RESUMEN
Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8â¶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.
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Displasia Broncopulmonar , Conducto Arterioso Permeable , Hipertensión Pulmonar , Neumonía Asociada al Ventilador , Sepsis , Lactante , Masculino , Recién Nacido , Humanos , Embarazo , Femenino , Displasia Broncopulmonar/epidemiología , Recien Nacido Prematuro , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/epidemiología , Estudios Retrospectivos , Nomogramas , Conducto Arterioso Permeable/complicaciones , Conducto Arterioso Permeable/epidemiología , Neumonía Asociada al Ventilador/complicaciones , Cesárea/efectos adversos , Edad Gestacional , Factores de RiesgoRESUMEN
Objective: To investigate the current situation of human milk (HM) feeding in hospitalized very low and extremely low birth weight infants. Methods: The study retrospectively extracted the data of 601 infants with birth weight <1 500 g, and admitted within 24 hours after birth to the Neonatal Intensive Care Unit of Nanjing Maternity and Child Health Care Hospital from January 2016 to December 2018. The infants were grouped into exclusive mother's-own-milk (MOM) group, donor human milk (DHM) group (partial or none MOM), and mixed (HM and formula) feeding group according to the feeding strategy. Qualitative and quantitative variables in the three groups were compared with One-way ANOVA, Kruskal-Wallis test, Chi-square test or Fisher exact test. Kappa and McNemar test were used for consistency testing. Results: Among the 601 infants (309 boys and 292 girls), 6 (1.0%) infants had never been fed with MOM. The gestational age and birth weight were (29.3±1.9) weeks and 1 260(1 115, 1 400) g in 601 infants. A total of 8 (1.3%) infants were grouped into MOM group, 542 (90.2%) were grouped into DHM group, and 51 (8.5%) were grouped into mixed feeding group. The percentage of enteral feedings with MOM in the stage of hospitalization 1-7 d, 8-14 d and 15-28 d were 73.6% (42.9%, 86.7%), 97.5% (78.6%, 100.0%) and 99.3% (93.0%, 100.0%), respectively (H=414.95, P<0.01), and the pairwise comparison suggested that the stage of hospitalization 1-7 d was the lowest (adjusted both P<0.05). The average weight adjusted daily dose of MOM were 9.7 (4.3, 18.2), 59.1 (26.5, 93.5) and 116.0 (60.3, 142.6) ml/(kg·d) in the stage of hospitalization 1-7 d, 8-14 d and 15-28 d, respectively (H=759.75, P<0.01), and the pairwise comparison suggested that the stage of hospitalization 1-7 d was the lowest (adjusted both P<0.05). The weight adjusted daily dose of MOM in exclusive MOM group, DHM and Mixed feeding group were 95.2 (40.0, 117.2), 82.9(53.6, 103.1) and 55.7 (16.6, 97.5) ml/(kg·d), respectively (H=10.78, P=0.005).Additionally, the percentage and weight adjusted daily dose of MOM showed a general consistency of 0.703 (P>0.05, Kappa=0.408). Conclusions: The rate of exclusive MOM feeding is low, especially during the first 7 days of hospitalization. The percentage of total enteral feedings with MOM and the average weight adjusted daily dose of MOM can well evaluate the situation of HM feeding during hospitalization quantitively.
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Fenómenos Fisiológicos Nutricionales del Lactante , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido de muy Bajo Peso , Leche Humana , Femenino , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Embarazo , Estudios RetrospectivosRESUMEN
Previous studies have demonstrated that the red nucleus (RN) participates in the modulation of neuropathic pain and plays both a facilitated role by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), and an inhibitory role through the anti-inflammatory cytokine IL-10. In this study, we sought to investigate the expressions and roles of transforming growth factor-beta (TGF-ß), a potent anti-inflammatory cytokine, as well as its type 1 receptor (TGF-ß-R1) in the RN in normal and neuropathic pain rats. Immunohistochemistry showed that TGF-ß and TGF-ß-R1 were constitutively expressed in the RN of normal rats, and co-localized with neurons and all three glial cell types, astrocytes, microglia and oligodendrocytes. Following spared nerve injury (SNI), the expression levels of TGF-ß and TGF-ß-R1 were significantly down-regulated in the RN contralateral (but not ipsilateral) to the nerve injury side of rats at one week and reached the lowest level at two weeks after SNI, and both of them were co-localized with neurons and oligodendrocytes but not with astrocytes and microglia. Microinjection of different doses of anti-TGF-ß antibody (250, 125, 50 ng) into the unilateral RN of normal rats dose-dependently decreased the mechanical withdrawal threshold of contralateral (but not ipsilateral) hind paw and induced significant mechanical hypersensitivity, which was similar to mechanical allodynia induced by peripheral nerve injury. In contrast, microinjection of different doses of recombinant rat TGF-ß1 (500, 250, 100 ng) into the RN contralateral to the nerve injury side of SNI rats dose-dependently increased the paw withdrawal threshold and significantly alleviated mechanical allodynia induced by SNI. These results suggest that TGF-ß in the RN participates in nociceptive processing and plays antinociceptive effects under normal physiological condition and in the development of neuropathic pain induced by SNI.
