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1.
Life Sci ; : 117451, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088213

RESUMO

AIMS: Electro-acupuncture pretreatment (EAP) plays a protective role in myocardial ischemia (MI) injury. However, the underlying mechanism remains unclear. A growing body of evidence suggests postinfarction inflammatory response directly affects the remodeling of ventricular function. The purpose of this study was to investigate whether EAP alleviates MI through NLRP3 inflammasome inhibition. MATERIALS AND METHODS: We constructed an AMI model by ligating the left anterior descending (LAD) coronary artery after 3 days of EAP with C57BL/6 mice. Echocardiography and TTC staining were employed to evaluate cardiac function and infarct size after 24 h of ischemia. HE staining and immunohistochemistry were employed to determine inflammatory level. Then, inflammasome activation was detected by western blotting, and macrophage polarization and neutrophil infiltration were observed by flow cytometry. KEY FINDINGS: Our preliminary findings showed that EAP reduced the infarct area and increased fractional shortening (FS) and ejection fraction (EF) and decreased the degree of inflammation after AMI injury. Meanwhile, EAP inhibited the expression of NLRP3, cleaved caspase-1 and IL-1ß in ischemia myocardial tissue, companied by inhibiting the expression of F4/80+, CD11b+, CD206low macrophages and activated M2 macrophage, and decreasing Ly-6G+CD11b+ neutrophils in ischemia myocardial and spleen tissue. SIGNIFICANCE: EAP inhibits the activation of NLRP3 inflammasome, promotes M2 polarization of macrophages and reduces the recruitment of neutrophils in damaged myocardium, thereby decreases the infarct size and improves the cardiac function.

2.
Anticancer Drugs ; 31(2): 123-130, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31815763

RESUMO

Cisplatin (CDDP) is the most effective chemotherapeutic drug against lung carcinoma. However, the emergence of resistant clones has severely limited its clinical application. We found that the cisplatin-resistant lung carcinoma cell line A549/CDDP had increased levels of the phosphorylated gap junction protein Cx43 and SRC tyrosine kinase, and low levels of total Cx43 protein and reduced gap junction formation. The SRC kinase inhibitor PP2 increased the expression of total Cx43 protein and enhanced cisplatin sensitivity, indicating that activated SRC kinase induces chemoresistance by decrease total Cx43 level. Furthermore, Cx43 gene silencing in the drug-resistant cell lines abrogated the sensitizing effect of PP2. Taken together, targeting SRC kinase by PP2 reverses cisplatin resistance by upregulating Cx43 protein levels, indicating a novel pathway of cisplatin resistance that may be amenable to therapeutic intervention.

3.
Int J Clin Pharmacol Ther ; 58(1): 50-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670654

RESUMO

OBJECTIVE: Patients with cerebral hemorrhage are often prone to intracranial infection, and meropenem is recommended for treatment. But whether the widely used dosing regimen (1 g, 2-hour infusion, every 12 hours) is suitable for antibiotic therapy is still unclear. The purpose of this study was to perform pharmacokinetic/pharmacodynamic (PK/PD) analyses of meropenem in both plasma and cerebrospinal fluid (CSF) in these patients. MATERIALS AND METHODS: Ten patients were enrolled in the present study. The blood samples and CSF samples were taken at predetermined time points and determined by our previously developed HPLC method. Pharmacokinetic parameters were then calculated, and the probability of target attainment (PTA) was calculated by the time that drug concentrations were above the minimum inhibitory concentration (%T>MIC). RESULTS: The peak meropenem concentration (Cmax) of 17.79 ± 3.38 µg/mL in plasma was reached at 2 hours, and the area under the curve (AUC) was 46.95 ± 4.37 h×µg/mL. The Cmax of 6.51 ± 1.11 µg/mL in CSF was reached at 3.50 ± 0.53 hours, and the AUC was 24.53 ± 4.28 h×µg/mL. The average penetration rate of meropenem in these patients was 52.25%. In the case where the MIC value was ≤ 1 µg/mL and using 40%T>MIC as a PK/PD index, the PTA of meropenem in both plasma and CSF were able to provide good coverage with MIC ≤ 1 µg/mL. CONCLUSION: In conclusion, this is the first study on the PK/PD analysis of meropenem in both plasma and CSF in patients with cerebral hemorrhage. The results will assist in selecting appropriate dosing regimens of meropenem in these patients.


