Important role of the hepatic vagus nerve in glucose uptake and production by the liver

We examined the role of the hepatic vagus nerve in hepatic and peripheral glucose metabolism. To assess endogenous glucose production (EGP), hepatic uptake of first-pass glucose infused intraportally (HGU), and the metabolic clearance rate of glucose (MCR), rats were subjected to hepatic vagotomy (HV, n = 7) or sham operation (SH, n = 8), after 10 days, they were then subjected to a euglycemic-hyperinsulinemic clamp together with a portal glucose load in the 24-hour fasting state. Metabolic parameters were determined by the dual-tracer method using stable isotopes. During the experiment, [6,6-2H2]glucose was continuously infused into the peripheral vein. To maintain euglycemia (4.5 mmol/L), insulin (54 pmol x kg(-1) x min(-1)) and glucose were infused peripherally after the 90-minute tracer equilibration and 30-minute basal periods, and glucose containing 5% enriched [U-13C]glucose was infused intraportally (50 micromol x kg(-1) x min(-1)) for 120 minutes (clamp period). EGP was significantly higher in HV rats versus SH rats during the basal period (64.3 +/- 7.6 v 43.6 +/- 5.3 micromol x kg(-1) x min(-1), P < .005)) and was comparable to EGP in SH rats during the clamp period (9.3 +/- 21.5 v 1.1 +/- 11.7 micromol x kg(-1) x min(-1)). HGU was reduced in HV rats compared with SH rats during portal glucose infusion (5.9 +/- 2.4 v 10.1 +/- 3.2 micromol x kg(-1) x min(-1)). The MCR in HV rats was significantly higher than in SH rats in the basal period (11.0 +/- 2.0 v 7.9 +/- 0.8 mL x kg(-1) x min(-1), P < .01)) and was comparable to the MCR in SH rats during the clamp period (41.9 +/- 10.0 and 36.6 +/- 5.7 mL x kg(-1) x min(-1)). We conclude that innervation of the hepatic vagus nerve is important for the regulation of hepatic glucose production in the postabsorptive state and HGU in the postprandial state.     

Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer

Conclusions: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the prognostic value depended on the carcinoma site. Objectives: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. Methods: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. Results: The median serum level of SCC-Ag was 1.1 ng/ml (range 0–20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.     

Drastic Therapy for Listerial Brain Abscess Involving Combined Hyperbaric Oxygen Therapy and Antimicrobial Agents

Background

Listeria monocytogenes (L. monocytogenes) is a rare causative pathogen of brain abscess that is often found in immunocompromised patients. Although patients with supratentorial listerial abscesses showed a longer survival with surgical drainage, the standard therapy for patients with subtentorial lesions has not been established.

Case Report

We report herein a patient with supra- and subtentorial brain abscesses caused by L. monocytogenes infection. These abscesses did not respond to antibiotics, and his symptoms gradually worsened. Drainage was not indicated for subtentorial lesions, and the patient was additionally treated with hyperbaric oxygen therapy, which dramatically reduced the volume of abscesses and improved the symptoms.

Conclusions

This is the first report of drastic therapy for a patient with listerial brain abscesses involving combined antibiotics and hyperbaric oxygen therapy. The findings suggest that hyperbaric oxygen therapy is a good option for treating patients with deep-seated listerial abscesses and for who surgical drainage is not indicated.     

Development of 68Ga-labeled tin colloids for evaluating phagocytic function of Kupffer cells using preclinical PET imaging

Annals of Nuclear Medicine - This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET)...     

The role of PML in hematopoietic and leukemic stem cell maintenance

The tumor suppressor promyelocytic leukemia (PML) was first identified as a component of PML–RARα fusion protein, one of the initiating cytogenetic abnormalities in acute promyelocytic leukemia. PML is now known to have diverse functions regulating the DNA-damage response, apoptosis, senescence, and angiogenesis. Recent investigations have identified PML as a regulator of metabolic pathways in stem cell compartments, including the hematopoietic system, and have provided researchers with new strategies for controlling stem cell maintenance and differentiation. Studies of PML in leukemia-initiating cells demonstrate that PML is also an essential component of their maintenance, which has drawn tremendous attention to PML from scientists in various stem cell fields. Here, we review research into PML and its associated pathways, including recent studies of PML as it relates to stem cell biology, as well as our finding that PML regulates fatty acid oxidation, which is essential to the maintenance of normal hematopoietic stem cells. We also discuss the therapeutic potential of controlling PML-associated pathways. In particular, we describe promising evidence for the use of arsenic trioxide in the treatment of chronic myeloid leukemia.     

Aspirin and non-aspirin NSAIDs increase risk of colonic diverticular bleeding: a systematic review and meta-analysis

Lower gastrointestinal bleeding is a frequent cause of hospitalization, particularly in the elderly, and its incidence appears to be on the rise. Colonic diverticular bleeding is the most common form of lower gastrointestinal bleeding and is responsible for 30–40 % of bleeding episodes. Risk factors associated with diverticular bleeding include obesity, hypertension, anticoagulants, diabetes mellitus, and ischemic heart disease. Recent studies have suggested a relationship between usage of non-steroidal anti-inflammatory drugs (NSAIDs) and colonic diverticular bleeding; however, most studies were small with wide confidence intervals. We identified studies by searching the PubMed and Scopus databases (from inception through 31 December 2012) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with fixed-effects and random-effects models. A total of six studies (five case–control studies and one cohort study) met inclusion criteria for analysis. Non-aspirin NSAIDs (NANSAIDs) and aspirin were associated with an increased risk of colonic diverticular bleeding (summary RR = 2.48, 95 % CI 1.86–3.31), with moderate heterogeneity among these studies (P heterogeneity = 0.11, I ² = 44.4 %). Stratification to evaluate the heterogeneity found that both NANSAIDs (summary RR = 2.24, 95 % CI 1.63–3.09; 5 studies) and aspirin (summary RR = 1.73; 95 % CI 1.31–2.30; 3 studies) were associated with the risk of diverticular bleeding. Aspirin/NANSAIDs use was strongly and consistently associated with an increased risk of colonic diverticular bleeding. Further studies are needed to stratify individuals at risk of diverticular bleeding associated with the use of these agents.     

Relaxed pericranial flap for distraction osteogenesis to treat craniosynostosis: a technique for wound reinforcement—technical note

Purpose

Although distraction osteogenesis has been widely accepted to treat craniosynostosis, it occasionally results in wound complications. Positing that they are attributable to the tense pericranium under the scalp, we developed a simple technique to relax the pericranial flap.

Methods

In 12- to 15-month-old infants (mean 13 months), we placed a coronal skin incision and dissected the scalp at the subgaleal layer. Then, we peeled the intact pericranium away from the skull along the planned osteotomy to obtain flaps with pedicles on the caudal part. After osteotomy and setting of the distraction device, the pericranial flaps freed from the scalp flap were repositioned to fit the osteotomy line, dura, and distraction device. The galea and skin were approximated layer by layer.

Results

The shape of the skull was successfully corrected, and the bone defect created by expansion was filled by osteogenesis in all patients. During a mean follow-up period of 42.2 months, we encountered no wound complications.

Conclusions

The replaced relaxed pericranium closely adhered to the osteotomy, and the distraction device facilitated vascular growth and bone restoration. Bone resorption was prevented and skin expansion promoted. In patients with iatrogenic dural injury, the pericranium over the injured dura serves as a barrier to prevent cerebrospinal fluid leakage.