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1.
FASEB J ; 38(1): e23291, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38095283

RESUMO

Myocardial infarction (MI) is characterized by a significant loss of cardiomyocytes (CMs), and it is suggested that reactive oxygen species (ROS) are involved in cell cycle arrest, leading to impaired CM renewal. Thioredoxin-1 (Trx-1) scavenges ROS and may play a role in restoring CM renewal. However, the truncated form of Trx-1, Trx-80, can compromise its efficacy by exerting antagonistic effects. Therefore, a Trx-1 mimetic peptide called CB3 was tested as an alternative way to restore CMs. This study aimed to investigate the effects of Trx-1, Trx-80, and CB3 on mice with experimental MI and study the underlying mechanism of CB3 on CMs. Mouse cardiac parameters were quantified by echocardiography, and infarction size and fibrosis determined using Trichrome and Picro-Sirius Red staining. The study found that Trx-1 and CB3 improved mouse cardiac function, reduced the size of cardiac infarct and fibrosis, and decreased the expression of cardiac inflammatory markers. Furthermore, CB3 polarized macrophages into M2 phenotype, reduced apoptosis and oxidative stress after MI, and increased CM proliferation in cell culture and in vivo. CB3 effectively protected against myocardial infarction and could represent a new class of compounds for treating MI.


Assuntos
Infarto do Miocárdio , Tiorredoxinas , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Peptídeos/metabolismo , Apoptose , Fibrose , Remodelação Ventricular , Miocárdio/metabolismo , Modelos Animais de Doenças
2.
Artigo em Inglês | MEDLINE | ID: mdl-39110274

RESUMO

BACKGROUND: Fibulin-2 (FBLN2) is a secreted extracellular matrix (ECM) glycoprotein and has been identified in the mouse mammary gland, in cap cells of terminal end buds (TEBs) during puberty, and around myoepithelial cells during early pregnancy. It is required for basement membrane (BM) integrity in mammary epithelium, and its loss has been associated with human breast cancer invasion. Herein, we attempted to confirm the relevance of FBLN2 to myoepithelial phenotype in mammary epithelium and to assess its expression in molecular subtypes of human breast cancer. METHODS: The relationship between FBLN2 expression and epithelial markers was investigated in pubertal mouse mammary glands and the EpH4 mouse mammary epithelial cell line using immunohistochemistry, immunocytochemistry, and immunoblotting. Human breast cancer mRNA data from the METABRIC and TCGA datasets from Bioportal were analyzed to assess the association of Fbln2 expression with epithelial markers, and with molecular subtypes. Survival curves were generated using data from the METABRIC dataset and the KM databases. RESULTS: FBLN2 knockdown in mouse mammary epithelial cells was associated with a reduction in KRT14 and an increase in KRT18. Further, TGFß3 treatment resulted in the upregulation of FBLN2 in vitro. Meta-analyses of human breast cancer datasets from Bioportal showed a higher expression of Fbln2 mRNA in claudin-low, LumA, and normal-like breast cancers compared to LumB, Her2 +, and Basal-like subgroups. Fbln2 mRNA levels were positively associated with mesenchymal markers, myoepithelial markers, and markers of epithelial-mesenchymal transition. Higher expression of Fbln2 mRNA was associated with better prognosis in less advanced breast cancer and this pattern was reversed in more advanced lesions. CONCLUSION: With further validation, these observations may offer a molecular prognostic tool for human breast cancer for more personalized therapeutic approaches.

3.
BMC Cardiovasc Disord ; 24(1): 167, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504152

RESUMO

BACKGROUND: Paclitaxel is a chemotherapeutic agent commonly used for ovarian, lung, breast carcinoma, and Kaposi's sarcoma. Its common side effects include hypersensitivity reaction, bone marrow suppression, and peripheral neuropathy. However, a rare and life-threatening side effect is paclitaxel-induced myocardial infarction. CASE PRESENTATION: A 71-year-old man with type 2 diabetes mellitus, hypertension, heavy smoking history, previous coronary artery disease with percutaneous coronary intervention (PCI) in left anterior descending artery (LAD), and non-small lung cancer presented with non-ST elevation myocardial infarction during infusion of paclitaxel infusion. Coronary angiogram showed de novo three vessel disease with 70% stenosis in ostial to distal left main artery (LM) and 80% in-stent re-stenosis in proximal to mid left anterior descending artery. CONCLUSIONS: Physicians should be keeping this in mind when dealing with patients on paclitaxel, especially if they have previous risk factors for coronary artery disease.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Intervenção Coronária Percutânea , Masculino , Humanos , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Paclitaxel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Constrição Patológica/etiologia , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia
4.
BMC Microbiol ; 23(1): 355, 2023 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980505

