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Find video protocols related to scientific articles indexed in Pubmed.
Transcutaneous Electrical Nerve Stimulation Attenuates Postsurgical Allodynia and Suppresses Spinal Substance P and Proinflammatory Cytokine Release in Rats.
Phys Ther
PUBLISHED: 09-11-2014
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Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain.
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Wound Dehiscence as a Cataract Surgery-Associated Postoperative Complication in Patients Previously Treated With Alpha-1 Blocker Tamsulosin-A Population-Based Study in Taiwan.
Am. J. Ophthalmol.
PUBLISHED: 08-23-2014
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To compare the cataract surgery-related complications between patients with and without tamsulosin treatment.
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The risk of acute coronary syndrome after retinal artery occlusion: a population-based cohort study.
Br J Ophthalmol
PUBLISHED: 08-21-2014
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To investigate the risk of acute coronary syndrome (ACS) following retinal artery occlusion (RAO).
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Pre-existing hyperlipidaemia increased the risk of new-onset anxiety disorders after traumatic brain injury: a 14-year population-based study.
BMJ Open
PUBLISHED: 07-19-2014
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Anxiety disorders (ADs) are common after traumatic brain injury (TBI). However, the risk factors of new-onset ADs remain unclear. This study was aimed at evaluating the incidence and risk factors for new-onset ADs, including pre-existing hyperlipidaemia and three major comorbidities (diabetes mellitus, hypertension and cardiovascular disease), in patients with TBI.
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Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells.
Arch. Toxicol.
PUBLISHED: 07-01-2014
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Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. Exposure of neuro-2a cells to oxygen/glucose deprivation (OGD) or cobalt chloride decreased cell viability and induced cell apoptosis in time-dependent manners. In parallel, OGD caused augmentation of cellular Bax and cytochrome c levels, a reduction in the mitochondrial membrane potential (MMP), activation of caspase-3, and fragmentation of DNA. miR-1 was induced in neuro-2a cells by OGD. Knocking down miR-1 expression using specific antisense inhibitors significantly alleviated OGD-induced neuronal death. Administration of OGD to neuro-2a cells induced heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search revealed that miR-1-specific binding elements exist in the 3'-untranslated region of HSP-70 mRNA. Overexpression of miR-1 simultaneously attenuated OGD-induced HSP-70 mRNA and protein expressions. In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax-mitochondrion-caspase protease pathway.
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Fractional Thermolysis by Bipolar Radiofrequency Facilitates Cutaneous Delivery of Peptide and siRNA with Minor Loss of Barrier Function.
Pharm. Res.
PUBLISHED: 05-29-2014
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In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated.
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High-frequency transcutaneous electrical nerve stimulation attenuates postsurgical pain and inhibits excess substance P in rat dorsal root ganglion.
Reg Anesth Pain Med
PUBLISHED: 05-01-2014
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Transcutaneous electrical nerve stimulation (TENS) is a common therapeutic modality for pain management, but its effectiveness in skin/muscle incision and retraction (SMIR)-evoked pain is unknown. We aimed to examine the effects of TENS on postoperative pain and the levels of substance P (SP), N-methyl-D-aspartate receptor 1 (NR1), and interleukin 1? (IL-1?) in rat dorsal root ganglion (DRG).
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Intrathecal orphenadrine elicits spinal block in the rat.
Eur. J. Pharmacol.
PUBLISHED: 04-25-2014
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The purpose of this study was to estimate the local anesthetic effect of orphenadrine, an anti-muscarinic agent, in spinal anesthesia and its comparison with the local anesthetic lidocaine. After the rat was injected intrathecally, the spinal block of orphenadrine and lidocaine was constructed in a dosage-dependent fashion. The potency and duration of spinal anesthesia with orphenadrine were compared with that of lidocaine. Our data demonstrated that orphenadrine and lidocaine elicited dose-dependent spinal blockades on the motor function, sensory, and proprioception. On the 50% effective dose (ED50) basis, the ranks of potency in motor function, nociception, and proprioception were orphenadrine>lidocaine (P<0.01). At equipotent doses (ED25, ED50, ED75), the block duration elicited by orphenadrine was greater than that elicited by lidocaine (P<0.01). Orphenadrine, but not lidocaine, exhibited longer duration of nociceptive/sensory blockade than that of motor blockade at equipotent doses. Ineffective-dose orphenadrine as adjuvant did not enhance spinal anesthesia with lidocaine. The preclinical data revealed that orphenadrine with a more sensory-selective action over motor block exhibited more potent and longer spinal anesthesia when compared to lidocaine.
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Epidemiology and mortality of hip fracture among patients on dialysis: Taiwan National Cohort Study.
Bone
PUBLISHED: 04-16-2014
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Chronic kidney disease increases the risk for hip fractures. Hip fractures are associated with increased mortality, decreased quality of life, and higher economic burden. To determine whether dialysis modality is associated with a higher incidence of hip fractures in patients with end-stage renal disease (ESRD), we used the Taiwan National Health Insurance Research Database to examine the records of 51,473 patients who began dialysis between 1999 and 2005. The patients were followed until death, transplantation, dialysis cessation, or 31 December 2008. The follow-up period was (mean±SD) 4.14±2.48 years. The cumulative incidence rate of hip fracture was calculated using Kaplan-Meier methods. Predictors of hip fracture were determined using Cox models. During the study period, 1903 patients had a hip fracture. The overall incidence rate of hip fracture was 89.21/10,000 patient-years. Patients on hemodialysis (HD) had a 31% higher incidence of hip fracture than those on peritoneal dialysis (PD) (HR 1.31, 95% CI: 1.01-1.70). Patients ?65 years old had more than 13 times the risk of a hip fracture than did those 18-44 years old (HR: 13.65; 95% CI: 10.12-18.40). Other factors that increased the risk of a hip fracture were a prior hip fracture (HR: 1.44; 95% CI: 1.15-1.80), osteoporosis (HR: 1.24; 95% CI: 1.07-1.45), DM (HR: 1.66; 95% CI: 1.51-1.83), and liver cirrhosis (HR: 1.37, 95% CI: 1.15-1.64). The overall in-hospital mortality rate was 3.2%. The cumulative survival rates after a hip fracture were 74.6% at one year and only 29.6% at seven years. Our findings supported the notion that being on HD is a risk for hip fracture. Additionally, old age, female gender, a prior hip fracture, osteoporosis, DM and liver cirrhosis were also risk factors for hip fracture in patients with ESRD and undergoing dialysis.
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Obstructive sleep apnea and risk of osteoporosis: a population-based cohort study in Taiwan.
J. Clin. Endocrinol. Metab.
PUBLISHED: 04-15-2014
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Obstructive sleep apnea (OSA) is associated with metabolic, endocrine, and cardiovascular diseases. It is characterized by repetitive episodes of apnea/hypopnea and hypoxia in tissues, which might also impact bone metabolism. This study investigates the possible association between OSA and osteoporosis.
