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1.
J Steroid Biochem Mol Biol ; 234: 106402, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37734284

RESUMO

The effects of acupuncture on the protein and gene expression of oestrogen receptors (ERs) alpha (α) and beta (ß) in testosterone-induced benign prostatic hyperplasia (BPH) in rats remains unclear. In this study, rats were randomly divided into four groups (n = 10 per group). The rats in the blank group did not receive any treatment, while the rats in the model group were injected intraperitoneally with testosterone propionate for 28 days to establish the BPH model and then randomly sub-divided into a control group, an acupuncture group and a finasteride group (positive control group). Dissections were performed after rats were anesthetized with isoflurane, and then the weight and volume of the prostate were then measured. The expression of ERs was detected via immunohistochemistry, western blot and real-time polymerase chain reaction. The results showed that ERα was discontinuously distributed in epithelial cells and expressed in large quantities in stromal cells, and ERß was aggregated and expressed in hyperplastic nodules. Acupuncture and finasteride could significantly improve the distribution of ERα and ERß which suggested that acupuncture and finasteride could improve BPH. There was no significant difference in ERα messenger ribonucleic acid (mRNA) expression among the groups, but the ERß mRNA expression in the finasteride group showed a significant difference compared with the control and acupuncture groups. The mechanism of the acupuncture treatment of BPH may be related to the increased transcription level of ERß mRNA in prostate tissues, the improved distribution of ERα expression in epithelial cells and the aggregation expression of ERs in hyperplastic nodules.


Assuntos
Terapia por Acupuntura , Hiperplasia Prostática , Masculino , Humanos , Ratos , Animais , Finasterida/farmacologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/terapia , Hiperplasia Prostática/metabolismo , Receptores de Estrogênio/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Testosterona , RNA Mensageiro
2.
Pharmacology ; 107(7-8): 386-397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35609521

RESUMO

INTRODUCTION: Sufentanil is used with ropivacaine in labor pain management but it can have respiratory depression. Dexmedetomidine is effective to maintain hemodynamic stability in parturient women and allow awake intubation. However, dexmedetomidine is suggested only in patients with major cardiovascular disease that mandates stable hemodynamics (Reference ID: 3987541-USFDA). The objective of the study was to compare different doses of ropivacaine either with sufentanil or with dexmedetomidine for epidural anesthesia regarding labor pain management. METHODS: Parturient women have received 0.125% ropivacaine with 0.5-µg/mL sufentanil (SR1 cohort, n = 115), or 0.08% ropivacaine with 0.5-µg/mL sufentanil (SR2 cohort, n = 109), or 0.125% ropivacaine with 0.5-µg/mL dexmedetomidine (DR1 cohort, n = 124), or 0.08% ropivacaine with 0.5-µg/mL dexmedetomidine (DR2 cohort, n = 135) for epidural anesthesia during vaginal delivery or cesarean section. RESULTS: At 2-h postpartum, the visual analog scale score of parturient women of the DR2 cohort was fewer than that of parturient women of the SR1 (p < 0.0001, q = 4.162) and the SR2 (p < 0.0001, q = 7.568) cohorts and statistically the same as that of parturient women of the DR1 cohort (p < 0.0001, q = 3.087). Bradycardia and itching were reported in parturient women of the DR2 and the DR1 cohorts while nausea, vomiting, and urinary retention at 6 h were reported in parturient women of the SR1 and the SR2 cohorts. In the DR2 cohort, there were fewer numbers of parturient women with bradycardia (4 vs. 19, p < 0.0001, q = 6.613) and hypotension (2% vs. 1%) than those in the DR1 cohort. The child born by women of the DR2 cohort had high partial arterial pressure of oxygen than those born by women of the DR1 (p < 0.0001, q = 18.663), the SR1 (p < 0.0001, q = 29.366), and the SR2 (p < 0.0001, q = 24.039) cohorts. DISCUSSION/CONCLUSION: Epidural 0.08% ropivacaine with 0.5-µg/mL dexmedetomidine is an effective and safe anesthetic regimen for hypertensive parturient women and their newborns. LEVEL OF EVIDENCE: III. Technical Efficacy Stage: 4.


