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1.
Org Biomol Chem ; 22(25): 5159-5169, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38860854

RESUMEN

Indoles, indolines and hydronaphthylamines are ubiquitous structural motifs in natural products, pharmaceuticals, and biologically active molecules. In this paper, we report the synthesis of aminodihydronaphthyl-substituted indoles and indolines via a Ru-catalyzed carbamoyl-directed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes. In the presence of Cu(OAc)2 and AgSbF6, [Ru(p-cymene)Cl2]2 catalyzes the reaction of 1-carbamoylindoles with 7-azabenzonorbornadienes to produce 2-(1-amino-1,2-dihydronaphthalen-2-yl)indoles. Under the same conditions, the reaction of 1-carbamoylindolines with 7-azabenzonorbornadienes affords 7-(1-amino-1,2-dihydronaphthalen-2-yl)indolines. In both cases, the reactions yield cis-configured products.

2.
Antimicrob Agents Chemother ; 59(7): 4121-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25941216

RESUMEN

Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.


Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Área Bajo la Curva , Determinación de Punto Final , Femenino , Guanina/uso terapéutico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Seroconversión , Resultado del Tratamiento , Adulto Joven
3.
J Am Chem Soc ; 136(27): 9598-607, 2014 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-24927223

RESUMEN

Porphodilactones represent the porphyrin analogues, in which the peripheral bonds of two pyrrole rings are replaced by lactone moieties. They provide an opportunity to investigate how ß-substituent orientation of porphyrinoids modulates the electronic structures and optical properties, in a manner similar to what is observed with naturally occurring chlorophylls. In this work, a comprehensive description of the synthesis, characterization, and optical properties of meso-tetrakispentafluorophenylporphodilactone isomers is first reported. The ß-dilactone moieties are found to lie at opposite pyrrole positions (trans- and cis-configurations are defined by the relative orientations of the carbonyl group when one lactone moiety is fixed), in accordance with earlier computational predictions (Gouterman, M. J. Am. Chem. Soc. 1989, 111, 3702). The relative orientation of the ß-dilactone moieties has a significant influence on the electronic structures and photophysical properties. For example, the Qy band of trans-porphodilactone is red-shifted by 19 nm relative to that of the cis-isomer, and there is a 2-fold increase in the absorption intensity, which resembles the similar trends that have been reported for natural chlorophyll f and d. An in depth analysis of magnetic circular dichroism spectral data and TD-DFT calculations at the B3LYP/6-31G(d) level of theory demonstrates that the trans- and cis-orientations of the dilactone moieties have a significant effect on the relative energies of the frontier π-molecular orbitals. Importantly, the biological behaviors of the isomers reveal their different photocytotoxicity in NIR region (>650 nm). The influence of the relative orientation of the ß-substituents on the optical properties in this context provides new insights into the electronic structures of porphyrinoids which could prove useful during the development of near-infrared absorbing photosensitizers.


Asunto(s)
Clorofila/farmacología , Lactonas/farmacología , Rayos Láser , Compuestos Organometálicos/farmacología , Fármacos Fotosensibilizantes/farmacología , Absorción Fisicoquímica , Muerte Celular/efectos de los fármacos , Clorofila/análogos & derivados , Clorofila/química , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Lactonas/síntesis química , Lactonas/química , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Teoría Cuántica , Relación Estructura-Actividad
4.
J Cardiothorac Surg ; 18(1): 251, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612706

RESUMEN

BACKGROUND: Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. METHODS: This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan-Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. RESULTS: The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P < 0.001) and the 11th JES N staging (P < 0.001), with a c-index of 0.638 (95% CI: 0.592-0.683) for AJCC N staging and 0.627 (95% CI: 0.583-0.670) for JES N staging (P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC (P < 0.001) and the 11th JES systems (P < 0.001), with a c-index of 0.658 (95% CI: 0.616-0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589-0.668) for the11th JES stage grouping (P = 0.211). CONCLUSIONS: The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Estadificación de Neoplasias , Anciano , Humanos , Persona de Mediana Edad , Pueblos del Este de Asia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
5.
Indian J Pediatr ; 84(2): 124-127, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27465820

RESUMEN

OBJECTIVE: To investigate the changes in lymphocyte subsets that are caused by infection with different pathogens in children with hand, foot, and mouth disease. METHODS: T lymphocyte subsets were measured in the patients' peripheral blood, and serum, throat swab, and fecal samples were tested for enterovirus. RESULTS: Fecal and throat swab samples exhibited similar positive detection rates, and were significantly more likely to be positive, compared to serum samples (P < 0.01). The EV71-positive group exhibited significantly lower CD4 + TM cell counts (QR: 1.058), compared to the CD4 + TM cell counts in the CoxA16-positive group (QR: 1.391; P < 0.05). CONCLUSIONS: Throat swab and fecal samples exhibited significantly higher positive detection rates, compared to serum samples. In addition, EV71-infected children exhibited significantly lower CD4+ T-cell counts, compared to CoxA16-infected children, which suggests that EV71 infection may be associated with a poorer prognosis.


