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1.
J Chem Phys ; 158(8): 084108, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36859109

RESUMEN

As correlation strength has a key influence on the simulation of strongly correlated materials, many approaches have been proposed to obtain the parameter using first-principles calculations. However, a comparison of the different Coulomb strengths obtained using these approaches and an investigation of the mechanisms behind them are still needed. Taking lanthanide metals as an example, we research the factors that affect the effective Coulomb interaction strength, Ueff, by local screened Coulomb correction (LSCC), linear response (LR), and constrained random-phase approximation (cRPA) in the Vienna Ab initio Simulation Package. The Ueff LSCC value increases from 4.75 to 7.78 eV, Ueff LR is almost stable at about 6.0 eV (except for Eu, Er, and Yb), and Ueff cRPA shows a two-stage decreasing trend in both light and heavy lanthanides. To investigate these differences, we establish a scheme to analyze the coexistence and competition between the orbital localization and the screening effect. We find that LSCC and cRPA are dominated by the orbital localization and the screening effect, respectively, whereas LR shows the balance of the competition between the two factors. Additionally, the performance of these approaches is influenced by different starting points from the Perdew-Burke-Ernzerhof (PBE) and PBE + U, especially for cRPA. Our results provide useful knowledge for understanding the Ueff of lanthanide materials, and similar analyses can also be used in the research of other correlation strength simulation approaches.

2.
Acta Pharmacol Sin ; 41(4): 572-580, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31705124

RESUMEN

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.


Asunto(s)
Células-Madre Neurales/citología , Enfermedad de Parkinson/terapia , Trasplante de Células Madre , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Administración Intranasal , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos C57BL , Imagen Óptica , Enfermedad de Parkinson/genética , Reacción en Cadena de la Polimerasa , Tomografía Computarizada por Tomografía de Emisión de Positrones , Distribución Tisular , Circonio/química
3.
J Chem Phys ; 153(3): 034101, 2020 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-32716184

RESUMEN

A solid solution is one of the important ways to enhance the structural and functional performance of materials. In this work, we develop a structural modeling approach to solid solutions based on the similar atomic environment (SAE). We propose a similarity function associated with any type of atom cluster to describe quantitatively the configurational deviation from the desired solid-solution structure that is fully disordered or contains short-range order (SRO). In this manner, the structural modeling for solid solutions is transferred to a minimization problem in the configuration space. Moreover, we strive to enhance the practicality of this approach. The approach and implementation are demonstrated by cross validations with the special quasi-random structure method. We apply the SAE method to the typical quinary CoCrFeMnNi high-entropy alloy, continuous binary Ta-W alloy, and ternary CoCrNi medium-entropy alloy with SRO as prototypes. In combination with ab initio calculations, we investigate the structural properties and compare the calculation results with experiments.

4.
Biomed Chromatogr ; 34(12): e4903, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32428305

RESUMEN

We present a simple and robust LC-MS/MS assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. The LC-MS/MS method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. The serum samples were digested with trypsin at 50°C for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. The tryptic peptides were chromatographically separated using a C18 column (2.1 × 50 mm, 2.6 µm) with mobile phases of 0.1% formic acid in water and acetonitrile. The other monoclonal antibody, infliximab, was used as internal standards to minimize the variability during sample processing and detection. A unique peptide for each monoclonal antibody was simultaneously quantified using LC-MS/MS in the multiple reaction monitoring mode. Calibration curves were linear from 2.0 to 400 µg/mL. The intra- and inter-assay precision (%CV) was within 8.9 and 7.4% (except 10.4 and 15.1% for lower limit of quantitation), respectively, and the accuracy (%Dev) was within ±13.1%. The other validation parameters were evaluated, and all results met the acceptance criteria of the international guiding principles. Finally, the method was successfully applied to a pharmacokinetics study after a single-dose intravenous drip administration to cynomolgus monkeys.


