Increased Serum Transaminases Research Articles

Clinical Features in Boys with Duchenne/Becker Muscular Dystrophy: A Tertiary Center Experience

Background: Dystrophin-related muscular dystrophies are a group of diseases caused by mutations in the dystrophin gene that are inherited in an X-linked recessive manner. Objectives: We aimed to discuss the clinical, laboratory, genetic, treatment, and prognostic features, as well as diagnostic clues, of our DMD/BMD patients. Methods: The medical records of 39 children who were followed up with DMD/BMD diagnoses at Bursa Uludağ University Faculty of Medicine Child Neurology Clinic between August 2018 and September 2023 were evaluated retrospectively. DMD or BMD is diagnosed by genetic testing or muscle biopsy. Results: All patients were male, and the age of symptom onset was 3.44 ± 2.7 years (range: 1 - 12.2 years). Twenty-two cases were symptomatic, presenting with difficulty walking (N = 17), difficulty climbing stairs (N = 14), and getting tired quickly (N = 11). Seventeen cases were initially asymptomatic, identified through elevated CK, AST, and ALT levels. Conclusions: Early recognition that increased serum transaminase and CK levels reflect muscle disease accelerates the diagnosis of underlying conditions and protects patients from unnecessary, invasive, and costly diagnostic testing.

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells.

To design new CARs targeting hepatitis B virus (HBV), we isolated human monoclonal antibodies recognizing the HBV envelope proteins from single B cells of a patient with a resolved infection. HBV-specific memory B cells were isolated by incubating peripheral blood mononuclear cells with biotinylated hepatitis B surface antigen (HBsAg), followed by single-cell flow cytometry-based sorting of live, CD19+ IgG+ HBsAg+ cells. Amplification and sequencing of immunoglobulin genes from single memory B cells identified variable heavy and light chain sequences. Corresponding immunoglobulin chains were cloned into IgG1 expression vectors and expressed in mammalian cells. Two antibodies named 4D06 and 4D08 were found to be highly specific for HBsAg, recognized a conformational and a linear epitope, respectively, and showed broad reactivity and neutralization capacity against all major HBV genotypes. 4D06 and 4D08 variable chain fragments were cloned into a 2nd generation CAR format with CD28 and CD3zeta intracellular signaling domains. The new CAR constructs displayed a high functional avidity when expressed on primary human T cells. CAR-grafted T cells proved to be polyfunctional regarding cytokine secretion and killed HBV-positive target cells. Interestingly, background activation of the 4D08-CAR recognizing a linear instead of a conformational epitope was consistently low. In a preclinical model of chronic HBV infection, murine T cells grafted with the 4D06 and the 4D08 CAR showed on target activity indicated by a transient increase in serum transaminases, and a lower number of HBV-positive hepatocytes in the mice treated. This study demonstrates an efficient and fast approach to identifying pathogen-specific monoclonal human antibodies from small donor cell numbers for the subsequent generation of new CARs.

Protective Effects of Propolis and Chitosan Nanoparticles against Ibuprofen-Induced Hepatotoxicity in Albino Rats.

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1β and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities.

Oleuropein, a phenolic component of Olea europaea L. ameliorates CCl4-induced liver injury in rats through the regulation of oxidative stress and inflammation.

This study aimed to assess the hepatoprotective role of oleuropein (Olp), a phenolic compound found in olive, against carbon tetrachloride (CCl4)-induced liver damage in rats. The research involved male albino rats, which received intraperitoneal injections of 100 mg/kg b.w. of oleuropein for 8 consecutive weeks before being subjected to carbon tetrachloride (CCl4) at a dosage of 1.0 ml/kg b.w. Changes induced by CCl4 in antioxidant and inflammatory marker levels were assessed using ELISA assay kits. Moreover, CCl4-induced liver tissue architecture alteration, fibrosis, and expression pattern of protein were evaluated by performing H&E, Sirius red, Masson trichrome, and immunohistochemistry staining. Increased serum transaminases and massive hepatic damage were observed by this liver toxicant. The hepatic injury was further evidenced by a significant decrease in antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione (GSH) and Total Antioxidant Capacity (T-AOC)]. The administration of CCl4 resulted in an increased inflammatory response, which was measured by C-reactive protein, interleukin-6, as well as tumor necrosis factor-alpha. Olp as a curative regimen led to significant attenuation in the inflammatory response and oxidative/nitrosative stress. This polyphenol treatment improved the hepatic tissue architecture and decreased fibrosis. In the CCl4 treatment group, the expression pattern of IL-6 protein was high, whereas expression was decreased after Olp, as evidenced by immunohistochemistry staining. The study suggests that oleuropein treatment has the potential to reduce liver damage caused by CCl4 induction by inhibiting oxidative stress and inflammation and maintaining liver tissue architecture. This could make it a promising treatment option for liver pathogenesis.

