Infection with the liver fluke Opisthorchis viverrini (Digenea) (Poirier, 1886) causes bile duct injury and periductal fibrosis by chronic overproduction of inflammatory-mediators and eventually results in cholangiocarcinoma development. While extensive research works have been done on O. viverrini infection-associated changes of bile ducts and periductal fibrosis, little attention was paid on morphological and biochemical changes of the bile canaliculi (BC), the origin of bile flow. We aimed to investigate the morphological and functional alterations of BC in the liver of hamsters infected with O. viverrini at one and three months post-infection. Ultrastructural changes of BC showed dilatation of BC and significant reduction of the density of microvilli as early as at one month post-infection. Immunohistochemistry revealed that CD10, a BC marker, expression was reduced early as one month post-infection. The mRNA expression of the genes encoding molecules related to bile secretion including bile acid uptake transporters (slc10a1 and slco1a1), bile acid dependent (abcb11) and independent (abcc2) bile flow and bile acid biosynthesis (cyp7a1 and cyp27a1) were significantly decreased at one month post-infection in association with the reduction of bile volume. In contrast, the expression of the mRNA of bile acid regulatory genes (fxr and shp-1) was significantly increased. These changes essentially persisted up to three months post-infection. In conclusion, O. viverrini infection induces morphological and functional changes of BC in association with the decrease of bile volume.
Laparoscopic cholecystectomy (LC) is the treatment of choice for gall stones but is associated with an increased risk of bile duct injury (BDI). A BDI detected during LC may be repaired if a biliary surgeon is available but the easiest and safest option for a general surgeon is to place drains in the subhepatic fossa to covert the acute BDI into a controlled external biliary fistula (EBF). Most BDIs are diagnosed in the postoperative period and result in bile leak. Treatment is with percutaneous catheter drainage and endoscopic stenting of the bile duct; early repair is not recommended. Repair, in the form of hepatico-jejunostomy (HJ), should be performed by a biliary surgeon after a delay of 4−6 weeks when the EBF has closed. BDI is a common cause of medico-legal suit and a large burden on healthcare costs. Most BDIs can be prevented by adhering to the principles of safe cholecystectomy., Laparoskopická cholecystektomie (LC) je léčbou volby u žlučových kamenů, avšak je spojená se zvýšeným rizikem poranění žlučových cest (bile duct injury − BDI). Pokud je BDI detekováno během LC, může se řešit ihned, pokud je dostupný hepatobiliární chirurg, ale nejjednodušší a nejbezpečnější postup pro všeobecného chirurga je umístění drénů do podjaterní krajiny a převedení akutní BDI na řízenou zevní biliární píštěl (external biliary fistula − EBF). Většina BDI jsou diagnostikované až v pooperačním období, kdy vzniká biliární leak. Léčbou je drenáž perkutánním katetrem a endoskopické zavedení stentu do žlučovodu; časná reparace se nedoporučuje. Reparace ve formě hepatikojejunostomie (HJ) by měla být provedena hepatobiliárním chirurgem s odstupem 4−6 týdnů poté, co se uzavře EBF. BDI jsou častou příčinou zdravotnicko-právních žalob a významně zatěžují náklady ve zdravotnictví. Většině BDI se dá předejít dodržováním principů bezpečné cholecystektomie., and V. K. Kapoor
Úvod: Existuje mnoho studií věnujících se problematice biliárních komplikací po jaterních resekcích. Přes zlepšení operační techniky a perioperační péče má incidence této komplikace spíše vzrůstající charakter. Byly analyzovány četné prediktivní faktory. Na jejich vliv na vznik biliárního leaku doposud nepanuje shoda. Za cíl analýzy jsme si stanovili zhodnotit incidenci biliárního leaku, jeho vliv na mortalitu a na dobu hospitalizace na našem pracovišti. Současně jsme provedli rozbor známých prediktivních faktorů. Metoda: Autoři retrospektivně analyzují soubor 146 nemocných, u kterých byla na Chirurgické klinice 2. LF Univerzity Karlovy a ÚVN, Praha v období 2010–2013 provedena jaterní resekce. K vyhodnocení