Willy Chou

Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury

BACKGROUND Pro-inflammatory cytokines and free radicals damage renal tissue leading to acute kidney injury (AKI) during sepsis. Bone morphogenetic protein-7 (BMP-7) represses tumour necrosis factor (TNF)-α-induced inflammatory responses and protects kidney from injury. The sedative agent, propofol, has immunomodulatory and antioxidative properties. The present study investigated whether propofol could reduce AKI in caecal ligation and puncture (CLP) mice and the possible mechanism behind this. METHODS Mice were treated with propofol or saline immediately and 12 h after CLP surgery. Kidney injury, survival and cytokine expressions of CLP mice were observed 24 h after CLP surgery. In vitro, lipopolysaccharide (LPS)-stimulated rat mesangial cells (RMCs) or hydrogen peroxide (H(2)O(2))-exposed murine kidney epithelial cells (M1) were treated with propofol. The expression of BMP-7, TNF-α and monocyte chemotactic protein (MCP)-1 in CLP mice kidney, RMCs or M1 cells was determined by RT-PCR. Free radical generation and cell death of RMCs and M1 cells were analysed. Nuclear factor (NF)-κB and peroxisome proliferator-activated receptor (PPAR)-γ expressions in LPS-stimulated RMCs were determined by western blotting. RESULTS Propofol increased survival and ameliorated AKI in CLP mice. Propofol increased BMP-7 expression but decreased TNF-α and MCP-1 expressions in the kidney of CLP mice and LPS-stimulated RMCs. Propofol also inhibited free radical generation and cell death in LPS-stimulated RMCs and decreased the TNF-α expression and cell death in H(2)O(2)-exposed M1 cells. Moreover, propofol decreased NF-κB but increased PPAR-γ expression in LPS-stimulated RMCs. CONCLUSIONS Propofol treatment could protect kidney from sepsis-induced AKI by increasing BMP-7 expression, decreasing inflammatory cytokines and inhibiting oxidative stress.

Exercise pretraining protects against cerebral ischaemia induced by heat stroke in rats

Background: In the rat brain, heat-stroke-induced damage to cerebral neurons is attenuated through heat-shock-induced overexpression of heat-shock protein 72 (HSP72). Objective: To ascertain whether progressive exercise preconditioning induces HSP72 expression in the rat brain and prevents heat-stroke-induced cerebral ischaemia and injury. Methods: Male Wistar rats were randomly assigned to either a sedentary group or an exercise group. Those in the exercise group progressively ran on a treadmill 5 days/week, for 30–60 min/day at an intensity of 20–30 m/min for 3 weeks. The effects of heat stroke on mean arterial pressure, cerebral blood flow, brain ischaemia markers (glutamate, lactate/pyruvate ratio and nitric oxide), a cerebral injury marker (glycerol) and brain neuronal damage score in the preconditioned animals were compared with effects in unexercised controls. Heat stroke was induced by exposing urethane-anaesthetised animals to a temperature of 43°C for 55 min, which caused the body temperature to reach 42°C. Results: Three weeks of progressive exercise pretreatment induced HSP72 preconditioning in the brain and conferred significant protection against heat-stroke-induced hyperthermia, arterial hypotension, cerebral ischaemia and neuronal damage; it also prolonged survival. Conclusions: Exercise for 3 weeks can improve heat tolerance as well as attenuate heat-stroke-induced cerebral ischaemia in rats. The maintenance of mean arterial pressure and cerebral blood flow at appropriate levels in the rat brain may be related to overexpression of HSP72.

isobolographic Analysis of Epinephrine With Bupivacaine, Dextromethorphan, 3-methoxymorphinan, or Dextrorphan on Infiltrative Anesthesia in Rats : dose-response Studies

