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1.
J Gen Physiol ; 153(12)2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34757374

RESUMO

JGP study shows that a mechanosensitive complex containing Piezo1 and Pannexin1 couples osmotic pressure to ATP secretion in bile duct cholangiocytes.


Assuntos
Bile , Canais Iônicos , Células Epiteliais , Canais Iônicos/genética
2.
J Agric Food Chem ; 69(44): 13190-13199, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34723485

RESUMO

The metabolic fate of a newly developed herbicide, epyrifenacil, (ethyl[(3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]phenoxy}pyridin-2-yl)oxy]acetate, S-3100), in rats was determined using 14C-labeled epyrifenacil. When it was administered orally to rats at 1 mg/kg, around 73-74% of the dose was absorbed, metabolized, and mainly excreted into feces within 48 h. The elimination of radioactivity in plasma and tissues was rapid, suggesting that exposure of epyrifenacil and metabolites is small. Metabolite analysis revealed that epyrifenacil was rapidly ester-cleaved to M1 and then mainly excreted into bile or further metabolized. No parent was detected in plasma, tissues, and urine. Remarkably, M1 was mainly distributed in the liver (at a concentration of 70-112 times higher than in plasma at a low dose). Furthermore, a significant sex-related difference was observed in urinary excretion of M1. Considering the above observations with those in the literature, the organic anion-transporting polypeptide (OATP) likely plays a role on the active transport of M1 in the liver and kidney.


Assuntos
Líquidos Corporais , Herbicidas , Administração Oral , Animais , Bile , Fezes , Ratos , Distribuição Tecidual
3.
Wiad Lek ; 74(9 cz 1): 2232-2234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34725307

RESUMO

Clonorchiasis is a parasitic disease caused by Clonorchis sinensis. Parasite colonies can develop not only in the bile and pancreatic ducts but also in the gastric wall. This is confirmed by the described clinical case of perforated gastric ulcer, the morphological study of which revealed parasite colonies in the wall of the organ.


Assuntos
Clonorquíase , Clonorchis sinensis , Parasitos , Animais , Bile , Clonorquíase/complicações , Clonorquíase/diagnóstico , Clonorquíase/tratamento farmacológico , Humanos
4.
BMC Surg ; 21(1): 356, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600501

RESUMO

BACKGROUND: Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear. CASES PRESENTATION: We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis. CONCLUSION: The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.


Assuntos
Hepatectomia , Pancreatite , Doença Aguda , Bile , Hepatectomia/efeitos adversos , Humanos , Fígado , Pancreatite/diagnóstico , Pancreatite/etiologia
6.
Curr Protoc ; 1(10): e256, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34610200

RESUMO

Understanding the kinetics and spatiotemporal interactions of living cells within the tissue environment requires real-time imaging. The introduction of two-photon microscopy has substantially boosted the power of live intravital imaging, making it possible to obtain information of individual cells in near-physiologic conditions within intact tissues nondestructively. Intravital imaging of the liver has proved useful in understanding its 3D structure, function, and dynamic cellular interactions. Recently we have shown that integrity of the blood-bile barrier in different physiologic and pathophysiologic conditions can be imaged in real time using intravital microscopy. Here we discuss the real-time intravital imaging method to visualize blood-bile barrier integrity in the murine liver. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Live imaging in the mouse liver Support Protocol: Monitoring vital signs of the mouse during live liver imaging Basic Protocol 2: Visualizing blood and bile transport using intravital microscopy.


Assuntos
Microscopia Intravital , Fígado , Animais , Bile , Diagnóstico por Imagem , Testes Diagnósticos de Rotina , Fígado/diagnóstico por imagem , Camundongos
7.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638808

RESUMO

Tissue-nonspecific alkaline phosphatase (TNAP) is mainly known for its necessary role in skeletal and dental mineralization, which relies on the hydrolysis of the mineralization inhibitor inorganic pyrophosphate (PPi). Mutations in the gene encoding TNAP leading to severe hypophosphatasia result in strongly reduced mineralization and perinatal death. Fortunately, the relatively recent development of a recombinant TNAP with a bone anchor has allowed to correct the bone defects and prolong the life of affected babies and children. Researches on TNAP must however not be slowed down, because accumulating evidence indicates that TNAP activation in individuals with metabolic syndrome (MetS) is associated with enhanced cardiovascular mortality, presumably in relation with cardiovascular calcification. On the other hand, TNAP appears to be necessary to prevent the development of steatohepatitis in mice, suggesting that TNAP plays protective roles. The aim of the present review is to highlight the known or suspected functions of TNAP in energy metabolism that may be associated with the development of MetS. The location of TNAP in liver and its function in bile excretion, lipopolysaccharide (LPS) detoxification and fatty acid transport will be presented. The expression and function of TNAP in adipocyte differentiation and thermogenesis will also be discussed. Given that TNAP is a tissue- and substrate-nonspecific phosphatase, we believe that it exerts several crucial pathophysiological functions that are just beginning to be discovered.