RESUMO

BACKGROUND: Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae), followed by antimicrobial screening against various bacterial and fungal strains. RESULTS: Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium, Fusarium, and Aspergillus. The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1-16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans. CONCLUSION: These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production of undiscovered compounds different from the antibiotics classes.


Assuntos
Anti-Infecciosos , Corchorus , Corchorus/microbiologia , Simulação de Acoplamento Molecular , Escherichia coli , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Fungos , Antibacterianos/metabolismo , Aspergillus , Sementes/microbiologia
5.
Gynecol Endocrinol ; 39(1): 2247098, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37573873

RESUMO

BACKGROUND: Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. METHODS: A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. RESULTS: Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. CONCLUSION: Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.


Assuntos
Hormônio Antimülleriano , Síndrome do Ovário Policístico , Adulto , Feminino , Humanos , Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia , Prolactina/sangue , Sensibilidade e Especificidade , Vitamina D/sangue , Estudos de Casos e Controles , Distúrbios Menstruais/patologia
6.
World J Microbiol Biotechnol ; 40(1): 10, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947912

RESUMO

Melanin is a brown-black pigment with significant roles in various biological processes. The tyrosinase enzyme catalyzes the conversion of tyrosine to melanin and has promising uses in the pharmaceutical and biotechnology sectors. This research aims to purify and immobilize the tyrosinase enzyme from Pseudomonas sp. EG22 using cellulose-coated magnetic nanoparticles. Various techniques were utilized to examine the synthesized nanoparticles, which exhibited a spherical shape with an average diameter of 12 nm and a negative surface potential of - 55.7 mV with a polydispersity index (PDI) of 0.260. Comparing the immobilized magnetic tyrosinase enzyme with the free enzyme, the study's findings showed that the immobilized tyrosinase enzyme had optimal activity at a pH of 6 and a temperature of 35 °C, and its activity increased as the concentration of tyrosine increased. The study investigated the antibacterial and anticancer bioactivity of the enzyme's melanin product and found that it exhibited potential antibacterial activity against a multi-drug resistant strain including S. aureus and E. coli. The produced melanin also demonstrated the potential to decrease cell survival and induce apoptosis in initiation cells.


Assuntos
Nanopartículas de Magnetita , Monofenol Mono-Oxigenase , Melaninas , Celulose , Nanopartículas de Magnetita/química , Pseudomonas , Escherichia coli , Staphylococcus aureus , Enzimas Imobilizadas/química , Tirosina , Antibacterianos/farmacologia
7.
Radiat Environ Biophys ; 61(2): 263-277, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35396948

RESUMO

Hypoxia is a condition in which proliferating tumor cells are deprived of oxygen due to limited blood supply from abnormal tumor microvasculature. This study aimed to investigate the molecular changes that occur in tumor cell hypoxia with special emphasis placed on the efficacy of chemotherapeutic and radiation-related effects. Four commercially available chemotherapeutic agents: cisplatin, cyclophosphamide, doxorubicin, and 5-fluorouracil, were tested for their cytotoxic activity on the cancer cell lines PC3 (prostate), HepG2 (liver), and MCF-7 (breast). Tumor cell lines under hypoxia were treated with both IC50 concentrations of the different chemotherapeutic agents and irradiated with 5 and 10 Gy using a 137Cs gamma source. Hypoxia-inducible factor-1α (HIF-1α) protein levels were examined using an ELISA assay. Hypoxic cells showed a significant change in cell viability to all chemotherapeutic agents in comparison to normoxic controls. HepG2 cells were more resistant to the cytotoxic drug doxorubicin compared to other cancer cell lines. The flow cytometric analysis showed that hypoxic cells have lower levels of total apoptotic cell populations (early and late apoptosis) compared to normoxic cells suggesting decreased hypoxia-induced apoptosis in cancer cells. The highest reduction in HIF-1α level was observed in the MCF-7 cell line (95.5%) in response to the doxorubicin treatment combined with 10 Gy irradiation of cells. Chemoradiotherapy could result in minimal as well as a high reduction of HIF-1α based on cell type, type of chemotherapy, and amount of ionizing radiation. This study highlights future research work to optimize a combined chemoradiotherapeutic regime in individual cancer cell hypoxia.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Humanos , Hipóxia , Masculino , Doses de Radiação , Hipóxia Tumoral
8.
Breast Cancer Res ; 23(1): 90, 2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565423

