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1.
Chin Med J (Engl) ; 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-32032081

RESUMEN

OBJECTIVE: Labor is a complex process and labor pain presents challenges for analgesia. Epidural analgesia (EA) has a well-known analgesic effect and is commonly used during labor. This review summarized frequently encountered and controversial problems surrounding EA during labor, including the labor process and maternal intrapartum fever, to build knowledge in this area. DATA SOURCES: We searched for relevant articles published up to 2019 in PubMed using a range of search terms (eg, "labor pain," "epidural," "analgesia," "labor process," "maternal pyrexia," "intrapartum fever"). STUDY SELECTION: The search returned 835 articles, including randomized control trials, retrospective cohort studies, observational studies, and reviews. The articles were screened by title, abstract, and then full-text, with a sample independently screened by two authors. Thirty-eight articles were included in our final analysis; 20 articles concerned the labor process and 18 reported on maternal pyrexia during EA. RESULTS: Four classic prospective studies including 14,326 participants compared early and delayed initiation of EA by the incidence of cesarean delivery. Early initiation following an analgesia request was preferred. However, it was controversial whether continuous use of EA in the second stage of labor induced adverse maternal and neonatal outcomes due to changes in analgesic and epidural infusion regimens. There was a high incidence of maternal pyrexia in women receiving EA and women with placental inflammation or histologic chorioamnionitis compared with those receiving systemic opioids. CONCLUSIONS: Early EA (cervical dilation ≥1 cm) does not increase the risk for cesarean section. Continuous epidural application of low doses of analgesics and programmed intermittent epidural bolus do not prolong second-stage labor duration or impact maternal and neonatal outcomes. The association between EA and maternal pyrexia remains controversial, but pyrexia is more common with EA than without. A non-infectious inflammatory process is an accepted mechanism of epidural-related maternal fever.

2.
Chin Med J (Engl) ; 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31996543

RESUMEN

BACKGROUND: In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. METHODS: In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 µg norepinephrine (group N; n = 52) or 100 µg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. RESULTS: Compared to group P, women in group N had a higher CO (standardized CO 5.8 ±â€Š0.9 vs. 5.3 ±â€Š1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ±â€Š17.2 vs. 60.0 ±â€Š13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ±â€Š174 vs. 996 ±â€Š182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ±â€Š11.6 vs. 75.0 ±â€Š7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05). CONCLUSIONS: Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

3.
Medicine (Baltimore) ; 98(51): e18311, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31860981

RESUMEN

BACKGROUND: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine. METHODS: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 µg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 µg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected. RESULTS: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ±â€Š11 vs 75 ±â€Š11, P = .04, difference: 4.7 ±â€Š2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ±â€Š9.6 vs 8.4 ±â€Š13.5 bpm, P = .003, difference: 3.1 ±â€Š1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar. CONCLUSION: Infusion of 4 µg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.


Asunto(s)
Anestesia Raquidea/métodos , Cesárea/efectos adversos , Efedrina/uso terapéutico , Hipotensión/prevención & control , Norepinefrina/uso terapéutico , Adulto , Anestesia Raquidea/efectos adversos , Presión Sanguínea/efectos de los fármacos , Cesárea/métodos , Método Doble Ciego , Efedrina/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipotensión/etiología , Infusiones Intravenosas , Norepinefrina/administración & dosificación , Embarazo
4.
Med Sci Monit ; 25: 8797-8806, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31748499

