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1.
Zhonghua Wai Ke Za Zhi ; 61(12): 1074-1079, 2023 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-37932143

RESUMO

Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 µmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.


Assuntos
Apendicite , Idoso , Feminino , Masculino , Humanos , Apendicite/cirurgia , Modelos Estatísticos , Nomogramas , Prognóstico , Estudos Retrospectivos , Dor Abdominal , Bilirrubina
2.
Zhonghua Wai Ke Za Zhi ; 60(4): 363-371, 2022 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-35272428

RESUMO

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Estudos Retrospectivos
3.
Acta Gastroenterol Belg ; 84(1): 51-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639693

RESUMO

Background and study aims: To investigate the safety and efficacy of splenectomy for hepatolenticular degeneration (HLD) patients with PLT less than 20 × 109/L. Patients and methods: A total of 244 HLD patients with hypersplenism underwent splenectomy. According to the preoperative PLT values, the patients were divided into three groups : group A of 53 patients with PLT < 20 × 109/L ; group B of 92 patients with 20 × 109/L ≤ PLT ≤ 30 × 109/L ; group C of 99 patients with PLT > 30 × 109/L. General information including : blood cell counts, liver function , coagulation function 1 day before sugery and 1, 7, 14 days after surgery ; intraoperative blood loss ; operation time ; vital signs at the beginning, at 60 minutes and the end of the operation. Pressure and blood oxygen ; postoperative drainage ; postoperative complications and mortality. Results: Blood cell counts, liver function, and coagulation function were improved after splenectomy in three groups (P<0.05) ; there was no significant difference in blood loss, operation time, vital signs during the operation, postoperative drainage, postoperative complications and mortality between three groups (P>0.05). Conclusion: For HLD patients with hypersplenism, it is safe and effective to conduct splenectomy under PLT < 20 × 109/L.


Assuntos
Degeneração Hepatolenticular , Hiperesplenismo , Laparoscopia , Humanos , Hiperesplenismo/etiologia , Hiperesplenismo/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esplenectomia , Resultado do Tratamento
4.
Zhonghua Yi Xue Za Zhi ; 96(13): 1026-30, 2016 Apr 05.
Artigo em Chinês | MEDLINE | ID: mdl-27055795

RESUMO

OBJECTIVE: To explore the effect of icariin on the proteomic expression profile of bone microvascular endothelial cells of human femoral head against steroids-induced lesion using protein chip system in vitro. METHODS: Bone microvascular endothelial cells (BMECs) in cancellous bone of femoral head were isolated and harvested in vitro.The model of BMECs injury induced by glucocorticoid and icariin preconditioning was established. The apoptosis of BMECs were detected with terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)methods. The proteomic expression profile of BMECs in each group were detected by protein chip system. RESULTS: The apoptosis rates of hydrocortisone groups (46.9%±5.8%, 78.0%±8.5%) were significantly higher than that of normal group(4.8%±1.3%), meanwhile the apoptosis rate of icariin+ hydrocortisone groups(15.2%±7.7%, 44.6%±5.3%)significantly decreased compared with hydrocortisone group (P<0.001). The results of protein chip showed that the expression of granulocyte colony-stimulating factor (G-CSF) in the hydrocortisone group decreased compared with the control group, meanwhile the expression of IL-4 increased. The expression of G-CSF in the icariin+ hydrocortisone groups increased compared with the hydrocortisone group, meanwhile the expression of IL-4 decreased.No appreciable change was found in the expression of apoptotic factors. CONCLUSION: The therapy effect of icariin for steroid-induced necrosis of femoral head might be related with the protective action to BMECs and the moderating effect of promoting the proteins expression of pro-angiogenesis factor and inhibiting expression of inflammatory factor.


