Retraction Note: BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

The article "BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells", by F.-H. Li, L. Xiang, L. Ran, S. Zhou, Z. Huang, M. Chen, W.-F. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (4): 1397-1407-DOI: 10.26355/eurrev_201902_17096-PMID: 30840260 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer regarding a possible overlap in Figure 2A, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The journal investigation revealed a duplication in Figure 2A between BNIP1 panels, migration and invasion, respectively and in Control and invasion panels. Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors have been informed about the journal's investigation but remained unresponsive. https://www.europeanreview.org/article/17096 This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

[Risk factors and prevention for implant treatment in patients with periodontitis].

In patients with periodontitis, due to problems of periodontal tissue infection as well as soft and hard tissues defects, it may lead to implant infection, gingival papilla loss, soft tissue recession and poor coordination with adjacent teeth. For such patients, periodontal infection should be actively controlled before dental implant therapy. In consideration of insufficient soft and hard tissues, alveolar ridge preservation and soft tissue augmentation procedure can be used to preserve or increase soft and hard tissues as much as possible. Multi-disciplinary treatment is often needed for occlusion problems and coordination with adjacent tooth. Periodontal maintenance treatment of implants and natural teeth is also necessary after implant therapy. This paper discussed these risk factors and strategies for prevention and control, in order to provide some clinical guidances for the implant treatment of periodontitis patients.

[Management of liver transplantation perioperative period in acute-on-chronic liver failure].

Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. METHODS: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. RESULTS: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. CONCLUSIONS: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.

BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.

OBJECTIVE: BNIP1, a member of the BH3-only protein family, plays essential roles in a variety of biological processes. However, the mechanism and function of BNIP1 are still unknown in cervical cancer. We aim to explore the roles of BNIP1 on cervical cancer cell proliferation, apoptosis, migration, and invasion abilities by mTOR signaling pathway. PATIENTS AND METHODS: qRT-PCR and Western blot assays were performed to assess BNIP, mTOR, and p70S6K1 expressions. CCK-8, transwell and flow cytometry assays were used to measure the representative proliferation, migration, invasion, and apoptosis abilities. RESULTS: Our findings indicated that BNIP1 is down-expressed in cervical cancer tissues and cells, and was negatively associated with lymphatic metastasis. Overexpression of BNIP1 suppressed proliferation, migration and invasion, and promoted apoptosis of cervical cancer cells. Silence of BNIP1 by siRNAs accelerated proliferation, migration and invasion, and inhibited apoptosis of cervical cancer cells. In addition, we found that BNIP1 significantly inhibited mTOR, p70S6K1, and p-p70S6K1 expressions; BNIP1 affected the proliferation, apoptosis, migration, and invasion abilities of cervical cancer cells by regulating mTOR expression. CONCLUSIONS: BNIP1 can be considered a marker for cervical carcinoma therapy.

Supraglottic jet oxygenation and ventilation enhances oxygenation during upper gastrointestinal endoscopy in patients sedated with propofol: a randomized multicentre clinical trial.

BACKGROUND: Hypoventilation is the main reason for hypoxia during upper gastrointestinal endoscopy procedures with sedation. The key to preventing hypoxia is to maintain normal ventilation during the procedure. We introduced supraglottic jet oxygenation and ventilation (SJOV) through a new Wei nasal jet tube (WNJ) to reduce the incidence of hypoxia in patients sedated with propofol during upper gastrointestinal endoscopy procedures. METHODS: In a multicentre, prospective randomized single-blinded study, 1781 outpatients undergoing routine upper gastrointestinal endoscopy who were sedated with propofol by an anaesthetist were randomized into the following three groups: the supplementary oxygen via nasal cannula group [nasal cannula oxygen: O 2 (2 litres min -1 ) was administered via a nasal cannula]; the supplementary oxygen via WNJ group [WNJ oxygen: O 2 (2 litres min -1 ) was administered through a WNJ]; and the SJOV via WNJ group (WNJ SJOV: SJOV was administered via WNJ) at three centres from March 2015 to July 2016. The primary outcome of interest was the incidence of hypoxia (peripheral oxygen saturation of 75-89%). Other adverse events were also recorded. RESULTS: Supraglottic jet oxygenation and ventilation decreased the incidence of hypoxia from 9 to 3% ( P <0.0001). No severe hypoxia occurred in the WNJ SJOV group, one instance occurred in the WNJ oxygen group, and two instances were observed in the nasal cannula oxygen supply control group. Supraglottic jet oxygenation and ventilation-related minor adverse events increased significantly within 1 min after the procedure but decreased 30 min later. CONCLUSIONS: The use of SJOV during upper gastrointestinal endoscopy for patients who are sedated with propofol reduces the incidence of hypoxia, with minor and tolerable adverse events. Supraglottic jet oxygenation and ventilation has a favourable risk-to-benefit ratio and may improve patient safety. CLINICAL TRIAL REGISTRATION: NCT02436018.

