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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 989-999, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621906

RESUMO

This study aims to investigate the effect of Naotaifang(NTF) on the proteins associated with microglial polarization and glial scar in the rat model of cerebral ischemia reperfusion injury(CIRI). The CIRI model was established by middle cerebral artery occlusion/reperfusion. The 48 successfully modeled rats were randomized into model 7 d, model 14 d, NTF 7 d, and NTF 14 d groups(n=12). In addition, 12 SD rats were selected as the sham group. The NTF group was administrated with NTF suspension at 27 g·kg~(-1)·d~(-1) by gavage, and the sham, model 7 d, and model 14 d groups were administrated with the same volume of normal saline every day by gavage for 7 and 14 days, respectively. After the intervention, Longa score was evaluated. The infarct volume was measured by 2,3,5-triphenyl-2H-tetrazolium chloride(TTC) staining. Morris water maze and open field tests were carried out to evaluate the spatial learning, memory, cognitive function, and anxiety degree of rats. Hematoxylin-eosin(HE) staining was employed to observe the morphological structure and damage of the brain tissue. The immunofluorescence assay was employed to measure the expression of glial fibrillary acidic protein(GFAP) and glial scar. Western blot was employed to determine the protein levels of GFAP, neurocan, phosphacan, CD206, arginase-1(Arg-1), interleukin(IL)-1ß, IL-6, and IL-4. Compared with the sham, model 7 d and model 14 d groups showed cerebral infarction of different degrees, severe pathological injury of cerebral cortex and hippocampus, neurological impairment, reduced spatial learning and memory, cognitive dysfunction, severe anxiety, astrocyte hyperplasia, thickening penumbra glial scar, and up-regulated protein levels of IL-1ß, IL-6, GFAP, neurocan, phosphacan, CD206, and Arg-1(P<0.01). Compared with the model group, NTF 7 d and NTF 14 d groups improved spatial learning, memory, and cognitive function, reduced anxiety, improved nerve function, reduced cerebral infarction volume, reduced astrocyte hyperplasia, thinned penumbra glial scar, down-regulated the protein levels of GFAP, neurocan, phosphacan, IL-6, and IL-1ß, and up-regulated the protein levels of IL-4, CD206, and Arg-1(P<0.05 or P<0.01). NTF exerts a neuroprotective effect on CIRI by inducing the M2 polarization of microglia, inhibiting inflammatory response, and reducing the formation of glial scar.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Ratos , Animais , Microglia/metabolismo , Gliose/patologia , Ratos Sprague-Dawley , Hiperplasia , Interleucina-4 , Interleucina-6 , Neurocam , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores , Infarto da Artéria Cerebral Média , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo
2.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4305-4313, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36046856

RESUMO

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Traumatismo por Reperfusão , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Cálcio/metabolismo , Humanos , Mitocôndrias/patologia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle
3.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5406-5417, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36471954

RESUMO

Cerebral ischemia-reperfusion injury(CIRI) is a complex cascade process and seriously hinders the recovery of patients with acute ischemic stroke, which has become an urgent public health issue to be addressed. Silent information regulators(SIRTs) are a family of nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, capable of deacylating the histone and non-histone lysine groups. Accumulating evidence has demonstrated that SIRTs are able to regulate the pathological processes such as oxidative stress, inflammatory response, mitochondrial dysfunction, and programmed cell death of CIRI through post-translational deacetylation, and exert the neuroprotection function. In this study, we reviewed the papers about the role and regulatory mechanisms of SIRTs in the pathological process of CIRI published in the past decade. Further, we summarized the research advance in the prevention and treatment of CIRI with Chinese medicine targeting SIRTs and the related signaling pathways. This review will provide new targets and theoretical support for the clinical application of Chinese medicine in treating CIRI during the occurrence of ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Traumatismo por Reperfusão , Sirtuínas , Humanos , Isquemia Encefálica/enzimologia , Isquemia Encefálica/terapia , AVC Isquêmico/enzimologia , AVC Isquêmico/terapia , Medicina Tradicional Chinesa , Estresse Oxidativo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Sirtuínas/metabolismo
4.
Endoscopy ; 53(9): 914-919, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33580488