RESUMEN

BACKGROUND The pathogenesis of chemotherapy-induced neuropathy, a dose-dependent adverse effect of cisplatin, involves mitochondrial dysfunction. PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy removes damaged mitochondria under various pathological conditions. The objective of this study was to determine mitophagy status and its effects on mitochondrial function and neuronal cell damage after cisplatin treatment using an in vitro model of cisplatin-induced neurotoxicity. MATERIAL AND METHODS PC12 cells were transfected with Parkin or Parkin siRNA using lentiviral particles and Lipofectamine 3000™, respectively, and then were exposed to 10 µM cisplatin. The expression of autophagic proteins was measured by Western blot analysis. Mitophagy in PC12 cells was detected by confocal microscopy analysis of mitochondria-lysosomes colocalization and autophagic flux. The effects of PINK1/Parkin-mediated mitophagy on cisplatin-induced neurotoxicity were assessed via mitochondrial function, neuritic length, nuclear diameter, and apoptosis. RESULTS Cisplatin activated PINK1/Parkin-mediated mitophagy in PC12 cells. Autophagic flux analysis revealed that cisplatin inhibits the late stage of the autophagic process. The knockdown of Parkin suppressed cisplatin-induced mitophagy, aggravating cisplatin-induced depolarization of mitochondria, cellular ATP deficits, reactive oxygen species outburst, neuritic shortening, nuclear diameter reduction, and apoptosis, while Parkin overexpression enhanced mitophagy and reversed these effects. CONCLUSIONS PINK1/Parkin-regulated mitophagy can protect against cisplatin-related neurotoxicity, suggesting therapeutic enhancement of mitophagy as a potential intervention for cisplatin-induced peripheral neuropathies. The interference of cisplatin with autophagosome-lysosome fusion may be partly responsible for cisplatin-induced neurotoxicity.

5.
Biomed Res Int ; 2019: 7505260, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31032362

RESUMEN

Background: Repeated or continuous chronic psychological stress may induce diverse neuropsychiatric disorders; however, the underlying mechanisms remain unclear. In this study, we explored the expression profiles of long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, in mice after repeated social defeat (RSD) stress to explore their potential involvement in the development of anxiety-like behaviors. Main Methods: RNA-sequencing was used to screen all differentially expressed (DE) lncRNAs and mRNAs between the RSD and control groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for confirmation of the RNA-sequencing results. The function of DE lncRNAs was predicted by Gene Ontology (GO) enrichment and pathway analyses of target mRNAs. In addition, the functional regulatory network of the target mRNAs was constructed to reveal potential relationships between lncRNAs and their target genes with bioinformatics approaches. Key Findings: In mice experiencing RSD, 373 and 454 lncRNAs, along with 1142 and 654, mRNAs were significantly upregulated and downregulated, respectively. The detailed regulatory network included 126 eligible lncRNA-mRNA pairs. Among them, 14 genes such as Arhgef1, Chchd2, Fam107a, Dlg1, Nova2, Dpf1, and Shank3 involved in neurite growth, neural development, and synaptic plasticity were direct targets of the DE lncRNAs. qRT-PCR of four of the DE lncRNAs and mRNAs confirmed the reliability of RNA-sequencing. GO clustering analyses showed that the top enriched biological process, cellular component, and molecular function terms were synaptic transmission, neuron spine, and glutamate receptor binding, respectively. Further, the top three significant enriched pathways were synaptic adhesion-like molecule (SALM) protein interactions at the synapses, trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as glutamate binding, activation of AMPA receptors, and synaptic plasticity. Significance: Hundreds of lncRNAs and mRNAs are dysregulated after RSD, and many of these lncRNAs might participate in the development of anxiety-like behaviors via multiple complex mechanisms such as target regulation. Available informatics evidence highlighted the likely role of synapse dysfunction and abnormal synaptic neurotransmission in these behaviors. Thus, our findings provide potential candidate biomarkers or intervention targets for chronic psychological stress-induced neuropsychiatric disorders.


Asunto(s)
Corteza Prefrontal/metabolismo , ARN Largo no Codificante/genética , Estrés Psicológico/genética , Animales , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes/genética , Humanos , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Corteza Prefrontal/fisiopatología , ARN Mensajero/genética , Análisis de Secuencia de ARN , Estrés Psicológico/fisiopatología
6.
Mol Pain ; 15: 1744806919847366, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30977423

RESUMEN

Neuropathic pain developing after peripheral or central nerve injury is the result of pathological changes generated through complex mechanisms. Disruption in the homeostasis of excitatory and inhibitory neurons within the central nervous system is a crucial factor in the formation of hyperalgesia or allodynia occurring with neuropathic pain. The central GABAergic pathway has received attention for its extensive distribution and function in neural circuits, including the generation and development of neuropathic pain. GABAergic inhibitory changes that occur in the interneurons along descending modulatory and nociceptive pathways in the central nervous system are believed to generate neuronal plasticity, such as synaptic plasticity or functional plasticity of the related genes or proteins, that is the foundation of persistent neuropathic pain. The primary GABAergic plasticity observed in neuropathic pain includes GABAergic synapse homo- and heterosynaptic plasticity, decreased synthesis of GABA, down-expression of glutamic acid decarboxylase and GABA transporter, abnormal expression of NKCC1 or KCC2, and disturbed function of GABA receptors. In this review, we describe possible mechanisms associated with GABAergic plasticity, such as central sensitization and GABAergic interneuron apoptosis, and the epigenetic etiologies of GABAergic plasticity in neuropathic pain. Moreover, we summarize potential therapeutic targets of GABAergic plasticity that may allow for successful relief of hyperalgesia from nerve injury. Finally, we compare the effects of the GABAergic system in neuropathic pain to other types of chronic pain to understand the contribution of GABAergic plasticity to neuropathic pain.