RESUMO

BACKGROUND: During pregnancy, the mouse mammary ductal epithelium branches and grows into the surrounding stroma, requiring extensive extracellular matrix (ECM) and tissue remodelling. It therefore shows parallels to cancer invasion. We hypothesised that similar molecular mechanisms may be utilised in both processes, and that assessment of the stromal changes during pregnancy-associated branching may depict the stromal involvement during human breast cancer progression. METHODS: Immunohistochemistry (IHC) was employed to assess the alterations within the mouse mammary gland extracellular matrix during early pregnancy when lateral branching of the primary ductal epithelium is initiated. Primary mouse mammary fibroblasts from three-day pregnant and age-matched non-pregnant control mice, respectively, were 3D co-cultured with mammary epithelial cells to assess differences in their abilities to induce branching morphogenesis in vitro. Transcriptome analysis was performed to identify the underlying molecular changes. A signature of the human orthologues of the differentially expressed matrisome RNAs was analysed by Kaplan-Meier and multi-variate analysis in two large breast cancer RNA datasets (Gene expression-based Outcome for Breast cancer Online (GOBO) und Kaplan-Meier Plotter), respectively, to test for similarities in expression between early-pregnancy mouse mammary gland development and breast cancer progression. RESULTS: The ECM surrounding the primary ductal network showed significant differences in collagen and basement membrane protein distribution early during pregnancy. Pregnancy-associated fibroblasts (PAFs) significantly enhanced branching initiation compared to age-matched control fibroblast. A combined signature of 64 differentially expressed RNAs, encoding matrisome proteins, was a strong prognostic indicator of distant metastasis-free survival (DMFS) independent of other clinical parameters. The prognostic power could be significantly strengthened by using only a subset of 18 RNAs (LogRank P ≤ 1.00e-13; Hazard ratio (HR) = 2.42 (1.8-3.26); p = 5.61e-09). The prognostic power was confirmed in a second breast cancer dataset, as well as in datasets from ovarian and lung cancer patients. CONCLUSIONS: Our results describe for the first time the early stromal changes that accompany pregnancy-associated branching morphogenesis in mice, specify the early pregnancy-associated molecular alterations in mouse mammary fibroblasts, and identify a matrisome signature as a strong prognostic indicator of human breast cancer progression, with particular strength in oestrogen receptor (ER)-negative breast cancers.


Assuntos
Neoplasias da Mama/genética , Matriz Extracelular/genética , Fibroblastos/metabolismo , Glândulas Mamárias Animais/metabolismo , RNA/genética , Animais , Membrana Basal/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Técnicas de Cocultura , Colágeno/metabolismo , Células Epiteliais/citologia , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/citologia , Perfilação da Expressão Gênica , Humanos , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Camundongos , Morfogênese , Gravidez , Prognóstico , RNA/metabolismo
9.
BMC Musculoskelet Disord ; 22(1): 983, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819061

