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1.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198754

RESUMO

BACKGROUND: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Parquetina nigrescens (HELEPN) against d-galactose-induced testicular injury. METHODS: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. RESULTS: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. CONCLUSION: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.


Assuntos
Apocynaceae/química , Galactose/efeitos adversos , Infertilidade Masculina/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Testículo/lesões , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Gonadotropinas/metabolismo , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Distribuição Aleatória , Ratos , Ratos Wistar , Análise do Sêmen , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
2.
Am J Speech Lang Pathol ; 30(4): 1819-1845, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34232693

RESUMO

Purpose Research comparing different biofeedback types could lead to individualized treatments for those with residual speech errors. This study examines within-treatment response to ultrasound and visual-acoustic biofeedback, as well as generalization to untrained words, for errors affecting the American English rhotic /ɹ/. We investigated whether some children demonstrated greater improvement in /ɹ/ during ultrasound or visual-acoustic biofeedback. Each participant received both biofeedback types. Individual predictors of treatment response (i.e., age, auditory-perceptual skill, oral somatosensory skill, and growth mindset) were also explored. Method Seven children ages 9-16 years with residual rhotic errors participated in 10 treatment visits. Each visit consisted of two conditions: 45 min of ultrasound biofeedback and 45 min of visual-acoustic biofeedback. The order of biofeedback conditions was randomized within a single-case experimental design. Acquisition of /ɹ/ was evaluated through acoustic measurements (normalized F3-F2 difference) of selected nonbiofeedback productions during practice. Generalization of /ɹ/ was evaluated through acoustic measurements and perceptual ratings of pretreatment/posttreatment probes. Results Five participants demonstrated acquisition of practiced words during the combined treatment package. Three participants demonstrated a clinically significant degree of generalization to untreated words on posttreatment probes. Randomization tests indicated one participant demonstrated a significant advantage for visual-acoustic over ultrasound biofeedback. Participants' auditory-perceptual acuity on an /ɹ/-/w/ identification task was identified as a possible correlate of generalization following treatment. Conclusions Most participants did not demonstrate a statistically significant difference in acoustic productions between the ultrasound and visual-acoustic conditions, but one participant showed greater improvement in /ɹ/ during visual-acoustic biofeedback. Supplemental Material https://doi.org/10.23641/asha.14881101.


Assuntos
Transtorno Fonológico , Adolescente , Biorretroalimentação Psicológica , Criança , Humanos , Distribuição Aleatória , Fala , Fonoterapia , Estados Unidos
3.
Cardiovasc Ther ; 2021: 5596590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113390

RESUMO

Introduction: In the animal model, preconditioning is a powerful weapon against ischemic damage. The reason why the human heart cannot be protected from ischemic damage by preconditioning remains unclear. There are assumptions that the lack of preconditioning in humans is caused by concomitant diseases such as dyslipoproteinemia and arteriosclerosis. This study investigates whether dyslipoproteinemia and the resulting arteriosclerosis can be a cause of a reduced precondition effect of heart in mice. Methods: LDL receptor-deficient mice were fed a long-term (14-16 weeks) high-fat atherogenic diet to induce arteriosclerosis. Arteriosclerosis was identified by histological examination and vessel contraction tests. LDLR-/- and wild-type mice were randomly assigned to anesthetic-induced, remote ischemic, or no preconditioning. All mice were subjected to 45 minutes of coronary artery occlusion and 180 minutes of reperfusion. The area at risk and infarct size were determined by Evans Blue and triphenyltetrazolium chloride staining. Results: Histopathological examination showed atherosclerosis in high-fat atherogenic fed LDLR-/- mice, and the vessel relaxation capacity was significantly reduced compared to wild-type mice. In the wild type, as expected, infarct size was significantly reduced by preconditioning compared to the control. In LDLR-/- mice, infarct size was significantly reduced by preconditioning compared to the control. Surprisingly, the LDLR-/- control group also had a significantly reduced infarct size compared to the wild-type control group. Conclusion: We were able to demonstrate that a high-fat diet morphologically and functionally triggered atherosclerosis in LDLR-/- mice. Interestingly, LDLR-/- mice with an atherogenic diet had smaller infarct sizes compared to wild-type mice. Moreover, preconditioning additionally reduced myocardial infarct size in LDLR-/- mice. A long-term high-fat atherogenic diet and preconditioning seem to result in additive cardioprotection in LDLR-/- mice.


