Preventive Intrathecal Injection of Bupivacaine Alleviated Microglia Activation and Neuropathic Pain in a Rat Model of Chronic Constriction Injury.

Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic administration of bupivacaine have been previously reported. In this study, the preventive effects of intrathecal bupivacaine administration against neuropathic pain were revealed in a rat model of sciatic nerve chronic constriction injury (CCI). Using a CCI rat model, pain hypersensitivity, characterized by mechanical allodynia and thermal hyperalgesia, correlated well with microglia M1 polarization, activation and pro-inflammatory cytokine expression in both spinal cord dorsal horns and sciatic nerves. Bupivacaine attenuated pain behaviors and inflammatory alternations. We further identified that the Interferon Regulatory Factor 5 (IRF5)/P2X Purinoceptor 4 (P2X4R) and High Mobility Group Box 1 (HMGB1)/Toll-Like Receptor 4 (TLR4)/NF-κB inflammatory axes may each play pivotal roles in the acquisition of microglia M1 polarization and pro-inflammatory cytokine expression under CCI insult. The relief of pain paralleled with the suppression of microglia M1 polarization, elevation of microglia M2 polarization, and inhibition of IRF5/P2X4R and HMGB1/TLR4/NF-κB in both the spinal cord dorsal horns and sciatic nerve. Our findings provide molecular and biochemical evidence for the anti-neuropathic effect of preventive bupivacaine.

Wild Bitter Melon Extract Regulates LPS-Induced Hepatic Stellate Cell Activation, Inflammation, Endoplasmic Reticulum Stress, and Ferroptosis.

The activation of hepatic stellate cells (HSCs) is a key component of liver fibrosis. Two antifibrosis pathways have been identified, the reversion to quiescent-type HSCs and the clearance of HSCs through apoptosis. Lipopolysaccharide- (LPS-) induced HSCs activation and proliferation have been associated with the development of liver fibrosis. We determined the pharmacological effects of wild bitter melon (WM) on HSC activation following LPS treatment and investigated whether WM treatment affected cell death pathways under LPS-treated conditions, including ferroptosis. WM treatment caused cell death, both with and without LPS treatment. WM treatment caused reactive oxygen species (ROS) accumulation without LPS treatment and reversed the decrease in lipid ROS production in HSCs after LPS treatment. We examined the effects of WM treatment on fibrosis, endoplasmic reticulum (ER) stress, inflammation, and ferroptosis in LPS-activated HSCs. The western blotting analysis revealed that the WM treatment of LPS-activated HSCs induced the downregulation of the connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), integrin-ß1, phospho-JNK (p-JNK), glutathione peroxidase 4 (GPX4), and cystine/glutamate transporter (SLC7A11) and the upregulation of CCAAT enhancer-binding protein homologous protein (CHOP). These results support WM as an antifibrotic agent that may represent a potential therapeutic solution for the management of liver fibrosis.

Oridonin Attenuates Lipopolysaccharide-Induced ROS Accumulation and Inflammation in HK-2 Cells.

Renal tubulointerstitial inflammation plays an important role in chronic kidney disease (CKD). Inflammation reduction is a good strategy to combat CKD. Oridonin, an ent-kaurane diterpenoid isolated from Rabdosia rubescens (Donglingcao), is considered as an effective natural candidate for the treatment of anti-inflammatory, antiviral, and antibacterial activities, including liver fibrosis and many tumors; however, no study has demonstrated its effect on lipopolysaccharide- (LPS-) induced renal inflammation. To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells (HK-2 cells), the expression levels of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) were evaluated by Western blot analysis and 2',7'-dichlorofluorescein diacetate (DCF-DA) staining, respectively. The level of intracellular ROS increased in a dose-dependent manner following LPS treatment, whereas oridonin inhibited this effect, suggestive of its ability to prevent ROS accumulation. As the mitogen-activated protein kinase (MAPK) family of enzymes plays an important role in physiological responses, we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation. Oridonin also attenuated RAW 264.7 cell chemotaxis towards LPS-treated HK-2 cells. Taken together, oridonin protected against LPS-induced inflammation including ROS accumulation, JNK activation, NF-κB nuclear translocation in HK-2 cells, and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells. Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells.

Endoscopic Sclerotherapy with a Large Volume of High Concentration of Cyanoacrylate for Jejunal Variceal Bleeding bys Single-Balloon Enteroscopy.

Jejunal varices are a rare manifestation of portal hypertension, and they are associated with a high mortality and poor prognosis when bleeding occurs. A bleeding jejunal varix is much more challenging to diagnose and manage because of its anatomic location. Herein, we describe the case of a 62-year-old man with active jejunal variceal bleeding who presented with massive hematochezia and hypovolemic shock. He was treated successfully with a high volume and concentration of a glue mixture as endoscopic sclerotherapy using single-balloon enteroscopy in the intensive care unit. Enteroscopic sclerotherapy is an effective option for jejunal variceal bleeding.

