Bilirubin Research Articles

Studying the association between single nucleotide polymorphisms of metabolizing enzymes and the therapeutic serum levels of calcineurin inhibitors in Egyptian liver transplant patients

BackgroundMany clinical variables might impact the pharmacokinetics of calcineurin inhibitors (CIs). Different alleles of cytochromes P450 (CYP)3A4/5 and drug transporter P-glycoprotein are the main variables. Other variables include relocated type, treatment duration after transplantation, age, sex, dietary consumption, medications used and renal or hepatic impairment. Tacrolimus and cyclosporine are two main CIs extensively used in organ transplantation. Both drugs are metabolized by CYP3A4 and CYP3A5 isoforms, and single-nucleotide polymorphisms in these genes have been displayed to influence CIs pharmacokinetics. Another important gene is the pregnane X receptor (PXR), which manages the statement of a variety of genes including CYP3A4 genes. PXR has a clinical significance in CIs metabolism. The liver is the essential site for CIs metabolism. A decreased clearance with a prolonged CIs half-life was occurred in patients with impaired liver compared with patients with normal liver function. The presence of different genetic and clinical factors that may affect calcineurin inhibitors trough levels will consequently affect their immunosuppressant effect after liver transplantation.PurposeThis study aims to determine the effect of different genetic polymorphisms in CYP3A4 1B rs2740574 and PXR A7635G rs6785049 and other clinical factors that may affect calcineurin inhibitors pharmacokinetics after liver transplantation.ResultsThe presence of T allele in CYP3A4 gene was associated with elevated DATLs with P values of 0.00, 0.00, 0.007 and 0.00 after tacrolimus doses 4, 30, 60 and 90, respectively. Regarding PXR gene, the presence of G allele was associated with elevated DATLs in cyclosporine. About 432 correlations were tested in both drugs. In CYP3A4 genotype CC, male sex was associated with elevated DATLs interpreted by strong positive correlations and statistically significant difference in all DATLs, except DATL 60 (P value 0.374). No strong association was found between low hemoglobin levels and DATLs in almost all the follow-up periods. There were many positive relations between increased total and direct bilirubin and increased DATLs.ConclusionsStudying the various genetics and clinical factors that may affect calcineurin inhibitors serum concentrations is very essential for successful treatment plans after organ transplantation. These different factors may interact with each other and these complicated interactions may complicate the patient’s conditions post-transplantation. Considering all these complicated interactions is very crucial in monitoring treatment plans, especially in the presence of other comorbidities or chronic diseases. More studies with large number of patients should be conducted to explore more consequences of these interacting variables of treatment plans of these patients and all studied parameters in this study should be considered while monitoring patients after transplantation.

Model-based characterization of total serum bilirubin dynamics in preterm infants.

This study aims to characterize the age-related natural dynamics of total serum bilirubin (TSB) in preterm infants through a mathematical model and to study the model parameters as potential biomarkers for detecting associated morbidities. We proposed an exponential decay model and applied it to each infant. Patient-specific parameters were obtained by minimizing the error between measured TSB and model output. Modeling evaluation was based on root-mean-square error (RMSE). The occurrence of high-risk clinical events was analyzed based on RMSE. In a subset of the CARESS-Premi study involving 373 preterm infants (24-32 weeks' gestation), 72 patient-specific models were fitted. RMSE ranged from 1.20 to 40.25 µmol/L, with a median [IQR] of 8.74 [4.89, 14.25] µmol/L. Our model effectively characterized TSB dynamics for 72 patients, providing valuable insights from model parameters and fitting errors. To our knowledge, this is the first long-term mathematical description of natural TSB decay in preterm infants. Furthermore, the model was able to estimate the occurrence of clinical events such as necrotizing enterocolitis, as reflected by the relatively high RMSE. Future implications include the development of model-based clinical decision support systems for optimizing NICU monitoring and detecting high-risk events. The study characterizes the natural dynamics of total serum bilirubin in preterm infants (24-32 weeks' gestation) using a patient-specific exponential decay model. The model describes patient-specific patterns of TSB evolution from day three to the first weeks, providing a median [IQR] root-mean-squared error of 8.74 [4.89, 14.25] µmol/L. Complementary to previous studies focusing on the first 72-96 h, our study emphasizes the later decay course, contributing to a comprehensive long-term characterization of the natural TSB dynamics in preterm infants. The proposed model holds potential for clinical decision support systems for the optimization of NICU monitoring and high-risk event detection.

