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1.
BMC Anesthesiol ; 17(1): 5, 2017 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-28125969

RESUMEN

BACKGROUND: To potentially optimize intubation skill teaching in an American Heart Association® Airway Management Course® for novices, we investigated the transfer of skills from video laryngoscopy to direct laryngoscopy and vice versa using King Vision® and Macintosh blade laryngoscopes respectively. METHODS: Ninety volunteers (medical students, residents and staff physicians) without prior intubation experience were randomized into three groups to receive intubation training with either King Vision® or Macintosh blade or both. Afterwards they attempted intubation on two human cadavers with both tools. The primary outcome was skill transfer from video laryngoscopy to direct laryngoscopy assessed by first attempt success rates within 60 s. Secondary outcomes were skill transfer in the opposite direction, the efficacy of teaching both tools, and the success rates and esophageal intubation rates of Macintosh blade versus King Vision®. RESULTS: Performance with the Macintosh blade was identical following training with either Macintosh blade or King Vision® (unadjusted odds ratio [OR] 1.09, 95% confidence interval [95% CI] 0.5-2.6). Performance with the King Vision® was significantly better in the group that was trained on it (OR 2.7, 95% CI 1.2-5.9). Success rate within 60 s with Macintosh blade was 48% compared to 52% with King Vision® (OR 0.85, 95% CI 0.4-2.0). Rate of esophageal intubations with Macintosh blade was significantly higher (17% versus 4%, OR 5.0, 95% CI 1.1-23). CONCLUSIONS: We found better skill transfer from King Vision® to Macintosh blade than vice versa and fewer esophageal intubations with video laryngoscopy. For global skill improvement in an airway management course for novices, teaching only video laryngoscopy may be sufficient. However, success rates were low for both devices.


Asunto(s)
Manejo de la Vía Aérea/instrumentación , Personal de Salud/educación , Laringoscopios , Laringoscopía/educación , Transferencia de Experiencia en Psicología , Cadáver , Competencia Clínica , Femenino , Humanos , Intubación Intratraqueal/instrumentación , Laringoscopía/instrumentación , Masculino , Grabación en Video
2.
Anesth Analg ; 122(2): 330-48, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26797549

RESUMEN

The vascular endothelium is one of the largest organs in the body and consists of a single layer of highly specialized cells with site-specific morphology and functions. Endothelial cells play a vital role in the regulation of vascular tone in arterial, venous, microvascular, and lymphatic vascular beds. The endothelium also coordinates angiogenesis and controls cell adhesion, fluid homeostasis, and both innate and adaptive immunity. Fundamental research has shown that general and local anesthetics markedly modulate the biological activities of endothelial cells under aerobic and ischemia-reperfusion conditions, making the endothelium an important target of anesthetics in the cardiovascular system. Halogenated volatile anesthetics provide significant anti-inflammatory actions and protect the endothelium against ischemia-reperfusion injury, despite their inhibiting effects on endothelium-dependent vasorelaxation. They provide not only acute but also potential long-term, beneficial effects. Although many effects of IV anesthetics on endothelial function are controversial, or completely unexplored, propofol and opioids appear to have the most favorable profile with respect to the preservation of endothelial function. Some opioids and ketamine have stereoselective effects on the endothelium. Finally, there is experimental evidence to suggest important effects of anesthetics on the regulation of vascular permeability, proliferation of stem cells, including endothelial progenitor cells, and promotion or inhibition of tumor growth, potentially related to alterations in angiogenesis. However, most of these findings are from in vitro experiments and await confirmation in an in vivo setting. Thus, the clinical implications of these interactions remain uncertain.


Asunto(s)
Anestésicos/farmacología , Endotelio Vascular/efectos de los fármacos , Anestésicos/efectos adversos , Animales , Permeabilidad Capilar/efectos de los fármacos , Endotelio Vascular/fisiología , Humanos , Neovascularización Fisiológica/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos
3.
Biochim Biophys Acta ; 1842(7): 1041-51, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24667322

