The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (∼30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (∼20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (∼50–60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient fractionation and western blotting analysis. In conclusion, this study is the first direct evidence of a cholinergic imbalance in the brain as a consequence of liver failure and points to the possible role of the cholinergic system in the pathogenesis of hepatic encephalopathy.

Classical studies of cholinesterase activity during liver dysfunction have focused on butyrylcholinesterase (BuChE), whereas acetylcholinesterase (AChE) has not received much attention. In the current study, liver and plasma AChE levels were investigated in rats with cirrhosis induced after 3 weeks of bile duct ligation (BDL). BDL rats showed a pronounced decrease in liver AChE levels (˜50%) compared with sham-operated (non-ligated, NL) controls; whereas liver BuChE appeared unaffected. A selective loss of tetrameric (G4) AChE was detected in BDL rats, an effect also observed in rats with carbon tetrachloride-induced cirrhosis. In accordance, SDS-PAGE analysis showed that the major 55-kd immunoreactive AChE band was decreased in BDL as compared with NL. A 65-kd band, attributed in part to inactive AChE, was increased as became the most abundant AChE subunit in BDL liver. The overall decrease in AChE activity in BDL liver was not accompanied by a reduction of AChE transcripts. The loss of G4 was also reflected by changes observed in AChE glycosylation pattern attributable to different liver AChE forms being differentially glycosylated. BDL affects AChE levels in both hepatocytes and Kupffer cells; however, altered AChE expression was mainly reflected in an alteration in hepatocyte AChE pattern. Plasma from BDL rats had approximately 45% lower AChE activity than controls, displaying decreased G4 levels and altered lectin-binding patterns. In conclusion , the liver is an important source of serum AChE; altered AChE levels may be a useful biomarker for liver cirrhosis. (Hepatology 2006;43:444–453.)

1) To determine the perception of safety of health professionals and non-health professionals in a university hospital; 2) describe the climate of safety with its strengths and weaknesses; 3) evaluate the negatively valued dimensions and establish areas of improvement. A cross-sectional and descriptive study carried out at the San Juan University Hospital in Alicante, where the results of the assessment of the safety culture level are collected using Hospital Survey On Patient Safety survey of the Agency for Healthcare Research and Quality adapted to Spanish language. The response rate was 35.36%. The group with the greatest participation was the physician (32.3%) and the service most involved, urgencies (9%). 86.4% had contact with the patient. 50% of workers rated the safety climate between 6 and 8 points. 82.8% did not report any adverse events in the last year. The professionals with the greatest security culture were the pharmacists and with the worst culture, the guards. No strength was identified globally. There were two dimensions that behaved like a weakness: 9 (staffing) and 10 (management support for patient safety). The patient's perception of safety is good, although it can be improved. No strengths have been identified. The weaknesses identified are staffing, management support for patient safety, handoffs and transitions, and safety perception.

Background: Microbiologic studies suggest that complicated (CAA) and uncomplicated (UAA) acute appendicitis are different entities. Routine peritoneal fluid cultures continue to be controversially related to a low positive rate, found mainly in UAA; to isolation of typical micro-organisms with expected susceptibilities; and to a community-acquired intra-abdominal infection. The aim of this study was to describe microbiologic isolates in CAA and UAA and the usefulness of peritoneal fluid cultures to determine the susceptibilities to our antibiotic therapy guidelines. Methods: This study was a retrospective review of a prospective database collected at University San Juan Hospital (Spain) between June 2014 and June 2017. Complicated acute appendicitis was defined as gangrenous or perforated, whereas UAA was defined as phegmonous or suppurative. Our antibiotic recommendations are amoxicillin-clavulanic acid and in patients with β-lactam allergies, metronidazole plus aztreonam, and an aminoglycoside (gentamicin or tobramycin). Microbiologic cultures were performed in 264 patients, 157 with a CAA and 107 with a UAA. Results: The positive culture rate was significantly higher in CAA (59%) than in UAA (24.3%). Gram-positive cocci (51.6% CAA; 23.1% UAA), including Streptococcus constellatus (29% CAA; 3.8% UAA), and anaerobes (67.7% CAA; 42.3% UAA) were significantly more common in CAA. The rates of antibiotic resistance were amoxicillin-clavulanic acid 14% (17.2% CAA; 3.8% UAA), gentamicin or tobramycin 8.4% (9.7% CAA; 3.8% UAA), ciprofloxacin 5.9% (6.5% CAA; 3.8% UAA), and ertapenem 10.9% (14% CAA; 0 UAA). Conclusions: The culture-positive rate was higher in CAA, with different isolates and susceptibilities than in UAA, identifying a higher frequency of gram-positive cocci (including S. constellatus) and anaerobes. We recommend obtaining peritoneal fluid cultures in CAA, which frequently will lead to a change in the antimicrobial drug therapy guidelines, creating specific recommendations in AA.