Assuntos
Anestésicos/farmacologia , Aterosclerose/patologia , Dislipidemias/patologia , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/patologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Distribuição Aleatória , Receptores de LDL/deficiência
4.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071132

RESUMO

Demethoxycurcumin (DMC), a derivate of curcumin, has been shown to induce apoptotic cell death in human glioblastoma multiforme GBM 8401 cells via cell cycle arrest and induction of cell apoptosis. However, there is no report showing DMC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigated the effects of DMC on GBM8401 cells in vivo. At first, we established a luciferase-expressing stable clone named GBM 8401/luc2. Second, mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate a xenograft tumor mice model. After inoculation, tumor volume reached 100-120 mm3, and all mice were randomly divided into three groups: Group I was treated with 110 µL phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 30 mg/kg of DMC, and Group III with 60 mg/kg of DMC. Mice from each group were given the oral treatment of DMC by gavage for 21 days. The body weight and tumor volume were recorded every 3 days. DMC significantly decreased the tumor volumes, and 60 mg/kg treatment showed a higher decrease in tumor volumes than that of 30 mg/kg, However, DMC did not affect the body weights. The photons emitted from mice tumors were detected with Xenogen IVIS imaging system, DMC at both doses decreased the total photon flux and 60 mg/kg treatment of DMC has low total photon flux than that of 30 mg/kg. The tumor volumes and weights in 60 mg/kg treatment of DMC were lower than that of 30 mg/kg. Immunohistochemical analysis was used to measure protein expression of tumors and results showed that DMC treatment led to lightly staining with anti-Bcl-2 and -XIAP and 60 mg/kg treatment of DMC has lighter staining with anti-Bcl-2 and -XIAP than that of 30 mg/kg. The higher dose (60 mg/kg) of DMC has higher signals of cleaved-caspase-3 than that of the lower dose (30 mg/kg). Furthermore, the hematoxylin and eosin (H&E) staining of liver tissues showed no significant difference between DMC-treated and control-groups. Overall, these observations showed that DMC suppressed tumor properties in vivo and DMC may be used against human glioblastoma multiforme in the future.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Diarileptanoides/uso terapêutico , Glioblastoma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Diarileptanoides/toxicidade , Genes Reporter , Glioblastoma/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Distribuição Aleatória , Carga Tumoral , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/análise , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/análise
5.
Toxins (Basel) ; 13(6)2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064255

RESUMO

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.


Assuntos
Aflatoxina B1/envenenamento , Micotoxicose/tratamento farmacológico , Ocratoxinas/envenenamento , Silimarina/administração & dosagem , Zeolitas/administração & dosagem , Ração Animal , Animais , Bacillus licheniformis , Bacillus subtilis , Galinhas , Micotoxicose/metabolismo , Micotoxicose/patologia , Distribuição Aleatória , Saccharomyces cerevisiae
6.
Res Vet Sci ; 138: 90-99, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34126450