RESUMEN

Insulin-like growth factor-II (IGF-II) is a naturally occurring peptide that exerts known pleiotropic effects ranging from metabolic modulation to cellular development, growth and survival. IGF-II triggers its actions by binding to and activating IGF (IGF-I and IGF-II) receptors. In this study, we assessed the neuroprotective effect of IGF-II on corticosterone-induced oxidative damage in adult cortical neuronal cultures and the role of IGF-II receptors in this effect. We provide evidence that treatment with IGF-II alleviates the glucocorticoid-induced toxicity to neuronal cultures, and this neuroprotective effect occurred due to a decrease in reactive oxygen species (ROS) production and a return of the antioxidant status to normal levels. IGF-II acts via not only the regulation of synthesis and/or activity of antioxidant enzymes, especially manganese superoxide dismutase, but also the restoration of mitochondrial cytochrome c oxidase activity and mitochondrial membrane potential. Although the antioxidant effect of IGF-I receptor activation has been widely reported, the involvement of the IGF-II receptor in these processes has not been clearly defined. The present report is the first evidence describing the involvement of IGF-II receptors in redox homeostasis. IGF-II may therefore contribute to the mechanisms of neuroprotection by acting as an antioxidant, reducing the neurodegeneration induced by oxidative insults. These results open the field to new pharmacological approaches to the treatment of diseases involving imbalanced redox homeostasis. In this study, we demonstrated that the antioxidant effect of IGF-II is at least partially mediated by IGF-II receptors.


Asunto(s)
Antioxidantes/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/farmacología , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Receptor IGF Tipo 2/metabolismo , Animales , Células Cultivadas , Complejo IV de Transporte de Electrones/metabolismo , Glucocorticoides/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
4.
Eur J Anaesthesiol ; 31(11): 620-5, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24296819

RESUMEN

BACKGROUND: Severe postoperative pain is a major problem after unilateral and bilateral foot surgery. Continuous regional anaesthesia is often used for unilateral surgery. However, for bilateral surgery, the incidence of complications of continuous bilateral compared with unilateral regional anaesthesia is unknown. OBJECTIVES: To assess the incidence of catheter-related complications of bilateral compared with unilateral continuous regional anaesthesia. DESIGN: A prospective observational study. SETTING: Bellinzona Regional Hospital, a tertiary teaching hospital. PATIENTS: Patients (n = 130) scheduled for elective bilateral or unilateral hallux valgus repair treated with continuous popliteal sciatic nerve block using a continuous infusion of ropivacaine 0.15% at 5 ml h for each popliteal catheter by elastomeric pumps. INTERVENTIONS: The incidence of catheter-related complications, effectiveness, pain levels at rest and with motion, patient satisfaction for the first three postoperative days and the incidence of ambulatory visits or readmissions after discharge were measured. A follow-up for neurological or other complications related to regional anaesthesia was performed 6 to 8 weeks after surgery. MAIN OUTCOME MEASURE: The incidence of catheter-related complications comparing bilateral with unilateral continuous sciatic popliteal nerve block. RESULTS: There were no differences in the incidence of catheter-related complications between the groups. Pain scores at rest and with motion were comparable between the groups. All patients were fit for discharge home 3 days after surgery. Patient satisfaction was similar between the groups. There were no unplanned ambulatory visits or readmissions due to complications in either group. No complications related to regional anaesthesia were reported during the follow-up. CONCLUSION: The complication rate, effectiveness and patient satisfaction of bilateral continuous popliteal sciatic nerve block was comparable with unilateral continuous sciatic popliteal nerve block. The follow-up showed that bilateral continuous sciatic popliteal nerve block does not increase the complication rate. However, an outpatient-based study should confirm these data prior to introduction in the ambulatory setting.


Asunto(s)
Amidas/administración & dosificación , Pie/cirugía , Bloqueo Nervioso/métodos , Procedimientos Ortopédicos/métodos , Nervio Ciático/efectos de los fármacos , Adulto , Anciano , Amidas/efectos adversos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hallux Valgus/tratamiento farmacológico , Hallux Valgus/cirugía , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Procedimientos Ortopédicos/efectos adversos , Estudios Prospectivos , Ropivacaína
5.
Am J Sports Med ; 52(5): 1165-1172, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38456291