Asunto(s)
Anticuerpos Monoclonales Humanizados/sangre , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Trastuzumab/sangre , Animales , Anticuerpos Monoclonales Humanizados/farmacocinética , Femenino , Modelos Lineales , Macaca fascicularis , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Trastuzumab/farmacocinética
5.
Phys Rev Lett ; 123(13): 136802, 2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31697526

RESUMEN

Beryllium has recently been discovered to harbor a Dirac nodal line (DNL) in its bulk phase and the DNL-induced nontrivial surface states (DNSSs) on its (0001) surface, rationalizing several already-existing historic puzzles [Phys. Rev. Lett. 117, 096401 (2016)PRLTAO0031-900710.1103/PhysRevLett.117.096401]. However, to date the underlying mechanism as to why its (0001) surface exhibits an anomalously large electron-phonon coupling effect (λ_{e-ph}^{s}≈1.0) remains unresolved. Here, by means of first-principles calculations, we show that the coupling of the DNSSs with the phononic states mainly contributes to its novel surface e-ph enhancement. Besides the fact that the experimentally observed λ_{e-ph}^{s} and the main Eliashberg coupling function (ECF) peaks are reproduced well in our current calculations, we decompose the ECF α^{2}F(k,q;v) and the e-ph coupling strength λ(k,q;v) as a function of each electron momentum (k), each phonon momentum (q), and each phonon mode (v), evidencing the robust connection between the DNSSs and both α^{2}F(k,q;v) and λ(k,q;v). The results reveal the strong e-ph coupling between the DNSSs and the phonon modes, which contributes over 80% of the λ_{e-ph}^{s} coefficient on the Be (0001) surface. It highlights that the anomalously large e-ph coefficient on the Be (0001) surface can be attributed to the presence of its DNL-induced DNSSs, clarifying the long-debated mechanism.

6.
Zhonghua Nan Ke Xue ; 25(6): 504-508, 2019 Jun.
Artículo en Zh | MEDLINE | ID: mdl-32223084

RESUMEN

OBJECTIVE: To investigate the association of the grades of histologic prostatic inflammation (HPI) with prostate cancer in biopsy specimens for male patients with total serum PSA (tPSA) of 4-10 µg/L. METHODS: We performed prostate biopsy for 200 patients with tPSA of 4-10 µg/L from January 2015 to December 2017. We determined the location, extent and intensity of HPI and analyzed the correlation of the grades of HPI with the risk of prostate cancer. RESULTS: Of the 200 biopsy specimens, BPH was detected in 169 (84.5%) and PCa in 31 (15.5%). Statistically significant differences were found in the positive rates of PCa between grades 1, 2 and 3 HPI, which were 19.3%, 25.8% and 54.8% based on the location (P < 0.01), 77.4%, 19.4% and 3.2% based on the extent (P < 0.01), and 51.6%, 29.0% and 19.4% based on the intensity of the lesion (P < 0.01), but not in the positive rates of BPH (P > 0.05). Multivariate logistic regression analysis showed that the risk of PCa was correlated negatively with the location (95% CI: 0.052-0.407, OR = 0.113, P = 0.001, r = -2.078) and extent of HPI (95% CI: 0.068-0.819, OR = 0.231, P = 0.023, r = -1.526) but not correlated with its intensity (95% CI: 0.796-4.193, OR = 1.804, P = 0.215). The positive predictive value, negative predictive value, sensitivity and specificity of the combined application of the location and extent of HPI in differentiating PCa from BPH were 51.2%, 90.3%, 91.5% and 50.8%, respectively. CONCLUSIONS: The location and extent of HPI are negatively while its intensity is not correlated with the risk of PCa. The grading of HPI based on its location and extent could help reduce the repetition of prostate biopsy.


Asunto(s)
Neoplasias de la Próstata/complicaciones , Prostatitis/complicaciones , Prostatitis/diagnóstico , Biopsia , Humanos , Masculino , Antígeno Prostático Específico/sangre
7.
Acta Pharmacol Sin ; 38(5): 710-718, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28317872