Assuntos
Antibacterianos/farmacocinética , Hemorragia Cerebral , Drenagem , Meropeném/farmacocinética , Antibacterianos/sangue , Antibacterianos/líquido cefalorraquidiano , Humanos , Meropeném/sangue , Meropeném/líquido cefalorraquidiano , Testes de Sensibilidade Microbiana , Método de Monte Carlo
4.
Biomed Pharmacother ; 121: 109502, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707351

RESUMO

Signal transducer and activator of transcription 3 (STAT3) protein frequently overexpressed in many malignancies and plays an essential role in regulating proliferation, apoptosis, migration and invasion in cancer cells. However, No STAT3 inhibitor was used clinically. In this study, we evaluated the toxic potential of a novel STAT3 inhibitor, 6Br-6a in breast cancer cell lines. The anti-cancer effect and underlying mechanism of 6Br-6a on MDA-MB-231 and MCF-7 cells were determined in vitro and in xenograft mouse model. Our data demonstrated that 6Br-6a significantly induced cell cycle arrest and cell apoptosis in breast cancer via blocking the activation of STAT3. Finally, we verified these inhibitory effects of 6Br-6a in the MDA-MB-231 xenograft mouse model. In conclusion, 6Br-6a effectively inhibited activation of STAT3 and induced cell cycle arrest and apoptosis via regulating cyclin D1 and Bcl-2 expression. All of these data indicate that 6Br-6a could be a potential candidate for the treatment of breast cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31391859

RESUMO

Background: Simple obesity has become a global risk to health of human beings. Acupuncture, as one of traditional Chinese medicine therapies, has been widely used in obesity treatment in recent years. However, the individual heterogeneity which makes acupuncture's efficiency unstable leads to some controversy. So more evidence-based results are necessary to judge the effectiveness of acupuncture in treatment of simple obesity. Compared with clinical trials, animal experiments are controllable, and the underlying mechanism is more likely to be explored. Last but not the least, more and more experimental studies on acupuncture for animal obesity have been published. Therefore, we conducted the systematic review and meta-analysis to evaluate the effectiveness of acupuncture in treating simple obesity in animal experiments. Methods: Randomized Controlled Trials (RCTs) on acupuncture for simple obesity animal models were searched from six databases: PubMed, MEDLINE, CNKI, VIP, WanFang Date, and CMB from inception to February 2017 and updated on April 12, 2019. RevMan 5.3 software was used for meta-analysis. Treatment effects were summarized as relative risk (RR) and Standard mean difference (SMD) with 95% of confidence interval (CI). Results: A total of 108 trials involving 5731 rats were included. Meta-analysis showed that acupuncture had better effect on reducing weight (SMD -2.60, 95%CI: -2.93 to -2.26, p<0.00001) and Lee's index (SMD -2.62, 95%CI:-3.18 to -2.06, p<0.00001) compared with control group. However, the methodological quality of included studies was generally poor. Details of blinding were not reported in most studies. In spite of high heterogeneity being observed on the merged data, sensitivity analysis using the leave-one-out approach, subgroup analysis based on different acupuncture techniques, and rat strains and meta-regression all failed to find the sources of heterogeneity. The asymmetric funnel plot suggested publication bias. Besides, adverse events were not reported in any reports. Conclusions: Our review provided positive evidence of acupuncture for simple obesity. Unfortunately, none of the firm conclusions can be drawn due to methodological flaws, high heterogeneity, and publication bias. More high-quality trials are needed in future to get objective conclusions.

