RESUMO
BACKGROUND: IDX184 is a liver-targeted nucleotide prodrug that selectively inhibits HCV NS5B polymerase. METHODS: This randomized, double-blind, placebo-controlled, ascending-dose study investigated the antiviral activity, safety and pharmacokinetics of IDX184 plus pegylated interferon-α2a and ribavirin (P/R) in treatment-naive patients with genotype-1 HCV. A total of 81 patients with baseline HCV RNA≥5 log10 IU/ml, alanine aminotransferase ≤3× upper limit of normal and compensated liver disease were dosed. Sequential cohorts of 20 patients, randomized 16:4 (active:placebo), received IDX184 for 14 days at rising daily doses of 50, 100, 150 or 200 mg in combination with P/R for 14 days. RESULTS: At the end of triple dosing, HCV RNA changes from baseline (mean ±sd log10) and proportion of patients achieving undetectable viral load (<15 IU/ml) based on the efficacy-evaluable population were -2.7 ±1.3 (13%), -4.0 ±1.7 (50%), -4.2 ±1.9 (50%), -4.1 ±1.2 (40%), -4.3 ±1.5 (29%) and -3.7 ±1.2 (25%) for the 50 mg once daily, 50 mg twice daily, 100 mg once daily, 150 mg once daily, 100 mg twice daily and 200 mg once daily IDX184 doses, respectively. P/R alone resulted in a reduction of -1.5 ±1.3 log10 with only 6% of patients with undetectable viral load. Patients with genotypes-1a or -1b responded similarly. No viral breakthrough or resistance associated with IDX184 was observed. Anti-HCV activity of IDX184 correlated with plasma exposure of its nucleoside metabolite 2'-methylguanosine. Most adverse events were mild or moderate in severity and were consistent with those associated with P/R. The most common adverse events were fatigue and headache. CONCLUSIONS: IDX184 in combination with P/R for 14 days was well tolerated and demonstrated greater antiviral activity with more patients achieving undetectable viral load than P/R.
Assuntos
Antivirais/uso terapêutico , Guanosina Monofosfato/análogos & derivados , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacocinética , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Genótipo , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/efeitos adversos , Guanosina Monofosfato/farmacocinética , Guanosina Monofosfato/uso terapêutico , Hepatite C/genética , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/farmacocinética , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Polimorfismo Genético , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ribavirina/farmacocinética , Resultado do Tratamento , Carga ViralRESUMO
PURPOSE: To study the effects of nanostructured titanium fabricated via surface plastic deformation on Saos-2 cell adherence, proliferation and differentiation in vitro. METHODS: Nanostructured titanium surfaces were prepared using plastic deformation and divided into three groups: group I (30 minutes, n=6), group II (60 minutes, n=6) and group III (90 minutes, n=6), according to the time of preparation. The untreated titanium was used as control group. Saos-2 cell line was cultured on different titanium surfaces. The features of titanium surface and the effects of nanostructured titanium surfaces on cell adherence, proliferation and shape were examined using fluorescence microscope, LSCM and MTT tests. RT-PCR was used to assess the alteration of BMP-4 gene expression. The data was analyzed for ANOVA with SAS6.0 software package. RESULTS: The results of SEM showed that plastic deformation for 60 and 90 minutes yielded nanostructured titanium surface. The nanostructured titanium surface significantly promoted Saos-2 cell adherence (P<0.05). Group II (60 minutes) had more extensive spreading on titanium surfaces than the control group. Group II (60 minutes) and group III (90 minutes) had significantly higher BMP-4 gene expression in Saos-2 cells than control group (P<0.05). CONCLUSIONS: The biological behavior of Saos-2 cells on nanostructured titanium surface fabricated via plastic deformation for 60 minutes is better than other groups. Surface plastic deformation may be a potential method to yield nanostructured surface of titanium.
