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1.
Eur Rev Med Pharmacol Sci ; 27(7): 2908-2918, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37070891

RESUMEN

OBJECTIVE: The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula. MATERIALS AND METHODS: A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections. RESULTS: Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression. CONCLUSIONS: KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.


Asunto(s)
Depresión , Medicamentos Herbarios Chinos , Proteómica , Proteoma , Animales , Ratones , Masculino , Estrés Psicológico , Hígado , Modelos Animales , Distribución Aleatoria , Lóbulo Frontal/metabolismo , Medicamentos Herbarios Chinos/farmacología
2.
Trials ; 21(1): 465, 2020 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493411

RESUMEN

BACKGROUND: Osteoporosis is becoming more prevalent in aging societies worldwide, and the economic burden attributable to osteoporotic fractures is substantial. The medications presently available to treat osteoporosis have side effects. Acupuncture is widely used for treating osteoporotic postmenopausal women because it is non-invasive and has fewer side effects, but the powerful clinical evidence for its efficacy remains insufficient. Our study intends to explore the effect of overall adjustment acupuncture (OA) in the treatment of postmenopausal osteoporosis (PMOP). METHODS/DESIGN: This study is a randomized, sham-controlled, patient- and assessor-blinded trial and aims to evaluate the effect of OA in women with PMOP. We will recruit 104 women aged 45-70 years with a diagnosis of PMOP. Participants will be randomly allocated in a 1:1 ratio to the OA group and the sham acupuncture (SA) group. Both groups will receive real herbal medicine treatment as a basic treatment twice a day for 3 months, the OA group receives real acupuncture treatment and the SA group receives placebo acupuncture treatment (non-penetrating, sham skin-needle therapy, sham cupping). All patients will receive acupuncture treatment twice per week for 3 months. The primary outcome is bone mineral density (BMD) and the secondary outcomes include estradiol (E2), follicle-stimulating hormone (FSH), bone gla protein (BGP), bone alkaline phosphatase (BALP), total antioxidant capacity (TAC), advanced oxidation protein products (AOPP), PPARγ, ß-catenin, FoxO3a levels, visual analog pain scale score (VAS), Traditional Chinese medicine (TCM) syndrome scores and quality of daily life score (QOL). Outcome measures will be collected at baseline, middle of the treatment (1.5 months), the end of treatment (3 months). The present protocol followed the SPIRIT guidelines and fulfills the SPIRIT Checklist. CONCLUSION: This study will be conducted to compare the efficacy of OA versus SA. This trial should help to evaluate whether OA can effectively prevent and treat PMOP by improving the estrogen levels of postmenopausal women. The mechanism is to improve the imbalance of osteogenic differentiation and lipogenesis of bone-marrow cells under oxidative stress. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800017581. Registered on 5 August 2018. URL: http://www.chictr.org.cn.


Asunto(s)
Terapia por Acupuntura/métodos , Osteoporosis Posmenopáusica/terapia , Terapia por Acupuntura/efectos adversos , Densidad Ósea , Método Doble Ciego , Estradiol/uso terapéutico , Femenino , Humanos , Estudios Multicéntricos como Asunto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(1): 49-52, 2019 Feb 18.
Artículo en Chino | MEDLINE | ID: mdl-30773543