RESUMEN

BACKGROUND: Previous studies have shown that dexamethasone has a positive effect on postoperative pain control, opioid consumption, nausea, and vomiting and length of hospital stay after arthroplasty surgery. PURPOSE/HYPOTHESIS: The purpose of this study was to assess whether adding perioperative dexamethasone to our current pain regimen after hip arthroscopy is more effective than a placebo. It was hypothesized that dexamethasone would reduce postoperative pain, reduce opioid consumption, improve subjective pain and nausea scores, and reduce the number of vomiting events. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 50 patients requiring unilateral elective hip arthroscopy were randomized to receive intravenous dexamethasone immediately before induction of anesthesia and at 8 am on the first postoperative day (2 ×12 mg) or a placebo (sodium chloride 0.9%). The patient, the surgeons, the treating anesthesiologist, and the involved nursing and physical therapy personnel were blinded to group assignment. The primary outcome was postoperative pain, and secondary outcomes were opioid consumption and nausea scores-assessed using a translated revised version of the American Pain Society Patient Outcome Questionnaire 6 hours postoperatively and on days 1 and 2-and vomiting events. A clinical follow-up was performed 12 weeks postoperatively to assess adverse events. RESULTS: The mean age at inclusion was 29 years in both groups. Postoperative pain levels did not differ significantly in most instances. Opioid requirements during the hospitalization in the dexamethasone group were significantly lower than those in the placebo group (31.96 ± 20.56 mg vs 51.43 ± 38 mg; P = .014). Significantly fewer vomiting events were noted in the dexamethasone group (0.15 ± 0.59 vs 0.65 ± 0.91; P = .034). Descriptive data and surgical parameters did not differ significantly. CONCLUSION: Perioperative intravenous dexamethasone significantly reduced postoperative opioid consumption by 40% without compromising pain level and safety, as no corticosteroid-related side effects were observed. Dexamethasone may be a valuable adjuvant to a multimodal systemic pain regimen after hip arthroscopy. REGISTRATION: NCT04610398 (ClinicalTrials.gov identifier).


Asunto(s)
Analgésicos Opioides , Artroscopía , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Artroscopía/efectos adversos , Dexametasona/uso terapéutico , Método Doble Ciego , Náusea/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Vómitos/tratamiento farmacológico
6.
Cell Mol Life Sci ; 69(7): 1153-65, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21984601

RESUMEN

Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1α overexpression also protected against MPTP-induced striatal loss of dopamine, and mitochondria from PGC-1α transgenic mice showed an increased respiratory control ratio compared with wild-type animals. To modulate PGC-1α, we employed the small molecular compound, resveratrol (RSV) that protected dopaminergic neurons against the MPTP-induced cell degeneration almost to the same extent as after PGC-1α overexpression. As studied in vitro, RSV activated PGC-1α in dopaminergic SN4741 cells via the deacetylase SIRT1, and enhanced PGC-1α gene transcription with increases in SOD2 and Trx2. Taken together, the results reveal an important function of PGC-1α in dopaminergic neurons to combat oxidative stress and increase neuronal viability. RSV and other compounds acting via SIRT1/PGC-1α may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.


Asunto(s)
Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson/metabolismo , Transactivadores/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Encéfalo/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Ratones Transgénicos , Mitocondrias/metabolismo , Estrés Oxidativo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Transactivadores/genética , Factores de Transcripción
7.
A A Pract ; 17(3): e01671, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36930793

RESUMEN

Osteoarthritis frequently results in chronic pain and has a major impact on patients' quality of life. We present a case series of 20 patients with chronic hip pain who received a posterior quadratus lumborum block with the aim of improving their pain and, consequently, their quality of life. The results showed global improvement in pain and quality of life. These preliminary results support our conclusion. Posterior quadratus lumborum block is a safe and minimally invasive option for refractory chronic hip pain.


Asunto(s)
Dolor Crónico , Bloqueo Nervioso , Humanos , Calidad de Vida , Dolor Postoperatorio , Bloqueo Nervioso/métodos , Dolor Crónico/terapia
8.
Can J Anaesth ; 59(10): 958-62, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22829027