miR-206 inhibits human laryngeal squamous cell carcinoma cell growth by regulation of cyclinD2.

OBJECTIVE: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressd in many malignancies and crucial to tumorigenesis. Herein, we identified the role and mechanism of miR-206 in laryngeal squamous cell carcinoma (LSCC) growth. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect the relative expression level of miR-206 in LSCC tissues. Crystal violet and flow cytometry were conducted to explore the effects of miR-206 on the proliferation and cell cycle of human LSCC cell line, respectively. The impact of miR-206 overexpression on putative target cyclinD2 were subsequently verified via Western blot. Tumor growth assay was performed to testify the effect of miR-206 on the tumor growth in vivo. RESULTS: MiR-206 expression was frequently (p < 0.05) down-regulated in LSCC specimens. Overexpression of miR-206 in Hep-2 cell inhibited the proliferation by blocking the G1/S transition as well as suppressed the growth of xenograft tumors in mice, implying that miR-206 functions as a tumour suppressor in the progression of LSCC. Overexpression of miR-206 significantly decreased (p < 0.05) the protein level of cyclinD2, which has previously been identified as a direct targets of miR-206. CONCLUSIONS: Altogether, our results identify a crucial tumour suppressive role of miR-206 in LSCC growth, at least partly via up-regulation of cyclinD2 protein levels, and suggest that miR-206 might be a candidate prognostic predictor or an anticancer therapeutic target for LSCC patients.

Sevoflurane has no adverse effects on renal function in cirrhotic patients: a comparison with propofol.

BACKGROUND: Cirrhotic patients are prone to developing renal dysfunction after anaesthesia and surgery. However, no consensus has been reached whether sevoflurane could have adverse effects on renal function in cirrhotic patients. We hypothesised that the use of sevoflurane for general anaesthesia would lead to post-operative renal dysfunction in cirrhotic patients undergoing liver resection. METHODS: A total of 200 patients undergoing liver resection were randomly assigned to a propofol or sevoflurane group. The influence of sevoflurane or propofol on renal function was evaluated by the maximal change, the difference between the pre-operative baseline and the highest values of serum creatinine and blood urea nitrogen measured at day 1, 3 and 6 post-operatively. RESULTS: The maximal change in serum creatinine after liver resection was -4.52 (5.78) µmol/l and -3.37 (7.34) µmol/l with P = 0.398, and that in blood urea nitrogen was 0.41 (1.49) mmol/l and 0.93 (1.54) mmol/l with P = 0.098 between the sevoflurane group (n = 52) and the propofol group (n = 50), respectively. CONCLUSIONS: Sevoflurane does not seem to impair post-operative renal function in cirrhotic patients undergoing liver resection.

Functional up-regulation of P2X3 receptors in dorsal root ganglion in a rat model of bone cancer pain.

BACKGROUND: Cancer-induced bone pain remains a clinical challenge due to the poor understanding of the mechanisms. Recent study revealed extracellular adenosine triphosphate (ATP) and P2X receptors may be implicated in nociceptive signalling under cancer pain state. Therefore, here we investigated the potential role of P2X(3) receptor in a rat model of bone cancer pain. METHODS: Walker 256 tumour cells were inoculated into the left tibia of Wistar rats. The model was verified by X-ray imaging, pathology and behaviour examinations. The expression of P2X(3) receptors in dorsal root ganglia (DRG) was examined. Functional significance of altered P2X(3) receptors was investigated by measuring influx upon α,ß-meATP stimulation in acutely dissociated DRG neurons. Moreover, A-317491, an antagonist of P2X(3) receptors, was administrated intrathecally or locally to evaluate its analgesia effect in the cancer pain animals. RESULTS: The P2X(3) receptor was up-regulated for about 50% in DRG neurons in rats with bone cancer at both protein and mRNA levels and correlated with the pain behaviour in bone cancer rats. A 51.9% increase of α,ß-me ATP (10 µM, for 4 s) evoked transient response currents and a higher percentage of neurons responsive to the application of α,ß-me ATP was detected in bone cancer rats. Intrathecal or local injection of A-317491 significantly attenuated pain behaviour induced by bone cancer. CONCLUSIONS: These results suggest that the P2X(3) receptor is functionally up-regulated in DRG in cancer rats. P2X(3) receptor is a promising target for therapeutic intervention in cancer patients for pain management.