Assuntos
Células Endoteliais/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Flavonoides/efeitos adversos , Glucocorticoides/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/metabolismo , Proteômica , Apoptose , Células Endoteliais/metabolismo , Humanos , Interleucina-4 , Osteócitos , Esteroides
5.
J Dent Res ; 95(5): 496-505, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26848068

RESUMO

It is well known that the service life of contemporary composite restoration is unsatisfactory, and longevity of dentin bonding is one of the major culprits. Bonding is essentially a hybridization process in which dental substrate and adhesive resin interact with each other through an exchange process. Thus, the longevity of dentin bonding can only be improved with enhanced qualities in substrate, adhesive resin, and their interaction within the hybridization zone. This review aims to collect and summarize recent advances in utilizing nonthermal atmospheric plasmas (NTAPs)-a novel technology that delivers highly reactive species in a gaseous medium at or below physiologic temperature-to improve the durability of dentin bonding by addressing these 3 issues simultaneously. Overall, NTAP has demonstrated efficacies in improving a number of critical properties for dentin bonding, including deactivation of oral pathogens, modification of surface chemistry/properties, resin polymerization, improvement in adhesive-dentin interactions, and establishment of auxiliary bonding mechanism. While a few preliminary studies have indicated the benefit of NTAP to bond strength and stability, additional researches are warranted to employ knowledge acquired so far and to evaluate these properties in a systematic way.


Assuntos
Resinas Compostas/química , Colagem Dentária , Restauração Dentária Permanente/métodos , Adesivos Dentinários/química , Gases em Plasma/química , Antibacterianos/química , Dentina/microbiologia , Dentina/ultraestrutura , Humanos , Polimerização , Estresse Mecânico , Propriedades de Superfície
6.
Bone Joint Res ; 4(4): 56-64, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25837672

RESUMO

OBJECTIVES: The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. METHODS: The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. RESULTS: After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. CONCLUSION: This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64.

7.
Exp Neurol ; 269: 56-66, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25819102

RESUMO

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Programmed death of neuronal cells plays a crucial role in acute and chronic neurodegeneration following TBI. The tumor suppressor protein p53, a transcription factor, has been recognized as an important regulator of apoptotic neuronal death. The p53 inactivator pifithrin-α (PFT-α) has been shown to be neuroprotective against stroke. A previous cellular study indicated that PFT-α oxygen analog (PFT-α (O)) is more stable and active than PFT-α. We aimed to investigate whether inhibition of p53 using PFT-α or PFT-α (O) would be a potential neuroprotective strategy for TBI. To evaluate whether these drugs protect against excitotoxicity in vitro, primary rat cortical cultures were challenged with glutamate (50mM) in the presence or absence of various concentrations of the p53 inhibitors PFT-α or PFT-α (O). Cell viability was estimated by LDH assay. In vivo, adult Sprague Dawley rats were subjected to controlled cortical impact (CCI, with 4m/s velocity, 2mm deformation). Five hours after injury, PFT-α or PFT-α (O) (2mg/kg, i.v.) was administered to animals. Sensory and motor functions were evaluated by behavioral tests at 24h after TBI. The p53-positive neurons were identified by double staining with cell-specific markers. Levels of mRNA encoding for p53-regulated genes (BAX, PUMA, Bcl-2 and p21) were measured by reverse transcription followed by real time-PCR from TBI animals without or with PFT-α/PFT-α (O) treatment. We found that PFT-α(O) (10 µM) enhanced neuronal survival against glutamate-induced cytotoxicity in vitro more effectively than PFT-α (10 µM). In vivo PFT-α (O) treatment enhanced functional recovery and decreased contusion volume at 24h post-injury. Neuroprotection by PFT-α (O) treatment also reduced p53-positive neurons in the cortical contusion region. In addition, p53-regulated PUMA mRNA levels at 8h were significantly reduced by PFT-α (O) administration after TBI. PFT-α (O) treatment also decreased phospho-p53 positive neurons in the cortical contusion region. Our data suggest that PFT-α (O) provided a significant reduction of cortical cell death and protected neurons from glutamate-induced excitotoxicity in vitro, as well as improved neurological functional outcome and reduced brain injury in vivo via anti-apoptotic mechanisms. The inhibition of p53-induced apoptosis by PFT-α (O) provides a useful tool to evaluate reversible apoptotic mechanisms and may develop into a novel therapeutic strategy for TBI.


