Plasma Bilirubin Concentration Research Articles

Evaluation of the effect of daily cow's milk production on liver enzyme levels

Objective: The aim of the study was to determine the possible impact of the total daily amount of skim milk on the level of bilirubin and liver enzymes through regression analysis. 
 
 Materials and Methods: The study included 63 Holstein-Friesian cows. They were formed in 3 groups, based on the amount of daily milk production. Peripheral blood was punctured, through which the activities of total bilirubin were analyzed (μmol/L), as well as liver enzymes: alanine aminotransferase – ALT (U/L), aspartate aminotransferase – AST (U/L), lactate dehydrogenase – LDH (U/L) and alkaline phosphatase – ALP (U/L). 
 
 Results: The lowest concentration of total bilirubin in blood plasma was recorded in the group of cows that have the lowest daily milk production (1.295 ± 0.255 µmol/L), and highest concentration is in cows that produce the most milk (1.855 ± 0.159 µmol/L), but intergroup differences are not significant. Regression analysis found a statistically significant relationship between the amount of produced daily milk and the concentration of total bilirubin (R2=0.132, p=0.0050.05). 
 
 Conclusion: The activities of bilirubin and liver enzymes in the examined cows were in physiological balance. This indicates that the cows on the farm are raised in modern and good zootechnical and feeding conditions. In such conditions, dairy cows are able to maintain blood composition and homeostatic integrity within physiological limits and adequate reproductive and productive capacity.

Genetics of Plasma Bilirubin and Associations between Bilirubin and Cardiometabolic Risk Profiles in Danish Children and Adolescents.

Bilirubin is the end product of heme catabolism, mainly produced by the breakdown of mature red blood cells. Due to its anti-inflammatory, antioxidant, antidiabetic, and antilipemic properties, circulating bilirubin concentrations are inversely associated with the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality in adults. Some genetic loci associated with circulating bilirubin concentrations have been identified by genome-wide association studies in adults. We aimed to examine the relationship between circulating bilirubin, cardiometabolic risk factors, and inflammation in children and adolescents and the genetic architecture of plasma bilirubin concentrations. We measured fasting plasma bilirubin, cardiometabolic risk factors, and inflammatory markers in a sample of Danish children and adolescents with overweight or obesity (n = 1530) and in a population-based sample (n = 1820) of Danish children and adolescents. Linear and logistic regression analyses were performed to analyze the associations between bilirubin, cardiometabolic risk factors, and inflammatory markers. A genome-wide association study (GWAS) of fasting plasma concentrations of bilirubin was performed in children and adolescents with overweight or obesity and in a population-based sample. Bilirubin is associated inversely and significantly with a number of cardiometabolic risk factors, including body mass index (BMI) standard deviation scores (SDS), waist circumference, high-sensitivity C-reactive protein (hs-CRP), homeostatic model assessment for insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), triglycerides, and the majority of measured inflammatory markers. In contrast, bilirubin was positively associated with fasting plasma concentrations of alanine transaminase (ALT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SDS), and the inflammatory markers GH, PTX3, THBS2, TNFRSF9, PGF, PAPPA, GT, CCL23, CX3CL1, SCF, and TRANCE. The GWAS showed that two loci were positively associated with plasma bilirubin concentrations at a p-value threshold of <5 × 10-8 (rs76999922: β = -0.65 SD; p = 4.3 × 10-8, and rs887829: β = 0.78 SD; p = 2.9 × 10-247). Approximately 25% of the variance in plasma bilirubin concentration was explained by rs887829. The rs887829 was not significantly associated with any of the mentioned cardiometabolic risk factors except for hs-CRP. Our findings suggest that plasma concentrations of bilirubin non-causally associates with cardiometabolic risk factors in children and adolescents.

Crosslinked Bifunctional Particles for the Removal of Bilirubin in Hyperbilirubinemia Cases.

This work describes the development of styrene-divinylbenzene (St-DVB) particles with polyethylene glycol methacrylate (PEGMA) and/or glycidyl methacrylate (GMA) brushes for the removal of bilirubin from blood in haemodialyzed patients. Bovine serum albumin (BSA) was immobilized onto the particles using ethyl lactate as a biocompatible solvent, which allowed the immobilization of up to 2 mg BSA/g of particles. The presence of albumin on the particles increased their capacity for bilirubin removal from phosphate-buffered saline (PBS) by 43% compared to particles without albumin. The particles were tested in plasma, finding that St-DVB-GMA-PEGMA particles that had been wetted in ethyl lactate with BSA reduced the concentration of bilirubin in plasma by 53% in less than 30 min. This effect was not observed in particles without BSA. Therefore, the presence of albumin on the particles enabled quick and selective removal of bilirubin from plasma. Overall, the study highlights the potential use of St-DVB particles with PEGMA and/or GMA brushes for bilirubin removal in haemodialyzed patients. The immobilization of albumin onto the particles using ethyl lactate increased their capacity for bilirubin removal and enabled quick and selective removal from plasma.