7.
Med Sci Monit ; 25: 1093-1101, 2019 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-30738019

RESUMEN

BACKGROUND This study aimed to compare the efficacy and safety of bolus norepinephrine, phenylephrine, and ephedrine in parturient with preeclampsia who had hypotension during cesarean delivery under spinal anesthesia. MATERIAL AND METHODS One hundred and sixty-six parturient women with preeclampsia who had a baseline systolic blood pressure (SBP) <80% during spinal anesthesia for cesarean section were divided into three treatment groups; bolus norepinephrine 4 µg (group N) (n=56), phenylephrine 50 µg (group P) (n=55), and ephedrine 4 mg (group E) (n=55). Primary outcomes included overall SBP and heart rate (HR) until delivery. Secondary outcomes included the incidence of tachycardia (HR >120 bpm), bradycardia (HR <60 bpm), hypertension (SBP >120% baseline), number of boluses of vasopressor required and episodes of hypotension, maternal side effects, and neonatal outcome. RESULTS Overall HR in group N was significantly increased compared with group P (80.5±12 vs. 76.6±6.9 bpm; P=0.04), and significantly lower compared with group E (80.5±12 vs. 84.9±7.1 bpm; P=0.02). Parturients in group N had fewer episodes of bradycardia compared with group P (3.6% vs. 21.8%; RR=0.26l; 95% CI, 0.07-0.73; P=0.004) and fewer episodes of tachycardia compared with group E (16.1% vs. 36.4%; RR 0.54; 95% CI, 0.29-0.90; P=0.02). CONCLUSIONS A bolus dose of norepinephrine showed similar efficacy to phenylephrine but improved maternal and neonatal safety in parturients with preeclampsia with hypotension during cesarean section under spinal anesthesia.


Asunto(s)
Hipotensión/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Adulto , Anestesia Raquidea , Presión Sanguínea , Cesárea , China , Efedrina/administración & dosificación , Efedrina/uso terapéutico , Femenino , Frecuencia Cardíaca , Humanos , Norepinefrina/administración & dosificación , Norepinefrina/uso terapéutico , Parto , Fenilefrina/administración & dosificación , Fenilefrina/uso terapéutico , Preeclampsia/tratamiento farmacológico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Tratamiento
8.
Medicine (Baltimore) ; 98(5): e14331, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30702617

RESUMEN

BACKGROUND: Phenylephrine is the current "gold standard' vasopressor used to treat maternal hypotension in women undergoing cesarean delivery with spinal anesthesia. Since 2015, various studies have explored the use of norepinephrine to manage maternal hypotension. We conducted this systematic review and meta-analysis of available randomized controlled trials (RCTs) to compare the efficacy and safety of norepinephrine and phenylephrine for the prevention and treatment of maternal hypotension. METHODS: A systematic literature search was conducted using electronic databases, including PubMed, MEDLINE, Embase (Embase.com), and the Cochrane CENTRAL register of controlled trials. Parturients underwent cesarean delivery with spinal anesthesia and received norepinephrine to prevent or treat hypotension were considered. Maternal outcomes, including incidences of hypotension, hypertension, bradycardia, intraoperative nausea and vomiting (IONV), maternal cardiac output (CO), and blood pressure (BP) control precision, as well as neonatal Apgar scores and umbilical cord blood analyses, were compared between groups. RESULTS: Three RCTs in 4 reports published between 2015 and 2018 were finally identified with a total of 294 parturients. We found there was no difference in effectiveness between norepinephrine and phenylephrine for the treatment of maternal hypotension (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.37-1.10, P = .11), and there was no difference in the occurrence of hypertension (OR 0.74; 95% CI 0.33-1.62, P = .45). Of note, compared to the phenylephrine group, parturients in the norepinephrine group were less likely to experience bradycardia (OR 0.29; 95% CI 0.12-0.68, P = .005) and IONV (OR 0.54; 95% CI, 0.29-0.99, P = .04). Further, we did not observe a difference between the two vasopressors in the incidence of neonatal Apgar scores < 7 at 1  and 5 minutes or in umbilical vein (UV) blood gas. However, evidence is insufficient to draw conclusions regarding the greater maternal CO and better BP control precision with the use of norepinephrine. CONCLUSION: This systematic review and meta-analysis shows norepinephrine provides similar efficacy to manage maternal hypotension compared to phenylephrine; additionally, showing advantage regarding certain side effects like bradycardia and IONV reduction. Accordingly, norepinephrine is a promising alternative to phenylephrine. However, before routine clinical application, more studies are warranted.