Assuntos
Analgesia Epidural , Anestesia Epidural , Dexmedetomidina , Trabalho de Parto , Amidas/farmacologia , Analgésicos/farmacologia , Anestesia Epidural/efeitos adversos , Anestésicos Locais/farmacologia , Bradicardia , Cesárea/efeitos adversos , Criança , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Ropivacaina/farmacologia , Sufentanil/efeitos adversos
3.
Int J Nanomedicine ; 16: 8049-8065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938072

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of Curcuma longa capable of hematoma volume and associated neurological damage in the context of ICH. Despite exhibiting therapeutic promise, the efficacy of Cur is challenged by its poor water solubility, limited oral bioavailability and inability to efficiently transit across the physiological barriers. Polymer-based nanoparticles (NPs) have widely been employed to aid in drug delivery efforts owing to their ideal biocompatibility and their ability to improve the bioavailability and pharmacokinetics of specific drugs of interest. METHODS: In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells. RESULTS: The resultant Cur-NPs were spherical and exhibited a particle size of 127.31±2.73 nm, a PDI of 0.21±0.01 and a zeta potential of -0.25±0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells. CONCLUSION: These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.


Assuntos
Curcumina , Ferroptose , Nanopartículas , Animais , Hemorragia Cerebral , Curcumina/farmacologia , Cães , Sistemas de Liberação de Medicamentos , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Peixe-Zebra
4.
Front Psychiatry ; 12: 703516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413798

RESUMO

Depression is a prevalent mental disease characterized by persistent low mood, lack of pleasure, and exhaustion. Acupoint catgut embedding (ACE) is a kind of modern acupuncture treatment, which has been widely used for the treatment of a variety of neuropsychiatric diseases. To investigate the effects and underlying mechanism of ACE on depression, in this study, we applied ACE treatment at the Baihui (GV20) and Dazhui (GV14) acupoints of corticosterone (CORT)-induced depression model mice. The results showed that ACE treatment significantly attenuated the behavioral deficits of depression model mice in the open field test (OFT), elevated-plus-maze test (EPMT), tail suspension test (TST), and forced swimming test (FST). Moreover, ACE treatment reduced the serum level of adreno-cortico-tropic-hormone (ACTH), enhanced the serum levels of 5-hydroxytryptamine (5-HT), and noradrenaline (NE). Furthermore, metabolomics analysis revealed that 23 differential metabolites in the brain of depression model mice were regulated by ACE treatment for its protective effect. These findings suggested that ACE treatment ameliorated depression-related manifestations in mice with depression through the attenuation of metabolic dysfunction in brain.

5.
Front Pharmacol ; 12: 629379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815110

RESUMO

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.

6.
Nanoscale ; 13(6): 3827-3840, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33565555

RESUMO

Intracerebral hemorrhage (ICH) is a neurological disorder resulting from the nontraumatic rupture of blood vessels in the brain. Ferroptosis is a newly identified form of programmed cell death, which is an important pathological feature of ICH injury. At present, the therapeutic efficacy of ICH treatment is far from satisfactory, so it is urgent to develop a safer and more effective method to treat ICH injury. Resveratrol (Res), a widely used nonflavonoid polyphenol compound, plays a neuroprotective role in many diseases. However, its poor oral bioavailability limits its clinical application in ICH. Polymer nanoparticles (NPs) are a commonly used drug delivery matrix material with good biocompatibility. To improve its bioavailability and accumulation in the brain, we used NPs to encapsulate Res. These spherical Res nanoparticles (Res-NPs) had a particle size of 297.57 ± 7.07 nm, a PDI of 0.23 ± 0.02 and a zeta potential of -5.45 ± 0.27 mV. They could be taken up by Madin-Darby canine kidney (MDCK) cells through a variety of nonspecific endocytosis mechanisms, mainly mediated by clathrin and plasma membrane microcapsules. After entering the cell, Res-NPs tend to accumulate in the endoplasmic reticulum and lysosomes. In a zebrafish model, we observed that Res-NPs could transport across physiological barriers. In a Sprague-Dawley (SD) rat model, we found that Res-NPs had more desirable improvements in Res accumulation within the plasma and brain. Moreover, we demonstrated that Res-NPs were able to inhibit ferroptosis induced by erastin in HT22 mouse hippocampal cells, which are commonly used in in vitro studies to examine neuronal differentiation and neurotoxicity implicated in brain injuries or neurological diseases. Finally, in an ICH mouse model, we confirmed that Res-NPs are a safer and effective treatment for ICH injury. Collectively, Res-NPs are effective to improve Res brain delivery and its therapeutic efficacy in ICH treatment.


