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PURPOSE: Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury. METHODS: Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice. RESULTS: Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment. CONCLUSION: These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.
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Proteínas Quinasas Activadas por AMP/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Curcuma/química , Curcumina/farmacología , Animales , Antiinflamatorios/farmacología , Bencimidazoles/farmacología , Quimiocina CXCL2/metabolismo , Lipopolisacáridos/farmacología , Pulmón/metabolismo , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Naftalimidas/farmacología , Neutrófilos/metabolismo , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
There is a lack of information on critical care in Korea. The aim of this study was to determine the current status of Korean intensive care units (ICUs), focusing on the organization, characteristics of admitted patients, and nurse and physician staffing. Critical care specialists in charge of all 105 critical care specialty training hospitals nationwide completed a questionnaire survey. Among the ICUs, 56.4% were located in or near the capital city. Only 38 ICUs (17.3%) had intensive care specialists with a 5-day work week. The average daytime nurse-to-patient ratio was 1:2.7. Elderly people ≥ 65 yr of age comprised 53% of the adult patients. The most common reasons for admission to adult ICUs were respiratory insufficiency and postoperative management. Nurse and physician staffing was insufficient for the appropriate critical care in many ICUs. Staffing was worse in areas outside the capital city. Much effort, including enhanced reimbursement of critical care costs, must be made to improve the quality of critical care at the national level.
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Cuidados Críticos/organización & administración , Personal de Enfermería en Hospital/estadística & datos numéricos , Médicos/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Hospitales , Humanos , Unidades de Cuidados Intensivos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , República de Corea , Encuestas y CuestionariosRESUMEN
Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3ß or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3ß, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3ß but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.
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Camellia sinensis/química , Cardiotónicos/farmacología , Catequina/análogos & derivados , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/prevención & control , Animales , Cardiotónicos/aislamiento & purificación , Catequina/aislamiento & purificación , Catequina/farmacología , Muerte Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Masculino , Daño por Reperfusión Miocárdica/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-DawleyRESUMEN
Propofol is an anesthetic drug with antioxidant and anti-inflammatory properties. We previously found that propofol attenuated lipopolysaccharide-induced acute lung injury in rabbits. This study was performed to evaluate the effects of propofol on lung injury caused by collapse and reventilation in rabbits. The wet/dry weight ratio of the lung, lung injury scores, percentage of polymorphonuclear leukocytes, albumin concentration, malondialdehyde, and interleukin-8 levels in bronchoalveolar lavage fluid were significantly increased in both lungs of the reventilation group. The degree of increase in these parameters was more significant in the right (reventilated) than in the left (non-reventilated) lung. Propofol attenuated these changes. These findings suggest that reventilation of a collapsed lung can cause injury in the contralateral non-reventilated lung as well as the reventilated lung. Propofol may provide a beneficial effect on lung injury induced by collapse and reventilation of the lung.
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Lesión Pulmonar/tratamiento farmacológico , Propofol/uso terapéutico , Albúminas/análisis , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Inflamación/tratamiento farmacológico , Interleucina-8/análisis , Recuento de Leucocitos , Lipopolisacáridos , Lesión Pulmonar/etiología , Masculino , Malondialdehído/análisis , Neutrófilos , Atelectasia Pulmonar/complicaciones , Ventilación Pulmonar , ConejosRESUMEN
BACKGROUND: Nitrous oxide (N2O) and remifentanil both have anesthetic-reducing and antinociceptive effects. We aimed to determine the anesthetic requirements and stress hormone responses in spinal cord-injured (SCI) patients undergoing surgery under sevoflurane anesthesia with or without pharmacodynamically equivalent doses of N2O or remifentanil. METHODS: Forty-five chronic, complete SCI patients undergoing surgery below the level of injury were randomly allocated to receive sevoflurane alone (control, n = 15), or in combination with 67% N2O (n = 15) or target-controlled infusion of 1.37 ng/ml remifentanil (n = 15). Sevoflurane concentrations were titrated to maintain a Bispectral Index (BIS) value between 40 and 50. Measurements included end-tidal sevoflurane concentrations, mean arterial blood pressure (MAP), heart rate (HR), and plasma catecholamine and cortisol concentrations. RESULTS: During surgery, MAP, HR, and BIS did not differ among the groups. Sevoflurane concentrations were lower in the N2O group (0.94 ± 0.30%) and the remifentanil group (1.06 ± 0.29%) than in the control group (1.55 ± 0.34%) (P < 0.001, both). Plasma concentrations of norepinephrine remained unchanged compared to baseline values in each group, with no significant differences among groups throughout the study. Cortisol levels decreased during surgery as compared to baseline values, and returned to levels higher than baseline at 1 h after surgery (P < 0.05) without inter-group differences. CONCLUSIONS: Remifentanil (1.37 ng/ml) and N2O (67%) reduced the sevoflurane requirements similarly by 31-39%, with no significant differences in hemodynamic and neuroendocrine responses. Either remifentanil or N2O can be used as an anesthetic adjuvant during sevoflurane anesthesia in SCI patients undergoing surgery below the level of injury.
