scholarly journals Infection by Gram-Negative Organisms via the Biliary Route Results in Greater Mortality than Portal Venous Infection

2003 ◽  
Vol 10 (4) ◽  
pp. 664-669 ◽  
Author(s):  
D. Rohan Jeyarajah ◽  
Mariusz L. Kielar ◽  
Nicole Frantz ◽  
Guy Lindberg ◽  
Christopher Y. Lu

ABSTRACT Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD50) for E. coli injected into the bile duct was 50 CFU/animal; the LD50 for E. coli injected into the portal vein was 5 × 107 CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 2-7 ◽  
Author(s):  
Miguel Angel Dias ◽  
Reginaldo Ceneviva ◽  
Jorge Elias Jr. ◽  
Sergio Zucoloto ◽  
Caroline Floreoto Baldo ◽  
...  

PURPOSE: To evaluate liver alterations caused by biliary obstruction and drainage. METHODS: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB. RESULTS: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow. CONCLUSION: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing.


2006 ◽  
Vol 291 (1) ◽  
pp. G91-G94 ◽  
Author(s):  
D. Rohan Jeyarajah ◽  
Mariusz L. Kielar ◽  
Hoosein Saboorian ◽  
Prameela Karimi ◽  
Nicole Frantz ◽  
...  

Biliary obstruction in the setting of hepatic bacterial infection has great morbidity and mortality. We developed a novel murine model to examine the effect of biliary obstruction on the clearance of hepatic Escherichia coli infection. This model may allow us to test the hypothesis that biliary obstruction itself adversely affects clearance of hepatic infections even if the bacteria are introduced into the liver by a nonbiliary route. We ligated the bile ducts of C57BL/6 mice on days − 1, 0, or + 1, relative to a day 0 portal venous injection of E. coli. We monitored survival, hepatic bacterial growth, pathology, and IL-10 protein levels. The role of IL-10 in this model was further examined using IL-10 knockout mice. Mice with bile duct ligation at day +1 or 0, relative to portal venous infection at day 0, had decreased survival compared with mice with only portal venous infection. The impaired survival was associated with greater hepatic bacterial growth, hepatic necrosis, and increased production of IL-10. Interestingly, the transgenic knockout of IL-10 resulted in impaired survival in mice with bile duct ligation and portal venous infection. Biliary obstruction had a dramatic detrimental effect on hepatic clearance of portal venous E. coli infection. This impaired clearance is associated with increased IL-10 production. However, transgenic knockout of IL-10 increased mortality after hepatic infection.


2001 ◽  
Vol 16 (2) ◽  
pp. 75-81 ◽  
Author(s):  
Gracinda De Lourdes Jorge ◽  
Luiz Sergio Leonardi ◽  
Ilka de Fatima Santana Ferreira Boin ◽  
Orlando de Castro e Silva Jr ◽  
Cecilia Amelia Fazzio Escanhoela

The aim of this study was to describe a method for the induction of experimental secondary biliary fibrosis (SBF). Forty-seven Wistar rats were submitted to hepatic duct obstruction (OB group) for thirty days without ligature, section or cannulization causing interruption of biliary flow. This technique was carried out by simple traction of the bile duct passing it through the xiphoid appendix. Nine rats were submitted to a sham operation for bile duct stricture and seven rats comprised the control group. Blood samples were collected for the measurement of total bilirubin (TB), alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver fragments were removed for morphological study. Thirty days after surgery TB, AP, ALT and AST levels were significantly increased in the hepatic duct ligation group compared to the sham operated group and the presence of SBF in the OB group was confirmed by morphological study of the liver. There was technical failure in 31.92% cases. The survival was 100% at fifteen days and 82.97% at the end of the experiment. We concluded that this simple surgical technique may be used to study the consequence of bile duct obstruction which could be a reversible process depending on the obstruction time. This technique can be carried out from cholestasis to fibrosis.


2013 ◽  
Vol 68 (1) ◽  
pp. e45
Author(s):  
Philippe Guillaume ◽  
David Virley ◽  
Sylvie Bézivin ◽  
Sonia Rompion ◽  
Guillaume Froget

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Mehmet Bilgin ◽  
Hüseyin Toprak ◽  
Mehmet Burgazli ◽  
S. Sennur Bilgin ◽  
Ritvan Chasan ◽  
...  

Purpose. In this study, our purpose was to investigate the diagnostic efficacy of the dynamic contrast-enhanced magnetic resonance imaging (MRI) method in the patients with bile duct obstruction.Materials and Methods. 108 consecutive patients (53 men, 55 women, mean age;55.77±14.62, range 18–86 years) were included in this study. All the patients underwent conventional upper abdomen MRI using intravenous contrast material (Gd-DTPA) and MRCP in 1.5 Tesla MRI scanner. MRCP images were evaluated together with the T1 and T2w images, and both biliary ducts and surrounding tissues were examined for possible pathologies that may cause obstruction.Results. MRI/MRCP findings compared with final diagnoses, MRI/MRCP in the demonstration of bile duct obstruction sensitivity 96%, the specificity 100%, and accuracy 96.3%, in the detection of presence and level of obstruction, the sensitivity 96.7%, specificity 100%, and accuracy 97.2%, in the diagnosis of choledocholithiasis, the sensitivity 82.3%, specificity 96%, and accuracy 91.7%, and in the determination of the character of the stenosis, sensitivity 95.6%, specificity 91.3%, and accuracy 94.5% were found.Conclusion. The combination of dynamic contrast-enhanced MRI and MRCP techniques in patients with suspected biliary obstruction gives the detailed information about the presence of obstruction, location, and causes and is a highly specific and sensitive method.


1993 ◽  
Vol 85 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Christopher P. Day ◽  
Alastair D. Burt ◽  
Ashley Stj. M. Brown ◽  
Mark K. Bennett ◽  
Desmond J. Farrell ◽  
...  

1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as ‘second-messengers’ and regulation of phosphatidate phosphohydrolase activity could control the balance between them. 2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the ‘metabolic’ form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide. 3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis). 4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82±0.3 nmol of Pi min−1 mg−1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 ±0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 ±0.5, n = 6). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was unchanged in the 10 days after CCl4 treatment but increased progressively in common bile duct-ligated rats (e.g. day 28: ‘sham’ operation, 1.97 ±0.3, chronic bile duct ligation, 6.91 ±1.24 nmol of Pi min−1 mg−1 of protein). N-Ethylmaleimide-insensitive phosphatidate phosphohydrolase activity correlated closely with the degree of fibrosis in humans and rats. N-Ethylmaleimide-sensitive phosphatidate phosphohydrolase activity was unchanged after CCI4 treatment or common bile duct ligation and was not increased in cirrhotic livers. 5. Plasma membrane N-ethylmaleimide-insensitive phosphatidate phosphohydrolase increases in liver fibrosis but not regeneration. Stimulation of phosphatidate phosphohydrolase activity with its effect on the diacylglycerol/phosphatidate ratio may play a role in transduction of the fibrosis signal.


2003 ◽  
Vol 58 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Ivete Bedin Prado ◽  
Marília Harumi Higuchi dos Santos ◽  
Fábio Pinatel Lopasso ◽  
Kiyoshi Iriya ◽  
Antonio Atílio Laudanna

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.


2020 ◽  
Vol 7 (9) ◽  
pp. 2830
Author(s):  
Widhitomo . ◽  
Nurhayat Usman ◽  
Reno Rudiman

Background: The aim of this study was to evaluate the potential inhibiting effects of vitamin C as an antioxidant against liver fibrosis and lipid peroxidation in the bile duct ligation- induced biliary obstruction of Wistar rats.Methods: A total of 25 male Wistar albino rats were divided into five groups: sham operated, control (bile duct ligation/BDL) without given vitamin C, BDL with vitamin C 75 mg, BDL with vitamin C 150 mg, and BDL with vitamin C 225 mg. Each group contained 5 animals. Vitamin C was given orally on day 3 after operation and after 14 days following vitamin C administration, all animals were performed laparotomy to obtain liver tissue samples for histopathological investigation of liver fibrosis and blood samples for malondialdehyde (MDA) as lipid peroxidation measurement.Results: The changes demonstrating hepatic fibrosis including moderate to markedly thickened wall of central veins, localized to diffuse perisinusoidal fibrosis, enlarged portal track, increased number of septa, and thickened width of septa were observed in BDL groups. MDA measurement were also observed in all groups. Treatment of biliary obstruction in BDL groups with vitamin C given orally attenuated liver damage. Both the MDA measurement and histopathologic investigation of hepatic fibrosis were observed to be reduced with the vitamin C treatment.Conclusions: Our data indicate that vitamin C inhibited liver fibrosis and lipid peroxidation in bile duct ligation-induced biliary obstruction of Wistar rats. 


1984 ◽  
Vol 67 (6) ◽  
pp. 647-652 ◽  
Author(s):  
Stuart R. Simpson ◽  
K. Rahman ◽  
D. Billington

1. Alkaline phosphodiesterase I was present in rat liver at approx. 100-fold greater activity than alkaline phosphatase, and in rat bile at approx. 25-fold greater activity. 2. Rat serum alkaline phosphodiesterase I was increased 6-fold whilst serum alkaline phosphatase was increased only 2-fold 96 h after bile duct ligation. 3. In contrast to alkaline phosphatase, hepatic alkaline phosphodiesterase I was not affected by bile duct ligation, suggesting its raised serum activity was due to bile regurgitation rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 8 and 96 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphodiesterase I. 5. It is suggested that alkaline phosphodiesterase I offers a potentially useful indicator of biliary obstruction in the rat.


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