Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice

Sirtuin 1 (SIRT1) is a mammalian NAD⁺-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-κB), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.     

Extremely Low Frequency Magnetic Field Modulates the Level of Neurotransmitters

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and γ -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.     

Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats

It has been shown that the extracts including eupatilin and quercetin-3-β-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-β-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-α expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-α expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-β-D-glucuronopyranoside may inhibit acute colitis.     

Intraductal papillary mucinous neoplasm of the biliary tract with cardiac metastasis: A case report

Introduction:Intraductal papillary mucinous neoplasm of the biliary tract (IPNB) is a rare, low-grade neoplasm limited to the bile duct mucosa. The malignant transformation rate is low, and there have been limited reports of metastasis to other organs. Herein, we presented a rare case of a patient who was diagnosed with IPNB concurrent with invasive adenocarcinoma after surgery and was diagnosed with cardiac metastasis 6 months later.Patient concerns:A 61-year-old male patient presented with abdominal pain to a local clinic. He was diagnosed with intrahepatic cholangiocarcinoma with pancreatitis and transferred to our hospital.Diagnosis:Diagnostic testing (magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography) revealed a papillary neoplasm and invasive adenocarcinoma with papillary neoplasm in the periampullary lesion.Interventions:Pancreaticoduodenectomy, right hemihepatectomy, and left lateral sectionectomy of the liver were performed. After surgery, we planned gemcitabine-based adjuvant chemotherapy.Outcomes:Upon completion of the sixth gemcitabine chemotherapy cycle, a hyperechoic, oval-shaped mass (1.3 × 2.6 cm) was found on the outer wall of the right atrium. Resection of a cardiac tumor in the right atrium and patch repair were performed.Conclusion:To our knowledge, no other case of cardiac metastasis found during observation after surgery for an IPNB has been described. IPNBs are known to be less aggressive and to have a lower metastasis rate than intraductal papillary mucinous neoplasms; therefore, the number of case reports describing metastasis after surgery is relatively low. Our case suggests that close observation is necessary in patients diagnosed with an IPNB.     

Recurrent rectal prolapse

PURPOSE: The aim of this study was to assess the clinical and functional outcome of surgery for recurrent rectal prolapse and compare it with the outcome of patients who underwent primary operation for rectal prolapse. METHODS: All patients who underwent surgery for rectal prolapse were evaluated for age, gender, procedure, anorectal manometry and electromyography findings, and morbidity. The results for patients who underwent surgery for recurrent rectal prolapse were compared with a group of patients matched for age, gender, surgeon, and procedure who underwent primary operations for rectal prolapse. RESULTS: A total of 115 patients underwent surgery for rectal prolapse. Twenty-seven patients, 10 initially operated on at this institution and 17 operated on elsewhere, underwent surgery for recurrent rectal prolapse. These 27 patients were compared with 27 patients with primary rectal prolapse operated on in our department. In the recurrent rectal prolapse group, prior surgery included rectopexy in 7 patients, Delorme's procedure in 7 patients, perineal rectosigmoidectomy in 7 patients, anal encirclement procedure in 4 patients, and resection rectopexy in 2 patients. Operations performed for recurrence were perineal rectosigmoidectomy in 14 patients, resection rectopexy in 8 patients, rectopexy in 2 patients, pelvic floor repair in 2 patients, and Delorme's procedure in 1 patient. There were no statistically significant differences between the groups in preoperative incontinence score (recurrent rectal prolapse, 13.6±7.8vs. rectal prolapse, 12.7±7.2; range, 0–20) or manometric or electromyography findings, and there were no significant differences in mortality (0vs. 3.7 percent), mean hospital stay (5.4±2.5vs. 6.9±2.8 days), anastomotic complications (anastomotic stricture (0vs. 7.4 percent), anastomotic leak (3.7vs. 3.7 percent) and wound infection (3.7vs. 0 percent)), postoperative incontinence score (2.8±4.8vs. 1.5±2.7), or recurrence rate (14.8vs. 11.1 percent) between the two groups at a mean follow-up of 23.9 (range, 6–68) and 22 (range, 5–55) months, respectively. The overall success rate for recurrent rectal prolapse was 85.2 percent. CONCLUSION: The outcome of surgery for rectal prolapse is similar in cases of primary or recurrent prolapse. The same surgical options are valid in both scenarios.Funded in part by a generous grant from the Eleanor Naylor Dana Charitable Trust Fund and the Caporella Family.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Variation in intraocular pressure caused by repetitive positional changes during laparoscopic colorectal surgery: a prospective,randomized, controlled study comparing propofol and desflurane anesthesia