PROTECTIVE EFFECT OF COMBINATION OF ETHANOLIC EXTRACTS OF XIMENIA AMERICANA AND TERMINALIA MACROPTERA AGAINST ALCOHOL-INDUCED HEPATOTOXICITY IN RATS

Objective: The aim of this study was to evaluate the hepatoprotective effect of the combination. Methods: Serum liver markers, tissue antioxidant activity, and histological changes in the livers of rats from the blank, negative (distilled water), positive (silymarin 100 mg/kg bw), and test (combination 500 mg/kg bw) groups were measured after 7 days of pretreatment and induction of hepatotoxicity by 10 g/kg bw alcohol every 12 h for 48 h. Results: Rats in the negative control group showed a highly significant (p<0.001) increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (BT) levels by 281.13%, 221.7%, and 93.44%, respectively, compared to rats in the blank group. Pretreatment with the combination resulted in a highly significant (p<0.001) decrease in AST, ALT, and BT levels of 69.19%, 62.24%, and 41.52%, respectively. The study of tissue oxidative stress parameters revealed a very significant (p<0.01) increase in superoxide dismutase (123.08%), glutathione (131.66%), and catalase (49.01%) activities and a significant (p<0.05) decrease in malondialdehyde concentration (59.72%) in the group pretreated with the combination compared with the negative control group. Steatosis and necrosis estimated at 50% were observed in rats in the negative control group. In contrast, necrosis observed in the group pre-treated with the combination was <10%. Conclusion: These data suggest that the combination is effective in preventing the elevation of biochemical markers and the imbalance of enzymatic and non-enzymatic antioxidant systems caused by alcohol.

Abnormally low serum albumin levels are associated with abnormal bone mineral density and osteoporotic fractures: a retrospective studies

BackgroundMany studies have indicated that abnormal bone mineral density (BMD) is related to abnormal liver and kidney function, but the effect of serum albumin level on abnormal BMD and osteoporotic fracture is still controversial. The aim of this retrospective study was to investigate the effects of serum albumin levels on abnormal BMD and osteoporotic fractures.MethodsThe study included 538 patients through the electronic medical records of inpatients and outpatients stored at Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology. A multivariate logistic regression model was employed to test the relationship between serum albumin levels and abnormal BMD, and the effect of serum albumin levels on osteoporotic fractures was verified through the U test. Correlation between age, sex, kidney stones, coronary heart disease, hypertension, diabetes, fatty liver disease, haemoglobin (HB), mean corpuscular haemoglobin concentration (MCHC), platelets (PLT), platelet distribution width (PDW), lymphocytes (LYMP), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), uric acid (UA), total bilirubin (TBIL), total cholesterol (TC), high-density lipoprotein (HDL) and abnormal BMD were analysed by logistic regression modelling after excluding confounding factors.ResultsThe ALB level in osteoporotic patients was 41.70 (36.40–45.00) g/L, which was significantly lower than those in the normal BMD and reduced BMD groups. The odds ratio (OR) (95% confidence interval [CI]) between the osteoporosis and normal BMD groups was 0.445 (0.394–0.502); the OR (95% CI) between the osteoporosis and reduced BMD groups was 0.395 (0.341–0.459). In the subgroup analysis by whether or not a fracture was present, the OR (95% CI) was 0.073 (0.045–0.119).ConclusionsALB is a protective factor against osteoporosis and osteoporotic fractures, suggesting that it may have the potential to predict osteoporosis onset and fractures.