RESUMO

BACKGROUND: The medical consortium is an intensive and disease-specific association that integrates tertiary public hospitals and medical examination centers in China. We aimed to evaluate the feasibility of the medical consortium for screening upper gastrointestinal (GI) cancers (MCSC) by magnetically controlled capsule gastroscopy (MCCG). METHODS: 6627 asymptomatic subjects underwent MCCG as part of health check-ups in the MCSC between March and November 2018. Relevant clinical data were collected and analyzed. RESULTS: The MCSC detected 32 patients with upper GI cancer (0.48 %) confirmed by pathology. The detection rate of early gastric cancer was 16.67 % (4 /24). Gastric polyps, ulcers, and submucosal tumors were found in 15.54 %, 3.76 %, and 3.17 % of subjects, respectively. The whole GI preparation and operation process were well tolerated. CONCLUSIONS: The MCSC was a feasible model for upper GI cancer screening, especially for asymptomatic subjects. Further prospective studies with better operational quality control are warranted.


Assuntos
Endoscopia por Cápsula , Neoplasias Gástricas , Detecção Precoce de Câncer , Estudos de Viabilidade , Gastroscopia , Humanos , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico
5.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6139-6148, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34951241

RESUMO

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.


Assuntos
Gliose , Acidente Vascular Cerebral , Astrócitos , Axônios/patologia , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Gliose/patologia , Humanos , Medicina Tradicional Chinesa , Regeneração Nervosa , Acidente Vascular Cerebral/tratamento farmacológico
6.
J Am Chem Soc ; 140(12): 4391-4400, 2018 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-29494136

RESUMO

We report a new quasi-one-dimensional compound KMn6Bi5 composed of parallel nanowires crystallizing in a monoclinic space group C2/ m with a = 22.994(2) Å, b = 4.6128(3) Å, c = 13.3830(13) Å and ß = 124.578(6)°. The nanowires are infinite [Mn6Bi5]- columns each of which is composed of a nanotube of Bi atoms acting as the cladding with a nanorod of Mn atoms located in the central axis of the nanotubes. The nanorods of Mn atoms inside the Bi cladding are stabilized by Mn-Mn bonding and are defined by distorted Mn-centered cluster icosahedra of Mn13 sharing their vertices along the b axis. The [Mn6Bi5]- nanowires are linked with weak internanowire Bi-Bi bonds and charge balanced with K+ ions. The [Mn6Bi5]- nanowires were directly imaged by high-resolution transmission electron microscopy and scanning transmission electron microscopy. Magnetic susceptibility studies show one-dimensional characteristics with an antiferromagnetic transition at ∼75 K and a small average effective magnetic moment (1.56 µB/Mn for H ∥ b and 1.37 µB/Mn for H ⊥ b) of Mn from Curie-Weiss fits above 150 K. Specific heat measurements reveal an electronic specific heat coefficient γ of 6.5(2) mJ K-2(mol-Mn)-1 and a small magnetic entropy change Δ Smag ≈ 1.6 J K-1 (mol-Mn)-1 across the antiferromagnetic transition. In contrast to a metallic resistivity along the column, the resistivity perpendicular to the column shows a change from a semiconducting behavior at high temperatures to a metallic one at low temperatures, indicating an incoherent-to-coherent crossover of the intercolumn tunneling of electrons.