RESUMEN

JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3.0 and 3.1 nmol/L, respectively. Furthermore, JS-001 displayed distinct species cross-reactivity: it could bind to the PD-1 antigen on the peripheral blood mononuclear cells (PBMCs) of humans and cynomolgus monkeys, but not to those of mice and woodchucks; the Kd values for the interaction between JS-001 and PD-1 antigens on CD8+ T cells of human and cynomolgus monkey were 2.1 nmol/L and 1.2 nmol/L, respectively. In vitro, treatment with JS-001 (0.01-10 µg/mL) dose-dependently stimulated human T cell proliferation, as well as IFN-γ and TNF-α secretion. In HBsAg-vaccinated cynomolgus monkeys, the expression of PD-1+/CD4+ and PD-1+/CD8+ was significantly elevated, intramuscular injection of JS-001 (1 and 10 mg/kg) resulted in dramatic decreases in PD-1+/CD4+ and PD-1+/CD8+ expression in a dose-dependent manner, which was supported by PD-1 receptor occupancy (RO) results. In the PK study, 18 cynomolgus monkeys treated with single, ascending doses of 1, 10, and 75 mg/kg, and another 6 cynomolgus monkeys received 10 mg/kg successive administration. The plasma clearance of JS-001 followed a linear PK profile with single administration in the 1 and 10 mg/kg groups and a non-linear PK profile in the 75 mg/kg group. In the successive 10 mg/kg administration group, no drug accumulation was observed. But the AUC from the last exposure was lower than that of the first administration, which was probably due to the production of ADAs, as demonstrated in immunogenicity study. These non-clinical data are encouraging and provide a basis for the efficacy and safety of JS-001 in clinical trials.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacocinética , Receptor de Muerte Celular Programada 1/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Antígeno B7-H1/metabolismo , Proliferación Celular , Humanos , Macaca fascicularis , Marmota , Ratones , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/química , Unión Proteica , Linfocitos T/citología , Linfocitos T/efectos de los fármacos
8.
Phys Rev Lett ; 116(5): 057002, 2016 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-26894729

RESUMEN

Observation of high-temperature superconductivity in compressed sulfur hydrides has generated an irresistible wave of searches for new hydrogen-containing superconductors. We herein report the prediction of high-T_{c} superconductivity in tellurium hydrides stabilized at megabar pressures identified by first-principles calculations in combination with a swarm structure search. Although tellurium is isoelectronic to sulfur or selenium, its heavier atomic mass and weaker electronegativity makes tellurium hydrides fundamentally distinct from sulfur or selenium hydrides in stoichiometries, structures, and chemical bondings. We identify three metallic stoichiometries of H_{4}Te, H_{5}Te_{2}, and HTe_{3}, which are not predicted or known stable structures for sulfur or selenium hydrides. The two hydrogen-rich H_{4}Te and H_{5}Te_{2} phases are primarily ionic and contain exotic quasimolecular H_{2} and linear H_{3} units, respectively. Their high-T_{c} (e.g., 104 K for H_{4}Te at 170 GPa) superconductivity originates from the strong electron-phonon couplings associated with intermediate-frequency H-derived wagging and bending modes, a superconducting mechanism which differs substantially with those in sulfur or selenium hydrides where the high-frequency H-stretching vibrations make considerable contributions.

9.
Yao Xue Xue Bao ; 51(7): 1068-76, 2016 07.
Artículo en Zh | MEDLINE | ID: mdl-29897179

RESUMEN

Aptamers are randomly selected from single-stranded oligonucleotide libraries by systematic evolution of ligands technology exponential enrichment(SELEX). They bind to various targets like metal ions, nucleic acids, proteins, small organic compounds, and even entire organisms. Candidate aptamers are predicted to be highly effective in producing targeting effects for certain diseases like cancer, macular degeneration, acute coronary syndrome, von Willebrand factor related disorder disease and so on. Aptamers may also serve as drug-carriers helping drugs to be released in specific regions and tissues. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising to develop aptamer-drug conjugates(ApDCs) for targeted-oriented therapy. Deep investigation into Ap DCs discovery and development may promote the process of biological and biomedical analysis. In this review, we summarize the advances of drug discovery and drug delivery using aptamers in basic and clinical trials in recent years, and meanwhile analyze its advantages and challenges in biomedical studies.