Associations between milk infrared-predicted plasma biomarkers of stress resilience and fertility in dairy cattle: insights for enhancing breeding programs and herd management

Fertility is a crucial aspect of dairy herd efficiency and sustainability. Among factors influencing fertility in dairy cattle, metabolic stress and systemic inflammation of animals are of main relevance, especially in the postpartum stage when ovarian activity begins and cows are inseminated. Our study aimed to infer the associations between milk infrared-predicted blood biomarkers of stress resilience and fertility traits, namely the interval from calving to first service (iCF), days open (DO), and the pregnancy rate at first service (PRF) in a multi-breed population of 89,097 dairy cows. The blood metabolites (15 blood biomarkers related to hepatic damage and function, oxidative stress, and inflammation/innate immunity) were predicted using milk Fourier-transform mid-infrared (MIR) spectroscopy. A gradient boosting machine (GBM) approach with leave-one-batch-out cross-validation (R2 range from 0.45 to 0.82) was implemented to an independent calibration database of 1,367 lactating cows reared in 5 herds. Calibration equations were then applied to a population database of 1,799,186 MIR milk spectral data, that were then merged with fertility data collected by the Breeders Federation of Alto Adige (Bolzano province, Italy) generating a final database of 285,145 records. The 2 databases were merged according to the milk test day (and thus the MIR spectrum) closest to the date of insemination. The interval fertility traits were fitted as the hazard of either receiving the first service after calving at time t for iCF or becoming pregnant after calving at time t for DO in a Cox proportional-hazards model. Statistical analyses were performed including in the model the number of lactations, year of calving, and herd as fixed effects. The independent effect of the MIR-based predictions of metabolites was also included with each metabolite evaluated separately and discretized into 7 levels based on percentiles. Pregnancy rate at first service, on the other hand, was analyzed using logistic regression and the same explanatory variables. The metabolites linked to liver function and damage, such as aspartate aminotransferase, total bilirubin, and alkaline phosphatase, had a relevant influence on iCF and DO in terms of the hazard ratio (HR). Relevant results were also obtained for the biomarkers related to oxidative stress and inflammation/innate immunity. Specifically, increasing levels of ceruloplasmin, total reactive oxygen metabolites, and advanced oxidation protein products resulted in a relevant decrease in the HR of cows becoming pregnant. The logistic regression analysis did not reveal any significant effect of the aforementioned biomarkers on PRF, indicating that the effects of the stress response mainly concern the resumption of the ovarian cycle after calving. The results for the associations of the predicted biomarkers of the stress response with iCF and DO were consistent with expected physiological patterns. In conclusion, the predicted biomarkers investigated revealed to be promising novel phenotypes for assessing animal health and welfare, in the view of enhancing fertility in dairy cattle also through selective breeding, thus improving the overall efficiency of dairy herds.

Clinical Results of Percutaneous Transhepatic Biliary Drainage With Different Hepatic Access and Methods in the Treatment of Obstructive Jaundice.