RESUMO

BACKGROUND: Clinical guideline recommendations are against early magnetic resonance imaging (eMRI) within the first 4 to 6 weeks of conservative management of acute low back pain (LBP) without "clinical suspicion" of serious underlying conditions (red flags). There is some limited evidence that a significant proportion of patients with LBP receive eMRI non- indicated by clinical guidelines, which could be associated with increased length of disability (LOD). The aim of this systematic review was to investigate whether eMRI for acute LBP without red flags is associated with increased LOD. The LOD was defined as the number of disability days (absence from work). METHODS: Medline, EMBASE, and CINAHL bibliographic databases were searched from inception until June 5, 2021. Two reviewers independently assessed the methodological quality of included studies using the Newcastle-Ottawa scale and extracted data for the review. The search identified 324 records, in which seven studies met the inclusion criteria. Three of the included studies used the same study population. Owing to between-study heterogeneity, a narrative synthesis of results was used. RESULTS: All included studies were of good methodological quality and consistently reported that patients with acute LBP without red flags who received eMRI had increased LOD compared to those who did not receive eMRI. Three retrospective cohort studies reported that the eMRI groups had a higher mean LOD than the no eMRI groups ranging from 9.4 days (95% CI 8.5, 10.2) to 13.7 days (95% CI 13.0, 14.5) at the end of 1-year follow-up period. The remaining studies reported that the eMRI groups had a higher hazard ratio of work disability ranging between 1.75 (95% CI 1.23, 2.50) and 3.57 (95% CI 2.33, 5.56) as compared to the no eMRI groups. CONCLUSION: eMRI is associated with increased LOD in patients with acute LBP without red flags. Identifying reasons for performing non-indicated eMRI and addressing them with quality improvement interventions may improve adherence to clinical guidelines and improve disability outcomes among patients with LBP.


Assuntos
Dor Aguda , Dor Lombar , Humanos , Dor Lombar/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Retrospectivos
10.
Cardiol Young ; 31(8): 1297-1305, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33602381

RESUMO

BACKGROUND: Rhabdomyoma is the most common cardiac tumour in children. It is usually associated with tuberous sclerosis complex caused by mutations in TSC-1 or TSC-2 genes. This tumour typically regresses by unknown mechanisms; however, it may cause inflow or outflow obstruction that necessitates urgent surgery. Here we investigate the clinical features and the genetic analysis of patients with tuberous sclerosis complex presenting with large rhabdomyoma tumours. We also investigate the potential role of autophagy and apoptosis in the pathogenesis of this tumour. METHODS: All the patients with cardiac rhabdomyoma referred to Aswan Heart Centre from 2010 to 2018 were included in this study. Sanger sequencing was performed for coding exons and the flanking intronic regions of TSC1 and TSC2 genes. Histopathological evaluation, immunohistochemistry, and western blotting were performed with P62, LC3b, caspase3, and caspase7, to evaluate autophagic and apoptotic signaling. RESULTS: Five patients were included and had the clinical features of tuberous sclerosis complex. Three patients, who were having obstructive tumours, were found to have pathogenic mutations in TSC-2. The expression of two autophagic markers, P62 and LC3b, and two apoptotic markers, caspase3 and caspase7, were increased in the tumour cells compared to normal surrounding myocardial tissue. CONCLUSION: All the patients with rhabdomyoma were diagnosed to have tuberous sclerosis complex. The patients who had pathogenic mutations in the TSC-2 gene had a severe disease form necessitating urgent intervention. We also demonstrate the potential role of autophagy and apoptosis as a possible mechanism for tumourigenesis and regression. Future studies will help in designing personalised treatment for cardiac rhabdomyoma.


Assuntos
Neoplasias Cardíacas , Rabdomioma , Esclerose Tuberosa , Testes Genéticos , Neoplasias Cardíacas/genética , Humanos , Mutação , Rabdomioma/genética , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética
11.
Int J Mol Sci ; 21(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003281

