Bile Concentrations Research Articles

Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study.

The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking. To provide clinical in vivo data on the concentration of AVI in bile fluid as a surrogate for hepatobiliary excretion. A single dose of 2000/500 mg CAZ/AVI was administered prolonged over 2 h to 10 patients prior to abdominal surgery, with bile samples available in nine patients in this phase IIb study (DRKS-ID: DRKS00023533). Antibiotic concentrations in plasma (0-8 h), bile (after resection) and pharmacodynamic parameters were determined. The mean concentration across individuals in bile was 33.5 mg/L (±20.5 mg/L) for CAZ and 7.1 mg/L (±3.5 mg/L) for AVI, resulting in bile/plasma ratios of 0.58 (±0.26) and 0.61 (±0.18). The Cmax in plasma was 87.2 mg/L (±25.0 mg/L) for CAZ and 18.6 mg/L (±6.29 mg/L) for AVI, with AUC0-∞ values of 351 h·mg/L (±104 h·mg/L) and 72.1 h·mg/L (±32.1 h·mg/L), respectively. Plasma concentrations of both CAZ and AVI remained more than 50% of the dosing interval above the minimum inhibitory concentrations (T>MIC > 50%; MICCAZ = 8 mg/L, MICAVI = 1 mg/L) in all patients. No antibiotic-associated side effects were reported during the 30-day follow-up. The concentrations of CAZ and AVI in bile suggest their potential as a valuable therapeutic option for multi-resistant biliary infections.

20 Trace metal homeostasis in growing cattle

Abstract Apparent trace metal absorption and tissue retention upon incremental levels of supplemental Zn, Cu, and Mn were studied in growing cattle. A total of 60 Holstein bulls were enrolled for the study and fed for 28 d a diet consisting of barley straw (15%), molasses (10%) and pelleted concentrate (75%; Zn = 78 ppm, Cu = 15 ppm, Mn = 91 ppm). Thereafter, 20 bulls were randomly selected and slaughtered for determination of baseline tissue trace metal composition. The remaining 40 bulls [body weight (BW) = 394 ± 20 kg] were then blocked based on BW in 8 blocks of 5 bulls each. Bulls within a block were randomly assigned one of the diets differing in supplemental levels of Zn, Cu, and Mn (all from sulfate form) with the following dietary contents of Zn, Cu and Mn, respectively: No supplement (38, 7, and 47 ppm), Dose 1 (61, 11, and 68 ppm), Dose 2 (78, 15 and 91 ppm), Dose 3 (123, 26, 136 ppm) or Dose 4 (195, 43, and 214 ppm). These diets were fed for 12 wk, and complete collection of feces and urine were performed on wk 4, 8 and 12 for assessment of trace metals balance and apparent absorption. Gastrointestinal tissues, whole organs (heart, liver, spleen, and kidney), bile, cervical vertebra, and tibia were collected at slaughterhouse from all bulls. All samples were dried, ground, and analyzed for minerals. Data were processed using dietary treatment as a continuous variable and also as categorial variable. Both approaches adjusted for the fixed effect of block (Proc Mixed, SAS 9.4). Whole-body Zn, Cu and Mn balance quadratically increased (P < 0.05) with supplementation, with a significantly higher values for Dose 4 compared with all other dietary treatment (Figure 1, P < 0.05). Dose 4 also led to a 2-fold increase in urinary Zn and Cu excretions (P < 0.05), and a 4-fold increase in urinary Mn excretion (P < 0.01). Although magnitudes of change were moderate (8 to 15%), increasing dietary Zn supply linearly increased spleen Zn content (P = 0.03), and tended to increase ruminal and hepatic Zn content (P < 0.10). Hepatic Cu linearly increased from 264 to 667 mg/kg DM with increasing dietary Cu supply (P < 0.01), whereas Cu concentration in bile only increased at Doses 4 and 5 (P < 0.01). Increasing Mn supply resulted in quadratic increase of ruminal and biliary Mn content from 340 to 1140 mg/kg DM, and from 0.32 to 1.38 mg/L, respectively. Small intestine and cecum Mn concentrations linearly and quadratically increased (about 2-fold increase, P < 0.05) with incremental supply of Mn. Homeostatic regulation mechanisms were apparently overwhelmed at the greatest Zn, Cu and Mn supplementation levels evaluated in this study.