Percutaneous transhepatic biliary drainage (PTBD) is a common procedure for biliary obstruction jaundice caused by biliary tract obstruction. PTBD can be performed using external or external-internal methods, by the right or left lobe approach. However, differences in both the method used and the hepatic approach may affect success rates and complications. Therefore, this study aimed to examine the outcomes and complications of PTBD and compare them according to different methods and hepatic approaches. Patients who underwent PTBD procedures in our interventional radiology department due to benign or malignant pathologies between March 2021 and March 2024 were included in the study. The diagnoses of the patients, and total and direct bilirubin values before and after the procedure were recorded. The clinical results and the complications of PTBD were compared statistically according to the hepatic approach and method. Univariate logistic regression analysis was performed to determine significant factors associated with PTBD success and complications. Sixty patients were included in our study (32 men, 28 women; mean age: 67.14±13.61y). The most common indication was malignant bile duct obstruction (90%). The obstruction was mostly at the level of the common bile duct (46.7%). The success rate of PTBD was the highest with the left-side external biliary drainage approach (left-side external biliary drainage, 81.2%; right-side internal-external biliary drainage, 77.8%; right-side external biliary drainage, 69.2%; P=0.596). The complication rate was higher for right-side access (right side 15.9%, left side 12.5%, P=0.744). Univariate logistic regression analysis revealed that PTBD success in females was 5 times higher than in males [Exp(B): 5.000, β: 1.609, P<0.05]. Univariate logistic regression analysis revealed that methods used, entry lobes, and entry levels did not significantly affect PTBD success and complication incidence (P>0.05). All approaches and methods used during PTBD were associated with low complications and high success rates. Nevertheless, external biliary drainage with right hepatic access has the lowest clinical success rate and a higher complication rate than the left-lobe approach. We observed that left-sided external biliary drainage was the most successful method and had fewer complications.

Surgical aspects of treatment a patient with choledocholithiasis after gastropancreatoduodenectomy resection

Cholelithiasis is a common problem in surgery. The pathological basis of the disease is a imbalance between cholesterol, bilirubin and bile acid metabolism. There are several risk factors for cholelithiasis, both modifiable and non-modifiable. Complications of this pathology most often require surgical intervention: either planned or emergency. One of such complications is choledocholithiasis. Most often, choledocholithiasis occurs as a result of migration of stones from the gallbladder, less often of stones form in the bile ducts. In the world and Russian literature, many works are devoted to the etiology, pathogenesis and the treatment of patients with choledocholithiasis. The diagnosis is confirmed using advanced imaging methods, such as magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography. A widely used method of treatment is endoscopic retrograde cholangiopancreatography in combination with endoscopic papillosphincterotomy. However, in case of severe choledocholithiasis, including with an altered anatomical picture, standard methods do not always allow to achieve the desired result. This article describes a clinical case of successful treatment of a patient with choledocholithiasis that developed two years after gastropancreatoduodenal resection for adenocarcinoma of the major duodenal papilla.

Clinical findings and prognostic factors for immediate survival in 33 dogs undergoing surgery for biliary peritonitis.

To report demographics, clinical signs, physical examination, diagnostic test results, surgical findings, and prognostic factors for in-hospital postoperative mortality following biliary peritonitis surgery in dogs. Retrospective, multi-institutional cohort study. Thirty-three client-owned dogs. The medical records of dogs that underwent surgery for biliary peritonitis between 2015 and 2021 were reviewed. Dogs were included if they had a definitive diagnosis of biliary peritonitis and a surgery report. Information on demographics, clinical signs and duration, physical examination findings, laboratory and diagnostic imaging results, surgery, perioperative medical treatment, and complications for each patient was obtained. Statistical analyses were performed to identify risk factors that affected survival. Cholecystectomy was the procedure most frequently performed (31/33, 94%). The overall mortality rate was 36% (12/33). Survival was affected negatively by hyperbilirubinemia (p = .049), administration of vasopressors (p = .002), renal dysfunction (p = .008), and number of postoperative complications (p = .005). A mortality rate of 50% was observed in dogs with a total bilirubin level greater than 60.5 μmol/L. There was no difference in mortality rate between septic and nonseptic biliary effusions. New prognostic factors associated with in-hospital postoperative mortality in dogs treated surgically for biliary peritonitis were identified, while others that had been reported previously were confirmed. A preoperative bilirubin threshold value associated with a 50% mortality was identified. Additional information that could help to predict survival in dogs with biliary peritonitis has been provided. However, further research is warranted.