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart muscle disease, with a prevalence of at least 1 in 500 in the general population. The disease is pleiotropic and is characterized by an increased stiffness of the myocardium, partly due to changes in the extracellular matrix (ECM), with elevated levels of interstitial fibrosis. Myocardial fibrosis is linked to impaired diastolic function and possibly phenotypic heterogeneity of HCM. The ECM consists of a very large number of proteins, which actively interact with each other as well as with myocardial cells. The role of other multiple components of the ECM in HCM has not been defined. Fibulin-2 is a glycoprotein component of the ECM, which plays an important role during embryogenesis of the heart; however, its role in adult myocardium has not been adequately studied. We here describe, for the first time, abnormal expression of fibulin-2 in the myocardium in patients with HCM as compared to normal controls. This abnormal expression was localized in the cytoplasm of myocardial cells and in the interstitial fibroblasts. In addition, fibulin-2 levels, measured by ELISA, were significantly elevated in the serum of patients with HCM as compared to normal controls.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Cardiomiopatia Hipertrófica/genética , Proteínas da Matriz Extracelular/genética , Matriz Extracelular/genética , Miocárdio/metabolismo , Adulto , Remodelamento Atrial/genética , Cardiomiopatia Hipertrófica/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose/genética , Fibrose/patologia , Regulação da Expressão Gênica/genética , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenótipo
13.
Parasitol Res ; 118(12): 3519-3533, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673833

RESUMO

The main objective of this work is preparation of mesoporous silica nanoparticles loaded with praziquantel (PZQ-Si) in order to enhance the therapeutic efficacy of praziquantel (PZQ). Mice were experimentally infected with Schistosoma mansoni and treated 6 weeks post-infection with PZQ in different doses via either oral or intraperitoneal (IP) routes. PZQ in the same doses orally administered to S. mansoni-infected mice was used as a drug control, and infected and non-infected non-treated mice served as positive and negative controls, respectively. PZQ-Si exhibited good physicochemical attributes in terms of small uniform size (105 nm), spherical shape, and PZQ entrapment efficiency (83%). A maximum antischistosomal effect was achieved using orally administered PZQ-Si as reflected by total worm burden, tissue egg count, oogram pattern, and hepatic granuloma count and diameter. The biomarkers related to liver oxidative stress status and immunomodulatory effect (serum TNF-α and IL-10) were significantly improved. Data obtained implied that IP route was less efficacious for the delivery of PZQ-Si. Encapsulation of PZQ permits the reduction of the used therapeutic dose of PZQ. Hepatic DNA fragmentation, measured by comet assay, was significantly improved in infected mice treated with maximum dose of PZQ-Si as compared to positive or PZQ control groups. The results indicate that mesoporous silica NP is a promising safe nanocarrier for PZQ potentiating its antischistosomal, antioxidant, immunomodulatory, and anti-inflammatory action in animal model infected with S. mansoni. From a practical standpoint, PZQ-Si using a lower dose of PZQ could be suggested for effective PZQ antischistosomal mass chemotherapy.


Assuntos
Anti-Helmínticos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Praziquantel/administração & dosagem , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Modelos Animais de Doenças , Humanos , Fígado/parasitologia , Masculino , Camundongos , Nanopartículas/química , Praziquantel/química , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Dióxido de Silício/química
15.
Jpn J Clin Oncol ; 46(12): 1088-1094, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27608646

RESUMO

OBJECTIVE: The primary objective of this study was to investigate the safety and tolerability and to confirm the recommended dose of the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab in combination with docetaxel in Japanese patients with metastatic/locally advanced breast cancer. METHODS: In this multicenter, single-arm, Phase Ib trial, eligibility criteria included: 20 years or older, Eastern Cooperative Oncology Group performance status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2-negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients received docetaxel (75 mg/m2) followed by ramucirumab (10 mg/kg) on Day 1 of 21-day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose-limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics, immunogenicity and antitumor activity were examined. RESULTS: Seven patients were treated. Most adverse events were mild to moderate. Two patients during Cycle 1 experienced a dose-limiting toxicity; one patient each experienced Grade 3 febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities subsequently resolved. No patients discontinued study therapies during Cycle 1. Four serious adverse events were possibly related to ramucirumab in combination with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic analysis revealed low total body clearance and long apparent terminal elimination half-life (~7-12 days). Partial response was reported in four patients. CONCLUSIONS: The combination of ramucirumab and docetaxel was tolerable in female Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with docetaxel (75 mg/m2) was confirmed as the recommended dose among Japanese patients, supporting its use in future studies.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Humanizados , Povo Asiático , Neoplasias da Mama/patologia , Docetaxel , Esquema de Medicação , Quimioterapia Combinada , Feminino , Gengivite/etiologia , Meia-Vida , Humanos , Japão , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neutropenia/etiologia , Receptor ErbB-2/metabolismo , Taxoides/efeitos adversos , Taxoides/farmacocinética , Resultado do Tratamento , Ramucirumab
16.
Parasitol Res ; 114(2): 453-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25352240