Assuntos
Adesão Celular , Nanopartículas , Titânio , Diferenciação Celular , Proliferação de Células , Humanos , Microscopia Eletrônica de Varredura , Osteoblastos , Plásticos , Propriedades de SuperfícieRESUMO
PURPOSE: To investigate the clinical application value of serum tumor markers detection combined with support vector machine (SVM) model in the diagnosis of oral squamous cell carcinoma. METHODS: Serum levels of neuron-specific enolase (NSE), cancer antigen 242 (CA242), cancer antigen 19-9 (CA199), carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), cancer antigen 72-4 (CA724), cancer antigen 21-1 (CA211) and alpha fetoprotein (AFP) were detected with enzyme-linked immunosorbent assay (ELISA) and time-resolved fluoroimmunoassay (TRFIA) in 163 oral squamous cell carcinoma patients and 160 healthy persons. All the data was analyzed with SVM; the SVM models for diagnosis of oral squamous cell carcinoma were created, trained and validated by cross validation. RESULTS: Among the 163 oral squamous cell carcinoma patients, there were 128 males and 35 females with the male-to-female ratio of 3.66:1; the age ranged from 30 to 85 years old with a mean age of 59.3 years old; according to the primary site of tumor, 72 cases in tongue, 34 in gingiva, 22 in buccal mucosa, 15 in palatal mucosa, 13 in floor of mouth, 4 in lip and 3 in retromolar region; according to the TNM-UICC classification, there were 33 patients at stage T1, 72 at T2, 44 at T3, 14 at T4, 119 at N0, 42 at N1, 2 at N2, 159 at M0, 4 at M1, 27 at clinical stage I, 51 at stage II, 52 at III, and 33 at IV; according to the pathological differentiation grade, 109 tumors were well differentiated, 42 were moderately differentiated and 12 were poorly differentiated. Five serum tumor markers of CA211, CA199, TPA, CA724 and NSE were selected optimally to create the optimal SVM model for diagnosis of oral squamous cell carcinoma. The accuracy, specificity, sensitivity and positive predictive value of the optimal SVM model were 88.54%, 93.13%, 84.05% and 92.57%, respectively. CONCLUSION: From the results, SVM model combined with 5 optimal serum tumor markers is suggested to be used in the diagnosis of oral squamous cell carcinoma. Supported by Shanghai Leading Academic Discipline Project (Grant No.Y0203).
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Bucais/diagnóstico , Máquina de Vetores de Suporte , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores , Antígeno Carcinoembrionário , Feminino , Humanos , Queratinas , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To evaluate the effect of Yishenqinghuo recipe on biological characteristic of rat bone marrow stromal cells (BMSCs) and search for the function and mechanism of this recipe in treatment of periodontitis. METHODS: 12- to 15-month-old SD rats were allocated into 5 groups. Group A: control group (with no periodontitis model, fed with the same dosage of saline as Group D); Group B: model group (with periodontitis model, fed with the same dosage of saline as Group D); Group C: high dosage group (with periodontitis model, fed with a high dosage of medicine); Group D: middle dosage group (with periodontitis model, fed with a middle dosage of medicine); and Group E: low dosage group (with periodontitis model, fed with a low dosage of medicine). Ten days later, serums were collected from all the five groups for in vitro cultivation of BMSCs. RESULTS: There was displayed a similarity in effect between the serum collected from Group C1 (serum collected 0.5 h after the last gavage of Group C) and that from Group A after the last gavage, the effect being the best in terms of proliferation of BMSCs. A comparison with the other groups had revealed a striking difference (P < 0.01), with Group B having turned out to be the worst. The serum from Group C2 (serum collected 1 h after the last gavage of Group C) after the last gavage could best enhance the generation and activity of ALP, having demonstrated a significant difference (P < 0.01) in comparison with the other groups. CONCLUSION: Yishenqinghuo recipe can improve the proliferation of BMSCs and facilitate the differentiation to osteoblast.