7.
Clin Gastroenterol Hepatol ; 14(9): 1266-1273.e1, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27211503

RESUMO

BACKGROUND & AIMS: Diseases of the stomach, including gastric cancer and peptic ulcer, are the most common digestive diseases. It is impossible to visualize the entire stomach with the passive capsule currently used in practice because of the large size of the gastric cavity. A magnetically controlled capsule endoscopy (MCE) system has been designed to explore the stomach. We performed a prospective study to compare the accuracy of detection of gastric focal lesions by MCE vs conventional gastroscopy (the standard method). METHODS: We performed a multicenter blinded study comparing MCE with conventional gastroscopy in 350 patients (mean age, 46.6 y), with upper abdominal complaints scheduled to undergo gastroscopy at a tertiary center in China from August 2014 through December 2014. All patients underwent MCE, followed by conventional gastroscopy 2 hours later, without sedation. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of detection of gastric focal lesions by MCE, using gastroscopy as the standard. RESULTS: MCE detected gastric focal lesions in the whole stomach with 90.4% sensitivity (95% confidence interval [CI], 84.7%-96.1%), 94.7% specificity (95% CI, 91.9%-97.5%), a positive predictive value of 87.9% (95% CI, 81.7%-94.0%), a negative predictive value of 95.9% (95% CI, 93.4%-98.4%), and 93.4% accuracy (95% CI, 90.83%-96.02%). MCE detected focal lesions in the upper stomach (cardia, fundus, and body) with 90.2% sensitivity (95% CI, 82.0%-98.4%) and 96.7% specificity (95% CI, 94.4%-98.9%). MCE detected focal lesions in the lower stomach (angulus, antrum, and pylorus) with 90.6% sensitivity (95% CI, 82.7%-98.4%) and 97.9% specificity (95% CI, 96.1%-99.7%). MCE detected 1 advanced gastric carcinoma, 2 malignant lymphomas, and 1 early stage gastric tumor. MCE did not miss any lesions of significance (including tumors or large ulcers). Among the 350 patients, 5 reported 9 adverse events (1.4%) and 335 preferred MCE over gastroscopy (95.7%). CONCLUSIONS: MCE detects focal lesions in the upper and lower stomach with comparable accuracy with conventional gastroscopy. MCE is preferred by almost all patients, compared with gastroscopy, and can be used to screen gastric diseases without sedation. Clinicaltrials.gov number: NCT02219529.


Assuntos
Endoscopia por Cápsula/métodos , Gastroscopia/métodos , Gastropatias/diagnóstico , Adolescente , Adulto , Idoso , Animais , China , Feminino , Humanos , Magnetismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Centros de Atenção Terciária , Adulto Jovem
8.
Yi Chuan ; 38(1): 17-27, 2016 01.
Artigo em Zh | MEDLINE | ID: mdl-26787520

RESUMO

Drosophila melanogaster, an important model organism for studying life science, has contributed more to the research of genetics, developmental biology and biomedicine with the development of genome editing techniques. Drosophila genome-editing techniques have evolved from random mutagenesis to precise genome editing and from simple mutant construction to diverse genome editing methods since the 20th century. Chemical mutagenesis, using Ethyl methanesulfonate (EMS), is an important technique to study gene function in forward genetics, however, the precise knockout of Drosophila genes could not be achieved. The gene targeting technology, based on homologous recombination, has accomplished the precise editing of Drosophila genome for the first time, but with low efficiency. The CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)-mediated precise genome editing is simple, fast and highly efficient compared with the gene targeting technology in Drosophila. In this review, we focus on Drosophila gene knockout, and summarize the evolution of genome editing techniques in Drosophila, emphasizing the development and applications of gene targeting, zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR/Cas9 techniques.


Assuntos
Drosophila melanogaster/genética , Evolução Molecular , Engenharia Genética/métodos , Genoma de Inseto , Mutagênese , Animais , Sistemas CRISPR-Cas , Edição de RNA
9.
Zhongguo Zhong Yao Za Zhi ; 40(1): 73-8, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25993791

RESUMO

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.


Assuntos
Química Farmacêutica/métodos , Dermatite/tratamento farmacológico , Portadores de Fármacos/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Glicosídeos/química , Glicosídeos/farmacocinética , Nanopartículas/química , Tripterygium/química , Animais , Química Farmacêutica/instrumentação , Dermatite/imunologia , Emulsões/química , Feminino , Humanos , Interleucina-4/imunologia , Interleucina-8/imunologia , Camundongos , Camundongos Endogâmicos ICR
10.
Tumour Biol ; 35(7): 6831-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24729126

RESUMO

A number of studies have shown that obesity is implicated in the susceptibility to several cancers. However, the association between obesity and cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively assess the association between overweight or obesity and the incidence of cholangiocarcinoma. A literature search was performed for cohort and case-control studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases. Studies were included if they reported odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or overweight. Normal weight, overweight, and obesity were defined when the body mass index (BMI) was 18.5-24.9, 25-29.9, and ≥ 30 kg/m(2), respectively. Excess body weight was defined as BMI ≥ 25 kg/m(2). Ten studies met the inclusion criteria, which included five cohort and five case-control studies. Compared with normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95 %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel plot revealed no evidence for publication bias. Obesity is associated with the increased risk of cholangiocarcinoma, which needs to be confirmed by long-term cohort studies.