RESUMO

With the rapid development of the poultry breeding industry and highly intensive production management, the losses caused by stress responses are becoming increasingly serious. To screen candidate genes related to chicken stress and provide a basis for future research on the molecular mechanisms governing the effects of stress on chicken immune function, we successfully constructed a chicken stress model by exogenously introducing corticosterone (CORT). RNA-seq technology was used to identify and analyze the mRNA and enrichment pathways of the thymus in the stress model group and the control group. The results showed that there were 101 significantly differentially expressed genes (SDEGs) (Padj < 0.05, |log2fold changes| ≥ 1 and FPKM >1), of which 44 were upregulated genes, while 57 were downregulated genes. Gene Ontology (GO) enrichment analysis found that the terms related to immunity or stress mainly included antigen processing and presentation, positive regulation of T cell-mediated immunity, and immune effector process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the main pathways related to immunity or stress were the PPAR signaling pathway, NOD-like receptor signaling pathway, and intestinal immune network for IgA production. Among the SDEGs, XCL1, HSPA8, DMB1 and BAG3 are strongly related to immunity or stress and may be important genes involved in regulating stress affecting the immune function of chickens. The above results provide a theoretical reference for subsequent research on the molecular regulatory mechanisms by which stress affects the immune function of poultry.


Assuntos
Galinhas/genética , Imunidade/genética , Timo/imunologia , Transcriptoma , Animais , Galinhas/imunologia , Distribuição Aleatória , Estresse Fisiológico/imunologia , Timo/metabolismo
7.
Fish Shellfish Immunol ; 115: 86-94, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091037

RESUMO

A 56-day trial was conducted to evaluate the effects of dietary lutein pigment on growth, biochemical, and immuno-physiological parameters of the oriental river prawn. Prawns were fed five formulated diets containing different lutein levels, 0 (control), 50, 100, 150, and 200 mg/kg. Growth performance, except hepatosomatic index, was affected by different lutein levels, and biochemical parameters (urea, uric acid, glucose, creatinine, and triglycerides) decreased. However, high-density and low-density lipoprotein elevated significantly compared to the control treatment. Furthermore, calcium, phosphorus, and cholesterol did not show a significant difference. Hemato-immunological parameters (albumin, total protein, cortisol, lysozyme, phenoloxidase, total hemocyte count, granular cells, semi-granular cells, hyaline cells, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase), and hepatopancreatic antioxidant statuses (total antioxidant capacity, superoxide dismutase, catalase, and malondialdehyde), were significantly affected; however, alkaline phosphatase and glutathione peroxidase were not affected by lutein treatments. By increasing dietary lutein levels, digestive enzyme activities, total bacteria count, total carotenoid content, significantly increased. Conversely, lactic acid bacteria were not affected. Overall, the research results demonstrated that adding 200 mg/kg of lutein to the diet improved growth performance, biochemical and immuno-physiological parameters of the oriental river prawn.


Assuntos
Luteína/metabolismo , Palaemonidae/imunologia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Luteína/administração & dosagem , Palaemonidae/química , Palaemonidae/crescimento & desenvolvimento , Distribuição Aleatória
8.
Fish Shellfish Immunol ; 115: 212-220, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34146675

RESUMO

Eight weeks feeding experiment was managed to evaluate the impacts of dietary addition of pineapple peel powder (PAPP) and Lactobacillus plantarum CR1T5 (LP) individual or mixed on growth performance, skin mucus and serum immunities, as well as disease resistance of Nile tilapia. Fish (average weight 20.91 ± 0.11 g) were fed four diets: Diet 1 (0 g kg-1 PAPP and 0 CFU g-1 L. plantarum, Diet 2 (10 g kg-1 PAPP), Diet 3 (108 CFU g-1L. plantarum), and Diet 4 (10 g kg-1 PAPP + 108 CFU g-1L. plantarum). Serum and mucus immune responses, as well as growth rate, were assessed every 4 weeks. Ten fish were chosen for the challenge test with Streptococcus agalactiae after 8 weeks post-feeding. The findings showed that PAPP and/or LP diets increased (P ≤ 0.05) growth performance, skin mucus, and serum immune responses. The best data were obtained in fish fed a mixture of PAPP and LP. Nevertheless, no variation (P > 0.05) was recorded between groups fed PAPP or LP. The relative survival percentage (RSP, %) in Diet 2, Diet 3, and Diet 4 was 46.15%, 50.0%, and 73.08%. Fish fed mixture of PAPP + LP recorded the best (P < 0.05) survival rate versus other treatments. The current findings recommended using a mixture of PAPP and LP as promising functional additives for aquaculture practice.