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BACKGROUND: Urinary trypsin inhibitors (UTI) have been widely used for the treatment of diseases including disseminated intravascular coagulation, shock, and pancreatitis. Since UTI synthesis is likely to be reduced in patients who have undergone liver resection, the incidence of inflammatory reactions may be increasing accordingly. For such patients, the liver enzyme increases after the operation can reflect liver damage. The purpose of this study was to examine if ulinastatin can inhibit liver enzyme increases after liver resection. METHODS: After receiving Institutional Review Board approval, a retrospective chart review was performed on 201 patients who underwent hepatic resection from 2006 to 2010. We divided the records into the control (n = 69) and ulinastatin (n = 132) groups according to the use of intraoperative ulinastatin and compared the preoperative and postoperative laboratory test results. The number of patients who had > 400 U/L elevation of aspartate transaminase (AST) level after surgery was compared between the 2 groups. RESULTS: The mean AST, alanine transaminase (ALT), and total bilirubin levels after liver resection were significantly lower in the ulinastatin group than in the control group. The number of patients who showed an AST > 400 U/L after liver resection was significantly higher in the control group (odds ratio = 3.02). CONCLUSIONS: Ulinastatin attenuates the elevation of hepatic enzymes and bilirubin after liver resection.
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Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3ß was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% ± 5.3% in the sauchinone group vs 44.4% ± 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3ß was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.
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Benzopiranos/farmacología , Dioxoles/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/prevención & control , Fosforilación , RatasRESUMEN
BACKGROUND: A low fraction of inspired oxygen (FiO(2)) increases venous deoxygenated hemoglobin concentrations, making the color of the blood darker. The present study was aimed to determine the effects of FiO(2) on the ability to discriminate venous from arterial blood. METHODS: One-hundred and sixty surgical patients undergoing percutaneous central venous access of the internal jugular vein were randomly assigned to receive an FiO(2) of 0.2, 0.4, 0.6, or 1.0 (n = 40 each) for at least 20 min prior to central line placement under general anesthesia. Vascular access was achieved with a 22-gauge needle; 2 ml of blood was withdrawn and shown to three physicians including the operator. Each of them was asked to identify the blood as 'arterial', 'venous' or 'not sure'. Simultaneous blood gas analysis of the samples was performed on blood taken from the puncture site and the artery after visual comparison to confirm blood's origin and hemodynamic measurements. RESULTS: Lowering FiO(2) progressively increased venous deoxygenated hemoglobin concentrations (2.24 ± 1.12, 3.30 ± 1.08, 3.66 ± 1.15, and 3.71 ± 1.33 g/dl) in groups having an FiO(2) of 1.0, 0.6, 0.4 and 0.2, respectively (P < 0.001), thereby facilitating the 'venous' blood identification (P < 0.001). Neither heart rate nor mean arterial pressure differed among the groups. None developed hypoxemia (percutaneous hemoglobin oxygen saturation < 90%) in any group during the study period. CONCLUSIONS: A low FiO(2) increases venous deoxygenated hemoglobin levels, thereby facilitating the recognition by clinicians of its venous origin in percutaneous central venous catheterization under general anesthesia.