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Forced treadmill running suppresses postincisional pain and inhibits upregulation of substance P and cytokines in rat dorsal root ganglion.
J Pain
PUBLISHED: 04-07-2014
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Exercise causes a variety of psychophysical effects (eg, alterations in pain sensation). Tissue injury induces mediator releases in the spinal cord resulting in pain hypersensitivity; however, the contribution of the dorsal root ganglion (DRG) is poorly understood. In this study, we tested if forced treadmill running can attenuate postoperative pain and alter substance P (SP) or proinflammatory cytokine level in the DRG by using a rat model of skin/muscle incision and retraction (SMIR). We evaluated mechanical sensitivity to von Frey stimuli (6 and 15 g) and expression of SP, interleukin-1?, and interleukin-6 in the DRG of sham-operated sedentary rats, SMIR sedentary rats, sham-operated rats with forced treadmill running, and SMIR rats with forced treadmill running. At postoperative day 8, trained rats ran for 5 days per week for 4 weeks on a treadmill 70 minutes/d with an intensity of 18 m/min. On postoperative day 6, SMIR sedentary rats displayed a significant mechanical hypersensitivity that persisted until postoperative day 35. By comparison, SMIR-operated rats, which received forced treadmill running, exhibited a quick recovery from mechanical hypersensitivity. SMIR sedentary rats showed an upregulation of SP, interleukin-1?, and interleukin-6 in the DRG at postoperative days 14 and 28, whereas SMIR-operated rats receiving forced treadmill running reversed this upregulation at postoperative day 28. We concluded that forced treadmill running alleviated persistent postincisional pain caused by SMIR surgery. This appears to be protective against postoperative pain, which probably relates to the downturn in excess SP, interleukin-1?, and interleukin-6 in the DRG.
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Insomnia subtypes and the subsequent risks of stroke: report from a nationally representative cohort.
Stroke
PUBLISHED: 04-03-2014
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The studies assessing the impact of insomnia on stroke are still lacking. We aim to investigate insomnia in relation to subsequent stroke during the 4-year follow-up.
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Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
Eur. J. Pharmacol.
PUBLISHED: 03-28-2014
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The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) ?mol/kg]>propranolol [9.21 (9.08-9.42) ?mol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 ?mol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 ?mol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 ?mol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.
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Time sensitivity factor of single pulmonary nodule: a new cancer characteristic metabolic parameter by (18) F-FDG PET.
Biomed Res Int
PUBLISHED: 03-25-2014
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To calculate the time sensitivity factor (S) for discriminating the solitary pulmonary nodule (SPN) by FDG PET at different time points.
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Volume-outcome associations after major hepatectomy for hepatocellular carcinoma: a nationwide Taiwan study.
J. Gastrointest. Surg.
PUBLISHED: 03-24-2014
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The objective of this study was to explore volume-outcome associations after major hepatectomy for hepatocellular carcinoma (HCC).
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Co-administration of memantine with epinephrine produces a marked peripheral action in intensifying and prolonging analgesia in response to local skin pinprick in rats.
Neurosci. Lett.
PUBLISHED: 01-11-2014
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The purpose of this study was to examine the effect of epinephrine as adjuvant for memantine or lidocaine as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we evaluated the effects of adding epinephrine to memantine or lidocaine on infiltrative cutaneous analgesia. Lidocaine, a known local anesthetic, was used as control. We found that epinephrine, memantine, and lidocaine produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. On a 50% effective dose (ED50) basis, the relative potencies were epinephrine [0.012 (0.006-0.020)?mol]>memantine [4.010 (3.311-4.988)?mol]>lidocaine [6.177 (5.333-7.218)?mol] (P<0.05 for each comparison). Mixtures of epinephrine (2.7nmol or 13.7nmol) with drugs (memantine or lidocaine) at ED50 or ED95, respectively, enhanced the potency and prolonged the duration of action on infiltrative cutaneous analgesia. Intraperitoneal injection of co-administration of drugs (memantine or lidocaine) at ED95 with epinephrine (13.7nmol) produced no cutaneous analgesia (data not shown). Epinephrine, memantine, and lidocaine were shown to have local anesthetic effects as infiltrative cutaneous analgesia. Epinephrine increased the duration and potency of memantine and lidocaine as an infiltrative anesthetic.
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Impact of ester promoieties on transdermal delivery of ketorolac.
J Pharm Sci
PUBLISHED: 01-10-2014
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Different types of ketorolac ester prodrugs incorporating tert-butyl (KT), benzyl (KB), heptyl (KH), and diketorolac heptyl (DKH) promoieties were synthesized for the comparison of percutaneous penetration. The prodrugs were characterized according to their melting point, capacity factor, lipophilicity, solubility in 30% ethanol/buffer, enzymatic hydrolysis, in vitro skin permeation, hair follicle accumulation, and in vivo skin tolerance. Interactions between the prodrugs and esterases were predicted by molecular docking. Both equimolar suspensions and saturated solutions in 30% ethanol/pH 7.4 buffer were employed as the applied dose. All of the prodrugs exhibited a lower melting point than ketorolac. The lipophilicity increased in the following order: ketorolac < KT < KB < KH < DKH. The prodrugs were rapidly hydrolyzed to the parent drug in esterase medium, skin homogenate, and plasma, with KT and KB exhibiting higher degradation rates. KT exhibited the highest skin permeation, followed by KB. The flux of KT and KB exceeded that of ketorolac by 2.5-fold and twofold, respectively. KH and DKH did not improve ketorolac permeation but exhibited a sustained release behavior. KT and KH revealed selective absorption into follicles and a threefold greater follicular uptake compared with ketorolac. KB, KH, and DKH slightly but significantly increased transepidermal water loss (TEWL) after consecutive administration for 7 days, whereas ketorolac and KT exhibited no influence on TEWL. According to the experimental results, it can be concluded that an optimal balance between lipophilicity and aqueous solubility is important in the design of a successful prodrug. The acceptable skin tolerance for safe application is also an important consideration.
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Erectile dysfunction and risk of end stage renal disease requiring dialysis: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Previous studies have suggested that erectile dysfunction (ED) is an independent risk factor for macrovascular disease. Very few studies have evaluated the relationship between ED and risk of end stage renal disease (ESRD) requiring dialysis.
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Renal transplantation: relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure. a nationwide population-based study.
Int J Med Sci
PUBLISHED: 01-01-2014
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BACKGROUND AND OBJECTS: We explored the relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure (including death).
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One-year mortality associations in hemodialysis patients after traumatic brain injury--an eight-year population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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This study aimed to investigate the one-year mortality associations in hemodialysis patients who underwent neurosurgical intervention after traumatic brain injury (TBI) using a nationwide database in Taiwan.
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Obstructive sleep apnea and the risk of atopic dermatitis: a population-based case control study.