Assuntos
Ananas/química , Ciclídeos/imunologia , Resistência à Doença , Imunidade Inata , Lactobacillus plantarum/química , Probióticos/metabolismo , Ração Animal/análise , Animais , Aquicultura , Ciclídeos/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/efeitos dos fármacos , Frutas/química , Imunidade Inata/efeitos dos fármacos , Pós/administração & dosagem , Pós/química , Probióticos/administração & dosagem , Distribuição Aleatória
9.
J Fish Dis ; 44(8): 1191-1200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34061996

RESUMO

Water temperature is one of the most common physiological stressors in aquaculture. Previous studies demonstrate that organisms require miRNA activity for survival in various unfavourable environmental conditions. However, the detailed role of miRNA in response to low-temperature stress is still unclear. This study was conducted to construct a comprehensive miRNA dataset for the Penaeus vannamei after low-temperature stress. A total of 329 known miRNAs and 60 putative novel miRNAs were identified. Among them, 17 miRNAs were identified with the most significant differences, and they were found to be involved in stimulation or stress processes. The main enriched target pathways of the 17 miRNAs were the Hippo signalling pathway, autophagy, apoptosis and MAPK signalling. In addition, all the 17 miRNAs identified were up-regulated, suggesting that miRNA by inhibiting the expression of target genes constitutes an effective strategy for Penaeus vannamei to cope with low-temperature stress. The 35-putative target of the 17 miRNAs was related to apoptosis and autophagy-related proteins, such as Pxt, DRAM2, cytochrome c, ATG2B, JNK, ATG4 and API5. The analysis of miRNA expression profiles contributes to the understanding of the molecular mechanisms of low-temperature tolerance in Penaeus vannamei. This study's findings enrich current miRNA resources and offer the possibility to validate the involvement of 17 miRNAs in the response of shrimp to low-temperature stress.


Assuntos
Adaptação Fisiológica , Temperatura Baixa/efeitos adversos , MicroRNAs/metabolismo , Penaeidae/fisiologia , Estresse Fisiológico , Animais , Penaeidae/genética , Distribuição Aleatória
10.
Jt Dis Relat Surg ; 32(2): 347-354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34145810

RESUMO

OBJECTIVES: This study aims to evaluate the effect of adipose-derived stromal vascular fraction (SVF) on osteochondral defects treated by hyaluronic acid (HA)-based scaffold in a rabbit model. MATERIALS AND METHODS: Eighteen white New Zealand rabbits were randomly grouped into the experimental group (n=9) and control group (n=9). In all groups, osteochondral defects were induced on the weight-bearing surfaces of the right femoral medial condyles, and a HA-based scaffold was applied to the defect area with microfractures (MFs). In this study, 1 mL of adipose-derived SVF was injected into the knee joints of the rabbits in the experimental group. For histological and macroscopic evaluation, four rabbits were randomly selected from each group at Week 4, and the remaining rabbits were sacrificed at the end of Week 8. Macroscopic assessments of all samples were performed based on the Brittberg scoring system, and microscopic evaluations were performed based on the O'Driscoll scores. RESULTS: Samples were taken at Weeks 4 and 8. At Week 4, the O'Driscoll scores were significantly higher in the control group than the experimental group (p=0.038), while there was no significant difference in the Brittberg scores between the two groups (p=0.108). At Week 8, the O'Driscoll score and Brittberg scores were statistically higher in the experimental group than in the control group (p=0.008 and p=0.007, respectively). According to the microscopic evaluation, at the end of Week 8, the cartilage thickness was greater in the experimental group, and nearly all of the defect area was filled with hyaline cartilage. CONCLUSION: Application of adipose-derived SVF with MF-HA-based scaffold was better than MF-HA-based scaffold treatment in improving osteochondral regeneration. Therefore, it can be used in combination with microfracture and scaffold to accelerate cartilage regeneration, particularly in the treatment of secondary osteoarthritis.


