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

RESUMEN

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.


Asunto(s)
Apendicitis , Anciano , Femenino , Masculino , Humanos , Apendicitis/cirugía , Modelos Estadísticos , Nomogramas , Pronóstico , Estudios Retrospectivos , Dolor Abdominal , Bilirrubina
2.
Zhonghua Wai Ke Za Zhi ; 60(4): 363-371, 2022 Apr 01.
Artículo en Zh | MEDLINE | ID: mdl-35272428

RESUMEN

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.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Nomogramas , Pronóstico , Estudios Retrospectivos
3.
Zhonghua Yi Xue Za Zhi ; 96(13): 1026-30, 2016 Apr 05.
Artículo en Zh | MEDLINE | ID: mdl-27055795

RESUMEN

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.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Necrosis de la Cabeza Femoral/inducido químicamente , Flavonoides/efectos adversos , Glucocorticoides/efectos adversos , Factor Estimulante de Colonias de Granulocitos/metabolismo , Proteómica , Apoptosis , Células Endoteliales/metabolismo , Humanos , Interleucina-4 , Osteocitos , Esteroides
4.
Genet Mol Res ; 12(3): 2442-54, 2013 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-23420404

RESUMEN

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.


Asunto(s)
Proteínas Fúngicas/genética , Genes Fúngicos , Glicerolfosfato Deshidrogenasa/genética , Penicillium/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Glicerolfosfato Deshidrogenasa/química , Glicerolfosfato Deshidrogenasa/metabolismo , Datos de Secuencia Molecular , Penicillium/genética , Filogenia
5.
Acta Gastroenterol Belg ; 84(1): 51-56, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33639693

RESUMEN

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.


Asunto(s)
Degeneración Hepatolenticular , Hiperesplenismo , Laparoscopía , Humanos , Hiperesplenismo/etiología , Hiperesplenismo/cirugía , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Esplenectomía , Resultado del Tratamiento
6.
J Biomed Mater Res B Appl Biomater ; 80(1): 211-9, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16850477

RESUMEN

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.


Asunto(s)
Argón/química , Contaminación de Equipos/prevención & control , Escherichia coli/crecimiento & desarrollo , Micrococcus luteus/crecimiento & desarrollo , Esterilización , Escherichia coli/ultraestructura , Infecciones por Escherichia coli/prevención & control , Calor , Viabilidad Microbiana , Micrococcus luteus/ultraestructura , Microscopía Electrónica de Rastreo , Esterilización/instrumentación , Esterilización/métodos , Factores de Tiempo
7.
Rev Sci Instrum ; 78(1): 015104, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17503943

RESUMEN

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.


Asunto(s)
Argón , Electroquímica , Helio , Presión Atmosférica , Electroquímica/instrumentación , Electroquímica/métodos , Electrodos , Interacciones Hidrofóbicas e Hidrofílicas , Humectabilidad
8.
J Dent Res ; 95(5): 496-505, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26848068

RESUMEN

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.


Asunto(s)
Resinas Compuestas/química , Recubrimiento Dental Adhesivo , Restauración Dental Permanente/métodos , Recubrimientos Dentinarios/química , Gases em Plasma/química , Antibacterianos/química , Dentina/microbiología , Dentina/ultraestructura , Humanos , Polimerizacion , Estrés Mecánico , Propiedades de Superficie
9.
Chem Biol Interact ; 157-158: 363-5, 2005 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-16429486

RESUMEN

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.


Asunto(s)
Butirilcolinesterasa/farmacología , Neuronas/efectos de los fármacos , Neurotoxinas/antagonistas & inhibidores , Animales , Butirilcolinesterasa/química , Carbamatos/antagonistas & inhibidores , Cabras , Humanos , Neuronas/enzimología , Neuronas/patología , Neurotoxinas/farmacología , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología
10.
Pharmazie ; 60(9): 674-6, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16222867

RESUMEN

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.