Asunto(s)
Anestesia Raquidea/efectos adversos , Cesárea/efectos adversos , Hipotensión/tratamiento farmacológico , Norepinefrina/uso terapéutico , Fenilefrina/uso terapéutico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Femenino , Humanos , Hipotensión/etiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/etiología
9.
Mol Pain ; 14: 1744806918798408, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30105933

RESUMEN

Neuropathic pain is a common chronic pain condition with mechanisms far clearly been elucidated. Mounting preclinical and clinical studies have shown neuropathic pain is highly associated with histone acetylation modification, which follows expression regulation of various pain-related molecules such as mGluR1/5, glutamate aspartate transporter, glutamate transporter-1, GAD65, Nav1.8, Kv4.3, µ-opioid receptor, brain-derived neurotrophic factor, and certain chemokines. As two types of pivotal enzymes involved in histone acetylation, histone deacetylases induce histone deacetylation to silence gene expression; in contrast, histone acetyl transferases facilitate histone acetylation to potentiate gene transcription. Accordingly, upregulation or blockade of acetylation may be a promising intervention direction for neuropathic pain treatment. In fact, numerous animal studies have suggested various histone deacetylase inhibitors, Sirt (class III histone deacetylases) activators, and histone acetyl transferases inhibitors are effective in neuropathic pain treatment via targeting specific epigenetic sites. In this review, we summarize the characteristics of the molecules and mechanisms of neuropathy-related acetylation, as well as the acetylation upregulation and blockade for neuropathic pain therapy. Finally, we will discuss the current drug advances focusing on neuropathy-related acetylation along with the underlying treatment mechanisms.


Asunto(s)
Regulación de la Expresión Génica/fisiología , Histonas/metabolismo , Neuralgia/etiología , Traumatismos de los Nervios Periféricos/complicaciones , Acetilación , Animales , Citocinas/genética , Citocinas/metabolismo , Epigenómica , Humanos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo
10.
Exp Mol Med ; 50(2): e445, 2018 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-29504609

RESUMEN

Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory. Correspondingly, dopamine (DA) content shows the reverse characteristic change to MIF with a time-dependent curve in post-surgical behavior. The levels of both MIF and DA are reversed by the MIF tautomerase inhibitor ISO-1, and a negative relationship exists between MIF and DA. The reversed role of ISO-1 also affects tyrosine hydroxylase expression. Furthermore, CCI induces Th promoter CpG site methylation in the L-SC and VTA areas, and this effect could be abated by ISO-1 administration. G9a/SUV39H1 and H3K9me2/H3K9me3 enrichment within the Th promoter region following CCI in the L-SC and VTA was also decreased by ISO-1. In cultured dopaminergic neurons, rMIF enhanced the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.