Assuntos
Tecido Adiposo , Cartilagem Articular/fisiologia , Cartilagem Hialina/fisiologia , Ácido Hialurônico/uso terapêutico , Regeneração , Viscossuplementos/uso terapêutico , Tecido Adiposo/citologia , Animais , Artroplastia Subcondral , Cartilagem Articular/lesões , Fêmur , Articulação do Joelho , Transplante de Células-Tronco Mesenquimais , Coelhos , Distribuição Aleatória
11.
Jt Dis Relat Surg ; 32(2): 377-382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34145814

RESUMO

OBJECTIVES: In this mechanical study, we aimed to compare two different screw trajectories in terms of durability against axial loads on oblique scaphoid fractures using composite bone models. MATERIALS AND METHODS: Oblique osteotomies were made along the dorsal sulcus of 14 composite scaphoid bone models. Following this, all bone models were randomly classified. One group of bones were fixed with a screw placed perpendicular to the osteotomy line and the other group was fixed with a screw placed centrally down the long axis of the scaphoid bone. Each scaphoid bone model was positioned on a mechanical testing machine. Subsequently, axial loading tests were applied on each bone model to measure the amount of loading required to cause 2-mm displacement and failure on the osteotomy side and maximum displacement at the time of failure on scaphoid bone models. RESULTS: There was no statistically significant difference in load to 2-mm displacement and failure between the two groups (p>0.05). Also, there was no statistically significant difference between the two groups in terms of maximum displacement seen on failure (p>0.05). CONCLUSION: In our study, we found that the stability of the screws which laid perpendicular to the fracture line and parallel to the long axis of the scaphoid was the same in fixing oblique scaphoid fractures.


Assuntos
Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Osso Escafoide/cirurgia , Humanos , Modelos Anatômicos , Osteotomia , Distribuição Aleatória , Osso Escafoide/lesões , Suporte de Carga
12.
Biomed Environ Sci ; 34(5): 356-363, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34059172

RESUMO

Objective: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. Methods: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. Results: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. Conclusion: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.


Assuntos
Dieta , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Homocisteína/metabolismo , Sarcosina/análogos & derivados , Animais , Biomarcadores/metabolismo , Cromatografia Líquida , Fígado/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Sarcosina/administração & dosagem , Sarcosina/metabolismo
13.
Int J Oral Maxillofac Implants ; 36(3): e42-e50, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115064

RESUMO

PURPOSE: To evaluate the formation of reactive oxygen species in human leukocytes promoted by bone substitutes that are different in origin and morphology used for jawbone tissue regeneration. MATERIALS AND METHODS: This preclinical prospective randomized crossover study involved 10 subjects, from whom venous blood samples were taken. Leukocytes were separated and standardized. Sixty experimental samples consisted of leukocytes incubated with allogeneic, xenogeneic, or alloplastic bone substitutes at different bone weights (12.5 and 25 mg). The control samples consisted only of incubated leukocytes. Reactive oxygen species were quantitatively determined with the fluorimetric method. Statistical analysis was carried out using SPSS 23 software. RESULTS: The highest average reactive oxygen species values were obtained in the allogeneic bone substitute group (P < .05), while the xenogeneic bone substitute group and control group presented equal reactive oxygen species formation rates (P > .05). A proportional difference (P < .05) of reactive oxygen species emission was obtained between different masses of bone substitute in the samples. CONCLUSION: Allogeneic and alloplastic bone substitutes affect leukocytes and promote reactive oxygen species emission. Xenogeneic bone substitute presents no leukocyte stimulation and maintains anti-inflammatory conditions. Larger bone substitute mass provokes greater oxidative stress.


Assuntos
Substitutos Ósseos , Leucócitos , Espécies Reativas de Oxigênio , Estudos Cross-Over , Humanos , Projetos Piloto , Estudos Prospectivos , Distribuição Aleatória
14.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947138

RESUMO

Ovarian clear cell carcinoma (OCCC) is a rare but chemorefractory tumor. About 50% of all OCCC patients have inactivating mutations of ARID1A, a member of the SWI/SNF chromatin-remodeling complex. Members of the SWI/SNF remodeling have emerged as regulators of the energetic metabolism of mammalian cells; however, the role of ARID1A as a modulator of the mitochondrial metabolism in OCCCs is yet to be defined. Here, we show that ARID1A loss results in increased mitochondrial metabolism and renders ARID1A-mutated cells increasingly and selectively dependent on it. The increase in mitochondrial activity following ARID1A loss is associated with increase in c-Myc expression and increased mitochondrial number and reduction of their size consistent with a higher mitochondrial cristae/outer membrane ratio. Significantly, preclinical testing of the complex I mitochondrial inhibitor IACS-010759 showed it extends overall survival in a preclinical model of ARID1A-mutated OCCC. These findings provide for the targeting mitochondrial activity in ARID1A-mutated OCCCs.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Antineoplásicos/uso terapêutico , Proteínas de Ligação a DNA/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Oxidiazóis/uso terapêutico , Piperidinas/uso terapêutico , Fatores de Transcrição/antagonistas & inibidores , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Oxidiazóis/farmacologia , Fosforilação Oxidativa/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Piperidinas/farmacologia , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Distribuição Aleatória , Esferoides Celulares , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Poult Sci ; 100(6): 101147, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33940283

RESUMO

Growth performance and physiological responses of feeding modified soy protein concentrate (MSPC, 72% CP) in the starter phase were investigated. A total of 1,216 d old male Ross x Ross 708 broiler chicks were placed in 32 floor pens based on BW, fed one of 4 (n = 8) corn-soybean meal-based diets formulated with 0, 7.7, 10.0 or 12.5% MSPC for 10 d and transitioned to common diets to d 42. Feed intake, BW, and mortality were measured. Samples of birds were bled on d 10 for plasma uric acid (PUA) and subsequently necropsied for organs weight and samples of pancreatic tissues for enzyme activity, jejunal tissues for enzyme activity and histomorphology and ceca digesta for microbial activity. Litter moisture was determined on d 36 and 42 and sample of birds were necropsied on d 42 for breast yield and ceca digesta sample for microbial activity. Feeding MSPC linearly (P < 0.001) increased starter growth performance. Overall (d 0-42), MSPC linearly (P = 0.05)improved FCR; The FCR was 1.566, 1.535, 1.488 and 1.527 for 0.0, 7.7, 10.0, and 12.5% MSPC, respectively. Feeding MSPC linearly (P ≤ 0.04) increased breast yield and decreased small intestine length, gizzard digesta pH, and PUA. Breast yield was 230, 238, 246, and 252 g/kg BW for 0.0, 7.7, 10.0, and 12.5% MSPC, respectively. Pancreatic and jejunal chymotrypsin and trypsin activities and histomorphology were not (P > 0.10) influenced by the diets. On d 10, MSPC linearly (P < 0.05) reduced ceca digesta abundance of Ruminococcaceae, E. Coli, and Clostridium but increased abundance of Bifidobacterium and the ratio of Lactobacilli and E. Coli. Birds fed MSPC showed linear (P = 0.01) increase in abundance of Bifidobacterium on d 42. Feeding MSPC linearly increased ceca digesta acetic (P = 0.01) and reduced propionic (P = 0.048), and iso butyric (P = 0.003) in 10 d old broiler chicken. In conclusion, up to 12.5% MSPC inclusion in the starter phase increased growth performance through to d 42 linked to enhanced gut health through reduction of enteric pathogens.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Galinhas , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais , Escherichia coli , Masculino , Distribuição Aleatória , Proteínas de Soja
16.
Stud Health Technol Inform ; 281: 1124-1125, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042868

RESUMO

Randomization is an inherent part of Randomized Clinical Trials (RCTs), typically requiring the split of participants in intervention and control groups. We present a web service supporting randomized patient distribution, developed in the context of the MyPal project RCT. The randomization process is based on a block permutation approach to mitigate the risk of various kind of biases. The presented service can be used via its web user interface to produce randomized lists of patients distributed in the various study groups, with a variant block size. Alternatively, the presented service can be integrated as part of wider IT systems supporting clinical trials via a REST interface following a micro-service architectural pattern.


Assuntos
COVID-19 , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Internet , Distribuição Aleatória , SARS-CoV-2
17.
PLoS One ; 16(5): e0251661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34019562

RESUMO

BACKGROUND: Understanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has implications for patient management. Our aim was to determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR. METHODS: This population-based retrospective study was conducted in March-April 2020 in the Helsinki Capital Region, Finland. Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, with sufficient data in their medical records for grading of clinical suspicion were eligible. In addition to examining the first RT-PCR test of repeat-tested individuals, we also used high clinical suspicion for COVID-19 as the reference standard for calculating the sensitivity of SARS-CoV-2 RT-PCR. RESULTS: All 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women) admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals (mean [SD] age, 45.4 [17.2] years; 69.1% women) was sampled from epidemiological line lists by systematic quasi-random sampling. The sensitivity (95% CI) for laboratory confirmed cases (repeat-tested patients) was 85.7% (81.5-89.1%) inpatients; 95.5% (92.2-97.5%) outpatients, 89.9% (88.2-92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the sensitivity (95% CI) was: 67.5% (62.9-71.9%) inpatients; 34.9% (31.4-38.5%) outpatients; 47.3% (44.4-50.3%) all. CONCLUSIONS: The clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations, and when using RT-PCR as a reference for other tests.


Assuntos
Teste de Ácido Nucleico para COVID-19/normas , Adulto , Idoso , Teste de Ácido Nucleico para COVID-19/métodos , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Kit de Reagentes para Diagnóstico/normas
18.
Oxid Med Cell Longev ; 2021: 6657529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986917

RESUMO

The cardioprotective effect of sevoflurane postconditioning (SPostC) is lost in diabetes that is associated with cardiac phosphatase and tensin homologue on chromosome 10 (PTEN) activation and phosphoinositide 3-kinase (PI3K)/Akt inactivation. T-LAK cell-originated protein kinase (TOPK), a mitogen-activated protein kinase- (MAPKK-) like serine/threonine kinase, has been shown to inactivate PTEN (phosphorylated status), which in turn activates the PI3K/Akt signaling (phosphorylated status). However, the functions of TOPK and molecular mechanism underlying SPostC cardioprotection in nondiabetes but not in diabetes remain unknown. We presumed that SPostC exerts cardioprotective effects by activating PTEN/PI3K/Akt through TOPK in nondiabetes and that impairment of TOPK/PTEN/Akt blocks diabetic heart sensitivity to SPostC. We found that in the nondiabetic C57BL/6 mice, SPostC significantly attenuated postischemic infarct size, oxidative stress, and myocardial apoptosis that was accompanied with enhanced p-TOPK, p-PTEN, and p-Akt. These beneficial effects of SPostC were abolished by either TOPK kinase inhibitor HI-TOPK-032 or PI3K/Akt inhibitor LY294002. Similarly, SPostC remarkably attenuated hypoxia/reoxygenation-induced cardiomyocyte damage and oxidative stress accompanied with increased p-TOPK, p-PTEN, and p-Akt in H9c2 cells exposed to normal glucose, which were canceled by either TOPK inhibition or Akt inhibition. However, either in streptozotocin-induced diabetic mice or in H9c2 cells exposed to high glucose, the cardioprotective effect of SPostC was canceled, accompanied by increased oxidative stress, decreased TOPK phosphorylation, and impaired PTEN/PI3K/Akt signaling. In addition, TOPK overexpression restored posthypoxic p-PTEN and p-Akt and decreased cell death and oxidative stress in H9c2 cells exposed to high glucose, which was blocked by PI3K/Akt inhibition. In summary, SPostC prevented myocardial ischemia/reperfusion injury possibly through TOPK-mediated PTEN/PI3K/Akt activation and impaired activation of this signaling pathway may be responsible for the loss of SPostC cardioprotection by SPostC in diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sevoflurano/farmacologia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Coração/efeitos dos fármacos , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Inibidores da Agregação Plaquetária/farmacologia , Distribuição Aleatória , Ratos , Transdução de Sinais/efeitos dos fármacos
19.
Stud Health Technol Inform ; 281: 952-956, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042814