RESUMEN

OBJECTIVE: To retrospectively analyze the results of treatment outcome by surgery combined with 125I brachytherapy and correlative factors of adenoid cystic carcinoma (ACC). METHODS: In the study, 75 patients with primary ACC of oral and maxillofacial region were treated by surgery combined with 125I seeds brachytherapy. Radical resection or subtotal resection was applied for the tumor. The brachytherapy treatment planning system was used to create implant plans with the prescribed dose of 60 Gy to 120 Gy. The 125I seeds were implanted intraoperatively or postoperatively. The regular follow-up was required. The Kaplan-Meier method was used to assess the tumor control rate and the patients' survival rates. Meanwhile, the Cox regression analysis was used to find out the prognostic factors. RESULTS: Local control rates at the end of 3 and 5 years were as follows: T1-T2, 92.2% and 82.0%; T3-T4, 82.6% and 82.6%; and overall, 90.0% and 78.8%. The disease-free survival rates were 74.9% and 54.3%, respectively. The overall survival rates for all the patients were 86.0% and 79.6%, respectively at the end of 3 and 5 years and were 91.3% and 91.3% for T1-T2 patients vs. 73.9% and 59.7% for T3-T4 patients. Distant metastasis-free survival rates at the end of 3 and 5 years were 84.4% and 76.7%, respectively. The distant metastasis-free survival rates at the end of 3 and 5 years were 83.4% and 79.6% with T1-T2 lesion compared with 86.0% and 67.8% with T3-T4 lesion. According to the COX univariate analysis and multivariate analysis, the risk of local recurrence would be raised by the age. Tumor stage and tumor site were the prognostic factors of the overall survival rates. CONCLUSION: 125I brachytherapy conducted as an adjuvant therapy postoperatively of ACC of oral and maxillofacial region can acquire satisfactory localregional control, distant metastasis-free survival, disease-free survival and overall survival. Tumors are prone to recur on the older patients. Patients having advanced tumor stage or tumor located in the nasal cavity or sinuses will suffer lower survival rates.


Asunto(s)
Braquiterapia , Carcinoma Adenoide Quístico , Terapia Combinada , Humanos , Radioisótopos de Yodo , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia
4.
Artículo en Inglés | MEDLINE | ID: mdl-29681968

RESUMEN

Dementia is a persistent disorder of the mental processes and is strongly related to depression. However, the performance of current antidepression medicine is far from satisfactory. Herbal extract provides an excellent source to identify compounds for possible drug development against depression. Here, HerboChips were employed to search herbal compounds that could bind nerve growth factor (NGF). By screening over 500 types of herbal extracts, the water extract of Ginkgo Folium, the leaf of Ginkgo biloba, showed a strong binding to NGF. The herbal fractions showing NGF binding were further isolated and enriched. By using LC-MS/MS analysis, one of the NGF binding fractions was enriched, which was further identified as quercetin, a major flavonoid in Ginkgo Folium. Quercetin, similar to Ginkgo Folium extract, could enhance the effect of NGF in cultured PC 12 cells, including potentiation of neurite outgrowth and phosphorylation of Erk-1/2. This is the first report of discovering an NGF binding compound by using HerboChips from herbal extracts, which could be further developed for antidepression application.

5.
Clin Radiol ; 73(3): 259-265, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29032942

RESUMEN

AIM: To evaluate the value of the aspartate aminotransferase-to-platelet ratio index (APRI) for hepatocellular carcinoma (HCC) patients who underwent transarterial chemoembolisation (TACE). MATERIALS AND METHODS: A total of 315 patients were enrolled, who were randomly divided into the training cohort (n=158) and the validation cohort (n=157). The optimal cut-off value of the APRI was determined using the X-tile software in the training cohort, and was validated in the validation cohort. Several serum-based markers, neutrophil-to-lymphocyte (N/L) and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratios were included to compare with the APRI. To predict individual survival rate, independent predictors were included to build a nomogram. RESULTS: Using the X-tile, a cut-off value of the APRI as 0.40 was yielded to distinguish patients with distinct outcomes in the training cohort, but failed for the N/L and ALT/AST ratios. In the training cohort, 66 patients with high APRI had poorer survival (p<0.001) than did 92 patients with low APRI. Using the same cut-off value of APRI, 61 patients with high APRI had poorer survival (p<0.001) than did 96 patients with low APRI in the validation cohort. Furthermore, a nomogram, including the APRI, TACE cycles, tumour size, and tumour number, was built based on the training cohort, and validated well in the validation cohort (concordance index [C-index] 0.713). CONCLUSION: The APRI is a promising marker to predict treatment response and outcome for HCC patients after TACE treatment.


Asunto(s)
Aspartato Aminotransferasas/sangre , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Recuento de Plaquetas , Adulto , Anciano , Alanina Transaminasa/sangre , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico por imagen , Aceite Etiodizado/administración & dosificación , Femenino , Fluoroscopía , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Programas Informáticos , Análisis de Supervivencia , Resultado del Tratamiento
6.
Antiviral Res ; 112: 113-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25453344

RESUMEN

INTRODUCTION: This study evaluates polyomavirus JC (JCV) large T antigen (LTA) as a potential target for drug development. LTA is a hexameric protein with a helicase activity that is powered by ATP binding and hydrolysis. The helicase and ATPase function is critical for viral replication. METHODS: Recombinant JCV LTA was produced in an Escherichia coli based expression plasmid. ATPase activity was measured using the malachite green assay. A high throughput screen was completed using a brain-biased library of 75,000 drug-like compounds selected for physicochemical properties consistent with blood-brain barrier permeability. RESULTS: Five compounds showed non-competitive inhibition of ATPase activity with an EC50 ⩽ 15 µM. Modest antiviral activity was demonstrated in an immunofluorescence assay for JCV VP-1 expression in COS7 cells (EC50 15, 18, 20, 27, and 52 µM respectively). The compounds also inhibited viral replication in a real time PCR assay at comparable concentrations. LD50 in the MTS96 and Cell TiterGlo assays was >100 µM for all compounds in COS7 as well as HEK293 cells. However, two compounds inhibited cell proliferation in culture with IC50 values of 43 and 34 µM respectively. Despite substantial amino acid similarity between polyomavirus JC, BK and SV40 proteins, these compounds differ from those previously reported to inhibit SV40 LTA ATPase in chemical structure as well as a non-competitive mechanism of inhibition. CONCLUSION: LTA ATPase is a valid target for discovery. Additional screening and chemical optimization is needed to develop clinically useful compounds with less toxicity, which should be measured by metabolic as well as cell proliferation assays.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antígenos Virales de Tumores/metabolismo , Antivirales/aislamiento & purificación , Antivirales/farmacología , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Virus JC/enzimología , Adenosina Trifosfatasas/genética , Animales , Antígenos Virales de Tumores/genética , Línea Celular , Chlorocebus aethiops , Colorimetría/métodos , Evaluación Preclínica de Medicamentos , Escherichia coli/genética , Escherichia coli/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Virus JC/efectos de los fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Replicación Viral/efectos de los fármacos
7.
Artículo en Inglés | MEDLINE | ID: mdl-24371453

RESUMEN

Effects of mulberry leaf-related extracts (MLREs) on hydrogen peroxide-induced DNA damage in human lymphocytes and on inflammatory signaling pathways in human aortic endothelial cells (HAECs) were studied. The tested MLREs were rich in flavonols, especially bombyx faces tea (BT) in quercetin and kaempferol. Polyphenols, flavonoids, and anthocyanidin also abounded in BT. The best trolox equivalent antioxidant capacity (TEAC) was generated from the acidic methanolic extracts of BT. Acidic methanolic and water extracts of mulberry leaf tea (MT), mulberry leaf (M), and BT significantly inhibited DNA oxidative damage to lymphocytes based on the comet assay as compared to the H2O2-treated group. TNF- α -induced monocyte-endothelial cell adhesion was significantly suppressed by MLREs. Additionally, nuclear factor kappa B (NF- κ B) expression was significantly reduced by BT and MT. Significant reductions were also observed in both NF- κ B and activator protein (AP)-1 DNA binding by MLREs. Significant increases in peroxisome proliferator-activated receptor (PPAR) α and γ DNA binding by MLREs were also detected in M and MT extracts, but no evidence for PPAR α DNA binding in 50 µ g/mL MT extract was found. Apparently, MLREs can provide distinct cytoprotective mechanisms that may contribute to its putative beneficial effects on suppressing endothelial responses to cytokines during inflammation.

8.
Strahlenther Onkol ; 189(6): 502-7, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23625361

RESUMEN

BACKGROUND AND PURPOSE: This retrospective study was to evaluate the local control and survival of (125)I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. PATIENTS AND METHODS: A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received (125)I brachytherapy alone from 2001-2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100-160 Gy. RESULTS: Patients were followed for 12-122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5 %, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1 %, respectively. Tumors > 6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up. CONCLUSION: (125)I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.


Asunto(s)
Braquiterapia/métodos , Carcinoma Adenoide Quístico/radioterapia , Neoplasias Faciales/radioterapia , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Boca/radioterapia , Neoplasias Nasales/radioterapia , Neoplasias de las Glándulas Salivales/radioterapia , Neoplasias de la Base del Cráneo/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoide Quístico/patología , Niño , Progresión de la Enfermedad , Neoplasias Faciales/patología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Neoplasias Nasales/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/patología , Neoplasias de la Base del Cráneo/patología , Adulto Joven
9.
Malays J Nutr ; 17(1): 19-30, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22135862

RESUMEN

INTRODUCTION: Nutrition and HIV are closely related. Any immune impairment as a result of HIV leads to malnutrition, which in turn, can also lead to reduced immunity, thus contributing to a more rapid progression to AIDS. METHODS: This cross-sectional study determined the nutritional status of children living with HIV and are receiving antiretroviral medication in the Klang Valley. A total of 95 children aged one to eighteen years old were recruited between September 2008 and February 2009. Data collected included socio-economic status, anthropometric measurements, dietary intake, medical history and serum levels of selected micronutrients specific for immunity. RESULTS: The mean age of the children was 8.4 +/- 3.9 years and the mean duration on antiretroviral medications was 68.3 +/- 38.3 months. Anthropometric assessment found that 9.5% of the children were underweight and 31.6% were overweight. In contrast, 20.8% were stunted and 14.6% severely stunted. Biochemical indicators showed that 10.4% had deficiency in vitamin A while 12.5% had deficiency in selenium. Total cholesterol and HDL-C levels were found to be low in 30.5% and 10.5% of the children respectively. CONCLUSION: Dietary assessment showed almost all the children did not achieve the recommended energy intake for their age groups and almost half of the children did not achieve the RNI for selenium and vitamin A. This study provides an insight on the nutritional status of children living with HIV.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Enfermedades Carenciales/epidemiología , Infecciones por VIH/tratamiento farmacológico , Estado Nutricional , Adolescente , Composición Corporal , Niño , Preescolar , Estudios Transversales , Enfermedades Carenciales/etiología , Enfermedades Carenciales/fisiopatología , Femenino , Humanos , Lactante , Malasia/epidemiología , Masculino , Selenio/deficiencia , Clase Social , Deficiencia de Vitamina A/epidemiología
10.
Stud Health Technol Inform ; 163: 403-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21335829

RESUMEN

Ultrasonography is the lowest cost no risk medical imaging technique. However, reading an ultrasonographic (US) image as well as performing a good US probe positioning remain difficult tasks. Education in this domain is today performed on patients, thus limiting it to the most common cases. In this paper, we present a cost effective simulator that allows US image practice and realistic probe manipulation from CT data. More precisely, we tackle the issue of providing a realistic interface for the probe manipulation with a basic haptic feedback.


Asunto(s)
Biorretroalimentación Psicológica/instrumentación , Instrucción por Computador/métodos , Modelos Biológicos , Tacto , Ultrasonografía/instrumentación , Ultrasonografía/métodos , Interfaz Usuario-Computador , Biorretroalimentación Psicológica/métodos , Simulación por Computador , Análisis Costo-Beneficio , Francia , Humanos , Interpretación de Imagen Asistida por Computador/instrumentación , Interpretación de Imagen Asistida por Computador/métodos , Enseñanza/métodos , Transductores/economía , Ultrasonografía/economía
11.
J Biomol Screen ; 13(9): 870-8, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18812568

RESUMEN

Calpain activation is hypothesized to be an early occurrence in the sequence of events resulting in neurodegeneration, as well as in the signaling pathways linking extracellular accumulation of beta-amyloid (Abeta) peptides and intracellular formation of neurofibrillary tangles. In an effort to identify small molecules that prevent neurodegeneration in Alzheimer's disease by early intervention in the cell death cascade, a cell-based assay in differentiated Sh-SY5Y cells was developed using calpain activity as a read-out for the early stages of death in cells exposed to extracellular Abeta. This assay was optimized for high-throughput screening, and a library of approximately 120,000 compounds was tested. It was expected that the compounds identified as calpain inhibitors would include those that act directly on the enzyme and those that prevented calpain activation by blocking an upstream step in the pathway. In fact, of the compounds that inhibited calpain activation by Abeta with IC(50) values of <10 microM and showed little or no toxicity at concentrations up to 30 microM, none inhibit the calpain enzyme directly.


Asunto(s)
Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/química , Enfermedad de Alzheimer/metabolismo , Calcio/química , Calpaína/química , Muerte Celular , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Ácido Egtácico/análogos & derivados , Ácido Egtácico/química , Humanos , Luminiscencia , Tamizaje Masivo/métodos , Enfermedades Neurodegenerativas/patología , Factores de Tiempo
12.
Xenobiotica ; 38(5): 465-81, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18421621

RESUMEN

1. Ginkgo biloba is one of the most popular herbal medicines worldwide due to its memory-enhancing and cognition-improving effects. The current study was designed to investigate the effects of five major constituents (bilobalide, ginkgolide A, B, quercetin, and kaempferol) in the standardized G. biloba extract EGb 761 on various cytochrome P450s (CYPs) in rats. 2. The activity of CYP450 was measured by the quantification of six metabolites from multiple cytochrome P450 probe substrates using a validated liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) method. The levels of messenger RNA (mRNA) and protein of various CYPs were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. 3. Bilobalide significantly induced the activity, protein, and mRNA expression of CYP3A1 and 1A2, and increased CYP2E1 activity and CYP2B1/2 protein expression in a dose-dependent manner. 4. Ginkgolide A, B, quercetin, and kaempferol did not affect CYP3A1, but induced CYP1A2 in a dose-dependent manner. EGb 761 and the five individual constituents had no effects on rat CYP2D2, 2C11 and 2C7. 5. The results indicate that bilobalide, and to a lesser extent ginkgolide A, B, quercetin, and kaempferol, play a key role in the effects of EGb 761 on CYP induction. Further study is needed to elucidate the mechanism of CYP3A induction by EGb 761 and bilobalide.


Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , Flavonoides/farmacología , Ginkgo biloba/química , Ginkgólidos/farmacología , Animales , Ciclopentanos/farmacología , Sistema Enzimático del Citocromo P-450/genética , Inducción Enzimática/efectos de los fármacos , Flavonoides/química , Furanos/farmacología , Expresión Génica/efectos de los fármacos , Ginkgólidos/química , Quempferoles/farmacología , Lactonas/farmacología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Quercetina/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Xenobiotica ; 38(4): 382-98, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18340563

RESUMEN

1. The study aimed to investigate the pharmacokinetics of cryptotanshinone in a hydroxylpropyl-beta-cyclodextrin-included complex in dogs and rats. 2. Animals were administrated the inclusion complex of cryptotanshinone and the concentrations of cryptotanshinone and its major metabolite tanshinone IIA were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. 3. Cryptotanshinone in inclusion complex was absorbed slowly after an oral dose, and the C(max) and AUC(0-)(t) were dose-proportional. The bioavailability of cryptotanshinone in rats was (6.9% +/- 1.9%) at 60 mg kg(-1) and (11.1% +/- 1.8%) in dogs at 53.4 mg kg(-1). The t(1/2) of the compound in rats and dogs was 5.3-7.4 and 6.0-10.0 h, respectively. Cryptotanshinone showed a high accumulation in the intestine, lung and liver after oral administration, while the lung, liver and heart had the highest level following intravenous dose. Excretion data in rats showed that cryptotanshinone and its metabolites were mainly eliminated from faeces and bile, and the dose recovery rate was 0.02, 2.2, and 14.9% in urine, bile, and faeces, respectively. 4. The disposition of cryptotanshinone in an inclusion complex was dose-independent and the bioavailability was increased compared with that without cyclodextrin used to formulate the drug. Cryptotanshinone was distributed extensively into different organs. Excretion of cryptotanshinone and its metabolites into urine was extremely low, and they were mainly excreted into faeces and bile.


Asunto(s)
Fármacos Cardiovasculares/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Drogas en Investigación/farmacocinética , Fenantrenos/farmacocinética , Fenantrolinas , Salvia miltiorrhiza , beta-Ciclodextrinas/farmacocinética , 2-Hidroxipropil-beta-Ciclodextrina , Abietanos , Administración Oral , Animales , Fármacos Cardiovasculares/administración & dosificación , Perros , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Drogas en Investigación/administración & dosificación , Femenino , Masculino , Fenantrenos/administración & dosificación , Fenantrolinas/química , Ratas , Salvia miltiorrhiza/química , Distribución Tisular , beta-Ciclodextrinas/administración & dosificación
14.
Xenobiotica ; 38(2): 185-222, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18197559

RESUMEN

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg(-1), TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C(max) and AUC(0-)(t) of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration-time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C(max) and AUC(0-)(t) of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and testes. TSIIA was metabolized by rat CYP2C, 3A and 2D, as ticlopidine, ketoconazole and quinidine all inhibited TSIIA metabolism in rat liver microsomes. Taken collectively, these findings indicate that multiple factors play important roles in determining the pharmacokinetics of TSIIA.


Asunto(s)
Isquemia Miocárdica/tratamiento farmacológico , Fenantrenos/farmacocinética , Abietanos , Animales , Células CACO-2 , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Espectrometría de Masas , Microsomas Hepáticos/metabolismo , Modelos Animales , Fenantrenos/uso terapéutico , Fenantrenos/orina , Raíces de Plantas/química , Ratas , Ratas Sprague-Dawley , Salvia miltiorrhiza/química , Factores de Tiempo
15.
Int J Sports Med ; 29(3): 232-7, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17614014

RESUMEN

The aim of this study was to compare the flexibility of the upper extremities in collegiate students involved in Aikido (a kind of soft martial art attracting youth) training with those involved in other sports. Fifty freshmen with a similar frequency of exercise were divided into the Aikido group (n = 18), the upper-body sports group (n = 17), and the lower-body sports group (n = 15) according to the sports that they participated in. Eight classes of range of motion in upper extremities were taken for all subjects by the same clinicians. The Aikido group had significantly better flexibility than the upper-body sports group except for range of motion in shoulder flexion (p = 0.22), shoulder lateral rotation (p > 0.99), and wrist extension (p > 0.99). The Aikido group also had significantly better flexibility than the lower-body sports group (p < 0.01) and the sedentary group (p < 0.01) in all classes of range of motion. The upper-body sports group was significantly more flexible in five classes of range of motion and significantly tighter in range of motion of wrist flexion (p < 0.01) compared to the lower-body sports group. It was concluded that the youths participating in soft martial arts had good upper extremities flexibility that might not result from regular exercise alone.


Asunto(s)
Articulaciones/fisiología , Artes Marciales/fisiología , Rango del Movimiento Articular/fisiología , Extremidad Superior/fisiología , Adolescente , Artrometría Articular , Femenino , Humanos , Masculino , Pronación/fisiología , Supinación/fisiología
16.
Cancer ; 109(3): 502-9, 2007 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-17154178

RESUMEN

BACKGROUND: Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS: From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS: T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSION: T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.