In vitro probiotic potential of lactic acid bacteria isolated from the intestines of Muscovy ducks.

The current study was conducted to isolate, test and characterize molecularly and physiologically lactic acid bacteria from the intestines of Muscovy ducks to evaluate their probiotic potential for poultry farming. Three hundred lactic acid bacteria from the gastrointestinal tract of Muscovy ducks were isolated. The strains were phenotypically characterized by observing cell morphology, performing Gram staining, catalase production, and testing their ability to grow in MRS broth at different temperatures, pH values, NaCl concentrations, bile concentration, and in compatibility tests between strains. Nine strains were selected based on their resilience. Eight strains were identified using molecular techniques. These strains exhibited significant tolerance to acidic pH, bile salts, and NaCl, essential for probiotic function. All isolates inhibited the growth of Salmonella enterica serotype Typhimurium (DT104) and Enteropathogenic Escherichia coli serotype O86:H34 (EPEC), showcasing their antimicrobial potential. Antibiotic susceptibility testing revealed 100% resistance to clindamycin and erythromycin but high susceptibility to ampicillin and vancomycin. Growth was observed at various temperatures, indicating mesophilic characteristics. Compatibility tests confirmed their suitability for probiotic formulations. Genomic analysis identified the strains primarily as Enterococcus. Conclusively, the study identified eight out of nine selected lactic acid bacteria strains from Muscovy ducks as autochthonous probiotics, showing resilience to treatments and compatibility for consortium formulation. These strains are suitable for in vivo testing for potential poultry farming applications. Further research on their molecular mechanisms and in vivo effects is needed.

Biomimetic Synthesis of Calcium Carbonate in Bile in the presence of Amino Acids

Thermodynamic and experimental modeling of calcium carbonate crystallization in a model solution of human bile has been carried out. The process of calcium carbonate (calcite and vaterite) crystallization from solutions containing bile has been studied. It is shown that differences in the phase and group composition of the samples arise depending on the synthesis parameters. It has been established that in the presence of 1 wt. % bile, calcite is formed, and an increase in the concentration of bile in the initial solution from 5 to 100 wt. % contributes to the crystallization of vaterite. It is shown that the mass of the solid phase increases with an increase in the concentration of bile in the initial solution. The dissolution of the synthesized samples was performed in 0.9 wt. % NaCl solution and 0.05 M EDTA solution. It was found that the presence of bile components in the composition of solid samples reduces the rate of their dissolutions.

Probiotic evaluation, adherence capability and safety assessment of Lactococcus lactis strain isolated from an important herb “Murraya koenigii”

Lactic acid bacteria (LAB) isolated from medicinal herb Murraya koenigii, commonly known as curry leaf, which promotes the growth and maintenance of gut microbiota, were studied for their probiotic potential. The key objective of this research was to isolate and evaluate probiotic characteristics, test adherence capabilities, and confirm their safety. Lactococcus lactis (MKL8), isolated from Murraya koenigii, was subjected to in vitro analysis to assess its resistance to the gastric environment, ability to adhere Caco-2 cells, anti-microbial activity, hydrophobicity, auto-aggregation, and safety profiling through MTT assay and hemolytic. MKL8 exhibited growth at 0.5% phenol concentrations (> 80%) and was able to survive in conditions with high bile concentrations (> 79%) and a relatively low pH (72%-91%). It shows high tolerance to high osmotic conditions (> 73%) and simulated gastric juice (> 72%). Additionally, MKL8 demonstrated strong hydrophobicity (85%), auto-aggregation (87.3%-91.7%), and adherence to Caco-2 cells. Moreover, it had an inhibitory effect against pathogens too. By performing the hemolytic and MTT assays, the non-toxicity of MKL8 isolate was examined, and it exhibited no harmful characteristics. Considering MKL8's resistance to gastrointestinal tract conditions, high surface hydrophobicity, non-toxicity, and ability to inhibit the tested pathogens, it can be concluded that MKL8 demonstrated promising probiotic properties and has potential for use in the food industry.

Challenges of the Application of In Vitro Digestion for Nanomaterials Safety Assessment.