RESUMEN

PURPOSE: Continuous regional anesthesia applied as pain therapy at home is clinically established standard practice after upper and lower limb surgery. Persistent motor block at discharge or after continuous infusion of local anesthetics, however, might lead to complications related to the insensate extremity. We report a rare case of a foot fracture due to stumbling after continuous sciatic nerve block at home and discuss the related clinical implications. CLINICAL FEATURES: After uncomplicated ambulatory foot surgery under regional anesthesia, a patient was discharged with a continuous sciatic popliteal nerve block for pain therapy at home. After stumbling, the patient remained symptom-free even until catheter removal three days after surgery. Radiography done one week after surgery revealed a styloid fracture of the fifth metatarsal bone. Her subsequent recovery was uneventful. CONCLUSIONS: The true incidence of complications related to falls at home associated with lower extremity blockade remains unknown, as symptoms of possible complications may be masked by the effects of the local anesthetic. However, with increasing use of postoperative regional anesthesia, it is mandatory to develop and adhere to clinical care maps, and to elaborate and teach strategies to further enhance patient safety.


Asunto(s)
Anestesia de Conducción/efectos adversos , Traumatismos de los Pies/etiología , Pie/patología , Bloqueo Nervioso/efectos adversos , Accidentes por Caídas , Anciano , Procedimientos Quirúrgicos Ambulatorios/métodos , Anestesia de Conducción/métodos , Anestésicos Locales/administración & dosificación , Femenino , Pie/diagnóstico por imagen , Pie/cirugía , Traumatismos de los Pies/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Servicios de Atención de Salud a Domicilio , Humanos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Radiografía , Nervio Ciático
9.
Anesthesiol Clin ; 40(3): 491-509, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36049877

RESUMEN

Acute compartment syndrome (ACS) is a potential orthopedic emergency that leads, without prompt diagnosis and immediate treatment with surgical fasciotomy, to permanent disability. The role of regional anesthesia (RA) for analgesia in patients at risk for ACS remains unjustifiably controversial. This critical review aims to improve the perception of the published literature to answer the question, whether RA techniques actually delay or may even help to hasten the diagnosis of ACS. According to literature, peripheral RA alone does not delay ACS diagnosis and surgical treatment. Only in 4 clinical cases, epidural analgesia was associated with delayed ACS diagnosis.


Asunto(s)
Anestesia de Conducción , Síndromes Compartimentales , Anestesia Local , Síndromes Compartimentales/diagnóstico , Síndromes Compartimentales/cirugía , Extremidades , Fasciotomía/métodos , Humanos
10.
Minerva Anestesiol ; 87(2): 165-173, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33319949

RESUMEN

BACKGROUND: Upper abdominal wall surgical incisions may lead to a severe postoperative pain. Therefore, adequate analgesia is important. Here we investigate whether the low serratus-intercostal interfascial plane block (SIPB) achieves an effective analgesia, considering opioids consumption, pain control and recovery quality in upper abdominal surgeries. METHODS: This blinded, randomized controlled study was conducted on 102 patients undergoing open upper abdominal wall surgery under general anesthesia. All patients who received serratus-intercostal plane block at the eighth rib as analgesic technique were included in SIPB group and in control group those who received continuous intravenous morphine analgesia. Pain scores in numeric verbal scale (NVS) and opioids consumption at 0, 6, 12, 24 and 48 hours postoperatively were assessed. The quality of the postoperative recovery was evaluated using the QoR-15 questionnaire at 24 hours. RESULTS: This study showed lower postoperative opioid consumption at 24 hours (P<0.0001; 4.17 mg vs. 41.52 mg of morphine) and better pain control (P<0.005) with mean pain scores (NVS 1.8±1.5 vs. 4.8±1.6) in group 0 (SIPB). The global QoR-15 scores 24 hours postoperatively were higher (better quality) in the SIPB group (122 vs. 100). CONCLUSIONS: The low serratus-intercostal interfascial plane block (SIPB) provides efficient analgesia leading to a saving of opioids and improvement of the recovery quality in patients undergoing upper abdominal wall surgeries.