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Neuralgia/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Núcleo Rojo/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Analgésicos/administración & dosificación , Animales , Anticuerpos/administración & dosificación , Astrocitos/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Masculino , Microglía/metabolismo , Microinyecciones , Neuralgia/tratamiento farmacológico , Neuronas/metabolismo , Oligodendroglía/metabolismo , Umbral del Dolor/efectos de los fármacos , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/inmunología , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Proteínas Recombinantes/administración & dosificación , Núcleo Rojo/efectos de los fármacos , Nervio Ciático/lesiones , Factor de Crecimiento Transformador beta/administración & dosificaciónRESUMEN
Traumatic shock is a serious threat to life and health. The aim of this study is to investigate the effect of different resuscitation fluid compositions on the emergency resuscitation for patients with traumatic shock. Sixty patients were enrolled and divided into two groups, Group A and Group B. The patients in Group A were treated with resuscitation fluid, with 2:1 ratio of crystal (0.9% sodium chloride injection) and colloid (hydroxyethyl starch 40 injection). The patients in Group B were treated with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40). Both vital signs and fluid dosage were monitored and recorded. At the beginning of resuscitation (T0) and 30 min (T1), 60 min (T2) and 120 min (T3) after resuscitation, indicator parameters including hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), arterial blood lacic acid (LA) and C-reactive protein (CRP) were monitored and recorded. Tissue oxygenation and hemodynamic profile were also analyzed. At T1, T2and T3after fluid resuscitation, the heart rates of the patients in Group B were lower than those in Group A, whereas the average arterial pressure in Group B was significantly higher than that in Group A. Notably, significant decreases of HB and HCT were detected at T1, T2and T3compared with T0 in Group A. In contrast, no significant difference was shown in detected HCT at T2and T3compared with T0 in Group B, while the detected HB value was smaller. a statistically significant decrease of LA was detected at T1, T2and T3in Group A and Group B compared with that at T0. At T2and T3in Group A and Group B, a statistically significant increase of PT was detected compared with the beginning of resuscitation. At T2and T3after resuscitation, CRP in both Group A and Group B was significantly increased compared with that upon admission to hospital, and was lower in Group B than in Group A.
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Resucitación , Choque Traumático/terapia , Urgencias Médicas , Femenino , Hematócrito , Hemoglobinas/análisis , Humanos , Derivados de Hidroxietil Almidón/administración & dosificación , Masculino , Solución Salina Hipertónica/administración & dosificación , Choque Traumático/sangreRESUMEN
Cervical cancer is a multifactorial disease involving a complex interplay between genetic and environmental factors. An important role of HIF-1α in cervical cancer carcinogenesis has been studied by multiple researches. We hypothesized that there is a possible association between HIF-1α gene polymorphisms and the risk of cervical cancer in Chinese women. In a case-control study of 518 cervical cancer patients and 553 cancer-free controls, we genotyped three single-nucleotide polymorphisms (SNPs) (rs11549465, rs11549467 and rs2057482) of HIF-1α using the TaqMan SNP Genotyping Assays and assessed its associations with the cervical cancer risk. Besides, 17 cervical cancer tissues were used to assess the expression of the mature mRNA expression of HIF-1α by real-time quantitative reverse transcription PCR. We found that a significantly increased risk of cervical cancer was associated with the CC genotype of rs2057482 in the 3´-untranslated region (3'-UTR) of HIF-1α (odds ratio (OR), 1.44; 95% confidence interval (CI), 1.11-1.88), compared with the CT/TT genotypes. Moreover, the carriers of CT/TT genotypes had significantly decreased HIF-1α mRNA expression levels compared to those with CC genotype. No association was observed between the two polymorphisms (rs11549465, rs11549467) and cervical cancer risk. So that, our results provided the first insight into rs2057482 polymorphism of in the 3´-untranslated region of HIF-1α contributed to the risk of cervical cancer in a Chinese population and thus may serve as a reliable predictive factor of cervical cancer.