Assuntos
Fosfatase Alcalina/metabolismo , Metabolismo Energético , Termogênese , Adipócitos/metabolismo , Fosfatase Alcalina/genética , Animais , Bile/metabolismo , Diferenciação Celular , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Hipofosfatemia/genética , Hipofosfatemia/metabolismo , Lipopolissacarídeos/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Mutação
8.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638955

RESUMO

Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1HepKO mice). Sgpl1HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5-2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.


Assuntos
Aldeído Liases/genética , Aldeído Liases/metabolismo , Bile/metabolismo , Fígado/metabolismo , Esfingolipídeos/sangue , Animais , Células Cultivadas , Ceramidas/metabolismo , LDL-Colesterol/metabolismo , Técnicas de Inativação de Genes , Hepatócitos/metabolismo , Homeostase/genética , Lisofosfolipídeos/metabolismo , Camundongos , Camundongos Knockout , Fenótipo , Receptores de LDL/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo
9.
Am J Case Rep ; 22: e933505, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34690343

RESUMO

BACKGROUND Biliary leak is a relatively uncommon but potentially severe complication of liver transplantation. Duct of Luschka (also known as subvesical bile ducts) is a term that refers to a number of accessory biliary ducts. While leaks from Ducts of Luschka are well-described in the field of hepatobiliary surgery, only 2 case reports of such leaks exist in the setting of liver transplant. CASE REPORT We report the first case of a Duct of Luschka biliary leak seen after DCD liver transplant in a 41-year-old woman with cirrhosis secondary to primary sclerosing cholangitis. The patient underwent surgical re-exploration in the immediate postoperative period due to bilious output from a surgical drain. A Duct of Luschka was found intraoperatively at the gallbladder fossa and was oversewn. Apart from immunosuppression-related neutropenia, the patient recovered uneventfully. CONCLUSIONS Given the variability in preoperative detection of subvesical bile ducts, accessory bile duct leak remains an important consideration in the liver transplant perioperative period. The prevalence of Ducts of Luschka and the relative risk of leakage from such subvesical bile ducts in liver transplants compared to cholecystectomies are unclear. Further research into anatomical accessory bile duct variants and preoperative techniques for detecting such ducts is warranted.


Assuntos
Doenças dos Ductos Biliares , Transplante de Fígado , Adulto , Bile , Ductos Biliares , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos
10.
J Cell Biol ; 220(10)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34515738

RESUMO

Hepatocytes display a unique biaxial polarity with shared apical luminal connections between adjacent hepatocytes that merge into a network of bile canaliculi. Belicova et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202103003) discovered that hepatocyte apical membranes generate Rab35-dependent extensions that traverse the lumen and are essential for bile canalicular formation and maintenance.


Assuntos
Canalículos Biliares , Bile , Polaridade Celular , Hepatócitos , Morfogênese
11.
Molecules ; 26(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34577166

RESUMO

Lactobacillus sp. have long been studied for their great potential in probiotic applications. Recently, proteomics analysis has become a useful tool for studies on potential lactobacilli probiotics. Specifically, proteomics has helped determine and describe the physiological changes that lactic acid bacteria undergo in specific conditions, especially in the host gut. In particular, the extracellular proteome, or exoproteome, of lactobacilli contains proteins specific to host- or environment-microbe interactions. Using gel-free, label-free ultra-high performance liquid chromatography tandem mass spectrometry, we explored the exoproteome of the probiotic candidate Lactobacillus mucosae LM1 subjected to bile treatment, to determine the proteins it may use against bile stress in the gut. Bile stress increased the size of the LM1 exoproteome, secreting ribosomal proteins (50S ribosomal protein L27 and L16) and metabolic proteins (lactate dehydrogenase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenases, among others) that might have moonlighting functions in the LM1 bile stress response. Interestingly, membrane-associated proteins (transporters, peptidase, ligase and cell division protein ftsH) were among the key proteins whose secretion were induced by the LM1 bile stress response. These specific proteins from LM1 exoproteome will be useful in observing the proposed bile response mechanisms via in vitro experiments. Our data also reveal the possible beneficial effects of LM1 to the host gut.


