Avenaciolides: potential MurA-targeted inhibitors against peptidoglycan biosynthesis in methicillin-resistant Staphylococcus aureus (MRSA).

Discovery of new antibiotics for combating methicillin-resistant Staphylococcus aureus (MRSA) is of vital importance in the post-antibiotic era. Here, we report four avenaciolide derivatives (1-4) isolated from Neosartorya fischeri, three of which had significant antimicrobial activity against MRSA. The morphology of avenaciolide-treated cells was protoplast-like, which indicated that cell wall biosynthesis was interrupted. Comparing the structures and minimum inhibitory concentrations of 1-4, the α,ß-unsaturated carbonyl group seems to be an indispensable moiety for antimicrobial activity. Based on a structural similarity survey of other inhibitors with the same moiety, we revealed that MurA was the drug target. This conclusion was validated by (31)P NMR spectroscopy and MS/MS analysis. Although fosfomycin, which is the only clinically used MurA-targeted antibiotic, is ineffective for treating bacteria harboring the catalytically important Cys-to-Asp mutation, avenaciolides 1 and 2 inhibited not only wild-type but also fosfomycin-resistant MurA in an unprecedented way. Molecular simulation revealed that 2 competitively perturbs the formation of the tetrahedral intermediate in MurA. Our findings demonstrated that 2 is a potent inhibitor of MRSA and fosfomycin-resistant MurA, laying the foundation for the development of new scaffolds for MurA-targeted antibiotics.

Post-pancreaticoduodenectomy hemorrhage: risk factors, managements and outcomes.

BACKGROUND: Post-pancreaticoduodenectomy (PD) hemorrhage (PPH) is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with PPH. METHODS: A total of 840 patients with PD between 2000 and 2010 were retrospectively analyzed. Among them, 73 patients had PPH: 19 patients had early PPH and 54 had late PPH. The assessment included the preoperative history of disease, pancreatic status and surgical techniques. Other postoperative complications were also evaluated. RESULTS: The incidence of PPH was 8.7% (73/840). There were no independent risk factors for early PPH. Male gender (OR=4.40, P=0.02), diameter of pancreatic duct (OR=0.64, P=0.01), end-to-side invagination pancreaticojejunostomy (OR=5.65, P=0.01), pancreatic fistula (OR=2.33, P=0.04) and intra-abdominal abscess (OR=12.19, P<0.01) were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8% (15/54). Initial endoscopy was operated in 12 patients (22.2%), initial angiography in 19 (35.2%), and relaparotomy in 15 (27.8%). Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure, hemorrhagic shock, sepsis and uncontrolled rebleeding. CONCLUSIONS: Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH, surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.

Improving Dental Implant Outcomes: CNN-Based System Accurately Measures Degree of Peri-Implantitis Damage on Periapical Film.

As the popularity of dental implants continues to grow at a rate of about 14% per year, so do the risks associated with the procedure. Complications such as sinusitis and nerve damage are not uncommon, and inadequate cleaning can lead to peri-implantitis around the implant, jeopardizing its stability and potentially necessitating retreatment. To address this issue, this research proposes a new system for evaluating the degree of periodontal damage around implants using Periapical film (PA). The system utilizes two Convolutional Neural Networks (CNN) models to accurately detect the location of the implant and assess the extent of damage caused by peri-implantitis. One of the CNN models is designed to determine the location of the implant in the PA with an accuracy of up to 89.31%, while the other model is responsible for assessing the degree of Peri-implantitis damage around the implant, achieving an accuracy of 90.45%. The system combines image cropping based on position information obtained from the first CNN with image enhancement techniques such as Histogram Equalization and Adaptive Histogram Equalization (AHE) to improve the visibility of the implant and gums. The result is a more accurate assessment of whether peri-implantitis has eroded to the first thread, a critical indicator of implant stability. To ensure the ethical and regulatory standards of our research, this proposal has been certified by the Institutional Review Board (IRB) under number 202102023B0C503. With no existing technology to evaluate Peri-implantitis damage around dental implants, this CNN-based system has the potential to revolutionize implant dentistry and improve patient outcomes.

