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3.
Acta Anaesthesiol Scand ; 63(5): 659-667, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30536525

RESUMEN

BACKGROUND: A preliminary study has shown effective cancer pain relief by intrathecal betamethasone (ITB). However, further evidence is needed to support this new approach. METHODS: Cancer patients with opioid-resistant pain received lumbar intrathecal administration of betamethasone 2 or 3 mg once a week for 28 days. Immediate and short-term analgesia (using a percentage pain reduction scale and a numerical rating scale, NRS) and long-term analgesia (using NRS) were assessed. Patients were classified into two groups according to the most painful site of metastasis: vertebral column and/or surrounding nerve plexus metastases (group A) and other metastases distal from the vertebral column (group B). RESULTS: A total of 104 patients received ITB. Pain relief was observed not only in the lower half but also in the upper half of the body. The proportion of group A patients who experienced immediate analgesia was 81% (47/58), which was significantly greater than that of group B (P < 0.001). A decrease in NRS scores 1 day after ITB administration was observed in significantly more patients in group A than in group B (P < 0.001). Long-term analgesia was also recorded in a greater proportion of patients in group A than in group B in the 7-day (59%, 38/64 vs 6%, 2/33) and 28-day periods (71%, 40/56 vs 31%, 8/26) (P < 0.001). No adverse effects related to neurotoxicity were recorded. CONCLUSION: Intrathecal injection of betamethasone produced analgesia for opioid-resistant cancer pain, and may be a potent therapeutic option for intolerable pain from vertebral column and/or surrounding nerve plexus metastases.


Asunto(s)
Analgésicos/administración & dosificación , Betametasona/administración & dosificación , Dolor en Cáncer/tratamiento farmacológico , Anciano , Analgésicos/farmacología , Betametasona/efectos adversos , Betametasona/farmacología , Neoplasias Óseas/fisiopatología , Neoplasias Óseas/secundario , Femenino , Humanos , Inyecciones Espinales , Masculino , Persona de Mediana Edad
4.
Immunopharmacol Immunotoxicol ; 39(4): 225-232, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28555511

RESUMEN

Dexmedetomidine, an α2-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-α or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine's anti-inflammatory effect is primarily via the stimulation of the α2-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.


Asunto(s)
Anestésicos Intravenosos/farmacología , Dexmedetomidina/farmacología , Inflamación/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Carragenina/farmacología , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/metabolismo , Interleucina-6/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
5.
Masui ; 66(5): 550-553, 2017 May.
Artículo en Inglés, Japonés | MEDLINE | ID: mdl-29693947

RESUMEN

A 37-year-old female patient with myotonic dystrophy was scheduled for laparoscopic cholecystectomy for gall stone under general anesthesia with continuous propofol infusion. Rocuronium was administered with careful monitoring using TOF- Watch®, measuring train-of-four count (Tc), TOF ratio (Tr), and posttetanic count The total amount of rocuronium was 70 mg ; 0.6 mg .kg⁻1 for anesthetic induction and 0.3 mg .kg⁻1 when Tc exceeded 1. When the operation was completed, Tc was 4, Tr was uncountable and she showed reaction to calling her name. Then sugammadex 2 mg .kg⁻1, rapidly antagonized the neuromuscular block, such that the Tr recovered to 100% but tidal volume was 250 ml in 3 minutes. Additional dorsage of sugammadex, 2 mg .kg⁻1, was required for tidal volume to recover to 530 ml. After 20 minutes of first administration of sugammadex, we extubated the tracheal tube without respiratory depression. To avoid respiratory depression, we did not use postoperative opioids. Intraoperative transversus abdominis plane block and postoperative thoracic epidural block with ropivacaine were successful for postoperative pain relief.