Assuntos
Benzotiazóis/farmacologia , Lesões Encefálicas/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Tolueno/análogos & derivados , Animais , Apoptose/fisiologia , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Neurônios/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Tolueno/farmacologia , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo
8.
Genet Mol Res ; 12(3): 2442-54, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23420404

RESUMO

Penicillium expansum produces large amounts of lipase, which is widely used in laundry detergent and leather industry. We isolated the glyceraldehyde-3-phosphate dehydrogenase gene (PeGPD) from P. expansum PE-12 through reverse transcriptase PCR and 5'-3' rapid amplification of cDNA ends (RACE-PCR). The gene is 1266 bp long, including an ORF of 1014 bp, encoding a polypeptide chain of 337 amino acids. A phylogenetic tree based on GPD proteins showed that P. expansum is close to Aspergillus species, but comparatively distant from P. marneffei. Southern blot results revealed a single copy of PeGPD, and expression analysis gave evidence of high expression levels. PeGPD genes have potential for genetic engineering of P. expansum for industrial lipase production.


Assuntos
Proteínas Fúngicas/genética , Genes Fúngicos , Glicerolfosfato Desidrogenase/genética , Penicillium/enzimologia , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Glicerolfosfato Desidrogenase/química , Glicerolfosfato Desidrogenase/metabolismo , Dados de Sequência Molecular , Penicillium/genética , Filogenia
9.
J Biomed Mater Res A ; 101(4): 963-72, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22965926

RESUMO

In this article, the plasma surface modification effects on the chemical, mechanical, and biological properties of electrospun poly (ε-caprolactone) (PCL) random nanofiber meshes (NFMs) were investigated by adjusting plasma chemistry, that is, using glow discharges of N(2) +H(2), NH(3) +O(2), and Ar+O(2) gas mixtures. The surface property changes of electrospun PCL NFMs after those plasma treatments were examined by water contact angle measurements and X-ray photoelectron spectroscopy. The experimental results showed that the plasma treatments introduced polar groups onto the surfaces and thus increased the surface hydrophilicity. From tensile test data, plasma treatment had limited effect on the mechanical properties of PCL random NFMs. The biological properties of the plasma-treated PCL NFMs were examined by cell proliferation assays using mouse osteoblast cells (MC3T3-E1). It was found that the plasma-treated PCL NFMs gave a higher proliferation rate and improved cell adhesion properties as compared with the untreated controls.


Assuntos
Materiais Biocompatíveis , Teste de Materiais , Nanofibras/química , Osteoblastos/metabolismo , Poliésteres/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Camundongos , Osteoblastos/citologia
10.
Rev Sci Instrum ; 78(1): 015104, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17503943

RESUMO

A cold plasma brush is generated at atmospheric pressure with low power consumption in the level of several watts (as low as 4 W) up to tens of watts (up to 45 W). The plasma can be ignited and sustained in both continuous and pulsed modes with different plasma gases such as argon or helium, but argon was selected as a primary gas for use in this work. The brush-shaped plasma is formed and extended outside of the discharge chamber with typical dimension of 10-15 mm in width and less than 1.0 mm in thickness, which are adjustable by changing the discharge chamber design and operating conditions. The brush-shaped plasma provides some unique features and distinct nonequilibrium plasma characteristics. Temperature measurements using a thermocouple thermometer showed that the gas phase temperatures of the plasma brush are close to room temperature (as low as 42 degrees C) when running with a relatively high gas flow rate of about 3500 ml/min. For an argon plasma brush, the operating voltage from less than 500 V to about 2500 V was tested, with an argon gas flow rate varied from less than 1000 to 3500 ml/min. The cold plasma brush can most efficiently use the discharge power as well as the plasma gas for material and surface treatment. The very low power consumption of such an atmospheric argon plasma brush provides many unique advantages in practical applications including battery-powered operation and use in large-scale applications. Several polymer film samples were tested for surface treatment with the newly developed device, and successful changes of the wettability property from hydrophobic to hydrophilic were achieved within a few seconds.


Assuntos
Argônio , Eletroquímica , Hélio , Pressão Atmosférica , Eletroquímica/instrumentação , Eletroquímica/métodos , Eletrodos , Interações Hidrofóbicas e Hidrofílicas , Molhabilidade
11.
J Biomed Mater Res B Appl Biomater ; 80(1): 211-9, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16850477

