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1.
Article in Chinese | WPRIM | ID: wpr-928736

ABSTRACT

OBJECTIVE@#To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma.@*METHODS@#Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified.@*RESULTS@#44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013).@*CONCLUSION@#CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.


Subject(s)
Histones , Humans , Multiple Myeloma/genetics , Neoplasm Recurrence, Local , Oligopeptides/therapeutic use , Prognosis , Receptors, CXCR4
2.
Article in Chinese | WPRIM | ID: wpr-935752

ABSTRACT

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.


Subject(s)
Animals , HSP27 Heat-Shock Proteins , Oligopeptides , Rats , Rats, Wistar , Silicon Dioxide , Silicosis/metabolism
4.
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
5.
Int. braz. j. urol ; 45(3): 459-467, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1012312

ABSTRACT

ABSTRACT Purpose: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated an increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. Materials and Methods: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. Results: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95μg/l to 0.16μg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the first or the second scan. Conclusion: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.


Subject(s)
Humans , Male , Aged , Organometallic Compounds , Prostatic Neoplasms/pathology , Membrane Glycoproteins , Radiopharmaceuticals , Positron Emission Tomography Computed Tomography/methods , Androgen Antagonists/therapeutic use , Neoplasm Metastasis/diagnostic imaging , Oligopeptides/therapeutic use , Reference Values , Time Factors , Reproducibility of Results , Prostate-Specific Antigen/blood , Neoplasm Grading , Middle Aged , Neoplasm Recurrence, Local/pathology
6.
Article in Chinese | WPRIM | ID: wpr-774212

ABSTRACT

A diblock copolymer, poly(ethylene glycol) methacrylate-block-glycidyl methacrylate (PEGMA-GMA), was prepared on glass substrate by surface-initiated atom transfer radical polymerization (SI-ATRP), and endothelial specific peptide Arg-Glu-Asp-Val (REDV) was immobilized at the end of the PEGMA-GMA polymer brush by ring opening reaction through the rich epoxy groups in the GMA. The structure and hydrophilicity of the polymer brushes were characterized by static water contact angle, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The results showed that the REDV modified copolymer brushes were successfully constructed on the glass substrates. The REDV peptide immobilized onto surface was quantitatively characterized by ultraviolet-visible spectroscopy (UV-VIS). The blood compatibility of the coating was characterized by recalcification time and platelet adhesion assay. The results showed that the polymer coating had good blood compatibility. The multifunctional active polymer coating with PEGMA and peptide produced an excellent prospect in surface construction with endothelial cells selectivity.


Subject(s)
Biocompatible Materials , Cells, Cultured , Endothelial Cells , Glass , Humans , Immobilized Proteins , Methacrylates , Oligopeptides , Platelet Adhesiveness , Polyethylene Glycols , Polymers , Surface Properties
7.
Braz. j. med. biol. res ; 52(11): e8441, 2019. graf
Article in English | LILACS | ID: biblio-1039261

ABSTRACT

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.


Subject(s)
Animals , Male , Rats , Oligopeptides/pharmacology , Anxiety , Behavior, Animal/drug effects , Crotalid Venoms/chemistry , Depression , Exploratory Behavior/drug effects , Oligopeptides/isolation & purification , Behavior, Animal/physiology , Proline/isolation & purification , Proline/pharmacology , Rats, Wistar
8.
Braz. j. med. biol. res ; 52(1): e7844, 2019. tab, graf
Article in English | LILACS | ID: biblio-974274