Effect of Rhodiola rosea Rhizome and Punica granatum Fruit Peel on the Metabolic Processes and Physiological Activity of Rats Fed with Excessively Fat Diet.

Rhodiola rosea (golden root) and Punica granatum (pomegranate), as well as a number of other species of medicinal plants, exert an array of biological effects: adaptogenic, antioxidant and anti-inflammatory. However, there are not enough contemporary studies of their influence on metabolic processes, especially in cases of imbalanced diet. Lipid dysregulation is the main reason for many diseases, including obesity, cardiovascular disorders, non-alcoholic fatty liver disease, hypertension, atherosclerosis and insulin resistance. Recently, a growing amount of evidence has suggested the positive effects of certain natural nutrients on lipid metabolism. The work aims to define the general effect of golden root rhizome and pomegranate peel on physiological activity and metabolic processes in model animals fed with excessively fat diet. This study is relevant for the development of drugs and food additives for treatment and prophylaxis of metabolism disorders. In a 30-day experiment, we determined the effect of golden root (Rhodiola rosea L.) rhizome and pomegranate (Punica granatum L.) peel on the physiological activity and metabolic processes of 24 laboratory rats consuming a high-fat diet. The physical activity was evaluated according to the mass gain of animals and change in the relative mass of the internal organs, and also the functional conditions of the central nervous system, as demonstrated by the indicators of the locomotor activity and emotional status, determined in the open field test. The influence on the metabolic processes was revealed by biochemical and clinical blood analyses. Body mass of rats fed with golden root (R. rosea) reached 125.8 % of the initial body mass; when fed on pomegranate (P. granatum), it reached 123.9 %; and the control group reached only 111.5 % of the initial body mass. The rhizomes of R. rosea in the diet of male rats during the month of the experiment did not cause significant changes in the relative organ mass, and the pomegranate peel fruits led to a decrease in the thymus relative mass, as well as liver and brain. R. rosea rhizomes in the rats' diet led to an increase in the activity of alkaline phosphatase, and also to a decrease in the concentration of urea and urea nitrogen. Diet supplemented with R. rosea also contributed to a strong decrease in plasma concentrations of bilirubin and triglycerides (up to 57.0 % compared with the concentration in the control group). The rhizomes of R. rosea contributed to an unreliable decrease in the atherogenicity index. The pomegranate peel also greatly increased alkaline phosphatase activity and reduced plasma triglyceride concentrations. In addition, in rats consuming the peel of P. granatum, blood glucose concentration decreased. Under the influence of P. granatum, a strong increase in the atherogenic index of plasma (up to 518.6 % of the control) was observed because of a decrease in the concentration of high-density lipoproteins (up to 57.1 %) and a simultaneous elevation of the concentration of low-density lipoproteins (up to 158.3 % of the control). Open field test between groups remained without significant changes. The results indicate that the rhizome of R. rosea and peel of P. granatum are safe as food additives to high-fat diet and did not cause pathological changes and side effects, and at the same time significantly influence the metabolic processes (lipid and carbohydrate). Our study theoretically substantiates the use of R. rosea rhizome and P. granatum peel for the production of nutraceutical and pharmacological products for the correction of metabolic disorders of people and animals. Doses and periods of their application require further research.

Destabilization of Atherosclerotic Plaque by Bilirubin Deficiency.