Asunto(s)
Bloqueo Nervioso , Analgésicos Opioides/uso terapéutico , Humanos , Morfina , Dolor Postoperatorio/prevención & control , Estudios Prospectivos
11.
N Am Spine Soc J ; 6: 100059, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35141624

RESUMEN

BACKGROUND: Lower urinary tract dysfunction is common in the early postoperative phase after spine surgery. Although it is essential for an optimal patient management to balance benefits and harms, it is not known which patient benefit from a perioperative indwelling catheter. We therefore evaluated urological parameters prior and after spine surgery performing a quality assessment of our current clinical practice in bladder management. METHODS: Preoperatively, all patients completed the International Prostate Symptom Score and were interviewed for urological history. Decision for preoperative urethral catheter placement was individually made by the responsible anesthesiologist according to an in-house protocol. Within and between group analyses using univariate and probability matching statistics were performed for patients with intraoperative urethral catheter-free management (n = 54) and those with a preoperatively placed catheter (n = 46). Post void residual (PVR) was measured prior and after surgery or after removal of the urethral catheter, respectively. The outcome measures consisted of postoperative urinary retention (POUR) and postoperative urological complications (PUC), defined as POUR and any catheter-related adverse events. RESULTS: Hundred patients undergoing spine surgery were prospectively evaluated. Sixteen of the 54 (30%) patients with urethral catheter-free management developed POUR. Length of surgery and volume of intravenous infusion were associated with POUR (p < 0.05). In the 46 preoperatively catheterized patients, re-catheterization was required in 6 (13%). In a fairly homogenous subgroup of 72 patients with a probability of PUC between 15 and 40%, no significant association between intraoperative urethral catheter-free management and the occurrence of PUC was found (odds ratio 2.09, 95% confidence interval 0.69 to 6.33; p = 0.193). CONCLUSIONS: In case of postoperative PVR monitoring allowing de novo catheterization as appropriate, urethral catheter-free management seems to be a valuable option in spine surgery since it does not to increase PUC but minimizes unnecessary catheterizations with their related complications.

12.
J Neural Transm (Vienna) ; 117(6): 681-7, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20387084

RESUMEN

The role of the ATP-gated receptor, P2X(7), has been evaluated in the unilateral 6-OHDA rat model of Parkinson's disease using the P2X(7) competitive antagonist A-438079. Nigral P2X(7) immunoreactivity was mainly located in microglia but also in astroglia. A-438079 partially but significantly prevented the 6-OHDA-induced depletion of striatal DA stores. However, this was not associated with a reduction of DA cell loss. Blockade of P2X(7) receptors may represent a novel protective strategy for striatal DA terminals in Parkinson's disease and warrants further future investigation.


Asunto(s)
Dopamina/metabolismo , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2 , Piridinas/uso terapéutico , Receptores Purinérgicos P2/metabolismo , Tetrazoles/uso terapéutico , Ácido 3,4-Dihidroxifenilacético/metabolismo , Adrenérgicos/toxicidad , Análisis de Varianza , Animales , Encéfalo/metabolismo , Recuento de Células/métodos , Cromatografía Líquida de Alta Presión/métodos , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Degeneración Nerviosa/complicaciones , Vías Nerviosas/metabolismo , Oxidopamina/toxicidad , Enfermedad de Parkinson/etiología , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7 , Estadísticas no Paramétricas
13.
J Adv Res ; 23: 37-45, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32071790

RESUMEN

Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative α-synucleinopathies including Parkinson's disease. Whether aSyn up-regulation is the cause or the protective reaction to α-synucleinopathies remains unresolved. Remarkably, the accumulation of aSyn is involved in cancer. Here, the neuroblastoma SH-SY5Y cell line was genetically engineered to overexpress aSyn at low and at high levels. aSyn cytotoxicity was assessed by the MTT and vital-dye exclusion methods, observed at the beginning of the sub-culture of low-aSyn overexpressing neurons when cells can barely proliferate exponentially. Conversely, high-aSyn overexpressing cultures grew at high rates while showing enhanced colony formation compared to low-aSyn neurons. Cytotoxicity of aSyn overexpression was indirectly revealed by the addition of pro-oxidant rotenone. Pretreatment with partially reduced graphene oxide, an apoptotic agent, increased toxicity of rotenone in low-aSyn neurons, but, it did not in high-aSyn neurons. Consistent with their enhanced proliferation, high-aSyn neurons showed elevated levels of SMP30, a senescence-marker protein, and the mitosis Ki-67 marker. High-aSyn overexpression conferred to the carcinogenic neurons heightened tumorigenicity and resistance to senescence compared to low-aSyn cells, thus pointing to an inadequate level of aSyn stimulation, rather than the aSyn overload itself, as one of the factors contributing to α-synucleinopathy.