Histopathological changes and oxidative stress associated with Fascioliasis in bovines.

Fascioliasis, a prevalent disease in livestock globally, is primarily caused by the trematode parasites Fasciola hepatica and Fasciola gigantica. This parasitic infection leads to significant economic repercussions. In this study, our objective was to gain insight into the pathophysiological consequences of Fascioliasis in cattle through the evaluation of metabolic, oxidative stress, and histological parameters. A thorough investigation was carried out on the liver of 197 bovines after their slaughter, which unveiled the occurrence of Fascioliasis, with a prevalence rate of 13.2% observed. The bovine that were infected exhibited notable increase in serum transaminases (ALT, AST, and ALP) and malondialdehyde (MDA) and catalase (CAT) while the decrease in glutathione (GSH) and superoxide dismutase (SOD) levels. The lipid profile analysis of infected cattle revealed alterations in the cholesterol and triglyceride levels. Moreover, the histopathological examination revealed a range of hepatic lesions associated with Fascioliasis, including necrosis, inflammation, fibrosis, and proliferative alterations. The bile ducts also displayed distinct pathological changes, including hyperplasia, thickening, and edema, and harbored various developmental stages of Fasciola spp. highlighting the parasitic infestation's effects on the biliary system. These results highlight the serious effects of Fascioliasis on lipid metabolism and the oxidative damage that is induced in the livers of cattle. Thus, Fasciola infestation in bovine causes alteration in biochemical and antioxidant activities, which are considered as important factors in the diagnosis of Fascioliasis.

Lysosomal acid lipase deficiency: features of manifestation in patients of the Moscow region

Lysosomal acid lipase deficiency (LALD) is a rare, chronic, progressive disease based on a defect in the LIPA gene encoding lysosomal acid lipase, early diagnosis of which may be difficult due to the diversity of the clinical picture. The purpose of the study. To evaluate the early clinical and laboratory symptoms of LALD, the timing of manifestation and diagnosis in patients of the Moscow region. Materials and methods. The analysis of the medical documentation of 6 patients with a confirmed diagnosis of lysosomal acid lipase deficiency by the results of enzyme diagnostics and DNA-diagnostics registered in the Moscow region: 5 children aged 2 to 16 years, one patient aged 19 years. Boys - 3, girls - 3. Results. In 3 patients (50%), the first symptoms of the disease were detected before the age of 1 year, in two children (33%) - from 1 to 2 years, in one child - at the age of 5 years. The most common early clinical symptom was cytolysis syndrome and hepatosplenomegaly, less often dyspeptic manifestations (flatulence, diarrhea). The average age of onset of the disease is 1.5 years. The duration of follow-up ranged from 1 year to 14 years. On average, the duration of the diagnostic search was 6.75 years, and the average age of diagnosis was 8.25 years. At the time of diagnosis confirmation, all patients showed signs of hepatosplenomegaly, diffuse changes in liver parenchyma, increased serum transaminases, hypercholesterolemia, increased LDL and decreased HDL. Excess of ALT values up to 2 norms was diagnosed in one child (17%), from 2 to 3 norms - in 3 children (50%), from 3 to 5 norms - in 2 children (33%). AST is less than 2 norms - in 2 children (33%), from 2 to 3 norms - in 3 (50%), in 1 child - 5-6 norms (17%). The absolute majority of patients (83%) had c894G>A mutations in the LIPA gene in a homozygous state. Conclusion. LALD is a rare disease, the diagnosis of which is difficult due to the frequent asymptomatic course or non-specific clinic. In most children, the disease manifests at an early age (up to 3-5 years), and the most common symptoms are increased liver transaminases and hepatosplenomegaly. ALT and AST activity, as a rule, does not exceed 2-3 norms. The signs characteristic of DL are detected randomly during examination for other diseases. Due to the non-specificity of clinical symptoms, the duration of diagnosis varies from several months to several years. The main modern method of diagnosing LALD is enzyme diagnostics and DNA diagnostics. If a child has hepatolienal syndrome, a persistent increase in markers of cytolysis and dyslipidemia, caution should be exercised and the necessary diagnostic examinations should be carried out in a timely manner to exclude LALD.