The influence of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra on rat liver function and structure

Background. Tea mistletoe (Scurrula atropurpurea (Blume)) and mango mistletoe (Dendrophthoe pentandra) have been known as a potential medicine for several diseases.Objective: to investigate the effect of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra (MESA-DP) on rat liver function and structure using serological and histopathological analysis.Material and methods. This study was experimental during 28 days using 20 rats divided into four groups (Group 1 as a control, while Groups 2, 3, and 4 were given MESA-DP at doses 250, 500, and 1,000 mg/kg of body weight, respectively). The liver histopathological structure was observed using hematoxylin-eosin staining. The liver function assessment included total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Data were analyzed using a one-way ANOVA analysis (ANalysis Of VAriance) and performed via SPSS Statistics 17.0 (IBM, USA).Results. The administration of MESA-DP did not show significant differences at all doses for the liver rat function in total bilirubin, SGOT, SGPT, albumin, cholesterol and triglycerides (p&gt;0.05), while globulin, total protein, HDL and LDL showed significant results (p&lt;0.05). The liver histopathological structure showed the number of pyknotic, karyorrhectic and karyolytic cells in rats after MESA-DP administration compared to controls, which grew with increasing dose.Conclusion. The liver function in rats after being exposed to MESA-DP was not affected in terms of total bilirubin, SGOT, SGPT, albumin, cholesterol, and triglyceride levels. However, using MESA-DP increased the necrotic liver cells. It may be beneficial for the liver health of experimental animals taking into account the correct dosage.

Global Leadership Initiative on Malnutrition criteria: Clinical benefits for patients with gastric cancer.

Malnutrition is a prevalent condition among patients with gastric cancer and is associated with poor survival outcomes. This study aimed to evaluate the clinical utility of the Global Leadership Initiative on Malnutrition (GLIM) criteria in predicting survival among patients with gastric cancer. The multicenter retrospective cohort study (INSCOC study) included 1406 patients enrolled between December 2012 and April 2020, with follow-up data collected until June 2023. Various indices for muscle evaluation, such as calf circumference (CC) and body weight-standardized hand grip strength (HGS/W), were used to diagnose malnutrition. Kaplan-Meier curves were used to analyze the relationship between nutrition status, as defined by GLIM criteria, and survival outcomes in these patients. The analysis revealed that using CC or HGS/W as positive indicators of malnutrition effectively identified patients with survival-related malnutrition. The incidence of malnutrition was 54.5%, with patients' median overall survival times of 1169 days for stage I and 575 days for stage II cancer (P < 0.001). Malnutrition was identified as an independent risk factor for survival. Additionally, a nomogram developed through Cox regression analysis demonstrated precise predictive capability, incorporating factors such as tumor node metastasis staging, Karnofsky Performance Status Scale, direct bilirubin levels, and nutrition intervention. The study concludes that the GLIM criteria are effective in diagnosing malnutrition and predicting survival in patients with gastric cancer. Nutrition interventions significantly enhance survival outcomes, underscoring the importance of standardized nutrition treatments in improving patient prognosis.

Bilirubin-Modified Chondroitin Sulfate-Mediated Multifunctional Liposomes Ameliorate Acute Kidney Injury by Inducing Mitophagy and Regulating Macrophage Polarization.

Acute kidney injury (AKI) is a dynamic process associated with inflammation, oxidative stress, and lipid peroxidation, in which mitochondrial mitophagy and macrophage polarization play a critical role in the pathophysiology. Based on the expression of the CD44 receptor on renal tubular epithelial cells (RTECs) and activated M1 macrophages being abnormally increased, accompanied by up-regulation of reactive oxygen species (ROS) during AKI, the conjugates of bilirubin (BR), an endogenous antioxidant which has the property of anti-inflammation, and chondroitin sulfate (CS) with CD44-targeting property could be a promising therapeutic carrier. In this study, we develop a CD44-targeted/ROS-responsive CS-BR-mediated multifunctional liposome loading celastrol (CS-BR@CLT) for the targeted therapy of AKI. CS-BR@CLT is shown to selectively accumulate in AKI mouse kidneys via targeting of CD44 receptors. Treatment with CS-BR@CLT significantly ameliorates acute kidney injury caused by ischemia-reperfusion and protects renal function. Mechanistically, CS-BR@CLT inhibits apoptosis, protects mitochondria, promotes autophagy, regulates macrophage polarization, and alleviates interstitial inflammation. Overall, our study demonstrates that CS-BR@CLT could be a promising strategy to ameliorate acute kidney injury.