The rupture of atherosclerotic plaque contributes significantly to cardiovascular disease. Plasma concentrations of bilirubin-a byproduct of heme catabolism-inversely associate with risk of cardiovascular disease, although the link between bilirubin and atherosclerosis remains unclear. To assess the role of bilirubin in atherosclerotic plaque stability, we crossed Bvra-/- with Apoe-/- mice and used the tandem stenosis model of plaque instability. Human coronary arteries were obtained from heart transplant recipients. Analysis of bile pigments, heme metabolism, and proteomics were performed by liquid chromatography tandem mass spectrometry. MPO (myeloperoxidase) activity was determined by in vivo molecular magnetic resonance imaging, liquid chromatography tandem mass spectrometry analysis, and immunohistochemical determination of chlorotyrosine. Systemic oxidative stress was evaluated by plasma concentrations of lipid hydroperoxides and the redox status of circulating Prx2 (peroxiredoxin 2), whereas arterial function was assessed by wire myography. Atherosclerosis and arterial remodeling were quantified by morphometry and plaque stability by fibrous cap thickness, lipid accumulation, infiltration of inflammatory cells, and the presence of intraplaque hemorrhage. Compared with Bvra+/+Apoe-/- tandem stenosis littermates, Bvra-/-Apoe-/- tandem stenosis mice were deficient in bilirubin, showed signs of increased systemic oxidative stress, endothelial dysfunction, as well as hyperlipidemia, and had a higher atherosclerotic plaque burden. Heme metabolism was increased in unstable compared with stable plaque of both Bvra+/+Apoe-/- and Bvra-/-Apoe-/- tandem stenosis mice and in human coronary plaques. In mice, Bvra deletion selectively destabilized unstable plaque, characterized by positive arterial remodeling and increased cap thinning, intraplaque hemorrhage, infiltration of neutrophils, and MPO activity. Proteomic analysis confirmed Bvra deletion enhanced extracellular matrix degradation, recruitment and activation of neutrophils, and associated oxidative stress in unstable plaque. Bilirubin deficiency, resulting from global Bvra deletion, generates a proatherogenic phenotype and selectively enhances neutrophil-mediated inflammation and destabilization of unstable plaque, thereby providing a link between bilirubin and cardiovascular disease risk.

Synthesis, characterization, and biological verification of asialoglycoprotein receptor-targeted lipopolysaccharide-encapsulated PLGA nanoparticles for the establishment of a liver fibrosis animal model.

Liver fibrosis is generally preceded by various liver injuries and often leads to chronic liver diseases and even cirrhosis. Therefore, a liver fibrosis animal model is the cornerstone for the development of therapeutic strategies for hepatic diseases. Although administration of hepatotoxic substances and/or bile duct ligation have been widely performed to construct the in vivo model over the last decades, they are seriously hindered by time-consuming protocols, high mortality, and instability, indicating that an effective and safe approach for the induction of liver fibrosis is still urgently needed nowadays. In this study, we have developed asialoglycoprotein receptor (ASGPR)-targeted lipopolysaccharide (LPS)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles named ALPNPs for establishing an animal model of liver fibrosis. The ALPNPs are characterized as having a spherical nanostructure with size of 182.9 ± 8.89 nm and surface charge of -8.3 ± 1.48 mV. An anti-ASGPR antibody bound to the surface of the nanoparticles with a crosslinking efficiency of 95.03% allows ALPNPs to have hepatocyte-binding specificity. In comparison to free LPSs, the ALPNPs can induce higher aspartate aminotransferase and total bilirubin concentrations in plasma, reduce the blood flow rate in the portal system and the kidneys, and increase vascular resistance in the liver, kidneys, and collateral shunting vasculature. Based on histological and RNA-seq analyses, the ALPNPs can provide similar capability on inducing hepatic inflammation and fibrosis compared to free LPS but possess higher liver targetability than the naked drug. In addition, the ALPNPs are less toxic in organs other than the liver in comparison to free LPS, demonstrating that the ALPNPs do not elicit off-target effects in vivo. Given the aforementioned efficacies with other merits such as biocompatibility and drug release controllability provided by PLGA, we anticipate that the developed ALPNPs are highly applicable in establishing animal models of liver fibrosis in pre-clinical studies.

Associations of a liver health index with health, milk yield, and reproductive performance in dairy herds in the northeastern United States

The objective was to evaluate a liver health index (LHI) by evaluating its association with negative health events, milk yield, and risk of pregnancy within 150 d in milk (DIM). In a retrospective cohort study, an LHI was calculated based on plasma albumin, cholesterol, and bilirubin concentrations for 265 primiparous and 611 multiparous cows 3 to 12 DIM enrolled across 72 farms in the northeastern United States. Mixed effects linear regression models were used to evaluate if (1) metritis (MET), (2) displaced abomasum (DA), (3) clinical ketosis (CK), (4) one or more of the 3 disorders (MET, DA, or CK), (5) 2 or more of the 3 disorders (MET, DA, or CK), or (6) culling within 30 DIM was associated with LHI. Mixed effects linear regression models were used to evaluate if LHI was associated with 305-d mature equivalent milk at the fourth test day (ME305; mean ± standard deviation: 114 ± 13 DIM) and a Cox proportional hazards model was used to evaluate if LHI was associated with pregnancy within 150 DIM. Cows that were diagnosed with MET, DA, CK, one or more of the disorders, 2 or more of the disorders, or were culled within 30 DIM had a lower LHI than cows that were not diagnosed with a disorder or culled. A 1-unit increase in LHI was associated with a 154 ± 38 kg increase in ME305 and a 8% increased risk of pregnancy within 150 DIM [hazard ratio (95% confidence interval): 1.08 (1.03 to 1.14)] for multiparous cows; however, we did not identify a relationship between LHI and ME305 or pregnancy within 150 DIM for primiparous cows. These results suggest that the LHI is associated with health, milk yield, and pregnancy within 150 DIM for multiparous cows and health for primiparous cows; therefore, the LHI can be used as a tool to evaluate transition cow success.