Assuntos
Colangiocarcinoma/epidemiologia , Obesidade/epidemiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Colangiocarcinoma/complicações , Colangiocarcinoma/patologia , Humanos , Obesidade/complicações , Obesidade/patologia , Sobrepeso , Fatores de Risco
11.
Biomed Chromatogr ; 26(10): 1276-81, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22334234

RESUMO

Tetramethylpyrazine (TMP) is one of the most important active ingredients of a Chinese herb Ligusticum wallichii Franchat, which is widely used for the treatment of cardiovascular diseases. Several factors may affect TMP exposure after topical administration, resulting in large variability and demanding further elucidation of drug distribution. This paper describes a new efficient reliable LC-MS/MS assay for the determination of TMP in dermal microdialysate, where TMP was separated on an Agilent C(18) column (3.5 µm, 100 mm × 2.1 mm i.d.) using a mixture of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow-rate of 0.3 mL/min. The retention time was 1.89 min for TMP and 1.17 min for the internal standard (caffeine). Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for TMP was not altered through the implant lifetime. The validation and sample analysis results showed that the method is precise, accurate and well suited to support dermal microdialysis experiments.


Assuntos
Cromatografia Líquida/métodos , Microdiálise/instrumentação , Pirazinas/análise , Espectrometria de Massas em Tandem/métodos , Abdome/cirurgia , Análise de Variância , Animais , Calibragem , Estabilidade de Medicamentos , Eletrodos Implantados , Desenho de Equipamento , Modelos Lineares , Masculino , Microdiálise/métodos , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Tela Subcutânea/cirurgia
12.
Yao Xue Xue Bao ; 47(2): 244-9, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22512039

RESUMO

Investigation of the pharmacokinetics of paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments by the skin-blood synchronous microdialysis coupled with LC/MS is reported in this study. The microdialysis systems were established by linear probes and concentric circles probes. In vivo recovery of paeonol in skin is (69.7 +/- 4.8) % and in blood is (51.6 +/- 7.2)%. The paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments were administered to rats. PBS (pH 7.4) served as perfused solution. The perfusion rate was 5 microL x mL(-1) and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by LC/MS. The results showed that paeonol microemulsion and microemulsion-based gels significantly raised the drug concentrations in skin more than that of paeonol ointments. The paeonol microemulsion-based gels has similar bioavailability as the paeonol ointments in blood, but its blood drug concentrations were steadier. The paeonol microemulsion-based gels may be developed into a new preparation for dermis eczema. The skin-blood synchronous microdialysis technique proved to be a new method for the pharmacokinetics study of transdermal delivery systems.


Assuntos
Acetofenonas/farmacocinética , Sistemas de Liberação de Medicamentos , Absorção Cutânea , Acetofenonas/administração & dosagem , Acetofenonas/sangue , Acetofenonas/metabolismo , Administração Cutânea , Animais , Disponibilidade Biológica , Cromatografia Líquida , Emulsões , Géis , Masculino , Espectrometria de Massas , Microdiálise , Ratos , Ratos Sprague-Dawley , Pele/metabolismo
13.
Bioorg Med Chem Lett ; 20(15): 4464-7, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20591664

RESUMO

Herein we describe the discovery of compound 3g, a potent positive inotropic agent compared with the standard drug, milrinone. Compound 3g was developed from a series of 2-(4-substitutedbenzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl) acetamides found in an evaluation of inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities, but 3g was the most potent, with 7.68+/-0.14% increased stroke volume (milrinone 2.38+/-0.05%) at 1 x 10(-5)M in our in vitro study. The chronotropic effects of compounds having significant inotropic effects were also evaluated.


