C2-ceramide inhibits LPS-induced nitric oxide production in RAW 264.7 macrophage cells through down-regulating the activation of Akt

The effect of C(2)-ceramide, a membrane-permeable ceramide analogue, on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was studied. The non-toxic concentration of C(2)-ceramide inhibited LPS-induced NO production. It was due to the attenuated expression of the inducible type of NO synthase (iNOS). C(2)-ceramide did not influence the phosphorylation of a series of mitogen-activated protein (MAP) kinases in response to LPS. On the other hand, C(2)-ceramide down-regulated the phosphorylation of Akt in LPS-stimulated RAW 264.7 cells, followed by the impairment of nuclear factor (NF)-kappaB activation. Moreover, the Akt dominant-negative mutant inhibited LPS-induced NO production. C(2)-ceramide was suggested to inhibit LPS-induced NO production through down-regulating the activation of Akt.     

Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease

Alzheimer's disease (AD) is the most common progressive dementia and is pathologically characterized by brain deposition of amyloid‐β (Aβ) peptide as senile plaques. Inflammatory and immune response pathways are chronically activated in AD patient brains at low levels, and likely play a role in disease progression. Like microglia, activated astrocytes produce numerous acute‐phase reactants and proinflammatory molecules in the AD brain. One such molecule, S100B, is highly expressed by reactive astrocytes in close vicinity of β‐amyloid deposits. We have previously shown that augmented and prolonged activation of astrocytes has a detrimental impact on neuronal survival. Furthermore, we have implicated astrocyte‐derived S100B as a candidate molecule responsible for this deleterious effect. To evaluate a putative relationship between S100B and AD pathogenesis, we crossed transgenic mice overexpressing human S100B (TghuS100B mice) with the Tg2576 mouse model of AD, and examined AD‐like pathology. Brain parenchymal and cerebral vascular β‐amyloid deposits and Aβ levels were increased in bigenic Tg2576‐huS100B mice. These effects were associated with increased cleavage of the β‐C‐terminal fragment of amyloid precursor protein (APP), elevation of the N‐terminal APP cleavage product (soluble APPβ), and activation of β‐site APP cleaving enzyme 1. In addition, double transgenic mice showed augmented reactive astrocytosis and microgliosis, high levels of S100 expression, and increased levels of proinflammatory cytokines as early as 7–9 months of age. These results provide evidence that (over)‐expression of S100B acts to accelerate AD‐like pathology, and suggest that inhibiting astrocytic activation by blocking S100B biosynthesis may be a promising therapeutic strategy to delay AD progression. © 2009 Wiley‐Liss, Inc.     

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for large superficial colorectal neoplasias including ileocecal lesions

Background

Large superficial neoplasias of the ileocecal region pose an increased degree of complexity for endoscopic resection. This study aimed to evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) for large superficial colorectal neoplasias including ileocecal lesions.

Methods

A total of 33 superficial colorectal neoplasias, including eight neoplasias in the ileocecal region, were treated with ESD from December 2005 to April 2009. Therapeutic efficacy, complications, and follow-up results were retrospectively evaluated among three groups: ileocecal region, colon, and rectum.

Results

The mean size of all resected neoplasias was 35 ± 15 mm (range, 20–80 mm) and that of all resected specimens was 41 ± 15 mm (range, 23–82 mm). The mean procedural time was 121 ± 90 min (range, 22–420 min). The difference in mean values among the three groups was not significant. The overall rate of en bloc resection was 91% (30/33). Histopathologically, both the lateral and vertical margins in the specimens resected en bloc tested negative (30/30). The rate for en bloc resection in the ileocecal region did not differ significantly from that for the other two groups (p = 0.20 compared with the rate for the colon and p = 0.12 compared with the rate for the rectum). Complications such as perforation and postoperative bleeding did not occur in the ileocecal group. No recurrence was observed in any cases during the mean follow-up period of 20 ± 12 months (range, 4–44 months).

Conclusions

The ESD approach is safe and effective for treating large superficial neoplasias of the ileocecal region such as other colorectal neoplasias.     

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for superficial esophageal neoplasia. Is it safe for elderly patients?

Background

Safety and efficacy of endoscopic submucosal dissection (ESD) for esophageal neoplasias have not been adequately investigated in elderly patients. This study was designed to evaluate the safety and efficacy of ESD for esophageal neoplasias in elderly patients.

Methods

Fifty-three superficial esophageal neoplasias treated with ESD using a combination of small-caliber-tip transparent hood and flex knife from May 2006 to June 2009 were divided into elderly group (aged 70 years or older: 25 lesions in 23 patients) and nonelderly group (younger than aged 70 years: 28 lesions in 25 patients). Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively.