Asunto(s)
Neuronas Dopaminérgicas/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Neuralgia/etiología , Neuralgia/metabolismo , Traumatismos de los Nervios Periféricos/complicaciones , Traumatismos de los Nervios Periféricos/metabolismo , Animales , Biomarcadores , Islas de CpG , Metilación de ADN , Modelos Animales de Enfermedad , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Expresión Génica , Histonas/genética , Histonas/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Masculino , Ratones , Neurotransmisores/metabolismo , Umbral del Dolor , Traumatismos de los Nervios Periféricos/genética , Regiones Promotoras Genéticas , Neuropatía Ciática/complicaciones , Neuropatía Ciática/metabolismo , Neuropatía Ciática/patología , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismo
11.
Biomed Res Int ; 2018: 1869189, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30687737

RESUMEN

Maternal hypotension commonly occurs during spinal anesthesia for cesarean delivery, with a decrease of systemic vascular resistance recognized as a significant contributor. Accordingly, counteracting this effect with a vasopressor that constricts arterial vessels is appropriate, and the pure α-adrenergic receptor agonist phenylephrine is the current gold standard for treatment. However, phenylephrine is associated with dose-dependent reflex bradycardia and decreased cardiac output, which can endanger the mother and fetus in certain circumstances. In recent years, the older, traditional vasopressor norepinephrine has attracted increasing attention owing to its mild ß-adrenergic effects in addition to its α-adrenergic effects. We search available literature for papers directly related to norepinephrine application in spinal anesthesia for elective cesarean delivery. Nine reports were found for norepinephrine use either alone or compared to phenylephrine. Results show that norepinephrine efficacy in rescuing maternal hypotension is similar to that of phenylephrine without obvious maternal or neonatal adverse outcomes, and with a lower incidence of bradycardia and greater cardiac output. In addition, either computer-controlled closed loop feedback infusion or manually-controlled variable-rate infusion of norepinephrine provides more precise blood pressure management than equipotent phenylephrine infusion or norepinephrine bolus. Thus, based on the limited available literature, norepinephrine appears to be a promising alternative to phenylephrine; however, before routine application begins, more favorable high-quality studies are warranted.


Asunto(s)
Hipotensión/tratamiento farmacológico , Norepinefrina/administración & dosificación , Norepinefrina/efectos adversos , Fenilefrina/administración & dosificación , Vasoconstrictores/administración & dosificación , Vasoconstrictores/efectos adversos , Anestesia Obstétrica/métodos , Anestesia Raquidea/métodos , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Cesárea/métodos , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas/métodos , Infusiones Parenterales/métodos , Embarazo , Resistencia Vascular/efectos de los fármacos
12.
Obstet Gynecol ; 130(5): 1097-1103, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-29016499

RESUMEN

OBJECTIVE: To evaluate whether maintaining a motor-sparing epidural analgesia infusion affects the duration of the second stage of labor in nulliparous parturients compared with a placebo control. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving nulliparous women with term cephalic singleton pregnancies who requested epidural analgesia. All women received epidural analgesia for the first stage of labor using 0.08% ropivacaine with 0.4 micrograms/mL sufentanil with patient-controlled epidural analgesia. At the onset of the second stage of labor, women were randomized to receive a blinded infusion of the same solution or placebo saline infusion. The primary outcome was the duration of the second stage of labor. A sample size of 200 per group (400 total) was planned to identify at least a 15% difference in duration. RESULTS: Between March 2015 and September 2015, 560 patients were screened and 400 patients (200 in each group) completed the study. Using an intention-to-treat analysis, the duration of the second stage was similar between groups (epidural 52±27 minutes compared with saline 51±25 minutes, P=.52). The spontaneous vaginal delivery rate was also similar (epidural 193 [96.5%] compared with saline 198 [99%], P=.17). Pain scores were similar between groups at each measurement during the second stage. More women who received placebo reported satisfaction scores of 8 or less (epidural 32 [16%] compared with saline 61 [30.5%], P=.001). CONCLUSION: Maintaining the infusion of epidural medication had no effect on the duration of the second stage of labor compared with a placebo infusion. Maternal and neonatal outcomes were similar. A low concentration of epidural local anesthetic does not affect the duration of the second stage of labor. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Register, http://www.chictr.org.cn/enindex.aspx, ChiCTR-IOR-15005875.


