Wen-Tien Wu

Low-dose erythropoietin aggravates endotoxin-induced organ damage in conscious rats

Endotoxin shock can induce the production of several inflammatory mediators such as TNF-alpha, IL-6, and IL-1beta, leading to multiple organ dysfunction and death. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R), expressed in a wide variety of non-hematopoietic tissues, to induce a range of pleiotropic cytoprotective actions. We investigated the effects of low doses of EPO (300U/kg, intravenous administration) on the physiopathology and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Escherichia coli lipopolysaccharide (20mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48h after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured at 0, 1, 3, 6, 9, 12, 18, 24, and 48h after sepsis. Serum TNF-alpha, IL-6, and IL-1beta level was measured at 1h after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-alpha, IL-6, IL-1beta levels, and HR, while it decreased MAP. EPO further increased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, and CPK), inflammatory biomarkers (TNF-alpha, IL-6, and IL-1beta) and did not affect MAP and HR after LPS. EPO disserved endotoxin shock-induced liver, kidney, lung, and small intestine damage in conscious rats. In conclusion, pre-treatment with low doses of EPO increased the release of TNF-alpha, IL-6, and IL-1beta, along with aggravating endotoxin shock-induced markers of organ injury in conscious rats.

Expansive open-door laminoplasty secured with titanium miniplates is a good surgical method for multiple-level cervical stenosis

BackgroundLaminoplasty is an effective procedure for treating cervical spondylotic myelopathy (CSM). Little information is available regarding the surgical outcomes of expansive open-door laminoplasty (EOLP) when securing with titanium miniplates without bone grafting. This study is aimed to elucidate the efficacy of and problems associated with EOLP secured with titanium miniplates without bone grafting, thereby enhancing future surgical outcomes.MethodsThis is a retrospective study. The study participants comprised 104 patients who underwent cervical EOLP secured with titanium miniplates without bone graft for CSM treatment between August 2005 and March 2011. The clinical results were evaluated based on the Japanese Orthopedic Association (JOA) and Nurick scores. The radiographic outcomes were determined based on plain film and magnetic resonance imaging findings, which were assessed and compared.ResultsLateral cervical spine X-rays exhibited improvement in the Pavlov ratio of the spinal canal at 1 day postoperation, and this ratio did not change at 1 year postoperation. The mean cervical curvature from C2 to C7 decreased 0.21° ± 10.09° and the mean cervical range of motion was deteriorated by 35% at 12 months (P < 0.05). The Nurick score improved from 3.19 ± 1.06 to 0.92 ± 1.32 (P < 0.05). The mean JOA recovery rate was 75% ± 21.1% at 1 year. The mean level of postoperative neck pain at 3 months was 3.09 ± 2.31, as determined using the visual analogue scale (VAS). Increased age, concomitant thoracolumbar stenosis, depression disorder, and preexisting myelomalacia negatively affected the JOA recovery rate (P < 0.05). A decreased preoperative Nurick score and superior sensory function in the upper extremities were powerful predictors of an enhanced JOA recovery rate. The postoperative complications involved hematoma formation 0.9%, reversible C5 nerve palsy 2.8%, and moderate to severe neck pain (VAS ≥ 4) 42%. No cases of lamina closure or collapse were observed.ConclusionEOLP secured with titanium miniplates without bone grafting is a safe and effective surgical method for treating most patients with CSM.

Erythropoietin protects severe haemorrhagic shock-induced organ damage in conscious rats.