7.
Zhen Ci Yan Jiu ; 44(5): 313-8, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31155861

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of interleukin-8 (IL-8), interleukin-10 (IL-10), tyrosine hydroxylase (TH), ß3-adrenergic receptor (ß3AR), and endothelial nitric oxide synthase (eNOS) in myocardial tissue in ischemic myocardial injury rats, so as to reveal its underlying mechanisms in myocardial protection via anti-inflammation and sympathetic nerve remodeling. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided into sham-operation (sham, n=9), sham +EA (n=9), model (n=15) and EA (n=15) groups. The myocardial ischemia (MI) model was established by ligation of the left anterior descending branch of the left coronary artery. EA (2 Hz/15 Hz,1.5-2 mA) was applied to bilateral "Neiguan" (PC6) for 30 min, once daily for 4 days. The myocardial infarct size was detected by 2, 3, 5 triphenyltetrazolium chloride (TTC) staining, myocardial histopathological changes and inflammatory infiltration were assessed by H.E. staining, and the expression of IL-8, IL-10, TH, ß3AR, and eNOS in the myocardium was determined by using Western blot. RESULTS: Compared with the sham group, a marked myocardial infarction was found in the left ventricle tissue, accompanied with disordered arrangement of myocardial fibers and higher degree of inflammatory cell infiltration, and increased expression of IL-8, TH, ß3AR and eNOS in the myocardium in the model group (P<0.01), but without significant change in the expression of IL-10 (P>0.05). After EA intervention and in comparison with the model group, the myocardial infarct size was significantly reduced (P<0.01), the severity of inflammatory cell infiltration and disordered arrangement of myocardial fibers were relieved, and the expression of IL-10 and eNOS proteins were significantly up-regulated (P<0.05), and the markedly up-regulated expression of IL-8, TH, and ß3AR were significantly suppressed in the EA group (P<0.01).. CONCLUSION: EA intervention can reduce the myocardial infarct size (protective effect) in MI rats possibly by reducing inflammatory reaction and sympathetic nerve remodeling.


Assuntos
Eletroacupuntura , Infarto do Miocárdio , Animais , Citocinas , Masculino , Miocárdio , Ratos , Ratos Sprague-Dawley
8.
Front Psychiatry ; 10: 353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244685

RESUMO

Objective: This study investigated the influence of electroacupuncture (EA) and its potential underlying mechanisms on adipose tissue in obese mice. Methods: Three-week-old male C56BL/6 mice were randomly divided to feed or not to feed high-fat diet (HFD), named HFD group and chow diet (CD) group, respectively. After 12 weeks, CD and HFD mice were randomly divided into two groups, respectively, to receive or not receive EA for 4 weeks. Body weight (BW) was monitored. Intraperitoneal glucose tolerance test and metabolic chamber recordings were performed. Blood samples and adipose tissue were collected for the analysis of leptin, triglyceride levels, and fat browning-related proteins. Results: EA significantly reduced food intake, BW, and white adipose tissue (WAT)/BW ratio; decreased the adipocyte size and serum concentrations of triglyceride (TG) and cholesterol; and increased oxygen consumption in HFD mice. Compared with the CD mice, the HFD mice had elevated fasting serum glucose level and impaired glucose tolerance; however, these parameters were decreased by EA treatment. Meanwhile, EA promoted the protein and mRNA expressions of UCP1, PRDM16, and PGC-1α in adipose tissue, and activated sympathetic nerves via p-TH, A2AR, and ß3AR in white adipose tissue. Conclusions: EA reduced food intake, BW, TG, and cholesterol, and improved glucose tolerance in HFD mice. This ameliorative effect of EA on obesity-related symptoms associated with its promoted adipose tissue plasticity via activating sympathetic nerves.