Considering the increase in the production and use of nanomaterials (NM) in food/feed and food contact materials, novel strategies for efficient and sustainable hazard characterization, especially in the early stages of NM development, have been proposed. Some of these strategies encompass the utilization of in vitro simulated digestion prior to cytotoxic and genotoxic assessment. This entails exposing NM to fluids that replicate the three successive phases of digestion: oral, gastric, and intestinal. Subsequently, the resulting digestion products are added to models of intestinal cells to conduct toxicological assays, analyzing multiple endpoints. Nonetheless, exposure of intestinal cells to the digested products may induce cytotoxicity effects, thereby posing a challenge to this strategy. The aim of this work was to describe the challenges encountered with the in vitro digestion INFOGEST 2.0 protocol when using the digestion product in toxicological studies of NM, and the adjustments implemented to enable its use in subsequent in vitro biological assays with intestinal cell models. The adaptation of the digestion fluids, in particular the reduction of the final bile concentration, resulted in a reduced toxic impact of digestion products.

Effect of Bile on Hemodynamics and Blood Micro-Rheological Parameters in Experimental Models of Bilhemia.

As a rare complication of liver injury and certain interventions, bile can enter the bloodstream depending on the pressure gradient, resulting in bilhemia. Its micro-rheological and hemodynamic effects are still unclear. We aimed to study these parameters in experimental bilhemia models. Under general anesthesia, via laparotomy, bile was obtained by gallbladder puncture from pigs and by choledochal duct cannulation from rats. In vitro, 1 µL and 5 µL of bile were mixed with 500 µL of anticoagulated autologous blood. The systemic effect was also assessed (i.v. bile, 200 µL/bwkg). Hemodynamic and hematological parameters were monitored, and red blood cell (RBC) deformability and aggregation were determined. RBC deformability significantly decreased with the increasing bile concentration in vitro (1 µL: p = 0.033; 5 µL: p < 0.001) in both species. The RBC aggregation index values were concomitantly worsened (1 µL: p < 0.001; 5 µL: p < 0.001). The mean arterial pressure and heart rate decreased by 15.2 ± 6.9% and 4.6 ± 2.1% in rats (in 10.6 ± 2.6 s) and by 32.1 ± 14% and 25.2 ± 11.63% in pigs (in 48.3 ± 18.9 s). Restoration of the values was observed in 45 ± 9.5 s (rats) and 130 ± 20 s (pigs). Bilhemia directly affected the hemodynamic parameters and caused micro-rheological deterioration. The magnitude and dynamics of the changes were different for the two species.

Probiotic Potential of Autochthonous Lactobacillus against Avian Pathogenic Escherichia coli

Background: The aim of current study was to investigate the probiotic potential of autochthonous Lactobacillus species against pathogenic Escherichia coli in poultry. Method: A total of 73 samples were collected from cloacal swabs and tissues of desi and commercial chicken. The Lactobacillus were isolated based on cultural, biochemical and molecular teats. The probiotic potency was tested in vitro and antimicrobial activity and ABST was carried by Agar well diffusion and disc diffusion methods, respectively. Nucleotide sequencing was done by Sanger sequencing. Haemolysis and gelatin hydrolysis assays were used as safety testes. Result: From 73 cloacal swabs and tissues of desi and commercial chicken, 56 Lactobacillus were isolated of which 22 showed high autoaggregation and hydrophobicity potential. Based on survivability at acidic pH (2.5) and bile concentrations (0.5%), 16 isolates were selected and were subjected to well diffusion assay against pathogenic E. coli. All the isolates showed zone of inhibition against E. coli ranging from 10 -18 mm. ABST revealed that all the isolates are sensitive to chloramphenicol, ampicillin and erythromycin and 75% of the isolates were resistant to streptomycin, gentamicin and vancomycin. Only one isolate out of 16 tested was non hemolytic and none of the isolates tested positive for gelatine hydrolysis. Sequencing result of selected isolate revealed 96.82% of its similarity to Lactobacillus fermentum.

Integrated data from intravital imaging and HPLC-MS/MS analysis reveal large interspecies differences in AFB1 metabolism in mice and rats.

