Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

Introduction

Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model.

Methods

We used male Wistar rats. Animals in the intervention arm received a bolus of 50 U/kg of DA or saline injected into the tail vein after lipopolysaccharide (LPS) administration. We measured cytokine (tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-10) and HMGB1 levels in serum and lung tissue at regular intervals for 12 h following LPS injection. The mouse macrophage cell line RAW 264.7 was assessed following stimulation with LPS alone or concurrently with DA with identification of HMGB1 and other cytokines in the supernatant.

Results

Survival was significantly higher and lung histopathology significantly improved among the DA (50 U/kg) animals compared to the control rats. The serum and lung HMGB1 levels were lower over time among DA-treated animals. In the in vitro study, administration of DA was associated with decreased production of HMGB1. In the cell signalling studies, DA administration inhibited the phosphorylation of IκB.

Conclusion

DA decreases cytokine and HMGB1 levels during LPS-induced inflammation. As a result, DA ameliorated lung pathology and reduces mortality in endotoxin-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of cytokines and HMGB1.     

High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats

Objective High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood. Design and setting Prospective controlled animal study in a university laboratory. Materials Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein. Measurements and results Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways. Conclusions High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Bone marrow stromal cells protect and repair damaged neurons through multiple mechanisms

A surprising shortage of information surrounds the mechanism by which bone marrow stromal cells (BMSC) restore lost neurologic functions when transplanted into the damaged central nervous system. To clarify the issue, the BMSC were cocultured with the neurons using two paradigms: the cell-mixing coculture technique and three-dimensional coculture technique. The green fluorescent protein (GFP)-expressing BMSC were cocultured with the PKH-26-labelled neurons, using cell mixing coculture technique. GFP-positive, PKH-26-negative cells morphologically simulated the neurons and significantly increased the expression of MAP-2, Tuj-1, nestin, and GFAP. GFP/nestin-positive, PKH-26-negative cells increased from 13.6% +/- 6.7% to 32.1% +/- 15.5% over 7 days of coculture. They further enhanced Tuj-1 expression when cocultured with neurons exposed to 100 microM of glutamate for 10 min. About 20-30% of GFP-positive cells became positive for PKH-26 through coculture with the neurons, but the doubly positive cells did not increase when cocultured with glutamate-exposed neurons. Alternatively, the BMSC significantly ameliorated glutamate-induced neuronal damage when cocultured with the three-dimensional coculture technique. The protective effect was more prominent when coculture was started prior to glutamate exposure than when coculture was started just after glutamate exposure. ELISA analysis revealed that the BMSC physiologically produce NGF, BDNF, SDF-1alpha, HGF, TGFbeta-1, and IGF-1 and significantly enhanced the production of NGF and BDNF when cocultured with glutamate-exposed neurons. These findings strongly suggest that the BMSC may protect and repair the damaged neurons through multiple mechanisms, including transdifferentiation, cell fusion, and production of growth factors.     

Electroencephalography-guided resection of dysembryoplastic neuroepithelial tumor: case report

A 3-year-old girl presented with a dysembryoplastic neuroepithelial tumor in the right cingulate gyrus manifesting as epilepsy refractory to anticonvulsant medication. Computed tomography and magnetic resonance imaging revealed a cystic tumor in the right cingulate gyrus. The tumor was removed under intraoperative electrocorticography guidance. Abnormal spikes recorded adjacent to the tumor disappeared immediately after total removal. Histological examination showed a multinodular, multicystic structure, satisfying the criteria for the diagnosis of dysembryoplastic neuroepithelial tumor. She has remained seizure-free for more than 4 years without complications. In this case, intraoperative electrocorticography was very useful to identify the possible focus and prevent unnecessary resection of the adjacent tissue. Total removal of the tumor resulted in a dramatic reduction of seizure activity.     

A new training method to improve deep microsurgical skills using a mannequin head

Neurosurgeons need fine and special microsurgical techniques, such as the ability to suture deep microvasculature. Intensive training is required to perform microsurgery, especially in deep microvascular anastomosis. There have been many previous reports of training methods for typical microsurgical techniques, including suturing of surgical gloves, Silastic tubes, living animals, and chicken wing arteries. However, there have been no reports of training methods to improve deep microsurgical skills under the various hand positions specific to neurosurgical operation. Here, we report a new training method using a mannequin head, water balloons, and clay to mimic actual deep microsurgery in the brain. This method allows trainees to experience microsurgery under various hand positions to approach the affected areas located at various depths in the brain from various angles.     