9.
Exp Ther Med ; 17(5): 3800-3806, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30988766

RESUMO

Currently available treatments for Parkinson's disease (PD) do not delay or prevent disease development and progression. DL-3-n-butylphthalide (NBP), isolated from Apium graveolens seeds, alleviates oxidative damage and mitochondrial dysfunction. It has been revealed to reduce the loss of dopamine neurons in pre-clinical PD models, and has been approved for the treatment of ischemic stroke patients. The purpose of the present study was to examine whether NBP has the capacity provide a benefit for PD patients and to slow disease progression. A randomized, controlled trial was performed between September 2014 and December 2016. Pairs of patients matched by age, gender and off-medication Unified PD Rating Scale motor subscale (UPDRS-III) scores, were randomly assigned to an NBP treatment group and a control group. All patients continued their originally prescribed medication regimen and those in the NBP group were administered NBP at 200 mg three times daily for 24 weeks. Primary outcome measures were changes in UPDRS-III, including tremor score and non-tremor score, the Pittsburgh sleep quality index (PSQI) and the PD 39-items questionnaire (PDQ) scores. Assessments were completed by blinded evaluators at baseline and 12, 24 and 48 weeks after randomization. All patients were monitored for adverse events (AEs). A total of 103 patients were enrolled in the present study. The NBP group exhibited significantly greater improvements in the non-tremor, PSQI and PDQ-39 scores than the control group, which generally exhibited no improvement. NBP-associated AEs were uncommon and primarily consisted of mild gastrointestinal symptoms. In conclusion, over the 6-month treatment period, NBP was safe and effective for improving the symptoms and impairing the progression of patients with PD (Trial registry number, ChiCTR1800018892).

10.
Cancer Lett ; 442: 396-408, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439541

RESUMO

Intratumoral injection of chemotherapy agents may be employed in the treatment of cancers. However, its anti-tumor efficacy is significantly impeded by collagen fibers in the tumor which decrease drug penetration into the tumor tissues. To improve the penetration, collagen inhibiting drug exposure is required. In this study, microspheres were fabricated by the modified double emulsion-solvent evaporation method as the drug delivery system of losartan potassium (LP MSs), with 5% gelatin as the inner phase. The collagen inhibiting experiment analyzed by Sirius Red stains demonstrated that LP MSs may effectively inhibit collagen I synthesis in B16 tumors. In addition, 15% F127 was used as the solvent to fix the formulations at the injection site, with poly (α-l-glutamate) grafted polyethylene glycol mono methyl ether (PLG-g-mPEG)-cisplatin loaded nanoparticles (CDDP NPs) as the model drug. The in vivo live imaging system showed that formulations dissolved in 15% F127 had 54.91% CDDP NPs retained in tumors at the end of 10 days, in comparison with 19.72% for those solved in water, suggesting strong intratumoral retention property of the in situ gel. In addition, confocal laser scanning microscope (CLSM) and Energy-Dispersive Analysis of X-ray spectroscopy combined with scanning electron microscope (SEM-EDAX) tests showed that LP MSs can effectively enhance the distribution and penetration of CDDP NPs within tumors. Furthermore, tumors i.t. treated with LP MSs/CDDP NPs gel could be significantly halted, or even reduced to 200 mm3, comparing with a volume of about 12000 mm3 incontrol group at the end of the anti-tumor effect experiment. These results provided important guiding principles for prolonged and localized drug delivery system of intratumoral collagen inhibitor. The improvements of intratumoral penetration method made in this study provided practical significance for the treatment of cancer, especially for mass tumors.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Portadores de Fármacos , Colágenos Fibrilares/biossíntese , Gelatina/química , Losartan/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Polietilenoglicóis/química , Ácido Poliglutâmico/análogos & derivados , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Cisplatino/química , Cisplatino/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Géis , Injeções Intralesionais , Losartan/química , Losartan/metabolismo , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/ultraestrutura , Camundongos Endogâmicos C57BL , Microesferas , Ácido Poliglutâmico/química , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos
11.
Biomed Pharmacother ; 109: 1523-1531, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551404