[Influence of obstructive jaundice on postoperative complications and mortality after pancreaticoduodenectomy: analysis of the 25-year single-center data].

OBJECTIVE: To study the influence of the depth of jaundice, the duration of jaundice and preoperative biliary drainage (PBD) on postoperative complications and mortality after pancreaticoduodenectomy (PD). METHODS: A retrospective review was performed of the medical records of 1025 patients who underwent PD between June 1986 and December 2010. The patients comprised 659 men and 366 women, ranging from 4 to 81 years old with a mean age of (54 ± 12) years. The indications for PD were malignant disease in 869 patients (84.78%) and benign or borderline tumors in 156 patients (15.22%). The operative procedures performed were pylorus-preserving modification in 279 patients and conventional PD, i.e. Whipple's operation in 746 patients. Complications after PD were compared among the different groups which was classified according to the depth of obstructive jaundice, the duration of obstructive jaundice and whether undergoing preoperative biliary drain or not, and the analysis was made by variance analysis and χ(2) test respectively. RESULTS: The depth of jaundice did not significantly affect the incidence of complications after PD except for the hemorrhage complication (χ(2) = 11.06, P = 0.03). The duration of jaundice had no much influence on the postoperative complications and mortality. PBD could not reduce the postoperative complications and mortality, however, it would increase the incidence of postoperative incision infection (χ(2) = 9.84, P = 0.01). No significant relationship was observed between the duration of PBD and the postoperative complications and mortality. CONCLUSIONS: Either the depth or duration of obstructive jaundice has no relationship with the postoperative complications and mortality after PD but the postoperative hemorrhage. Patients undergoing PD can not be benefited from PBD. Consequently, PBD should not be performed routinely, but it can be used in some serious patients with severe depth of jaundice who can not received surgery at once.

[Surgical management and outcome of solid-pseudopapillary tumor of pancreas: a series of 58 cases].

OBJECTIVE: To study the surgical management of solid-pseudopapillary tumor of the pancreas (SPTP) and its characteristics of outcome. METHODS: Fifty-eight patients with SPTP of the pancreas admitted from January 2001 to December 2010 were retrospectively analyzed. There were 7 male and 51 female patients, with an average age of 30 years (ranging 9 to 70 years). Most patients were symptomatic before admission; the most common symptom was abdominal pain. Of the 58 patients, 21 patients underwent pancreaticoduodenectomy, 30 patients underwent distal pancreatectomy, 6 patients underwent central pancreatectomy, 1 patient underwent simple tumor enucleation, and 1 patients underwent duodenum-preserving pancreatic head resection. RESULTS: The average length of stay in hospital was 23.8 days (ranging 12 to 64 days). Thirteen patients (22.4%) developed postoperative complications, including grade A postoperative pancreatic fistula of 8 cases, gastrointestinal tract bleeding of 1 case, pleural effusion of 2 cases, wound infection and fat liquefaction of 2 cases. Two patients underwent reoperation due to gastrointestinal tract bleeding or wound infection. There was no hospital death. Forty-four patients were followed-up for 7 to 136 months with an average of 41 months. All the 44 patients were alive, while 8 patients developed dyspepsia and 4 patients developed diabetes mellitus. There were no tumor recurrences or metastasis. CONCLUSIONS: SPTP is found primarily in young women. Excellent prognosis would be achieved with surgical resection.

Water adsorption characteristic and its impact on pore structure and methane adsorption of various rank coals.

Coalbed methane not only is a new clean energy source, but also has potential damage to ecological environment. Water and methane coexist in coal reservoir; understanding the adsorption of water on coal and its impact on pore structure and methane adsorption of coal is vital to evaluate the reserves and productivity of coalbed methane. In the paper, water adsorption characteristics of various rank coals are firstly investigated by ten mathematical models. The modified Dent model provides a best fit, followed by GAB and Dent models. For GAB model, the primary site adsorption is more difficult to reach saturation, and the contribution rate of the secondary site adsorption is surprisingly high at P/P0 approaching 0, which can be attributed to the possible overestimation of GAB monolayer adsorption capacity and secondary site adsorption. Besides, the low-rank coal sample YZG2 exhibits more prominent hysteresis than middle- to high-rank coals. The low-pressure hysteresis can be attributed to the water-water interactions over the primary site and the strengthened binding forces of water molecules in the water desorption process. In contrast, the high-pressure hysteresis largely depends on pore structure of coal such as ink-bottle pores, especially for the studied sample YZG2. Besides, pore analyses by low-temperature nitrogen adsorption method show that the pre-adsorbed water has remarkable influence on micropores smaller than 10 nm, and the micropores smaller than 4 nm almost disappear for water-equilibrated coals, which is closely related to the formed water clusters and capillary water in pore throats. This finding reveals that more methane gas can only be adsorbed in the larger pores of moist coal, and provides an explanation for water weakening methane adsorption capacity.