Assuntos
Nanopartículas , Peixe-Zebra , Animais , Encéfalo , Hemorragia Cerebral/tratamento farmacológico , Cães , Camundongos , Ratos , Ratos Sprague-Dawley , Resveratrol
7.
Chin Med ; 13: 46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181771

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) significantly affects women's health and well-being. To explore the pharmacological basis of the Erxian decoction (EXD) action in PCOS therapy, a network interaction analysis was conducted at the molecular level. METHODS: The active elements of EXD were identified according to the oral bioavailability and drug-likeness filters from three databases: traditional Chinese medicine system pharmacology analysis platform, TCM@taiwan and TCMID, and their potential targets were also identified. Genes associated with PCOS and established protein-protein interaction networks were mined from the NCBI database. Finally, significant pathways and functions of these networks were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine the mechanism of action of EXD. RESULTS: Seventy active compounds were obtained from 981 ingredients present in the EXD decoction, corresponding to 247 targets. In addition, 262 genes were found to be closely related with PCOS, of which 50 overlapped with EXD and were thus considered therapeutically relevant. Pathway enrichment analysis identified PI3k-Akt, insulin resistance, Toll-like receptor, MAPK and AGE-RAGE from a total of 15 significant pathways in PCOS and its treatment. CONCLUSIONS: EXD can effectively improve the symptoms of PCOS and our systemic pharmacological analysis lays the experimental foundation for further clinical applications of EXD.

8.
Oncotarget ; 8(25): 41256-41264, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28476033

RESUMO

Several studies have reported the use of dexmedetomidine (DEX) plus opioids for flexible bronchoscopy in both adults and children. To determine whether DEX plus sufentanil (SF) is safe for children, 142 children undergoing flexible bronchoscopy were assigned to one of three groups, each of which received the same SF loading dose and similar DEX and SF maintenance doses, but different loading doses of DEX: DS1 (DEX 0.5 µg·kg-1), DS2 (DEX 1.0 µg·kg-1), and DS3 (DEX 1.5 µg·kg-1). The Ramsay sedation scale was maintained at 3 in all groups. Results showed that anesthesia onset time was shorter, and the perioperative hemodynamic profile was more stable, in the DS3 group. The number of intraoperative movements was also lowest in the DS3 group. The time to first dose of rescue midazolam and lidocaine was significantly longer, but the total corresponding accumulated doses were lower in the DS3 group. Although the time to recovery prior to discharge from the post anesthesia care unit was longer, the overall incidence of tachycardia was lower in the DS3 group, and it received the highest bronchoscopist satisfaction score among the three groups. We therefore conclude that high-dose DEX plus SF can be safely and efficaciously used in children undergoing flexible bronchoscopy.