RESUMO

AIMS: To determine the causes of adverse reactions associated with Xuebijing injection and provide medical evidence for its safe and rational post-marketing use in clinical practice. MATERIALS AND METHODS: We used prospective nested case-control and prescription sequence analysis designs. Using data from the Hospital Information System, patients exhibiting trigger signals after receiving Xuebijing injection were classified as suspected allergic patients. Logistic regression analysis was performed on the risk factors associated with Xuebijing-induced allergic reactions. Randomized controlled and cohort studies on adverse drug reactions to Xuebijing injection were screened from databases and the results were subjected to meta-analysis. RESULTS: The overall incidence of allergic reactions or anaphylaxis tended to increase with dosage and patient's age. Moreover, compared with Xuebijing alone, co-administration of Xuebijing with other drugs or agents (including Ringer's sodium acetate solution, reduced glutathione, aspirin-DL-lysine, and torasemide) increased the risk of adverse reactions. The use of glucose as a vehicle also provoked a greater incidence of allergic reactions than that by the use of 0.9% w/v sodium chloride as a vehicle. Adverse reactions occurred more frequently in patients receiving indicated dosages than in those receiving off-label dosages. CONCLUSIONS: Adverse reactions to Xuebijing injections were correlated with vehicle type, dosage, age, and drug combination. There was no clear association between patient's condition at admission and suspected adverse reactions to Xuebijing injection. Factors influencing the adverse reactions to Xuebijing injection must be fully considered in clinical practice.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Hipersensibilidade/etiologia , Injeções/efeitos adversos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
12.
Materials (Basel) ; 11(8)2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30065194

RESUMO

Bitumen ageing is a very complex process and poses a threat to the performance of pavements. In the present work, a fluorescence spectrophotometer was employed to research the change rule of components and the structure of bitumen after the ageing process. The Thin Film Oven Test (TFOT) and Ultraviolet (UV) light treatment were carried out as ageing methods. The properties and components of bitumen were tested before and after aging. The 2D and 3D fluorescence spectra of bitumen were analyzed. The vector of fluorescence peak was calculated for evaluating the ageing process. The results indicated that the ideal concentration of bitumen- tetrachloromethane solution was 0.1 g/L or smaller for avoiding the fluorescence quenching. The coordinates of fluorescent peak appeared "blue-shift" after ageing due to the change of aromatics. In addition, bitumen has already occurred serious ageing when the magnitude of a vector is more than 36.

13.
J Mol Neurosci ; 65(4): 507-513, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30073555

RESUMO

Exposure of neonatal animals to anesthetics may cause developmental functional changes and acute structural anomalies in the brain. Clonidine, an α2-adrenoceptor agonist, functions as an analgesic and sedative and protects against brain injury. Nevertheless, whether clonidine protects the developing brain from damage caused by sevoflurane (SEVO) anesthesia remains unclear. Seven-day-old rats were exposed to 3% SEVO for 6 h, during which time either clonidine or saline was injected three times. The arterial blood gases, respiratory rate, and anesthesia level of each rat were evaluated. Western blot analysis was employed to detect proinflammatory cytokines, NF-κB, and cleaved-caspase-3. Surgical anesthesia was adequately induced by SEVO. No rats died during the study. Compared with untreated rats, SEVO induced production of cleaved-caspase-3. Administration of clonidine and SEVO significantly reduced apoptosis. Moreover, nuclear translocation and NF-κB phosphorylation were inhibited by clonidine, and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) production decreased after SEVO administration. Marked apoptosis in the brain was induced by SEVO anesthesia. Clonidine treatment provided significant protection against SEVO-induced apoptosis.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Anestésicos Inalatórios/efeitos adversos , Encéfalo/efeitos dos fármacos , Clonidina/farmacologia , Éteres Metílicos/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Anestésicos Inalatórios/toxicidade , Animais , Apoptose , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Éteres Metílicos/toxicidade , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Sevoflurano
14.
Biomed Res Int ; 2018: 5214369, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850531