OBJECTIVE Erythropoietin (EPO) has pleiotropic cytoprotective actions. We investigated the effects of EPO on the physiopathology and cytokine levels after haemorrhagic shock (HS) in conscious rats. METHODS Rats received an intravenous injection of 300 U/kg EPO over 10 min followed by HS via withdrawal of 60% of total blood volume from a femoral arterial catheter (6 ml/100 g body weight) over 30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 18 h after the start of blood withdrawal. Levels of biochemical parameters, including haemoglobin, GOT, GPT, BUN, creatinine (Cr), LDH, CPK, and lactate were measured at 30 min before the induction of HS and 0, 1, 3, 6, 9, 12, and 18 h after HS. Cytokine levels, including TNF-alpha and IL-6, in serum were measured at 1, 9, and 18 h after HS. The kidneys, liver, lungs, and small intestine were removed for pathology assessment at 48 h after HS. RESULTS HS significantly increased HR, blood GOT, GPT, BUN, Cr, LDH, CPK, lactate, TNF-alpha, and IL-6 levels and decreased haemoglobin and MAP in rats. Pre-treatment with EPO improved survival rate, preserved the MAP, decreased the tachycardia and markers of organ injury, suppressed the release of TNF-alpha and IL-6 after HS in rats. CONCLUSION Pre-treatment with EPO suppresses the release of serum TNF-alpha and IL-6, along with decreasing the levels of markers of organ injury associated with HS, with such actions ameliorating HS-induced organ damage in rats.

LOW-DOSE PROPOFOL AMELIORATES HAEMORRHAGIC SHOCK-INDUCED ORGAN DAMAGE IN CONSCIOUS RATS

1 Propofol is an anti‐inflammatory agent commonly used for general anaesthesia and sedation in intensive care unit patients. Haemorrhagic shock (HS) followed by resuscitation can induce the production of several inflammatory mediators, such as tumour necrosis factor (TNF)‐a and interleukin (IL)‐10, leading to multiple organ dysfunction and death. 2 In the present study, we investigated the effects of treatment with high‐dose (10 mg/kg per h) and low‐dose (1 mg/kg per h) propofol after HS on the physiopathology and cytokine levels in conscious rats. 3 The experiments were designed to induce HS by withdrawing 40% of total blood volume from a femoral artery catheter (6 mL/100 g bodyweight) over 30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 48 h after the start of blood withdrawal. Levels of biochemical parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were measured 30 min before and 0, 1, 3, 6, 9, 12, 18, 24 and 48 h after the end of the 30 min blood withdrawal period. Serum cytokine levels, including TNF‐a and IL‐10, were measured at 1, 6, 12, 24 and 48 h after HS. The kidneys, liver, lungs and small intestine were removed for pathological assessment 48 h after HS. 4 In the present study, HS significantly increased blood GOT, GPT, BUN, LDH, CPK, TNF‐a and IL‐10 levels in conscious rats. Post‐treatment with high‐dose propofol accentuated systemic hypotension, increased serum TNF‐a and IL‐10 levels and increased the severity of organ damage after HS. In contrast, post‐treatment with low‐dose propofol did not affect MAP, but did suppress increased serum levels of the inflammatory cytokines and improved the survival rate after HS, thus protecting rats against HS‐induced organ damage. 5 In conclusion, post‐treatment with low‐dose propofol ameliorated HS‐induced markers of organ injury, suppressed the release of TNF‐a and IL‐10 and protected against HS‐induced liver, kidney, lung and small intestine damage in conscious rats. These findings suggest the need to investigate whether low‐dose propofol may be beneficial for patients with HS‐induced organ damage.

Vitamin D3 Reduces Tissue Damage and Oxidative Stress Caused by Exhaustive Exercise.

Exhaustive exercise results in inflammation and oxidative stress, which can damage tissue. Previous studies have shown that vitamin D has both anti-inflammatory and antiperoxidative activity. Therefore, we aimed to test if vitamin D could reduce the damage caused by exhaustive exercise. Rats were randomized to one of four groups: control, vitamin D, exercise, and vitamin D+exercise. Exercised rats received an intravenous injection of vitamin D (1 ng/mL) or normal saline after exhaustive exercise. Blood pressure, heart rate, and blood samples were collected for biochemical testing. Histological examination and immunohistochemical (IHC) analyses were performed on lungs and kidneys after the animals were sacrificed. In comparison to the exercise group, blood markers of skeletal muscle damage, creatine kinase and lactate dehydrogenase, were significantly (P < 0.05) lower in the vitamin D+exercise group. The exercise group also had more severe tissue injury scores in the lungs (average of 2.4 ± 0.71) and kidneys (average of 3.3 ± 0.6) than the vitamin D-treated exercise group did (1.08 ± 0.57 and 1.16 ± 0.55). IHC staining showed that vitamin D reduced the oxidative product 4-Hydroxynonenal in exercised animals from 20.6% to 13.8% in the lungs and from 29.4% to 16.7% in the kidneys. In summary, postexercise intravenous injection of vitamin D can reduce the peroxidation induced by exhaustive exercise and ameliorate tissue damage, particularly in the kidneys and lungs.