Functionalization of Poly(styrene-co-methyl methacrylate) Particles for Selective Removal of Bilirubin.

Hyperbilirubinemia is one of the main causes of death in patients with severe hepatic problems, which justifies the research for bilirubin removal solutions. In this study, St-MMA particles with PEGMA and/or GMA brushes were synthesized. First, the recipe for St-MMA was optimized and then adapted for PEGMA and GMA incorporation. Different solvents were then assayed to improve the BSA immobilization capacity of the particles. Ethyl lactate proved to be the best solvent, reaching a BSA immobilization capacity improvement of up to 60% for St-MMA-GMA-PEGMA particles. These particles also presented the best results for BR removal from PBS. No significant differences in the final capacity for BR removal from PBS media were observed when BSA was attached to the particles; however, the kinetics were greatly improved, requiring half the time. Finally, St-MMA-GMA-PEGMA particles that were wetted in EL with BSA reduced the bilirubin concentration in plasma from levels that threaten the survival of critical patients to levels close to those of healthy individuals in less than 30 min. On the contrary, particles without BSA were unable to remove bilirubin from plasma. Thus, the attachment of albumin to the particles plays a key role in selectively reducing bilirubin levels.

A purely solid-state based method for bilirubin levels determination in plasma.

In the past half-century, the advent of solid-state electronics, i.e., microcontrollers, transistors, photodiodes, light-emitting diodes and more, has led to the improvement of the tools we, as a human race, need and use in our daily lives. Solid-state electronics has specifically contributed significantly to the field of biomedical engineering and has allowed various round-the-clock point-of-care testing applications. These include handheld, wearable, and implantable sensors and devices for accelerated interventions. Furthermore, miniaturization has accelerated the implementation of low-cost and energy-efficient systems with increased performance. In this paper, we have used optical techniques along with the benefits of solid-state electronics to measure bilirubin concentration in plasma with concentrations projected from healthy individuals to hyperbilirubinemia (0 - 30 mg/dL). Traditionally, full-range spectrophotometry is the gold standard optical method and provides the most accurate results but suffers from instrument complexity. Thus, this paper proposes and investigates the measurement of bilirubin by using a dual-wavelength approach combined with photodegradation kinetics. By tracking the changes in the spectral characteristics of bilirubin for 10 minutes (~3 J/cm2), a new model was built to measure bilirubin concentrations and distinguish between low vs high and risky vs non-risky levels. Results show a high positive correlation between the optical responses and concentration (R-square > 0.93) with an average accuracy of ~1.4 mg/dL. On top of that, the technique's viability for point-of-care testing of bilirubin levels was studied using a system-on-chip optical module. Thus, this could help suggest neonatal therapeutic interventions, including enteral feeding, phototherapy, and blood transfusion.

Contribution of genetic factors to high rates of neonatal hyperbilirubinaemia on the Thailand-Myanmar border.

Very high unconjugated bilirubin plasma concentrations in neonates (neonatal hyperbilirubinaemia; NH) may cause neurologic damage (kernicterus). Both increased red blood cell turn-over and immaturity of hepatic glucuronidation contribute to neonatal hyperbilirubinaemia. The incidence of NH requiring phototherapy during the first week of life on the Thailand-Myanmar border is high (approximately 25%). On the Thailand-Myanmar border we investigated the contribution of genetic risk factors to high bilirubin levels in the first month of life in 1596 neonates enrolled in a prospective observational birth cohort study. Lower gestational age (<38 weeks), mutations in the genes encoding glucose-6-phosphate dehydrogenase (G6PD) and uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1 were identified as the main independent risk factors for NH in the first week, and for prolonged jaundice in the first month of life. Population attributable risks (PAR%) were 61.7% for lower gestational age, 22.9% for hemi or homozygous and 9.9% for heterozygous G6PD deficiency respectively, and 6.3% for UGT1A1*6 homozygosity. In neonates with an estimated gestational age ≥ 38 weeks, G6PD mutations contributed PARs of 38.1% and 23.6% for "early" (≤ 48 hours) and "late" (49-168 hours) NH respectively. For late NH, the PAR for UGT1A1*6 homozygosity was 7.7%. Maternal excess weight was also a significant risk factor for "early" NH while maternal mutations on the beta-globin gene, prolonged rupture of membranes, large haematomas and neonatal sepsis were risk factors for "late" NH. For prolonged jaundice during the first month of life, G6PD mutations and UGT1A1*6 mutation, together with lower gestational age at birth and presence of haematoma were significant risk factors. In this population, genetic factors contribute considerably to the high risk of NH. Diagnostic tools to identify G6PD deficiency at birth would facilitate early recognition of high risk cases.