Posttraumatic stress disorder in mothers of children who have undergone surgery for congenital disease at a pediatric surgery department

Purpose

The aim of the study was to investigate posttraumatic stress disorder (PTSD) in mothers of children who have undergone surgery for congenital disease at a pediatric surgery department.

Methods

A questionnaire survey was carried out in 145 mothers of children who had undergone surgery and were still alive. For comparison, the mothers were categorized into 3 groups according to the severity of their child's disease.

Results

Of the 145 mothers, 29 (20%) were likely to be diagnosed as having developed PTSD at the time of the survey. Posttraumatic stress disorder symptoms correlated with factors such as anxiety and condition of the child. In terms of the disease severity of the child, factors such as anxiety tended to be observed more frequently in the higher disease severity group, whereas the proportion of mothers likely to be diagnosed as having developed PTSD was smallest in the moderate-severity group.

Conclusions

Twenty percent of the mothers of children had probably developed PTSD. In the moderate-severity group, there seemed to be a factor that alleviated PTSD symptoms. Because mothers provided effective care for the symptoms of children in the moderate-severity group, this observation suggests that participation of the mother in their child's treatment might prevent them from developing PTSD symptoms.     

A development of atheromatous plaque is restricted by characteristic arterial wall structure at the carotid bifurcation

BACKGROUND: It is said atheromatous plaque is located very focally, but there have been few reports regarding this matter. Various aspects of the pathogenesis of the development of atheromatous plaque at the carotid bifurcation have previously been discussed. We have noted the correlation of plaque localization with characteristics of the cervical carotid artery wall. METHODS: Morphological and histopathologic changes in the carotid bifurcation were examined in 72 cadaver cases with or without atheromatous plaque. We determined the level at which the wall structure changed to muscular artery from elastic artery and analyzed its influence on the development of atheromatous plaque. RESULT: Atheromatous plaques at the distal site of the ICA extended within 0 to 37 mm from the carotid bifurcation. The proximal side of the CCA more than 5 mm away from the bifurcation was elastic artery, whereas the distal side of the ICA more than 15 mm from the bifurcation was muscular artery. The area of the carotid bifurcation between elastic artery and muscular artery was a transitional zone. Approximately 80% of them were located within 15 mm, and these areas were coincident with the transitional zone. CONCLUSION: Most atheromatous plaque was located in the transitional zone. The arterial wall structure is related to the development of atheromatous plaque at the cervical carotid bifurcation.     

Feasibility of percutaneous radiofrequency ablation for intrathoracic malignancies: a large single-center experience

BACKGROUND: Radiofrequency ablation (RFA) has become an accepted alternative for treating intrathoracic malignancies; however, the incidence and characteristics of peri- and postprocedural complications are not well described. The purpose of the study was to assess the safety and technical feasibility of percutaneous RFA in unresectable intrathoracic malignancies. METHODS: Percutaneous RFA was performed in patients with intrathoracic malignancies between June 2001 and December 2004. In total, 366 tumors were treated in 137 patients in 211 sessions. All patients were nonsurgical candidates or had refused surgery. Three hundred and thirty-six lesions were subjected to RFA for the treatment of metastases and 30 lesions for primary lung carcinoma. RESULTS: Although no procedural mortality occurred, 2 patients died during the course of the study because of intractable pneumothorax and massive hemoptysis (0.9%). The overall major complication rate was 17.1% (pneumothoraces requiring tube drainage in 25, pleuritis in 6, pleural effusion requiring tube drainage in 4, lung abscess in 1, and intrapulmonary hemorrhage with hemothorax in 1). Minor complications included pneumothoraces not requiring tube drainage in 108 sessions, pleural effusion without drainage in 34, hemosputum in 9, nausea and/or vomiting in 3, subcutaneous emphysema in 3, cough in 2, skin burn in 2, atelectasis in 1, and subileus in 1. High fever and/or chest pain were seen in 33.8% and 39.3% of patients, respectively. CONCLUSIONS: With over 200 procedures, RFA appears to be a safe and minimally invasive option with negligible mortality and little morbidity in selected patients with unresectable intrathoracic malignancies.