PLoS ONE
PUBLISHED: 01-01-2014
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Obstructive sleep apnea (OSA) is associated with systemic inflammation and induces various comorbid medical diseases. To date, no study has explored the relationship between OSA and atopic dermatitis (AD), an inflammatory and autoimmune skin disorder. This study investigated the longitudinal risk for AD in patients with OSA.
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Phosphoproteomics and bioinformatics analyses of spinal cord proteins in rats with morphine tolerance.
PLoS ONE
PUBLISHED: 01-01-2014
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Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance.
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Epidemiology and mortality among dialysis patients with parathyroidectomy: Taiwan ?National Cohort Study.
J. Nephrol.
PUBLISHED: 12-05-2013
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Background and objectives: Parathyroidectomy (PTx) is usually necessary in patients with end-stage renal disease (ESRD) on dialysis. Risk factors for higher PTx rates are controversial. The objectives of this study were to identify the risk factors for PTx in patients on dialysis and evaluate the mortality after PTx.  ?Methods: We analyzed data obtained from the National Health Insurance Research Database and included 35,162 ESRD dialysis patients. Kaplan-Meier method was used to calculate the incidence of PTx and survival rate after PTx. Cox proportional hazards models were used to identify the risk factors.  ?Results: The PTx rate was 8.09 per 1,000 patient-years. Stratified on the basis of gender and diabetic mellitus (DM), the highest incidence rate of PTx was in females without DM. Stratified by age and DM, the highest incidence rate of PTx was in those aged 18-44 years without DM. The significant risk factors for PTx were younger age, female (hazard ratio (HR) 1.409, 95% confidence interval (CI): 1.257-1.580), DM (HR 0.479, 95% CI: 0.413-0.555), peritoneal dialysis (HR 1.657, 95% CI: 1.418-1.938) and hypertension (HTN) (HR 1.317, 95% CI: 1.162-1.492). The cumulative survival rates after ?PTx were 97.1%, 94.5%, 82.8% and 77.4% at the first, second, fifth and seventh year, respectively. Only ?age was significantly associated with higher mortality ?after PTx.?Conclusions: Higher PTx rates were found in dialysis ?patients who were female and younger, did not have DM, were on peritoneal dialysis and had HTN. Advanced age was associated with a higher mortality after PTx.
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Increased risk of mortality among haemodialysis patients with or without prior stroke: a nationwide population-based study in Taiwan.
Indian J. Med. Res.
PUBLISHED: 09-24-2013
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Patients with prior stroke (PS) undergoing chronic dialysis are at a high risk of mortality. However, little is known about the cumulative risk and survival rate of dialysis patients with long-term follow up. The aim of this study was to assess risks for mortality between patients with and without PS undergoing chronic haemodialysis (HD).
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Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats.
Pharmacol Rep
PUBLISHED: 06-08-2013
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Although nisoxetine has been shown to elicit infiltrative cutaneous local anesthesia, the inhibition of voltage-gated Na(+) channels by nisoxetine has not been reported. The aim of this study was to evaluate the effect of nisoxetine on Na(+) currents and its efficacy on spinal anesthesia.
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Epidemiology and mortality of new-onset diabetes after dialysis: Taiwan national cohort study.
Diabetes Care
PUBLISHED: 05-30-2013
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We examined the predictors and risks associated with pre-existing versus new-onset diabetes mellitus (DM) after initiation of chronic dialysis therapy in end-stage renal disease (ESRD) patients.
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Application of quinidine on rat sciatic nerve decreases the amplitude and increases the latency of evoked responses.
J Anesth
PUBLISHED: 05-12-2013
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Multi-modality electrophysiological techniques were performed to assess the effects of quinidine on peripheral nerve conduction.
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A dose-response study on the efficacy of tricyclic antidepressants on reducing morphine-withdrawal symptoms.
Acta Anaesthesiol Taiwan
PUBLISHED: 05-04-2013
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Acute detoxification may lead to withdrawal syndrome. The syndrome is sufficiently aversive in those who are morphine-dependents and thus it hinders abstinence. The opioids are most often used clinically to lighten this syndrome. Here, we evaluated the effects of tricyclic antidepressants (TCAs) in treating physical dependence to opioids upon acute detoxification in mice.
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Exercise training attenuates postoperative pain and expression of cytokines and N-methyl-D-aspartate receptor subunit 1 in rats.
Reg Anesth Pain Med
PUBLISHED: 05-04-2013
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Exercise creates a variety of psychophysical effects, including altered pain perception. We investigated whether physical exercise reduces postincisional pain and cytokine and N-methyl-D-aspartate receptor 1 (NR1) expression in a rat model of skin/muscle incision and retraction (SMIR)-evoked pain.
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The use of carbetapentane for spinal anesthesia and use-dependent block of sodium currents.
Eur. J. Pharmacol.
PUBLISHED: 04-18-2013
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Although carbetapentane produces skin (peripheral) infiltrative analgesia, the underlying mechanism of carbetapentane in local anesthesia is not well understood. The purpose of the study was to examine the effect of carbetapentane on voltage-gated Na(+) channels and its efficacy on spinal (central) anesthesia. We evaluated the effects of carbetapentane on rat motor and pain behavior (when administered intrathecally) and on voltage-gated sodium channels in differentiated neuronal NG108-15 cells. Carbetapentane exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade (P<0.05). Carbetapentane was more potent than lidocaine (P<0.05) in spinal anesthesia. Intrathecal 5% dextrose (vehicle) elicited no spinal anesthesia. Lidocaine, used as a positive control, demonstrated concentration- and state-dependent effects on tonic block of voltage-gated Na(+) currents (IC?? of 49.6 and 194.6 µM at holding potentials of -70 and -100 mV, respectively). Carbetapentane was more potent (IC?? of 36.3 and 62.2 µM at holding potentials of -70 and -100 mV, respectively). Carbetapentane showed a much stronger frequency-dependence of block than lidocaine: with high frequency stimulation (3.33 Hz), 50 µM lidocaine produced an additional 30% blockade, while the same concentration of carbetapentane produced 70% more block. These results revealed carbetapentane had a more potent and prolonged spinal blockade with a more sensory/nociceptive-selective action over motor blockade in comparison with lidocaine. Spinal anesthesia with carbetapentane could be through inhibition of voltage-gated Na(+) currents.
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Increased risk of deep neck infection among HIV-infected patients in the era of highly active antiretroviral therapy---a population-based follow-up study.
BMC Infect. Dis.