Asunto(s)
Absorción Intestinal , Redes Neurales de la Computación , Inteligencia Artificial , Fenómenos Químicos , Química Farmacéutica , Química Física , Humanos , Preparaciones Farmacéuticas/química , Valor Predictivo de las Pruebas
11.
Bone Joint Res ; 4(4): 56-64, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25837672

RESUMEN

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.

12.
Exp Neurol ; 269: 56-66, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25819102

RESUMEN

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.


Asunto(s)
Benzotiazoles/farmacología , Lesiones Encefálicas/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Oxígeno/metabolismo , Tolueno/análogos & derivados , Animales , Apoptosis/fisiología , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Neuronas/metabolismo , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Tolueno/farmacología , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/metabolismo
13.
Acta Neurol Scand Suppl ; 176: 74-84, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11261809

RESUMEN

Phenserine, a phenylcarbamate of physostigmine, is a new potent and highly selective acetylcholinesterase (AChE) inhibitor, with a > 50-fold activity versus butyrylcholinesterase (BChE), in clinical trials for the treatment of Alzheimer's disease (AD). Compared to physostigmine and tacrine, it is less toxic and robustly enhances cognition in animal models. To determine the time-dependent effects of phenserine on cholinergic function, AChE activity, brain and plasma drug levels and brain extracellular acetylcholine (ACh) concentrations were measured in rats before and after phenserine administration. Additionally, its maximum tolerated dose, compared to physostigmine and tacrine, was determined. Following i.v. dosing, brain drug levels were 10-fold higher than those achieved in plasma, peaked within 5 min and rapidly declined with half-lives of 8.5 and 12.6 min, respectively. In contrast, a high (> 70%) and long-lasting inhibition of AChE was achieved (half-life > 8.25 h). A comparison between the time-dependent plasma AChE inhibition achieved after similar oral and i.v. doses provided an estimate of oral bioavailability of 100%. Striatal, in vivo microdialysis in conscious, freely-moving phenserine-treated rats demonstrated > 3-fold rise in brain ACh levels. Phenserine thus is rapidly absorbed and cleared from the body, but produces a long-lasting stimulation of brain cholinergic function at well tolerated doses and hence has superior properties as a drug candidate for AD. It selectively inhibits AChE, minimizing potential BChE side effects. Its long duration of action, coupled with its short pharmacokinetic half-life, reduces dosing frequency, decreases body drug exposure and minimizes the dependence of drug action on the individual variations of drug metabolism commonly found in the elderly.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/farmacocinética , Fisostigmina/farmacología , Fisostigmina/farmacocinética , Administración Oral , Enfermedad de Alzheimer/patología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Inhibidores de la Colinesterasa/administración & dosificación , Modelos Animales de Enfermedad , Semivida , Infusiones Intravenosas , Masculino , Fisostigmina/administración & dosificación , Fisostigmina/análogos & derivados , Ratas , Ratas Endogámicas F344 , Tacrina/administración & dosificación , Tacrina/farmacocinética , Tacrina/farmacología
14.
FEBS Lett ; 221(2): 325-6, 1987 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-3622772

RESUMEN

The S-configuration for (+)-primaquine prepared from the racemate by chemical resolution was established by solid-state X-ray analysis of the (+)-1-phenylethylurea obtained with R-(+)-1-phenylethylisocyanate.


Asunto(s)
Isocianatos , Primaquina , Cianatos , Conformación Molecular , Urea , Difracción de Rayos X
15.
FEBS Lett ; 234(1): 127-30, 1988 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-3391264

RESUMEN

Reaction of (-)-eseroline (1) with alkyl, aryl and aralkylisocyanates afforded a series of carbamate analogues of (-)-physostigmine (2) which were assayed for inhibition of acetyl- and butyrylcholinesterase (AChE and BChE, respectively) in vitro. Included in this study were two N-alkyl-substituted carbamates 9 and 14 obtained from (-)-eseroline (1) with dialkylcarbamoyl chlorides, and allophanates 12 and 13 obtained as by-products in the reaction of 1 and benzylcarbamoyl eseroline (8) with benzyl isocyanate. Whereas none of the analogues studied was more potent than 2 against electric eel AChE, and carbamates 6, 7 and 8 were all more than 3 times more potent against human plasma BChE than 2.