ABSTRACT

Necroptosis is a regulated cell death mechanism. However, it is unknown whether necroptosis is involved in the death of tumor necrosis factor-α (TNF-α)-treated osteoblasts. Therefore, we conducted the study with TNF-α, Nec-1 (a specific inhibitor of necroptosis), and Z-IETD-FMK (a specific inhibitor of apoptosis) to determine whether necroptosis plays a role in the death of TNF-α-treated osteoblast cell line MC3T3-E1. Cell viability, cell death, and lactate dehydrogenase (LDH) release were assayed to evaluate cytotoxicity. Specific marker proteins receptor interacting protein kinase (RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) for necroptosis, and cleaved caspase 3 for apoptosis were detected by western blot, and mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). We found that TNF-α inhibited cell proliferation in a dose- and time-dependent manner. Nec-1 plus Z-IETD-FMK restored cell viability and significantly decreased LDH release. In addition, TNF-α alone increased the cell population of AV+PI−, while Z-IETD-FMK caused a shift in the cell population from AV+PI− to AV+PI+. Furthermore, TNF-α significantly increased protein cleaved caspase 3. TNF-α plus Z-IETD-FMK significantly increased the proteins RIPK3 and MLKL phosphorylation in MC3T3-E1 cells, while the changes in mRNA levels of RIPK3, MLKL, and caspase 3 were not consistent with the changes in the corresponding protein expression levels. In conclusion, TNF-α induced preferentially apoptosis in osteoblast cell line and necroptosis played a decisive role when TNF-α-induced death was inhibited by the inhibitor of apoptosis. Combined treatment with Nec-1 and Z-IETD-FMK protected mouse osteoblasts from death induced by TNF-α.


Subject(s)
Animals , Rabbits , Osteoblasts/pathology , Tumor Necrosis Factor-alpha/pharmacology , Caspase 8/drug effects , Caspase Inhibitors/pharmacology , Necrosis/pathology , Oligopeptides/pharmacology , Osteoblasts/drug effects , Phosphorylation , Cell Survival/drug effects , Imidazoles/pharmacology , Indoles/pharmacology , L-Lactate Dehydrogenase/pharmacology
9.
Journal of Experimental Hematology ; (6): 1887-1893, 2019.
Article in Chinese | WPRIM | ID: wpr-781523

ABSTRACT

OBJECTIVE@#To evaluate the efficacy and safety of carfilzomib in the treatment of multiple myeloma (MM).@*METHODS@#Computer was used to search PubMed, EMbase, Cochrane library and MEDLINE databases for carfilzomib treatment of MM. Clinical features and results were extracted and meta-analysis was performed using Stata12.0 software.@*RESULTS@#Twelve eligible Phase I/II, II and III clinical trials of carfilzomib were extracted and 2 487 MM patients involved in evaluable. The summary analysis showed that the rate of complete response (CR) of carfilzomib treatment was 28%, the rate of ≥very good partial response (VGPR) was 73%, and the rate of overall response rate (0RR) was 93%; the 1-year progression-free survival (PFS) rate of MM patients was 93%, the 2-year PFS rate was 85%, and the 3-year PFS rate was 74%. Three randomized controlled trials showed a significant improvement in ORR [OR=1.644, 95% CI=(1.056, 2.560) ] (P<0.05) and clinical benefit rate (CBR) in MM patients [OR=1.595, 95%) CI=(1.044, 2.435) ] (P<0.05). Compared with the control group, the OR of cardiotoxicity (P<0.05) was significantly increased, while that of peripheral neuropathy (P>0.05) was not significantly changed.@*CONCLUSION@#Compared with traditional treatments, carfilzomib significantly improves survival in the patients with multiple myeloma without increasing the incidence of peripheral neuropathy, but the incidence of cardiotoxicity seems higher.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Humans , Multiple Myeloma , Drug Therapy , Oligopeptides , Therapeutic Uses , Remission Induction
10.
Article in Chinese | WPRIM | ID: wpr-771877