Hierarchical zeolites comprising orthogonally stacked bundles of zeolite nanosheets for catalytic and adsorption applications.

The synthesis of hierarchical MFI zeolites comprising orthogonally stacked bundles of zeolite nanosheets using a new type of triblock structure-directing agents (SDAs) was reported. The textural properties, including the degree of nanosheet branching and the spacing between adjacent nanosheets, could be controlled by changing the length of the linkers in the triblock SDAs. The hierarchical pure-silica silicalite-1 materials exhibited high and stable catalytic activity for the vapor-phase Beckmann rearrangement of cyclohexanone oxime with high selectivity of ε-caprolactam. On the other hand, the hierarchical ZSM-5 materials showed high adsorption capacity of Pb2+ ion following a Langmuir-type adsorption behavior. After being deposited with Pd nanoparticles, the hierarchical Pd/ZSM-5 nanocomposites exhibited high activity in the aqueous-phase hydrogenation of phenol to cyclohexanone at room temperature. The results show promise of the disclosed hierarchical zeolites for catalytic and adsorption applications.

Neferine induces p38 MAPK/JNK1/2 activation to modulate melanoma proliferation, apoptosis, and oxidative stress.

BACKGROUND: Melanoma is a malignant skin cancer that has a poor prognosis in advanced patients. The aim of the present study was to investigate the antitumor role of neferine in melanoma. METHODS: A375 and C32 cells were selected as research vectors in vitro. Cell counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, transwell, and flow cytometry assay were used to examined cell malignant phenotypes. Mitochondrial dysfunction was detected by 5,50,6,60-tetrachloro-1,10,3,30-tetraethyl-imidacarbocyanine iodide staining and enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) generation was measured using oxidation sensitive fluorescent probe. The phosphorylation activity of p38 and Jun-N-terminal kinase (JNK) 1/2 were examined by Western blot. A xenograft model was established via the subcutaneous injection of A375 cells into the right flank of BALB/c mice in vivo. RESULTS: Neferine (2.5, 5, or 10 µM) treatment inhibited proliferation, invasion, and enhanced apoptotic rate of A375 and C32 cells. Neferine treatment induced abnormal changes in mitochondrial membrane potential. Further studies showed that neferine could significantly increase the production of reactive oxygen species (ROS) and 3,4-methylenedioxyamphetamine (MDA) content, decreased the superoxide dismutase (SOD) level. Neferine (5, 10, or 20 mg/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells in vivo, and the expression of Ki67+ and survivin+ decreased. Notably, neferine also activated the phosphorylation of p38 and JNK1/2. CONCLUSIONS: Neferine inhibits the proliferative and invasion ability of melanoma cells and promotes their apoptosis, ameliorating the malignant progression of melanoma, likely achieved by upregulating the phosphorylation levels of p38 mitogen-activated protein kinase and JNK1/2.

Proteome and microbiota analysis highlight Lactobacillus plantarum TWK10 supplementation improves energy metabolism and exercise performance in mice.

Lactobacillus plantarum TWK10 (LP10) is a probiotic known to improve endurance exercise performance. Here, we analyze the proteomics and metagenomic changes in a LP10 supplemented mouse model. Male ICR mice were divided into two groups (n = 8) to receive by oral gavage either vehicle or of LP10 for 6 weeks. Proteins changes by LP10 treatment were subjected to the Ingenuity Pathway Analysis (IPA) to provide corroborative evidence for differential regulation of molecular and cellular functions affecting metabolic processes. Fecal samples were obtained from each mouse, and the microbial community profile analyzed by pyrosequencing of the 16S rRNA genes. Of the 880 identified proteins, 25 proteins were significantly downregulated and 44 proteins were significantly upregulated in the LP10 treated compared to vehicle group. LP10 supplementation shift in the gut microbiota to butyrate-producing members and provided from lipid oxidation since peroxisomal fatty acid oxidation in liver.