RESUMO

The anaerobic fermentation of crop straw and animal wastes is increasingly used for the biogas and green energy generation, as well as reduction of the environmental pollution. The anaerobic cofermentation of corn stalks inoculated by cow dung was found to achieve higher biogas production and cellulose biodegradation. In this study, the effect of mixing corn stalks with cow dung at five different fermentation stages (0, 7, 15, 23, and 31 days of the total fermentation cycle of 60 days) on the further cofermentation process was explored, in order to optimize the corn straw utilization rate and biogas production capacity. In addition, the straw microstructure evolution was investigated by the SEM and XRD methods to identify the optimal conditions for the straw biodegradation process enhancement. The five test groups exhibited nearly identical total biogas productivity values but strongly differed by daily biogas yields (the maximal biogas generation rate being 524.3 ml/d). Based on the degradation characteristics of total solids (TS), volatile solids (VS), and lignocellulose, groups #1 and #3 (0 and 15 days) had the most significant degradation rates of VS (43.73%) and TS (42.07%), respectively, while the largest degradation rates of cellulose (62.70%) and hemicellulose (50.49%) were observed in group #4 (23 days) and group #1 (0 days), respectively. The SEM analysis revealed strong microstructural changes in corn stalks after fermentation manifested by multiple cracks and striations, while the XRD results proved the decrease in peak intensity of cellulose 〈002〉 crystal surface and the reduced crystallinity after cofermentation. The results of this study are assumed to be quite instrumental to the further optimization of the corn stalk anaerobic digestion by inoculation with digested manure for lignocellulose degradation enhancement and biogas productivity improvement.


Assuntos
Biodegradação Ambiental , Biocombustíveis , Lignina , Esterco , Zea mays/química , Anaerobiose , Animais , Bovinos , Fermentação , Lignina/análise , Lignina/química , Lignina/metabolismo , Difração de Raios X
15.
J Biomed Opt ; 23(5): 1-11, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29729091

RESUMO

This study investigated the relationships of systemic low-frequency oscillations (sLFOs) measured at different peripheral sites in resting state, during passive leg raising (PLR), and during a paced breathing (PB) test. Twenty-five healthy subjects (21 to 57 years old; males: 13 and females: 12) were recruited for these experiments. During the experiments, the fluctuations of oxyhemoglobin concentration were measured at six peripheral sites (left and right toes, fingertips, and earlobes) using a multichannel near-infrared spectroscopy instrument developed by our group. We applied cross-correlation and frequency component analyses on the data. The results showed that the sLFO signals in the symmetric peripheral sites were highly correlated, with time delays close to zero, whereas the correlation coefficients decreased between the sLFO signals of asymmetric sites, with delays up to several seconds. Furthermore, in PLR/PB tests, we found that PB caused wider and more robust changes in hemoglobin concentrations at peripheral sites compared to PLR. Among six peripheral sites, earlobes were the most sensitive to these perturbations, followed by fingertips, and then toes. Lastly, we showed that the perturbation signals may have different coupling mechanisms than the sLFO signals. The study deepened our understanding of the sLFO signals and establishes baseline measures for developing perfusion biomarkers to assess peripheral vascular integrity.


Assuntos
Processamento de Sinais Assistido por Computador , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Pavilhão Auricular/fisiologia , Feminino , Dedos/irrigação sanguínea , Voluntários Saudáveis , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Oxiemoglobinas/análise , Doenças Vasculares Periféricas , Dedos do Pé/irrigação sanguínea , Adulto Jovem
16.
Drug Dev Ind Pharm ; 44(10): 1591-1597, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29847181

RESUMO

The objective of this study was to develop agomelatine (AGM) intramuscular sustained release PLA microparticles by using solvent evaporation combined with wet milling technology. The final preparation had a regular and homogeneous particle size of approximately 35 µm, as measured by laser diffraction particle size analysis and scanning electron microscopy (SEM). The drug was confirmed to be within the carrier in an amorphous state through differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD) experiments. Additionally, Fourier transform infrared spectroscopy (FT-IR) analysis was applied to confirm that there was hydrogen bonding between the drug and polymer at the molecular level. In vitro release experiments indicated that the drug could achieve long-term sustained release over the period of one month, with only a 3.07% burst release, due to the involvement of the polymer and removal of drug adsorbed on the surface during the wet grinding process. The dominant release mechanism was considered to be diffusion of the drugs in the initial period. Following this, with the hydrolysis of PLA to form a colloidal viscous layer, drug release is due to the combined effect of diffusion and erosion of the polymer matrix. Additionally, drug release behavior is closely related to the degradation mechanism of the polymer carrier. The results suggest that AGM could be developed as a potential delivery system for long-acting intramuscular administration with extensive application prospects.