RESUMO

This study investigated the bacterial inactivation/sterilization effects of a new atmospheric plasma source, which is a brush-shaped argon glow discharge created under 1 atm pressure. Such an atmospheric plasma brush requires extremely low power of less than 20 W to operate; and therefore is essentially a low-temperature discharge as confirmed by gas-phase temperature measurements. Two bacteria, Escherichia coli (E. coli) and Micrococcus luteus (M. luteus), seeded in various media were subjected to plasma treatment and their survivability was examined. It was found that such argon atmospheric plasma brush is very effective in destruction of the bacteria cells. With nutrient broth and standard methods agar as supporting media, a cell reduction in a level of 6 orders of magnitude was observed for E. coli within 3-4 min plasma treatment. A similar level of cell reduction was also observed for M. luteus in the two media with 2 or 3 min plasma treatment. The plasma treatment effects on the bacteria cell structures were also examined using scanning electron microscopy and the cell structure damages due to the plasma exposure were observed on both bacteria. The possible sterilization mechanism of the argon plasmas is also discussed in this article.


Assuntos
Argônio/química , Contaminação de Equipamentos/prevenção & controle , Escherichia coli/crescimento & desenvolvimento , Micrococcus luteus/crescimento & desenvolvimento , Esterilização , Escherichia coli/ultraestrutura , Infecções por Escherichia coli/prevenção & controle , Temperatura Alta , Viabilidade Microbiana , Micrococcus luteus/ultraestrutura , Microscopia Eletrônica de Varredura , Esterilização/instrumentação , Esterilização/métodos , Fatores de Tempo
12.
Pharmazie ; 60(9): 674-6, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16222867

RESUMO

An artificial neural network model is developed to predict percent human intestinal absorption (%FA) of compounds from their molecular structural parameters. These parameters are the polar molecular surface area (PSA), the fraction of polar molecular surface area (FPSA, polar molecular surface area/ molecular surface area), the sum of the net atomic charges of oxygen atoms (Q(O)), the sum of the net atomic charges of nitrogen atoms with net negative atomic charges (Q(N)), the sum of the net atomic charges of hydrogen atoms attached to oxygen or nitrogen atoms (Q(H)), and the number of carboxyls (nCOOH). For a training set of 85 compounds anda test set of 10 compounds, root mean squared errors (RMSE) between experimental %FA valuesand calculated/predicted %FA values are 8.86% and 14.1%, respectively.


Assuntos
Absorção Intestinal , Redes Neurais de Computação , Inteligência Artificial , Fenômenos Químicos , Química Farmacêutica , Físico-Química , Humanos , Preparações Farmacêuticas/química , Valor Preditivo dos Testes
13.
Chem Biol Interact ; 157-158: 363-5, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16429486

RESUMO

Previous studies in rodents and nonhuman primates have demonstrated that pretreatment with cholinesterases can provide significant protection against behavioral and lethal effects of nerve agent intoxication. Human butyrylcholinesterase (HuBuChE) purified from plasma has been shown to protect against up to 5 x LD50s of nerve agents in guinea pigs and non-human primates, and is currently being explored as a bioscavenger pretreatment for human use. A recombinant form of HuBuChE has been expressed in the milk of transgenic goats as a product called Protexia. Protexia was supplied by Nexia Biotechnologies (Que., Canada) as a purified solution with a specific activity of 600 U/mg. Initial in vitro studies using radiolabeled 3H-soman or 3H-DFP (diisopropyl fluorophosphate) demonstrated that these inhibitors specifically bind to Protexia. When Protexia was mixed with soman, sarin, tabun or VX using varying molar ratios of enzyme to nerve agent (8:1, 4:1, 1:1 and 1:4, respectively), the data indicated that 50% inhibition of enzyme activity occurs around the 1:1 molar ratio for each of the nerve agents. Protexia was further characterized for its interaction with pyridostigmine bromide and six unique carbamate inhibitors of cholinesterase. IC50 and Ki values for Protexia were determined to be very similar to those of HuBuChE purified from human plasma. These data suggest that Protexia has biochemical properties very similar to those HuBuChE when compared in vitro. Together these data the continued development of the goat milk-derived recombinant HuBuChE Protexia as a potential bioscavenger of organophosphorus nerve agents.