Asunto(s)
Carbamatos/farmacología , Inhibidores de la Colinesterasa , Fisostigmina/análogos & derivados , Acetilcolinesterasa , Animales , Butirilcolinesterasa/sangre , Fenómenos Químicos , Química , Electrophorus , Humanos , Indoles , Fisostigmina/farmacología
16.
J Med Chem ; 31(12): 2297-300, 1988 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-3193422

RESUMEN

(-)-N1-Benzylnorphysostigmine (4), prepared from synthetic (-)-O-methyl-N1-noreseroline (1) by N-benzylation, ether cleavage, and reaction of (-)-N1-benzylnoreseroline (3) with methyl isocyanate, was the intermediate used to prepare the title compounds. Catalytic debenzylation of 4 afforded (-)-N1-norphysostigmine (5), and (-)-eseramine (6) was obtained by reaction of 5 with methyl isocyanate. Reductive N-methylation of 5 gave (-)-physostigmine (9) while reaction of 5 with allyl bromide and phenethyl bromide afforded carbamates 7 and 8, respectively. Data on the in vitro potencies (IC50) and activities of certain of these compounds (4-8) as inhibitors of electric eel acetyl cholinesterase are reported. (-)-N1-Norphysostigmine (5) was found to be similarly potent against AChE as (-)-physostigmine (9).


Asunto(s)
Inhibidores de la Colinesterasa/síntesis química , Fisostigmina/análogos & derivados , Animales , Inhibidores de la Colinesterasa/farmacología , Electrophorus , Metilación
17.
J Med Chem ; 40(18): 2895-901, 1997 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-9288171

RESUMEN

N(8)-Benzylesermethole (6) was prepared from 5-methoxytryptamine (1) in five steps. Resolution of compound 6 by dibenzoyl- and ditoluyltartaric acid provided enantiomers (-)- and (+)-7. After demethylation, reaction with isocyanates and catalytic debenzylation over hydrogen, the total syntheses of (-)- and (+)-N(8)-norphysostigmine [(-)- and (+)-11] and (-)- and (+)-N(8)-norphenserine [(-)- and (+)-12] were accomplished, (-)-N(8)-Norphysostigmine [(-)-11] and (-)-N(8)-norphenserine [(-)-12] were also obtained by transformations of natural physostigmine [(-)-13] and phenserine [(-)-14] prepared from (-)-13. The absolute configurations and optical purity of compounds (-)-11, (-)-12, (+)-11, and (+)-12 were confirmed by a comparison of their optical rotations with those of the compounds synthesized from physostigmine [(-)-13]. The anticholinesterase activities of N(8)-nor- and N(8)-substituted analogues, (-)- and (+)-9, -10, -11, -12, 15, and 16, were compared with those of physostigmine [(-)- and (+)-13] and phenserine [(-)- and (+)-14] and are reported.


Asunto(s)
Acetilcolinesterasa/sangre , Butirilcolinesterasa/sangre , Inhibidores de la Colinesterasa/síntesis química , Fisostigmina/análogos & derivados , Acetilcolinesterasa/aislamiento & purificación , Butirilcolinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Eritrocitos/enzimología , Humanos , Indicadores y Reactivos , Isomerismo , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fisostigmina/síntesis química , Fisostigmina/química , Fisostigmina/farmacología , Relación Estructura-Actividad
18.
Neuroreport ; 9(1): 171-6, 1998 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-9592071