Parenteral lipid nutrition in congenital gastrointestinal malformation operated cases

Background: Congenital gastrointestinal malformation (CGIM) cases require immediate surgical correction after birth and proper nutrition to meet energy demands. Among the macronutrients, lipids are considered the major energy source, playing a vital role in parenteral nutrition. However, the time of their initiation remains unclear. We compared the data of CGIM cases where lipids were given from the first post-surgical day to those where parenteral lipids were initiated on the second or third day of surgery and then reevaluated them on the seventh day of parenteral nutrition.Methods: We collected the data of patients who had undergone surgical correction for CGIM and were kept on parenteral nutrition including lipids from day 1 of surgery labeling them as group 1. Group 2 comprised of neonates having lipid parenteral nutrition started from day 2 or 3 of surgery. Both groups were reevaluated on the 7th day of parenteral nutrition. Statistical analysis was performed.Results: Group 1 had higher total bilirubin (TB) statistically significant (p-value=0.0299), as well as lower lipase (p-value=0.0286), and lower total lipids (p-value=0.0365). The values were lower of triglycerides (p-value=0.0365), and total lipids (p-value=0.0365), on day 1. Comparing both groups, all biochemical parameters were found to be statistically significant.Conclusion: Lipid deficiency and overload should be carefully evaluated, especially in neonates having undergone recent surgical interventions, which increase their nutritional demands. No adverse effects were seen in our study related to parenteral lipid emulsion administration in post-surgical congenital gastrointestinal malformation cases. Early initiation of parenteral lipid regimens can provide better outcomes.Keywords: Congenital gastrointestinal malformations; Intravenous lipid emulsions; Parenteral nutrition; Gestational age; Milk formula

Comparison of BiliCocoon phototherapy with overhead phototherapy in hyperbilirubinemic neonates. A randomized clinical trial.

Around 2-6% of term or late preterm neonates receive phototherapy for hyperbilirubinemia. Standard treatment today is overhead phototherapy. A new device has been developed, the BiliCocoon, where the neonates are "wrapped" presumably making them more comfortable. The aim was to compare the efficacy and performance of the BiliCocoon with overhead LED phototherapy. A randomized open-label multicenter trial in three Danish neonatal units. Healthy hyperbilirubinemic neonates, gestational age ≥33 weeks and postnatal age 24 h to 14 days were randomized to 24 hours' of treatment with BiliCocoon or overhead blue LED phototherapy with an equal level of irradiance. A mixed effect model with random effect by center was used to compare the percentage decrease in total serum bilirubin (TSB) between the treatments. Totally 83 neonates were included. Mean TSB reduction in the BiliCocoon group (N = 42), adjusted for baseline TSB, was significantly lower than in the overhead LED group (N = 41), 29% vs. 38% (p-value < 0.01). Overall difference in temperature by treatment (BiliCocoon vs overhead) was 0.70 [0.37; 1.02] °C, p-value < 0.01. Bilirubin reducing efficacy of BiliCocoon was lower than that of overhead phototherapy, but it was sufficient for nearly all neonates during 24 hours of treatment. The BiliCocoon has a bilirubin reducing efficacy, sufficient for almost all neonates during 24 hours of phototherapy. The BiliCocoon does not have an equal bilirubin reducing efficacy as overhead phototherapy. The duration of light exposure was longer for the neonates treated in the BiliCocoon. A few neonates can be exclusively breastfed in the BiliCocoon throughout the treatment. The reason for stopping breastfeeding in the BiliCocoon was most often, that the neonates developed hyperthermia.