Asunto(s)
Distrofia Miotónica/cirugía , gamma-Ciclodextrinas , Adulto , Androstanoles , Anestesia Epidural , Anestesia General , Colecistectomía Laparoscópica , Femenino , Humanos , Bloqueo Nervioso , Bloqueo Neuromuscular , Propofol , Insuficiencia Respiratoria , Rocuronio , Sugammadex
6.
BMC Anesthesiol ; 16(1): 104, 2016 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-27776485

RESUMEN

BACKGROUND: The local anesthetic lidocaine can affect intra- and extra-cellular signaling pathways in both neuronal and non-neuronal cells, resulting in long-term modulation of biological functions, including cell growth and death. Indeed, lidocaine was shown to induce necrosis and apoptosis in vitro. While several studies have suggested that lidocaine-induced apoptosis is mitochondrial pathway-dependent, it remains unclear whether reactive oxygen species (ROS) are involved in this process and whether the observed cell death can be prevented by antioxidant treatment. METHODS: The effects of lidocaine and antioxidants on cell viability and death were evaluated using SH-SY5Y cells, HeLa cells, and HeLa cell derivatives. Cell viability was examined via MTS/PES ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt]/phenazine ethosulfate) assay. Meanwhile, cell apoptosis and necrosis were evaluated using a cell death detection assay with Annexin V-FITC and PI staining, as well as by assaying for caspase-3/7 and caspase-9 activity, and by measuring the release of lactate dehydrogenase, respectively. Mitochondrial transmembrane potential (ΔΨm) was assessed using the fluorescent probe tetramethylrhodamine ethyl ester. RESULTS: Lidocaine treatment resulted in suppression of the mitochondrial electron transport chain and subsequent attenuation of mitochondrial membrane potential, as well as enhanced ROS production, activation of caspase-3/7 and caspase-9, and induction of apoptosis and necrosis in SH-SY5Y cells in a dose- and time-dependent manner. Likewise, the anesthetics mepivacaine and bupivacaine also induced apoptosis in SH-SY5Y cells. Notably, the antioxidants N-acetyl cysteine (NAC) and Trolox successfully scavenged the mitochondria-derived ROS and suppressed local lidocaine-induced cell death. CONCLUSIONS: Our findings demonstrate that the local anesthetics lidocaine, mepivacaine, and bupivacaine inhibited the activity of mitochondria and induced apoptosis and necrosis in a dose-dependent manner. Furthermore, they demonstrate that treatment with the antioxidants NAC, Trolox, and GGA resulted in preservation of mitochondrial voltage and inhibition of apoptosis via suppression of caspase activation.


Asunto(s)
Acetilcisteína/farmacología , Antioxidantes/farmacología , Lidocaína/farmacología , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/administración & dosificación , Anestésicos Locales/farmacología , Antioxidantes/administración & dosificación , Apoptosis/efectos de los fármacos , Bupivacaína/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromanos/farmacología , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mepivacaína/administración & dosificación , Mitocondrias/efectos de los fármacos , Neuroblastoma/metabolismo , Factores de Tiempo
7.
Korean J Anesthesiol ; 69(5): 460-467, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27703626

RESUMEN

BACKGROUND: Previous studies reported a higher mortality risk and a greater need for renal replacement therapy in patients administered hydroxyethyl starch (HES) rather than other fluid resuscitation preparations. In this study, we investigated the association between 6% HES 70/0.5 use and postoperative acute kidney injury (AKI) in gastroenterological surgery patients. METHODS: We conducted retrospective full-cohort and propensity-score-based analyses of patients who underwent gastroenterological surgery between June 2011 and August 2013 in a Japanese university hospital. The study sample comprised 66 AKI and 2,152 non-AKI patients in the full-cohort analysis and 35 AKI and 1,269 non-AKI patients in the propensity-score-based analysis. Propensity scores were calculated using an ordered logistic regression model in which the dependent variable comprised three groups based on HES infusion volumes (0, 1-999, and ≥ 1,000 ml). The association between HES groups and postoperative AKI incidence was analyzed using multiple logistic regression models. Other candidate independent variables included patient characteristics and intraoperative measures. RESULTS: In the full-cohort analysis, 40 (60.6%) AKI patients were diagnosed as "risk", 15 (22.7%) as "injury," and 11 (16.7%) as "failure". In the propensity-score-based analysis, the corresponding values were 22 (62.9%), 8 (22.9%), and 5 (14.3%). There was no significant association between total infused HES and postoperative AKI incidence in either the full-cohort or the propensity-score-based analysis (P = 0.168 and P = 0.42, respectively). CONCLUSIONS: AKI incidence was not associated with clinical 6% HES 70/0.5 administration in gastroenterological surgery patients treated at a single center.

8.
Masui ; 65(2): 164-7, 2016 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-27017773

RESUMEN

The stiff-person syndrome (SPS) is a rare autoimmune neurologic disorder that affects the gamma-aminobutyric acid (GABA) mediated inhibitory network in the central nervous system with anti-glutamic acid decarboxylase (GAD) antibodies. SPS is characterized by muscle rigidity and painful episodic spasms in axial and lower limb muscles. This case report describes successful peri-operative management of a 61-year-old female (height, 158 cm; weight, 60 kg, ASA-PS 2) with her right upper arm fracture who was scheduled for open reduction and internal fixation. This patient had bulbar paralysis, dysphagia and muscle rigidity associated with a high titer of anti-GAD auto antibodies (2,800 U x ml(-1)). She was diagnosed as SPS and has been treated with predonisolone (30 mg x day(-1)) and diazepam (20 mg x day(-1)) for 1 year. Predonisolone (15 mg) and diazepam (30 mg) was given orally before induction of general anesthesia with propofol, remifentanil and rocuronium bromide. Posture change from supine to beach-chair position led to sudden drop in blood pressure to 38/25 mmHg, which recovered promptly by injecting intravenous ephedrine hydrochloride (28 mg) and hydrocortisone (100 mg). Postanesthetic course was uneventful without postoperative neurologic abnormalities.


Asunto(s)
Anestesia/métodos , Síndrome de la Persona Rígida/fisiopatología , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Persona de Mediana Edad , Postura
9.
JA Clin Rep ; 2(1): 19, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-29497674

RESUMEN

BACKGROUND: Ultiva™ contains the potent short-acting µ-opioid receptor agonist remifentanil hydrochloride, and it is commonly administered intravenously during general anesthesia. It is not approved for epidural or intrathecal use in clinical practice because it contains glycine as an acidic buffer. However, at this moment, very limited information is available on epidural administration of Ultiva™. CASE PRESENTATION: We report the accidental administration of 300 µg of remifentanil and 2.25 mg of glycine into the epidural space after emergence from general anesthesia for distal pancreatectomy and the complete time course of its consequences. The respiratory depression occurred at 5 min after the administration, and complete loss of consciousness was observed at 8 min. The patient was re-intubated and underwent mechanical respiration. At 45 min (33 min after re-intubation), spontaneous respiration resumed, she was responsive to commands, and her orientation returned. She was extubated successfully. CONCLUSIONS: These consequences might have resulted from the diffusion of the components of Ultiva™ into not only systemic circulation but also the cerebrospinal fluid. Moreover, the complex pathophysiology might be associated with remifentanil, as well as glycine present in Ultiva™.

10.
Korean J Anesthesiol ; 68(2): 193-5, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25844141

RESUMEN

Involuntary movement during and after neuraxial anesthesia, such as spinal and epidural anesthesia, is rarely observed. In this report, we describe a case of myoclonus-like involuntary movement of the upper extremities in a patient undergoing a planned repeat cesarean section under spinal anesthesia with bupivacaine that completely subsided after administration of 2 mg of midazolam. The myoclonus-like movement did not recur or cause any apparent neurological side effects.

11.
J Immunotoxicol ; 12(3): 261-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25046027

RESUMEN

Propofol is an intravenous drug widely used for anesthesia and sedation. Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have only been demonstrated in vitro, this study sought to ascertain whether similar effects might also be observed in vivo. In the current studies, effects of propofol were tested in a murine model of arachidonic acid-induced ear inflammation. Specifically, propofol - as a pre-treatment -- was intraperitoneally and then topical application of arachidonic acid was performed. After 1 h, tissue biopsies were collected and tested for the presence of edema and for levels of inflammatory mediators. The results indicated that the administration of propofol significantly suppressed ear edema formation, tissue myeloperoxidase activity, and tissue production of both prostaglandin E2 and cysteinyl leukotrienes. From the data, it can be concluded that propofol could exert anti-COX and anti-5-LOX activities in an in vivo model and that these activities in turn could have, at least in part, suppressed arachidonic acid-induced edema formation in the ear.


Asunto(s)
Anestésicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Propofol/administración & dosificación , Administración Intravenosa , Animales , Araquidonato 5-Lipooxigenasa/metabolismo , Ácido Araquidónico/administración & dosificación , Dinoprostona/metabolismo , Oído/patología , Oído/cirugía , Edema/inducido químicamente , Edema/inmunología , Humanos , Inflamación/inducido químicamente , Inflamación/inmunología , Leucotrieno D4/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Peroxidasa/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo
12.
J Anesth ; 28(5): 681-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24554247

RESUMEN

PURPOSE: To investigate the association between steroid medication before hospital admission and barotrauma in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). METHODS: An observational single-center retrospective study was conducted using patients admitted to the general intensive care unit (ICU) of a university hospital in Japan. We analyzed 149 mechanically ventilated patients with ARDS hospitalized between March 2008 and March 2011. ARDS was identified according to criteria from the Berlin Definition. Barotrauma was defined as pneumothorax, subcutaneous emphysema, or mediastinal emphysema occurring during mechanical ventilation in the ICU. The influence of steroid medication before hospital admission on barotrauma was studied using multiple logistic regression analysis. RESULTS: There were no differences in baseline patient characteristics except for congestive heart failure, peak pressure during mechanical ventilation, and steroid pulse therapy between the barotrauma and non-barotrauma groups. Logistic regression analysis showed that peak pressure ≥35 cmH2O was associated with barotrauma in patients with ARDS [odds ratio (OR), 17.34; P < 0.01], whereas steroid medication before hospital admission was not a significant factor for barotrauma (OR, 1.63; P = 0.51). CONCLUSIONS: Barotrauma in ARDS patients was associated with higher pressure during mechanical ventilation but not with steroid medication before hospital admission.


Asunto(s)
Barotrauma/epidemiología , Glucocorticoides/uso terapéutico , Respiración Artificial , Síndrome de Dificultad Respiratoria/terapia , Anciano , Femenino , Hospitalización , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Japón/epidemiología , Masculino , Enfisema Mediastínico/epidemiología , Persona de Mediana Edad , Neumotórax/epidemiología , Estudios Retrospectivos , Enfisema Subcutáneo/epidemiología
13.
Masui ; 63(10): 1083-8, 2014 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-25693333

RESUMEN

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.


Asunto(s)
Androstanoles/antagonistas & inhibidores , Periodo de Recuperación de la Anestesia , Anestesia General , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes/antagonistas & inhibidores , Bromuro de Vecuronio/antagonistas & inhibidores , gamma-Ciclodextrinas/farmacología , Adulto , Androstanoles/administración & dosificación , Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Rocuronio , Sugammadex , Bromuro de Vecuronio/administración & dosificación , gamma-Ciclodextrinas/administración & dosificación
14.
Immunopharmacol Immunotoxicol ; 35(5): 558-66, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23927488

RESUMEN

Dexmedetomidine is a highly-selective α2-adrenergic receptor agonist used for sedation of critically ill patients in an intensive care setting. Dendritic cells (DCs) in peripheral tissues sense certain foreign antigens and ingest and process them, while migrating to the regional lymph node. Then, DCs present the processed antigen on their surface to stimulate the clonal proliferation of cognitive lymphocytes, leading to the establishment of adaptive immunity. In murine bone marrow-derived DCs, dexmedetomidine significantly delayed the intracellular proteolytic degradation of ovalbumin, while it did not affect phagocytosis, decreased the expression of the surface molecules I-A(b) and CD86, and suppressed cognitive helper T-cell proliferation. Furthermore, dexmedetomidine significantly suppressed DC migration both in vitro, using a Matrigel migration assay, and in vivo, using a foot pad-popliteal lymph node migration assay, which may be ascribed to the inhibition of type IV collagenase/gelatinase activity. Finally, vaccination with dexmedetomidine-treated DCs significantly suppressed the contact hypersensitivity reaction in vivo. These results indicate that dexmedetomidine may suppress immunity by inhibiting DC antigen processing/presentation and migration.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Movimiento Celular/efectos de los fármacos , Células Dendríticas/inmunología , Dexmedetomidina/farmacología , Fagosomas/inmunología , Proteolisis/efectos de los fármacos , Traslado Adoptivo , Animales , Presentación de Antígeno/efectos de los fármacos , Presentación de Antígeno/inmunología , Movimiento Celular/inmunología , Colágeno/química , Células Dendríticas/citología , Células Dendríticas/enzimología , Dermatitis por Contacto/enzimología , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/terapia , Combinación de Medicamentos , Laminina/química , Masculino , Ratones , Fagosomas/metabolismo , Proteoglicanos/química , Vacunación
15.
Masui ; 62(4): 439-41, 2013 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-23697197

RESUMEN

We report that the transversus abdominis plane block (TAP block) can be performed under ultrasound guidance using not a linear probe but a convex probe in a markedly obese patient undergoing laparoscopy-assisted distal gastrectomy. The TAP block is effective for providing perioperative analgesia. The common probe for the TAP block is a high-frequency linear probe, which can not depict the deeper tissues. We used a low-frequency convex probe for TAP block, which clearly showed the spread of local anesthetics in TAP block in a markedly obese patient. A convex probe is preferable for TAP block in markedly obese patients.


Asunto(s)
Bloqueo Nervioso/métodos , Obesidad Mórbida/complicaciones , Adulto , Analgesia/métodos , Gastrectomía/métodos , Humanos , Laparoscopía , Masculino
16.
Masui ; 62(4): 458-61, 2013 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-23697202

RESUMEN

A 69-year-old woman with Rh-negative blood type was scheduled for total pelvic exenteration. Despite having prepared suspected amount of blood, we were forced to transfuse Rh-positive blood after use of anti-D immunoglobulin (0.25 mg) for unexpected massive hemorrhage. Although some strategies (blood-withdrawal system, vascular embolization, discontinuation of operation, et al.) for reduction of incompatible transfusion were considered, we fortunately could acquire additional matched blood after transfusion of Rh-positive blood (4 units), and the operation was completed. On postoperative days 1-2, we administered anti-D immunoglobulin (each 0.25 mg) prophylactically. It is reported that 0.02 mg immunoglobulin prevents sensitization against 1 ml transfused red cells. In this case, total dose of immunoglobulin was not enough, but antiD antibody was not detected over 6 months nonetheless. Two reasons were speculated for lack of anti-D anti body; this patient was immune-suppressed for chemoradiation against rectal cancer, and remaining Rh-positive red cells in her body were of small amount because of massive hemorrhage. Anyway, anti-D globulin administration with the aim of complete neutralization against incompatible transfusion is considered impossible, as there are few Rh-negative people in Japan. It is necessary to prepare sufficient matched blood for major surgery of Rh-negative patients, and to consider above-described strategies. Unavoidable Rh incompatible transfusion needs long-term (about 6 months) follow-up based on erythrocyte life-span and time of antibody production.


Asunto(s)
Pérdida de Sangre Quirúrgica , Isoinmunización Rh/prevención & control , Globulina Inmune rho(D)/uso terapéutico , Reacción a la Transfusión , Anciano , Femenino , Humanos
17.
J Intensive Care ; 1(1): 4, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-25705399

RESUMEN

BACKGROUND: Although some studies conducted outside of Japan have addressed the effectiveness of intravenous immunoglobulins (IVIG) in treating infections, the dosing regimens and amounts used in Japan are very different from those reported. Here, we investigate the effectiveness of single-dose administration of IVIG in sepsis patients in Japan. METHODS: We analyzed 79 patients admitted to the intensive care unit (ICU) of a tertiary care institution due to severe sepsis or septic shock. Patients were randomly divided into a group that was administered standard divided doses of IVIG (5 g/day for 3 days, designated the S group) or a group that was administered a standard single dose of IVIG (15 g/day for 1 day, H group); freeze-dried sulfonated human IVIG was used. The longitudinal assessment of procalcitonin (PCT) levels, C-reactive protein (CRP) levels, white blood cell count, blood lactate levels, IL-6 levels, Sequential Organ Failure Assessment (SOFA) score, and Systemic Inflammatory Response Syndrome (SIRS) was conducted. We also assessed mechanical ventilation duration (days), ICU stay (days), 28-day survival rate, and 90-day survival rate. RESULTS: The study showed no significant differences in PCT levels, CRP levels, 28-day survival rate, and 90-day survival rate between the two groups. However, patients in the H group showed improvements in the various SIRS diagnostic criteria, IL-6 levels, and blood lactate levels in the early stages after IVIG administration. In light of the non-recommendation of IVIG therapy in the Surviving Sepsis Campaign Guidelines 2012, our findings of significant early post-administration improvements are noteworthy. IVIG's anti-inflammatory effects may account for the early reduction in IL-6 levels after treatment, and the accompanying improvements in microcirculation may improve blood lactate levels and reduce SOFA scores. However, the low dosages of IVIG in Japan may limit the anti-cytokine effects of this treatment. Further studies are needed to determine appropriate treatment regimens of single-dose IVIG. CONCLUSIONS: In this study, we investigated the effectiveness of single-dose IVIG treatment in patients with severe sepsis or septic shock. Although there were no significant effects on patient prognoses, patients who were administered single-dose IVIG showed significantly improved IL-6 levels, blood lactate levels, and disease severity scores.

18.
J Immunotoxicol ; 10(3): 262-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-22953970

RESUMEN

Leukotrienes, divided into cysteinyl leukotrienes (CysLTs), which are important mediators of asthmatic responses, and leukotriene B4 (LTB4), a chemotactic and chemokinetic agent for leukocytes, are potent lipid mediators generated from arachidonic acid by 5-lipoxygenase (5-LO). Leukotrienes are also considered to have immunoregulatory and pro-inflammatory actions. Propofol is an intravenous anesthetic widely used for anesthesia and sedation that is alleged to possess anti-inflammatory properties. The present study examined the effect of propofol on leukotriene production by dendritic cells (DC). In murine bone marrow-derived DC, propofol significantly suppressed CysLT and LTB4 production after short-term stimulation with zymosan. The protein levels of cytosolic phospholipase A2 and 5-LO, or arachidonic acid release from plasma membranes, were not affected by the presence of propofol. Although zymosan treatment induced or enhanced the phosphorylation of ERK1/2, p-38 MAPK, and JNK, which presumably up-regulates the activity of 5-LO, the presence of propofol had no additional effect on the phosphorylation status of any of these MAPKs. Similarly, zymosan significantly increased the concentration of intracellular calcium, which is the most crucial activator of 5-LO, but no additional concentration changes were observed with the addition of propofol. Lastly, in an in-vitro cell-free ferrous oxidation-xylenol orange assay, propofol significantly inhibited the 5-LO activity of purified human recombinant 5-LO enzyme with an IC50 of ~7.5 µM. Thus, propofol's inhibition of 5-LO is not likely restricted to the circumstances surrounding the production of leukotrienes from DC, but applicable to other types of immune and non-immune cells that produce leukotrienes. The 5-LO-inhibiting activity of propofol may, at least in part, contribute to the well-known anti-inflammatory activity of propofol.


Asunto(s)
Anestésicos Intravenosos/farmacología , Antiinflamatorios/farmacología , Araquidonato 5-Lipooxigenasa/inmunología , Células de la Médula Ósea/inmunología , Células Dendríticas/inmunología , Leucotrieno B4/inmunología , Propofol/farmacología , Animales , Araquidonato 5-Lipooxigenasa/biosíntesis , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Membrana Celular/inmunología , Membrana Celular/metabolismo , Células Dendríticas/citología , Células Dendríticas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/inmunología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/inmunología , Humanos , Leucotrieno B4/biosíntesis , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/inmunología , Masculino , Ratones , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología
19.
Masui ; 61(9): 1003-5, 2012 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-23012839

RESUMEN

This case report describes a successful outcome of mirtazapine treatment in a patient with difficult post-thoracotomy pain. A 63-year-old man received thoracotomy for the resection of esophageal tumor. The pain continued 2 years after the operation. Allodynia was present in the region of the intercostal nerves from the surgical wound. Remedies such as clonazepam, amitriptyline, gabapentin, and acetaminophen were not effective, and epidural block effect was only temporal. The patient experienced a reduction in shooting pain after taking pregabalin; however, he still suffered from persistent pain and, mirtazapine was additionally administrated. One month after this, shooting and persistent pain was reduced, and the patient's appetite was improved, which had been present since the thoracotomy. Since then, his weight slightly increased and the administration of mirtazapine was stopped in accordance with the patient's request. The pain became worse again. Therefore, mirtazapine, commonly used as an antidepressant agent, was considered to be beneficial for neuropathic pain as an analgesic adjuvant.


Asunto(s)
Antagonistas Adrenérgicos alfa/administración & dosificación , Antidepresivos Tricíclicos/administración & dosificación , Esofagectomía , Mianserina/análogos & derivados , Neuralgia/tratamiento farmacológico , Dolor Intratable/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Humanos , Masculino , Mianserina/administración & dosificación , Persona de Mediana Edad , Mirtazapina , Toracotomía , Factores de Tiempo , Resultado del Tratamiento
20.
J Immunotoxicol ; 8(4): 359-66, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22035152

RESUMEN

Propofol is an intravenous anesthetic that is widely used for anesthesia and sedation. Dendritic cells (DC) are one of the crucial immune cells that bridge innate and adaptive immunity, in which DC process antigens during innate immune responses to present them to naïve T-cells, leading to an establishment of adaptive immunity. Prostaglandin (PG)-E(2) may be secreted by DC into the microenvironment, considerably influencing DC phenotype and function, and thus determining the fate of adaptive immunity. Since propofol suppresses PGE(2) production in murine macrophages, the primary purpose of the present study was to determine whether propofol also suppresses PGE(2) production in DC. Assuming a positive finding of such suppression, we tested whether this also leads to alterations of interleukin (IL)-12 and IL-10 production and DC surface marker expression, both of which can be modulated by PGE(2). In bone marrow-derived DC, propofol significantly suppressed the PGE(2) production after lipopolysaccharide stimulation. Cyclo-oxygenase (COX) protein expression and arachidonic acid release were unaffected, while COX enzyme activity was significantly inhibited by propofol. The propofol-induced COX inhibition did not lead to the increased production of cysteinyl leukotrienes and leukotriene-B(4). Endogenous COX inhibition with propofol, as well as with the selective COX-2 inhibitor, NS-398, did not affect IL-12 and IL-10 production from DC. The surface expression of I-A(b) and CD40 on DC was not changed, while that of CD86 slightly increased, with both propofol and NS-398; expression of CD80 was not affected with propofol, but increased slightly with NS-398. Finally, endogenous COX inhibition with either propofol or NS-398 did not significantly affect the ability of DC to induce allogeneic T-cell proliferation. It is concluded that the intravenous anesthetic propofol suppresses COX enzyme activity in DC, with no consequences with respect to IL-12/IL-10 production and allogeneic T-cell proliferation, while minimal consequences were observed in surface molecule expression.


Asunto(s)
Anestésicos Intravenosos/toxicidad , Células Dendríticas/efectos de los fármacos , Dinoprostona/metabolismo , Propofol/toxicidad , Animales , Biomarcadores/metabolismo , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Inhibidores de la Ciclooxigenasa/farmacología , Células Dendríticas/metabolismo , Quimioterapia Combinada , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nitrobencenos/farmacología , Sulfonamidas/farmacología , Tromboxanos/metabolismo
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