ABSTRACT

OBJECTIVE@#To investigate the effect of Carfilzomib on mantle cell lymphoma (MCL), and to compare with effect of Bortezomib.@*METHODS@#The Jeko-1 cells and primary MCL cells were treated with Carfilzomib for 24, 48 and 72 h, then the inhibitory rate was detected using CCK-8. Lymphocytes derived from healthy volunteer were served as cell controls. Bortezomib and Cyclophosphamide (CTX) were served as medicinal controls. At the same time, the apoptosis of cells treated with different drugs was detected using flow cytometry.@*RESULTS@#The inhibitory effect of Carfilzomib on Jeko-1 cells and primary MCL cells was exhibited with time-dependent and concentration-dependent manners (P<0.01, r=0.393, r=0.650, rJ=0.473, r=0.417), but the effect on lymphocytes derived from healthy volunteer only showed time-dependence (P<0.01, r=0.928). Under the same concentration, Carfilzomib exhibited the proliferation Jeko-1 cells stronger than Bortezomib (P<0.01), but the same inhibition on primary MCL cells was not significantly different from that on lymphocytes derived from healthy volunteer (P>0.05). Under clinical recommended concentration, Carfilzomib had a stronger inhibitory effect on primary MCL cells than that of Bortezomib (P<0.01). Cell apoptosis assay showed that under the same concentration the ability of Carfilzomib to induce cell apoptosis was significantly stronger than that of Bortezomib (P<0.05).@*CONCLUSION@#Carfilzomib can inhibit the growth of MCL cells, its inhibitory rate on the MCL cells is higher than that of Bortezomib.


Subject(s)
Antineoplastic Agents , Apoptosis , Bortezomib , Cell Line, Tumor , Cell Proliferation , Humans , Lymphoma, Mantle-Cell , Oligopeptides
11.
Article in Chinese | WPRIM | ID: wpr-775933

ABSTRACT

OBJECTIVE@#To observe the effects of moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) on bone morphology, metabolism and ERα of bone marrow mesenchymal stem cells (MSCs) in the ovariectomized rats and explore the underlying mechanism of moxibustion at Guanyuan (CV 4) and Sanyinjiao (SP 6) on the regulation of bone metabolism.@*METHODS@#A total of 60 SD rats were randomized into a normal group (20 rats) and an ovariectomy group (40 rats). In the normal group, no any treatment was provided. In the ovariectomy group, the classical ovariectomy was adopted to set up the osteoporosis model. In the 13th week after ovariectomy, 10 rats were collected from each of the normal group and the ovariectomy group for model identification. After model identification, the ovariectomy group was subdivided into a model group, an estradiol group and a moxibustion group, 10 rats in each one. In the normal group and the model group, the gavage was provided with 2 mL 0.9% sodium chloride solution, once a day. In the estradiol group, the gavage was provided with 17β-estradiol 100 μg/(kg•d), once a day. In the moxibustion group, moxibustion was applied at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6), 15 min at each acupoint, once a day. The 6 treatments were as one course, with 1 day of interval, 12 courses were required. After 12-week intervention, the dual-energy X-ray was adopted to determine the bone mineral density (BMD) and bone mineral content of the whole body in living condition. After sacrificed, HE staining was adopted to observe femur structure, the enzyme-linked immunosorbent assay was to determine the absorbance of estradiol (E) and alkaline phosphatase (ALP) in serum and the real-time quantitative PCR method was to determine the mRNA expressions of ERα of MSCs in tibia and femur.@*RESULTS@#Compared with the model group, BMD was increased obviously in the pelvis and spine in the moxibustion group and the estradiol group (0.05). Compared with the model group, the bone trabeculas were stronger and well connected in the moxibustion group, indicated by HE staining. Compared with the model group, the concentrations of E in serum were increased obviously in the estradiol group and the moxibusiton group (both <0.01), and ALP concentrations reduced obviously in the estradiol group and the moxibustion group (both <0.001), the mRNA expressions of ERα in MSCs increased in the estradiol group and the moxibustion group (both <0.001).@*CONCLUSION@#Moxibustion at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) effectively increases BMD and bone strength in the ovariectomized rats and the mechanism may be related to the improvement of serum E concentration, the decrease of serum ALP concentration and the up-regulation of mRNA expression of ERα in MSCs.