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Regiones no Traducidas 3'/genética , Predisposición Genética a la Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , ARN Mensajero/análisis , Riesgo , Neoplasias del Cuello Uterino/etiologíaRESUMEN
This report describes the association between birth weight (BW) and obesity. Screening of 478 citations from five electronic databases resulted in the inclusion of 33 studies, most of medium quality. The meta-analysis included 20 of these published studies. The 13 remaining articles did not provide sufficient dichotomous data and were systematically reviewed, revealing results consistent with the meta-analysis. Our results revealed that high BW (>4000 g) was associated with increased risk of obesity (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.91-2.24) compared with subjects with BW ≤ 4000 g. Low BW (<2500 g) was associated with decreased risk of obesity (OR, 0.61; 95% CI, 0.46-0.80) compared with subjects with BW ≥ 2500 g. However, when two studies exhibited selection bias were removed, the results indicated no significant association between low BW and obesity (OR, 0.77; 95% CI, 0.58-1.04). Sensitivity analyses showed that differences in the study design, sample size and quality grade of the study had an effect on the low BW/obesity association, which low BW was not associated with the risk of obesity in cohort studies, studies with large sample sizes and studies with high quality grades. Pooled results were similar when normal birth weight (2500-4000 g) was used as the reference category. Subgroup analyses based on different growth and developmental stages (pre-school children, school children and adolescents) also revealed that high BW was associated with increased risk of obesity from childhood to early adulthood. No significant evidence of publication bias was present. These results suggest that high BW is associated with increased risk of obesity and may serve as a mediator between prenatal influences and later disease risk.
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Peso al Nacer , Obesidad/epidemiología , Adolescente , Niño , Preescolar , Intervalos de Confianza , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Oportunidad Relativa , Factores de RiesgoRESUMEN
We performed a systematic review describing obesity/intelligent quotient (IQ) association, particularly childhood IQ in relation to adulthood obesity. After screening 883 citations from five electronic databases, we included 26 studies, most of medium quality. The weighted mean difference (WMD) of the full IQ (FIQ)/obesity association in the pre-school children was -15.1 (P > 0.05). Compared with controls, the WMD of FIQ and performance IQ of obese children were -2.8 and -10.0, respectively (P < 0.05), and the WMD of verbal IQ was -7.01 (P > 0.05). With increasing obesity, the FIQ in pre-school children declined, with a significant difference for severely obese children and FIQ. In pubertal children, a slightly different effect of FIQ and obesity emerged. Two studies reported an inverse FIQ/obesity association in adults, but it was non-significant after adjusting for educational attainment. Four papers found that childhood FIQ was inversely associated with adult body mass index, but after adjusting for education, became null. Overall there was an inverse FIQ/obesity association, except in pre-school children. However, after adjusting for educational attainment, FIQ/obesity association was not significantly different. A lower FIQ in childhood was associated with obesity in later adulthood perhaps with educational level mediating the persistence of obesity in later life.