[Determinants of long-term survival after pancreaticoduodenectomy for ampulla of Vater carcinoma].

OBJECTIVE: To investigate the determinants of long-term survival for ampulla of Vater carcinoma treated by pancreaticoduodenectomy. METHODS: A total of 77 patients with ampulla of Vater carcinoma undergoing pancreaticoduodenectomy were reviewed. Kaplan-Meier method was used to analyze the survival rate. Independent t test was used for statistical comparison and COX regression model for multivariate analysis. RESULTS: No patient died as a result of surgery. The overall 5-year survival was 40.7%. Univariate analysis showed that perioperative serum carcinoembryonic antigen (CEA) level (P = 0.012), tumor invasion depth (P = 0.000), UICC stage (P = 0.000) and tumor size (P = 0.001) were significant prognostic factors of ampulla of Vater carcinoma; in multivariate analysis, only the tumor size (P = 0.000) was an independent prognostic factor of ampulla of Vater carcinoma. CONCLUSION: Pancreaticoduodenectomy is associated with significant survival. Tumor size is the most important influencing factor of outcome after pancreaticoduodenectomy; in addition, perioperative serum CEA level, tumor invasion depth and UICC stage may also influence the survival rate, there exists a need for further follow-up studies.

Effects of portal venous arterialization on acute occlusion of hepatic artery in rats.

BACKGROUND: A fatal complication after liver transplantation is anastomotic embolization of the hepatic artery. In order to solve this problem, the portal venous arterialization (PVA) is used to reconstruct the hepatic arterial blood flow. The purpose of this study was to investigate the influence of PVA on rats with acute occlusion of hepatic artery. METHODS: Rat PVA models were established and then randomly divided into Group 1 (control group), Group 2 (jaundice group), Group 3 (bile duct recanalization group), and Group 4 (portal vein arterilization group). Recanalization of the common bile duct and PVA were performed 5 days after bile duct ligation in the rats. The influence of the PVA on general conditions, hepatic changes of structure and function, portal vein pressure and hepatic micrangium were observed for one month. RESULTS: Five days after common bile duct ligation the serum bilirubin, transaminase and alkaline phosphatase levels were significantly increased. Compared with group 1, there was a statistically significant difference (P < 0.01). These rats then underwent bile duct recanalization and PVA. After a month, the liver functions and microscopic structures completely returned to normal and, compared with group 1, there was no statistically significant difference in portal vein pressure (P > 0.05). Vascular casting samples showed that hepatic sinusoids were slightly thicker and more filled than normal ones and although they had some deformations, the hepatic sinusoids were still distributed around the central vein in radial form. CONCLUSION: Within a month after operation, bile duct recanalization and PVA do not show obvious adverse effects on liver hemodynamics and hepatic micrangium, and the liver function and microscopic structure can return to normal.

The discovery of novel heat-stable keratinases from Meiothermus taiwanensis WR-220 and other extremophiles.

Billions of tons of keratin bio-wastes are generated by poultry industry annually but discarded that result in serious environmental pollution. Keratinase is a broad spectrum protease with the unique ability to degrade keratin, providing an eco-friendly way to convert keratin wastes to valuable amino acids. In this report, a feather-degrading thermophilic bacterium, Meiothermus taiwanensis WR-220, was investigated due to its ability to apparently complete feather decay at 65 °C in two days. By genomics, proteomics, and biochemical approaches, the extracellular heat-stable keratinase (MtaKer) from M. taiwanensis WR-220 was identified. The recombinant MtaKer (rMtaKer) possesses keratinolytic activities at temperatures ranging from 25 to 75 °C and pH from 4 to 11, with a maximum keratinolytic activity at 65 °C and pH 10. The phylogenetic and structural analysis revealed that MtaKer shares low sequence identity but high structural similarity with known keratinases. Accordingly, our findings have enabled the discovery of more keratinases from other extremophiles, Thermus and Deinococcus. Proteins encoded in the extremophiles shall be evolved to be functional in the extreme conditions. Hence, our study expands the current boundary of hunting keratinases that can tolerate extreme conditions for keratin wastes biorecycle and other industrial applications.

[Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors].

OBJECTIVE: To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs. METHODS: We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm). RESULTS: In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups. CONCLUSION: Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.

Pure Laparoscopic Versus Open Liver Resection for Primary Liver Carcinoma in Elderly Patients: A Single-Center, Case-Matched Study.

Pure laparoscopic liver resection (PLLR) has been reported to be as safe and effective as open liver resection (OLR) for liver lesions, and it is associated with less intraoperative blood loss, shorter hospital stay, and lower complication rate. However, studies comparing PLLR with OLR in elderly patients were limited. The aim of this study was to analyze the short-term outcome of PLLR versus OLR for primary liver carcinoma (PLC) in elderly patients.Between January 2008 and October 2014, 30 consecutive elderly patients (≥70 years) who underwent PLLR for PLC were included into analysis. Sixty patients who received OLR for PLC during the same study period were also included as a case-matched control group. Patients were well matched in terms of age, sex, comorbid illness, Child Pugh class, American Society of Anesthesiologists grade, tumor size, tumor location, and extent of hepatectomy.No significant differences were observed with regard to patient preoperative baseline status, median tumor size (Group PLLR 4.0 cm vs Group OLR 5.0 cm, P = 0.125), tumor location, extent of hepatectomy, and operation time (Group PLLR 133 minutes vs Group OLR 170 minutes, P = 0.073). Compared with OLR, the PLLR group displayed a significantly less frequent Pringle maneuver application (10.0% vs 70.0%, P < 0.001), less blood loss (100 vs 300 mL; P < 0.001), shorter hospital stay (5 vs 10 days; P < 0.001), and lower total hospitalization cost ($9147.50 vs $10,867.10, P = 0.008). The postoperative complication rates were similar between groups (Group PLLR 10.0% vs Group OLR 16.7%; P = 0.532). There was no hospital mortality in both groups.PLLR for PLC is as safe and feasible as OLR, but with less blood loss, shorter hospital stay, and lower hospitalization cost for selected elderly patients.

Clinicopathological characteristics and prognostic factors of intrahepatic biliary cystadenocarcinoma.

BACKGROUND: Surgical resection is generally considered the main curative treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs, but controversy exists regarding the prognosis for IBCAs. This study aimed to describe the clinicopathological characteristics of IBCA and identify prognostic factors that may influence the survival of patients treated with surgical procedures. METHODS: Thirty-four patients with histologically confirmed IBCA treated between January 2000 and June 2014 were included. The clinical characteristics of patients with IBCA were compared with those of 41 patients with intrahepatic biliary cystadenoma (IBC); factors that significant difference were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox proportional hazards regression models. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: IBCAs had a strong female predominance, and the most common presenting symptoms were abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older patients, in more male patients, and were associated statistically significant abnormal increase in alanine aminotransferase (P = 0.01) and total bilirubin (P = 0.04). Mural nodules were more frequently seen with IBCAs and may associate with malignancy. It was difficult to differentiate between IBC and IBCA based on laboratory examination and imaging findings. Although complete resection is recommended, enucleation with negative margins also achieved good outcomes. Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive tumor type were independent prognostic factors for overall survival. CONCLUSIONS: It remains difficult to distinguish between cystadenomas and cystadenocarcinomas based on laboratory examination and image findings. Complete resection is recommended for curative treatment, and patients should be closely followed postoperatively, particularly those with invasive tumors.

The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions.

In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO3(2-) and DCCM/SeO3(2-) complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

An efficient and selective method for preparing glycosyl sulfoxides by oxidizing glycosyl sulfides with OXONE or t-BuOOH on SiO2.

Silica gel adsorbed with OXONE or t-BuOOH was used as a mild oxidant to selectively oxidize glycosyl sulfides to corresponding sulfoxides in good yields and without sulfones formation. This method was also found compatible with various other functional groups in the glycosides.