Prevalence, risk factors and metabolic predictors associated with subclinical ketosis on dairy cattle in Batna, Eastern of Algeria

Economic impact of subclinical ketosis (SCK) in dairy herds resulted from a decreased productivity, reproductive performances, and health condition. In Algeria, data availability regarding the prevalence of SCK in dairy cows were limited. The present study is a contribution in that direction and aimed to determine the prevalence of SCK between 2 and 50 days postpartum whereas investigating herd- and cow-level risk factors and the metabolic profile associated, on two bovine populations imported and native. The study was conducted with 16 typical representative local dairy cow herds (n = 100; 2–12 years old; located at Merouana, Batna Province) with data collected in a period comprised between August and February of the following year. Concentration of cows’ plasma beta-hydroxybutyrate (BHBA) was used for the diagnosis, with values equal or higher than 1.2 mmol/L chosen as the threshold for SCK detection. Other key associated zootechnical parameters such as body condition score (BCS) were monitored at the same sampling points. Logistic regression analyses were carried out to characterize association between parameters. The average SCK prevalence was 9% and resulted highest during first- and second-week postcalving, with a peak in the first week. The herd size (< 30 lactating cows) and BCS (≤ 3) were risk factors associated with SCK prevalence. At the cow-level, risks of SCK increased in thin individuals (P = 0.058; odds ratio (OR) = 5.00, 95% confidence interval (CI) = 0.95–26.32). At the herd-level, risks of SCK increased in smaller frame size herds (P = 0.047; OR = 8.76, 95% CI = 1.03–74.49). Most cases of SCK were observed in native cows compared to imported. Interestingly, linear stepwise regression showed a good relationship between BHBA and total bilirubin (P = 0.0001; R2 = 0.59). There were significant differences between healthy and ketotic cows regarding plasma concentration of bilirubin (P = 0.003), glucose (P = 0.001), alanine aminotransferase (ALT) (P = 0.008), creatinine (P = 0.007), and sodium (P = 0.02). According to receiver operating characteristic (ROC) curve analysis, the best parameter for SCK prediction is total bilirubin with more than 4.09 g/L as a cutoff point (77.78% sensitivity and 94.51% specificity). According to metabolic profile and feeding data we suggest that most cases of SCK observed in our study are type I. Further studies are required to validate other metabolic predictors for SCK and investigate adaptation of imported cows in semiarid regions in Algeria.

Environmental exposure and clinical correlates of hepatocellular carcinoma in New York City: a case only study.

In the U.S., Hepatocellular carcinoma (HCC) incidence rates have increased. We aimed to determine whether environmental exposure plays a role in the high incidence of HCC observed in New York City. We conducted a hospital-based case only study to examine the prevalence of aflatoxin B1 (AFB1)- and polycyclic aromatic hydrocarbon (PAH)-albumin adducts and the distribution of adducts by different characteristics of HCC patients. Blood samples were collected from 155 HCC patients for biomarker analyses.We observed that about 46% and 49% of cases had detectable AFB1- and PAH-albumin adducts, respectively. There were significant differences between AFB1-albumin adducts and selected factors such as HCV infection status (p = 0.04), diabetes (p = 0.03) and Barcelona Clinic Liver Cancer stage (p = 0.02). Cases with detectable PAH-albumin adducts had a smoking history compared with those with nondetectable levels (p = 0.04). The level of AFB1-albumin adducts was positively correlated with plasma bilirubin (rs = 0.32, p < 0.0001) and adiponectin concentrations (rs = 0.28, p = 0.0005). The level of aflatoxin B1-albumin adducts was negatively associated with blood albumin concentration (rs = -0.28, p = 0.0009) and plasma DNA LINE-1 methylation (rs = -0.16, p = 0.04). Our study provides additional evidence that environmental exposures including to aflatoxin might drive the high incidence of HCC observed in the New York City.