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Inteligencia/fisiología , Obesidad/psicología , Adolescente , Factores de Edad , Niño , Preescolar , Escolaridad , Femenino , Humanos , Pruebas de Inteligencia , MasculinoRESUMEN
Hydrogen sulfide (H2S) is a naturally occurring gas that may act as an endogenous signaling molecule. In the brain, H2S is mainly produced by cystathionine beta-synthase (CBS) and its cellular effects have been attributed to interactions with N-methyl-D-aspartate (NMDA) receptors and cyclic adenosine 3',5'-monophosphate (cAMP). In contrast, direct vasodilator actions of H2S are most probably mediated by opening smooth muscle ATP-sensitive K+ (K(ATP)) channels. In the hypothalamus, K(ATP) channel-dependent mechanisms are involved in CNS-mediated regulation of blood pressure. In this report, we investigated the hypothesis that H2S may act via K(ATP) channels in the hypothalamus to regulate blood pressure. Mean arterial blood pressure (MAP) and heart rate were monitored in freely moving rats via a pressure transducer placed in the femoral artery. Drugs were infused via a cannula placed in the posterior hypothalamus. Infusion of 200 microM sodium hydrogen sulfide (NaHS), an H2S donor, into the hypothalamus of freely moving rats reduced MAP and heart rate. Infusion of 300 nM to 3 microM gliclazide dose-dependently blocked the effect of 200 microM NaHS. Infusion of the CBS activator, s-adenosyl-L-methionine (0.1 mM and 1 mM), likewise decreased MAP. Infusion of the CBS inhibitors aminooxyacetic acid (10 mM) and hydroxylamine (20 mM) increased MAP but did not block the effects of infusion of 200 microM NaHS. These data indicate that actions of H2S in the hypothalamus decrease blood pressure and heart rate in freely moving rats. This effect appears to be mediated by a K(ATP) channel-dependent mechanism and mimicked by endogenous H2S.
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Adenosina Trifosfato/metabolismo , Presión Sanguínea/fisiología , Sulfuro de Hidrógeno/metabolismo , Hipotálamo/metabolismo , Canales de Potasio/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Cistationina betasintasa/efectos de los fármacos , Cistationina betasintasa/metabolismo , Inhibidores Enzimáticos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hipotálamo/efectos de los fármacos , Masculino , Movimiento , Canales de Potasio/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Survivin, a member of apoptosis protein inhibitor family, is upregulated in various malignancies, especially in chemotherapy- and/or radiation-resistant cell lines. In this study, the correlation between the level of survivin expression and degree of apoptosis was investigated in three ovarian cancer lines (two chemoresistant cell lines SKOV-3 and OVCAR-3, as well as one chemosensitive cell line OV2008) treated with 5 microg/ml of cisdiamminedichloroplatinum (cisplatin, CDDP) for 24 h, 2 Gy of (60)Co irradiation, or 5 microg/ml CDDP for 3 h plus 2 Gy of (60)Co, respectively. We also evaluated the survivin mRNA abundance in patients with advanced ovarian cancers during CDDP treatment. In the ovarian cancer cell lines, survivin mRNA abundance and protein contents were significantly increased after the treatments while the apoptotic rates did not change in SKOV-3 and OVCAR-3. Moreover, in OVA2008 cells the expression of survivin decreased and the apoptotic rate significantly increased after CDDP and combined treatments. Survivin mRNA was not detectable in normal ovarian tissues and benign ovarian tumors. However, it was observed in the resected tumor specimens from 20 patients with advanced ovarian cancer. These results suggested that survivin may play an important role in the resistance to chemotherapy and radiotherapy in ovarian cancer cell lines and in the progression of ovarian tumors. Survivin may also provide a pivotal prognostic implication for epithelial ovarian carcinomas.
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Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Neoplasias Ováricas/genética , Adulto , Anciano , Apoptosis , Proliferación Celular , Terapia Combinada , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/radioterapia , ARN Mensajero/genética , SurvivinRESUMEN
An extracellular lipase from Pseudomonas sp. was purified to homogeneity by extraction, Bio-gel P-10 chromatography and Superose 12B chromatography, and a 37-fold purification was attained. The purified enzyme showed a single band when it was subjected to SDS/PAGE and isoelectric focusing. The SDS/PAGE electrophoresis indicated a molecular mass of 30 kDa for this lipase. Its isoelectric point was 4.5. The optimum pH and temperature for hydrolysis were 7.0-9.0 and 45-60 degrees C, respectively. The enzyme was stable between pHs 6 and 12 and below 60 degrees C. In the presence of Ca(2+) and Bi(3+), the lipase activity was dramatically enhanced by 250% and 154%, respectively. Fe(3+), Fe(2+), Al(3+), Zn(2+) and Mn(2+) could inhibit this lipase, but Ag(+) and Pb(2+) showed no influence on hydrolysis activity. Properties of purified lipase for lactonization in organic solvent were also determined. The purified lipase displayed the characteristic of 'pH memory' in organic media. This lipase was also thermostable in organic solvent with an optimum temperature range from 45 to 60 degrees C. Salt dramatically affected the lactonization activity of this lipase.