Assuntos
Acetamidas/química , Azepinas/química , Benzoxazinas/química , Compostos de Benzil/química , Cardiotônicos/síntese química , Acetamidas/síntese química , Acetamidas/farmacologia , Animais , Cardiotônicos/química , Cardiotônicos/farmacologia , Átrios do Coração/fisiopatologia , Milrinona/farmacologia , Coelhos
14.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 3): m246, 2010 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-21580202

RESUMO

In the title compound, [Mn(2)(C(8)H(7)O(2))(2)Cl(2)(C(13)H(14)N(2))(4)](n), the two Mn(II) atoms lie on inversion centers and are connected by the N-heterocyclic ligands into a wave-like lamellar framework structure. One Mn(II) atom is covalently bonded to two Cl atoms and the other to two benzyl-acetate anions; both Mn atoms show distorted octahedral coordinations.

15.
Exp Ther Med ; 19(1): 115-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31853280

RESUMO

The radial force of esophageal stents may not completely change during extraction and therefore, the procedure of stent removal may cause tissue damage. The present study reports the manufacture of 2 novel detachable stents, which were designed to reduce tissue damage through their capacity to be taken or fall apart prior to removal and evaluated the supporting properties of these stents and the extent of local mucosal injury during their removal. The stents were manufactured by braiding, heat-setting, coating and connecting. The properties of the stents were evaluated by determining the following parameters: Expansion point, softening point, stent flexibility, radial compression ratio and radial force. A total of 18 rabbits with induced esophageal stricture were randomly assigned to 3 groups as follows: Detachable stent (DS) group, biodegradable stent (BS) group and control group. The stricture rate, complications, survival, degradation and stent removal were observed over 8 weeks. The stents of the DS and BS groups provided a similar supporting effect. The stricture rate, incidence of complications and survival were also similar between the 2 groups, while significant differences were noted between the DS and control groups and between the BS and control groups. In the BS group, the stents were degraded and moved to the stomach within 7 weeks (2 in 6 weeks and 3 in 7 weeks). The debris was extracted using biopsy forceps. In the DS group, all stents were easy to remove and 2 cases exhibited minor hemorrhage. In conclusion, the 2 types of novel detachable stent provided an equally efficient supporting effect in vitro and in vivo and may reduce the incidence of secondary injury during stent removal.

16.
Bioorg Med Chem Lett ; 19(9): 2392-5, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19356931

RESUMO

A series of 1-substituted-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) piperidine-4-carboxamides has been synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit-heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 1-(2-fluorobenzyl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)piperidine-4-carboxamide 6a was the most potent, increasing stroke volume by 11.92+/-0.35% (milrinone: 6.36+/-0.13%) at 1x10(-4)M.


Assuntos
Química Orgânica/métodos , Coração/efeitos dos fármacos , Piperidinas/química , Quinolinas/química , Animais , Cardiotônicos/síntese química , Cardiotônicos/farmacologia , Química Farmacêutica/métodos , Desenho de Fármacos , Ácidos Isonipecóticos/química , Milrinona/síntese química , Milrinona/farmacologia , Modelos Químicos , Miocárdio/metabolismo , Coelhos
17.
J Pharm Pharmacol ; 61(9): 1155-61, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19703364

RESUMO

OBJECTIVES: The aim was to prepare neoglycoprotein-based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo. METHODS: The neoglycoprotein of bovine serum albumin modified with mannose 6-phosphate was synthesised from mannose, and used as wall material to nanoencapsulate the model natural antifibrotic substance sodium ferulate using a desolvation method. The morphology, drug loading capacity, release in vitro and biodistribution in vivo of the nanoparticles were studied. Selectivity of the nanoparticles for hepatic stellate cells was evaluated by immunohistochemical analysis of fibrotic rat liver sections. KEY FINDINGS: The spherical nanoparticles were negatively charged with zeta potential ranging from -2.73 to -35.85 mV, and sizes between 100 and 200 nm with a narrow size distribution. Drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) could be achieved. in vitro, the nanoparticles showed an initial rapid continuous release followed by a slower sustained release. After intravenous injection into mice, the nanoparticles showed a slower elimination rate and a much higher drug concentration in liver compared with the sodium ferrate solution, and less distribution to the kidneys and other tissues. Immunohistochemistry indicated that the neoglycoprotein-based nanoparticles were taken up specifically by hepatic stellate cells. CONCLUSIONS: The nanoparticles may be an efficient drug carrier targeting hepatic stellate cells.