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BACKGROUND: Elevated systemic levels of pro-inflammatory cytokines cause hypotension during septic shock and induce capillary leakage in acute lung injury. Manassantin B has anti-inflammatory and anti-plasmoidal properties. This study examined the effects of manassantin B on lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. METHODS: RAW 264.7 macrophage cells were incubated without or with (1, 3 and 10 µM) manassantin B and without or with (100 ng/ml) LPS. Manassantin B dissolved in phosphate buffered saline was added to the medium 1 h prior to the addition of LPS. The degree of activation of mitogen-activated protein kinase (MAPK) including extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino terminal kinases (JNK) and p38 MAPK, and the level of interleukin (IL)-1ß were determined 30 min and 24 h after the addition of LPS respectively. RESULTS: Manassantin B inhibited the production of IL-1ß and attenuated the phosphorylations of ERK1/2 and p38 MAPK, but not that of JNK, in RAW 264.7 cells treated with LPS. CONCLUSIONS: Manassantin B reduces LPS-induced IL-1ß expression through effects on ERK1/2- and p38 MAPK-mediated pathways. Manassantin B has potential as a potent anti-inflammatory drug for use in pathological processes such as sepsis or acute lung injury.
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BACKGROUND: Curcumin, the active ingredient of turmeric (Curcuma longa), is known to have anti-inflammatory and antioxidative properties. The present study was aimed to determine the effect of curcumin in regional myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms involving the role of prosurvival kinases and apoptotic kinases. METHODS: Sprague-Dawley rats (n = 109) subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion followed by reperfusion were assigned to receive saline (control), curcumin (100 mg/kg), wortmannin (inhibitor of phosphatidylinositol-3-OH kinase [PI3K]-Akt), wortmannin + curcumin, U0126 (inhibitor of extracellular signal-regulated kinase [ERK1/2]), U0126 + curcumin, SB216763 (inhibitor of glycogen synthase kinase [GSK-3ß]), and SB216763 + curcumin 20 minutes before LAD occlusion. Infarct size was measured after 2 hours of reperfusion by triphenyl tetrazolium chloride staining. The phosphorylation of Akt, ERK1/2, GSK-3ß, p38, and c-Jun N-terminal kinases (JNK) was determined by immunoblotting after 10 minutes of reperfusion. RESULTS: Curcumin significantly reduced the infarct size compared with the control (33.1% ± 6.2% vs 50.1% ± 3.9%; P < .05). Wortmannin or U0126 alone did not affect the infarct size but abolished the curcumin-induced cardioprotective effect. Curcumin significantly enhanced the phosphorylation of Akt, ERK1/2, and GSK-3ß, while it reduced that of p38 and JNK. Wortmannin or U0126 abolished enhanced phosphorylation of GSK-3ß induced by curcumin. SB216763 alone or combined with curcumin reduced the infarct size and enhanced phosphorylation of GSK-3ß compared with the control. CONCLUSIONS: Preconditioning by curcumin effectively protects against regional myocardial I/R injury through the activation of prosurvival kinases involving PI3K-Akt, ERK1/2, and GSK-3ß, and attenuation of p38 and JNK.
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Antioxidantes/uso terapéutico , Cardiotónicos/uso terapéutico , Curcumina/uso terapéutico , Glucógeno Sintasa Quinasa 3/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Animales , Antiinflamatorios no Esteroideos/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/química , Cardiotónicos/antagonistas & inhibidores , Curcumina/química , Quimioterapia Combinada , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/uso terapéutico , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/química , Glucógeno Sintasa Quinasa 3 beta , Ventrículos Cardíacos/enzimología , Ventrículos Cardíacos/patología , Indoles/uso terapéutico , Masculino , Maleimidas/uso terapéutico , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
This study was undertaken to clarify the effects of urinary trypsin inhibitor (UTI) on lipopolysaccharide (LPS)-induced acute lung injury. Rabbits were randomly assigned to one of seven groups: saline only, UTI, LPS, pre- or post-UTI-high (infusion of UTI of 25,000 U/kg followed by 25,000 U/kg over 2 h), pre- or post-UTI-low (infusion of UTI of 2,500 U/kg followed by 2,500 U/kg over 2 h). UTI was administered 30 min before (pre-groups) or 15 min after (post-groups) LPS administration. Rabbits were mechanically ventilated with 40% oxygen for 6 h. LPS decreased peripheral blood leukocyte counts and increased wet/dry weight ratio of lung, lung injury score, neutrophil infiltration in lung, and IL-8 production in systemic blood and bronchoalveolar lavage fluid (BALF). Rabbits treated by UTI were protected from LPS-induced lung injury, as determined by wet/dry weight ratio, neutrophil infiltration in lung, lung injury score, and IL-8 in BALF levels. UTI attenuated LPS-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis-related lung injury.