Large interspecies differences between rats and mice concerning the hepatotoxicity and carcinogenicity of aflatoxin B1 (AFB1) are known, with mice being more resistant. However, a comprehensive interspecies comparison including subcellular liver tissue compartments has not yet been performed. In this study, we performed spatio-temporal intravital analysis of AFB1 kinetics in the livers of anesthetized mice and rats. This was supported by time-dependent analysis of the parent compound as well as metabolites and adducts in blood, urine, and bile of both species by HPLC-MS/MS. The integrated data from intravital imaging and HPLC-MS/MS analysis revealed major interspecies differences between rats and mice: (1) AFB1-associated fluorescence persisted much longer in the nuclei of rat than mouse hepatocytes; (2) in the sinusoidal blood, AFB1-associated fluorescence was rapidly cleared in mice, while a time-dependent increase was observed in rats in the first three hours after injection followed by a plateau that lasted until the end of the observation period of six hours; (3) this coincided with a far stronger increase of AFB1-lysine adducts in the blood of rats compared to mice; (4) the AFB1-guanine adduct was detected at much higher concentrations in bile and urine of rats than mice. In both species, the AFB1-glutathione conjugate was efficiently excreted via bile, where it reached concentrations at least three orders of magnitude higher compared to blood. In conclusion, major differences between mice and rats were observed, concerning the nuclear persistence, formation of AFB1-lysine adducts, and the AFB1-guanine adducts.

Oil spill in an amazon blackwater environment: Biochemical and physiological responses of local fish species

The accidental spill of petroleum asphalt cement (PAC) in São Raimundo (SR Harbor, located on the Rio Negro (Manaus, Amazonas, Brazil) was monitored through the analysis of polyciclic aromatic hydrocarbons (PAHs) in water and a set of biomarkers in fishes (exposure biomarkes: PAHs-type metabolites concentrations in bile; the activities of ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in liver. Effect biomarkers: lipid peroxidation concentration (LPO) in liver, acetylcholinesterase activity in brain, and genotoxic DNA damage in erythrocytes). Two fish species, Acarichthys heckelii and Satanoperca jurupari, were collected 10, 45, and 90 days after the PAC spill in São Raimundo. At the same time, fish were collected from the Tupé Sustainable Development Reserve (Tupé) which served as a reference area. The sampling periods were related to the rising waters of the natural flood pulse of the Rio Negro. Higher concentrations of PAHs in water were observed at 10 and 45 days and returned to the values of TP 90 days after the PAC spill, a period in which harbor waters rose about 0.2 m. Unlike the PAHs in water, biomarker responses in both fish species significantly increased following the PAC spill in SR. Hepatic ethoxyresorufin-O-deethylase (EROD), PAH-like metabolites in bile, and erythrocyte DNA damage increases, together with inhibition of acetylcholinesterase (AChE) activity in the brain were the most evident responses for both fish species. The calculated pyrolytic index showed mixed sources of PAHs (petrogenic and pyrolytic). The applied PCA-FA indicated important relationships between dissolved organic carbon (DOC) and PAHs concentrations in water, where DOC and PAHs concentrations contributed to biomarkers responses for both fish species in all collection periods.

Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux.

Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

In vitro Studies on Anticoccidial Effects of Healthy Sheep Bile against Eimeria magna and Eimeria exigua Oocysts and Sporozoites Isolated from Domestic Rabbits

Background: Coccidiosis is one of the most common diseases that hinder the raising of rabbits. The disease causes symptoms such as diarrhea and loss of appetite. Acute infection causes bloody feces and negatively affects fertility. Diarrhea may be bloody due to the intestinal epithelium withering off as many oocysts and merozoites burst out of the cells. This leads to the deaths of rabbits resulting in huge economic losses for commercial rabbit systems. Methods: The study aims to determine the optimal effective concentration of bile collected from healthy sheep gall bladder inhibiting in vitro sporulation and viability of E. magna and E. exigua oocysts and sporozoites isolated from rabbit intestine. Un-sporulated oocysts were exposed (1×102) to six treatments: 2.5% potassium dichromate solution as the non-treated control, four concentrations of bile (12.5%, 25%, 50% and 100%) and Toltrazuril 25 mg/ml as traditional medicine for anti-oocyst activities. In addition, 250, 500, 750 and 1000 mg/mL concentrations of bile were evaluated for effect on sporozoite viability. The oocysts were examined after 25, 50, 75 and 100 hours and sporozoites after 12 and 24 hours of treatment. Result: GC-Mass analysis showed that sheep bile contains 12 biologically active compounds. In addition, quantitative analysis revealed total phenols (50.65±0.5) and total flavonoids (9.39±0.4). After 100 hours of exposure, sheep bile was able to prevent sporulation of E. magna and E. exigua oocysts at 100% and 50% concentrations and the rate of inhibition was about 96% and 79%, respectively. Additionally, bile exhibited the least discouraging of 11% at a dose of 125 mg/mL and the highest suppression of 95% of E. magna and E. exigua sporozoites viable at 1000 mg/ml. Generally, the inhibition rate typically increased with longer incubation times and greater doses. Findings have scientifically validated the use of bile in fighting against coccidiosis. Additional studies are required to separate the active compounds found in bile and their mechanisms of action and potential applications in rabbit farms.