Asunto(s)
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgésicos/administración & dosificación , Dolor de Parto/tratamiento farmacológico , Segundo Periodo del Trabajo de Parto/efectos de los fármacos , Amidas/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Embarazo , Ropivacaína , Sufentanilo/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento
13.
Mol Pain ; 13: 1744806917729305, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28814147

RESUMEN

Background: Previous studies disclosed the pivotal role of methyltransferase complex G9a/Glp in the pathogenesis of neuropathic hypersensitivity induced by peripheral nerve injury. We observed that higher dose of G9a inhibitor improved nociceptive behavior, but the lower dose worsened pain. The aim of this study is to extensively observe the differential effect of various dosages of G9a/Glp inhibitors on nerve injury-induced allodynia. Materials and methods: After approval by the institutional ethical committee on pain research in conscious animals, C57BL/6 mice were used for measuring nociceptive behavior evoked with von Frey filaments after spared nerve injury. G9a/Glp inhibitor BIX01294 or UNC0638 was injected through the pre-buried intrathecal catheter. The dose­response curves of behavioral changes were depicted when inhibitors were administered once in bolus at the 14th day post spared nerve injury. Withdrawal behaviors were compared during the 49 days' observation window after spared nerve injury with various dosages of inhibitors injected intrathecally for 14 days. Results: Dose­behavior curves of a single bolus of both BIX01294 and UNC0638 displayed a "V"-shaped responses of allodynia withdrawal from lower through higher dose when measured at the 14th day post spared nerve injury. A threshold dose of 10.0 µg for BIX01294 and 80.0 µg for UNC0638 significantly worsened allodynia. However, daily bolus intrathecal injection for 14 days of both inhibitors lower or higher than these threshold doses prominently improved nociceptive behavior, producing contrasting results. On the same animal, threshold dose followed by a lower or higher dose with a 14 days' interval also showed contrast effect on nociceptive behavior, and a lower or higher dose to threshold dose sequence of inhibitor administration was vice versa. Conclusions: Methyltransferase complex G9a/Glp has a threshold role in mediating peripheral nerve injury-induced hypersensitivity at its low level versus high level through inhibiting and facilitating the nociceptive behavior, respectively.


Asunto(s)
Hiperalgesia/tratamiento farmacológico , Hipersensibilidad/complicaciones , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Quinazolinas/farmacología , Animales , Modelos Animales de Enfermedad , N-Metiltransferasa de Histona-Lisina/efectos de los fármacos , Hipersensibilidad/etiología , Inyecciones Espinales/métodos , Masculino , Ratones Endogámicos C57BL , Dolor/tratamiento farmacológico , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Traumatismos de los Nervios Periféricos/complicaciones
14.
Mol Pain ; 122016.
Artículo en Inglés | MEDLINE | ID: mdl-27562335

RESUMEN

The neural balance between facilitation and inhibition determines the final tendency of central sensitization. Nerve injury-induced hypersensitivity was considered as the results from the enhanced ascending facilitation and the diminished descending inhibition. The role of dopaminergic transmission in the descending inhibition has been well documented, but its underlying molecular mechanisms are unclear. Previous studies demonstrated that the lysine dimethyltransferase G9a/G9a-like protein (Glp) complex plays a critical role in cocaine-induced central plasticity, and given cocaine's role in the nerve system is relied on its function on dopamine system, we herein proposed that the reduced inhibition of dopaminergic transmission was from the downregulation of tyrosine hydroxylase expression by G9a/Glp complex through methylating its gene Th After approval by the Animal Care and Use Committee, C57BL/6 mice were used for pain behavior using von Frey after spared nerve injury, and Th CpG islands methylation was measured using bisulfite sequencing at different nerve areas. The inhibitor of G9a/Glp, BIX 01294, was administered intraventricularly daily with bolus injection. The protein levels of G9a, Glp, and tyrosine hydroxylase were measured with immunoblotting. Dopamine levels were detected using high-performance liquid chromatography. The expression of G9a but not Glp was upregulated in ventral tegmental area at post-injury day 4 till day 49 (the last day of the behavioral test). Correspondingly, the Th CpG methylation is increased, but the tyrosine hydroxylase expression was downregulated and the dopamine level was decreased. After the intracerebroventriclar injection of BIX 01294 since the post-injury days 7 and 14 for consecutive three days, three weeks, and six weeks, the expression of tyrosine hydroxylase was upregulated with a significant decrease in Th methylation and increase in dopamine level. Moreover, the pain after G9a/Glp inhibitor was attenuated significantly. In sum, methytransferase G9a/Glp complex partially controls dopaminergic transmission by methylating Th in peripheral nerve injury-induced neuropathic pain.


