Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.010
Filter
2.
Article in Chinese | WPRIM | ID: wpr-887969

ABSTRACT

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1βand TNF-αin serum and IL-1βand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1βlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.


Subject(s)
Animals , Drugs, Chinese Herbal , Hydrophobic and Hydrophilic Interactions , Indigo Carmine , Indigofera , Polyethylene Glycols , Rats
3.
Article in English | WPRIM | ID: wpr-887715

ABSTRACT

Objective@#To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months.@*Results@#In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( @*Conclusion@#During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.


Subject(s)
Adult , Antiviral Agents/therapeutic use , Cytokines/blood , Female , Guanine/therapeutic use , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Male , Polyethylene Glycols/therapeutic use , Prospective Studies , Recombinant Proteins/therapeutic use
4.
Article in Chinese | WPRIM | ID: wpr-880141

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics of patients with extranodal NK/T-cell lymphoma (ENKL), and to analyze the factors that affecting the survival and prognostic of patients treated with pegaspargase based chemotherapy.@*METHODS@#The clinical data of 61 ENKL patients treated in Peking Union Medical College Hospital from January 2015 to June 2019 were enrolled and retrospectively analyzed. The clinical characteristics, survival rate and influencing factors of prognostic in patients were investigated.@*RESULTS@#The male and female ratio in the whole group was 2.8∶1. The median age was 46 years old (range, 17-67 years old). 30 patients were in stage I/II, while 31 patients were in stage III/IV. The ratio of nasal and non-nasal type was 4.1∶1. The common sites of extranodal involvement were skin and subcutaneous tissue (26.2%), liver (14.8%), lung (13.1%) and gastrointestinal tract (13.1%). 9.8% of patients showed central nervous system involvement and 11.5% showed bone marrow involvement. The median follow-up time was 22 months (range, 1-53 months). The 2-year PFS and OS rates of patients in the whole group were 51.6% and 53.2%, respectively. The 2-year OS rate of patients at stage I/II was 87.5%, while that of patients at stage III/IV was only 21.2%, the difference showed statistically significant (P60 years old and Ann Arbor stage III-IV were the independent adverse factors that affecting the prognosis of PFS and OS (HR=3.681, 95% CI 1.322-10.250; HR=4.611, 95% CI 1.118-19.009).@*CONCLUSION@#The survival of ENKL patients has been significantly improved by pegaspargase based chemotherapy. Patients with stage I/II disease have achieved a relatively good 2-year OS rate of 87.5%, but the prognosis of stage III/IV and non-nasal type patients are still poor. Age>60 years old and Ann Arbor stage III/IV are independent adverse prognostic factors for ENKL patients.


Subject(s)
Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Asparaginase , Female , Humans , Lymphoma, Extranodal NK-T-Cell/pathology , Male , Middle Aged , Neoplasm Staging , Polyethylene Glycols , Prognosis , Retrospective Studies , Young Adult
5.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(1): 54-61, Jan.-Mar. 2020. tab, graf, ilus
Article in English | LILACS | ID: biblio-1090479

ABSTRACT

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the cancer with the highest incidence in childhood and adolescence, and pharmacotherapy is the primary form of treatment. Objective and methods A systematic review of the efficacy and safety of polyethylene glycol (PEG)-asparaginase in acute lymphoblastic leukemia therapy in children and adolescents was conducted to compare it with native Escherichia coli L-asparaginase. PubMed, Web of Science, Science Direct, Cochrane Library, Scopus, LILACS (Latin American and Caribbean Health Sciences Literature) and EMBASE databases were selected. The following outcomes were analyzed: complete remission of the disease, event-free survival, overall survival, anti-asparaginase antibody level, hypersensitivity reactions, asparaginase and asparagine serum levels, number of postdiagnosis events, and overall mortality. Five randomized controlled trials were included. Analysis of the quality of evidence and risk of bias was performed using the Cochrane recommendation tool and the GRADE system. Results The assessment results suggest that the level of certainty on the technology addressed is relatively weak from a methodological point of view. Evidence is insufficient to assess the effects on health outcomes because of the limited number and power of studies and important flaws in their design or conduct in classifying PEG-asparaginase as a superior drug or not, in the pharmacotherapy of ALL in children and adolescents. PEG-asparaginase can be used as a substitute for native E. coli L-asparaginase, demonstrating similar efficacy and safety. Conclusion The study may help decision-makers in the public health system to offer a more in-depth judgment on the therapeutic alternatives used to treat this neoplasm in children and adolescents.