Rosiglitazone ameliorates endotoxin-induced organ damage in conscious rats.

Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist. By inhibiting nuclear factor κB (NF-κB), it decreases tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) and has an anti-inflammatory effect. Endotoxin shock can induce the production of several inflammatory mediators such as TNF-α and IL-6, leading to multiple organ dysfunction and death. We investigated the effects of rosiglitazone (.3 mg/kg, intravenous administration) on the physiologic attributes and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae lipopolysaccharides (LPSs; 10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 24 hr after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, TNF-α, and IL-6 were measured at 0, 1, 3, 6, 12, and 24 hr after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, glucose, TNF-α, and IL-6 levels and HR, while also decreasing MAP. Rosiglitazone diminished the increase in HR, decreased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, CPK, glucose) and inflammatory biomarkers (TNF-α, IL-6), and did not affect MAP after LPS. In conclusion, rosiglitazone ameliorated endotoxin shock-induced markers of organ injury and suppressed the release of TNF-α and IL-6 in conscious rats.

Effects of Freshwater Clam Extract Supplementation on Time to Exhaustion, Muscle Damage, Pro/Anti-Inflammatory Cytokines, and Liver Injury in Rats after Exhaustive Exercise

The potent anti-inflammatory activities and tissue-protective effects of freshwater clams (Corbicula fluminea) have been well reported. The aim of this study was to determine the effects of freshwater clam extract (FCE) supplementation on time to exhaustion, muscle damage, pro- and anti-inflammatory cytokines, and liver injury in rats after exhaustive exercise. Thirty-two rats were divided into four groups: sedentary control (SC); SC group with FCE supplementation (SC+FCE); exhaustive exercise (E); and E group with FCE supplementation (E+FCE). The SC+FCE and E+FCE groups were treated with gavage administration of 20 mg/kg for seven consecutive days. Blood samples were collected for the evaluation of biochemical parameters. The cytokine levels of TNF-α and IL-10 were also examined. Twenty-four hours after exhaustive exercise, the rat livers were removed for H & E staining. The FCE supplementation could extend the time to exhaustion in exercised rats. The levels of CPK, LDH, AST, ALT, lactate, TNF-α and H & E stains of the liver injury were significantly decreased in the E+FCE group, but the blood glucose and IL-10 were significantly higher in comparison with the E group. This study suggests that FCE supplementation may improve endurance performance and reduce exercise-induced muscle damage, inflammatory stress and liver injury.

Deleterious effects of aggressive rapid crystalloid resuscitation on treatment of hyperinflammatory response and lung injury induced by hemorrhage in aging rats.

BACKGROUND Large-volume, rapid crystalloid infusion may increase endothelial cell damage and induce shear stress, potentially leading to multiple-organ dysfunction syndrome. Limited guideline data for fluid administration are currently available, especially for the aging population. The aim of the present study was to compare the degree of organ damage in conscious aging rats when different resuscitation speeds were used during the treatment of hemorrhagic shock (HS). METHODS Eighteen aging male Wistar-Kyoto rats were randomly divided into the following three groups: the control group, 30-min rapid resuscitation group, and 12-h slow resuscitation group. To mimic HS, 40% of the total blood volume was withdrawn. Fluid resuscitation (1:3) was given at 30 min after the blood withdrawal. Blood biochemical parameters including glucose, lactic acid, and lactate dehydrogenase (LDH) were measured along with the levels of serum and bronchoalveolar lavage fluid, tumor necrosis factor alpha (TNF-α), and interleukin 10 by enzyme-linked immunosorbent assay. The lungs were examined for pathologic changes, and the injury score at 24 h after HS was calculated. RESULTS Compared with slow-rate resuscitation, initially rapid and immediate resuscitation significantly increased the serum levels of glucose, LDH, and proinflammatory cytokines (TNF-α and interleukin 10), and bronchoalveolar lavage fluid levels of white blood cells, TNF-α, and LDH as well as produced pathologic changes in the organ. The lung injury scores were higher after induced HS in aging rats. CONCLUSIONS The slow and continuous (12 h) fluid resuscitation rate ameliorated HS-induced organ damage in conscious aging rats.