Asunto(s)
Encéfalo/metabolismo , Dopamina/metabolismo , Regulación hacia Abajo/fisiología , N-Metiltransferasa de Histona-Lisina/metabolismo , Hipersensibilidad/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Animales , Azepinas/farmacología , Cromatografía Líquida de Alta Presión , Islas de CpG/efectos de los fármacos , Islas de CpG/genética , Metilación de ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/etiología , Hipersensibilidad/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Quinazolinas/farmacología , Neuropatía Ciática/complicaciones , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Tirosina 3-Monooxigenasa/genética
15.
Ying Yong Sheng Tai Xue Bao ; 27(2): 345-53, 2016 Feb.
Artículo en Chino | MEDLINE | ID: mdl-27396104

RESUMEN

Independent measurements of stem sap flow in stems of Calligonum mongolicum and environmental variables using commercial sap flow gauges and a micrometeorological monitoring system, respectively, were made to simulate the variation of sap flow density in the middle range of Hexi Corridor, Northwest China during June to September, 2014. The results showed that the diurnal process of sap flow density in C. mongolicum showed a broad unimodal change, and the maximum sap flow density reached about 30 minutes after the maximum of photosynthetically active radiation (PAR) , while about 120 minutes before the maximum of temperature and vapor pressure deficit (VPD). During the studying period, sap flow density closely related with atmosphere evapor-transpiration demand, and mainly affected by PAR, temperature and VPD. The model was developed which directly linked the sap flow density with climatic variables, and good correlation between measured and simulated sap flow density was observed in different climate conditions. The accuracy of simulation was significantly improved if the time-lag effect was taken into consideration, while this model underestimated low and nighttime sap flow densities, which was probably caused by plant physiological characteristics.


Asunto(s)
Clima Desértico , Transpiración de Plantas , Polygonaceae/fisiología , Agua/fisiología , Atmósfera , China , Fotosíntesis , Tallos de la Planta/fisiología , Temperatura Ambiental
16.
Pharmacol Rep ; 68(4): 686-91, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27116700

RESUMEN

Opioids are still the most popular form of pain treatment, but many unavoidable side effects make opioids a big challenge in effective pain management. Opioid-induced hyperalgesia (OIH), a paradoxical phenomenon, portrays an increased sensitivity to harmful stimuli caused by opioid exposure. Changes in the neural modulation are considered a major contributor to the development of OIH. Activation of opioid receptors (ORs) and corresponding downstream molecules are the vital composition of functional performance of opioids. Increasing interests were proposed of the interaction between ORs and other neural transmitter systems such as glutamatergic, GABAergic and adrenergic ones to the genesis of OIH. G protein coupled µ-opioid receptor (MOR) was studied comprehensively on its role in the development of OIH. In addition to the relationship between MOR and other neurotransmitter receptors, a new intracellular MOR that has six transmembrane (6TM) domains was identified, and found to perform a pro-nociceptive task in contrast to the counterpart 7TM isoform. A mechanistic model of OIH in which both 6TM and 7TM MORs undergoing membrane redistribution upon opioid exposure is proposed which eventually facilitates the neurons more sensitive to nociceptive stimulation than that of the preceding opioid exposure.


Asunto(s)
Analgésicos Opioides/farmacología , Hiperalgesia/metabolismo , Receptores Opioides mu/efectos de los fármacos , Receptores Opioides mu/metabolismo , Humanos , Hiperalgesia/inducido químicamente , Isoformas de Proteínas/metabolismo
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(8): 2590-5, 2016 Aug.
Artículo en Chino | MEDLINE | ID: mdl-30074370

RESUMEN

Three-dimensional fluorescence spectroscopy is an emerging sensitive technology to detect organic pollution in water bodies. Based on this technique, a research group from Tsinghua University developed a novel instrument as a tool of pollution early-warning and pollution source identification,it has been put into use in A city in South China, for aqueous fingerprint monitoring and pollution sources identification under abnormal conditions. As a new monitoring method, it broke the limitation that traditional water quality monitoring technology could not provide directivity information of pollution source, and could detect abnormity of water quality quickly and identify pollution source accurately. In this paper, the process to identify pollution source during an abnormity incident of water quality in S River captured by the instrument was studied. When the instrument captured unidentified aqueous fingerprints during on-line monitoring, pollution intrusion process was inferred based on the variation of aqueous fingerprint figure and peak intensity. Then the pollution source identification was achieved by comparing the fingerprints between the polluted water body and possible pollution sources by the instrument. The source identification was verified with the changes of other water quality parameters such as pH, aniline, TOC and TN. The results showed that this early-warning and pollution source identification technique can quickly detect and release warning of abnormity of water quality and identify pollution sources accurately via monitoring aqueous fingerprints. The abnormity incident studied in this paper might be caused by dumping raw materials by a chemical plant located in upstream of the river.