Effect of Salvia officinalis and S. sclarea on rats with a high-fat hypercaloric diet

Phytotherapy for the correction of excess body weight is widely used. However, a comprehensive study of herbal preparations on the organism of model animals has been carried out only for a few plant species. Supplementing the diet of rats with closely related sage species (Salvia officinalis L. and S. sclarea L.) against the background of high-fat hypercaloric diet triggered multidirectional changes in their metabolism. The addition of crushed dry shoots of S. officinalis to the diet of animals led to a sharp increase in their body weight (up to 130.8% of the initial one in 30 days of the experiment). The body weight of the rats treated with S. sclarea for 30 days increased only up to 103.8% of their initial weight and was lower than in the control group. Addition of S. officinalis caused an increase in daily weight gain up to 253.1% of the control group, and S. sclarea – its decrease to 27.8% of the daily weight gain in the control group. In the S. officinalis group, the relative weight of the brain, spleen, and thymus decreased, while in the S. sclarea group, the relative weight of the thymus decreased and that of the colon increased. Under the influence of S. officinalis, the concentration of urea, total bilirubin, and triglycerides in the blood plasma of male rats decreased and the concentration of total protein and the activity of alkaline phosphatase increased. While consuming S. sclarea shoots, there was an increase of alkaline phosphatase activity in the rats’ blood, but atherogenic index (23.1% of the level of the control group) sharply dropped due to an increase in the concentration of high-density lipoprotein cholesterol (286.9% of the control) and a decrease in the concentration of low-density lipoprotein cholesterol (67.7% of control). In rats feeding on S. sclarea shoots, we observed a decrease in the concentration of triglycerides in the blood (39.9% of the control), a decrease in the activity of gamma-glutamyl transferase (62.8%), and an increase in the Ca/P ratio (132.5% of the control group). No significant changes were observed in CBC and WBC differential of male rats when eating S. officinalis and S. sclarea shoots. According to the results of the open field test, the physical and orientational activity of male rats under the influence of S. officinalis significantly decreased by the end of the experiment. Emotional status of rats, on the contrary, decreased when they ate dry crushed shoots of S. sclarea in the composition of the food. Thus, excess body weight of rats in the conditions of hypercaloric diet led to more pronounced deviations from the norm while consuming dry crushed shoots of S. officinalis. The addition of S. sclarea dry crushed shoots to the animals’ diet normalized the body weight in comparison with the control group, reduced the negative manifestations of obesity at the biochemical and organismal levels. In this regard, the substances that contains S. sclarea should be carefully studied for anti-atherosclerotic activity, and tea supplemented with S. sclarea shoots can be recommended as a corrective supplement in the diet of overweight people.

Maternal outcome of Crigler-Najjar syndrome type-2: Case report

Crigler-Najjar Syndrome type 2 [CN-2] is an uncommon inherited disorder characterized by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in one of the five exons of the UGT1A1 gene which codes for the enzyme hepatic uridine diphosphate glucoronosyl transferase-1, required for the conjugation and further excretion of bilirubin from the body via bile. Affected people are usually asymptomatic apart from jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbital in terms of reduction in bilirubin levels. Genetic testing confirms the finding of Crigler-Najjar syndrome. At least 20 different mutations of UGT1A1 have been associated with CN-2; all encode a bilirubin-uridine diphosphate glucuronosyl transferase-1 with markedly reduced but detectable enzymatic activity. Bilirubin concentrations are typically lower in CN-2, and plasma bilirubin levels can be reduced to 3 to 5 mg/dL by phenobarbital. Although uncommon in CN-2, bilirubin encephalopathy has occurred at all ages, typically associated with factors that temporarily elevation the plasma bilirubin concentration above baseline e.g. stress, prolonged fasting, an intercurrent illness like influenza. For this reason, phenobarbital therapy is often recommended. CN-2 is infrequent, and only a few pregnancies with this condition have been reported. The objective of the case study is to report a rare case of maternal CN-2 in the pregnancy and to evaluate whether pregnancy is safe in patients with the disease. A 29 years old mother with CN-2 had given birth to a baby girl by spontaneous vaginal delivery without complications. The newborn had mild unconjugated hyperbilirubinemia which was further treated by phototherapy and early morning sunlight. It can be concluded that that pregnancy need not be contraindicated in CN-2. Keywords: Hyperbilirubinemia, Phototherapy, UGT1A1 gene, Jaundice, Glucuronidation.

Hyperlipasemia in critically ill dogs with and without acute pancreatitis: Prevalence, underlying diseases, predictors, and outcome.