Pentobarbital reduces rhabdomyolysis-induced acute renal failure in conscious rats.

BACKGROUND Rhabdomyolysis is one of the causes of acute renal failure. Pentobarbital enhances the action of gamma-aminobutyric acid and suppresses the activities of nuclear factor (NF)-kappaB pathways. In this study, we used pentobarbital to study the effects on the glycerol-induced rhabdomyolysis with acute renal failure in conscious rats. METHODS Rhabdomyolysis was induced by intramuscular injection of 10 mL/kg of 50% glycerol in conscious rats. Ten minutes later, the rats received an intravenous injection of pentobarbital (10 mg/kg in 0.5 mL/h normal saline) or normal saline (0.5 mL/h). Biochemical substances, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK) were measured at 0 hour, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours. Rats were killed by decapitation at 48 hours after glycerol administration, and the kidneys were removed immediately for pathological findings and immunohistochemistry. RESULTS Intramuscular injection of glycerol significantly increased blood BUN, Cre, GOT, GPT, CPK levels and induced severe histopathologic damage in the kidneys. NF-kappaB and inducible nitric oxide synthase (iNOS) were increased, and E-cadherin was decreased after glycerol administration, as detected by immunohistochemistry in the kidneys. Posttreatment with pentobarbital decreased blood BUN, Cre, GOT, GPT, CPK levels, decreased the markers of kidney injury, and suppressed the release of NF-kappaB and iNOS after rhabdomyolysis. CONCLUSION Posttreatment with pentobarbital suppressed the activities of NF-kappaB and iNOS, decreased BUN, Cre, GOT, GPT, CPK levels, and decreased the markers of kidney injury after rhabdomyolysis. These actions ameliorated rhabdomyolysis-induced acute renal failure in conscious rats.

Laminoplasty with adjunct anterior short segment fusion for multilevel cervical myelopathy associated with local kyphosis

Background When treating patients who have multilevel cervical spondylotic myelopathy (MCSM) with short‐segment kyphosis, instability, or major anterior foci, long‐level anterior decompression with fusion is often a standard method but can cause obvious loss of range of motion and usually needs further posterior stabilization. For MCSM with correctable kyphosis or simple instability, laminectomy with lateral‐mass instrumented fusion is also a treatment of choice, but all the involved segments are immobilized. Combining expansive open‐door laminoplasty (EOLP) and anterior short‐segment fusion may be an alternative treatment to save more motion segments. Methods This study included 109 patients who exhibited MCSM with combined local kyphosis, instability, and anterior pathology, and received EOLP and concomitant anterior short‐segment fusion. The patients were enrolled from August 2005 to July 2012. Nurick scores and Japanese Orthopedics Association cervical myelopathy scores were used to evaluate the functional outcomes. Follow‐up plain films were collected and magnetic resonance imaging was conducted to assess the radiographic outcomes. Results One year after the operation, the Japanese Orthopedics Association recovery rate was 83.4 ± 16.6%. The improvement in the functional scores and decrease in neck pain were significant. The canal width improved without further collapse at 12 months. The preservation of range of motion was approximately 57% at 1 year. Conclusion EOLP with adjunct anterior short‐segment decompression fusion yields an excellent outcome for MCSM patients who exhibit concomitant short‐segment kyphosis, instability or major anterior pathology. Performing laminoplasty first is safer for the spinal cord due to its posterior shifting while anterior procedures are being done.