Assuntos
Acetamidas/farmacocinética , Química Farmacêutica/métodos , Microesferas , Solventes/farmacocinética , Tecnologia Farmacêutica/métodos , Acetamidas/administração & dosagem , Acetamidas/síntese química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/síntese química , Hipnóticos e Sedativos/farmacocinética , Injeções Intramusculares , Tamanho da Partícula , Solventes/administração & dosagem , Solventes/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
17.
Drug Des Devel Ther ; 12: 757-767, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670332

RESUMO

Aim: To evaluate the factors influencing suspected hypersensitivity and adverse systemic reactions after Shuxuening injection and to provide innovative ideas and methods for the reevaluation of post-marketing safety of Shuxuening. Methods: This study used a prospective, nested case-control study design, combined with a prescription sequence analysis design method. It classified patients who exhibited trigger signals after administration of Shuxuening injection as suspected allergic patients and made comparisons with patients who did not report adverse effects to calculate the correlation between relevant risk factors and suspected allergic reactions. Randomized controlled studies and cohort studies of the adverse drug reaction (ADR) of Shuxuening were performed using a computer database. Data retrieval was carried out by the foundation governing the individual database. Meta-analysis was performed by using R3.2.3 software to evaluate the ADRs of Shuxuening. Results: The results of real-world study showed that administration of Shuxuening in combination with potassium aspartate and magnesium, atorvastatin calcium, Shengmai injection, pantoprazole sodium, or high-dose medication was a risk factor for suspected allergic reactions. Meta-analysis showed that the incidence of adverse events was 5.84% (95% CI 0.0499; 0.0674), and serious adverse reaction rate was 4.36% (95% CI 0.0188; 0.0760) when Shuxuening was used in combination with these drugs. The incidence of allergic reaction was also influenced by the vehicle, duration of treatment, single dose, and indicated vs off-label use. Conclusion: Risk factors for adverse reaction following the use of Shuxuening injection in patients are associated with a single dose, vehicle, type of disease, and combination with potassium aspartate, atorvastatin calcium, Shengmai injection, injection with pantoprazole sodium, and other drugs. Physicians should be careful to follow guidelines when administering this drug. We further propose that the unique methodology used in this study may be useful for reevaluation of the safety of other traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Estudos de Casos e Controles , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Medicina Tradicional Chinesa , Estudos Prospectivos
18.
J Pharm Sci ; 107(7): 1879-1885, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29518401

RESUMO

The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydroalcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween 80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents, and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels. Dramatically increased transdermal permeation of LH within the azone contents between 0.25% and 0.75% indicated high transdermal enhancement efficiency of the molecular or micellar azone, and extra azone that existed as oil droplets did not fully exert transdermal penetration enhancement of LH. Although solubilizer (Tween 80) can greatly increase the solubility of azone, only small amount of Tween 80 (0.5%) in the gel significantly increased the steady-state flux of LH. Addition of extra amount of Tween 80 (>0.5%) reduced the amount of azone distributed in the skin, and thus decreased the transdermal drug permeation. The results partly elucidated the versatile effects of the dispersion states of azone on the transdermal permeation of hydrophilic drug from semisolid gels.