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Diagnostic value of biochemical markers in prediction of perforation in acute appendicitis: a cross-sectional study.

Acute appendicitis, despite being the most common surgery, can result in increased morbidity and mortality in the case of perforated appendicitis. Identifying a perforation early can reduce the impact on the patient. Bilirubin, C-reactive protein (CRP), and white blood cell (WBC) count have been shown to indicate perforation in appendicitis. A cross-sectional analytical study was conducted to observe the association between preoperative bilirubin, CRP, and white cell count with the histological findings of either the presence or absence of perforation of the appendix. The eligibility criteria included all patients above 18 years with appendicitis who were managed surgically in the study hospital, Shree Birendra Hosptial, between 1 December 2021 to 30 May 2022. The study was conducted after the approval from the ethics committee. Out of 150 patients, 112 had open surgery and 38 underwent laparoscopic appendectomy. One hundred thirty-four had non-perforated appendix and 16 cases had perforated appendix. The older age group was associated with appendiceal perforation more than the younger age group. Patients with a duration of symptoms less than 24 h and more than 72 h developed perforated appendicitis less frequently. The odds of encountering perforated appendicitis increased by 2.644 times per 0.972 rise in total bilirubin (P= 0.004) and the odds of encountering perforated appendicitis increased by 6.474 times per 1.868 rise in conjugated bilirubin (P= 0.003). There was no significant difference in total leucocyte count and neutrophil percentage among perforated and non-perforated groups. The diagnostic value of the CRP, total bilirubin, and conjugated bilirubin levels was strong and significant when used in combination rather than their individual performance in the diagnosis of perforated acute appendicitis.

The effect of different definitions of hepatic injury on incidence and mortality rates in the ICU patient population with secondary hepatic injury

ObjectiveThe aim was to investigate how different hepatic injury (HI) definitions used in the same study population change incidence and mortality rates and which would best diagnose secondary HI. DesignSingle-centre retrospective observational cohort study. SettingTertiary hospital ICU, ANKARA, Turkey. PatientsFour hundred seventy-eight adult patients were included in the study. InterventionsNone. Main variables of interestThree definitions of HI were compared. Taking the SOFA hepatic criteria (SOFA: Total bilirubin (TBL) > 1.2 mg/dl) as the gold standard, sensitivity, specificity, positive and negative predictive values, and accuracy of the modified 2017 definition by the American College of Gastroenterology (ACG) and the 2019 European Association for the Study of the Liver (EASL) were calculated. ResultsIncidence rates ranged from 10% to 45% according to the definition (p < 0.005), while mortality rates ranged from 38% to 57%. When the SOFA1.2 (TBL > 1.2 definition was taken as the gold standard, the diagnostic value of the ACG definition was high, and HI was found to be an independent risk factor that increased mortality four times. ConclusionsAccording to this study’s results, the incidence and mortality rates of secondary HI vary greatly depending on the definition used. A definition that includes minimal increases in ALT, AST, and TBL predicts mortality with reasonable incidence rates.

Allometric fat mass index and alanine aminotransferase attenuate the associations of platelet parameters with lung cancer risk

We have previously shown that body mass index attenuates a positive association of platelet count (PLT) and inverse of mean platelet volume (MPV) with lung cancer risk in men. It is unclear whether fat mass, lean mass, or liver function tests (LFTs) show similar attenuations. Using bioelectrical impedance measurements (UK Biobank cohort) and multivariable Cox proportional hazards models, we examined the associations of allometric fat-mass index (AFI, fat mass adjusted for height), allometric lean-mass index (ALI, fat-free mass adjusted for height and fat mass), and LFTs with lung cancer risk and their multiplicative and additive interactions with platelet parameters. Based on 1573 lung cancer cases in men and 1473 in women with body composition measurements (1541 in men; 1428 in women with biomarker measurements), AFI in women, ALI in both sexes, alanine aminotransferase (ALT) and total bilirubin in men were inversely associated, while gamma-glutamyl transferase in men and alkaline phosphatase in both sexes were positively associated with lung cancer risk. Only AFI and ALT interacted inversely with PLT and positively with MPV in men. The attenuation of the associations of platelet parameters with lung cancer risk by high-AFI and high-ALT in men suggests that adiposity-related factors hinder lung-cancer-related platelet associations.