Background and Objectives: The aims of this study were to establish the potencies of epinephrine, bupivacaine, dextromethorphan, 3‐methoxymorphinan, and dextrorphan and evaluate interactions of epinephrine with bupivacaine, dextromethorphan, 3‐methoxymorphinan, or dextrorphan as an infiltrative anesthetic. Bupivacaine, a common and long‐acting local anesthetic, was used as control. Methods: Dose‐dependent responses of epinephrine, dextromethorphan, 3‐methoxymorphinan, and dextrorphan on cutaneous analgesia were compared with bupivacaine in rats. The interactions of drugs were evaluated via an isobolographic analysis. Results: We found that epinephrine, bupivacaine, dextromethorphan, 3‐methoxymorphinan, and dextrorphan produced a dose‐dependent local anesthetic effect as infiltrative cutaneous analgesia. Relative potencies were epinephrine > bupivacaine > dextromethorphan > 3‐methoxymorphinan > dextrorphan (P < .01 for each comparison). Coadministration of bupivacaine with epinephrine produced a synergistic effect, and coadministration of dextromethorphan, 3‐methoxymorphinan, or dextrorphan with epinephrine produced an additive effect. Conclusions: Epinephrine, dextromethorphan, 3‐methoxymorphinan, and dextrorphan are known to have local anesthetic effects as infiltrative cutaneous analgesia in rats. Epinephrine increased the potency of bupivacaine, but not dextromethorphan, 3‐methoxymorphinan, or dextrorphan as an infiltrative anesthetic. The cutaneous analgesic effects of adding epinephrine to dextromethorphan, 3‐methoxymorphinan, or dextrorphan, are similar to combinations of 2 local anesthetics.

Anticancer agent 2-methoxyestradiol improves survival in septic mice by reducing the production of cytokines and nitric oxide.

Cytokine production is critical in sepsis. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits hypoxia-inducible factor 1&agr; (HIF-1&agr;) and is an antiangiogenic and antitumor agent. We investigated the effect of 2ME2 on cytokine production and survival in septic mice. Using i.p. LPS or cecal ligation and puncture (CLP), sepsis was induced in BALB/c mice that were simultaneously or later treated with 2ME2 or vehicle. Twelve hours after the LPS injection, serum and peritoneal fluid cytokine and nitric oxide (NO) levels were analyzed using enzyme-linked immunosorbent assay and the Griess reaction. Lung injuries were histologically analyzed, and liver and kidney injuries were biochemically analyzed. Survival was determined 7 days after LPS injection or CLP procedure. In vivo and in vitro effects of 2ME2 on LPS-induced macrophage inflammation were determined. The effect of 2ME2 on HIF-1&agr; expression, nuclear factor &kgr;B (NF-&kgr;B), and inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells, a murine macrophage cell line, was determined using Western blotting. 2-Methoxyestradiol treatment reduced LPS-induced lung, liver, and kidney injury. Both early and late 2ME2 treatment prolonged survival in LPS- and CLP-induced sepsis. 2-Methoxyestradiol significantly reduced IL-1&bgr;, IL-6, TNF-&agr;, and NO levels in septic mice as well as in LPS-stimulated peritoneal macrophages. 2-Methoxyestradiol treatment also reduced the LPS-induced expression of HIF-1&agr;, iNOS, and pNF-&kgr;B in RAW264.7 cells, as well as iNOS and pNF-&kgr;B expression in siHIF-1&agr;-RAW264.7 cells. 2-Methoxyestradiol prolongs survival and reduces lung, liver, and kidney injury in septic mice by inhibiting iNOS/NO and cytokines through HIF-1&agr; and NF-&kgr;B signaling.

Long-term Mortality Risk After Hyperglycemic Crisis Episodes in Geriatric Patients With Diabetes: A National Population-Based Cohort Study