PUBLISHED: 04-14-2013
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BACKGROUND: Deep neck infections (DNIs) in HIV-infected patients often produce severe complications, even death. Data on the incidence rates and risks of DNI among HIV-infected patients are scarce, particularly with the widespread use of highly active antiretroviral therapy (HAART). We evaluated the incidence rates and risks for DNI among HIV-infected patients and observed the long-term trends. METHODS: A total of 9888 new HIV-infected patients diagnosed in 2001--2007 were included and matched with 49440 randomly selected subjects. The HIV-infected subjects were offered free access to HAART. All subjects were traced until December 2009. A Kaplan-Meier analysis generated the cumulative DNI incidence rate. The adjusted hazard ratio was computed using Cox proportional hazard regressions. RESULTS: From the HIV-infected and comparison cohorts, 222 individuals (57.01 cases per 10000 person-years) and 735 individuals (35.54 cases per 10000 person-years) developed DNI, respectively. The log rank test indicated that patients with HIV had a significantly higher 8-year incidence rate of DNI than the control group (P < 0.0001). The adjusted hazard ratio for developing DNI after an HIV attack during the mean 3.94 years follow-up period was 1.59. The incidence rate and relative risk of DNI were 74.58 (per 10000 person-years) and 2.05 (P < 0.0001). Both figures were highest in the first follow-up year and decreased year-by-year thereafter. CONCLUSION: The risk of developing DNI is significantly elevated among HIV-infected patients, even with free access to HAART. Additional research is needed to examine the role of HAART in reducing the risk.
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Umbilical cord blood-derived CD34+ cells improve outcomes of traumatic brain injury in rats by stimulating angiogenesis and neurogenesis.
Cell Transplant
PUBLISHED: 04-12-2013
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Human umbilical cord blood cells (HUCBCs) have been shown to be beneficial in reducingneurological deficits in rats with brain fluid percussion injury (FPI). This study aimed toassess the basic mechanisms underlying the neuroprotective effects of HUCBCs derivedCD34+ cells. Rats were divided into three major groups: (i) sham-operated controls; (ii) FPIrats treated with PBS (phosphate buffered saline); (iii) FPI rats treated with 0.2%, 50%, or95% CD+ cells (in 5x105 cord blood lymphocytes and monocytes). Intravenous administrationof 0.3 ml of PBS, 0.2% CD34+ cells, 50% CD34+ cells, or 95% CD34+ cells was conductedimmediately after FPI. It was found that, 4 days post-FPI, CD34+ cells could be detected inthe ischemic brain tissues for 50% CD34+ cells- or 95% CD+ cells-treated FPI rats, but not forthe PBS-treated FPI rats or the 0.2% CD34+ cells-treated FPI rats. CD34+ cells (0.2%)-treatedFPI rats or PBS-treated FPI rats displayed neurological and motor deficits, cerebral contusionand apoptosis (e.g., increased numbers of both TUNEL-positive cells and caspase-3-positivecells), and activated inflammation (e.g., increased serum levels of tumor necrosis factoralpha).FPI-induced neurological motor dysfunction, cerebral contusion and apoptosis, andactivated inflammation could be attenuated by 50% CD34+ cells or 95% CD34+ cells therapy.In addition 50% or 95% CD34+ cells, but not PBS or 0.2% CD34+ cells, therapy significantlypromoted angiogenesis (e.g., increased numbers of both vasculoendothelial growth factorpositivecells and BrdU-endothelial double positive cells), neurogenesis (e.g., increasednumbers of both glial cell lines-derived neurotrophic factor-positive cells and BrdU/NeuNdouble positive cells) in the ischemic brain after FPI, and migration of endothelial progenitorcells from the bone marrow. Our data suggest that i.v. administration of HUCBCs-derivedCD34+ cells may improve outcomes of FPI in rats by stimulating both angiogenesis andneurogenesis.
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Systemic diphenidol reduces neuropathic allodynia and TNF-alpha overexpression in rats after chronic constriction injury.
Neurosci. Lett.
PUBLISHED: 04-05-2013
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Diphenidol has been shown to block voltage-gated Na(+) channels, which are associated with specific types of pain. Here, we evaluated the effects of diphenidol on chronic constriction injury (CCI)-evoked allodynia and expression of tumor necrosis factor-? (TNF-?). A peripheral nerve injury was elicited in rats by placing four loosely constrictive ligatures around the sciatic nerve. After intraperitoneal injection of diphenidol, rats were tested for evidence of mechanical allodynia prior to surgery, and on postoperative days 3, 6, 7, 11, 13 and 14. We showed that CCI rats received diphenidol caused dose-dependent increases in mechanical withdrawal threshold. Both diphenidol 2 and 10 ?mol/kg groups, but not 0.4 ?mol/kg diphenidol, displayed lower TNF-? level in the sciatic nerve than the CCI group (P<0.05) on day 7 after CCI. Our results support the conclusion that systemic diphenidol produced a dose-related inhibition of mechanical allodynia following chronic constriction injury of the sciatic nerve. This antiallodynic effect is related to the decrease of TNF-? expression in the sciatic nerve of CCI rats.
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The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting.
Eur. J. Pharmacol.
PUBLISHED: 03-20-2013
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Glucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs, are also effective, alone or combined with other antiemetics, for preventing nausea and vomiting. Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting, and in patients with only one or two risks for postoperative nausea and vomiting (PONV). Dexamethasone combined with 5-HT3 or tachykinin NK1 antagonists is also suggested for higher-level emetogenic chemotherapy and radiotherapy and for patients at high risk for PONV. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting.
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Cardiopulmonary Profile in Streptozotocin-Induced Type 1 Diabetic Rats during Systemic Endotoxemia.
J Diabetes Res
PUBLISHED: 02-25-2013
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This study was designed to determine the severity of cardiopulmonary dysfunction during systemic endotoxemia in type 1 diabetes. Thirty-two adult male Wistar rats were randomly assigned to a control group or to a group treated with streptozotocin (STZ) to create an animal model of type 1 diabetes. Survival time and cardiovascular parameters were continually monitored in urethane anaesthetized animals receiving intravenous infusion of endotoxin (lipopolysaccharide (LPS)) or saline. We also determined arterial blood gases, lung injury, and tumor necrosis factor-alpha (TNF- ? ) levels in serum and bronchoalveolar lavage fluid. Before LPS administration, the mean arterial pressure in STZ rats was significantly higher than that in normal rats. After LPS injection, the heart rate drop significantly in STZ rats than that in the control group. Also, the increased levels of TNF- ? in serum and lavage fluid after LPS treatment were significantly higher in STZ rats than those in normal rats. Survival time in STZ rats was shorter than that in normal rats after LPS application. Albumin content, wet/dry weight ratio of lung, and lung injury were indistinguishable between STZ and normal rats. These results indicate that the cardiopulmonary change which occurs during LPS-induced endotoxemia is minor in STZ-induced diabetic rats.
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Longitudinal trends of the healthcare-seeking prevalence and incidence of insomnia in Taiwan: an 8-year nationally representative study.
Sleep Med.
PUBLISHED: 02-05-2013
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We used insurance claims of a nationally representative population-based cohort to assess the longitudinal healthcare-seeking prevalence and incidence of insomnia.
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Wireless near-infrared spectroscopy system for determining brain hemoglobin levels in laboratory animals.