Subject(s)
Humans , Male , Female , Child , Adolescent , Asparaginase , Escherichia coli , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Polyethylene Glycols , Systematic Review
6.
Cad. Saúde Pública (Online) ; 36(2): e00036619, 2020. graf
Article in English | LILACS | ID: biblio-1055632

ABSTRACT

Abstract: Cost-effectiveness analysis is essential in health decision making. Several countries use it as synthesis of evidence to incorporate health technologies. The protease inhibitors (PI) boceprevir (BOC) and telaprevir (TVR) are indicated for chronic hepatitis C treatment and were incorporated in guidelines worldwide. Pre-marketing clinical trials showed higher sustained virological response rates in relation to previous therapies, but the incorporation of PIs generated a significant financial impact. The aim of this study was to discuss the relevance of cost-effectiveness analysis through a study that involved the inclusion of PIs in a clinical protocol. The analysis was part of a real-life study that included patients infected with hepatitis C virus genotype 1 treated in a tertiary university hospital in Brazil. Triple therapies (TT) with ribavirin (RBV), peginterferon α-2a (Peg-INF α-2a) and BOC or TVR were compared to dual therapy with RBV and Peg-INF α-2a. Sensitivity analysis of the cost-effectiveness ratio indicated an 88.2% chance of TTs presenting a higher cost per cure. The incremental cost-effectiveness ratios (ICER) exceeded the Brazilian gross domestic product (GDP) per capita by three times in all proposed scenarios. The sensitivity of ICER showed an 88.4% chance of TT not being cost-effective. The impact of PI incorporation was negative and the conduct about this could have been different if a previous cost-effectiveness analysis had been conducted.


Resumo: A análise de custo-efetividade tem sido essencial para a tomada de decisões em saúde. Diversos países utilizam esse tipo de análise como síntese das evidências para incorporar as tecnologias em saúde. Os inibidores de protease (IPs) boceprevir (BOC) e telaprevir (TVR) são indicados para o tratamento da hepatite C crônica e foram incorporados nas diretrizes internacionais. Os ensaios clínicos pré-marketing demonstraram taxas mais altas de resposta virológica sustentada em relação às terapias anteriores, mas a incorporação dos IPs gerou um impacto financeiro significativo. O estudo teve como objetivo discutir a relevância da análise de custo-efetividade, através de um estudo que envolveu a inclusão de IPs em um protocolo clínico. A análise fez parte de um estudo de vida real que incluiu pacientes com infecção pelo vírus da hepatite C, genótipo 1, tratados em um hospital universitário terciário no Brasil. As terapias triplas (TTs) com ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) e BOC ou TVR foram comparadas às terapias duplas com RBV e Peg-INF α-2a. A análise de sensibilidade da custo-efetividade indicou odds de 88,2% de TTs apresentarem custo mais elevado por paciente curado. Em todos os cenários propostos, as razões de custo-efetividade incremental (ICERs) superaram em três vezes o produto interno bruto (PIB) per capita brasileiro. A sensibilidade da ICER mostrou probabilidade de 88,4% das TTs não serem custo-efetivas. O impacto da incorporação dos IPs foi negativo, e a conduta teria sido diferente se tivesse sido realizada uma análise prévia de custo-efetividade.