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Lipasa/aislamiento & purificación , Pseudomonas/enzimología , Cromatografía por Intercambio Iónico , Medios de Cultivo , Electroforesis en Gel de Poliacrilamida , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Focalización Isoeléctrica , Lipasa/metabolismo , TemperaturaAsunto(s)
Catecolaminas/metabolismo , Unión Neuroefectora/fisiología , Neuropéptido Y/farmacología , Neuropéptido Y/fisiología , Norepinefrina/metabolismo , Adenosina Trifosfato/fisiología , Animales , Arterias/inervación , Calcio/metabolismo , Calcio/fisiología , Canales de Calcio/fisiología , Estimulación Eléctrica , Hipertensión/fisiopatología , Unión Neuroefectora/efectos de los fármacos , Células PC12 , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
Pheochromocytoma (PC)-12 cells express Y1, Y2, and Y3 neuropeptide Y (NPY) receptors when differentiated with nerve growth factor (NGF). The present work evaluated NGF-differentiated PC-12 cells as a model system to study modulation of NPY release by NPY autoreceptors. We demonstrated that both K+ and nicotine stimulated concomitant release of NPY and dopamine from differentiated PC-12 cells. We also showed in this study that NPY release from PC-12 cells was attenuated in a concentration-dependent manner by peptide YY (PYY)-(13-36), a selective agonist for the Y2 type of NPY receptors. This result demonstrated that NPY release could be modulated by NPY autoreceptors of the Y2 subtype. The inhibitory action of PYY-(13-36) may be mediated at least in part by inhibition of N-type Ca2+ channels, because PYY-(13-36) could not produce further inhibitory effects in the presence of a maximum effective concentration of omega-conotoxin, an N-type Ca2+-channel blocker. The inhibition by PYY-(13-36) could be blocked by pretreatment of cells with pertussis toxin, suggesting that an inhibitory GTP-binding protein was involved. Furthermore, the function of NPY autoreceptors could be modulated by other receptors such as beta-adrenergic and ATP receptors. The evoked release of NPY was also attenuated by ATP and adenosine, which have been shown to be colocalized and coreleased with NPY from sympathetic nerve terminals. These results suggest that PC-12 cells differentiated with NGF may be an ideal model to study regulatory mechanisms of NPY release and that autoreceptor-mediated regulation of NPY release appears to act through the Y2 subtype of the NPY receptor.
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Autorreceptores/fisiología , Neuropéptido Y/antagonistas & inhibidores , Células PC12/metabolismo , Receptores de Neuropéptido/fisiología , Animales , Técnicas Inmunológicas , Neuronas/metabolismo , Neurotransmisores/farmacología , Ratas , Receptores de Neurotransmisores/fisiología , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/metabolismoRESUMEN
A study hes been made on the essential oil from the crude drug Peilan (Eupatorium fortunei) and the plants E. japonicum, E. chinense and E. cannabinum. 71 constituents have been identified by GC-MS. Quantitative analysis has been carried out by GC. The study provides scientific methods for the identification of the crude drug "Peilan" and the quality control of the fresh and dried "Peilan".
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Compuestos Bicíclicos con Puentes/análisis , Medicamentos Herbarios Chinos/química , Aceites Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Control de Calidad , Especificidad de la EspecieRESUMEN
Intrathecal administration of 1-100 pmol endothelin-1 in urethan-anesthetized rats elicited a dose-dependent decrease in arterial pressure and a modest bradycardia. The depressor response was associated with a sustained hindquarters vasodilation and a modest transient mesenteric vasoconstriction, indicating disparate effects on regional vascular resistance. In contrast, renal sympathetic nerve activity was unaffected except at the highest dose of endothelin-1 (100 pmol). The depressor effect of intrathecal endothelin is unlikely to be due to spinal ischemia produced by vasoconstriction, since a much greater dose of endothelin was needed to produce an increase in spinal vascular resistance compared with the dose necessary to produce hindquarters vasodilation and the depressor effect. Unlike intravenous administration, intrathecal endothelin-1 and endothelin-3 produced indistinguishable effects on arterial pressure, heart rate, renal sympathetic nerve activity, spinal blood flow, and spinal vascular resistance, suggesting that the spinal neuronal endothelin receptors may be less selective than those in the blood vessels. The centrally mediated depressor effect and the selective regional hemodynamic actions of intrathecal endothelin suggest a role of spinal endothelin in regulating cardiovascular function.