Subject(s)
Animals , Bone Density , Estrogen Receptor alpha , Female , Mesenchymal Stem Cells , Moxibustion , Oligopeptides , Ovariectomy , Rats , Rats, Sprague-Dawley
12.
Article in Chinese | WPRIM | ID: wpr-775900

ABSTRACT

OBJECTIVE@#To explore the clinical effects on primary dysmenorrhea treated with moxibustion at Shenque (CV 8) and warm needling at Guanyuan (CV 4) and Sanyinjiao (SP 6).@*METHODS@#A total of 120 patients with primary dysmenorrhea were randomized into an observation group and a control group, 60 cases in each one. In the control group, the warm needling technique was used at Guanyuan (CV 4) and Sanyinjiao (SP 6). In the observation group, besides the same treatment as the control group, moxibustion was added at Shenque (CV 8). The treatment was given for 4 menstrual cycles consecutively. Before and after treatment, the score of the severity and the score of the total frequency in the retrospective scale of dysmenorrhea symptoms as well as the score of the visual analog scale (VAS) were recorded and compared in the patients between the two groups. Additionally, the safety of the two therapeutic methods was evaluated.@*RESULTS@#After treatment, the score of severity and the score of total frequency as well as VAS score of menstrual pain were all reduced as compared with those before treatment in the patients of the two groups (all 0.05).@*CONCLUSION@#The combined treatment of moxibustion at Shenque (CV 8) with the warm needling technique at Guanyuan (CV 4) and Sanyinjiao (SP 6) achieves the better clinical effects on primary dysmenorrhea as compared with the simple application of the warm needling technique at Guanyuan (CV 4) and Sanyinjiao (SP 6). This therapy is safety in clinical practice.


Subject(s)
Acupuncture Points , Dysmenorrhea , Therapeutics , Female , Humans , Moxibustion , Oligopeptides , Retrospective Studies
13.
Article in Chinese | WPRIM | ID: wpr-775046

ABSTRACT

OBJECTIVE@#To study the effect of PR-957 on the formation of A1 reactive astrocytes.@*METHODS@#The cerebral cortices of 1-day-old female rats were obtained and cultured for primary astrocytes. These cells were divided into 3 groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS (at a concentration of 5 μmol/L) for 48 hours; the LPS+PR-957 group was treated with PR-957 (at a final concentration of 200 nmol/L) for 1 hour and then LPS for 48 hours. Enzyme-linked immunosorbent assay was used to determine the expression of complement 3 (C3, a marker for A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α). Quantitative real-time PCR was used to determine the relative mRNA expression of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All the above experiments were repeated three times independently.@*RESULTS@#C3 expression was almost not observed in the control group, but was observed in both the LPS group and the LPS+PR-957 group, with significantly lower expression observed in the LPS+PR-957 group (P<0.05). The expression of TNF-α was consistent with that of C3. Compared with the control group, the LPS and the PS+PR-957 groups had significantly reduced mRNA expression levels of GPC6 and SPARCL1 but significantly increased mRNA expression level of LCN2 (P<0.001). Compared with the LPS group, the LPS+PR-957 group had significantly increased mRNA expression levels of GPC6 and SPARCL1 but significantly reduced mRNA expression level of LCN2 (P<0.001).@*CONCLUSIONS@#LPS can induce the transformation from astrocytes to A1 reactive astrocytes, and PR-957 can inhibit the formation of LPS-induced A1 reactive astrocytes.


Subject(s)
Animals , Astrocytes , Female , Lipopolysaccharides , Oligopeptides , Rats , Tumor Necrosis Factor-alpha
14.
Rev. Soc. Bras. Med. Trop ; 51(6): 731-736, Nov.-Dec. 2018. tab
Article in English | LILACS | ID: biblio-977101