Resumen: El análisis de coste-efectividad ha sido esencial para la toma de decisiones en salud. Diversos países utilizan este tipo de análisis como síntesis de evidencias para incorporar tecnologías en salud. Los inhibidores de proteasa (IPs) boceprevir (BOC) y telaprevir (TVR) se indican para el tratamiento de la hepatitis C crónica y fueron incorporados en directrices internacionales. Los ensayos clínicos pre-marketing demostraron tasas más altas de respuesta virológica sostenida, respecto a las terapias anteriores, pero la incorporación de los IPs generó un impacto financiero significativo. El objetivo del estudio fue discutir la relevancia del análisis de coste-efectividad, a través de un estudio que implicó la inclusión de IPs en un protocolo clínico. El análisis formó parte de un estudio de vida real que incluyó a pacientes con infección por el virus de la hepatitis C, genotipo 1, tratados en un hospital universitario terciario en Brasil. Las terapias triples (TTs) con ribavirina (RBV), peg-interferon α-2a (Peg-INF α-2a) y BOC o TVR se compararon con las terapias dobles con RBV y Peg-INF α-2a. El análisis de sensibilidad del coste-efectividad indicó odds de 88,2% de que las TTs presentaran un coste más elevado por paciente curado. En todos los escenarios propuestos, las razones de coste-efectividad incremental (ICERs) superaron tres veces el producto interno bruto (PIB) per cápita brasileño. La sensibilidad de la ICER mostró una probabilidad de que un 88,4% de las TTs no eran costo-efectivas. El impacto de la incorporación de los IPs fue negativo, y el resultado habría sido diferente si se hubiese realizado un análisis previo de coste-efectividad.


Subject(s)
Humans , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , Hepatitis C, Chronic/drug therapy , Oligopeptides , Antiviral Agents/economics , Polyethylene Glycols , Ribavirin , Recombinant Proteins , Brazil , Proline/analogs & derivatives , Interferon-alpha , Hepacivirus , Quality-Adjusted Life Years , Hepatitis C, Chronic/economics , Drug Therapy, Combination , Interferon alpha-2 , Genotype
7.
Braz. oral res. (Online) ; 34: e099, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132660

ABSTRACT

Abstract The composition of infiltrants can influence their physical properties, viscosity and depth of penetration (DP). Strategies are used to increase the DP, such as the addition of diluents or the use of heat. This study aimed to evaluate the effect of preheating and composition on physical properties and DP of infiltrants in demineralized enamel. The groups were assigned, and the following experimental formulations were made: 25%BisEMA +75%TEGDMA; 25%BisEMA +65%TEGDMA +10%ethanol; 25%BisEMA +65%TEGDMA +10%HEMA; 100%TEGDMA; 90%TEGDMA +10%ethanol; 90%TEGDMA +10%HEMA. The samples were photoactivated at two temperatures (25°C and 55°C). Degree of conversion (DC) was performed using an infrared spectrophotometer. Elastic modulus (E), flexural strength (FS) and contact angle (CA) tests were also performed. The DP of an infiltrant in demineralized enamel was determined by confocal laser scanning microscopy (CLSM) using an indirect labeling technique. The data were analyzed by two-way ANOVA and Tukey's test. DC increased after preheating in all the groups; however, 90%TEGDMA+10%ethanol showed the lowest DC for both temperatures, and the lowest E. Preheating did not influence E or FS. The CA increased at 55°C for most groups, but decreased for groups containing HEMA. Temperature did not seem to influence DP, and Icon showed the lowest DP values. The 100%TEGDMA composition showed more homogeneous penetration, whereas Icon showed heterogeneous and superficial penetration. The preheating technique does not improve all properties in all the material compositions. The composition of a material can influence and improve its properties.


Subject(s)
Dental Enamel , Polyethylene Glycols , Polymethacrylic Acids , Viscosity , Materials Testing , Bisphenol A-Glycidyl Methacrylate , Composite Resins , Elastic Modulus , Methacrylates
8.
J. appl. oral sci ; 28: e20190499, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1101251