BackgroundHyperlipasemia is frequent in critically ill people without evidence of acute pancreatitis (AP), and has been associated with increased morbidity and mortality.ObjectiveTo evaluate the prevalence of hyperlipasemia at admission and development of hyperlipasemia during hospitalization in critically ill dogs, explore factors associated with hyperlipasemia, and evaluate association with outcome.AnimalsCritically ill, client owned dogs (n = 1360), presented on emergency and admitted to the intensive care unit, that had 1,2‐o‐dilauryl‐rac‐glycero‐3‐glutaric acid‐(6′‐methylresorufin) ester (DGGR) lipase activity measured within 24 hours of admission.MethodsRetrospective cross‐sectional study of clinical and laboratory records.ResultsThe DGGR lipase activity was increased >3× the upper reference limit at admission in 216/1360 (16%) dogs, of which 70/216 (32%) had a clinical diagnosis of AP. Other primary conditions associated with hyperlipasemia were renal, endocrine, and immune‐mediated diseases, and upper airway obstruction. Predictors of hyperlipasemia at admission were prior glucocorticoid administration, vomiting and abdominal pain, increased age, plasma bilirubin and creatinine concentrations, and decreased hematocrit. Of dogs with repeat measurements, 78/345 (23%) had significantly increased lipase during hospitalization, of which 13/78 (17%) had a clinical diagnosis of AP. Other primary conditions associated with in‐hospital hyperlipasemia were renal and immune‐mediated disorders. Predictors of developing hyperlipasemia during hospitalization were hemodialysis events, increased plasma bilirubin and creatinine concentrations, and decreased hematocrit. Hyperlipasemia both at admission and during hospitalization was associated with longer hospitalization and higher mortality.Conclusions and Clinical ImportanceSignificant DGGR‐hyperlipasemia is frequent in critically ill dogs and associated with a variety of nonpancreatic conditions and negative outcome.

Morin attenuates dutasteride/tamsulosin-induced hepatic oxidative stress in rat

Dutasteride-Tamsulosin (DUT-TAM) is a combination drug for the treatment of symptoms of prostate enlargement (benign prostatic hyperplasia, BPH). Despite the efficacy, it is associated with some side effects, including hepatotoxicity. Therefore, this study investigated the attenuative effects of morin on DUT-TAMinduced organ toxicity. Twenty four male rats were divided into 4 groups (A-D) consisting of 6 animals each. Group A animals (control) were given olive oil, Group B animals were administered with DUT-TAM (5.4 mg/kg body weight of dutasteride + 3.4 mg/kg body weight of tamsulosin), Group C were given morin (100 mg/kg body weight) while group D animals were administered DUT-TAM and morin (5.4 mg/kg body weight dutasteride + 3.4 mg/kg body weight of Tamsulosin and 100 mg/kg body weight of morin). All the administrations were carried out orally for 14 days. DUT-TAM caused a significant increase in plasma bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by 62%, 45% and 18% in the DUT-TAM treated group respectively, compared with the control (P˂0.05). However, treatment with morin significantly decreased the DUT-TAM-induced increase in plasma bilirubin concentration as well as AST and ALT activities. Furthermore, DUT-TAM administration decreased the activities of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), as well as hepatic concentration of ascorbic acid and reduced glutathione (GSH) by 58%, 54%, 59%, 46% and 63% respectively, but increased malondialdehyde (MDA) level by 49% relative to the control (P˂0.05). However, treatment with morin significantly ameliorated the observed changes in these antioxidant parameters (P˂0.05). These data suggest that morin protects against hepatic toxicity, as well as oxidative stress induced by dutasteride-tamsulosin in rats.&#x0D; Keywords: Dutasteride, Tamsulosin, Prostate enlargement, Oxidative stress, Liver

The potential interaction between body condition score at calving and dietary starch content on productive and reproductive performance of early-lactating dairy cows

Improving reproductive performance is one of the most important factors affecting the profitability of dairy herds. This study investigated the effect of feeding a high starch (HS) diet and body condition score (BCS) at calving on blood metabolites, fertility and ovarian function and milk production in Holstein dairy cows. One hundred seventy-four multiparous cows were fed common close-up and early lactation diets during the first 15 days in milk (DIM). Cows were randomly assigned to 1 of 2 experimental diets from 16 until 50 DIM (n = 87 per group); normal starch (228 g/kg diet DM; NS) or HS (270 g/kg diet DM; HS) diets. Each treatment group was further subdivided based on BCS at calving as normal BCS (BCS ⩽ 3.5; normal BCS (NBCS); n = 45) or high BCS (HBCS) (BCS ⩾ 3.75; HBCS; n = 42). A significant difference was detected for increased milk production (47.24 v. 44.55 kg/day) and decreased milk fat (33.93 v. 36.33 g/kg) in cows fed HS or NS, respectively. Plasma glucose and insulin concentrations were significantly higher in cows fed the HS compared to the NS diet. Diets significantly affected DIM at first artificial insemination (AI, 79.51 ± 3.83 v. 90.40 ± 3.83 days for cows fed HS and NS diets, respectively). High BCS groups had greater milk fat content and elevated plasma nonesterified fatty acids (NEFA), β hydroxybutyrate (BHB) and bilirubin concentrations. In general, feeding higher starch diets to normal BCS cows during the first 50 DIM improved productive and reproductive performance of early-lactating dairy cows.

Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model.

BackgroundThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients is becoming a worldwide health burden. Studies have indicated, however, that the onset of NAFLD occurs during pre-diabetes, a condition that often precedes the onset of T2DM. Oleanolic acid has been reported to improve glucose homeostasis in diet-induced pre-diabetes; however, the effects of this triterpene on liver function have not been evaluated.PurposeThis study was aimed at evaluating the therapeutic effects of oleanolic acid (OA) on selected markers of NAFLD in a pre-diabetes rat model.Methods and materialsPre-diabetes was induced by exposing Sprague Dawley rats to a high-fat high-carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence and absence of dietary interventions for a period of 12 weeks. The effects of OA were evaluated on parameters including plasma triglycerides (TGs), very low-density lipoprotein (VLDL) particles, bilirubin, AST, ALT, SREBP and antioxidant profile while the livers were collected for histological analysis.ResultsThe findings of this study showed that the administration of OA to pre-diabetic rats ameliorated body/liver weights ratio and significantly decreased plasma triglycerides (TGs) and VLDL. Furthermore, OA also ameliorated hepatic oxidative stress, lowered the SREBP expression and intrahepatic TGs. In addition, OA administration decreased plasma concentrations of bilirubin and liver damage enzyme biomarkers.ConclusionThe findings of the study suggest that OA ameliorates the risk of developing pre-diabetes-related NAFLD through the prevention of intrahepatic fat accumulation while also lowering hepatic inflammation.

Association between plasma bilirubin and mortality

Introduction and aimIt has been proposed that plasma concentration of bilirubin, an endogenous antioxidant, is protective against diseases mediated by increased oxidative stress, including cardiovascular diseases (CVD) and cancer. To examine this hypothesis, we investigated the relationship between plasma bilirubin concentrations and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations (associated with increased bilirubin concentrations) with total/CVD and cancer mortality. Materials and methodsA nested case–control study was conducted within the Polish arm of the HAPIEE cohort. At baseline in 2002–2005, participants were examined in detail. Mortality follow-up (median (IQR) between blood draw and death was 3.7 (2.1–5.1) years) was performed by linkage with regional and national death registers. Plasma biomarkers were analysed in all subjects who died from any cause (cases, n=447) and in a random subsample of survivors (controls, n=1423). ResultsThere was a strong negative association between plasma bilirubin levels and total and cancer mortality, expressed more profoundly in men. The adjusted OR of deaths from all causes and cancer, comparing the highest vs. lowest plasma bilirubin categories were 0.61 (95% CI: 0.42–0.87) and 0.39 (0.24–0.65), respectively. There was no association of bilirubin with CVD mortality. The UGT1A1*28 allele, a genetic marker of raised bilirubin, was also negatively associated with total/cancer mortality, although the associations were not statistically significant. DiscussionBoth the observational and genetic associations support the negative relationship between bilirubin and total mortality; this association appears to be driven by cancer mortality, while that with CVD mortality is not evident.

ELEVATED UNCONJUGATED BILIRUBIN IN SCHIZOPHRENIC PATIENTS

Strategies for schizophrenic treatment still have been developed in order to increase their effectively, based on latest findings in the etio-pathology. Coincidence of hyperbilirubinemia, especially related to Gilbert’s Syndrome (GS), and schizophrenia/other psychiatric disorders, was reported in several studies although the pattern of this alteration is still controversial. Bilirubin could induce microglia to release pro-inflammatory cytokine that cause neuroinflammation, one of hypothetic etio-pathogenesis has been the most extensively studied recently. However, no data have been presented about this phenomenon in Indonesia. Therefore, this study aims to investigate plasma bilirubin concentration in psychotic spectrum.This study is cross sectional design that we examined both the total bilirubin and direct bilirubin of every psychotic patient admitted for the first time to Rumah Sakit Khusus Daerah (RSKD) Provinsi Sulawesi Selatan over a period of July—December 2012, by using health people as control. Diagnostic determination was set based on International Classification of Diseases (ICD) 10. Patients suffering from any disease such as anemia (decreased hemoglobin), liver diseases (elevated liver enzymes), or substance abuse were excluded. From 73 samples, we found that plasma UCB level was significantly elevated, higher in psychotic patients, especially schizophrenic group, than in the control. Total bilirubin rate was slightly increased in schizophrenic group compare to the others and two samples in this group showed hyperbilirubinemia. Further investigations are needed to ensure that whether the elevated UCB was related to GS and whether this condition has inflammatory effect.