ABSTRACT

Abstract INTRODUCTION: Chronic hepatitis C is a leading cause of liver disease. Infection triggers an immediate immune response in the host that is mediated by humoral/cellular mechanisms. T cells respond to infection via secretion of cytokines, which inhibit or stimulate one another, leading to cytokine imbalance and ultimately affecting treatment. Studies using interferon (IFN) and ribavirin (RBV) showed that TCD8+ cells and cytokine levels are associated with sustainable virological response (SVR). However, studies that investigated the effects of triple therapy (TT) are limited. METHODS: The study included hepatitis C virus (HCV)+ RNA, naives, genotype 1, ≥18 years, and advanced fibrosis (F≥3) patients. Samples were collected at baseline and after 12 weeks (W12) of TT. Six cytokines were analyzed by flow cytometry. RESULTS: Of 31 patients, four were excluded (two deaths, one interrupted TT, and one F2 patient). Of the 27 remaining patients, 21 (78%) were cirrhotic. SVR was achieved in 63% of the patients. The patients had a mean age of 55.11 ± 10.03 years. Analyses at baseline showed that the chemokine CCL5/Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) (p=0.04) and interleukin (IL)-6 (p=0.02), which was associated with SVR. RANTES (p=0.04) and IL-8 (p=0.01) levels were associated with SVR at W12. CONCLUSIONS Similar to patterns observed during double therapy, IL-6, IL-8, and RANTES levels were associated with SVR in TT, indicating the potential role of interferon in immune response to hepatitis C virus.


Subject(s)
Humans , Male , Female , Oligopeptides/administration & dosage , Antiviral Agents/administration & dosage , Proline/analogs & derivatives , Cytokines/blood , Hepatitis C, Chronic/drug therapy , Proline/administration & dosage , Prospective Studies , Treatment Outcome , Viral Load , Hepatitis C, Chronic/blood , Drug Therapy, Combination , Flow Cytometry , Genotype , Middle Aged
15.
Int. braz. j. urol ; 44(5): 892-899, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-975631

ABSTRACT

ABSTRACT Purpose: The purpose of our study was to evaluate the clinical impact of 68Ga-PSMA PET / CT in the setting of biochemical recurrence of prostate cancer. Materials and Methods: We retrospectively evaluated 125 prostate cancer patients submitted to the 68Ga-PSMA PET / CT due to biochemical recurrence. The parameters age, Gleason score, PSA levels, and the highest SUVmax were correlated to potential treatment changes. The highest SUVmax values were correlated with age and Gleason score. The median follow-up time was 24 months. Results: 68Ga-PSMA PET / CT led to a treatment change in 66 / 104 (63.4%) patients (twenty-one patients were lost to follow-up). There was a significant change of treatment plan in patients with a higher Gleason score (P = 0.0233), higher SUVmax (p = 0.0306) and higher PSA levels (P < 0.0001; median PSA = 2.55 ng / mL). Conclusion: 68Ga-PSMA PET / CT in prostate cancer patients with biochemical recurrence has a high impact in patient management.


Subject(s)
Humans , Male , Adult , Aged , Aged, 80 and over , Oligopeptides , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnostic imaging , Edetic Acid/analogs & derivatives , Prostate-Specific Antigen/blood , Positron Emission Tomography Computed Tomography/methods , Neoplasm Recurrence, Local/diagnostic imaging , Prostatic Neoplasms/therapy , Retrospective Studies , Follow-Up Studies , Sensitivity and Specificity , Neoplasm Grading , Middle Aged , Neoplasm Recurrence, Local/therapy
16.
Biomédica (Bogotá) ; 38(2): 232-243, ene.-jun. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-950942

