We consider parameter-dependent cocycles generated by nonautonomous difference equations. One of them is a discrete-time cardiac conduction model. For this system with a control variable a cocycle formulation is presented. We state a theorem about upper Hausdorff dimension estimates for cocycle attractors which includes some regulating function. We also consider the existence of invariant measures for cocycle systems using some elements of Perron-Frobenius theory and discuss the bifurcation of parameter-dependent measures.
In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeabili ty transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to prev iously published data, we found that phenformin, after a 5 min pr e-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potent ial. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca 2+ ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity., Z. Drahota ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The incidence of diabetes mellitus is rising worldwide. The aim of this prospective epidemiological study was to compare the effects of natural and surgical menopause on parameters of glucose metabolism. In a group of 587 repeatedly examined women, with a baseline age of 45-55 years, the following subgroups of women were separated: those after bilateral oophorectomy (BO, n=37) and those in natural menopause (NAT, n=380) including women menopausal already at baseline (POST, n=89). The study parameters including glycemia, insulinemia, HOMA-IR and betacell function using HOMA-β were determined at baseline and 6 years later. Over the study period, there was a marked rise in prediabetic and diabetic values of fasting glycemia; the percentage of women with diabetic values increased in the NAT (from 0.8 % to 3.9 %) and POST (from 2.2 % to 9.0 %) subgroups, with the highest prevalence in the BO subgroup (from 8.1 % to 10.8 %). While, among women with non-diabetic fasting glycemia, an increase in fasting glycemia was observed in all study subgroups, it was more marked in the BO subgroup than in the NAT and POST ones (p=0.02 both). This difference between NAT and BO was also found in the long-term trend of development of glycemia in non-diabetic women (p=0.014). Compared with natural menopause, bilateral oophorectomy may have an adverse effect on glucose metabolism., M. Lejsková, J. Piťha, S. Adámková, O. Auzký, T. Adámek, E. Babková, V. Lánská, Š. Alušík., and Obsahuje bibliografii
This review summarizes the importance of bile acids (BA) as important regulators of various homeostatic mechanisms with detailed focus on cytochrome P450 (CYP) enzymes. In the first part, synthesis, metabolism and circulation of BA is summarized and BA are reviewed as physiological ligands of nuclear receptors which regulate transcription of genes involved in their metabolism, transport and excretion. Notably, PXR, FXR and VDR are the most important nuclear receptors through which BA regulate transcription of CYP genes involved in the metabolism of
both BA and xenobiotics. Therapeutic use of BA and their derivatives is also briefly reviewed. The physiological role of BA interaction with nuclear receptors is basically to decrease production of toxic non-polar BA and increase their metabolic turnover towards polar BA and thus decrease their toxicity. By this, the activity of some drug-metabolizing CYPs is also influenced what could have clinically relevant consequences in cholestatic diseases or during the treatment with BA or their
derivatives.
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