Assuntos
Proteínas de Bactérias/análise , Bile/fisiologia , Lactobacillus/metabolismo , Proteínas de Membrana/análise , Proteínas de Membrana/metabolismo , Proteoma/análise , Proteoma/metabolismo , Proteínas de Bactérias/metabolismo , Cromatografia Líquida de Alta Pressão , Regulação da Expressão Gênica/fisiologia , Gluconeogênese/fisiologia , Glicólise/fisiologia , Proteômica/métodos , Proteínas Ribossômicas/análise , Estimulação Química , Espectrometria de Massas em Tandem
12.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3198-3204, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396737

RESUMO

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.


Assuntos
Índigo Carmim , Indigofera , Animais , Bile , Humanos , Interações Hidrofóbicas e Hidrofílicas , Extratos Vegetais , Ratos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34398726

RESUMO

A strictly anaerobic, resistant starch-degrading, bile-tolerant, autolytic strain, IPLA60002T, belonging to the family Ruminococcaceae, was isolated from a human bile sample of a liver donor without hepatobiliary disease. Cells were Gram-stain-positive cocci, and 16S rRNA gene and whole genome analyses showed that Ruminococcus bromii was the phylogenetically closest related species to the novel strain IPLA60002T, though with average nucleotide identity values below 90 %. Biochemically, the new isolate has metabolic features similar to those described previously for gut R. bromii strains, including the ability to degrade a range of different starches. The new isolate, however, produces lactate and shows distinct resistance to the presence of bile salts. Additionally, the novel bile isolate displays an autolytic phenotype after growing in different media. Strain IPLA60002T is phylogenetically distinct from other species within the genus Ruminococcus. Therefore, we propose on the basis of phylogenetic, genomic and metabolic data that the novel IPLA60002T strain isolated from human bile be given the name Ruminococcoides bili gen. nov., sp. nov., within the new proposed genus Ruminococcoides and the family Ruminococcaceae. Strain IPLA60002T (=DSM 110008T=LMG 31505T) is proposed as the type strain of Ruminococcoides bili.


Assuntos
Bile/microbiologia , Filogenia , Ruminococcus/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Humanos , RNA Ribossômico 16S/genética , Ruminococcus/isolamento & purificação , Análise de Sequência de DNA
14.
Can J Gastroenterol Hepatol ; 2021: 3351352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422710

RESUMO

Background: The occurrence of stones in the gallbladder or common bile duct and the symptoms and complications they cause is called gallstone disease. The symptoms of gallstone disease range from mild, nonspecific symptoms to a severe right quadrant abdominal pain. Characteristics of gallstone types in an Iranian population have not been well studied before and there are very limited studies on the demographic pattern of stone types in our country, so this study is one of the first studies on its kind on the epidemiology of gallstone types in Iran. As information on chemical components of the stone will help in the management and prevention of gallstones, in this study, we aimed to do chemical component analysis of gallstones including cholesterol, bilirubin, and calcium. Given the conflicting reports about the relationship between H. pylori infections and gallstone formation, this study aimed to investigate the relationship between H. pylori positivity in the bile specimen of Iranian patients with cholelithiasis and formation and type of stone. Methods: This prospective study reviewed a total of 196 patients who underwent cholecystectomy for symptomatic cholelithiasis at Shahid Beheshti Training and Research Hospital affiliated to the Yasuj University of Medical Sciences between September 2015 and May 2018. Chemical analysis of gallstone components performed using the colorimetry method. Microbiological analysis for H. pylori was done using the OnSite H. pylori Ag Rapid Test on the bile sample. For the validation test of bile, the H. pylori Rapid Stool Ag Test on stool was used, and Cohen's Kappa statistical analysis was done next. Results: There were significant associations between the stone types and age, chemical composition of the stones such as calcium, cholesterol, and bilirubin levels, and also H. pylori positivity and cholesterol and bilirubin levels; however, no significant association was found between the stone types and sex, H. pylori positivity and age, sex, stone types, and calcium level. The main bile and validity tests were matched to the substantial agreement according to Cohen's Kappa analysis. The most common drugs used were proton pump inhibitors, nonsteroidal anti-inflammatory drugs, antihypertensive drugs, and oral contraceptives. Conclusions: This study suggested that the chemical composition of the stones could predict the presence of bacteria, there is no correlation between H. pylori and gallstone formation, and some of the drugs could be predisposing factors for gallstones. This work provides an objective basis for further research into gallbladder stone formation; meanwhile, it has great significance in the treatment and prevention of gallbladder stones. Trial registration. The project was found to be in accordance to the ethical principles and the national norms and standards for conducting research in Iran with the approval ID IR.YUMS.REC.1399.147 and date 2020.09.23, and this project is the result of a residency dissertation to obtain the specialty in general surgery, which has been registered with the research project number 960159 in the Vice Chancellor for Research and Technology Development of the Yasuj University of Medical Sciences, Yasuj, Iran, URL: https://ethics.research.ac.ir/EthicsProposalViewEn.php?id=160634.