ABSTRACT

Abstract Enzymatic degradation of the hybrid layer can be accelerated by the activation of dentin metalloproteinases (MMP) during the bonding procedure. MMP inhibitors may be used to contain this process. Objective To evaluate the degree of conversion (DC%), dentin bond strength (µTBS) (immediate and after 1 year of storage in water), and nanoleakage of an experimental (EXP) and a commercial (SB) adhesive system, containing different concentrations of the MMP inhibitor GM1489: 0, 1 µM, 5 µM and 10 µM. Methodology DC% was evaluated by FT-IR spectroscopy. Dentin bond strength was evaluated by µTBS test. Half of beams were submitted to the µTBS test after 24 h and the other half, after storage for 1 year. From each tooth and storage time, 2 beams were reserved for nanoleakage testing. Data were analyzed using ANOVA and Tukey's test to compare means (α=0.05). Results All adhesive systems maintained the µTBS after 1 year of storage. Groups with higher concentrations of inhibitor (5 µM and 10 µM) showed higher µTBS values than groups without inhibitor or with 1 µM. The nanoleakage values of all groups showed no increase after 1 year of storage and values were similar for SB and EXP groups, in both storage periods. The inhibitor did not affect the DC% of the EXP groups, but the SB5 and SB10 groups showed higher DC% values than those of SB0 and SB1. Conclusions The incorporation of GM1489 in the adhesive systems had no detrimental effect on DC%. The concentrations of 5 µM GM1489 for SB and 5 µM or 10 µM for EXP provided higher μTBS than groups without GM1489, in the evaluation after 1 year of storage; whereas the concentration of inhibitor did not affect adhesive systems nanoleakage.


Subject(s)
Humans , Polyethylene Glycols/chemistry , Polymethacrylic Acids/chemistry , Dental Cements/chemistry , Dentin/chemistry , Matrix Metalloproteinase Inhibitors/chemistry , Methacrylates/chemistry , Reference Values , Surface Properties , Tensile Strength , Time Factors , Materials Testing , Reproducibility of Results , Analysis of Variance , Dental Bonding/methods , Spectroscopy, Fourier Transform Infrared , Statistics, Nonparametric , Dental Leakage , Dentin/drug effects , Dental Etching/methods
10.
Braz. J. Pharm. Sci. (Online) ; 56: e18973, 2020. graf
Article in English | LILACS | ID: biblio-1249174

ABSTRACT

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.


Subject(s)
In Vitro Techniques/methods , Efficacy/classification , Imatinib Mesylate/adverse effects , Polyethylene Glycols/analysis , Inhibitory Concentration 50 , MCF-7 Cells/classification , Drug Liberation/drug effects
11.
Article in Korean | WPRIM | ID: wpr-811446

ABSTRACT

Optimal bowel preparation is essential for a more accurate, comfortable, and safe colonoscopy. The majority of postcolonoscopy colorectal cancers can be explained by procedural factors, mainly missed polyps or inadequate examination. Therefore the most important goal of optimal bowel preparation is to reduce the incidence of colorectal cancer. Although adequate preparation should be achieved in 85–90% or more of all colonoscopy as a quality indicator, unfortunately 20–30% shows inadequate preparation. Laxatives for oral colonoscopy bowel preparation can be classified into polyethylene glycol (PEG)-electrolyte lavage solution, osmotic laxatives, stimulant laxatives, and divided into high-volume solution (≥3 L) and low-volume solution (<3 L). The updated 2019 European Society of Gastrointestinal Endoscopy (ESGE) guideline is broadly similar to the 2014 American Society for Gastrointestinal Endoscopy (ASGE) recommendations and reaffirms the importance of split-dosing. However, new ESGE guideline, unlike the 2014 ASGE recommendation, suggests the use of high volume or low volume PEG-based regimens as well as that of non-PEG based agents that have been clinically validated for most outpatient scenarios. For effective, safe, and highly adherent bowel preparation, physicians who prescribe and implement colonoscopy should properly know the advantages and limitations, the dosing, and the timing of regimens. Recently many studies have attempted to find the most ideal regimens, and more convenient, effective, and safe regimens have been developed by reducing the dosing volume and improving the taste. The high tolerability and acceptability of the new low-volume regimens suggest us how we should use it to increase the participation of the national colorectal cancer screening program.