The Efficacy of Flaxseed Oil on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent liver disorder and a leading cause of elevated liver enzymes. Previous research indicates that a diet rich in polyunsaturated fatty acids (PUFAs) can alleviate liver insulin resistance. This study investigates the therapeutic effects of flaxseed oil, a primary PUFA source, on NAFLD treatment. In a randomized clinical trial comprising 60 NAFLD patients diagnosed with NAFLD of grades 1, 2, and 3, participants were assigned to either a flaxseed oil capsule group or a placebo group for 2 months. Before the intervention, both groups showed no significant differences in examined parameters. However, after the intervention, the flaxseed oil group exhibited significant improvements in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), fasting blood sugar (FBS), and total bilirubin compared to the placebo group. Specifically, reductions were observed in AST (p=0.010), ALT (p=0.047), ALP (p<0.001), FBS (p=0.016), and total bilirubin (p=0.004). These findings suggest that flaxseed oil may hold promise as a therapeutic intervention for NAFLD, highlighting its potential in managing liver disease and metabolic parameters.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

056. Impacted CBD Stones in Ampula Vater Evacuated by Transduodenal Approach in A 48-year-old Patient at Prof. Dr. IGNG Ngoerah Hospital in 2024

Background: Cholecystolithiasis and choledocholithiasis are common biliary disorders that can lead to significant complications if left untreated. Among these complications, the formation of impacted CBD stones, particularly at the Ampulla of Vater, poses a unique clinical challenge. The Ampulla of Vater is the anatomical site where the common bile duct (CBD) and pancreatic duct converge, and its obstruction can lead to biliary colic, cholangitis, or pancreatitis. Urgent stone removal is critical for improving the patient’s condition. Case: A 48-year-old male patient presents to the emergency department with right upper abdominal pain since 10 days ago accompanied with icteric sclera since 10 days ago. There was nausea and vomiting when eating high-fat foods. The stools were brownish in color, the urine color was similar to tea color. The patient regularly takes UDCA 3 x 250 mg IO, simvastatin 1 x 20mg IO, curcuma 3 x1 tab IO, lansoprazole 2 x 30mg IO. Physical examination showed icteric eyes, jaundice, liver enlargement 2 fingers below costae arch with positive Murphy's sign. Complete blood examination showed leukocytosis, decreased hemoglobin, hypokalemia, as well as increased direct bilirubin, total bilirubin, and indirect bilirubin. BOF result showed sentinel loop on the right umbilical region suspected inflammatory process. MRI impression of choledocholithiasis causing dilatation of EHBD and IHBD proximal aspect without signs of cholangitis, hepatomegaly, simple cyst of left kidney (Bosniak I). Abdominal ultrasound with the conclusion of cholecystitis with dilatation and thickening of the ductus cysticus wall suspicious of inflammation, dilatation of the right and left IHBD, common hepatic duct, to the proximal common biliary duct, the presence of distal obstruction cannot be evaluated because it is covered by intestinal shadows, mild prostatic hypertrophy accompanied by prostate calcification. After Cholecystectomy and Explore CBD transduodenal, the patient was placed with thoracic drain with good outcome. Conclusion: The transduodenal approach to evacuating impacted CBD stones at the Ampulla of Vater is a valuable technique that can yield excellent outcomes in select cases. This case report underscores the importance of a tailored approach based on individual patient anatomy and stone characteristics.