J. Neurosci. Methods
PUBLISHED: 01-27-2013
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Traumatic brain injury (TBI) is usually caused by brain shaking or impact. It can affect normal brain function and may even lead to disability or death. However, there are very few studies on the associated physiologic changes in humans or animals. In this study, a non-invasive, wireless multi-channel near-infrared spectroscopy (NIRS) was developed to continuously monitor the concentration change of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (HbT) to elucidate changes in the physiological state of the brain during and after different strength impaction. The triphenyltetrazolium chloride (TTC) staining was also used to monitor changes of infarction volume after different strength impaction. The results indicated that the concentration changes of HbO2 and HbT, and the changes of infarction volumes were significantly related to the impact strength. In conclusion, the status of TBI can be clinically evaluated by detecting HbO2 and HbT changes. The system proposed here is stable, accurate, non-invasive, and mostly important wireless which can easily be used for TBI study.
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Medical attendance for lower urinary tract symptoms is associated with subsequent increased risk of outpatient visits and hospitalizations based on a nationwide population-based database.
PLoS ONE
PUBLISHED: 01-26-2013
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Lower urinary tract symptoms (LUTS), which encompass storage, voiding, and postmicturition symptoms, are highly prevalent and recognized globally. Based on a nationwide population-based database, this study tests the hypothesis that medical attendance for LUTS is associated with a subsequent increase in the number of outpatient visits and hospitalizations, with differences among medical specialties and age groups.
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Prolonged analgesic effect of amitriptyline base on thermal hyperalgesia in an animal model of neuropathic pain.
Eur. J. Pharmacol.
PUBLISHED: 01-23-2013
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The best analgesic drugs for neuropathic pain have a long duration of action, can be given via multiple routes, and can be used preemptively. We evaluated the antinociceptive effects and duration of action of subcutaneously injected amitriptyline base (AMT-Base) (in oil). A plantar test in a spinal nerve ligation (SNL) model of neuropathic pain in rats showed that typical amitriptyline HCl (AMT-HCl) (in saline) and AMT-Base had a significant dose-dependent antinociceptive effect: the antinociceptive duration of a single 100 ?mol/kg injection of AMT-HCl was 5 h and of AMT-Base was 24 h when given 7 days after a SNL, and of a single 200 ?mol/kg injection of AMT-Base was 39 days when given 1 h before and 4 days when given 7 days after a SNL. The post-ligation antinociceptive duration of AMT-Base was 4.8 times that of AMT-HCl, but the duration of preemptive (pre-ligation) AMT-Base treatment was 9.7 times that of AMT-Base. We can conclude that preemptive amitriptyline base provides long-lasting antinociception for neuropathic pain experimentally.
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Diphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat.
Fundam Clin Pharmacol
PUBLISHED: 01-08-2013
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Although diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long-lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose-dependent fashion. We showed that diphenhydramine, as well as bupivacaine displayed a dose-dependent cutaneous analgesia in response to dorsal cutaneous noxious stimuli. The relative potency (50% effective dose) was bupivacaine (0.023 [0.013-0.035]%) > diphenhydramine (0.078 [0.068-0.091]%; P < 0.001). On an equipotent basis, diphenhydramine had a similar duration of action to bupivacaine. Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.
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The new comorbidity index for predicting survival in elderly dialysis patients: a long-term population-based study.
PLoS ONE
PUBLISHED: 01-01-2013
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The worldwide elderly (? 65 years old) dialysis population has grown significantly. This population is expected to have more comorbid conditions and shorter life expectancies than the general elderly population. Predicting outcomes for this population is important for decision-making. Recently, a new comorbidity index (nCI) with good predictive value for patient outcomes was developed and validated in chronic dialysis patients regardless of age. Our study examined the nCI outcome predictability in elderly dialysis patients.
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The role of heat shock protein 70 in the protective effect of YC-1 on ?-amyloid-induced toxicity in differentiated PC12 cells.
PLoS ONE
PUBLISHED: 01-01-2013
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Neurodegenerative brain disorders such as Alzheimers disease (AD) have been well investigated. However, significant methods for the treatment of the progression of AD are unavailable currently. Heat shock protein 70 (Hsp70) plays important roles in neural protection from stress by assisting cellular protein folding. In this study, we investigated the effect and the molecular mechanism of YC-1, an activator of guanylyl cyclase (GC), on A?25-35-induced cytotoxicity in differentiated PC12 cells. The results of this study showed that A?25-35 (10 µM) significantly increased p25 protein production in a pattern that was consistent with the increase in ?-calpain expression. Moreover, A?25-35 significantly increased tau hyperphosphorylation and induced differentiated PC12 cell death. YC-1 (0.5-10 µM) prevented the cell death induced by A?25-35. In addition, YC-1 (1, 10 µM) significantly blocked A?25-35-induced ?-calpain expression and decreased the formation of p25 and tau hyperphosphorylation. Moreover, YC-1 (5-20 µM) alone or combined with A?25-35 (10 µM) significantly increased the expression of Hsp70 in differentiated PC12 cells. The neuroprotective effect of YC-1 was significantly attenuated by an Hsp70 inhibitor (quercetin, 50 µM) or in PC12 cells transfected with an Hsp70 small interfering RNA. However, pretreatment of cells with the GC inhibitor ODQ (10 µM) did not affect the neuroprotective effect of YC-1 against A?25-35 in differentiated PC12 cells. These results suggest that the neuroprotective effect of YC-1 against A?25-35-induced toxicity is mainly mediated by the induction of Hsp70. Thus, YC-1 is a potential agent against AD.
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Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-03-2011
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Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell-specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4-overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners.
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Spinal anesthesia with diphenhydramine and pheniramine in rats.
Eur. J. Pharmacol.
PUBLISHED: 08-30-2011
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The aim of this study was to evaluate the local anesthetic effects of pheniramine and diphenhydramine, two histamine H? receptor antagonists, on spinal anesthesia and their comparison with lidocaine, a commonly used local anesthetic. After rats were injected intrathecally with diphenhydramine and pheniramine, the dose-response curves were obtained. The potency and duration of diphenhydramine and pheniramine on spinal anesthesia were compared with lidocaine. We showed that diphenhydramine and pheniramine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED??) basis, the rank of potency of drugs was diphenhydramine=pheniramine>lidocaine (p<0.05 for the differences). In equianesthetic doses (ED??, ED??, and ED??), the block duration caused by diphenhydramine was longer than that caused by pheniramine or lidocaine (p<0.01 for the differences). Diphenhydramine, but not pheniramine or lidocaine, elicited longer duration of sensory block than that of motor block at the same dose of 1.75 ?mol. These preclinical data reported that diphenhydramine with a more sensory-selective action over motor blockade demonstrated more potent and longer-lasting spinal blockades, compared with pheniramine or lidocaine.
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Anticancer agent 2-methoxyestradiol improves survival in septic mice by reducing the production of cytokines and nitric oxide.