Assuntos
Antinematódeos/farmacocinética , Antirreumáticos/farmacocinética , Azepinas/química , Hidrogéis/química , Levamisol/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Antinematódeos/administração & dosagem , Antirreumáticos/administração & dosagem , Azepinas/farmacologia , Hidrogéis/farmacologia , Levamisol/administração & dosagem , Masculino , Micelas , Permeabilidade/efeitos dos fármacos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/metabolismo , Solubilidade
19.
Biomed Pharmacother ; 98: 826-833, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29571253

RESUMO

The effect of gap junction intercellular communication composed of connexin on cancer invasion/metastasis has been thoroughly explored; however, its effect on testicular cancer resistanced to chemotherapy is still unclear. In this study, we found that the capability of invasion and migration of I-10/DDP (cisplatin (DDP)-resistance) cells were elevated. Furthermore, the expression of Cx43 and the function of gap junction (GJ) in I-10/DDP cells were decreased compared with parental I-10 cells. Pharmacological inhibition of GJs by oleamide (Olea) enhanced invasion and migration. However, enhancement of GJs by retinoic acid (RA) decreased invasion and migration of I-10/DDP cells. To further clarify the invasion/migration inhibited effect of GJ in the testicular cancer resistanced to DDP, GJ function was modulated by overexpression and knockdown of Cx43 expression. Overexpression of Cx43 reduced invasion and migration of I-10/DDP cells. Conversely, knockdown of Cx43 expression increased invasion and migration of I-10/DDP cells. In summary, GJ composed of Cx43 inhibits I-10/DDP cells invasion and migration, and it may become the potential therapeutic target for testicular cancer chemotherapy.


Assuntos
Cisplatino/farmacologia , Conexina 43/metabolismo , Resistencia a Medicamentos Antineoplásicos , Junções Comunicantes/metabolismo , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Animais , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Junções Comunicantes/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Inativação Gênica/efeitos dos fármacos , Masculino , Camundongos , Invasividade Neoplásica , Metástase Neoplásica
20.
J Med Microbiol ; 67(3): 441-451, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29458539

RESUMO

PURPOSE: Avian colibacillosis is responsible for economic losses to poultry producers worldwide. To combat this, we aimed to develop an effective oral vaccine for chicken against O78 avian pathogenic Escherichia coli (APEC) infection through a Lactobacillus delivery system. METHODOLOGY: Eight Lactobacillus strains isolated from the intestines of broiler chickens were evaluated based on their in vitro adherence ability to assess their potential as a delivery vector. Fimbrial subunit A (FimA) and outer-membrane protein C (OmpC) of APEC with and without fusion to dendritic cell-targeting peptide (DCpep) and microfold cell-targeting peptide (Co1) were displayed on the surface of Lactobacillus saerimneri M-11 and yielded vaccine groups (pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, respectively). The colonization of the recombinant strains in vivo was assessed and the immunogenicity and protective efficacy of orally administered recombinant strains in chickens were evaluated. RESULTS: The colonization of the recombinant strains in vivo revealed no significant differences between the recombinant and wild-type strains. Chickens orally administered with vaccine groups showed significantly higher levels of OmpC/FimA-specific IgG in serum and mucosal IgA in cecum lavage, nasal lavage and stool compared to the pPG/M-11 group. After challenge with APEC CVCC1553, better protective efficacy was observed in chickens orally immunized with pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, but no significant differences were observed between the two groups. CONCLUSIONS: Recombinant chicken-borne L. saerimneri M-11 showed good immunogenicity in chickens, suggesting that it may be a promising vaccine candidate against APEC infections. However, the activity of mammalian DCpep and Co1 was not significant in chickens.


Assuntos
Infecções por Escherichia coli/veterinária , Vacinas contra Escherichia coli/imunologia , Proteínas de Fímbrias/imunologia , Imunogenicidade da Vacina , Lactobacillus/genética , Porinas/imunologia , Doenças das Aves Domésticas/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Ceco/imunologia , Galinhas , Escherichia coli/imunologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Fímbrias/genética , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/imunologia , Lactobacillus/isolamento & purificação , Porinas/genética , Doenças das Aves Domésticas/prevenção & controle
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