Results

The history of cerebral infarction or cardiopulmonary disease and the usage of antiplatelet agents or anticoagulants were significantly higher in elderly group (p 0.0050 and p 0.0013, respectively). Median procedural times in the elderly group and the nonelderly group were 93 ± 53 (range, 42–235) min and 95 ± 55 (range, 40–230) min (p 0.73), respectively. Median sizes of the neoplasias and the resected specimens were 14 ± 11 (range, 5–45) mm and 15 ± 17 (range, 5–83) mm (p 0.56), and 35 ± 12 (range, 18–60) mm and 38 ± 17 (range, 18–90) mm (p 0.38), respectively. En bloc resection rate was 100% in each group. Body temperature and white blood cell counts of the next day after ESD were significantly higher in the nonelderly group than in the elderly group (p 0.0087 and p 0.0043, respectively). There were no complications, such as postoperative bleeding or perforation, in each group. The median follow-up period of 23 ± 10 (range, 4–35) months in the elderly group revealed no local or distant metastasis.

Conclusions

ESD with a combination of small-caliber-tip transparent hood and flex knife is a safe and effective treatment for superficial esophageal neoplasia in elderly and nonelderly patients.     

Endoscopic submucosal dissection and preoperative assessment with endoscopic ultrasonography for the treatment of rectal carcinoid tumors

Background

Rectal carcinoid tumors 10 mm in diameter or smaller located within the submucosal layer can be cured by local excision including endoscopic treatment. But complete resection of these tumors with endoscopic polypectomy is difficult. This study aimed to evaluate the usefulness of endoscopic submucosal dissection (ESD) and endoscopic ultrasonography (EUS) for the treatment of rectal carcinoid tumors.

Methods

In this study, 22 rectal carcinoid tumors in 21 patients were evaluated with EUS and treated using ESD from January 2004 to December 2008.

Results

The mean size of the resected tumors was 6.1 mm (range, 2.0–10 mm) on histopathologic evaluations. When the sizes of the tumors shown by EUS and histopathologic evaluation were compared, the mean values were not significantly different. All the tumors were located within the submucosal layer, and the accuracy of the preoperative depth determination with EUS was 100% (22/22). The mean duration of the ESD procedure was 37 min (range, 20–71 min). The overall rate of en bloc resection with ESD was 100% (22/22). Although postoperative bleeding occurred in two cases (9%), both cases were successfully managed by endoscopic hemostasis. No perforation or recurrence was observed during the mean follow-up period of 30 months (range, 7–66 months).

Conclusions

Endoscopic submucosal dissection and preoperative assessment with EUS are effective for treating rectal carcinoid tumors and enabling en bloc resection.     

New parameters to represent the position of the aorta relative to the spine for pedicle screw placement

Parameters of the position of the aorta in previous reports were determined for anterior surgery. This study evaluated the relative position of the aorta to the spine by new parameters, which could enhance the safety of pedicle screw placement. Three parameters were defined in a new Cartesian coordinate system. We selected an entry point of a left pedicle screw as the origin. The transverse plane was determined to include both the bases of the superior facet and to be parallel to the upper endplate of the vertebral body. A line connecting the entry points of both sides was defined as the X-axis. The angle formed by the Y-axis and a line connecting the origin and the center of the aorta was defined as the left pedicle–aorta angle. The length of a line connecting the origin and the aorta edge was defined as the left pedicle–aorta distance. Distance from the edge of the aorta to the X-axis was defined as the pedicular line–aorta distance. These parameters were measured preoperatively in 293 vertebral bodies of 24 patients with a right thoracic curve. We simulated the placement of the pedicle screw with variable length and with some direction error. We defined a warning pedicle as that when the aorta enters the expected area of the screw. Sensitivity analysis was performed to find the warning pedicle ratio in 12 scenarios. The left pedicle–aorta angle averaged 29.7° at the thoracic spine and −16.3° at the lumbar spine; the left pedicle–aorta distance averaged 23.7 and 55.2 mm; the pedicular line–aorta distance averaged 18.3 and 51.0 mm, respectively. The ratio of warning pedicles was consistently high at T4–5 and T10–12. When a left pedicle screw perforates an anterior/lateral wall of the vertebral body, the aorta may be at risk. These new parameters enable surgeons to intuitively understand the position of the aorta in surgical planning or in placement of a pedicle screw.     

Assessment of pelvic hemodynamics during an open repair of an infrarenal abdominal aortic aneurysm

Purpose  

To assess the pelvic circulation during abdominal aortic aneurysm (AAA) repair by measuring the inferior mesenteric artery stump pressure (IMA-SP), penile blood flow, and gluteal blood flow.