Assuntos
Cálculos Biliares , Helicobacter pylori , Bile , Demografia , Cálculos Biliares/epidemiologia , Humanos , Irã (Geográfico)/epidemiologia , Estudos Prospectivos
15.
Mar Environ Res ; 170: 105434, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34333338

RESUMO

Studies that aim to characterise the susceptibility of the ecologically relevant and non-model fish polar cod (Boreogadus saida) to model carcinogens are required. Polar cod were exposed under laboratory conditions for six months to control, 0.03 µg BaP/g fish/week and 0.3 µg BaP/g fish/week dietary benzo(a)pyrene (BaP), a reference carcinogen. The concentrations of the 3-OH-BaP bile metabolite and transcriptional responses of genes involved in DNA adduct recognition (xpc), helicase activity (xpd), DNA repair (xpf, rad51) and tumour suppression (tp53) were assessed after 0, 1, 3 and 6 months of exposure, alongside body condition indexes (gonadosomatic index, hepatosomatic index and condition factor). Micronuclei and nuclear abnormalities in blood and spleen, and liver histopathological endpoints were assessed at the end of the experiment. Fish grew steadily over the whole experiment and no mortality was recorded. The concentrations of 3-OH-BaP increased significantly after 1 month of exposure to the highest BaP concentration and after 6 months of exposure to all BaP concentrations showing the biotransformation of the mother compound. Nevertheless, no significant induction of gene transcripts involved in DNA damage repair or tumour suppression were observed at the selected sampling times. These results together with the absence of chromosomal damage in blood and spleen cells, the subtle increase in nuclear abnormalities observed in spleen cells and the low occurrence of foci of cellular alteration suggested that the exposure was below the threshold of observable effects. Taken together, the results showed that polar cod was not susceptible to carcinogenesis using the BaP exposure regime employed herein.


Assuntos
Carcinógenos , Gadiformes , Animais , Benzo(a)pireno/toxicidade , Bile , Adutos de DNA/farmacologia
16.
BMJ Open ; 11(7): e049449, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326053

RESUMO

INTRODUCTION: Bile leakage is a frequent complication after liver resection associated with the need of interventional drainage, endoscopic retrograde cholangio pancreatography (ERCP) or reoperation. The intraoperative application of the white test could be a promising strategy to reduce the occurrence of bile leakages. Therefore, we propose to conduct the first multicentric randomised controlled trial with rate of postoperative bile leakage as primary endpoint with and without the white test. METHODS AND ANALYSIS: The Bile-Leakage Trial trial is an investigator-initiated randomised controlled, parallel group, double-blinded, multicentric, superiority trial in four Swiss centres. A total of 210 patients undergoing a resection of at least 2 liver segments will be randomly allocated intraoperatively to either the intervention (identification of open bile ducts with administration of 20-40 mL SMOFlipid5% in the bile tract) or the control group (identification with a white gauze on the liver resection surface).Primary outcome will be the comparison of the postoperative bile leakage rate in both groups within 30 days after liver resection, defined according to the classification of the International Study Group of Liver Surgery. Secondary outcomes will be operative and postoperative complication, including severity grade of the bile leakage, rate of ERCP, interventional drainage, morbidity, intensive care unit stay, and mortality. ETHICS AND DISSEMINATION: The cantonal ethics committees of all participating centres and Swissmedic approved the study. SMOFlipid20% consists of a mixture of oils, no side effects resulting from the intraoperative application of 20-40 mL in the biliary tract with consecutive enteral absorption are expected nor are side effects described in the literature. SMOFlipid20% will be diluted intraoperatively with isotonic saline solution to a concentration of 5%. The results of the BiLe-Trial will be submitted to a peer-reviewed journal regardless of the outcome. As this is an investigator-initiated trial, data are property of the sponsor investigator and can be obtained on request. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID: NCT04523701. Registered on 25 August 2020.Swiss National Clinical Trials Portal (SNCTP), ID: SNCTP000004200. Registered on 20 January 2021. PROTOCOL VERSION: V3.2_14-12-2020_clean.pdf.