Protective effects of lidocaine injected into the hepatoduodenal ligament on warm ischemia-reperfusion injury to the rat liver.

BACKGROUND: Ischemia-reperfusion (IR) injury to the liver is still a critical and daunting problem in the field of hepatobiliary surgery. Ischemic preconditioning (IP) of the liver serves as an effective approach against IR injury. This study was to develop a novel procedure that could mimic IP, but might be more feasible than IP during surgery. METHODS: Eighty-two SD rats were randomly divided into 5 groups. L group (n = 21): 0.4% lidocaine (10 mg/kg) was injected into the hepatoduodenal ligament 10 minutes before a 40-minute hepatic IR. IP group (n = 16): a 5-minute ischemia was followed by a 10-minute reperfusion prior to a 40-minute hepatic IR. ILR group (n = 15): after a 40-minute ischemia of the liver, 0.4% lidocaine (10 mg/kg) was injected into the hepatoduodenal ligament 10 minutes prior to a 40-minute reperfusion of the liver. IR group (n = 15): the liver of the rat was subjected to a 40-minute IR. Control group (n = 15): 0.9% sodium chloride was injected into the hepatoduodenal ligament without other treatments. The levels of plasma alanine transaminase (ALT) and aspartate transaminase (AST) were determined for each group after treatment. RESULTS: The mean concentrations of ALT and AST were (379.80 +/- 141.69) U/L and (606.05 +/- 220.26) U/L for the L group, (334.64 +/- 141.94) U/L and (625.68 +/- 267.06) U/L for the IP group, (523.36 +/- 170.35) U/L and (765.47 +/- 238.45) U/L for the ILP group, (524.29 +/- 163.59) U/L and (764.63 +/- 246.79) U/L for the IR group, and (150.90 +/- 27.05) U/L and (298.15 +/- 47.68) U/L for the control group (standard error of the mean). CONCLUSION: A significant decrease in ALT and AST levels was observed in the L and IP groups when compared to the ILR and IR groups (P < 0.05), but no significant difference in ALT and AST levels was observed in the L group when compared to the IP group (P > 0.05). These results suggest that pretreatment with lidocaine injected into the hepatoduodenal ligament prior to IR provides effective protection against subsequent IR injury to the liver. The novel approach of blocking innervation with lidocaine mimics hepatic IP, but is more convenient than IP at the time of liver surgery.

[Analysis of the early and late gene expression of lipopolysaccharide activated macrophages by cDNA microarray].

OBJECTIVE: To study the early and late changes in mRNA expression in macrophages in response to lipopolysaccharide (LPS) with a cDNA microarray approach using the Clontech Atlas microarray. METHODS: mRNA was isolated from unstimulated control and LPS stimulated murine peritoneal macrophages at 2 hours and 24 hours poststimulation, converted to (33)P radiolabeled cDNA, and hybridized to mouse array membranes. RESULTS: In macrophages being stimulated for 2 hours, 69 out of 1 176 genes were found to differ by over 3-fold compared with the control. Among them 44 genes were up-regulated and 25 genes were down-regulated. In macrophages stimulated for 24 hours, 11 genes were up-regulated and 26 genes were down-regulated compared with the control. Only 8 genes were identified both at 2 hours and at 24 hours poststimulation. The expressions of many genes encoding transcription factor, cytokines, cell signaling modulators and apoptosis associated proteins were found to have changed. Some genes that were not previously linked to this model, such as bric-a-brac (BTB) and cap-n-collar(CNC) homology 1(BACH1), early growth response protein 2 (EGR2), E47 interaction protein 1 (EIP1), Ngfi-A binding protein 2 (NAB2), myeloblastosis oncogene-like protein (MYBL2), neurofibromatosis 1 (NF1), ciliarry neurotropic factor (CNTF) and semaphorin 4A (Sema4A). CONCLUSION: This study has allowed us to identify genes that may potentially be regulated by LPS at early and late phase in macrophages. These may contribute to better understanding of the mechanism underlying LPS or bacteria induced inflammatory and immune response following infection and trauma.