Assuntos
Butirilcolinesterase/farmacologia , Neurônios/efeitos dos fármacos , Neurotoxinas/antagonistas & inibidores , Animais , Butirilcolinesterase/química , Carbamatos/antagonistas & inibidores , Cabras , Humanos , Neurônios/enzimologia , Neurônios/patologia , Neurotoxinas/farmacologia , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia
14.
Pharmazie ; 59(4): 282-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15125573

RESUMO

The Potts and Guy's model for skin permeability, log P = alpha log K - beta MV + delta where P is the permeability coefficient of a compound from aqueous solution through human skin in vitro, K and MV are octanol-water partition coefficient and molecular volume of the compound respectively, and alpha, beta, delta are constants, is examined for a data set of 53 miscellaneous compounds. The model will result in over-estimation for penetrants having higher hydrogen-bond donor activity and underestimation for penetrants having no hydrogen-bond donor. A predictive algorithm for skin permeability including the effects of hydrogen-bond on diffusivity is proposed: log P = alpha log K - beta MV - gamma Hb + delta where Hb is the descriptor of hydrogen-bonding capacity of penetrants and gamma is a constant. The calculated log P values from the latter model are in good accordance with respective experimental ones for the data set.


Assuntos
Algoritmos , Absorção Cutânea , Fenômenos Químicos , Físico-Química , Difusão , Humanos , Ligação de Hidrogênio , Modelos Biológicos , Octanóis/química , Permeabilidade , Valor Preditivo dos Testes , Solubilidade , Água/química
15.
Pharmazie ; 59(2): 126-30, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15025181

RESUMO

An artificial neural network model is developed to predict the ratios of the steady-state concentrations of drugs in the brain to those in the blood (log BB) from their molecular structural parameters. These molecular structural parameters are the molecular volume (V), the sum of the absolute values of the net atomic charges of oxygen and nitrogen atoms which are hydrogen-bond acceptors (Q(O, N)), and the sum of the net atomic charges of hydrogen atoms attached to oxygen or nitrogen atoms (Q(H)). For a training set of 56 compounds and a test set of 5 compounds, root mean squared errors (RMSE) between experimental log BB values and calculated/predicted log BB values were 0.236 and 0.258, respectively. These molecular structural parameters can be obtained easily from quantum chemical calculations. The model is suitable for the rapid prediction of the blood-brain barrier penetration of drugs.


Assuntos
Barreira Hematoencefálica , Redes Neurais de Computação , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Algoritmos , Eletroquímica , Ligação de Hidrogênio , Modelos Químicos , Permeabilidade , Relação Estrutura-Atividade
16.
Acta Pharmacol Sin ; 22(7): 663-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11749834

RESUMO

AIM: To predict the blood-brain barrier penetration by polar molecular surface area and molecular volume. METHODS: Polar molecular surface area and molecular volume are calculated by Monte Carlo method from the lowest energy conformation obtained using the semiempirical self-consistent field molecular orbital calculation AM1 method. The stepwise multiple regression analysis is used to derive the correlation equations between the ratios of the steady-state concentrations of the training compounds in the brain to in the blood (logBB)and their structural parameters. RESULTS: For a training set of 56 compounds, logBB values are well correlated with the sums of surface areas of oxygen and nitrogen atoms (SO,N, A2, excluding the nitrogen atoms in nitrogen molecule or in nitro) and molecular volumes (V, A3). The regression equation is logBB = -1.331 x 10(-5)V2 + 9.228 x 10(-3)V -0.02439 SO,N -0.4318 (n = 56, r = 0.9043). The calculated logBB values of a test set of 10 compounds from the model agree well with their experimental logBB values. CONCLUSION: The model is simple and effective. It can be used to predict the logBB values of candidate molecule in drug design.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Compostos Orgânicos/farmacocinética , Modelos Estruturais , Compostos Orgânicos/química , Análise de Regressão
17.
Proc Natl Acad Sci U S A ; 98(13): 7605-10, 2001 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-11404470