Assuntos
Bile , Hepatectomia , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Fígado , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Clin Chim Acta ; 521: 278-284, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34331951

RESUMO

BACKGROUND: Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels. METHOD: We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver. RESULTS: Spearman's rank correlation analysis with loge change revealed that presepsin levels were closely associated with loge-transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that loge-transformed SOFA score (ß-coefficient = 0.316), ALP level (ß-coefficient = 0.380), and creatinine level (ß-coefficient = 0.290) independently and significantly affected loge presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining. CONCLUSION: Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells.


Assuntos
Doenças Biliares , Sepse , Bile , Doenças Biliares/diagnóstico , Biomarcadores , Humanos , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Estudos Retrospectivos , Sepse/diagnóstico
18.
Toxicol Appl Pharmacol ; 426: 115636, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214573

RESUMO

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Genisteína/uso terapêutico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Aldeídos/metabolismo , Animais , Aspartato Aminotransferases/sangue , Bile/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Genisteína/farmacologia , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Herbicidas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Paraquat , Substâncias Protetoras/farmacologia , Ratos Wistar
19.
Fish Shellfish Immunol ; 117: 320-327, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34246784

RESUMO

The polymeric immunoglobulin receptor (pIgR) plays an important role in mediating the transcytosis of polymeric immunoglobulins (pIgs) to protect organisms against pathogen invasion. Here, a polyclonal antibody against grass carp (Ctenopharyngodon idellus) recombinant pIgR was developed by immunizing New Zealand white rabbit, and the responses of pIgR, IgM and IgZ were analyzed after bath immunization and intraperitoneal administration with Flavobacterium columnare. The results showed that pIgR transcription level was similar to IgM and IgZ, but pIgR rose much faster and peaked earlier than IgM and IgZ; the pIgR mRNA levels were higher in the skin and spleen for both immunized groups, while IgM and IgZ mRNA expression were higher in skin, gills, and intestines in bath immersion group, or spleen and head kidney in intraperitoneal immunization group. ELISA revealed that the IgM, IgZ and pIgR protein levels were up-regulated in skin mucus, gill mucus, gut mucus and bile, reaching a higher peak level earlier in skin mucus and gill mucus in bath immersion group, but a higher peak level in bile in injection group. Moreover, secretory component molecules were detected in grass carp's skin, gill and intestine mucus and bile, but not in serum, which molecular mass was near the theoretical mass obtained from the sequence of grass carp pIgR. These results demonstrated that bath and intraperitoneal immunization up-regulated pIgR and secretory Ig expression in secretions, which provided more insights into the role of pIgR in immunity and offer insight into ways of protecting teleost against pathogen invasion.


Assuntos
Carpas/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Infecções por Flavobacteriaceae/imunologia , Flavobacterium , Imunoglobulinas/imunologia , Animais , Bile/imunologia , Carpas/microbiologia , Infecções por Flavobacteriaceae/veterinária , Brânquias/imunologia , Muco/imunologia , Coelhos , Proteínas Recombinantes/imunologia , Pele/imunologia
20.
Molecules ; 26(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34279393

RESUMO

Sanguisorba tannins are the major active ingredients in Sanguisorba ofJicinalis L. (Rosaceae), one of the most popular herbal medicines in China, is widely prescribed for hemostasis. In this study, three kinds of tannins extract from Sanguisorba officinalis L. (Rosaceae), and the metabolites in vivo and in vitro were detected and identified by high-pressure liquid chromatography, coupled with linear ion trap orbitrap tandem mass spectrometry (HPLC-LTQ-Orbitrap). For in vivo assessment, the rats were administered at a single dose of 150 mg/kg, after which 12 metabolites were found in urine, 6 metabolites were found in feces, and 8 metabolites were found in bile, while metabolites were barely found in plasma and tissues. For in vitro assessment, 100 µM Sanguisorba tannins were incubated with rat liver microsomes, liver cytosol, and feces, after which nine metabolites were found in intestinal microbiota and five metabolites were found in liver microsomes and liver cytosol. Moreover, the metabolic pathways of Sanguisorba tannins were proposed, which shed light on their mechanism.


Assuntos
Sanguisorba/química , Taninos/farmacocinética , Animais , Bile/metabolismo , Fezes/química , Microbioma Gastrointestinal , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Taninos/análise , Taninos/química
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