Subject(s)
Colonoscopy , Colorectal Neoplasms , Endoscopy, Gastrointestinal , Humans , Incidence , Laxatives , Mass Screening , Outpatients , Polyethylene Glycols , Polyps , Therapeutic Irrigation
12.
Article in Korean | WPRIM | ID: wpr-811445

ABSTRACT

For improved examination of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE), bowel preparation is an essential issue. Multiple factors like air bubbles, food material in the small bowel, and gastric and small bowel transit time affect the small bowel visualization quality (SBVQ), diagnostic yield (DY) and cecal completion rate (CR). Bowel preparation with polyethylene glycol (PEG) solution enhances SBVQ and DY, but it has no effect on CR. Bowel preparation with PEG solution 2 L is similar to PEG 4 L in SBVQ, DY, and CR. Bowel preparation with fasting or PEG solution combined with anti-foaming agents like simethicone enhance SBVQ, but it has no effect on CR. Bowel preparation with prokinetics is not commonly recommended. Optimal timing for purgative bowel preparation has yet to be established. However, the studies regarding bowel preparation for DAE are not sufficient. European Society of Gastrointestinal Endoscopy (ESGE) recommends 8–12 hours fasting from solid food and 4–6 hours fasting from liquids prior to the antegrade DAE. For retrograde DAE, colonoscopy preparation regimen is recommended. This article reviews the literature and ESGE, 2013 Korean published guidelines regarding bowel preparation for VCE and DAE, following suggestion for optimal bowel preparation for VCE and balloon enteroscopy.


Subject(s)
Capsule Endoscopy , Cathartics , Colonoscopy , Endoscopy, Gastrointestinal , Fasting , Polyethylene Glycols , Simethicone
13.
Chinese Journal of Oncology ; (12): 617-623, 2020.
Article in Chinese | WPRIM | ID: wpr-826582

ABSTRACT

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.


Subject(s)
Antibiotics, Antineoplastic , Therapeutic Uses , Consensus , Doxorubicin , Therapeutic Uses , Drug-Related Side Effects and Adverse Reactions , Female , Hand-Foot Syndrome , Humans , Neoplasms , Drug Therapy , Polyethylene Glycols , Therapeutic Uses , Practice Guidelines as Topic , Stomatitis
15.
Article in Chinese | WPRIM | ID: wpr-878786

ABSTRACT

Orthogonal experiments were used to optimize the process parameters of curcumin TPP-PEG-PCL nanomicelles; the particle size, electric potential and morphology under the electron microscope were systematically detected for the curcumin TPP-PEG-PCL nanomicelles; and the stability and in vitro release of the curcumin TPP-PEG-PCL nanomicelles were investigated. With DID fluorescent dye as the fluorescent probe, flow cytometry was used to study the uptake of nanomicelles by breast cancer cells, and laser confocal microscopy was used to study the mitochondrial targeting and lysosomal escape functions of nanomicelles. Under the same dosage conditions, the effect of curcumin TPP-PEG-PCL nanomicelles on promoting the apoptosis of breast cancer cells was evaluated. The optimal particle size of curcumin TPP-PEG-PCL nanomicelle was(17.3±0.3) nm, and the Zeta potential was(14.6±2.6) mV in orthogonal test. Under such conditions, the micelle appeared as regular spheres under the transmission electron microscope. Fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote drug uptake by tumor cells, escape from lysosomal phagocytosis, and target the mitochondria. The cell survival rate and Hoechst staining positive test results showed that curcumin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of breast cancer cells. The curcumin TPP-PEG-PCL micelles can significantly reduce the mitochondrial membrane potential of breast cancer cells, increase the release of cytochrome C, significantly increase the expression of pro-apoptotic protein Bcl-2 and reduce the expression of anti-apoptotic Bax protein. These test results were significantly better than those of curcumin PEG-PCL nanomicelles and curcumin, with statistically significant differences. The results revealed that curcumin TPP-PEG-PCL nanomicelles can well target breast cancer cell mitochondria and escape from the lysosomal capture, thereby enhancing the drug's role in promoting tumor cell apoptosis.


Subject(s)
Apoptosis , Breast Neoplasms/drug therapy , Cell Line, Tumor , Curcumin/pharmacology , Humans , Lysosomes , Micelles , Mitochondria , Phosphatidylethanolamines , Polyethylene Glycols
16.
Chinese Journal of Biotechnology ; (12): 750-762, 2020.
Article in Chinese | WPRIM | ID: wpr-826901

ABSTRACT

PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.