Complete Freund’s adjuvant-induced arthritis in rats: Anti-inflammatory and antioxidant properties of Allanblackia gabonensis (guttiferae) aqueous extract

Objectives: Allanblackia gabonensis (Guttiferae) stem bark extract is generally used in Cameroonian traditional medicine for its beneficial activities as antibiotics, anti-inflammatory, and antinociceptive. However, the claimed chronic anti-inflammatory and antioxidant effects have not yet been largely elucidated scientifically. The present study was designed to evaluate the anti-inflammatory and antioxidant effects of A. gabonensis stem bark aqueous extract on Freund’s complete adjuvant (CFA)-induced arthritis in rats. Materials and Methods: Arthritis was induced by intradermal injection of CFA (0.1 mL) into the right hind paw of each rat. Pain relieving effects were measured in the treated animals using an analgesiometer and antioxidant activity determined by measuring oxidative stress parameters. In addition, the hematological index, serum nitric oxide (NO), and transaminase activities were evaluated in the experimental animals. Results: A. gabonensis significantly protected animals against pain from day 15 to 18 and decreased (P < 0.01) the paw edema from day 12 to the end of the experimentation (day 22). The number of white blood cells increased while the NO levels in serum and organs decreased in CFA animals as compared to the control group. An increase in serum transaminases was observed in the CFA group. A. gabonensis at the dose of 200 mg/kg significantly increased (36.36%) glutathione levels in the spleen in comparison with the CFA group. There was also a significant increase (P < 0.01) of liver and cardiac catalase in animals receiving extract at 100 and 200 mg/kg. Conclusion: Our findings revealed the anti-arthritic and antioxidant potential of A. gabonensis and, thus, validate its traditional claim.

Implications of deltamethrin on hematology, cardiac pathology, and gene expression in Nile tilapia (Oreochromis niloticus) and its possible amelioration with Shatavari (Asparagus racemosus).

Deltamethrin (DM) is one of the extensively used pyrethroids for controlling ectoparasites. Unfortunately, DM is highly toxic to fish as it primarily targets the sodium channels of the plasma membrane thereby affecting their cardiac and nervous systems. The present study investigated the protective efficacy of Shatavari (Asparagus racemosus) against DM-induced cardiotoxicity in Nile tilapia (Oreochromis niloticus). The fish were segregated into nine groups having 36 fish/group maintained in triplicates exposed to DM (1µg/L) and fed with a diet containing three different concentrations (10g, 20g, and 30g/kg feed) of aqueous extract of A. racemosus (ARE) for 21 days. DM caused significant alterations in the blood and serum parameters, and expression of cardiac and apoptotic genes compared to the control group. The ARE cotreatment significantly reduced the increase in serum transaminases, creatine kinase, and lactate dehydrogenase levels induced by DM. ARE facilitated the regain of electrolyte (sodium, potassium, chloride) homeostasis and antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione in DM-exposed fish. The cardiac histology exhibited loose separation of the cardiomyocytes and myofibrillar loss in the DM group which was ameliorated in the DM-ARE cotreatment group. Significant modulations were observed in the expression of cardiac-specific genes (gata4, myh6, tnT, cox1) and apoptosis signaling genes and proteins (HSP70, bax, bcl-2, caspase3), in the cotreatment group compared to the DM-exposed group. The current study suggests that ARE possesses potential cardioprotective properties that are effective in mitigating the toxic effects induced by DM via ameliorating oxidative stress, electrolyte imbalance, and apoptosis in tilapia.

Remdesivir: Effectiveness and Safety in Hospitalized Patients with COVID-19 (ReEs-COVID-19)-Analysis of Data from Daily Practice.

Remdesivir was the first antiviral approved for treating COVID-19. We investigated its patterns of use, effectiveness and safety in clinical practice in Greece. This is a retrospective observational study of hospitalized adults who received remdesivir for COVID-19 in September 2020-February 2021. The main endpoints were the time to recovery (hospital discharge within 30 days from admission) and safety. The "early" (remdesivir initiation within 24 h since hospitalization) and "deferred" (remdesivir initiation later on) groups were compared. One thousand and four patients (60.6% male, mean age 61 years, 74.3% with severe disease, 70.9% with ≥1 comorbidities) were included, and 75.9% of them were on a 5-day regimen, and 86.8% were in the early group. Among those with a baseline mild/moderate disease, the median (95% CI) time to recovery was 8 (7-9) and 12 (11-14) days for the early and deferred groups, respectively (p < 0.001). The corresponding estimates for those with a severe disease were 10 (9-10) and 13 (11-15) days, respectively (p = 0.028). After remdesivir initiation, increased serum transaminases and an acute kidney injury were observed in 6.9% and 2.1%, respectively. Nine (0.9%) patients discontinued the treatment due to adverse events. The effectiveness of remdesivir was increased when it was taken within 24 h since admission regardless of the disease severity. Remdesivir's safety profile is similar to that described in clinical trials and other real-world cohorts.

Class III Alcohol Dehydrogenase Plays a Key Role in the Onset of Alcohol-Related/-Associated Liver Disease as an S-Nitrosoglutathione Reductase in Mice.

Lipid accumulation in the liver due to chronic alcohol consumption (CAC) is crucial in the development of alcohol liver disease (ALD). It is promoted by the NADH/NAD ratio increase via alcohol dehydrogenase (ADH)-dependent alcohol metabolism and lipogenesis increase via peroxisome proliferator-activated receptor γ (PPARγ) in the liver. The transcriptional activity of PPARγ on lipogenic genes is inhibited by S-nitrosylation but activated by denitrosylation via S-nitrosoglutathione reductase (GSNOR), an enzyme identical to ADH3. Besides ADH1, ADH3 also participates in alcohol metabolism. Therefore, we investigated the specific contribution of ADH3 to ALD onset. ADH3-knockout (Adh3-/-) and wild-type (WT) mice were administered a 10% ethanol solution for 12 months. Adh3-/- exhibited no significant pathological changes in the liver, whereas WT exhibited marked hepatic lipid accumulation (p < 0.005) with increased serum transaminase levels. Adh3-/- exhibited no death during CAC, whereas WT exhibited a 40% death. Liver ADH3 mRNA levels were elevated by CAC in WT (p < 0.01). The alcohol elimination rate measured after injecting 4 g/kg ethanol was not significantly different between two strains, although the rate was increased in both strains by CAC. Thus, ADH3 plays a key role in the ALD onset, likely by acting as GSNOR.

The protective effect of 7-hydroxycoumarin against cisplatin-induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO-1 pathway.

Cisplatin (CIS) is an effective chemotherapy against different solid cancers. However, the adverse effects, including hepatotoxicity, limit its clinical use. 7-hydroxycoumarin (7-HC) possesses antioxidant and hepatoprotective activities, but its protective effect against CIS hepatotoxicity has not been investigated. This study evaluated the effect of 7-HC on liver injury, oxidative stress (OS), and inflammation provoked by CIS. Rats received 7-HC (25, 50, and 100mg/kg) orally for 2weeks followed by intraperitoneal injection of CIS (7mg/kg) at day 15. CIS increased serum transaminases, alkaline phosphatase (ALP), and bilirubin and provoked tissue injury accompanied by elevated reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO). Liver nuclear factor (NF)-κB p65, inducible NO synthase (iNOS), pro-inflammatory cytokines, Bax, and caspase-3 were upregulated, and antioxidant defenses and Bcl-2 were decreased in CIS-treated rats, while 7-HC prevented liver injury and ameliorated OS, inflammatory and apoptosis markers. In addition, 7-HC enhanced nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase (HO)-1 in CIS-administered rats and in silico studies revealed its binding affinity toward HO-1. In conclusion, 7-HC protected against CIS hepatotoxicity by mitigating OS and inflammatory response and modulating Nrf2/HO-1 pathway.

Calcitriol Protects against Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) overdose is one of the major causes of acute liver failure. Severe liver inflammation and the production of oxidative stress occur due to toxic APAP metabolites and glutathione depletion. Growing evidence has proved that vitamin D (VD) exerts anti-inflammatory and antioxidative functions. Our objective was to explore the protective role of calcitriol (VD3) in acute APAP-induced liver injury. Methods: Adult male mice were randomized into three groups; control (n = 8), APAP (n = 8), and VD3 group (n = 8). All mice, except controls, received oral administration of APAP (400 mg/kg) and were sacrificed 24 h later. In the VD3 group, calcitriol (10 µg/kg) was injected intraperitoneally 24 h before and after exposure to APAP. Blood samples were collected to assess serum aminotransferase and inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)]. Liver tissues were analyzed for hepatic glutathione (GSH), malondialdehyde (MDA), and histopathology. Results: APAP administration significantly increased serum aminotransferase, inflammatory cytokines, and induced cellular inflammation and necrosis. APAP also depleted hepatic GSH and elevated oxidative stress, as indicated by high MDA levels. In the APAP group, 25% of the mice (two out of eight) died, while no deaths occurred in the VD3 group. Treatment with calcitriol significantly reduced serum aminotransferase, TNF-α, and IL-6 levels in the VD3 group compared to the APAP group. Additionally, VD3 effectively restored GSH reserves, reduced lipid peroxidation, and attenuated hepatotoxicity. Conclusions: These findings demonstrate that VD3 prevents APAP-induced acute liver injury and reduces mortality in mice through its anti-inflammatory and antioxidative activity. Thus, VD3 might be a novel treatment strategy for APAP-induced hepatotoxicity.

Higher frequency of TMEM199-CDG in the southern mediterranean area is associated with c.92G>C (p.Arg31Pro) mutation

Congenital disorders of glycosylation (CDG) are genetic multisystem diseases, characterized by defective glycoconjugate synthesis. A small number of CDG with isolated liver damage have been described, such as TMEM199-CDG, a non-encephalopathic liver disorder with Wilson disease-like phenotype. Only eight patients with TMEM199-CDG have been described including seven Europeans (originating from Greece and Italy) and one Chinese. Three patients from southern Italy (Campania) shared the same known missense mutation pathogenetic variant NM_152464.3:c. 92G > C (p.Arg31Pro), also found in a Greek patient.Here we report a new patient from southern Italy (Sicily), with a homozygous c.92G > C p.(Arg31Pro) variant in TMEM199. The patient's phenotype is characterized by mild non-progressive hepatopathy with a normal hepatic echo structure. A persistent increase in serum transaminases, total and low-density lipoprotein cholesterol and low serum ceruloplasmin and copper levels and normal urinary copper excretion were observed. Matrix-assisted laser desorption/ionization mass spectrometry analyses showed abnormal N- and O- protein glycosylation, indicative of a Golgi processing defect and supporting the function of TMEM199 in maintaining Golgi homeostasis. TMEM199-CDG is an ultra-rare CDG relatively frequent in the southern Mediterranean area (7 in 9 patients, 77%). It is mainly associated with the c.92G > C (p.Arg31Pro) pathogenetic allele globally reported in 4 out of 7 families (57%), including one from Greece and three unrelated families from southern Italy. The almost uniform clinical phenotype described in patients with TMEM199-CDG appears to reflect a higher prevalence of the same variant in patients from the southern Mediterranean area.

ATM deficiency aggravates the progression of liver fibrosis induced by carbon tetrachloride in mice