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Presión Sanguínea/efectos de los fármacos , Endotelinas/farmacología , Anestesia , Animales , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Espinales , Riñón/inervación , Microcirculación/efectos de los fármacos , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas , Médula Espinal/irrigación sanguínea , Sistema Nervioso Simpático/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
The hemodynamic effects of sarafotoxin S6b (SRT) and endothelin-1 (ET-1) were studied in conscious, freely moving rats. Intravenous bolus administration of ET-1 produced an initial transient depressor response and skeletal muscle (hindquarters) vasodilation. This depressor activity was not observed after i.v. SRT except at a high dose. The initial fall in blood pressure was followed by a sustained pressor response and an increase in total peripheral resistance which were mediated, at least partially, by visceral (mesenteric) and skeletal muscle (hindquarters) vasoconstriction. The durations of the pressor responses and times required to achieve the peak pressor effects (peak time) were greater for ET-1 as compared to SRT. The results of qualitatively similar sustained hemodynamic effects and the strong correlation between the amplitude of the responses to ET-1 and SRT in individual rats suggest that the sustained pressor responses to these peptides are mediated by the same receptors, although the potency was significantly greater for ET-1 than for SRT. Furthermore, the initial depressor and sustained pressor responses appear to be mediated by distinct receptor subtypes inasmuch as the same dose of ET-1 was required for both vasodilator and vasoconstrictor activity but a higher dose of SRT was required to elicit its vasodilator as compared to constrictor effects. Thus, SRT may have relatively lower affinity for receptors mediating its initial hemodynamic responses whereas ET-1 binds with equal affinity to both receptors. These potent and vascular specific hemodynamic actions suggest a role of endothelin in regulating cardiovascular function.
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Endotelinas/farmacología , Hemodinámica/efectos de los fármacos , Vasoconstrictores/farmacología , Venenos de Víboras/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endotelinas/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Nifedipino/farmacología , Ratas , Ratas Endogámicas , Factores de Tiempo , Resistencia Vascular/efectos de los fármacos , Venenos de Víboras/administración & dosificaciónRESUMEN
In the isolated perfused rat mesenteric vascular bed pretreated with guanethidine and precontracted with methoxamine, periarterial nerve stimulation elicited a frequency-dependent and endothelium-independent vasodilation. The sustained vasodilation was slow-onset and reversible. It was resistant to propranolol or atropine but sensitive to tetrodotoxin and capsaicin suggesting that this is a nonadrenergic-noncholinergic vasodilation and is a neurogenic response. The vasodilation was abolished by anti-serum against calcitonin-gene related peptide (CGRP) in a concentration-dependent manner. These data suggest that the non-adrenergic-noncholinergic vasodilation is mediated by endogenous CGRP released from the primary sensory nerve terminals upon electrical stimulation. In addition to the vasodilator action, CGRP also inhibited nerve stimulation-induced and norepinephrine-induced vasoconstriction at extremely low concentrations. The inhibitory action of CGRP appeared to be mediated by postsynaptic mechanisms inasmuch as evoked norepinephrine release was not affected by CGRP when the vasoconstriction produced by norepinephrine or periarterial nerve stimulation was attenuated greatly by CGRP. These observations suggest that the vascular tone of the resistance vessels can be regulated by primary sensory nerve-derived CGRP.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/fisiología , Vasodilatación/fisiología , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Estimulación Eléctrica , Endotelio Vascular/fisiología , Técnicas In Vitro , Masculino , Mesenterio/fisiología , Norepinefrina/metabolismo , Perfusión , Nervios Periféricos/fisiología , Ratas , Ratas EndogámicasRESUMEN
We provide the first functional evidence that calcitonin gene-related peptide (8-37) induces a direct vasoconstriction and reversibly antagonizes vasodilation of the mesenteric arterial bed induced by calcitonin gene-related peptide (CGRP) suggesting that CGRP (8-37) is a competitive antagonist of vascular CGRP receptors. Vasodilation induced by periarterial nerve stimulation was inhibited both by CGRP (8-37) and by desensitization of CGRP receptors. These results further support the evidence that the periarterial nerve stimulation-induced nonadrenergic noncholinergic vasodilation of the mesenteric vasculature is mediated by endogenous CGRP and its receptors.