Perioperative thrombotic occlusion of left external iliac artery during anterior lumbar interbody fusion.

We report a case of thrombotic occlusion of left external iliac artery during the procedure of anterior lumbar interbody fusion. The diagnosis was confirmed by computed tomography angiography. The patient also developed severe rhabdomyolysis postoperatively. In spite of receiving emergent thromboendarterectomy, the patient expired on postoperative day 3. This report attempts to remind spinal surgeons and anesthesiologists of this rare but potentially fatal complication, and discuss the possible mechanism, management, and prevention.

Massive pulmonary embolism during orthopedic surgery.

A 90-year-old female patient undergoing surgery for knee and hip fractures under general anesthesia sustained cardiac arrest intraoperatively. The transesophageal echocardiography performed during resuscitation revealed massive pulmonary embolism with a 2 x 3 cm oval-shaped thrombus in the bifurcation of pulmonary artery. Anticoagulant therapy was administered immediately. Clinical symptoms were gradually improved, and transthoracic echocardiography performed 5 days later revealed no evidence of residual thromboemboli. Subsequently the patient developed liver and acute renal failures in consequence of hypoperfusion during the intraoperative resuscitation, and died of multiple organ failure 21 days after the procedure. We conclude that transesophageal echocardiography is a useful diagnostic instrument and should be utilized in high risk patient as early as possible, even before and during surgery.

Risk factors affecting adverse outcomes of cardiac surgery in patients aged 70 years and older.

BACKGROUND: The elderly segment of the population in Taiwan is increasing rapidly. According to the latest information from the Directorate-General of Budget, Accounting and Statistics, Executive Yuan, Taiwan, 1,553,367 civilians of the total population of 22,879,510 (6.8%) are seventy years old and older in 2007. The proportion of high-risk patients has increased dramatically owing to a greater number of elderly patients and increased number of average patients with heart diseases presenting for cardiac surgery. We analyzed the preoperative risk factors for in-hospital mortality, morbidity and the likelihood of prolonged intensive care unit (ICU) stay in elderly patients after cardiac surgery. METHODS: We retrospectively studied 952 adult patients who received cardiac surgery during a three-year period (from August 1, 2004 to December 31, 2006) at Taichung Veterans General Hospital. Patients were divided into a control group and a study group. The study group (n=395) exclusively consisted of patients aged seventy or over while the rest of the patients under study served as reference group (n=557). Continuous variables were compared using Student's t test, and categorical variables were compared using Pearson chi-square test. Variables associated with in-hospital mortality, major morbidity and prolonged ICU stay in univariate analysis with P < 0.05 were entered into multivariate analysis using logistic regression with a stepwise forward selection procedure to determine independent variables and identify variables associated with major adverse outcomes. RESULTS: Fifty-six (14.2%) patients died during their hospitalization in the study group and 46 (8.3%) in the reference group. Major mortality in the study group was 58.0% versus 39.7% in the reference group. The patients of the study group spent more days in the ICU than did patients of the reference group (8.7 +/- 12.0 versus 6.1 +/- 10.0 days, P < 0.05). In addition, 114 (28.9%) patients of the study group and 85 (15.3%) of the reference group spent more than 7 days in the ICU. Using multiple logistic regression analysis, risk factors affecting in-hospital mortality in the study group include impairment of renal function, reoperation, congestive heart failure (CHF), catastrophic event. Impaired renal function, complexity of surgical procedure, CHF, chronic obstructive pulmonary disease (COPD) and catastrophic state were significant factors affecting morbidity in the study group. CHF, COPD and catastrophic event contributed to prolonged ICU stay in the study group. CONCLUSIONS: The perioperative risk of cardiac surgery increases in older patient groups, and some risk factors have different influences on mortality, morbidity and ICU stay. Risk assessment in older cardiosurgical patients with convenient risk factors helps the clinicians to apply rational and cost-effective treatment strategies into practice.

Building collapse and human deaths resulting from the Chi-Chi Earthquake in Taiwan, September 1999.

In this study, the authors attempted to determine factors associated with earthquake deaths in the great Chi-Chi Earthquake that occurred on September 21, 1999, in Taiwan. An isoseismal map was used to identify life-threatening hazards. The vertical peak ground acceleration of ground motion intensity was deemed the most appropriate index for the evaluation of building collapse and mortality. Mortality increased with the increase in earthquake intensity, and building collapse, approaching the epicenter. The greatest number of collapsed buildings and human deaths occurred between the Chelungpu Fault and the Shuantun Fault. Individuals 65 yr of age and older were the most vulnerable to the impact. The authors' findings suggest that improvements in earthquake-resistant building design and construction, as well as improved medical rescue for the elderly, could reduce the level of exposure to earthquake hazards.