RESUMEN

The present study evaluated the interaction of the glutamatergic and acetylcholinergic systems in memory formation, with an overall emphasis on developing multi-system approaches for treating age-related cognitive decline and Alzheimer' s disease. Specifically, we used a 14-unit T-maze to investigate whether phenserine (PHEN), a long-acting acetylcholinesterase inhibitor, could overcome a learning deficit in rats induced by the NMDA receptor antagonist, 3-(+/-) 2-carboxypiperzin-4-yl) propyl phosphonic acid (CPP). Prior to drug treatment, 3-month-old male Fischer-344 rats were trained to criterion (13 of 15 shock avoidances) in a straight runway. Twenty-four hours later, rats were given i.p. injections of saline (SAL), CPP (9 mg/kg) + SAL or CPP + PHEN (0.25, 0.5 or 0.75 mg/kg) and received 15 massed training trials in a 14-unit T-maze. CPP significantly increased the number of errors made in the maze relative to controls, and phenserine significantly reduced the number of errors made relative to rats receiving CPP only, with the lowest dose being the most effective. These results provide further support of phenserine's potent, cognitive-enhancing properties, and suggest that combined modulation of glutamatergic and acetylcholinergic systems may be of potential benefit in developing new pharmacotherapies for Alzheimer's disease and age-related cognitive decline.


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Antagonistas de Aminoácidos Excitadores/farmacología , Discapacidades para el Aprendizaje/tratamiento farmacológico , Fisostigmina/análogos & derivados , Piperazinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Fisostigmina/uso terapéutico , Ratas , Ratas Endogámicas F344
19.
Toxicon ; 38(10): 1355-66, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10758271

RESUMEN

To investigate the hematological disorders after snakebite, we measured the maximum platelet aggregation rate (MAR), antithrombin III (AT-III) activity, alpha(2)-plasmin inhibitor (alpha(2)-PI) activity, concentration of fibrinogen (Fg) and fibrin degradation products (FDP) in 25 samples from 17 patients with snakebite in south China. The results obtained in the patients before application of antivenom and patients with Ophiophagus hannah (Oh.) bite were as follows: (1) the mean MAR values were significantly decreased in the case of the snakebites from Vipera russellii (Vr.) and Trimeresurus mucrosquamatus (Tm.); (2) the mean activities of AT-III were decreased in all patients in the present study; 3) the mean activities of alpha(2)-PI were significantly decreased in patients bitten by Deinagkistrodon acutus (Da.), Agkistrodon halys (Ah.), Vr., Trimeresurus stejnegeri (Ts.), Tm. and Naja naja atra (Nn.); (4) the mean concentrations of Fg were markedly decreased in patients bitten by Da., Ah., Vr., Ts. and Tm.; and (5) the mean levels of FDP were significantly increased in cases of Da., Vr. and Ts. bite, but not in Ah., Tm., Nn. and Oh. bite. The results of the present study indicate that disorders of platelet aggregation and the coagulation-fibrinolysis system are liable to occur in patients with snakebite from Da., Ah., Vr., Ts., Tm. and Nn. Furthermore, it appeared that disseminated intravascular coagulation (DIC) was evoked in some patients. Specific antivenom was found to be useful for improving the hemostatic disturbances after snakebite from Ah. and Nn.


Asunto(s)
Trastornos de la Coagulación Sanguínea/etiología , Mordeduras de Serpientes/complicaciones , Adolescente , Adulto , Animales , Antitrombina III/análisis , Antivenenos/uso terapéutico , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Niño , China , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria , Mordeduras de Serpientes/sangre , Mordeduras de Serpientes/tratamiento farmacológico , Venenos de Serpiente , Serpientes , alfa 2-Antiplasmina/análisis
20.
Laryngoscope ; 107(8): 1142-5, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9261023

RESUMEN

We measured the maximum aggregation rate (MAR) of platelets in 770 patients with malignant head and neck tumors, 55 patients with benign tumors of the head and neck, and 164 healthy people as a control group. The results were as follows: 1. the mean MAR value of patients with malignant tumors was significantly higher than the control group mean value; 2. prior to treatment, the mean MAR value increased with advancing tumor stage; 3. both MAR values of relapsed or metastasized patients and of nonsurvivors in stage III and IV increased significantly compared with survivors or patients recovering from malignant tumors. The results of the present study suggest that MAR values of patients with malignant tumors of the head and neck may serve as indicators in evaluating therapeutic procedures and prognosis.


Asunto(s)
Neoplasias de Cabeza y Cuello/sangre , Agregación Plaquetaria , Adolescente , Adulto , Anciano , Niño , China , Femenino , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valores de Referencia
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