The etomidate requirement is decreased in patients with obstructive jaundice.

BACKGROUND: Patients with obstructive jaundice have increased sensitivity to inhaled anesthetics. In rodent brain, bilirubin can enhance γ-aminobutyric acid A/glycinergic synaptic transmission. Etomidate is a nonbarbiturate hypnotic that induces sedation through γ-aminobutyric acid A receptors in the central nervous system. We tested the hypothesis that patients with obstructive jaundice have an altered sensitivity to etomidate. METHODS: The study design was a comparison of etomidate requirements to reach a Bispectral Index of 50 in patients with obstructive jaundice versus patients with chronic cholelithiasis and normal bilirubin levels. Etomidate was infused at 30 µg/kg/min until this end point was reached. RESULTS: The etomidate requirement in the obstructive jaundice group was lower than that in the control group (150±46 µg/kg vs 206±74 µg/kg, P=0.007). The average decrease in etomidate requirement was 56 µg/kg (95% confidence interval: 16-96 µg/kg). In addition, we found a significant negative correlation between serum total bilirubin and etomidate requirement with Pearson r of -0.545, and 95% confidence interval for r value (-0.791 to -0.148). All subjects were hemodynamically stable during the study. CONCLUSIONS: Etomidate requirements to reach a level of anesthesia defined by a Bispectral Index of 50 are reduced in patients with obstructive jaundice.

Scientific publications in international anaesthesiology journals: a 10-year survey.

Significant growth has been seen in the field of anaesthesiology in recent decades. The current geographic distribution of the publications on anaesthesia research may be different from ten years ago. We performed this literature survey to examine the national origin of articles published in international anaesthesiology journals and to evaluate their contribution to anaesthesia research. Articles published in 18 major anaesthesiology journals from 2000 to 2009 were identified from the PubMed database and the Science Citation Index. A total of 30,191 articles were published in the selected 18 journals from 2000 to 2009. The country responsible for the largest number of articles was the United States of America (29.4%), followed by the United Kingdom, Germany, Japan, Canada, Australia and France. Denmark, Switzerland and Finland had the largest number of articles per capita. Anesthesia & Analgesia published the most number of articles from 2000 to 2009, followed by Anesthesiology, Pain and the British Journal of Anaesthesia. The numbers of clinical studies and randomised controlled trials decreased markedly from 2000 to 2009.

A comparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia.

BACKGROUND: In this study, we compared liver function tests after hepatectomy with inflow occlusion as a function of propofol versus sevoflurane anesthesia. METHODS: One hundred patients undergoing elective liver resection with inflow occlusion were randomized into a sevoflurane group or a propofol group. General anesthesia was induced with 3 µg/kg fentanyl, 0.2 mg/kg cisatracurium, and target-controlled infusion of propofol, set at a plasma target concentration of 4 to 6 µg/mL, or sevoflurane initially started at 8%. Anesthesia was maintained with target-controlled infusion of propofol (2-4 µg/mL) or sevoflurane (1.5%-2.5%). The primary end point was postoperative liver injury assessed by peak values of liver transaminases. RESULTS: Transaminase levels peaked between the first and the third postoperative day. Peak alanine aminotransferase was 504 and 571 U/L in the sevoflurane group and the propofol group, respectively. Peak aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the propofol group. There were no significant differences in peak alanine aminotransferase or peak aspartate aminotransferase between groups. Other liver function tests including bilirubin and alkaline phosphatase, and peak values of white blood cell counts and creatinine, were also not different between groups. CONCLUSIONS: Sevoflurane and propofol anesthetics resulted in similar patterns of liver function tests after hepatectomy with inflow occlusion. These data suggest that the 2 anesthetics are equivalent in this clinical context.