RESUMO

The reduction in levels of the potentially toxic amyloid-beta peptide (Abeta) has emerged as one of the most important therapeutic goals in Alzheimer's disease. Key targets for this goal are factors that affect the expression and processing of the Abeta precursor protein (betaAPP). Earlier reports from our laboratory have shown that a novel cholinesterase inhibitor, phenserine, reduces betaAPP levels in vivo. Herein, we studied the mechanism of phenserine's actions to define the regulatory elements in betaAPP processing. Phenserine treatment resulted in decreased secretion of soluble betaAPP and Abeta into the conditioned media of human neuroblastoma cells without cellular toxicity. The regulation of betaAPP protein expression by phenserine was posttranscriptional as it suppressed betaAPP protein expression without altering betaAPP mRNA levels. However, phenserine's action was neither mediated through classical receptor signaling pathways, involving extracellular signal-regulated kinase or phosphatidylinositol 3-kinase activation, nor was it associated with the anticholinesterase activity of the drug. Furthermore, phenserine reduced expression of a chloramphenicol acetyltransferase reporter fused to the 5'-mRNA leader sequence of betaAPP without altering expression of a control chloramphenicol acetyltransferase reporter. These studies suggest that phenserine reduces Abeta levels by regulating betaAPP translation via the recently described iron regulatory element in the 5'-untranslated region of betaAPP mRNA, which has been shown previously to be up-regulated in the presence of interleukin-1. This study identifies an approach for the regulation of betaAPP expression that can result in a substantial reduction in the level of Abeta.


Assuntos
Precursor de Proteína beta-Amiloide/genética , Inibidores da Colinesterase/farmacologia , Interleucina-1/farmacologia , Fisostigmina/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , Regiões 5' não Traduzidas/genética , Astrocitoma , Sobrevivência Celular/efeitos dos fármacos , Cloranfenicol O-Acetiltransferase/análise , Cloranfenicol O-Acetiltransferase/genética , Cromonas/farmacologia , Meios de Cultivo Condicionados , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1/fisiologia , L-Lactato Desidrogenase/análise , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Morfolinas/farmacologia , Neuroblastoma , Fosfatidilinositol 3-Quinases/metabolismo , Fisostigmina/análogos & derivados , RNA Mensageiro/metabolismo , Proteínas Recombinantes/biossíntese , Transfecção , Células Tumorais Cultivadas
19.
J Neurochem ; 77(1): 220-8, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11279278

RESUMO

The tumor suppressor protein p53 is essential for neuronal death in several experimental settings and may participate in human neurodegenerative disorders. Based upon recent studies characterizing chemical inhibitors of p53 in preclinical studies in the cancer therapy field, we synthesized the compound pifithrin-alpha and evaluated its potential neuroprotective properties in experimental models relevant to the pathogenesis of stroke and neurodegenerative disorders. Pifithrin-alpha protected neurons against apoptosis induced by DNA-damaging agents, amyloid beta-peptide and glutamate. Protection by pifithrin-alpha was correlated with decreased p53 DNA-binding activity, decreased expression of the p53 target gene BAX and suppression of mitochondrial dysfunction and caspase activation. Mice given pifithrin-alpha exhibited increased resistance of cortical and striatal neurons to focal ischemic injury and of hippocampal neurons to excitotoxic damage. These preclinical studies demonstrate the efficacy of a p53 inhibitor in models of stroke and neurodegenerative disorders, and suggest that drugs that inhibit p53 may reduce the extent of brain damage in related human neurodegenerative conditions.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Isquemia Encefálica/tratamento farmacológico , Neurônios/efeitos dos fármacos , Convulsões/tratamento farmacológico , Tiazóis/farmacologia , Tolueno/análogos & derivados , Tolueno/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Benzotiazóis , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Caspase 3 , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ácido Glutâmico/farmacologia , Ácido Caínico , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Pró-Fármacos/farmacologia , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Convulsões/metabolismo , Proteína Supressora de Tumor p53/metabolismo
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 21(6): 826-8, 2001 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-12958906

RESUMO

The binding characteristics of methylene blue (MB) and bovine serum albumin (BSA) has been studied by fluorescence spectroscopy in aqueous solution. The results show that the equilibrium constant KA = 3.44 x 10(5) L.mol-1, the number of binding sites n = 1.03, and the quenching mechanism of fluorescence of BSA by MB is a static quenching procedure. The binding distance between MB and BSA and the energy transfer efficiency are obtained based on the theory of Förester spectroscopy energy transfer. The effect of MB on the conformation of BSA is further analyzed using synchronous fluorescence spectrometry.


Assuntos
Transferência de Energia , Azul de Metileno/química , Soroalbumina Bovina/química , Animais , Bovinos , Interações Medicamentosas , Azul de Metileno/metabolismo , Ligação Proteica , Conformação Proteica , Soroalbumina Bovina/metabolismo , Espectrometria de Fluorescência
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