Asunto(s)
Aptámeros de Nucleótidos/química , Sistemas de Liberación de Medicamentos , Descubrimiento de Drogas , Técnica SELEX de Producción de Aptámeros , Portadores de Fármacos , Ligandos , Ácidos Nucleicos , Proteínas
11.
Yao Xue Xue Bao ; 48(10): 1515-20, 2013 Oct.
Artículo en Zh | MEDLINE | ID: mdl-24417077

RESUMEN

As targeted drugs to B-cell malignancies, anti-CD20 monoclonal antibodies have been proved to be important in therapeutic antibody field. With three generations in more than ten years' development, the structures of these drugs have been improved, and many new indications have been found. Nowadays, these kinds of antibodies are not only used in the treatment of lymphoid malignancies, but also been proved to be useful in some autoimmune diseases treatment, and their new indications are still being expanded. With the optimization of their clinical dosage regimens, drug reaction has been increased, thus, therapeutic and side effects of anti-CD20 monoclonal antibody have been further improved as well. However, the exact mechanism of action of their combination therapy with other chemical drugs is still unclear, which remains to be further studied. This article reviewed new development of anti-CD20 therapeutic monoclonal antibodies research in recent years.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/inmunología , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Rituximab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Humanos
12.
World J Clin Cases ; 11(23): 5554-5558, 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37637701

RESUMEN

BACKGROUND: Jackstone is a rare entity of calculi in urinary tracts and has the characteristic appearance resembling toy jacks. They are nearly always reported to occur in the urinary bladder, we first report a rare case of jackstone located in the obstructed renal calyx. CASE SUMMARY: We report a 46-year-old man presenting with intermittent, painless gross hematuria and left flank pain. Urinary computed tomography revealed staghorn stones and secondary hydronephrosis. A jackstone with radiating branches was found in one of the dilated renal calyx. Percutaneous nephrolithotomy was performed and endoscopic images were recorded during the operation. Postoperative stone composition analysis revealed it as calcium oxalate monohydrate stones. CONCLUSION: Jackstones can occur in the renal collecting system besides the bladder. The unique appearance and imaging manifestations are the most important factors in the diagnosis of jackstones, and further exploration of the formation mechanism is required.

13.
J Phys Chem Lett ; 14(40): 8930-8939, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37768131

RESUMEN

Strongly correlated systems containing d/f electrons present a challenge to conventional density functional theory such as the local density approximation or generalized gradient approximation. We developed a doubly screened Coulomb correction (DSCC) approach to perform on-site Coulomb interaction correction for strongly correlated materials. The on-site Coulomb interaction between localized d/f electrons is self-consistently determined from a model dielectric function that includes both the static dielectric and Thomas-Fermi screening. We applied DSCC to simulate the electronic and magnetic properties of typical 3d, 4f, and 5f strongly correlated systems. The accuracy of DSCC is comparable to that of hybrid functionals but an order of magnitude faster. In addition, DSCC can reflect the difference in the Coulomb interaction between metallic and insulating situations, similar to the popular but computationally expensive constrained random phase approximation approach. This feature suggests that DSCC is also a promising method for simulating Coulomb interaction parameters.

14.
Acta Pharmacol Sin ; 33(8): 1047-54, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22728711

RESUMEN

AIM: DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODN10, in tumor-bearing mice. METHODS: B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODN10 or conventional CpG ODN1826 on the indicated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lymphocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were determined using [(3)H]-thymidine incorporation assay, 4-h (51)Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4 and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry. RESULTS: ODN10 (1, 5 and 25 mg/kg) significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with ODN1826. The immune status was suppressed in tumor-bearing mice. Both ODN10 and ODN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lymphocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting IL-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODN10 presented more potent activity, and displayed the most prominent immunostimulatory potential. CONCLUSION: ODN10 produces prominent immunomodulatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Th1-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos/uso terapéutico , Islas de CpG , Melanoma Experimental/tratamiento farmacológico , Oligodesoxirribonucleótidos/uso terapéutico , Animales , Femenino , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
15.
Yao Xue Xue Bao ; 47(7): 850-5, 2012 Jul.
Artículo en Zh | MEDLINE | ID: mdl-22993847

RESUMEN

RNA interference (RNAi), as a new technology of gene therapy, has been used in the studies of many diseases in vitro, however, targeting delivery of small interference RNA (siRNA) is still a bottleneck for clinical therapy of siRNA agents. Aptamer is a group of oligonucleotides with high affinity and targeting, and is becoming another important means of delivery for siRNA. In this review, we summarized siRNA delivery obstacles in vivo and recent attractive developments increatively using cell-internalizing aptamers to deliver siRNAs to target cells.


Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/terapia , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Aptámeros de Nucleótidos/administración & dosificación , Humanos , ARN Interferente Pequeño/administración & dosificación , Técnica SELEX de Producción de Aptámeros
16.
Yao Xue Xue Bao ; 46(11): 1370-3, 2011 Nov.
Artículo en Zh | MEDLINE | ID: mdl-22260032

RESUMEN

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.


Asunto(s)
Oligonucleótidos Antisentido/metabolismo , Oligonucleótidos Antisentido/farmacocinética , Oligonucleótidos Fosforotioatos/metabolismo , Oligonucleótidos Fosforotioatos/farmacocinética , Animales , Área Bajo la Curva , Electroforesis Capilar/métodos , Femenino , Semivida , Infusiones Intravenosas , Macaca mulatta , Masculino , Oligonucleótidos Antisentido/sangre , Oligonucleótidos Fosforotioatos/sangre , Extracción en Fase Sólida
17.
Curr Med Sci ; 41(3): 618-625, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34169424

RESUMEN

Recombinant batroxobin (S3101) is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system. A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies. Therefore, a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101. In this study, a sensitive bioanalytical method was developed and validated, using a Quanterix single molecular array (Simoa) assay. Moreover, to thoroughly assess the platform, enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed, and their performance was compared with that of this novel technology platform. The assay was validated in compliance with the current guidelines. Measurements with the Simoa assay were precise and accurate, presenting a valid assay range from 6.55 to 4000 pg/mL. The intra- and inter-run accuracy and precision were within -19.3% to 15.3% and 5.5% to 17.0%, respectively. S3101 was stable in human serum for 280 days at -20°C and -70°C, for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature (22°C-28°C), respectively, and after five and two freeze-thaw cycles at -70°C and -20°C, respectively. The Simoa assay also demonstrated sufficient dilution linearity, assay sensitivity, and parallelism for quantifying S3101 in human serum. The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.


Asunto(s)
Batroxobina/sangre , Ensayo de Inmunoadsorción Enzimática , Proteínas Recombinantes/sangre , Batroxobina/aislamiento & purificación , Batroxobina/farmacocinética , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Unión Proteica/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacocinética
18.
Acta Pharmacol Sin ; 31(11): 1500-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20953211

RESUMEN

AIM: To investigate the population pharmacokinetics of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) administered via subcutaneous (SC) injection in healthy Chinese volunteers and in Chinese patients with ankylosing spondylitis (AS). METHODS: Thirty-two healthy volunteers were randomly assigned to receive a single SC injection of 12.5, 25, 37.5, or 50 mg of rhTNFR-Fc. Twenty male patients with moderate AS were randomly assigned to receive seven consecutive SC injections of rhTNFR-Fc at either 25 mg twice a week (BIW) or 50 mg once a week (QW). Population pharmacokinetic (PK) analysis was applied to obtain PK parameters of rhTNFR-Fc by the NONMEM method. RESULTS: The data were best described by a one-compartment model with lag time. We found that gender had a significant effect on the apparent clearance (CL/F), with the male CL/F ratio being only 0.665 times the female ratio; the absorption coefficient (F) of multiple dosages of rhTNFR-Fc was only 0.674 times that of a single dosage. The outcome parameters were CL/F (female: 0.168 L/h, male: 0.110 L/h), the apparent volume of distribution (Vd/F: 15.5 L), the absorption rate constant (Ka) (single dosage: 0.0605 h⁻¹, multiple dosage: 0.0408 h⁻¹), and the lag time (T(lag): 1.03 h). The inter-individual variability in the CL/F, Vd/F, Ka, and T(lag) were 33.3%, 42.7%, 55.6%, and 81.8%, respectively. CONCLUSION: Chinese females have a higher CL/F than Chinese males, and multiple dosings can significantly decrease the absorption of rhTNFR-Fc (SC). The population PK parameters of rhTNFR-Fc in healthy Chinese volunteers and patients with AS were similar to those reported for subjects in published American studies.