biliárního leaku jsme užili současnou uznávanou klasifikaci ISGLS (International Study Group of Liver Surgery). Závažnost komplikace byla stanovena dle Clavien-Dindo. Statistickou významnost prediktivních faktorů jsme určili pomocí Fisherova exaktního testu a Studentova t-testu. Výsledky: Incidence biliárního leaku byla 21 %. Dle ISGLS bylo 6,5 % pacientů zařazeno do skupiny typu A, v 61,2 % se jednalo o leak B a v 32,3 % o leak typu C. Stupeň závažnosti dle Clavien-Dindo I-II, IIIa, IIIb, IV a V byl v poměru 19,3 %, 42 %, 9,7 %, 9,7 %, resp. 19,3 %. Jako statisticky významné jsme stanovili tyto faktory: operaci pro malignitu (p<0,001), velkou jaterní resekci (p=0,001), dobu operace (p<0,001), vyšší peroperační krevní ztrátu (p=0,02), konstrukci HJA (p=0,005), portální venózní embolizaci/two-stage chirurgii (p=0,009) a ASA skóre (p=0,02). Biliární leak významně prodloužil dobu hospitalizace (p<0,001). V souboru pacientů s biliárním leakem byla 23krát vyšší perioperační mortalita (p<0,001) než v souboru bez leaku. Závěr: Biliární leak je jednou z nejzávažnějších komplikací jaterních resekcí. Většina rizikových faktorů je těžko ovlivnitelných a na jejich vliv nepanuje jednoznačná shoda. Incidenci by mohly redukovat diskutované peroperační leak testy. V budoucnu bude třeba dále pracovat na zlepšení perioperačního managementu a techniky k prevenci vzniku této závažné komplikace. V léčbě se uplatňuje multidisciplinární přístup., Introduction: Many previous reports have focused on bile leakage after liver resection. Despite the improvements in surgical techniques and perioperative care the incidence of this complication rather keeps increasing. A number of predictive factors have been analyzed. There is still no consensus regarding their influence on the formation of bile leakage. The objective of our analysis was to evaluate the incidence of bile leakage, its impact on mortality and duration of hospitalization at our department. At the same time, we conducted an analysis of known predictive factors. Method: The authors present a retrospective review of the set of 146 patients who underwent liver resection at the Department of Surgery of the 2nd Faculty of Medicine of the Charles University and Central Military Hospital Prague, performed between 2010−2013. We used the current ISGLS (International Study Group of Liver Surgery) classification to evaluate the bile leakage. The severity of this complication was determined according to the Clavien-Dindo classification system. Statistical significance of the predictive factors was determined using Fisher‘s exact test and Student‘s t-test. Results: The incidence of bile leakage was 21%. According to ISGLS classification the A, B, and C rates were 6.5%, 61.2%, and 32.3%, respectively. The severity of bile leakage according to the Clavien-Dindo classification system – I-II, IIIa, IIIb, IV and V rates were 19.3%, 42%, 9.7%, 9.7%, and 19.3%, respectively. We determined the following predictive factors as statistically significant: surgery for malignancy (p<0.001), major hepatic resection (p=0.001), operative time (p<0.001), high intraoperative blood loss (p=0.02), construction of HJA (p=0.005), portal venous embolization/two-stage surgery (p=0.009) and ASA score (p=0.02). Bile leakage significantly prolonged hospitalization time (p<0.001). In the group of patients with bile leakage the perioperative mortality was 23 times higher (p<0.001) than in the group with no leakage. Conclusion: Bile leakage is one of the most serious complications of liver surgery. Most of the risk factors are not easily controllable and there is no clear consensus on their influence. Intraoperative leak tests could probably reduce the incidence of bile leakage. In the future, further studies will be required to improve the perioperative management and techniques to prevent such serious complications. Multidisciplinary approach is essential in the treatment., and K. Menclová, F. Bělina, J. Pudil, D. Langer, M. Ryska
In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohcpatic syndrome" is caused by toxic effects of uremia or by competition phenomena between variuos uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.
We investigated the gastric response to an ulcerogenic irritant and the change in gastric functions in an experimental rat model of obstructive jaundice, with or without biliary drainage. After biliary obstruction for 14 days, rats with ligated bile duct (BDL) were randomly divided into three groups: BDL group without biliary drainage, BDL followed by choledochoduodenostomy (CD) or a choledochovesical fistula (CVF). The gastric functions were evaluated 2 weeks after the surgery. Gastric damage, induced by orogastric administration of ethanol, was evaluated 30 min later using a lesion index and microscopic scoring was then performed on fixed stomachs. Basal gastric acid secretion was measured by the pyloric ligation method.The lesion index and maximum lesion depth did not differ in the BDL and sham groups, while they were significantly reduced in the CD group. Gastric acid output and secretory volume were reduced in the BDL group compared to the sham group, while these reductions were abolished in the CD group. Afferent denervation with capsaicin further reduced the ulcer index in the later group. Our data suggest that gastric mucosal susceptibility to injury is dependent on the normal flow of bile into the duodenal lumen, which appears to be a requirement for adaptive gastric cytoprotection., A. Cingi, R. Ahiskali, B. K. Oktar, M. A. Gülpinar, C. Yegen, B.Ç. Yegen., and Obsahuje bibliografii
The complex architecture of the liv er biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the preva lence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies., L. Sarnova, M. Gregor., and Obsahuje bibliografii
We give one sufficient and two necessary conditions for boundedness between Lebesgue or Lorentz spaces of several classes of bilinear multiplier operators closely connected with the bilinear Hilbert transform.
A mathematical model of the microalgal growth under various light regimes is required for the optimization of design parameters and operating conditions in a photobioreactor. As its modelling framework, bilinear system with single input is chosen in this paper. The earlier theoretical results on bilinear systems are adapted and applied to the special class of the so-called intermittent controls which are characterized by rapid switching of light and dark cycles. Based on such approach, the following important result is obtained in the present paper: as the light/dark cycle frequency is going to infinity, the value of resulting production rate in the microalgal culture goes to a certain limit value, which depends on average irradiance in the culture only. As a case study, the so-called three-state model of photosynthetic factory, being a simple four-parameter model, is analyzed. The present paper shows various numerical simulations for the model parameters previously published and analyzed experimentally in the biotechnological literature. These simulation results are in a very good qualitative compliance with the well-known flashing light experiments, thereby confirming viability of the approach presented here.
Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincin gly suggest that mildly elevated bilirubin concentrations are as sociated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with t hese results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of cor onary heart as well as peripher al vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonst rated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations., L. Vítek., and Obsahuje bibliografii
Většina léčiv se po absorpci váže na specifické bílkoviny krevní plazmy. Změny koncentrací plazmatických bílkovin ovlivní množství vázané a volné frakce jednotlivého léčiva a tím i jeho účinek. U starších pacientů se častěji setkáváme s hypalbuminemií danou především malnutricí a malabsorbcí, dále též nižší funkční synteticko u kapacitou jater a častějšími ztrátami proteinů. Tato hypalbuminemie zvyšuje volno u frakci léčiv a tím i účinnost léků, které se váží na albumin. Při chronických zánětech, infekcích, nádorových onemocněních se zvyšuje alfa-1- kyselý glykoprotein a tím se snižuje volná frakce léčiv, jež se váží na tuto bílkovinu akutní fáze. Proto je nutné v indikovaných případech vedle celkové hladiny léčiv v plazmě stanovovat plazmatické koncentrace volných frakcí: u léčiv, kde je známa významná vazba na proteiny a kde je úzké terapeutické rozmezí; u stavů, které vedou k změně hladiny proteinů v plazmě., Following their absorption, the majority of drugs bind to specific plasma proteins. Any change to plasma protein concentrations affects the proportion of bound and free fraction of the drug and thus also its effect. Older patients suffer more frequently from hypo albuminemia, mostly due to malnutrition and malabsorption but also due to lower functional capacity of the liver and recurring protein loses. This hypo albuminemi a increases the free fraction of drugs and thus the efficacy of the drugs that bind to albumin. Alfa-1-acid glycoprotein concentration increases in patients with chronic inflammatory diseases, infections and tumours and this leads to decrease in the free fraction of drugs that bind to this acute phase protein. Consequently, it is necessary in indicated cases to, apart from the total drug plasma concentrations, to also me asure plasma concentrations of free fractions: for drugs that are known to significantly bind to plasma proteins and that have narrow therapeutic index; in patients whose health status could result in plasma proteins levels deviations., Tomáš Adámek, Zoltán Paluch, Štefan Alušík, and Lit.: 16