Subject(s)
Animals , Antiviral Agents , Humans , Interferon alpha-2 , Metabolism , Interferon-alpha , Pharmacokinetics , Polyethylene Glycols , Pharmacokinetics , Protein Structure, Secondary , Rats , Recombinant Proteins , Pharmacokinetics , Pharmacology , Reproducibility of Results , Transglutaminases , Metabolism
17.
Article in Chinese | WPRIM | ID: wpr-879771

ABSTRACT

OBJECTIVE@#To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups.@*RESULTS@#A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P0.05).@*CONCLUSIONS@#The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.


Subject(s)
Child , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Neutropenia , Polyethylene Glycols , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prospective Studies , Recombinant Proteins
18.
Biosci. j. (Online) ; 35(6): 1829-1838, nov./dec. 2019. graf
Article in English | LILACS | ID: biblio-1049133

ABSTRACT

Salvia hispanica seedlings have stood out for their potentialities in nutrients for agri-food industries. Nevertheless, studies related to this species are still scarce, especially with respect to agronomic factors that enable its propagation and development. Hence, this study aimed to evaluate germination, vigor and osmotic adjustment of S. hispanica seeds and seedlings subjected to water and thermal stress. The experimental design was completely randomized, with treatments arranged in factorial scheme, corresponding to five levels of polyethylene glycol (PEG 6000) (0.0; -0.1; -0.2; -0.3 and -0.4 MPa) and five temperatures (20, 25, 30 and 20-30 °C), with four replicates of 50 seeds in each treatment. Germination test was set on blotter paper, moistened with PEG 6000 solutions at the previously mentioned potentials, under 8-h photoperiod. The following variables were analyzed: germination, germination speed index, seedling shoot length, seedling root length, seedling dry matter and contents of chlorophyll, carotenoids, amino acids, proline and sugars. Polyethylene glycol levels of -0.4 MPa at all temperatures and -0.3 MPa at 30 °C and 20-30 °C enable germination and vigor of S. hispanica seedlings. S. hispanica seedlings are able to perform osmotic adjustment under water stress conditions up to the level of -0.3 MPa, when grown from seeds germinated at temperatures of up to 25 ºC.


As sementes de S. hispanica têm se destacado pela sua potencialidade em nutrientes para as indústrias agroalimentares. No entanto, ainda são escassas as pesquisas relacionadas a esta espécie, principalmente no tocante aos fatores agronômicos que viabilizem a sua propagação e desenvolvimento. Com isso, objetivou-se verificar a germinação, vigor e ajustamento osmótico de sementes e plântulas de S. hispanicasubmetidas aos estresses hídrico e térmico. O delineamento experimental foi o inteiramente casualizado, com tratamentos distribuídos em esquema fatorial, correspondente a cinco níveis de polietileno glicol (PEG 6000) (0,0; -0,1; -0,2; -0,3 e -0,4 MPa) e quatro temperaturas (20, 25, 30 e 20-30 °C), com quatro repetições de 50 sementes para cada tratamento. Para isso, instalou-se o teste de germinação em substrato mata-borrão, umedecidos com soluções de PEG 6000 nos potenciais mencionados, sob fotoperíodo de 8 horas de luz. As variáveis analisadas foram germinação, índice de velocidade de germinação, comprimento de parte aérea e das raízes das plântulas, massa seca de plântulas, teores de clorofila e carotenoides, aminoácidos, prolina e açúcares. O nível de polietilenoglicol de -0,4 MPa para todas as temperaturas estudadas, e -0,3 MPa nas temperaturas de 30 °C e 20-30 °C inviabilizam a germinação e o vigor das plântulas de S. hispanica. As plântulas de S. hispanica são capazes de realizar ajuste osmótico sob condições de estresse hídrico até os níveis de -0,3 MPa, quando provenientes de sementes germinadas em temperaturas de até 25 ºC.