ABSTRACT

Resumen Introducción. La obtención de anticuerpos específicos capaces de detectar alérgenos del grupo 1 de ácaros del polvo doméstico representa una estrategia potencial de salud pública para reducir la exposición y la sintomatología clínica asociada con el asma y la rinitis alérgica. Objetivo. Producir y purificar anticuerpos aviares antialérgenos específicos del grupo 1 de los ácaros Dermatophagoides sp.y Blomia tropicalis utilizando la tecnología IgY. Materiales y métodos. Se diseñaron y sintetizaron oligopéptidos que evidenciaran epítopes inmunogénicos de los alérgenos Der p1, Der f1 y Blo t1 empleados posteriormente para producir anticuerpos IgY policlonales en gallinas Hy Line Brown. Las IgY presentes en las yemas de los huevos se purificaron mediante cromatografía tiofílica. Su inmunorreactividad y especificidad se determinaron mediante un inmunoensayo ELISA indirecto y Dot Blot. Resultados. Se obtuvo una reactividad elevada de las IgY contra epítopes de alérgenos presentes en extractos de cuerpo entero de D. farinae, D. pteronyssinus y B. tropicalis. Los niveles más altos de IgY se produjeron entre los días 32 y 40 de inmunización. Los anticuerpos mostraron mayor inmunorreactividad y especificidad en el reconocimiento de proteínas de D. farinae, con un límite de detección mayor de 0,03 µg de proteína total delcaroajo las condiciones experimentales analizadas. Las IgY purificadas no mostraron reactividad significativa frente al extracto de Periplaneta americana. Conclusión. La tecnología IgY permitió la producción de anticuerpos específicos contra alérgenos del grupo 1 de los ácaros del polvo al utilizar oligopéptidos sintéticos no glicosilados. Hasta donde se sabe, esta es la primera vez que se usan estos reactivos inmunológicos para la detección de ácaros de importancia médica.


Abstract Introduction: The use of specific antibodies capable of detecting allergens of the group 1 of house dust mites represents a potential strategy to reduce exposure and clinical symptomatology associated with asthma and allergic rhinitis. Objective: To produce and purify chicken antibodies specific for the dust mites Dermatophagoides sp. and B. tropicalis using the IgY technology. Materials and methods: We designed and synthesized oligopeptides showing immunogenic epitopes of Der p1, Der f1, and Blo t1. These were used to produce IgY antibodies in Hy Line Brown chickens. IgY were extracted from egg yolk using thiophilic chromatography. The immunogenicity and specificity were assayed by indirect ELISA and Dot Blot. Results: We obtained high reactivity of IgY antibodies against epitopes of allergens present in whole body mites extracts of D. farinae, D. pteronyssinus, and B. tropicalis. The highest IgY levels were registered between days 32 and 40 after immunization. The antibodies showed high immunoreactivity and specificity towards D. farinae proteins with detection limits above 0.03 µg of mite proteins under the experimental conditions used. Purified IgY did not show significant reactivity when binding to Periplaneta americana extract. Conclusion: The IgY technology allowed the production of specific antibodies against house dust mites group 1 allergens using non-glycosylated synthetic peptides. To our knowledge, this is the first time that this immunochemicals are used in the detection of mites of medical relevance.


Subject(s)
Animals , Oligopeptides/immunology , Immunoglobulins/immunology , Pyroglyphidae/immunology , Antigens, Dermatophagoides/immunology , Antibodies/immunology , Chickens
17.
Rev. Soc. Bras. Med. Trop ; 51(2): 146-154, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897067

ABSTRACT

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.


Subject(s)
Humans , Male , Female , Adult , Aged , Antiviral Agents/administration & dosage , Protease Inhibitors/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Oligopeptides/administration & dosage , Oligopeptides/adverse effects , Antiviral Agents/adverse effects , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Protease Inhibitors/adverse effects , Ribavirin/administration & dosage , Ribavirin/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Proline/administration & dosage , Proline/analogs & derivatives , Proline/adverse effects , Retrospective Studies , Treatment Outcome , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Hepacivirus/drug effects , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions , Interferon alpha-2 , Genotype , Middle Aged
18.
An. acad. bras. ciênc ; 90(1): 73-84, Mar. 2018. tab
Article in English | LILACS | ID: biblio-886885

ABSTRACT

ABSTRACT The adhesion ability of bacteria to abiotic surfaces has important implications in food industries, because these organisms can survive for long periods through the biofilm formation. They can be transferred from one place to another in the industry causing contamination of the food processing environment. In this study, the antibacterial and antibiofilm activities of the antimicrobial peptide P34, characterized as a bacteriocin-like substance (BLS P34) were tested against planktonic and sessile cells of Staphylococcus aureus and Enterococcus faecalis isolated from foods. The BLS P34 showed inhibitory effect against all planktonic cells of E. faecalis. The inhibition of biofilm formation and the eradication of pre-formed biofilm were evaluated with the crystal violet assay and with the reduction of 3-bromide [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium. The BLS P34 promoted a reduction of percentage of adhered microbial cells on the surface, not being able to perform the complete elimination of biofilm formation. The metabolic activity of S. aureus biofilms decreased considerably between 41-95%. However, E. faecalis cells showed up metabolically stimulated. The BLS P34 has the potential antibiofilm for the species S. aureus. Studies suggest more detailed approaches to a better understanding of the interactions between the antimicrobial and bacterial cells within the biofilm structure.