Asunto(s)
Enfermedad de Boca, Mano y Pie/sangre , Enfermedad de Boca, Mano y Pie/virología , Subgrupos de Linfocitos T , Preescolar , Heces/virología , Femenino , Humanos , Lactante , Masculino , Faringe/virología , Reacción en Cadena de la Polimerasa , Pronóstico
6.
World J Gastroenterol ; 21(32): 9598-606, 2015 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-26327767

RESUMEN

AIM: To compare the histological outcome of chronic hepatitis B (CHB) patients treated with entecavir (ETV) or lamivudine (LAM)-based therapy. METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis (baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baseline characteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ(2) test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test. RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74% (18/19) of the patients in the ETV arm and 95.65% (22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/mL. The majority of the patients (94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM (P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients (P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients (P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy. CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.


Asunto(s)
Antivirales/uso terapéutico , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Adulto , Biopsia , Distribución de Chi-Cuadrado , China , ADN Viral/sangre , Femenino , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Humanos , Hígado/patología , Hígado/virología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
7.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 47(12): 719-24, 2012 Dec.
Artículo en Zh | MEDLINE | ID: mdl-23328096

RESUMEN

OBJECTIVE: To isolate and culture the predominant anaerobes from the periodontal abscesses, and to test the antibiotic susceptibility and drug resistant genes of the strains. METHODS: The isolated strains were identified by both API20A biochemical method and polymerase chain reaction (PCR) method. The antibiotic susceptibility test was performed by agar dilution method. The resistant genes of the drug-resistant strains obtained were screened by PCR. RESULTS: The anaerobes were detected in 48% (28/58) of the samples and Prevotella melaninogenica (Pm) was mostly identified in 43% (12/28). API20A biochemical method had 82% (23/28) agreement with the 16SrRNA method in identification rate. Anaerobes were resistant to metronidazole, clindamycin and cefmetazole. The erythromycin-resistant methylase genes F (ermF) gene was detected in three of eight clindamycin resistant strains. None of them was found coded on bacterial plasmids. However, no metronidazole resistant gene was detected on drug resistant strains. CONCLUSIONS: Pm was the predominant species dectected in the periodontal abscess of the patients. The antibiotic agents should be used based on the genotypes and general condition of the patients.


Asunto(s)
Antibacterianos/farmacología , Bacterias Anaerobias/aislamiento & purificación , Farmacorresistencia Bacteriana , Absceso Periodontal/microbiología , Prevotella/aislamiento & purificación , Adulto , Cefmetazol/farmacología , Clindamicina/farmacología , Farmacorresistencia Bacteriana/genética , Eritromicina/farmacología , Femenino , Genes Bacterianos , Humanos , Masculino , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad
8.
Med Microbiol Immunol ; 198(1): 5-11, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18491134

RESUMEN

Antigen 85B (Ag85B) is an important immunodominant antigen of Mycobacterium tuberculosis, and is a very promising vaccine candidate molecule. Rv3425 is a member of the subgroup 3 of the PPE family, which does not exist in all BCG strains. In this study we constructed a new rBCG which included this united gene (Ag85B-Rv3425). The level of antigen-stimulated T cells expressing IFN-gamma was significantly higher in the C57BL/6 mice vaccinated with rBCG::Ag85B-Rv3425 than with BCG. In addition, the sera from mice immunized with rBCG::Ag85B-Rv3425 revealed an increase in the specific immunoglobulin G titers than that from mice immunized with BCG. Antigen specific IgG subclass analysis showed that rBCG::Ag85B-Rv3425 tended to facilitate IgG2a production, suggesting enhancement of predominant Th1 response which in turn may facilitate increased production of protective IFN-gamma. These results suggested that this rBCG::Ag85B-Rv3425 could be a strong vaccine candidate for further study.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Vacunas contra la Tuberculosis/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Femenino , Inmunoglobulina G/sangre , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos C57BL , Mycobacterium bovis/inmunología , Mycobacterium tuberculosis/inmunología , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/inmunología , Linfocitos T/inmunología , Vacunas contra la Tuberculosis/genética
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