Ataxia telangiectasia mutated (ATM) is a pivotal sensor during the DNA damage response that slows cell passage through the cell cycle checkpoints to facilitate DNA repair, and liver fibrosis is an irreversible pathological consequence of the sustained wound-healing process, However, the effects of ATM on the development of liver fibrosis are still not fully understood. Therefore, the aim of the study was to investigate the effects and potential mechanisms of ATM on the progression of liver fibrosis. Wild-type and ATM-deficient were administered with carbon tetrachloride (CCl4, 5 ml/kg, i.p.) for 8 weeks to induce liver fibrosis, and the liver tissues and serum were collected for analysis. KU-55933 (10 μM) was used to investigate the effects of ATM blockage on CCl4-induced hepatocyte injury in vitro. The results showed that ATM deficiency aggravated the increased serum transaminase levels and liver MDA, HYP, and 8-OHdG contents compared with the model group (p < 0.05). Sirius red staining showed that ATM deficiency exacerbated liver collagen deposition in vivo, which was associated with the activation of TGF-β1/Smad2 signaling. Furthermore, blocking ATM with KU-55933 exacerbated the production of ROS and DNA damage caused by CCl4 exposure in HepG2 cells, and KU-55933 treatment also reversed the downregulated expression of CDK1 and CDK2 after CCl4 exposure in vitro. Moreover, the loss of ATM perturbed the regulation of the hepatic cell ChK2-CDC25A/C-CDK1/2 cascade and apoptosis in vivo, which was accompanied by increased Ki67-positive and TUNEL-positive cells after chronic CCl4 treatment. In conclusion, our results indicated that ATM might be a critical regulator of liver fibrosis progression, and the underlying mechanisms of exacerbated liver fibrosis development in ATM-deficient mice might be associated with the dysregulation of hepatic cell proliferation and apoptosis.

The Diagnostic Value of Hepatic and Renal Biochemical Tests for the Detection of Preeclampsia Among Pregnant Women Attending the Antenatal Care Clinic at the University of Gondar Comprehensive Specialized Hospital, Gondar, Northwest Ethiopia.

BackgroundPreeclampsia has a deleterious effect on renal and liver function, which results in alterations of various biochemical tests. Therefore, the main aim of this study was to evaluate the role of some hepatic and renal biochemical tests in the diagnosis of preeclampsia.MethodsA comparative cross-sectional study was carried out on a total of 126 pregnant women after 20th week of gestation who attended at the University of Gondar Comprehensive Specialized Hospital. The participants were divided into two groups as cases and controls. The case group consisted of 63 preeclamptic women, whereas the control group had 63 age and gestational week matched normotensive pregnant women. From each participant, three milliliters of blood was collected, the serum part was separated, and selected biochemical tests were measured using Humastar 800 chemistry analyzer. An independent t-test and receiver operating characteristics were done using SPSS 20 for comparison and diagnostic value determination of different biochemical tests between the study groups.ResultsThe maternal serum aminotransferases, total bilirubin, Creatinine, and Urea levels were all significantly elevated in preeclamptic women compared to normotensive pregnant women. The receiver operating characteristics plots revealed that serum aspartate aminotransferase level had area under the curve of 0.89 (95% CI: 0.84–0.95) and can distinguish preeclampsia patients from normotensive pregnant women at cut-off value of ≥58.5 U/l with 74.6% sensitivity, 87.3% specificity, and 80.9% diagnostic accuracy. Serum Creatinine level had area under the curve of 0.91 (95% CI: 0.86–0.96), which enabled to indicate preeclampsia at a cut-off value ≥0.90 mg/dl with 77.8% sensitivity and 85.7% specificity.ConclusionAn increased serum aminotransferases, total bilirubin, creatinine, and Urea levels in pregnant women could indicate the development of preeclampsia, and needs to be investigated. Among biochemical tests, serum Creatinine level was the best diagnostic marker of preeclampsia, followed by serum aspartate aminotransferase level.

Effects of scoparone on non-alcoholic fatty liver disease revealed by RNA sequencing

Scoparone (SCO) is known to have curative effect of alleviating liver injury. The purpose of this study was to observe the therapeutic effect and possible mechanism of SCO against high-fat diet (HFD) induced non-alcoholic liver disease (NAFLD) through in vivo experiments and RNA sequencing. Male Kunming mice were fed with HFD for 8 weeks to establish a mouse model of NAFLD, and SCO was used to treat NAFLD. Histopathology and biochemical indicators were used to evaluate the liver injury and the efficacy of SCO. RNA sequencing analysis was performed to elucidate the hepatoprotective mechanism of SCO. Finally, the differentially expressed genes of cholesterol synthesis and fatty acid (triglyceride) synthesis pathways were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The histopathological results showed that HFD could lead to significant steatosis in mice, while SCO could alleviate liver steatosis remarkably in NAFLD mice. The determination of biochemical indicators showed that SCO could inhibit the increased serum transaminase activity and liver lipid level induced by HFD. RNA sequencing analysis of liver tissues found that 2742 and 3663 genes were significantly changed by HFD and SCO, respectively. SCO reversed the most of genes involved in cholesterol synthesis and fatty acid (triglyceride) metabolism induced by HFD. the results of the validation experiment were mostly consistent with the RNA sequencing. SCO alleviated liver injury and steatosis in NAFLD mice, which may be closely related to the regulation of cholesterol and fatty acid (triglyceride) metabolism.