Subject(s)
Animals , Oligopeptides/pharmacology , Staphylococcus aureus/drug effects , Bacteriocins/pharmacology , Enterococcus faecalis/drug effects , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Bacillus/isolation & purification , Bacillus/metabolism , Bacteriocins/isolation & purification , Bacterial Adhesion/drug effects , Microbial Sensitivity Tests , Analysis of Variance
19.
Rev. Soc. Bras. Med. Trop ; 51(1): 14-20, Jan.-Feb. 2018. tab
Article in English | LILACS | ID: biblio-897052

ABSTRACT

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.


Subject(s)
Humans , Male , Female , Adult , Aged , Protease Inhibitors/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Oligopeptides/administration & dosage , Ribavirin/administration & dosage , Proline/administration & dosage , Proline/analogs & derivatives , Clinical Protocols , Interferons/administration & dosage , Treatment Outcome , Hepatitis C, Chronic/virology , Drug Therapy, Combination , Sustained Virologic Response , Genotype , Middle Aged
20.
Article in Chinese | WPRIM | ID: wpr-689558

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of endomorphin-1 (EM-1) on the maturation phenotype, cytokine secretion, T cell proliferation and TLR4 expression in human peripheral blood dendritic cells (PBDCs) stimulated and induced by high glucose, and to explore the regulatory mechanism of EM-1 on DC immune function.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMNCs) were induced into immature dendritic cells (imDCs). The high glucose was used as the stimulating factor, and the EM-1 was used as the interventional factor. Then, the experiments were divided into normal glucose group (NG group), high glucose group (HG group), high glucose plus EM-1 group (EM group) and high glucose plus EM-1 and naloxone group (Nal group), respectively. The PBDC's phenotype changes were detected by flow cytometry; ELISA was used to detect the changes of cytokines secreted by PBDCs co-cultured with autologous lymphocytes; CFSE was used to detect the proliferation of T lymphocytes. TLR4 expression on PBDC surface was detected by RT-PCR.</p><p><b>RESULTS</b>Compared with HG group, the expression of PBDC surface molecules CD86, CCR7 and CD36 was up-regulated in EM group (P<0.01), while the change of CD83 expression was not statistically significant. However, IL-12 and IL-10 secreted by PBDCs and the proliferation index of T-lymphocytes stimulated by PBDCs were both decreased in EM group. Compared with EM group, the expression of CD86, CCR7 and CD36 was decreased in Nal group (P<0.01), while the expression of CD83 was almost unchanged (P>0.05). T-lymphocyte proliferation index was increased very significantly in Nal group (P<0.01). The gray ratio of TLR4 in HG group was higher than that in NG group, while the gray ratio in EM group's was very significantly lower than that in HG group's (P<0.01). These results indicate that the high glucose can promote the expression of PBDC TLR4, while the EM-1 inhibits the expression of TLR4.</p><p><b>CONCLUSION</b>EM-1 up-regulates the expression of PBDC surface molecules CD86, CCR7 and CD36 stimulated and induced by high glucose, but inhibites the induction of PBDC to maturity by high glucose. And the secreted inflammatory cytokines IL-12 and IL-10 inhibites the proliferation of T lymphocytes derived from PBDCs, while naloxone inhibites the effect of EM-1. EM-1 inhibites the expression of TLR4 on PBDC surface induced by high glucose.</p>


Subject(s)
Cell Differentiation , Cells, Cultured , Cytokines , Dendritic Cells , Glucose , Humans , Oligopeptides , Toll-Like Receptor 4
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