Дрожжи из соков кокоса и рафии: пробиотическая оценка in vitro

Eukaryotic probiotics currently attract a lot of scientific attention, with Saccharomyces cerevisiae and Saccharomyces boulardii being the most widely investigated probiotic yeasts. The range of yeast species with probiotic potential needs to be broadened. In this respect, juice-providing plants may diversify eukaryoti c probiotic sources for organism preference.&#x0D; This study tested the probiotic potential of Pichia kudriavzevii and Kluyveromyces marxianus isolated from coconut juice and Schizosaccharomyces pombe and Wickherhamomyces anomalus isolated from raffia palm juice in Nigeria. The in vitro tests used the optical density method to assay the tolerance to acid (pH 2, 3, 5), alkaline (pH 7.5, 8.0), gastric juice (30%), bile (1, 2, and 3%), and osmotic pressure (5, 10, 15, 20, 25, and 30% gluco se solution).&#x0D; All four yeasts survived in the test environments, exhibiting varying degrees of probiotic potential. After 96 h in simulated gastric juice, S. pombe outperformed K. marxianus and W. anomalus by 13 and 97.7% (p &lt; 0.05), respectively. W. anomalus appeared to be the least viable in 30% gastric juice. After 96 h in the acid media, all yeasts performed better at pH 3.0 than at pH 2.0, with roughly 89% (1.695/0.185 mean absorbance values) greater growth in pH 3.0 than in pH 2.0. The alkaline media had a better effect on the growth rate. P. kudriavzevii fared best at pH 2.0 and 3.0 for up to 96 h. All yeasts maintained viability in 1, 2, and 3% bile solutions, although the growth rate did not improve significantly in any of the assay periods. Only minimal growth increase was registered in increased bile concentrations. All samples demonstrated sustained viability in 5–30% glucose between 24 and 48 h of incubation. After 48 h of incubation, the yeast concentrations began to fall as the glucose concentration rose from 5 to 30%. P. kudriavzevii was the least affected after 96 h (41.8%) and demonstrated the best survival results by the four criteria tested in this study.&#x0D; If this species meets all other non-assayed parameters which qualify a microorganism as a probiotic, P. kudriavzevii obtained from Nigerian coconut juice can be recommended as a potential s ource of commercial probiotics.

Erratum: Ultrasonographic aspects of the gallbladder mucocele in 30 dogs: retrospective study

Gallbladder mucocele is characterized by hyperplasia of the gallbladder epithelium, increased mucus production, accumulation, and densification of the bile content, which can lead to biliary obstruction, necrosis, and rupture of the gallbladder wall. Its finding may be accidental or related to symptoms. A retrospective study (2016-2019) was carried out based on abdominal ultrasound examinations in dogs, correlating aspects of the gallbladder and biliary system in the mucocele with existing comorbidities. Thirty dogs diagnosed with biliary mucocele were evaluated, of which 46.66% had the disease at an early stage, and 53.33% showed a more advanced stage. Of these, 66.66% were related to endocrinopathies and hyperadrenocorticism. Signs of extrahepatic bile duct obstruction and biliary peritonitis were observed in two animals. Due to their potential risk of complications, follow-up ultrasound assessments are indicated in cases that opt for clinical treatment, not excluding the need for surgical intervention.

Correlation analysis between the in vivo bioavailability and in vitro bioaccessibility of nitro PAHs in soil: Application of simplified FOREhST in vitro methods based on the Chinese pharmacopoeia