Studi Penggunaan Obat Anti Tuberkulosis (OAT) Tahap Lanjutan pada Pasien Baru BTA Positif

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Tuberculosis will cause pain and death if not treated properly. OAT (Antituberculosis Drugs) is a treatment for tuberculosis patients. OAT has different dosage regimens and types of drugs. Treatment of TB patients consists of two phases (intensive and continuation phases). The continuation phase was at to kill dormant bacteria to prevent recurrence in patients. The purpose of this study was to determine and evaluate the pattern of using OAT in patients newly diagnosed rwith smear-positive at the continuation phase. This study is an observational descriptive study with results showing that the pattern of using OAT-KDT in patients was 89% and OAT-Separated was 11%. The pattern of using the OAT-KDT dose was 1x3 2KDT tablets. Another combination of antibiotics given to the patient is cotrimoxazole at a dose of 1x960mg. The side effect of OAT is an increase in serum transaminase and nausea each with a percentage of 23%. Based on the research, it can be concluded that the pattern of using OAT in Tuberculosis patients has followed the guidelines for the management of Tuberculosis treatment.

Elevated Serum Transaminase (SGOT/SGPT) and Sepsis in Burn Patients in a Tertiary Hospital, Surabaya, Indonesia

Highlights: There is no correlation between the increase of SGOT and sepsis. Correlation between the increase of SGPT and sepsis was significant founded. Abstract: Burns trigger hypermetabolic stress reactions that cause inflammatory responses. When there is a sustained or increased hypermetabolic reaction, the inflammatory response can be life-threatening, such as sepsis, and significantly impact hepatic metabolic function. After burns, varying degrees of liver injury are usually associated with burn severity. This study determined the correlation between elevated serum transaminases (SGOT/ SGPT) and sepsis in burn patients at a tertiary hospital of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from January 1, 2018, to December 31, 2020. This was a descriptive-analytic study with a retrospective cohort design. The data in this study included the demography of burn patients, causes of burns, inhalation trauma, burn severity, increased serum transaminase (SGOT/SGPT), mortality, and sepsis. This study found that the correlation between elevated serum transaminases (SGOT/SGPT) and sepsis was determined using the Spearman-Rho Rank statistical test. Burn patients with sepsis in the hospital were dominated by males (65.2%) and mostly aged 26-55 years (69.6%). The flame was found to be the highest cause of burns (80.4%), burn area above 20% (91.3%), the highest level of severity was major burn (91.3%), and no inhalation trauma (54.3%). In this study, there was an increase in SGOT of 69.6% and SGPT of 78.3%, with a mortality rate of 39.1%, with average inpatient days of 24 days. The correlation test between elevated serum transaminase (SGOT) and sepsis showed an insignificant relationship (p = 0.065, p&gt; 0.05) with a correlation coefficient of 0.200. In contrast, the correlation between elevated serum transaminase (SGPT) and sepsis was significant (p=0.006, p&lt;0.05) with a correlation coefficient of 0.296.