Assuntos
Ácidos Cumáricos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Cirrose Hepática/tratamento farmacológico , Manosefosfatos/administração & dosagem , Nanopartículas/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Animais , Ácidos Cumáricos/farmacocinética , Portadores de Fármacos/farmacocinética , Glicoproteínas/administração & dosagem , Glicoproteínas/síntese química , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Manosefosfatos/química , Camundongos , Ratos , Soroalbumina Bovina/química , Distribuição Tecidual
18.
Biomed Chromatogr ; 23(7): 692-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19309751

RESUMO

A sensitive and selective LC-MS/MS method was developed and validated for the determination of aconitine in microdialysate and rat plasma. Extraction of plasma sample was conducted by use of 1% trichloracetic acid and acetonitrile solution with 10 ng/mL internal standard (propafenone) spiked. Microdialysates were analyzed without sample purification. After sample preparation, 2 microL were injected and separated with an isocratic mobile phase consisting of acetonitrile:0.1% formic acid (60:40, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple-reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode. Overall, the assay exhibited good precision and accuracy. The diffusion properties of aconitine investigated in in vitro microdialysis experiments revealed unfavourable concentration dependence avertable by keeping a constant pH 5.77 using isotonic phosphate buffer solution as perfusate. The mean relative recoveries were 48.23% [coefficient of variation (CV 4.47%)] and 55.38% (CV 2.89%) for retrodialysis and recovery experiments, respectively. The in vivo recovery of aconitine was 34.48% (CV 3.05%) and was stable over the 6 h study period. Following characterization of aconitine both in vitro and in vivo microdialysis, the developed setting is suitable for application in pharmacokinetics and pharmacodynamics studies.


Assuntos
Aconitina/análise , Aconitina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Soluções para Diálise/química , Espectrometria de Massas em Tandem/métodos , Animais , Calibragem , Interpretação Estatística de Dados , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Modelos Lineares , Microdiálise/métodos , Propafenona/sangue , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Chem Pharm Bull (Tokyo) ; 57(10): 1045-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19801856

RESUMO

Focused on the natural biodegradable material of chitosan (CS), this investigation concerned its spray-dried nanoparticles-in-microparticles (NiMPs) modified with ulex europaeus agglutinin (UEA). Chitosan nanoparticles were obtained by ionotropic gelation process with pentasodium tripolyphosphate as gelatinizer. Then UEA lectin was bound onto the CS nanoparticles activated by glutaraldehyde. The conjugated spherical UEA-CS-NiMPs, prepared by spray drying method, exhibited 12-85% coupling efficiency of UEA depending upon the amount of activator glutaraldehyde. And the UEA-grafted particles showed additional higher binding tendency with bovine submaxillary gland mucin as compared to the plain chitosan microparticles. Furthermore, the activity and intrinsic fucose-specificity of UEA were still maintained after the covalent modification. It is thus evident that the UEA anchored CS-NiMPs might be used as a potential drug delivery system targeted to the specific regions of gastrointestinal tract.


Assuntos
Aglutininas/metabolismo , Quitosana/química , Mucinas/metabolismo , Nanopartículas/química , Glândula Submandibular/metabolismo , Ulex/metabolismo , Animais , Bovinos , Portadores de Fármacos/química , Glutaral/química , Ligação Proteica
20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 6): o1213, 2009 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-21583082

RESUMO

In the title compound, C(10)H(8)N(2)S(2)·C(4)H(6)O(2), both components of the cocrystal lie on crystallographic twofold rotation axes. In the di-2-pyridyl disulfide mol-ecule, the dihedral angle between the two pyridine rings is 66.6 (1)°. In the crystal structure, inter-molecular O-H⋯N and weak C-H⋯O hydrogen bonds link both types of mol-ecules into columns along the c axis.

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