Assuntos
Anestesia/métodos , Broncoscopia/métodos , Dexmedetomidina/administração & dosagem , Sufentanil/administração & dosagem , Analgésicos/administração & dosagem , Criança , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
9.
Front Pharmacol ; 7: 407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27833559

RESUMO

Background: Approximately 60% of patients experience moderate-to-severe pain after neurosurgery, which primarily occurs in the first 24-72 h. Despite this, improved postoperative analgesia solutions after neurosurgery have not yet been devised. This retrospective study was conducted to evaluate the effect of intra- and post-operative infusions of dexmedetomidine (DEX) plus sufentanil on the quality of postoperative analgesia in patients undergoing neurosurgery. Methods: One hundred and sixty-three post-neurosurgery patients were divided into two groups: Group D (DEX infusion at 0.5 µg·kg-1 for 10 min, then adjusted to 0.3 µg·kg-1·h-1 until incision suturing) and Group ND (no DEX infusion during surgery). Patient-controlled analgesia was administered for 72 h after surgery (Group D: sufentanil 0.02 µg·kg-1·h-1 plus DEX 0.02 µg·kg-1·h-1, Group ND: sufentanil 0.02 µg·kg-1·h-1) in this retrospective study. The primary outcome measure was postoperative sufentanil consumption. Hemodynamics, requirement of narcotic, and vasoactive drugs, recovery time and the incidence of concerning adverse effects were recorded. Pain intensity [Visual Analogue Scale (VAS)], Ramsay sedation scale (RSS) and Bruggemann comfort scale (BCS) were also evaluated at 1, 4, 8, 12, 24, 48, and 72 h after surgery. Results: Postoperative sufentanil consumption was significantly lower in Group D during the first 72 h after surgery (P < 0.05). Compared with Group ND, heart rate (HR) in Group D was significantly decreased from intubation to 20 min after arriving at post anesthesia care unit (PACU), while mean arterial pressure (MAP) in Group D was significantly decreased from intubation to 5 min after arriving at PACU (P < 0.05). The intraoperative requirements for sevoflurane, remifentanil, and fentanyl were approximately 35% less in Group D compared with Group ND. VAS at rest at 1, 4, and 8 h and with cough at 12, 24, 48, and 72 h after surgery were significantly lower in Group D (P < 0.05). Compared with Group ND, patients in Group D showed lower levels of overall incidence of tachycardia, hypertension, nausea, and vomiting (P < 0.05). There were no significant differences between the two groups in terms of baseline clinical characteristics, recovery time, RSS, and BCS (P > 0.05). Conclusions: DEX (0.02 µg·kg-1·h-1) plus sufentanil (0.02 µg·kg-1·h-1) could reduce postoperative opioid consumption and concerning adverse adverse effects, while improving pain scores. However, it did not influence RSS and BCS during the first 72 h after neurosurgery.

10.
Evolution ; 69(11): 2985-94, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26477885

RESUMO

Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators' perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner.


Assuntos
Evolução Biológica , Mimetismo Biológico , Aves/fisiologia , Borboletas/fisiologia , Comportamento Predatório , Asas de Animais/fisiologia , Animais , Borboletas/genética , Cor , Visão de Cores , Feminino , Masculino , Seleção Genética , Caracteres Sexuais
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-671137

RESUMO

Objective To compare the clinical effect and adverse reactions of different concentrations of dezocine epidural anesthesia for cesarean section.Methods According to digital table,120 cases of elective cesarean section were randomly divided into 4 groups with 30 cases in each group, the group D1 was given with dezocine 2.5mg,the group D2 with dezocine 5mg,the group D3 with dezocine 10mg,the group M with morphine 2mg.All the drugs used in postoperative epidural analgesia after cesarean section.To observe resting pain and conduct the VAS scoring at postoperative 4,8,12,24h and record various adveme reactions.Results The VAS scores at postoperative 4,8,12h in the group D1 were lower than those in the D2,D3,M with statistical difference(all P0.05).The VAS scores at postoperative 8h in the group D3 were lower than those in the D2,D3,M with statistical difference(all P0.05).The incidence rates of nause-a and vomiting the group M were higher than that in the group D1,D2 and D3,showing statistical difference among them(P<0.05).Conclusion Appropriate concentrations of dezocine used in postoperative epidural analgesia after cesarean section has definite effect and less adverse reactions.

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