Subject(s)
Polyethylene Glycols , Germination , Heat-Shock Response , Salvia , Dehydration , Stress, Physiological
19.
Int. j. odontostomatol. (Print) ; 13(3): 258-265, set. 2019. tab, graf
Article in English | LILACS | ID: biblio-1012419

ABSTRACT

ABSTRACT: The aim of this research was to perform a systematic review to identify the most frequent uses of PLA/ PGA in alveolar bone regeneration and their results. A study was designed to answer the question: What are the most frequent uses of PLA/PLGA and their copolymers in alveolar bone regeneration?. A systematic search was done on MEDLINE, EMBASE and LILACS from April 1993 to December 2017. The search string used on MEDLINE was: (((polylactic acid) OR PLA) OR PLA-based copolymers) OR PLA blends) OR PLA scaffolds)) AND ((("Bone Regeneration"[Mesh]) OR bone regeneration) OR guided bone regeneration). The search was complemented by a manual review of the references from the articles included. Most of the studies selected were weak and, regarding the most frequent uses of PLA/PGA, 13 studies used it as a resorbable membrane, two as an absorbable mesh, one as an absorbable screw and three as filling material. Based on our results, the authors consider that PLA/PGA requires a delicate relation between the mechanical resistance and the degradation process. PLA/PGA does not interrupt bone regeneration; however, the influence in cellular events related to bone regeneration and later osseointegration have not been identified.


RESUMEN: El objetivo de esta revisión fue realizar una revisión sistemática de la literatura para identificar los usos más frecuentes de PLA/PGA en regeneración ósea en área maxilofacial y sus resultados. Se diseñó un estudio para responder a la pregunta: ¿Cuáles son los usos más frecuentes de PLA/PLGA y sus copolímeros en regeneración ósea en el sector maxilofacial?. Los estudios seleccionados fueron en su mayoría débiles y sobre los usos más frecuentes de PLA/PGA, 13 estudios lo utilizaron como membrana reabsorbible, 2 estudios como malla absorbible, un estudio como tornillo absorbible y 3 estudios como material de relleno. En base a nuestros resultados, los autores estiman que PLA/PGA requiere una delicada relación entre la resistencia mecánica que ofrece y la degradación que se produce; PLA/ PGA no interrumpe la regeneración ósea, sin embargo, no se ha identificado la potencialidad o influencia que presenta en los eventos celulares de la regeneración y posterior oseointegración.


Subject(s)
Humans , Polyethylene Glycols/chemistry , Dental Implants , Alveolar Bone Loss/surgery , Bone Substitutes , Alveolar Ridge Augmentation/methods , Bone Regeneration , Bone Transplantation
20.
Electron. j. biotechnol ; 41: 81-87, sept. 2019. tab, graf, ilus
Article in English | LILACS | ID: biblio-1087242

ABSTRACT

Background: The search for innovative anti-tubercular agents has received increasing attention in tuberculosis chemotherapy because Mycobacterium tuberculosis infection has steadily increased over the years. This underlines the necessity for new methods of preparation for polymer-drug adducts to treat this important infectious disease. The use of poly(ethylene glycol)(PEG) is an alternative producing anti-tubercular derivatives. However, it is not yet known whether PEGylated isonicotinylhydrazide conjugates obtained by direct links with PEG are useful for therapeutic applications. Results: Here, we synthesized a PEGylated isoniazid (PEG-g-INH or PEG­INH) by gamma radiation-induced polymerization, for the first time. The new prodrugs were characterized using Raman and UV/Vis spectrometry. The mechanism of PEGylated INH synthesis was proposed. The in vitro evaluation of a PEGylated isonicotinylhydrazide macromolecular prodrug was also carried out. The results indicated that PEG­INH inhibited the bacterial growth above 95% as compared with INH, which showed a lower value (80%) at a concentration of 0.25 µM. Similar trends are observed for 0.1, 1, and 5 µM. Conclusions: In summary, the research suggests that it is possible to covalently attach the PEG onto INH by the proposed method and to obtain a slow-acting isoniazid derivative with little toxicity in vitro and higher antimycobacterial potency than the neat drug.


Subject(s)
Polyethylene Glycols/chemistry , Isoniazid/chemistry , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/chemistry , Polyethylene Glycols/pharmacology , Polymers , Spectrum Analysis, Raman , In Vitro Techniques , Prodrugs , Polymerization , Gamma Rays , Isoniazid/pharmacology , Antitubercular Agents/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL