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1.
Pain Physician ; 27(4): E395-E406, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38805535

RESUMEN

BACKGROUND: Glossopharyngeal neuralgia (GPN) is a condition that causes simultaneous headache and facial pain. The treatment for GPN is similar to the treatment for trigeminal neuralgia. Craniotomy microvascular decompression (MVD) or radiofrequency (RF) therapy is needed if conservative treatment with oral drugs fails. Therefore, the choice of radiofrequency therapy target is essential when treating GPN. However, finding the glossopharyngeal nerve simply by styloid process positioning is challenging. STUDY DESIGN: Prospective, clinical research study. SETTING: Department of Anesthesiology and Pain Medical Center, Jiaxing, China. OBJECTIVE: To compare the clinical effects of computed tomography (CT)-guided RF treatments on GPN when the triple localization of cervical CT, the transverse process of the atlas, and the styloid process is used to those achieved when the treatments are guided by the styloid process alone. METHODS: From August 2016 to December 2019, 19 cases of GPN neuralgia were treated by radiofrequency under the guidance of CT guided by the styloid process only. (These patients comprised the single localization (SL) of styloid process group, in whom the target of the RF treatments was the posterior medial side of half of the styloid process). From January 2020 to December 2022, 16 cases of GPN were treated by RF under the guidance of CT with cervical CTA (CT angiography), the transverse process of the atlas, and the styloid process. (These patients were placed in the TL group, in whom the target of RF therapy was the gap between the internal carotid artery and the internal jugular vein behind the horizontal styloid process at the lower edge of the transverse process of the atlas). Two percent lidocaine was injected subcutaneously at the needle insertion site, and a stylet with a 21-gauge blunt RF needle (model: 240100, manufacturer: Englander Medical Technology Co., Ltd.) was slowly advanced toward the target. After that, an RF probe was introduced, then low (2 Hz)- and high (50 Hz)-frequency currents of the RF instrument (model: PMG-230, Canada Baylis company) were applied to stimulate. A successful test was defined as a 0.5-1.0 mA current stimulation that could induce the original pain area in the pharynx, the inner ear, or both, without any abnormal irritation of the vagus or accessory nerves. If the first test was unsuccessful, then in the SL group, the needle tip's position was adjusted to the distal end of the styloid process, and in the triple localization (TL) group, the needle tip depth's was fine-tuned. A continuous RF treatment was given after a successful test. The RF temperature was 95ºC for 180 seconds. The time that the first puncture reached the target, the puncture paths, the success rate of the first test, the time that the glossopharyngeal nerve was found, the frequency of adjustments to the position of the RF needle, the incidence of intraoperative and postoperative complications, and the therapeutic effects were recorded. RESULTS: There were no significant differences in demographic data such as age, medical history, lateral classification, and pain score between the groups, but the TL group had a higher proportion of women than did the SL group. All patients' puncture targets were identified according to the designed puncture path before the operation. There was no difference between the 2 groups in the time of the first puncture to the target (5.05 ± 1.22 vs. 5.82 ± 1.51, P = 0.18), and the designed puncture depth (3.65 ± 0.39 vs. 4.04 ± 0.44). The difference in puncture angles (13.48 ± 3.56 vs. 17.84 ± 3.98, P < 0.01) was statistically significant, and in 8 cases in the SL group, the glossopharyngeal nerve could not be found after 60 minutes of testing, so the RF treatment was terminated. Meanwhile, this problem occurred in only 2 cases in the TL group. There were 3 cervical hematoma cases and 2 cases of transient hoarseness and cough in the SL group, whereas the TL group had, respectively, 0 and one cases of those issues. There was no death in either group. LIMITATIONS: More clinical data should be collected in future studies. CONCLUSION: When using RF as a treatment for GPN, the glossopharyngeal nerve is easier to find by using the triple positioning of the cervical CTA, the transverse process of the atlas and the styloid process as the target to determine the anterior medial edge of the internal carotid artery behind the styloid process at the level of the lower edge of the atlas transverse process. The glossopharyngeal nerve is more difficult to locate when only the posterior medial edge of the styloid process is targeted. The single-time effective rate of 180 seconds of RF ablation at 90ºC for GPN can reach 87.5% (14/16), suggesting the treatment's potential for clinical application.


Asunto(s)
Angiografía por Tomografía Computarizada , Enfermedades del Nervio Glosofaríngeo , Ablación por Radiofrecuencia , Humanos , Enfermedades del Nervio Glosofaríngeo/cirugía , Ablación por Radiofrecuencia/métodos , Estudios Prospectivos , Angiografía por Tomografía Computarizada/métodos , Femenino , Persona de Mediana Edad , Masculino , Atlas Cervical/cirugía , Atlas Cervical/diagnóstico por imagen , Anciano , Hueso Temporal/cirugía , Hueso Temporal/diagnóstico por imagen
2.
Mol Divers ; 26(3): 1567-1580, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34338914

RESUMEN

SHP2 is a protein tyrosine phosphatase (PTP) that can regulate the tyrosine phosphorylation level. Overexpression of SHP2 will promote the development of cancer diseases, so SHP2 has become one of the popular targets for the treatment of cancer. Studies have reported that both SHP099 and SHP844 are inhibitors of SHP2 and bind to different allosteric sites 1 and 2, respectively. Studies have shown that combining SHP099 with SHP844 will enhance pharmacological pathway inhibition in cells. This study uses molecular dynamic simulations to explore the dual allosteric targeted inhibition mechanism. The result shows that the residues THR108-TRP112 (allosteric site 1) move to LEU236-GLN245 (αB-αC link loop in PTP domain) , the residues of GLN79-GLN87 (allosteric site 2) get close to LEU262-GLN269 (αA-αB link loop in PTP domain) and HIS458-ARG465 (P-loop) come near to ARG501-THR507 (Q-loop) in SHP2-SHP099-SHP844 system, which makes the "inactive conformation" more stable and prevents the substrate from entering the catalytic site. Meanwhile, residue GLU110 (allosteric site 1), ARG265 (allosteric site 2), and ARG501 (Q-loop) are speculated to be the key residues that causing the SHP2 protein in auto-inhibition conformation. It is hoped that this study will provide clues for the development of the dual allosteric targeted inhibition of SHP2.


Asunto(s)
Neoplasias , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Regulación Alostérica , Sitio Alostérico , Humanos , Simulación de Dinámica Molecular , Neoplasias/tratamiento farmacológico , Proteína Tirosina Fosfatasa no Receptora Tipo 11/química , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo
3.
Water Sci Technol ; 84(8): 2079-2092, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34695032

RESUMEN

The traditional bioretention systems possess a remarkably low nitrogen and phosphorus removal effect. The removal rate fluctuates greatly, and even appears as negative removal of nitrogen and phosphorus. Four simulated bioretention experimental columns with different bilayer media, packing composition and structure were constructed. Based on the traditional fillers, the modified composite fillers with hydroxy-aluminum and modified vermiculite sludge particle (HAVSP) were added. The traditional filler (C1) and the modified composite filler (C2) were added respectively, moreover saturated zones were set up to enhance the effect of nitrogen and phosphorus removal. Removal of nutrients from experimental columns by simulated runoff efficiency was evaluated and compared. In addition, the effect of media depth on phosphorus retention and denitrifying enzyme activity in bioretention columns was also evaluated. The experimental column #2 filled with C2 had the optimum removal effect on TP (93.70%), however, the removal effect of TP by filling C1 experimental columns was insufficient (57.36%). Designed to remove nitrate (NO3--N) and total nitrogen, the experimental column #4 showed the best performance (83.54% and 92.15%, respectively). In this study, we propose a fold-flow bioretention system by filling HAVSP in combination with saturated zones. The runoff water quality can be effectively improved, and a new bioretention cell configuration can be provided for efficient stormwater treatment.


Asunto(s)
Fósforo , Purificación del Agua , Nitratos , Nitrógeno , Lluvia , Abastecimiento de Agua
4.
Virology ; 551: 16-25, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33010671

RESUMEN

Knowledge about the special characteristics of HIV-1 envelope (env) glycoproteins in rare individuals developing >90% neutralization breadth in Chinese subtype B' slow progressors may provide insights for vaccine design against local viruses. We performed a cross-sectional analysis on 7 samples. We tested the neutralization breadth and geometric mean ID50 titers (GMTs) of these samples, and divided them into hBCN+ and hBCN- group according to whether their neutralization breadth >90%. We obtained env sequences in these samples through single genome amplification (SGA) assay. By comparing with hBCN-, subtype B chronically infected group (B-SP), and Chinese subtype B group (B-Database), we analyzed the characteristics of the env sequences of hBCN+ group. Longer V1 and V4 regions with more glycosylation sites were found in hBCN+ samples compared to hBCN- samples. Further analysis compared to B-SP and B-Database showed that hBCN+ group exhibited unique extra-long V1 region containing higher proportion of N-glycan sites and additional cysteines.


Asunto(s)
Anticuerpos ampliamente neutralizantes/inmunología , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , China/epidemiología , Enfermedad Crónica , Estudios de Cohortes , Reacciones Cruzadas , Estudios Transversales , Infecciones por VIH/virología , VIH-1/genética , VIH-1/inmunología , Humanos , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología
5.
Artículo en Inglés | MEDLINE | ID: mdl-32164222

RESUMEN

Employees' voluntary green behavior (EVGB) is indispensable in realizing organizations' environmental sustainability objectives. Leaders can act as catalysts to shape the behavior of their employees. On EVGB, noticeably the missing link is investigating the influence of servant leadership and the mechanism through which it operates. Building upon self-determination and psychological empowerment theories, this research examined the impact of servant leadership on EVGB through the simple and sequential mediation of psychological empowerment and autonomous motivation for the environment (AME). Through systematic sampling, dyadic data were collected from 315 pairs of subordinates and supervisors working in the power sector organizations of Pakistan. Results were obtained by employing the partial least squares structural modeling (PLS-SEM) technique with Smart-PLS 3.2.8 software. Findings revealed that psychological empowerment and AME simply and sequentially mediate the influence of servant leadership on EVGB. Implications for theory and organizational practitioners are offered, accompanied by suggestions for future research.


Asunto(s)
Conservación de los Recursos Naturales , Empleo , Liderazgo , Organizaciones , Pakistán
6.
Exp Ther Med ; 18(2): 1196-1202, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31316614

RESUMEN

The present study aimed to investigate the role and underlying molecular mechanism of microRNA (miR)-125a-5p in hepatocellular carcinoma. The level of miR-125a-5p was detected using reverse transcription-quantitative polymerase chain reaction. TargetScan was used to investigate the association between miR-125a-5p and TP53-regulated inhibitor of apoptosis 1 (TRIAP1)/B cell lymphoma-2-like 2 protein (BCL2L2). Dual luciferase reporter assay was used to confirm this prediction. To investigate the role of miR-125a-5p in hepatocellular carcinoma (HCC) cells, miR-125a-5p was overexpressed in the human HCC cell line PLC/PRF/5 using miR-125a-5p mimics. Subsequently, cell proliferation, cell apoptosis and cell migration were studied using MTT assay, flow cytometry analysis and Transwell assay, respectively. Protein expression levels in the present study were measured by western blot analysis. Taken together, the present results suggested that miR-125a-5p was markedly downregulated in HCC cells. TRIAP1 and BCL2L2 were direct targets of miR-125a-5p and were upregulated in PLC/PRF/5 cells. miR-125a-5p upregulation inhibited PLC/PRF/5 cell viability and migration and induced cell apoptosis. In addition, miR-125a-5p overexpression increased the expression of caspase9 and apoptotic protease-activating factor 1. Notably, the present study revealed that all the effects on PLC/PRF/5 cells elicited by miR-125a-5p overexpression were eliminated by TRIAP1/BCL2L2 upregulation. In conclusion, miR-125a-5p was shown to be downregulated in hepatocellular carcinoma and its upregulation inhibited hepatocellular carcinoma cell growth and metastasis by targeting TRIAP1 and BCL2L2.

7.
J Biomol Struct Dyn ; 37(18): 4840-4851, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30661451

RESUMEN

Ectopic overexpression of protein tyrosine phosphatase of liver regeneration-1 (PTP4A1, also called PRL-1) markedly enhanced hepatocellular carcinoma (HCC) cells migration and invasion. The PTP4A1 trimerization played a vital role in mediating cell proliferation and motility. Biochemical and structural studies have proved that the compound 4AX, a well-known inhibitor for PRL1, directly binds to the PTP4A1 trimer interface and obstructs trimer formation of PTP4A1. However, the molecular basis of the ligand-4AX inhibition on PTP4A1 trimer conformations remains unclear. In this study, the docking analysis and the molecular dynamics simulation (MD simulation) study were performed to investigate how the molecule binding at each interface disrupted the trimer formation. The results suggested that the ligand-4AX attaching to the binding site changed the conformation of A:Q131, A:Q135 in the AC interface, C:R18, C:P96 in the CA interface and B:Q131 in the BA interface, leading to the weak interactions between subunits and thus resulting in the disruption of the PTP4A1 trimerization.


Asunto(s)
Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/química , Inhibidores Enzimáticos/química , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/química , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas/química , Sitios de Unión , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Movimiento (Física) , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios Proteicos , Multimerización de Proteína/efectos de los fármacos , Termodinámica
8.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 29(2): 169-173, 2017 Apr 07.
Artículo en Chino | MEDLINE | ID: mdl-29469320

RESUMEN

OBJECTIVE: To investigate the malaria knowledge of CDC staff and their demands on related training in malaria non-endemic areas, so as to provide the reference for planning the appropriate curriculum. METHODS: All the participants who were the staff of county CDCs all over Qinghai Province and attended the provincial training workshop were surveyed. A self-administered questionnaire survey was carried out and the data was statistically analyzed. RESULTS: A total of 115 participants were involved in this survey. They were mostly (85.21%) from county CDCs. The general knowledge of malaria among the respondents was well, and the average rate of correct answers was 70.35%. However, the answers to the general knowledge of malaria and anti-malaria treatment were not well enough. The rates of correct answers were 61.96% and 48.99% respectively. The differences among the groups of job title ranking, department of working and level of CDC were not significant (F = 0.13-2.02, all P > 0.05). The number of correct answers was significantly increased after the training course. The average score after the training was 79.20±15.16 while the pre-training score was 70.34±17.46 (t = 3.86, P < 0.05), especially in the answers to general malaria knowledge and malaria surveillance and response (t = 4.30, 4.97, both P < 0.05). The general knowledge of malaria was considered as the most need of training as 80% of the respondents voted "Yes", according to the demand analysis. There was no significant difference among the different groups (F = 0.61-3.11, both P > 0.05). CONCLUSIONS: The malaria knowledge is well mastered by the staff of CDCs in Qinghai Province, and the further training courses are requested and addressed in the target areas such as general malaria knowledge, anti-malaria treatment, malaria surveillance and response.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Malaria/terapia , China , Humanos , Encuestas y Cuestionarios , Estados Unidos
9.
Rev Sci Instrum ; 83(1): 013107, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22299929

RESUMEN

A novel XeF(C-A) laser which can be operated in repetition mode has been developed based on surface discharge optical pumping technique. Its maximum repetitive rate is up to 10 Hz. The influence of repetitive rate and gas flow rate on the stability of output energy is studied and the main factor which influences the stability of output energy is analyzed. The experimental results show that increasing the gas flow rate into laser chamber can improve the stability of the output energy. The ideal output energy results of 20 laser pulses under different repetitive rates and their optimal experimental conditions are presented. Output energies of more than 4 J and better stability can be obtained when the laser device operates at 1, 2, and 5 Hz, respectively. When the gas feed rate is larger than 53 l/s, the stability of output energy is improved obviously at the repetitive rate of 10 Hz, and the average energy of 20 laser pulses is up to 3.2 J.

10.
Indian J Biochem Biophys ; 49(6): 405-13, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23350274

RESUMEN

WRKY transcription factor proteins play important roles in diverse stress responses. In this study, we first cloned a novel WRKY from our constructed bacteriophage full-length cDNA library for cotton (Gossypium barbadense). The plants were stressed by exposure to a defoliating strain of Verticillium dahliae. The capacity of primary cDNA library was 1.28 x 10(6) PFU and the titer of the amplified cDNA library was > 10(10) PFU mL(-1). The recombination rate of the library was 94% and average insert size was about 1.1 kb. This novel gene, named GbWRKY1 was 1971 bp long and encodes a protein of 489 amino acids. It contains two characteristic WRKY domains and two zinc finger motifs. The sub-cellular assay indicated that GbWRKY1-GFP fusion protein was localized in the nucleus. Furthermore, Northern blot analysis showed that expression pattern of GbWRKY1 was similar among tissue types (roots, stems and leaves), but differed between pathogen-infiltrated and Czapek medium-infiltrated (untreated control) plants. Quantitative real-time PCR showed that GbWRKY1 could also be induced by salicylic acid (SA), methyl jasmonate (MeJA) and 1-aminocyclopropane-1-carboxylic acid (ACC). These findings clearly suggest that as a pathogen-inducible transcription factor GbWRKY1 plays an important role in plant defense responses.


Asunto(s)
Bacteriófagos/genética , Regulación de la Expresión Génica de las Plantas , Biblioteca de Genes , Genes de Plantas/fisiología , Gossypium/genética , Enfermedades de las Plantas/microbiología , Verticillium/fisiología , Secuencia de Aminoácidos , Aminoácidos Cíclicos/farmacología , Antifúngicos/farmacología , Northern Blotting , Clonación Molecular , Genes de Plantas/efectos de los fármacos , Gossypium/microbiología , Datos de Secuencia Molecular , Fármacos Neuroprotectores/farmacología , Filogenia , Enfermedades de las Plantas/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ácido Salicílico/farmacología , Homología de Secuencia de Aminoácido , Verticillium/efectos de los fármacos , Dedos de Zinc
11.
J Food Sci ; 76(5): C707-13, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22417416

RESUMEN

This article aims to determine the phenolic, tocopherol contents, and antioxidant capacities from fruits (juices, peels, and seed oils) of 6 Tunisian pomegranate ecotypes. Total anthocyanins were determined by a differential pH method. Hydrolyzable tannins were determined with potassium iodate. The tocopherol (α-tocopherol, γ-tocopherol, and δ-tocopherol) contents were, respectively, 165.77, 107.38, and 27.29 mg/100 g from dry seed. Four phenolic compounds were identified and quantified in pomegranate peel and pulp using the high-performance liquid chromatography/ultraviolet method: 2 hydroxybenzoic acids (gallic and ellagic acids) and 2 hydroxycinnamic acids (caffeic and p-coumaric acids). Juice, peel, and seed oil antioxidants were confirmed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) methods. The highest values were recorded in peels with 25.63 mmol trolox equivalent/100 g and 22.08 mmol TE/100 g for FRAP and ORAC assay, respectively. Results showed that the antioxidant potency of pomegranate extracts was correlated with their phenolic compound content. In particular, the highest correlation was reported in peels. High correlations were also found between peel hydroxybenzoic acids and FRAP ORAC antioxidant capacities. Identified tocopherols seem to contribute in major part to the antioxidant activity of seed oil. The results implied that bioactive compounds from the peel might be potential resources for the development of antioxidant function dietary food.


Asunto(s)
Antioxidantes/análisis , Frutas/química , Lythraceae/química , Extractos Vegetales/análisis , Polifenoles/análisis , Tocoferoles/análisis , Antocianinas/análisis , Cromanos/análisis , Ácidos Cumáricos/análisis , Ecotipo , Taninos Hidrolizables/análisis , Extractos Vegetales/química , Propionatos , Túnez
12.
Int J Food Sci Nutr ; 62(3): 200-6, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21118055

RESUMEN

Pomegranate seed oil is considered a powerful health-benefiting agent due to its anti-oxidative and anticarcinogenic properties. Lipids from 21 pomegranate cultivars (15 Tunisian and 6 Chinese) were extracted and fatty acids were identified. Total lipids (16% on a dry weight basis) are mainly unsaturated (ca. 88%). Qualitatively, the pomegranate fatty acid composition is identical. Quantitatively, the predominant fatty acid was linolenic acid (44.51-86.14%), followed by linoleic acid (3.57-13.92%), oleic acid (3.03-12.88%), palmitic acid (3.13-11.82%), stearic acid (1.68-15.64%), gadoleic acid (0.50-4.91%), lignoceric acid ( < 2.53%), arachidic acid ( < 1.70%) and myristic acid ( < 0.85%). Statistical methods revealed how Chinese and Tunisian pomegranate fatty acid contents may be affected by the sampling location.


Asunto(s)
Antineoplásicos Fitogénicos/análisis , Antioxidantes/análisis , Ácidos Grasos/análisis , Lythraceae/química , Aceites de Plantas/química , Semillas/química , China , Túnez
13.
Blood ; 112(8): 3434-43, 2008 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-18474728

RESUMEN

MDS is characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Development of effective treatments has been impeded by limited insight into pathogenic pathways governing dysplastic growth of hematopoietic progenitors. We demonstrate that smad2, a downstream mediator of transforming growth factor-beta (TGF-beta) receptor I kinase (TBRI) activation, is constitutively activated in MDS bone marrow (BM) precursors and is overexpressed in gene expression profiles of MDS CD34(+) cells, providing direct evidence of overactivation of TGF-beta pathway in this disease. Suppression of the TGF-beta signaling by lentiviral shRNA-mediated down-regulation of TBRI leads to in vitro enhancement of hematopoiesis in MDS progenitors. Pharmacologic inhibition of TBRI (alk5) kinase by a small molecule inhibitor, SD-208, inhibits smad2 activation in hematopoietic progenitors, suppresses TGF-beta-mediated gene activation in BM stromal cells, and reverses TGF-beta-mediated cell-cycle arrest in BM CD34(+) cells. Furthermore, SD-208 treatment alleviates anemia and stimulates hematopoiesis in vivo in a novel murine model of bone marrow failure generated by constitutive hepatic expression of TGF-beta1. Moreover, in vitro pharmacologic inhibition of TBRI kinase leads to enhancement of hematopoiesis in varied morphologic MDS subtypes. These data directly implicate TGF-beta signaling in the pathobiology of ineffective hematopoiesis and identify TBRI as a potential therapeutic target in low-risk MDS.


Asunto(s)
Hematopoyesis , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Animales , Antígenos CD34/biosíntesis , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Femenino , Humanos , Lentivirus/genética , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Modelos Biológicos , Proteínas Serina-Treonina Quinasas/metabolismo , Pteridinas/farmacología , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo
14.
Hypertension ; 50(4): 686-92, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17724276

RESUMEN

Inhibitors of angiogenic factors are known to be upregulated, and their levels increase in the maternal circulation before the onset of preeclampsia. We reproduced a previously characterized model of preeclampsia by adenoviral overexpression of the soluble vascular endothelial growth factor (VEGF) receptor sFlt-1 (also referred to as sVEGFR-1) in pregnant and nonpregnant Sprague-Dawley rats. Animals were treated with VEGF121 at 0, 100, 200, or 400 microg/kg once or twice daily (n=8 per group; 64 total) and compared with normal control animals (n=4 per group) by examination of systolic blood pressure, urinary albumin and creatinine, renal histopathology, and glomerular gene expression profiling. sFlt-1 expression induced hypertension with proteinuria and glomerular endotheliosis and significant changes in gene expression. VEGF121 treatment alleviated these symptoms and reversed 125 of 268 sFlt-1-induced changes in gene expression. VEGF121 had beneficial effects in this rat model of preeclampsia without apparent harm to the fetus. Further study of VEGF121 as a potential therapeutic agent for preeclampsia is warranted.


Asunto(s)
Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Riñón/patología , Preeclampsia/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Hipertensión/fisiopatología , Riñón/metabolismo , Preeclampsia/fisiopatología , Embarazo , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
15.
Trans R Soc Trop Med Hyg ; 101(10): 1051-2, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17604068

RESUMEN

An 8-year-old boy from Xuan-Han County, Sichuan Province, China presented with 6 months headache, nausea and vomiting. A computed tomography scan revealed multiple cerebral hemorrhages. Etiology of the cerebral hemorrhages was investigated by digital subtraction angiography, and cerebral aneurysm was entertained. Twenty-six days after his admission to the hospital, a flatworm emerged from the right eye of the patient. The worm was identified as Fasciola hepatica, based on the morphological characteristics of the worm.


Asunto(s)
Hemorragia Cerebral/parasitología , Fascioliasis/diagnóstico , Aneurisma Intracraneal/diagnóstico por imagen , Larva Migrans/diagnóstico , Animales , Angiografía Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagen , Niño , Diagnóstico Diferencial , Trastornos de Cefalalgia/parasitología , Humanos , Larva , Masculino , Náusea/parasitología , Vómitos/parasitología
16.
Brain Res ; 947(2): 191-8, 2002 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-12176160

RESUMEN

Stroke is the third leading cause of death in the US, with a prevalence of 750,000 patients per year, and a social cost estimated at $50 billion. Current therapeutics are targeted at restoring blood flow rather than on preventing the actual mechanisms associated with neuronal cell death. Here, we show that, following transient (2 h) middle cerebral artery occlusion (tMCAO) in male, Wistar rats, neuronal damage determined using MAP-2 staining increased progressively after the tMCAO. Notably, such neuronal degeneration was first associated with a decrease in p-Akt in both the focus and penumbra of the infarct region and, later with an increase in cytosolic cytochrome C levels in cortical neurons in the infarct area. These findings implicate that Akt alterations and consequent release of cytochrome C are involved in neuronal death. To further address this issue, NXY-059 (disodium 4-[(tert.-butylimino)methyl]benzene-1,3-disulfonate N-oxide) administered i.v. (30 mg/kg bolus, followed by 30 mg/kg/h infusion for up to 24 h), commencing 1 h after reperfusion, not only prevented the increase in infarct area but also attenuated the postreperfusion increase in neuronal cytosolic cytochrome C and the postperfusion decrease in neuronal p-Akt. Thus, NXY-059, by preventing mitochondrial cytochrome C release by maintaining activation of the Akt pathway, appears to protect neurons from damage after ischemia.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Encéfalo/efectos de los fármacos , Grupo Citocromo c/metabolismo , Fármacos Neuroprotectores/farmacología , Óxidos de Nitrógeno/farmacología , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas/metabolismo , Animales , Bencenosulfonatos , Western Blotting , Isquemia Encefálica/patología , Muerte Celular , Regulación hacia Abajo/efectos de los fármacos , Inmunohistoquímica , Masculino , Arteria Cerebral Media , Mitocondrias/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Regulación hacia Arriba/efectos de los fármacos
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