Shock
PUBLISHED: 08-16-2011
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Cytokine production is critical in sepsis. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits hypoxia-inducible factor 1? (HIF-1?) 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? expression, nuclear factor ?B (NF-?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?, IL-6, TNF-?, 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?, iNOS, and pNF-?B in RAW264.7 cells, as well as iNOS and pNF-?B expression in siHIF-1?-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? and NF-?B signaling.
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Predictors of longterm mortality in patients with and without systemic lupus erythematosus on maintenance dialysis: a comparative study.
J. Rheumatol.
PUBLISHED: 08-15-2011
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To compare the prognosis of patients with and without systemic lupus erythematosus (SLE) on dialysis and to determine the factors that affect survival after dialysis.
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Nisoxetine produces local but not systemic analgesia against cutaneous nociceptive stimuli in the rat.
Eur. J. Pharmacol.
PUBLISHED: 08-10-2011
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The aim of this study was to evaluate the local anesthetic effect of nisoxetine as infiltrative cutaneous analgesic. After rats were injected subcutaneously with nisoxetine, dose-response curves were constructed. The cutaneous anesthetic effect of nisoxetine or MK-801 (dizocilpine) was compared with lidocaine, a traditional local anesthetic. We found that nisoxetine and MK-801 acted like lidocaine and elicited dose-related cutaneous (local) anesthesia. The relative potency was nisoxetine>MK-801>lidocaine (P<0.01) as infiltrative anesthesia of skin. On an equianesthetic doses (20% effective dose [ED??], ED??, and ED??), nisoxetine produced longer action of cutaneous anesthesia than that of lidocaine or MK-801 (P<0.01). Coadministration of nisoxetine or lidocaine with MK-801 showed an additive cutaneous anesthesia. Neither local injection of a large dose of nisoxetine, MK-801 nor lidocaine in the thigh area produced cutaneous anesthesia (data not shown). In conclusion, nisoxetine had a local anesthetic effect as infiltrative cutaneous analgesia with durations of actions longer than that of lidocaine or MK-801. That N-methyl-d-aspartate receptors may not contribute to the cutaneous (local) anesthetic effect of nisoxetine or lidocaine.
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Risk of acute kidney injury after exposure to gadolinium-based contrast in patients with renal impairment.
Ren Fail
PUBLISHED: 07-22-2011
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Gadolinium-based contrast media (Gd-CM) are reported to induce acute kidney injury (AKI) in a high-risk population group at the usual dose for magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) examinations. We assessed gadolinium-induced nephropathy in patients with renal impairment who underwent MRI or MRA examinations, and evaluated the risk factors.
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Class I antiarrhythmic drugs produced a spinal anesthetic effect in rats.
Neurosci. Lett.
PUBLISHED: 06-24-2011
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Class I antiarrhythmic drugs are commonly used to treat cardiac rhythm disorders. Some of those drugs were recently reported to have both a cutaneous analgesic and a neural blocking effect. We evaluated whether these drugs have a spinal anesthetic effect. Three Class I antiarrhythmic drugs (class IA: quinidine, IB: mexiletine, and IC: flecainide) were tested. After they had been intrathecally injected in rats, the potencies and durations of these drugs on spinal anesthesia were recorded. Bupivacaine, a commonly used local anesthetic, and 5% dextrose solution were used as controls. Bupivacaine, flecainide, quinidine, and mexiletine produced a dose-related spinal blockade of motor function, proprioception, and nociception, but dextrose solution produced no spinal anesthetic effect. The descending order of potency was bupivacaine>flecainide>quinidine>mexiletine (p<0.05 for all differences). On an equipotent basis, flecainide, quinidine, and bupivacaine produced similar durations of action, all of which were significantly longer than that of mexiletine (p<0.05). In conclusion, intrathecal injections of Class I antiarrhythmic drugs produced a dose-related spinal anesthetic effect. These drugs may be potential candidates for developing new local anesthetics.
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Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain.
J. Pharm. Pharmacol.
PUBLISHED: 06-11-2011
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Quinidine, a class I anti-arrhythmic agent, is a sodium channel blocker that is more potent than lidocaine and mexiletine. This study tested pre-emptive intrathecal quinidine to attenuate neuropathic pain induced by lumbar spinal nerve ligation (SNL).
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Lidocaine for prolonged and intensified spinal anesthesia by coadministration of propranolol in the rat.
Neurosci. Lett.
PUBLISHED: 06-07-2011
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Although the coadministration of lidocaine with propranolol interferes with the metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In this report, we investigate whether propranolol can potentiate the effect of lidocaine. Rats received spinal anesthesia with lidocaine co-injected with propranolol. After intrathecal injections of drugs in rats, three neurobehavioral examinations (motor function, proprioception, and nociception) were performed. We showed that lidocaine and propranolol elicited a spinal blockade in motor function, proprioception, and nociception. Propranolol at the dose of 0.82 ?mol/kg produced no spinal anesthesia. Co-administration of lidocaine [50% effective dose (ED(50)) or ED(95)] and propranolol (0.82 ?mol/kg) produced greater spinal anesthesia than lidocaine (ED(50) or ED(95)), respectively. These preclinical findings demonstrated that propranolol and lidocaine displayed spinal anesthesia. When combined with propranolol, lidocaine elicited a supra-additive effect of spinal anesthesia.
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Docosahexaenoic acid promotes dopaminergic differentiation in induced pluripotent stem cells and inhibits teratoma formation in rats with Parkinson-like pathology.
Cell Transplant
PUBLISHED: 06-07-2011
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Parkinsons disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic (DA) neurons in the midbrain. Induced pluripotent stem (iPS) cells have shown potential for differentiation and may become a resource of functional neurons for the treatment of PD. However, teratoma formation is a major concern for transplantation-based therapies. This study examined whether functional neurons could be efficiently generated from iPS cells using a five-step induction procedure combined with docosahexaenoic acid (DHA) treatment. We demonstrated that DHA, a ligand for the RXR/Nurr1 heterodimer, significantly activated expression of the Nurr1 gene and the Nurr1-related pathway in iPS cells. DHA treatment facilitated iPS differentiation into tyrosine hydroxylase (TH)-positive neurons in vitro and in vivo and functionally increased dopamine release in transplanted grafts in PD-like animals. Furthermore, DHA dramatically upregulated the endogenous expression levels of neuroprotective genes (Bcl-2, Bcl-xl, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor) and protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis in iPS-derived neuronal precursor cells. DHA-treated iPS cells significantly improved the behavior of 6-hydroxydopamine (6-OHDA)-treated PD-like rats compared to control or eicosapentaenoic acid-treated group. Importantly, the in vivo experiment suggests that DHA induces the differentiation of functional dopaminergic precursors and improves the abnormal behavior of 6-OHDA-treated PD-like rats by 4 months after transplantation. Furthermore, we found that DHA treatment in iPS cell-grafted rats significantly downregulated the mRNA expression of embryonic stem cell-specific genes (Oct-4 and c-Myc) in the graft and effectively blocked teratoma formation. Importantly, 3 Tesla-magnetic resonance imaging and ex vivo green fluorescence protein imaging revealed that no teratomas were present in transplanted grafts of DHA-treated iPS-derived DA neurons 4 months after implantation. Therefore, our data suggest that DHA plays a crucial role in iPS differentiation into functional DA neurons and that this approach could provide a novel therapeutic approach for PD treatment.