Laparoscopic surgery is often prolonged and requires positional changes to facilitate surgical access. Previous studies reported intraocular pressure (IOP) changes in one fixed position. This study investigated the effect of desflurane and propofol anesthesia on IOP during repeated positional changes. A total of 46 patients undergoing laparoscopic colorectal surgery were randomized into desflurane or propofol groups. IOP was measured using a handheld tonometer at seven time points: before induction (baseline), after endotracheal intubation, after pneumoperitoneum, after the first Trendelenburg and right tilt position, after reverse Trendelenburg and right tilt position, after the second Trendelenburg and right tilt position and before endotracheal extubation. Trendelenburg positioning raised IOP in both groups. In the desflurane group, IOP at the first Trendelenburg position was 6.27 and 8.48 mmHg higher than baseline IOP in left and right eye, respectively; IOP at the second Trendelenburg position was 7 and 9.44 mmHg higher than baseline in left and right eye, respectively. In the propofol group, IOP at the first Trendelenburg position was 2.04 and 4.04 mmHg higher than baseline in left and right eyes, respectively. It was 3.04 and 4.87 mmHg higher than baseline in left and right eye, respectively, at the second Trendelenburg position. In the desflurane group, 56.52% patients exhibited high IOP (≥?25 mmHg) compared with 13.04% in the propofol group at the second Trendelenburg position in the right eyes (P?=?0.005). There was a positive correlation between IOP and peak inspiratory pressure (P?<?0.001). Propofol anesthesia mitigated wide variations in IOP caused by repetitive positional changes during laparoscopic colorectal surgery.     

Feasibility of a single-beat prospective ECG-gated cardiac CT for comprehensive evaluation of aortic valve disease using a 256-detector row wide-volume CT scanner: an initial experience

The aim of our study was to investigate the feasibility of single-beat prospective electrocardiogram (ECG)-gated cardiac computed tomography (CT) using a 256-detector row wide-volume CT scanner for functional and anatomical evaluation of the aortic valve (AV) and coronary arteries in patients with AV disease. A total of 50 patients who underwent cardiac CT scan with a wide-volume 256-detector row CT scanner for the evaluation of AV and aorta were retrospectively enrolled. Cardiac CT was performed using the prospective ECG-gated acquisition mode, and AV image quality was analyzed using a four-point grading system. Severity of aortic stenosis (AS) and aortic regurgitation (AR) were assessed by CT and correlated to that assessed by transthoracic echocardiography (TTE) based on kappa statistics (κ). Estimated radiation exposure was assessed. Among 50 patients, 44 underwent cardiac CT with single-beat acquisition. The median image quality score of AV was 3.0 on the systolic phase and 4.0 on the diastolic phase. Severity of AS and AR by CT showed moderate agreement with TTE. The mean effective radiation dose was 3.75?±?1.43 mSv for CT angiography. Using 256-detector row wide-volume CT, the single-beat cardiac CT is feasible for evaluation of AV disease and the coronary arteries, with acceptable image quality and a low radiation dose of 3.75 mSv.     

Paclitaxel-coated balloon treatment for functionally nonsignificant residual coronary lesions after balloon angioplasty

There is limited data on the efficacy of paclitaxel-coated balloon (PCB) compared to stents for de novo coronary lesions. The purpose of this study was to compare the efficacy of PCB treatment with stent implantation for de novo coronary lesions after successful plain old balloon angioplasty (POBA) guided by fractional flow reserve (FFR). In 200 patients scheduled for elective percutaneous coronary intervention (PCI) for de novo lesions, FFR was measured after POBA (POBA–FFR). If POBA–FFR was ≥?0.75, patients were treated with PCB (PCB group, n?=?78) or stent (Stent group, n?=?73). If POBA–FFR was <?0.75, stent was implanted as planned (Reference group, n?=?42). The primary endpoint was late lumen loss at 9 months and the secondary endpoint was adverse cardiac events (cardiac death, myocardial infarction, target lesion thrombosis, or repeat revascularization) at 12 months follow-up. There was no between-group differences in the POBA–FFR (0.87?±?0.05 in PCB, 0.89?±?0.06 in stent, p?=?0.101). At 9 months, late lumen loss was significantly lower in the PCB group compared to the Stent group (0.05?±?0.33 vs. 0.59?±?0.76 mm, p?<?0.001). Adverse cardiac events were not different between the PCB, Stent and Reference groups (2.6, 5.5, and 9.5% respectively; p?=?0.430 for PCB vs. Stent group; p?=?0.229 for the reference vs. both other groups). PCB treatment guided by POBA–FFR showed excellent 9 months angiographic and functional results, as well as comparable 12 months clinical outcomes, compared with stent implantation for de novo coronary lesions.