OBJECTIVE Hyperglycemic crisis is one of the most serious diabetes-related complications. The increase in the prevalence of diabetes in the geriatric population leads to a large disease burden, but previous studies of geriatric hyperglycemic crisis were focused on acute hyperglycemic crisis episode (HCE). This study aimed to delineate the long-term mortality risk after HCE. RESEARCH DESIGN AND METHODS This retrospective national population-based cohort study reviewed, in Taiwan’s National Health Insurance Research Database, data from 13,551 geriatric patients with new-onset diabetes between 2000 and 2002, including 4,517 with HCE (case subjects) (ICD-9 code 250.1 or 250.2) and 9,034 without HCE (control subjects). The groups were compared and followed until 2011. RESULTS One thousand six hundred thirty-four (36.17%) case and 1,692 (18.73%) control subjects died (P < 0.0001) during follow-up. Incidence rate ratios (IRRs) of death were 2.82 times higher in case subjects (P < 0.0001). The mortality risk was highest in the first month (IRR 26.56; 95% CI 17.97–39.27) and remained higher until 4–6 years after the HCE (IRR 1.49; 95% CI 1.23–1.81). After adjustment for age, sex, selected comorbidities, and monthly income, the mortality hazard ratio was still 2.848 and 4.525 times higher in case subjects with one episode and two or more episodes of hyperglycemic crisis, respectively. Older age, male sex, renal disease, stroke, cancer, chronic obstructive pulmonary disease, and congestive heart failure were independent mortality predictors. CONCLUSIONS Patients with diabetes had a higher mortality risk after HCE during the first 6 years of follow-up. Referral for proper education, better access to medical care, effective communication with a health care provider, and control of comorbidities should be done immediately after HCE.

Data Glove Embedded with 6-DOF Inertial Sensors for Hand Rehabilitation

A hand injury can have great impact on a persons daily life. However, the current manual evaluations of hand functions are imprecise and inconvenient. In this research, a data glove embedded with 6-axis inertial sensors is proposed. With the proposed angle calculating algorithm, accurate bending angles are measured to estimate the real-time movements of hands. This proposed system can provide physicians with an efficient tool to evaluate the recovery of patients and improve the quality of hand rehabilitation.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI.

Data glove embedded with 9-axis IMU and force sensing sensors for evaluation of hand function

A hand injury can greatly affect a persons daily life. Physicians must evaluate the state of recovery of a patients injured hand. However, current manual evaluations of hand functions are imprecise and inconvenient. In this paper, a data glove embedded with 9-axis inertial sensors and force sensitive resistors is proposed. The proposed data glove system enables hand movement to be tracked in real-time. In addition, the system can be used to obtain useful parameters for physicians, is an efficient tool for evaluating the hand function of patients, and can improve the quality of hand rehabilitation.

Role of physiotherapy and patient education in lymphedema control following breast cancer surgery

Introduction This retrospective cohort study evaluated whether education in combination with physiotherapy can reduce the risk of breast cancer-related lymphedema (BCRL). Methods We analyzed 1,217 women diagnosed with unilateral breast cancer between January 2007 and December 2011 who underwent tumor resection and axillary lymph node dissection. The patients were divided into three groups: Group A (n=415), who received neither education nor physiotherapy postsurgery; Group B (n=672), who received an educational program on BCRL between Days 0 and 7 postsurgery; and Group C (n=130), who received an educational program on BCRL between Days 0 and 7 postsurgery, followed by a physiotherapy program. All patients were monitored until October 2013 to determine whether BCRL developed. BCRL risk factors were evaluated using Cox proportional hazards models. Results During the follow-up, 188 patients (15.4%) developed lymphedema, including 77 (18.6%) in Group A, 101 (15.0%) in Group B, and 10 (7.7%) in Group C (P=0.010). The median period from surgery to lymphedema was 0.54 years (interquartile range =0.18–1.78). The independent risk factors for BCRL included positive axillary lymph node invasion, a higher (>20) number of dissected axillary lymph nodes, and having undergone radiation therapy, whereas receiving an educational program followed by physiotherapy was a protective factor against BCRL (hazard ratio =0.35, 95% confidence interval =0.18–0.67, P=0.002). Conclusion Patient education that begins within the first week postsurgery and is followed by physiotherapy is effective in reducing the risk of BCRL in women with breast cancer.

Clinical characteristics of hyperglycemic crises in patients without a history of diabetes.

Hyperglycemic crises without a history of diabetes have not been well studied. We compared the clinical characteristics of patients with and without a history of diabetes, and evaluated the glycated hemoglobin levels.