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Intrathecal propranolol displays long-acting spinal anesthesia with a more sensory-selective action over motor blockade in rats.
Eur. J. Pharmacol.
PUBLISHED: 05-25-2011
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To prevent cardiovascular effects of peripherally administered propranolol, the aim of this study was to evaluate the spinal anesthetic effect of propranolol, a Na(±) channel blocker. After rats were injected with drugs intrathecally, the spinal anesthetic effect of propranolol was compared with that of lidocaine, which is known to produce local anesthesia. We also evaluated the effect of the addition of clonidine with propranolol on spinal anesthesia. Our results showed that propranolol produced a dose-dependent spinal blockade in motor, proprioception, and nociception. On a 50% effective dose (ED(50)) basis, the spinal anesthetic effect of propranolol in motor, proprioception, and nociception [1.16 (1.01-1.34), 1.10 (0.92-1.31), 1.05 (0.89-1.24)] was equal to lidocaine [1.03 (0.94-1.13), 0.95 (0.84-1.07), 0.87 (0.79-0.96)], respectively. On an equipotent basis (0.5, 1.0, 2.5 ?mol), the sensory/nociceptive block duration caused by propranolol was longer than that caused by lidocaine (P?0.01). Co-administration of propranolol (1.1 ?mol) and clonidine (0.5 ?mol) produced greater spinal anesthesia than propranolol (1.1 ?mol) or clonidine (0.5 ?mol) alone. These preclinical findings demonstrated that propranolol produces similar spinal anesthesia to lidocaine and that ?(2)-adrenergic receptors also contribute to improve the quality and duration of the spinal anesthetic effect of propranolol. Propranolol with a more sensory-selective action over motor blockade elicited longer spinal blockade than did lidocaine.
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Isoflurane for spinal anesthesia in the rat.
Neurosci. Lett.
PUBLISHED: 05-12-2011
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Although isoflurane, a non-water soluble agent, has been known to block Na+ currents, its spinal anesthetic effect was not exposed. The aim of this experiment was to evaluate the local anesthetic effect of isoflurane in spinal anesthesia. After intrathecal injection of isoflurane on rats, the spinal anesthetic effect in motor function, proprioception and nociception were evaluated. Lidocaine, a common used local anesthetic, was used as control. Isoflurane acted like lidocaine and produced dose-related spinal blockades of motor function, proprioception and nociception. Although isoflurane [27.6 (25.4-30.0)] had less potency when compared with lidocaine [1.0 (0.9-1.1)] (P<0.001) in spinal anesthesia, it caused a much longer duration of spinal blockades than lidocaine at equianesthetic doses (P<0.001). Our results showed that when compared with lidocaine, isoflurane produced a less potency but much longer duration in spinal anesthesia.
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The local anesthetic effect of memantine on infiltrative cutaneous analgesia in the rat.
Anesth. Analg.
PUBLISHED: 04-27-2011
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Memantine blocks N-methyl-D-aspartate receptors and the Na(+) current, one principal mechanism of local anesthesia. Until now, no study mentioned that memantine had a local anesthetic effect, and therefore we investigated the local anesthetic effect of memantine.
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Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer.
Oncol. Rep.
PUBLISHED: 04-20-2011
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Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide. Let-7 family has been shown to function as a tumor suppressor through regulating multiple oncogenic signaling. Recent study reported that combined underexpression of miR-205 and let-7d showed negative correlation with the survival prognosis of head and neck cancer patients. However, the let-7d-involved mechanism in regulating OSCC is still unclear. In this study, we first demonstrated that let-7d expression was significantly decreased while Twist and Snail expression was increased in OSCC cancer cell lines and primary cultures as compared to normal human oral keratinocyte cells. To further investigate the role of let-7d in OSCC, we applied the SPONGE method to knock down let-7d in OECM-1 and two primary OSCC cell types. The results showed that knockdown of let-7d promote epithelial-mesenchymal transition (EMT) traits and migratory/invasive capabilities in OSCC cells. Furthermore, down-expression of let-7d significantly activated Twist and Snail expressions and chemo-resistant abilities of OSCC cells. Notably, overexpression of let-7d effectively reversed the EMT phenotype, blocked migratory/invasive abilities, and further increased the chemosensitivity in oral cancer tumor initiating ALDH1+ cells. In sum, these results show that let-7d negatively modulates EMT expression and also plays a role in regulating chemo-resistant ability in oral cancer.
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A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats.
Eur. J. Pharmacol.
PUBLISHED: 03-25-2011
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Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 ?g/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.
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Induced interleukin-19 contributes to cell-mediated immunosuppression in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.
Ann. Thorac. Surg.
PUBLISHED: 03-06-2011
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Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) promotes immunosuppression, which predisposes patients to infectious complications. We investigated the role of interleukin (IL)-19 in the functions of CD4+ T cells in patients undergoing CABG with CPB.
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Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
Neurosci. Lett.
PUBLISHED: 01-26-2011
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The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. On an ED(50) basis, the rank of drug potency was oxybuprocaine>bupivacaine>dextrorphan (P<0.01). Mixtures of clonidine (0.12?mol) with oxybuprocaine, bupivacaine or dextrorphan (ED(50) or ED(95)) extended the duration of action and increased the potency on infiltrative cutaneous analgesia. Among these drugs, the addition of clonidine to bupivacaine (amide type) elicits the most effective cutaneous analgesia. Clonidine at the dose of 0.12 and 0.24?mol did not produce cutaneous analgesia. Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type).
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Dexamethasone prevents postoperative nausea and vomiting: benefit versus risk.
Acta Anaesthesiol Taiwan
PUBLISHED: 01-24-2011
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Postoperative nausea and vomiting (PONV) is a common annoying experience after surgery. The overall incidence of PONV in adults is 20-30%; the incidence rate in patients of high-risk groups can be as high as 70-80%. Children are not exempted from attacking either; the incidence rate in children above the age of 3 is more than 40%. The incidence slowly drops after puberty, sharing the same rate with adults. Dexamethasone can be effective in preventing PONV in adults and children. Compared with other preventive medications, dexamethasone has equal or even better efficacy in reducing the incidence of PONV and has the advantages of low cost and longer effectiveness as well. Although the action mechanism of dexamethasone is hitherto not fully understood, animal studies have confirmed that the vomiting center in the brain stem plays a central role. A combination of dexamethasone with other antiemetics is more effective than any single drug alone. Additionally, the use of dexamethasone to prevent nausea and vomiting triggered by intravenous or epidural morphine for pain control can also offer a good therapeutic effect. To date, clinically, dexamethasone as a preventative drug against PONV has not caused fatal outcome; therefore, it is generally considered to be an effective and safe antiemetic. Nevertheless, its use in this regard may lead to adverse effects, principally postoperative hyperglycemia and infection.
