MONITORING OF THE EFFICACY AND SAFETY OF HIGH-DOSE ATORVASTATIN IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

Aim. To study the effectiveness of achievement of lipid profile target levels and safety of therapy with atorvastatin in different doses in patients with acute ST-segment elevation myocardial infarction (STEMI). Material and methods. The open prospective controlled single-center study included 90 patients with STEMI aged 32 to 65 years. In the first 24-96 hours from the disease onset the patients were randomized into two groups: the first group included 43 patients who received high-dose statin therapy – atorvastatin 80 mg/day (Group 1), the second group (Group 2) – 47 patients receiving atorvastatin 20 mg/day. Examination of patients with STEMI included the assessment of plasma lipid profile, blood levels of hepatic transaminases, creatine phosphokinase (CPK), C-reactive protein (CRP), brain natriuretic peptide (BNP), creatinine, glucose and glomerular filtration rate calculation. Results. A decrease in the level of low density cholesterol (LDC) by 52.4% (p 50% from the baseline – in another 26%. LDC decreased by 33% in Group 2 (p 50% – in 15% of patients. After 24 weeks, a statistically significant decrease in hepatic transaminase activity was found in the both groups in comparison with the baseline level. The level of CRP decreased 9.1 times (p<0.001) in Group 1, and 7.8 times (p<0.001) – in Group 2. Reduction in the level of BNP was also found in Group 1 by 60% (p=0.005), and in Group 2 – by 33.8% (p<0.001). The levels of CPK, creatinine and GFR in the both groups did not change. A comparable decrease in fasting glycemia was found after 24 weeks in the both groups. Conclusion. The revealed lipid-lowering and pleiotropic effects confirm the necessity of using atorvastatin 80 mg. The absence of changes in the level of transaminases, CPK, serious adverse effects indicates the safety of the use of high-dose statin therapy in STEMI patients for the secondary prevention of cardiovascular events.

Food-drug interaction: Anabolic steroids aggravate hepatic lipotoxicity and nonalcoholic fatty liver disease induced by trans fatty acids

Remains unknown if dietary lipids and anabolic steroids (AS) can interact to modify energy metabolism, hepatic structure and function. We investigated the impact of AS on gene expression, lipid profile, redox status and the development of nonalcoholic fatty liver disease (NAFLD) in mice treated with a diet rich in trans fatty acids. Seventy-two C57BL/6 mice were equally randomized into six groups and treated with a standard diet (SD) or high-fat diet (HFD) alone or combined with testosterone cypionate (10 or 20 mg/kg) for 12 weeks. When combined with a HFD, AS reduced plasma HDL cholesterol levels. It also upregulated SREBP-1, PPARα, SCD-1 and ACOX1 gene expression; plasma and hepatic triglyceride levels; oxidative stress; circulating hepatic transaminase levels and NAFLD severity. Our finding indicated that the activity of antioxidant enzymes such as catalase, glutathione-s-transferase and superoxide dismutase was attenuated by HFD, an effect whose implications for AS-induced hepatotoxicity requires further investigation. Increased lipid, protein and DNA oxidative damage as well as worsening NAFLD in response to the interaction of HFD and AS were also potentially associated with the ability of AS to amplify the activation of regulatory lipid metabolism genes that are also involved in the control of cellular redox balance.

Possible ways of pharmacological correction of ischemic liver damages using agonist of peripheral imidazoline receptors c7070

A comorbid condition both in diabetes mellitus and in metabolic syndrome is fatty dystrophy of the liver that further progresses to hepatic necrosis. In the article variants of pharmacological correction of ischemia-reperfusion of the liver with agonists of imidazoline receptor are proposed.&#x0D; Materials and Methods. The experiment was conducted on 70 rats of both sexes divided into 7 groups (n=10): intact group; pseudo-operated animals (incision of the abdominal wall without ligation of hepatic vessels); animals subject to ischemia/reperfusion without drug correction; animals subject to ischemia/reperfusion of the liver + metformin (50 mg/kg); animals subject to ischemia/reperfusion of the liver + moxonidine (1 μg/kg); animals subject to ischemia/reperfusion of the liver+С7070 (10 mg/kg). For evaluation coefficients were used calculated from the level of hepatic transaminases: alaninaminotranspherase (ALT), aspartataminotranspheras (AST), – and also from morphometric ratios of the areas of necrosis and deep ischemia of the liver on the basis of histological examination.&#x0D; Results. Agonist of peripheral imidazoline receptors C7070 reduces ischemic-reperfusion damages to the liver to a significantly larger extent than moxonidine and metformin. Hepatoprotective effect of C7070 was removed by preliminary introduction of peripheral imidazoline receptor blocker. ALT/AST coefficients for C7070, moxonidine and metformin were 72.8/62.13; 44.99/34.20 and 36.88/21.02, respectively. Coefficients of morphological hepatoprotective activity of the drugs were: С7070 – 82.61, moxonidine – 72.33, metformin – 38.96.&#x0D; Conclusion. Agonists of imidazoline receptors reliably and significantly reduce functional and morphological manifestations of ischemia/reperfusion of the liver.