In this study, the relative bioavailability (RBA) of nitrated polycyclic aromatic hydrocarbons (NPAHs) in soil samples (n = 30) was assessed using an in vivo mouse model. Based on the correlation between the bioaccessibility data obtained from the Tenax improved traditional Fed ORganic Estimation human Simulation Test (FOREhST) in vitro method (TITF) and the bioavailability data obtained from in vivo experiments, the TITF method was further optimized and simplified by referring to the “Pharmacopoeia of the People's Republic of China: Volume IV, 2020” to adjust the formulation and parameters of the gastrointestinal fluid (GIF) in order to establish a simpler and lower cost in vitro method for the determination of the bioaccessibilities of NPAHs. The dose-accumulation relationship of the in vivo experiment showed that the linear dose-response was better in adipose tissue (R2 = 0.77–0.93), and the accumulation of NPAHs in adipose tissue was higher than that in kidney or liver tissue. Depending on the mouse adipose model, the NPAHs-RBA ranged from 1.88 % to 73.92 %, and a strongly significant negative relationship (R2 = 0.94, p < 0.05) was found between the NPAHs-RBA and Log Kow. The simplified experiment of the TITF showed that the composition of the GIF medium had a significant effect on the bioaccessibilities of NPAHs. The NPAH bioaccessibilities measured by the Tenax improved simplified FOREhST method (TISF) (9.0–36.5 %) were higher than that of the traditional FOREhST method (6.8–22.8 %) but significantly lower than that of the TITF method (16.8–55.2 %). With an increase in the bile concentration in the GIF (from 6 to 10 g/L), the bioaccessibilities of NPAHs increased from 9.0 to 36.5 % to 12.9–42.4 %. The accuracies of the four in vitro methods for predicting the bioavailabilities of NPAHs was in the following order: Tenax improved simplified FOREhST method with increased bile concentration (TITF-IB) (R2 = 0.54–0.87) ≈ TITF (R2 = 0.55–0.85) > TISF (R2 = 0.41–0.77) > FOREhST (R2 = 0.02–0.68). These results indicated that the simple in vitro method could also effectively predict the bioavailabilities of NPAHs.

Benzodiazepinе derivative methanindiazenone modulates lipid metabolism in the liver of rats with rotenone-induced Parkinson’s syndrome

Parkinson’s disease (PD) is a neurodegenerative condition for which the exact causes remain elusive, and no effective treatments currently exist. The pathogenesis of PD is believed to involve oxidative stress, mitochondrial dysfunction, and lipid metabolism disorders. A benzodiazepine derivative JM-20 has demonstrated protective effects on mitochondria in both neurons and peripheral tissues of rats with rotenoneinduced Parkinson’s syndrome (PS). This study aimed to analyze bile composition and assess the impact of a new benzodiazepine derivative, methanindiazenone, on lipid metabolism in the liver of rats subjected to the rotenone model of PS. The results indicated that, compared to the control group, bile concentration of phospholipids, cholesterol, cholesterol esters, and triglycerides decreased by 24.3, 26.2, 25.8, and 27.5%, respectively. With methanindiazenone treatment at doses of 0.5 and 1.0 mg/kg, all these metrics reverted to the control level. However, in the rotenone+methanindiazenone 2.0 mg/kg group, the levels of phospholipids, cholesterol, and cholesterol esters (except for triglycerides) surpassed the control values by 33, 28.1, 28.4 and 33.5%, respectively. Methanindiazenone positively impacted the motor behavior of rats with the rotenone model of PS and enhanced their survival rates. Therefore, at doses of 0.5 and 1.0 mg/kg, methanindiazenone not only improved lipid metabolism in the liver but also the overall well-being of rats with the rotenone model of PS. However, a 2 mg/kg dose of methanindiazenone displayed toxic effects, as seen from the increased content of phospholipids, cholesterol, and cholesterol esters in bile. Hence, methanindiazenone holds potential as a therapeutic agent for PS and possibly other neurodegenerative diseases related to lipid metabolism impairment, but its use should be limited to doses of 0.5 and 1.0 mg/kg.

PSI-14 Weaning Stress Increases Bile Cysteine and Cysteinylglycine Concentrations in Pigs