14.
Brain Res ; 1706: 24-31, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30366018

RESUMEN

DYT1 dystonia is a neurological disease caused by a dominant mutation that results in the loss of a glutamic acid in the endoplasmic reticulum-resident protein torsinA. Currently, treatments are symptomatic and only provide partial relief. Multiple reports support the hypothesis that selectively reducing expression of mutant torsinA without affecting levels of the wild type protein should be beneficial. Published cell-based studies support this hypothesis. It is unclear, however, if phenotypes are reversible by targeting the molecular defect once established in vivo. Here, we generated adeno-associated virus encoding artificial microRNA targeting human mutant torsinA and delivered them to the striatum of symptomatic transgenic rats that express the full human TOR1A mutant gene. We achieved efficient suppression of human mutant torsinA expression in DYT1 transgenic rats, partly reversing its accumulation in the nuclear envelope. This intervention rescued PERK-eIF2α pathway dysregulation in striatal projection neurons but not behavioral abnormalities. Moreover, we found abnormal expression of components of dopaminergic neurotransmission in DYT1 rat striatum, which were not normalized by suppressing mutant torsinA expression. Our findings demonstrate the reversibility of translational dysregulation in DYT1 neurons and confirm the presence of abnormal dopaminergic neurotransmission in DYT1 dystonia.


Asunto(s)
Factor 2 Eucariótico de Iniciación/metabolismo , Chaperonas Moleculares/metabolismo , eIF-2 Quinasa/metabolismo , Animales , Cuerpo Estriado/metabolismo , Distonía/genética , Distonía/terapia , Distonía Muscular Deformante/genética , Distonía Muscular Deformante/metabolismo , Retículo Endoplásmico/metabolismo , Factor 2 Eucariótico de Iniciación/fisiología , Femenino , Humanos , Interneuronas/metabolismo , Masculino , Chaperonas Moleculares/genética , Mutación , Neuronas/metabolismo , Interferencia de ARN/fisiología , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Transducción de Señal/genética , eIF-2 Quinasa/fisiología
15.
A A Pract ; 13(5): 176-180, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31045588

RESUMEN

Shoulder surgery in the beach chair position is routinely performed, and central neurological events are rare but potentially devastating. We present a patient with transient neurological deficits after a sudden blood pressure drop with a simultaneous decrease of regional cerebral saturation values registered by cerebral oximetry. We reviewed published cases and proposed possible strategies to prevent the occurrence of similar complications in this context.


Asunto(s)
Ataque Isquémico Transitorio/diagnóstico , Monitoreo Intraoperatorio/métodos , Hombro/cirugía , Anciano , Circulación Cerebrovascular , Femenino , Humanos , Ataque Isquémico Transitorio/sangre , Resultado del Tratamiento
16.
J Clin Anesth ; 53: 40-48, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30292739

RESUMEN

STUDY OBJECTIVES: The aim of this study was to assess the impact of intravenous general anesthesia and controlled hypotension on cerebral saturation (rScO2), cerebral blood flow measured as middle cerebral artery blood flow velocity (Vmax MCA) and neurobehavioral outcome in patients scheduled for shoulder surgery in beach chair position. DESIGN: Prospective, assessor-blinded observational study. SETTING: University hospital, shoulder surgery operating room. PATIENTS: Forty ASA I-II patients scheduled for shoulder surgery in beach chair position and controlled hypotension. INTERVENTIONS: Neurological and neurobehavioral tests were performed prior and the day after surgery. The baseline data for near-infrared spectroscopy, bispectral index, cerebral blood flow, PaCO2 and invasive blood pressure (radial artery) were taken prior anesthesia and after anesthesia induction, after beach chair positioning and all 20 min after surgery start until discharge of the patient. MEASUREMENTS: Neurological and neurobehavioral tests, cerebral saturation (rScO2) using near-infrared spectroscopy, BIS, cerebral blood flow using Doppler of the middle cerebral artery (Vmax MCA), PaCO2 and invasive blood pressure assessed at heart and at the external acoustic meatus level. MAIN RESULTS: The incidence of cerebral desaturation events (CDEs) was 25%. The blood pressure drop 5 min after beach chair position measured at the acoustic meatus level in the CDE group was higher compared to patients without CDEs (p = 0.009) as was the rScO2 (p = 0.039) and the Vmax MCA (p = 0.002). There were no neurological deficits but patients with CDEs showed a greater negative impact on neurobehavioral tests 24 h after surgery compared to patients without CDEs (p = 0.001). CONCLUSIONS: In ASA I-II patients intravenous general anesthesia and controlled hypotension in the beach chair position affects cerebral blood flow and cerebral oxygenation with impact on the neurobehavioral outcome.