Asunto(s)
Antirreumáticos/farmacocinética , Inmunoglobulina G/sangre , Receptores del Factor de Necrosis Tumoral/sangre , Proteínas Recombinantes de Fusión/farmacocinética , Caracteres Sexuales , Espondilitis Anquilosante/metabolismo , Absorción , Adulto , Antirreumáticos/sangre , China , Relación Dosis-Respuesta a Droga , Etanercept , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Proteínas Recombinantes de Fusión/sangre , Espondilitis Anquilosante/sangre , Distribución Tisular , Adulto Joven
19.
Zhonghua Yi Xue Za Zhi ; 90(3): 148-52, 2010 Jan 19.
Artículo en Zh | MEDLINE | ID: mdl-20356546

RESUMEN

OBJECTIVE: To investigate the association between Trp2 allele polymorphism with degenerative disc disease (DDD) in a Chinese Han population. METHODS: A total of 125 DDD patients (58 males and 67 females, 51.8 +/- 7.6 years old), and 125 controls matched in sex and age (63 males and 62 females, 45.3 +/- 8.3 years old) were recruited in the case-control study. Their peripheral blood samples were collected for DNA isolation. Based on NCBI genebank, the corresponding single nucleotide polymorphisms (snp)-SNP1 (rs7533552) and SNP2 (rs2077871) were identified. Hardy-Weinberg equilibrium was analyzed both in case and control groups. Then the case group was classified into different clinical phenotypes according to severity of degeneration, sole or multi-disc degeneration and different affected discs. Genotyping of all selected SNPs was performed by SNP stream technology. The association analysis between phenotypes and SNPs was conducted. Pairwise linkage disequilibrium was calculated in control population using Haploview 4.0 software. RESULTS: SNP1 (rs7533552), SNP2 (rs2077871) and corresponding SNP of Trp2 allele were gentyped and both polymorphisms distributed in line with Hardy-Weinberg equilibrium in case and control groups. Allelic frequency of SNP1A, SNP1G, SNP2C and SNP2T (42%, 47%, 88% and 90% respectively) of case group were not significantly different from those of control group (48%, 53%, 88% and 10% respectively, all P > 0.05). Genotypic frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2CC, SNP2CT and SNP2TT in case group were not significantly different from those of control group (all P > 0.05). However there was an association with genotypic frequencies of SNP2 and severity of disc degeneration (chi(2) = 6.920, P = 0.031). CONCLUSION: Trp2 allele is one of risk factors for the development and severity of DDD in a Chinese Han population.


Asunto(s)
Desplazamiento del Disco Intervertebral/genética , Oxidorreductasas Intramoleculares/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Desplazamiento del Disco Intervertebral/etnología , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad
20.
Zhonghua Wai Ke Za Zhi ; 48(16): 1229-33, 2010 Aug 15.
Artículo en Zh | MEDLINE | ID: mdl-21055212

RESUMEN

OBJECTIVE: To evaluate and compare the efficacy and clinical results of cervical expansive open door laminoplasty (EOLP) with different hinge position. METHODS: From February 2006 to February 2007, a total of 102 cases with cervical spondylotic myelopathy were assessed in this randomized controlled trial. Fifty-seven patients underwent EOLP with the hinge located at the inner margin of the lateral mass classified as wide-open group. Forty-five cases who underwent EOLP with the hinge positioned at the lamina margin served as narrow-open group. The clinical results and radiological examinations of both groups were evaluated 24 months after surgery. RESULTS: There were no significant differences in operation time, bleeding quantity and recovery rate of Japanese Orthopaedic Association (JOA) scores. The incidence of C(5) palsy and severity of axial symptoms in the wide-open group were significantly lower than those in the narrow-open group (P < 0.05). There were no significant differences in cervical curvature index and range of motion between the two groups. CONCLUSIONS: Well-suited and appropriated inwardly shift the hinge could promote clinical outcomes after EOLP, especially decrease the incidence of the C(5) palsy and the severity of axial symptom, but it is contraindication for patients with ossification of posterior longitudinal ligament, ossification of ligament flavum and fluorosis cervical stenosis.


Asunto(s)
Vértebras Cervicales/cirugía , Osteofitosis Vertebral/cirugía , Estenosis Espinal/cirugía , Anciano , Descompresión Quirúrgica/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteofitosis Vertebral/complicaciones , Estenosis Espinal/complicaciones , Resultado del Tratamiento
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