RESUMO

The interaction of multiple computer systems during multi-center randomized controlled trials (RCTs) is a hurdle for IT-specialists as well as medical staff. A common workflow for the initial registration of a patient requires the generation of a pseudonym by a pseudonymization service, a manual transmission of the pseudonym to a randomization service, and a manual transfer of the pseudonym and assigned study arm into an electronic data capture (EDC) system. This interaction is often time consuming and error prone due to multiple system changes. Objective of this work is to enhance a commonly used EDC system, Research Electronic Data Capture (REDCap), as a single source of interaction for multi-center RCTs. This is achieved by providing two modules for a seamless integration of a pseudonymization service, i.e., Mainzelliste, and a randomization service, i.e., RandIMI. Thus, no site-specific system changes are required, which increases time efficiency and reduces errors. From a technical perspective, only authentication credentials and firewall exposure for a single system must be managed. To evaluate the usability of our implementation, the system usability scale was employed. The increase of time efficiency was measured in laboratory conditions by a comparison of the time for patient registrations with and without our modules. An "excellent" usability was shown and an average time reduction by nearly 64 %. Both open-source modules are available from the REDCap Repository of External Modules.


Assuntos
Fluxo de Trabalho , Humanos , Distribuição Aleatória
20.
Int Heart J ; 62(3): 627-635, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-33994505

RESUMO

To evaluate whether lowering plasma homocysteine (Hcy) levels at different doses of folic acid (FA) could reduce cardiac fibrosis and diastolic dysfunction in spontaneously hypertensive rats (SHRs) with hyperhomocysteinemia (Hhcy) and investigate the possible mechanism of action.We randomly divided 32 male SHRs into control, Hhcy, Hhcy + low-dose FA (LFA), and Hhcy + high-dose FA (HFA) groups. Echocardiography and Masson staining of cardiac tissue were used to assess diastolic function and cardiac fibrosis. Blood pressure (BP) and Hcy levels were measured during the experiment. We also measured the indicators of oxidative stress (OS) and examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes and proteins using real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting to explore the possible mechanism of action.FA treatment reversed SHR cardiomyocyte interstitial and perivascular collagen deposition and diastolic dysfunction exacerbated by Hhcy. These effects were associated with promoting the translocation of Nrf2 from the cytoplasm to the nucleus, activating HO-1 expression and inhibiting OS. However, HFA did not show any additional benefit from LFA in reducing cardiac injury.Even at a low dose, FA can ameliorate Hhcy-induced cardiac fibrosis and diastolic dysfunction in SHRs by activating Nrf2/HO-1 pathway and inhibiting OS, independent of BP, providing evidence for the efficacy of LFA in the treatment of hypertension associated with Hhcy.


Assuntos
Ácido Fólico/uso terapêutico , Cardiopatias/prevenção & controle , Hematínicos/uso terapêutico , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Animais , Diástole , Avaliação Pré-Clínica de Medicamentos , Fibrose , Coração/fisiopatologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Masculino , Miocárdio/patologia , Distribuição Aleatória , Ratos Endogâmicos SHR
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