Asunto(s)
Anestesia General/efectos adversos , Disfunción Cognitiva/etiología , Hipotensión Controlada/efectos adversos , Hipoxia Encefálica/etiología , Posicionamiento del Paciente/efectos adversos , Adulto , Anestesia General/métodos , Anestésicos Intravenosos/administración & dosificación , Presión Arterial/fisiología , Encéfalo/metabolismo , Circulación Cerebrovascular/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/prevención & control , Femenino , Humanos , Hipotensión Controlada/métodos , Hipoxia Encefálica/diagnóstico , Monitorización Neurofisiológica Intraoperatoria/métodos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Oxígeno/metabolismo , Posicionamiento del Paciente/métodos , Estudios Prospectivos , Articulación del Hombro/cirugía
17.
Cancers (Basel) ; 11(5)2019 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-31035321

RESUMEN

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

18.
Neuroreport ; 19(6): 657-60, 2008 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-18382281

RESUMEN

The possible neuroprotective role of a novel and highly selective cyclooxygenase-2 inhibitor GW637185X was studied in a model of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of nigrostriatal dopaminergic (DA) neurons in the mouse. Stereological and microdensitometrical analysis of nigral tyrosine hydroxylase-immunoreactive cell bodies and striatal tyrosine hydroxylase-immunoreactive terminals, respectively, showed that GW637185X exerted a full protection against MPTP-induced degeneration of the nigro-striatal pathway. In contrast to earlier studies, these findings demonstrate that acute inhibition of cyclooxygenase-2 can result in a full neuroprotective effect not only on nigral DA cell bodies, but also on striatal DA terminals in the mouse MPTP model.


Asunto(s)
Encéfalo/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Intoxicación por MPTP/tratamiento farmacológico , Degeneración Nerviosa/prevención & control , Fármacos Neuroprotectores/farmacología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Dopamina/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Degeneración Nerviosa/inducido químicamente , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Tirosina 3-Monooxigenasa/metabolismo
20.
Physiol Behav ; 94(3): 322-30, 2008 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-18346765

RESUMEN

The aim of our study was to examine the supramammillary (SuM) area involvement in spatial memory. Sprague-Dawley rats with chronically implanted cannula in the supramammillary area were trained in two spatial memory tasks with different memory demands: reference and working memory. In the spatial reference memory task, the rats received microinjections in the SuM area of tetrodotoxin (TTX) (0.5 ng diluted in 0.5 microL of saline) or saline (0.5 microL). The microinjections were administered 30 min before the spatial training (day 4) (to assess the effect on acquisition) and on the following two days (days 5 and 6) the training was conducted without microinjections (to study the effect on consolidation). On the last training day (day 7), in order to assess the retrieval of spatial information, the rats received the microinjections 30 min before the spatial training. The spatial working memory used was a delayed-matching-to-position (DMTP) task. Spatial training was performed for seven days. During the first three days of the spatial training, the rats achieved a good spatial knowledge and learnt the working memory rule necessary to solve the spatial task. On days 4 and 6, the rats received microinjections to study involvement of the SuM area in working memory. The results showed that temporary inactivation of SuM area impairs both the rat's ability to solve a spatial working memory task with DMTP demands and the recovery of spatial information in a spatial reference memory task. We suggest that SuM area is involved in the rearrangement of spatial information during spatial working memory tasks with DMTP memory demands.


Asunto(s)
Tubérculos Mamilares/fisiología , Trastornos de la Memoria/etiología , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Percepción Espacial/fisiología , Anestésicos Locales/toxicidad , Animales , Conducta Animal/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Masculino , Tubérculos Mamilares/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/patología , Memoria a Corto Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Microinyecciones/métodos , Ratas , Ratas Sprague-Dawley , Percepción Espacial/efectos de los fármacos , Tetrodotoxina/toxicidad , Factores de Tiempo
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