Possible ways of pharmacological correction of ischemic liver damages using agonist of peripheral imidazoline receptors c7070

A comorbid condition both in diabetes mellitus and in metabolic syndrome is fatty dystrophy of the liver that further progresses to hepatic necrosis. In the article variants of pharmacological correction of ischemia-reperfusion of the liver with agonists of imidazoline receptor are proposed.&#x0D; Materials and Methods. The experiment was conducted on 70 rats of both sexes divided into 7 groups (n=10): intact group; pseudo-operated animals (incision of the abdominal wall without ligation of hepatic vessels); animals subject to ischemia/reperfusion without drug correction; animals subject to ischemia/reperfusion of the liver + metformin (50 mg/kg); animals subject to ischemia/reperfusion of the liver + moxonidine (1 μg/kg); animals subject to ischemia/reperfusion of the liver+С7070 (10 mg/kg). For evaluation coefficients were used calculated from the level of hepatic transaminases: alaninaminotranspherase (ALT), aspartataminotranspheras (AST), – and also from morphometric ratios of the areas of necrosis and deep ischemia of the liver on the basis of histological examination.&#x0D; Results. Agonist of peripheral imidazoline receptors C7070 reduces ischemic-reperfusion damages to the liver to a significantly larger extent than moxonidine and metformin. Hepatoprotective effect of C7070 was removed by preliminary introduction of peripheral imidazoline receptor blocker. ALT/AST coefficients for C7070, moxonidine and metformin were 72.8/62.13; 44.99/34.20 and 36.88/21.02, respectively. Coefficients of morphological hepatoprotective activity of the drugs were: С7070 – 82.61, moxonidine – 72.33, metformin – 38.96.&#x0D; Conclusion. Agonists of imidazoline receptors reliably and significantly reduce functional and morphological manifestations of ischemia/reperfusion of the liver.

Risk factors for adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnant women

Intrahepatic cholestasis of pregnant women (ICPW) is associated with an increased risk of complications of pregnancy. Objective prognostic markers of adverse pregnancy outcomes except for a high level of bile acids (BA) in the mother's blood serum, exceeding 40 μmol/l, do not currently exist. However, the determination of the BA levels is not available in all laboratories, which indicates the need to search for other informative prognostic markers of complications of pregnancy in patients with ICPW. Objective: to determine the risk factors for adverse pregnancy outcomes in ICPW. Materials and methods. A prospective study included 97 pregnant women diagnosed with ICPW. The diagnosis was established with an increase in the serum level of the BA in excess of 10 μmol/l. Patients underwent clinical and laboratory examinations with assessment of biochemical markers of liver damage, antioxidant status (determination of superoxide dismutase, glutathione peroxidase, selenium, zinc level). Biochemical indices and severity of pruritus were assessed at the time of diagnosis of ICPW, after 1 and 2 weeks of treatment with ursodeoxycholic acid (UDCA) at a dose of 500 mg to 2 g per day. In the study of perinatal outcomes, the term of delivery, the method of delivery, the presence of signs of intrauterine fetal hypoxia, the state of the fetus at the time of birth were taken into account. Results of the study. In the observed group of patients, the incidence of preterm birth was 31.9%, intrauterine fetal hypoxia 29.9%, pre-eclampsia 23.7%, the need for a cesarean section due to the development of pregnancy complications arose in 40 (41.2%) cases. The risk factors for complications of pregnancy in patients with ICPW were: early onset and longer duration of ICPW, reactivation of cholestasis after its regression against the background of UDCA treatment and less effective treatment of skin itching in patients with manifest forms of ICPW. The laboratory markers of adverse pregnancy outcomes were a high level of maternal total serum BA and a low efficiency of its reduction against the background of treatment, a slow rate of decrease in hepatic transaminase activity against the background of treatment, a low level of antioxidant protection enzymes. The use of sex hormones during pregnancy promoted more frequent development of preeclampsia and increased the frequency of indications for cesarean delivery. The conclusion. Patients with early manifestation of ICPW and reactivation of cholestasis after its regression on the background of treatment, low effectiveness of treatment of pruritus, and also taking drugs of sex hormones require special attention and active management in connection with an increased risk of complications of pregnancy. It is advisable to carry out dynamic monitoring of the level of BA, hepatic transaminases and antioxidant enzymes in dynamics against the backdrop of treatment with ICPW to assess the effectiveness of treatment and timely prediction of possible complications of pregnancy.

Relevant pericardial effusion caused by cytomegalovirus infection in an immunocompetent patient: a case report

BackgroundCytomegalovirus infection is known to cause symptomatic disease in immunocompromised patients, while an infection in immunocompetent individuals normally causes few or no symptoms. We present the case of an immunocompetent adult patient with unexpected severe evolution.Case presentationAn otherwise healthy, 72-year-old Caucasian woman presented with complaints of progressive shoulder pain and dyspnoea on exertion. The blood test results showed elevated inflammation parameters and elevated hepatic transaminase levels. Radiologic examinations were carried out, and the computed tomography scan revealed a hepatomegaly and a chest X-ray showed evidence of a unilateral pleural effusion. A transthoracic echocardiography detected pericardial effusion with consecutive hemodynamic changes. Since it was considered that using ultrasound-guided pericardiocentesis could significantly increase the risk of liver injury due to hepatomegaly, a pericardial window was performed instead. Further investigation showed that our patient tested positive for an acute cytomegalovirus infection in the serologic tests. Laboratory findings included new evidence of immunoglobulin M seroconversion and high immunoglobulin G avidity, so we considered the possibility that a former cytomegalovirus infection may be coexisting with a new cytomegalovirus reinfection.ConclusionsIn immunocompetent individuals, a symptomatic cytomegalovirus primary infection or reinfection should be considered in patients presenting with pericardial effusion and serositis.