Targeting Galanin Receptor Signaling as a Novel Therapeutic Strategy for the Treatment of Fatty Liver Disease

BackgroundNon‐alcoholic fatty liver disease (NAFLD) is a common liver disease in the United States and is associated with dysregulated lipid metabolism and fat accumulation in hepatocytes (i.e. steatosis) leading to inflammation and fibrosis and cirrhosis. Galanin (Gal) is a neuropeptide with a role in food intake behavior and chronic upregulation of Gal is associated with increases in serum triglycerides, hyperinsulinemia, impaired glucose tolerance and hepatic steatosis. Targeting Gal receptor (GalR) signaling has been shown to have antifibrotic in models of cholestatic liver disease although the effects in NAFLD is unknown. The aim of this study was to evaluate the Gal/GalR axis in NAFLD and determined the effects of Gal Inhibition on the pathogenesis of NAFLD.MethodsC57Bl6 mice were fed a western diet (WD) consisting of high fat/high sugar/high cholesterol for a total of 16 weeks. At the 4 week time point, mice were treated with the GalR1/GalR2 antagonist, M40 (1 nmol, 3X per week for the duration of the experiment), or corresponding vehicle control. Serum and liver assays of Gal, triglycerides, and cholesterol were performed using commercially available kits. The expression of Gal, GalR1, GalR2, markers of steatosis (perilipin 2, PLIN2), biliary hyperplasia (cytokeratin 19, CK19), fibrosis (collagen type 1A1, Col1A1; α‐smooth muscle actin, α‐SMA) and inflammation (chemokine C‐C motif ligand 2, CCL2; tumor necrosis factor‐α, TNFα) by qPCR and immunostaining. Liver macrophages CD11b+ and CD68+ were quantified by immunohistochemistry (IHC). Liver lipid droplets (LD) were stained with Oil Red O. In vitro, HepG2 cells were used to assess the effects of M40 on palmitate (PA)‐induced LD formation.ResultsGal was significantly increased in the serum and liver of WD‐fed mice, with a corresponding increase in GalR1 and GalR2 expression. WD‐mice exhibited significant increase in serum transaminases, triglycerides and cholesterol compared to control mice, and M40 significantly reduced these indicators of liver injury. A drastic decrease in liver steatosis was also observed in M40‐treated WD‐mice compared to vehicle‐treated WD‐mice. M40 treatment also ameliorated WD‐induced increase in ductular reaction, fibrosis and liver inflammation in NAFLD mice. In vitro experiments confirmed that M40 decreased PA‐induced steatosis of HepG2.ConclusionsThe expression of Gal and its receptors GalR1 and GalR2, is enhanced in livers of mice on a WD. Treatment of WD‐fed mice with M40 reduces steatosis, intrahepatic biliary mass, fibrosis and inflammation. Therefore, targeting GalR1 and GalR2 may be a novel therapeutic option for the treatment of NAFLD.

Remdesivir administration for Japanese COVID-19 patients undergoing maintenance hemodialysis: a retrospective observation with six case reports

BackgroundThe mortality rate of novel coronaviral disease (COVID-19) patients undergoing dialysis is considerably higher than that of patients with normal kidney function. As of August 2021, only remdesivir has been approved in Japan as an antiviral drug for the treatment of COVID-19. However, in cases of kidney failure, remdesivir administration should be considered only if the therapeutic benefits outweigh the risks because of concern about the accumulation of its solubilizing excipient sulfobutylether-beta-cyclodextrin and subsequent renal tubular injury or liver injury. Recently, reports from overseas indicating the safety of the use of remdesivir for COVID-19 patients on dialysis have been gathered.Case presentationFrom June 2021, in our hospital, we started the administration of remdesivir to patients with moderate cases of COVID-19 undergoing hemodialysis, with careful consideration of the dosage and timing. Since then, six out of seven COVID-19 patients on hemodialysis who had received remdesivir have completely recovered. In a patient who died, the initial dose of remdesivir was administered after the case developed into severe COVID-19. All six patients who were able to start receiving remdesivir immediately at the stage of moderate COVID-19 recovered and were discharged without the need for mechanical ventilation. While, two out of four patients before May 2021 who had not been administered remdesivir at admission became severe, transferred to another tertiary hospital, and died. During and after remdesivir administration, no increase in serum transaminase to five times or more of the normal upper limit was observed in any of the cases. There were no other adverse drug reactions, such as infusion reaction, gastrointestinal symptoms, or anemia.ConclusionsWe were able to administer remdesivir to six Japanese patients with moderate COVID-19 on hemodialysis safely. It is expected that the safe use of remdesivir will bring an increase in treatment options for moderate cases of COVID-19 in dialysis patients as well as subsequent improvement in treatment outcomes. However, to confirm the efficacy and safety of such use, further careful observation in more cases is required.