Volatile anesthetics might be more beneficial than propofol for postoperative liver function in cirrhotic patients receiving hepatectomy.

Hepatic inflow occlusion during the liver surgery may result in a transient ischemia period followed by reperfusion, and may initiate liver injury and lead to postoperative liver dysfunction. Especially in cirrhotic patients, the tolerance time of ischemia is much shorter and the outcome would be worse. Recently, clinical trials had proved that volatile anesthetics rather than propofol can protect myocardial cells from ischemia reperfusion (IR) injury in cardiac surgery. Meanwhile, animal studies had revealed that volatile anesthetics could induce some endogenous protective molecules in the liver such as hypoxia induced factor-1 (HIF-1), heme oxygenase (HO) enzyme system and inducible nitric oxide synthase (iNOS), which make the volatile anesthetics posing the extraordinary anti-oxidative, anti-inflammatory, anti-apoptotic, and vasodilatory characteristics. However, there is still lack of trials to compare the postoperative outcomes such as liver function in cirrhotic patients undergoing liver surgery with inflow occlusion between volatile anesthetics and propofol anesthesia. Hence we hypothesize that with its anti-IR injury characteristics, volatile anesthetics might be the more appropriate choice in cirrhotic patients undergoing liver surgery with occlusion.

A clinical prospective comparison of anesthetics sensitivity and hemodynamic effect among patients with or without obstructive jaundice.

BACKGROUND: To compare isoflurane anesthesia in patients with or without hyperbilirubinemia undergoing hepatobiliary surgery. METHODS: Forty-two patients with obstructive jaundice and 40 control patients with normal liver function scheduled for hepatobiliary surgery under isoflurane anesthesia were studied. Anesthesia was induced with propofol (1.5-2 mg/kg) and remifentanil (2 microg/kg). After tracheal intubation, anesthesia was titrated using isoflurane in oxygen-enriched air, adjusted to maintain a bispectral index (BIS) value of 46-54. Ephedrine, atropine and remifentanil were used to maintain hemodynamic parameters within 30% of the baseline. The mean arterial blood pressure (MAP), heart rate (HR), drug doses and the time taken to recover from anesthesia were recorded. RESULTS: Demographic data, duration and BIS values were similar in both groups. Anesthesia induction and maintenance were associated with more hemodynamic instability in the patients with jaundice and they received more ephedrine and atropine and less remifentanil and isoflurane (51.1+/-24.2 vs. 84.6+/-20.3 mg/min; P for all <0.05) than control patients. Despite less anesthetic use, the time to recovery and extubation was significantly longer than that in control. CONCLUSION: Patients with obstructive jaundice have an increased sensitivity to isoflurane, more hypotension and bradycardia during anesthesia induction and maintenance and a prolonged recovery time compared with controls.

The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients?

BACKGROUND: Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol. METHODS: Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 micromol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 microg/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model. RESULTS: TBL was not a significant covariate of EC(50) for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were E(max)=75.77%, EC(50)=2.34 microg/ml, and gamma=1.82, and E(max)=47.83%, EC(50)=1.49 microg/ml, and gamma=1.88, respectively. CONCLUSIONS: We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 micromol/l had no effect on propofol pharmacodynamics observed by BIS and MAP.

Propofol pharmacokinetics in patients with obstructive jaundice.

The effect of obstructive jaundice on the distribution and elimination of propofol was studied in 15 patients with obstructive jaundice (total serum bilirubin, TBL >/= 17.1micromol.l(-1)) and in 15 control patients (TBL < 17.1micromol.l(-1)). Following an i.v. bolus dose of propofol (2-2.5 mg.kg(-1)) multiple arterial samples were obtained at timed intervals for 4 h and blood concentrations of propofol were measured by high pressure liquid chromatography. Compartmental analysis of propofol concentrations revealed a three-compartment model with elimination from a central compartment in all patients. Pharmacokinelic parameters: volumes of distribution at steady state (V(SS)), volumes of distribution at equilibrium (V(r)), volumes of the central compartment (V) and total body clearance (Cl) were similar in patients with obstructive jaundice (mean 12.3 (SD 6.0) litre.kg(-1), 32.99(21.42) litre.kg(-1), 0.241(0.131) litre.kg(-1), and 28.8(8.2) ml.min(-1).kg(-1) respectively) compared with contro1 group (11.9 (5.4) litre.kg(-1), 28.30(13.70) litre.kg(-1), 0.297(0.112) litre.kg(-1), and 33.9(7.6) ml.min(-1).kg(-1) respectively) (P>0.05). Half-times of the three phases (T(1/2)(alpha),T(1/2)(beta),T(1/2)(gamma)) were also similar between both groups.We conclude that in patients with obstructive jaundice the pharmacokinetics of propofol are similar to those of patients without obstructive jaundice.