Asunto(s)
Antígenos de Neoplasias/fisiología , ADN-Topoisomerasas de Tipo II/fisiología , Proteínas de Unión al ADN/fisiología , Neoplasias del Timo/enzimología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Cromosomas Humanos Par 17/genética , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Amplificación de Genes , Genes erbB-2/fisiología , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2/genética , Tasa de Supervivencia , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/radioterapia
17.
Osteoarthritis Cartilage ; 14(4): 377-83, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16359876

RESUMEN

OBJECTIVE: To investigate the effects of mucopolysaccharide induction after treatment by low power laser for experimental osteoarthritis (OA). METHODS: Seventy-two rats with three different degrees of papain induced OA over right knee joints were collected for helium-neon (He-Ne) laser treatment. The severity of induced arthritis was measured by 99mTc bone scan and classified into three groups (I-III) by their radioactivity ratios (right to left knee joints). The rats in each group were further divided into study subgroups (Is, IIs, and IIIs) and control subgroups (Ic, IIc, and IIIc) randomly. The arthritic knees in study subgroups received He-Ne laser treatment, and those in controls received sham laser treatment. The changes of arthritic severity after treatment and follow-up 2 months later were measured. The histopathological changes were evaluated through light microscope after disarticulation of sections (H.E. stain), and the changes of mucopolysaccharide density in cartilage matrix were measured by Optimas scanner analyzer after Alcian blue (AB) stain. The densities of mucopolysaccharide induced after treatment in arthritic cartilage were compared and correlated with their histopathological changes. RESULTS: The density of mucopolysaccharide rose at the initial stage of induced arthritis, and decreased progressively in later stages. The densities of mucopolysaccharide in treated rats increased upon complete laser treatment more than those of the controls, which is closely related with the improvement in histopathological findings, but conversely with the changes in arthritic severity. CONCLUSION: He-Ne laser treatment will enhance the biosynthesis of arthritic cartilage, and results in the improvement of arthritic histopathological changes.


Asunto(s)
Cartílago Articular/metabolismo , Glicosaminoglicanos/biosíntesis , Terapia por Luz de Baja Intensidad , Gases Nobles/uso terapéutico , Osteoartritis de la Rodilla/radioterapia , Animales , Cartílago Articular/patología , Cartílago Articular/efectos de la radiación , Glicosaminoglicanos/efectos de la radiación , Helio/uso terapéutico , Neón/uso terapéutico , Osteoartritis de la Rodilla/patología , Ratas
18.
Environ Geochem Health ; 27(1): 75-95, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15688133

RESUMEN

This paper reports the fluvial fluxes and estuarine transport of organic carbon and nutrients from a tropical river (Tsengwen River), southwestern Taiwan. Riverine fluxes of organic carbon and nutrients were highly variable temporally, due primarily to temporal variations in river discharge and suspended load. The sediment yield of the drainage basin during the study period (1995-1996, 616 tonne km(-2) year(-1)) was ca. 15 times lower than that of the long-term (1960-1998) average (9379 tonne km2 year(-1)), resulting mainly from the damming effect and historically low record of river water discharge (5.02 m3 s(-1)) in 1995. The flushing time of river water in the estuary varied from 5 months in the dry season to >4.5 days in the wet season and about 1 day in the flood period. Consequently, distributions of nutrients, dissolved organic carbon (DOC) and particulate organic carbon (POC) were of highly seasonal variability in the estuary. Nutrients and POC behaved nonconservatively but DOC behaved conservatively in the estuary. DOC fluxes were generally greater than POC fluxes with the exception that POC fluxes considerably exceeded DOC fluxes during the flood period. Degradation of DOC and POC within the span of flushing time was insignificant and may contribute little amount of CO2 to the estuary during the wet season and flood period. Net estuarine fluxes of nutrients were determined by riverine fluxes and estuarine removals (or additions) of nutrients. The magnitude of estuarine removal or addition for a nutrient was also seasonally variable, and these processes must be considered for net flux estimates from the river to the sea. As a result, nonconservative fluxes of dissolved inorganic phosphorus (deltaDIP) from the estuary are -0.002, -0.09 and -0.59 mmol m(-2) day(-1), respectively, for dry season, wet season and flood period, indicating internal sinks of DIP during all seasons. Due to high turbidity and short flushing time of estuarine water, deltaDIP in the flood period may be derived largely from geochemical processes rather than biological removal, and this deltaDIP should not be included in an annual estimate of carbon budget. The internal sink of phosphorus corresponds to a net organic carbon production (photosynthesis-respiration, p-r) during dry (0.21 mmol m(-2) day(-1)) and wet (9.5 mmol m(-2) day(-1)) seasons. The magnitude of net production (p-r) is 1.5 mol m(-2) year(-1), indicating that the estuary is autotrophic in 1995. However, there is a net nitrogen loss (nitrogen fixation-denitrification < 0) in 1995, but the magnitude is small (-0.17 mol m(-2) year(-1)).


Asunto(s)
Carbono/análisis , Monitoreo del Ambiente , Sedimentos Geológicos/análisis , Compuestos Orgánicos/análisis , Animales , Transporte Biológico , Carbono/metabolismo , Desastres , Nitrógeno/análisis , Nitrógeno/metabolismo , Compuestos Orgánicos/metabolismo , Fósforo/análisis , Fósforo/metabolismo , Ríos , Estaciones del Año , Cloruro de Sodio/análisis , Taiwán , Factores de Tiempo
19.
Eur J Clin Nutr ; 58(3): 481-7, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14985687

RESUMEN

OBJECTIVE: To investigate whether vitamin B(6) supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. DESIGN: A single-blind intervention study. SETTING: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. SUBJECTS: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. INTERVENTIONS: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B(6) (n=8), 10 mg vitamin B(6) (n=8), 50 mg vitamin B(6) (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B(12) (n=9) for 12 weeks. MAIN OUTCOME MEASURES: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B(6) status was assessed by direct measures (plasma pyridoxal 5'-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B(12) were measured. RESULTS: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B(6) when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B(12) supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B(6) supplemented groups, respectively; whereas folic acid combined with vitamin B(12) supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001). CONCLUSIONS: Our results indicate that vitamin B(6) supplementation alone is less effective than folic acid combined with vitamin B(12) in lowering plasma homocysteine concentrations in CAD patients. SPONSORSHIP: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Ácido Fólico/administración & dosificación , Homocisteína/sangre , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Método Simple Ciego , Resultado del Tratamiento , Vitamina B 12/sangre , Vitamina B 6/sangre
20.
Neurol Clin Neurophysiol ; 2004: 62, 2004 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-16012689

RESUMEN

Both an EEG P50 sensory gating deficit and abnormalities of the temporal lobe structure are considered characteristic of schizophrenia. The standard P50 sensory gating measure does not foster differential assessment of left- and right-hemisphere contributions, but its analogous MEG M50 component may be used to measure gating of distinct auditory source dipoles localizing to left- and right-hemisphere primary auditory cortex. The present study sought to determine how sensory gating ratio may relate to cortical thickness at the site of the auditory dipole localization. A standard auditory paired-click paradigm was used during MEG for patients (n=22) and normal controls (n=11). Sensory gating ratios were determined by measuring the strength of the 50 ms response to the second click divided by that of the first click (S2/S1). Cortical thickness was assessed by two reliable raters using 3D sMRI. Results showed that: (1) patients had a P50 and left M50 sensory gating deficit relative to controls; (2) cortex in both hemispheres was thicker in the control group; (3) in schizophrenia, poorer left-hemisphere M50 sensory gating correlated with thinner left-hemisphere auditory cortical thickness; and (4) poorer right-hemisphere M50 auditory sensory gating ratio correlated with thinner right-hemisphere auditory cortical thickness in patients. The MEG-assessed hemisphere-specific auditory sensory gating ratio may be driven by this structural abnormality in auditory cortex.


Asunto(s)
Corteza Auditiva/anatomía & histología , Corteza Auditiva/fisiología , Potenciales Evocados Auditivos/fisiología , Lateralidad Funcional/fisiología , Esquizofrenia/fisiopatología , Estimulación Acústica/métodos , Análisis de Varianza , Humanos , Magnetoencefalografía/métodos , Tamaño de los Órganos/fisiología
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