Abstract Weaning is a critical time for pigs that is associated with nutritional, social, and environmental stressors that lead to reduced feed intake and poor nutrient utilization. Cysteine is a sulfur amino acid and a key constituent of glutathione (GSH), a major intracellular antioxidant and potential regulator of intestinal redox status. Glutathione is present in biliary secretions and may be an important source of cysteine to intestine in newly weaned pigs. The objective of this study was to determine amino thiol and amino acid concentrations in bile. Piglets (initial BW = 7,233 ± 683 g) were either weaned on day 21 of age (W; n = 9) and euthanized after 2 d or remained on the sow until day 23 of age (NW; n = 9) and were euthanized. Weaned pigs were fasted and allowed free access to water. After euthanasia, bile (directly from the gallbladder), jejunum, and ileum samples were collected. Bile amino acids and bile amino thiols were analyzed by reversed phase HPLC following precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and 4-fluoro-7-aminosulfonylbenzofurazan, respectively. Reverse transcription quantitative real-time PCR was performed to measure cysteine transporter expression in jejunum and ileum. Cysteine concentration was greater in W than NW pigs (1,203 versus 324 ± 99 µmol/L; P &amp;lt; 0.0001). Both γ-glutamylcysteine (7.1 versus 2.2 ± 2.1 µmol/L), the direct precursor for GSH synthesis, and cysteinylglycine (203 versus 110 ± 30 µmol/L, the direct product of GSH degradation, were greater in W pigs than in NW pigs (P &amp;lt; 0.05). Bile GSH concentration tended to be greater in W than NW pigs (9.1 versus 5.3 ± 2.8 µmol/L; P = 0.07). Taurine, derived from cysteine oxidation, was greater in W than NW pigs (180 versus 91 ± 23 µmol/L; P &amp;lt; 0.05), whereas glutamate (11.4 versus 8.8 ± 1.9 µmol/L) and glycine (463 versus 403 ± 62 µmol/L), additional amino acid constituents of GSH, were not different between groups (P &amp;gt; 0.10). Expression of cysteine transporters SLC1A4, SLC1A5, SLC6A14, SLC6A19, SLC7A9, and SLC7A11 in jejunum and ileum were not different between groups (P &amp;gt; 0.10). Despite no feed intake after weaning, cysteine concentrations increase in bile. While this is likely due to bile accumulation in the gallbladder after weaning, high bile cysteine, cysteinylglycine, and glycine concentrations could potentially be a source of these amino acids for enterocytes during weaning stress.

Ultrasonographic aspects of the gallbladder mucocele in 30 dogs: retrospective study

Gallbladder mucocele is characterized by hyperplasia of the gallbladder epithelium, increased mucus production, accumulation, and densification of the bile content, which can lead to biliary obstruction, necrosis, and rupture of the gallbladder wall. Its finding may be accidental or related to symptoms. A retrospective study (2016-2019) was carried out based on abdominal ultrasound examinations in dogs, correlating aspects of the gallbladder and biliary system in the mucocele with existing comorbidities. Thirty dogs diagnosed with biliary mucocele were evaluated, of which 46.66% had the disease at an early stage, and 53.33% showed a more advanced stage. Of these, 66.66% were related to endocrinopathies and hyperadrenocorticism. Signs of extrahepatic bile duct obstruction and biliary peritonitis were observed in two animals. Due to their potential risk of complications, follow-up ultrasound assessments are indicated in cases that opt for clinical treatment, not excluding the need for surgical intervention.

The effect of Lignova sorbent to the concentration of interleukin-6 in the blood and bile in patients with mechanical jaundice of tumors etiology

The OBJECTIVE was to study changes of IL-6 concentration in the blood and bile in patients with MJ of tumor genesis by means of biliary sorption.METHODS AND MATERIALS. The investigation was conducted to study changes in the concentration of IL-6 in the blood and bile against the background of bile sorption in 105 patients with mechanical jaundice (MJ), the cause of obturation was a tumor of the periampullary zone. The patients are divided into two groups. The first group consisted of 51 patients, the second group included 54 patients. All patients of the main group underwent percutaneous perhepatic cholangiostomy for the purpose of decompression; bile sorption was performed using the domestic Lignov enterosorbent. The level of IL-6 in blood serum and bile was determined by enzyme immunoassay.RESULTS. The use of bile sorption in the treatment complex significantly changed the concentration of IL-6 in blood serum (P&lt;0.01) and bile. Determination of IL-6 in blood and bile makes it possible to more objectively assess the degree of cytokine-induced endogenous intoxication in response to ongoing therapeutic measures for tumors of the periampullary zone complicated by mechanical jaundice. The use of bile sorption contributes to a decrease in the concentration of the pro-inflammatory cytokine IL-6 in the blood and bile as an inducer of endogenous intoxication and a cascade of inflammatory processes in patients with tumors of the periampullary zone complicated by mechanical jaundice.CONCLUSION. Bile sorption application helps to decrease proinflammatory cytokine IL-6 concentration in blood and bile as an inductor of endogenous intoxication and inflammatory processes cascade.