18.
Medicine (Baltimore) ; 94(43): e1882, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26512604

RESUMEN

To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control.After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 µg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes.A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8-2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0-2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ±â€Š2.06) than that in the combination group ($9.76 ±â€Š3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes.The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids.


Asunto(s)
Amidas/administración & dosificación , Anestesia Epidural , Trabajo de Parto , Sufentanilo/administración & dosificación , Adulto , Amidas/efectos adversos , Femenino , Humanos , Embarazo , Ropivacaína , Sufentanilo/efectos adversos
19.
Med Sci Monit Basic Res ; 20: 164-9, 2014 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-25348794

RESUMEN

BACKGROUND: Social defect and chronic pain are 2 major health problems and recent data has demonstrated that they generally exist concurrently. However, a powerful evaluation model on the behavioral change is lacking. This study was designed to evaluate the behavioral curves using a statistically modeled trajectory analysis in neuropathic animals with or without social defect exposure. MATERIAL/METHODS: After approval by the institutional animal care committee, Sprague-Dawley rats were randomized into different interventional groups with 15 animals each. Sprague-Dawley rats underwent spared nerve injury (SNI) to establish the neuropathic pain model, of which the mechanical withdrawal threshold was measured using von Frey filaments for a period of 105 days. Otherwise, a modified version of the resident (Long-Evans rats)-intruder paradigm was applied to produce a social defect animal model through the elevated plus maze (EPM). After raw data collection, we modeled them into a powerful statistical effects analysis to build up the behavioral change tendency in single SNI or in combined SNI and social defect animals. RESULTS: The random and fixed effects analyses of the pain behavior after SNI were successfully modeled and demonstrated a gradient recovery tendency during the 15-week post-injury observational period. Correspondingly, SNI rats exhibited increased social defected symptoms, as indicated by the increased anxiety-like behavior in the EPM test. In addition, continuous social defect stress for 5 days or 10 days, respectively, partially attenuated and exacerbated SNI-induced allodynia in both random and fixed effects models. Five days but not 10 days social defect ameliorated SNI-associated anxiety-like behavior. CONCLUSIONS: These data suggest that statistically powerful analysis of nerve injury-induced neuropathic pain is a highly sensitive model to determine the behavioral change tendency and distinguish them among behavior curves with or without social defect, and the combination of SNI with resident-intruder paradigm may be a suitable model for behavior evaluation of neuropathic pain with social defect.


Asunto(s)
Conducta Animal , Neuralgia/patología , Conducta Social , Animales , Modelos Animales de Enfermedad , Masculino , Ratas Long-Evans , Ratas Sprague-Dawley , Nervio Ciático/lesiones , Nervio Ciático/patología
20.
Med Sci Monit ; 20: 1908-12, 2014 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-25306127

RESUMEN

Postoperative cognitive dysfunction (POCD) is a subtle disorder of thought processes, which may influence isolated domains of cognition and has a significant impact on patient health. The reported incidence of POCD varies enormously due to lack of formal criteria for the assessment and diagnosis of POCD. The significant risk factors of developing POCD mainly include larger and more invasive operations, duration of anesthesia, advanced age, history of alcohol abuse, use of anticholinergic medications, and other factors. The release of cytokines due to the systemic stress response caused by anesthesia and surgical procedures might induce the changes of brain function and be involved in the development of postoperative cognitive dysfunction. The strategies for management of POCD should be a multimodal approach involving close cooperation between the anesthesiologist, surgeon, geriatricians, and family members to promote early rehabilitation and avoid loss of independence in these patients.


Asunto(s)
Trastornos del Conocimiento/complicaciones , Complicaciones Posoperatorias , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/prevención & control , Humanos , Incidencia , Factores de Riesgo
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