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RETRACTED: Perceived health consequences, memory impairments, and subjective memory complaints of elderly individuals exposed to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan.
Environ. Res.
PUBLISHED: 01-21-2011
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The Publisher regrets that this article was an accidental duplication of an article in Computers and Geotechnics. The duplicate article has therefore been withdrawn.
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Enhancement of transdermal apomorphine delivery with a diester prodrug strategy.
Eur J Pharm Biopharm
PUBLISHED: 01-10-2011
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Diester prodrugs of apomorphine, diacetyl apomorphine (DAA), and diisobutyryl apomorphine (DIA) were synthesized, and their partition coefficients, capacity factor (log K), enzymatic hydrolysis, and in vitro permeation across nude mouse skin were characterized. The lipophilicity of the diesters was between that of apomorphine HCl and the apomorphine base. The prodrugs were chemically stable, but enzymatically unstable in esterase medium, skin homogenate, and human plasma. DAA showed a faster hydrolysis in plasma compared to DIA. Total fluxes (nmol/cm(2)/h) of the parent drug and prodrug were significantly greater after topical treatment with the diesters in aqueous solutions (water, 30% polyethylene glycol in water, and 30% glycerol in water) compared to treatment with HCl and base forms of apomorphine. DIA flux from deionized water was 51 nmol/cm(2)/h, which exceeded the flux of apomorphine HCl by 10-fold. The extent of parent drug regeneration after topical application ranged 51-88% and 34-61% for DAA and DIA, respectively, depending on the vehicles selected. Permeation measurements using intact and stratum corneum-stripped skins demonstrated that the viable epidermis/dermis was an important barrier to prodrug permeation. Nano-sized lipid emulsions were also used as carriers for apomorphine and its prodrugs. Diester prodrugs exhibited superior skin permeation compared to the parent drug when formulated into the emulsions. DAA and DIA fluxes from lipid emulsions were 11- and 3-fold higher than that of apomorphine HCl. The results in the present work suggest the feasibility of diester prodrugs for the transdermal delivery of apomorphine.
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Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury.
Nephrol. Dial. Transplant.
PUBLISHED: 09-23-2010
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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)-?-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.
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Tianeptine reduces morphine antinociceptive tolerance and physical dependence.
Behav Pharmacol
PUBLISHED: 08-04-2010
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Long-term use of morphine can cause neuronal dystrophic changes in specific areas of the brain. These changes may underlie the mechanism for developing morphine antinociceptive tolerance and physical dependence. We evaluated the effect of tianeptine, an antidepressant with prominent neuroprotective and neuroplastic properties, on the development of morphine antinociceptive tolerance and physical dependence. Male C57BL/6 mice were rendered tolerant to or dependent on morphine by subcutaneously injecting them with morphine (10 mg/kg) and intraperitoneally with saline or tianeptine (1, 3, or 5 mg/kg) twice daily for 6 days. The mice were given a daily tail-flick test 1 h after the first morphine injection to evaluate the development of their tolerance to morphine antinociception. To evaluate their physical dependence on morphine, 3 h after the final morphine injection on day 6, naloxone-HCl-precipitated (2 mg/kg, intraperitoneally) withdrawal symptoms were counted for 30 min, and body weight was checked 1 h after the naloxone injection. Tianeptine per se produced no antinociception, neither did it modify the antinociception produced by morphine, nor did it evoke the behavioral responses different from those in the saline controls. The combination of tianeptine with morphine significantly reduced the development of morphine antinociceptive tolerance and suppressed the incidence of naloxone-precipitated withdrawal symptoms. We conclude that tianeptine is an effective inhibitor of morphine-induced antinociceptive tolerance and physical dependence in mice. Our results would imply that comedication with tianeptine and morphine might benefit those who need long-term morphine treatment.
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Premarin improves outcomes of spinal cord injury in male rats through stimulating both angiogenesis and neurogenesis.
Crit. Care Med.
PUBLISHED: 07-27-2010
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To ascertain whether Premarin improves spinal cord injury outcomes in male rats by stimulating both angiogenesis and neurogenesis.
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The dose-dependent study of verapamil and diltiazem on spinal anesthesia in the rat.
Neurosci. Lett.
PUBLISHED: 05-15-2010
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The aim of this study evaluated the spinal anesthetic effect of verapamil and diltiazem. After rats were injected intrathecally with verapamil and diltiazem, dose-response curves were constructed. We evaluated the potency and duration of verapamil or diltiazem which compared with mepivacaine, a commonly used local anesthetic, in rats. Verapamil, diltiazem and mepivacaine produced a dose-dependent local anesthetic effect as spinal anesthesia. On a 50% effective dose (ED(50)) basis, the spinal anesthetic effect of verapamil was more potent than diltiazem or mepivacaine (P<0.01 for each comparison). On an equipotent basis (ED(25), ED(50), and ED(75)), the blockade duration of spinal anesthesia caused by diltiazem was longer than that caused by verapamil or mepivacaine (P<0.01 for each comparison). In summary, verapamil produced more potent spinal blockades, when compared with diltiazem or mepivacaine. Diltiazem demonstrated longer spinal blockades than did verapamil or mepivacaine.
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Phenothiazine-type antipsychotics elicit cutaneous analgesia in rats.
Acta Anaesthesiol Taiwan
PUBLISHED: 05-04-2010
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Local anesthetics exert their anesthetic and analgesic effects by blocking the sodium channels in the nervous system. Phenothiazine-type antipsychotics also block sodium channels, but the local anesthetic characteristics of these drugs have not been evaluated. The aim of this study was to evaluate the cutaneous analgesic effect of phenothiazine-type antipsychotics.
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Beneficial effects of magnolol in a rodent model of endotoxin shock.
Eur. J. Pharmacol.
PUBLISHED: 04-22-2010
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Magnolol is a compound extracted from the Chinese medicinal herb Magnolia officinalis. It has multiple pharmacological effects, notably as an anti-oxidant. The aim of this study was to evaluate the effects of magnolol on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anaesthetized Wistar rats. Magnolol (4 microg/kg, i.v.) was administered at 30 min after LPS injection. Post-treatment with magnolol significantly attenuated the deleterious haemodynamic changes (e.g., hypotension and bradycardia) caused by LPS. Meanwhile, magnolol significantly inhibited the elevation of plasma levels of tumor necrosis factor alpha, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and blood urine nitrogen caused by LPS. The induction of inducible nitrous oxide (NO) synthase and the overproduction of NO and superoxide anions by LPS were also significantly reduced by post-treatment with magnolol. Moreover, the plasma level of the thrombin-antithrombin complex following administration of LPS was also reduced by post-treatment with magnolol. Thus, the beneficial effects of magnolol on LPS-induced sepsis result from its anti-inflammatory, anti-coagulatory, and anti-oxidant effects.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.