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Lesión Pulmonar Aguda/prevención & control , Glicoproteínas/farmacología , Lipopolisacáridos/inmunología , Lesión Pulmonar Aguda/inmunología , Animales , Líquido del Lavado Bronquioalveolar/química , Interleucina-8/biosíntesis , Interleucina-8/sangre , Recuento de Leucocitos , Leucocitos/inmunología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Conejos , Distribución AleatoriaRESUMEN
PURPOSE: Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. MATERIALS AND METHODS: In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. RESULTS: The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5 ± 0.6°C, 1.6 ± 0.5°C and 2.3 ± 0.6°C, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. CONCLUSION: The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol.
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Anestesia General/métodos , Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Temperatura Corporal/efectos de los fármacos , Éteres Metílicos/administración & dosificación , Propofol/administración & dosificación , Anciano , Envejecimiento , Anestésicos Combinados/administración & dosificación , Regulación de la Temperatura Corporal/efectos de los fármacos , Emulsiones Grasas Intravenosas , Femenino , Humanos , Masculino , Persona de Mediana Edad , SevofluranoRESUMEN
We describe a new technique of single interfascial injection for 25 patients scheduled for transurethral bladder tumor resection. An ultrasound probe was placed at the midline of inguinal crease and moved medially and caudally to visualize the fascial space between the adductor longus (or pectineus) and adductor brevis muscles. We injected 20 mL 1% lidocaine containing epinephrine into the interfascial space using a transverse plane approach to make an interfascial injection, not an intramuscular swelling pattern. And just distally, firm pressure was applied for 3 min. Afterwards, surgery was performed under spinal anesthesia. The time required for identification and location of the nerve was 20 ± 15 and 30 ± 15 s, respectively. Adductor muscle strength, which was measured with a sphygmomanometer, decreased in all patients, from 122 ± 26 mmHg before blockade to 63 ± 11 mmHg 5 min after blockade. No movement or palpable muscle twitching occurred in 23 cases, slight movement of the thigh not interfering with the surgical procedure was observed in 1 case, thus the obturator reflex was successfully inhibited in 96% of cases. Ultrasound-guided single interfascial injection is an easy and successful technique for obturator nerve block.
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Bloqueo Nervioso/instrumentación , Bloqueo Nervioso/métodos , Nervio Obturador/efectos de los fármacos , Nervio Obturador/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Anciano , Anestesia Raquidea/métodos , Epinefrina/administración & dosificación , Femenino , Humanos , Inyecciones/métodos , Lidocaína/administración & dosificación , Masculino , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/inervación , Nervios Periféricos/diagnóstico por imagen , Muslo/diagnóstico por imagenRESUMEN
BACKGROUND: Although bone cancer-related pain is one of the most disruptive symptoms in patients with advanced cancer, patients are often refractory to pharmacological treatments; thus, more effective treatments for bone cancer pain are needed. We evaluated the analgesic efficacy of and interaction between intrathecal GR89696, a κ(2)-opioid receptor agonist, and interleukin (IL)-10 in a rat model of bone cancer pain. METHODS: The rat model of bone cancer pain was produced by right tibia intramedullary injection of rat breast cancer cells, and an intrathecal catheterization was performed. Ten days later, a paw-withdrawal threshold to mechanical stimulus by von Frey hairs was measured using the up-down method, after intrathecal administration of GR89696 and IL-10. The interaction between the 2 drugs was also evaluated using an isobolographic analysis. RESULTS: Intrathecal GR89696 and IL-10 significantly increased the paw withdrawal threshold of the cancer cell-implanted rat, in a dose-dependent manner, with 50% effective dose values (95% confidence interval) of 50.78 µg (31.80-80.07µg) and 0.83 µg (0.59-1.15 µg), respectively. Isobolographic analysis revealed a synergistic interaction between intrathecal GR89696 and IL-10. CONCLUSIONS: Intrathecally administered GR89696 and IL-10 attenuated bone cancer-induced pain, and the 2 drugs interacted synergistically in the spinal cord. These results raise the intriguing possibility of κ(2)-opioid receptor agonists and IL-10 as a new therapeutic approach for the management of bone cancer-associated pain.
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Analgésicos Opioides/administración & dosificación , Antiinflamatorios/administración & dosificación , Neoplasias Óseas/complicaciones , Interleucina-10/administración & dosificación , Dolor/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirrolidinas/administración & dosificación , Receptores Opioides kappa/agonistas , Tibia/patología , Animales , Conducta Animal/efectos de los fármacos , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Inyecciones Espinales , Dolor/etiología , Dolor/metabolismo , Dolor/fisiopatología , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores Opioides kappa/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: The injection pain of microemulsion propofol is frequent and difficult to prevent. This study examined the prevention of pain during microemulsion propofol injection by pretreatment with different doses of remifentanil or saline, and premixing of lidocaine. METHODS: One hundred sixty ASA physical status 1-2 adult patients scheduled for elective surgery were enrolled into one of four groups (n = 40, in each). The patients received saline (group LS), remifentanil 0.3 µg/kg (group LR 0.3), remifentanil 0.5 µg/kg (group LR 0.5), or remifentanil 1.0 µg/kg (group LR 1.0), and after 90 seconds received an injection of 2 mg/kg microemulsion propofol premixed with lidocaine 40 mg. Pain was assessed on a four-point scale during microemulsion propofol injection. RESULTS: The incidence of microemulsion propofol-induced pain was significantly lower in the LR 0.3, LR 0.5 and LR 1.0 groups than in the LS group (37.5%, 12.5% and 10% vs 65%, respectively). The LR 0.5 and LR 1.0 groups showed significantly less frequent and intense pain than the LR 0.3 group. However, both incidence and severity of pain were not different between LR 0.5 and LR 1.0 groups. CONCLUSIONS: The combination of remifentanil and lidocaine is effective in alleviating pain associated with a microemulsion propofol injection compared with just lidocaine. Remifentanil 0.5 µg/kg had a similar analgesic effect compared to the 1.0 µg/kg dose.
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BACKGROUND: Endotracheal intubation usually causes transient hypertension and tachycardia. The cardiovascular and arousal responses to endotracheal and endobronchial intubation were determined during rapid-sequence induction of anesthesia in normotensive and hypertensive elderly patients. METHODS: Patients requiring endotracheal intubation with (HT, n = 30) or without hypertension (NT, n = 30) and those requiring endobronchial intubation with (HB, n = 30) or without hypertension (NB, n = 30) were included in the study. Anesthesia was induced with intravenous thiopental 5 mg/kg followed by succinylcholine 1.5 mg/kg. After intubation, all subjects received 2% sevoflurane in 50% nitrous oxide and oxygen. Mean arterial pressure (MAP), heart rate (HR), plasma catecholamine concentration, and Bispectral Index (BIS) values, were measured before and after intubation. RESULTS: The intubation significantly increased MAP, HR, BIS values and plasma catecholamine concentrations in all groups, the peak value of increases was comparable between endotracheal and endobronchial intubation. However, pressor response persisted longer in the HB group than in the HT group (5.1 ± 1.6 vs. 3.2 ± 0.9 min, P < 0.05). The magnitude of increases in MAP and norepinephrine from pre-intubation values was greater in the hypertensive than in the normotensive group (P < 0.05), while there were no differences in those of HR and BIS between the hypertensive and normotensive groups. CONCLUSIONS: Cardiovascular response and arousal response, as measured by BIS, were similar in endobronchial and endotracheal intubation groups regardless of the presence or absence of hypertension except for prolonged pressor response in the HB group. However, the hypertensive patients showed enhanced cardiovascular responses than the normotensive patients.
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BACKGROUND: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. METHODS: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, α1 adrenergic and α2 adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. RESULTS: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. CONCLUSIONS: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.
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BACKGROUND: Pain upon the injection of propofol is a common adverse effect. This study was conducted to evaluate the analgesic effect of remifentanil and cold propofol during propofol injection for the induction of anesthesia and to determine if a combination of cold propofol and remifentanil produced additional analgesic efficacy. METHODS: A total of 160 patients aged 20-65 years old were randomly allocated into one of four groups (n = 40, in each). Control and remifentanil group patients received 2 mg/kg propofol that had been stored at room temperature (20-23â), while the cold and combination group received cold (4â) propofol. The patients received remifentanil 0.5 µg/kg IV in the remifentanil and combination groups or saline in the control and cold groups. Ninety seconds after administration the patients were administered propofol over a 30 second period. The pain intensity and incidence were then evaluated using a 4-point verbal rating scale. RESULTS: The incidence of pain was significantly reduced in groups that received remifentanil in the cold and combination groups when compared with the control group (27.5%, 30%, and 2.5% vs. 70%, respectively). Moreover, the severity of pain was significantly lower in groups that received remifentanil in the cold and combination groups when compared with the control group. The incidence and severity of pain from the propofol injection in the combination group was significantly lower than that in the remifentanil and cold groups. CONCLUSIONS: The combination of cold propofol and pretreatment with remifentanil more effectively reduced the incidence of pain upon the injection of propofol than either treatment alone.
RESUMEN
OBJECTIVES: Controversy exists regarding the efficacy of ligament prolotherapy in alleviating sacroiliac joint pain. The inconsistent success rates reported in previous studies may be attributed to variability in patient selection and techniques between studies. It was hypothesized that intra-articular prolotherapy for patients with a positive response to diagnostic block may mitigate the drawbacks of ligament prolotherapy. The purpose of this study was to evaluate the efficacy and long-term effectiveness of intra-articular prolotherapy in relieving sacroiliac joint pain, compared with intra-articular steroid injection. DESIGN: This was a prospective, randomized, controlled trial. SETTINGS/LOCATION: The study was conducted at an outpatient pain medicine clinic at Chonnam National University Hospital in Gwang-ju, Korea. SUBJECTS: The study included patients with sacroiliac joint pain, confirmed by ≥50% improvement in response to local anesthetic block, lasting 3 months or longer, and who failed medical treatment. INTERVENTIONS: The treatment involved intra-articular dextrose water prolotherapy or triamcinolone acetonide injection using fluoroscopic guidance, with a biweekly schedule and maximum of three injections. OUTCOME MEASURES: Pain and disability scores were assessed at baseline, 2 weeks, and monthly after completion of treatment. RESULTS: The numbers of recruited patients were 23 and 25 for the prolotherapy and steroid groups, respectively. The pain and disability scores were significantly improved from baseline in both groups at the 2-week follow-up, with no significant difference between them. The cumulative incidence of ≥50% pain relief at 15 months was 58.7% (95% confidence interval [CI] 37.9%-79.5%) in the prolotherapy group and 10.2% (95% CI 6.7%-27.1%) in the steroid group, as determined by Kaplan-Meier analysis; there was a statistically significant difference between the groups (log-rank p < 0.005). CONCLUSIONS: Intra-articular prolotherapy provided significant relief of sacroiliac joint pain, and its effects lasted longer than those of steroid injections. Further studies are needed to confirm the safety of the procedure and to validate an appropriate injection protocol.
Asunto(s)
Antiinflamatorios/uso terapéutico , Terapias Complementarias , Glucocorticoides/uso terapéutico , Glucosa/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Triamcinolona/uso terapéutico , Anciano , Femenino , Glucosa/administración & dosificación , Humanos , Inyecciones Intraarticulares/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Articulación SacroiliacaRESUMEN
We investigated the anti-inflammatory effects of sauchinone, a lignan isolated from Saururus chinensis, and the underlying mechanism in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. To assess the effects of sauchinone on LPS-induced macrophages activation, we measured the production of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2, and activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) 1/2, c-Jun amino terminal kinases and p38 mitogen-activated protein kinase, and NF-kappaB activation in RAW264.7 cells. Sauchinone decreased the production of TNF-alpha, but not MIP-2 production in RAW264.7 cells stimulated with LPS. Sauchinone also decreased c-Raf-MEK1/2-ERK1/2 phosphorylation and NF-kappaB activation in RAW264.7 cells stimulated with LPS. Our results show that sauchinone inhibits LPS-induced TNF-alpha expression in macrophages by suppression of NF-kappaB activation via ERK1/2 pathway, which may constitute anti-inflammatory effects of sauchinone.