Inhibition of cell proliferation and arrest of cell cycle progression by blocking chloride channels in human laryngeal cancer cell line Hep-2.

Chloride channel (ClC) is involved in normal physiological processes and pathology of various diseases. Although it is recognized that blockade of ClC inhibits the cell proliferation, it is not well understood the potential function of ClC in laryngeal cancer. In this study, we investigated the effect of the ClC inhibitor on cell proliferation, cell cycle progression in human laryngeal cancer cell line Hep-2, as well as the effect on the phosphorylation levels of ERK1/2 and AKT1. In this study crystal violet method was used to study the effect of the ClC inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid, NPPB, on Hep-2 cell proliferation. The impaction of the inhibitor on the cell cycle distribution was investigated by the flow cytometry (FCM). Western blot was performed to measure the phosphorylation levels of ERK1/2 and AKT1. Our data indicated ClC played an important role in Hep-2 cell proliferation and cell cycle. NPPB inhibited Hep-2 cell proliferation when compared with the controls. Blockade of ClC arrested cell cycle progression and suppressed the phosphorylation of ERK1/2 and AKT1 in Hep-2 cells by inhibition of cell proliferation by CIC inhibitor (NPPB) could be through arresting cell cycle progression, which is probably by suppressing phosphorylation of ERK1/2 and AKT1.

Transgenic mice overexpressing human acetylcholinesterase and the Swedish amyloid precursor protein mutation: effect of nicotine treatment.

Acetylcholinesterase (AChE) is shown to promote deposition of beta-amyloid (Abeta) peptides and to enhance Abeta toxicity. Tg2576 (transgenic mice carrying the Swedish mutation of amyloid precursor protein, APPswe) mice and mice overexpressing human synaptic acetylcholinesterase (AChE-S) were crossed (hAChE-Tg//APPswe), to study the effects of brain Abeta, from 1 to 10 months of age, under the constant influence of AChE-S. The effect of nicotine treatment was also evaluated in these mice since we have previously shown that nicotine dramatically decreases Abeta levels in single transgenic APPswe mice. Already at 1 and 3 months, hAChE-Tg// APPswe mice showed increased levels of cortical insoluble Abeta1-40 and Abeta1-42 compared with APPswe mice, whereas APPswe mice displayed increased soluble Abeta1-40. Abeta plaques were detected at 7 months, thus before onset of plaque formation in APPswe mice. No differences were found in [125I]alpha-bungarotoxin binding sites or hippocampal glial fibrillary acidic protein (GFAP) immunoreactivity between hAChE-Tg//APPswe, and APPswe mice at either 1 or 10 months of age. L(-)-Nicotine (final dose 0.45 mg/kg) treatment twice daily for 10 days to 14-month-old hAChE-Tg// APPswe mice increased cortical insoluble Abeta1-40 levels, while both L(-)- and D(+)-nicotine (final dose 0.45 mg/kg) increased soluble Abeta1-42. L(-)-Nicotine reduced hippocampal GFAP immunoreactivity both in hAChE-Tg//APPswe mice and non-transgenic controls, while D(+)-nicotine caused a decrease only in hAChE-Tg//APPswe mice. Moreover, D(+)-nicotine increased the [125I]alpha-bungarotoxin binding sites in the hippocampus, and cortex of the hAChE-Tg//APPswe mice. In conclusion, already at a very young age, hAChE-Tg// APPswe mice exhibit increased levels of aggregated Abeta compared with APPswe mice, due to the possible interaction between Abeta and AChE-S, whereas APPswe mice exhibit increased soluble Abeta. The interaction between Abeta and AChE-S may also explain the different effect of nicotine on Abeta pathology in the hAChE-Tg//APPswe mice. The results in this study emphasize the importance of using different transgenic mouse models for evaluating the effect of new drug candidates for the treatment of Alzheimer's disease.