RESUMO

Microsporidia spp. are obligate intracellular parasites which are very minute with sizes ranging from 1 to 10 µm. They have been increasingly recognized as human pathogens in AIDS and immunocompromised patients, mainly associated with life-threatening chronic diarrhea and systemic disease. For accurate identification of Microsporidia, permanent staining techniques are used to enable the examiner to use the ×100 objective which reveals the important details needed for diagnosis. On the other hand, ×10 and ×40 objectives are of no value in detection of such a minute organism. Until now, there is no study that demonstrates a rapid satisfactory technique for routine examination of wet mount by the oil-immersion lens. Glycerol jelly (GJ) reagent was previously studied for its benefit in fixing the cover slide of direct wet mounts instantly enabling the use of oil-immersion lens in examination that magnifies its role as a rapid technique for direct examination. The aim of this research is to identify Microsporidia by wet mounts immediately, using GJ reagent that enables the examiner to use the ×100 objective and to evaluate GJ wet mount as a method of identification. Glycerol jelly reagent was prepared (7 g gelatin dissolved in 50 ml boiling water was added to 10 ml glycerol) and added to fecal wet mounts stained by iodine and methylene blue. Wet mounts were examined using the ×100 objective. Satisfactory results were achieved in spite of the small size of Microsporidia, as both iodine and methylene blue stained the cytological structures; GJ reagent fixed the cover slide, maintained the high translucency of the films, and enabled the examiner to use the ×100 oil-immersion objective. We also compared fecal wet mounts stained by iodine and methylene blue + GJ with a stool sample stained by permanent stain modified Ziehl-Neelsen without GJ, and we found that fecal wet mounts stained by iodine and methylene blue + GJ were more clear. We concluded that glycerol jelly wet mount is an easy, fast, reliable, and cheap technique for identification of Microsporidia in direct smear, using the ×100 oil-immersion objective.


Assuntos
Gelatina , Glicerol , Microsporídios/isolamento & purificação , Microsporidiose/diagnóstico , Coloração e Rotulagem/métodos , Fezes/microbiologia , Humanos , Hospedeiro Imunocomprometido , Iodo , Azul de Metileno , Microsporidiose/microbiologia
17.
Arthroscopy ; 30(5): 622-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24725316

RESUMO

PURPOSE: To evaluate the clinical and functional outcome of endoscopic-assisted reconstruction of chronic ruptures of the Achilles tendon using free hamstring tendon autograft. METHODS: We present a case series of 15 patients who had chronic ruptures of the Achilles tendon (>6 weeks earlier) and underwent endoscopic-assisted reconstruction with a free hamstring autograft. The graft loop was passed through and fixed to the proximal stump of the tendon. The graft was then passed through suture to the distal stump and finally inserted into a tunnel in the anterior calcaneus to the Achilles tendon insertion and fixed with an bioabsorbable interference screw. The mean follow-up period was 27 months (SD, 3 months; range, 24 to 33 months). All patients underwent magnetic resonance imaging preoperatively, immediately postoperatively, and at follow-up 2 years postoperatively. All patients were functionally evaluated with the American Orthopaedic Foot & Ankle Society (AOFAS) score for the hindfoot preoperatively and postoperatively. Calf muscle power was evaluated by isokinetic strength testing at 2 years' follow-up. RESULTS: The mean size of the gap on preoperative magnetic resonance imaging was 49 mm (SD, 9 mm). The mean preoperative AOFAS score was 32.6 (SD, 7.5). There was a statistically significant improvement in the postoperative AOFAS score after 2 years to 90.8 (SD, 3.54) (P < .05). The mean time of return to all daily activities (except running and other sports) was 12.6 weeks (SD, 1.39 weeks). Isokinetic testing showed a nonsignificant deficit (<10%) between the involved and uninvolved plantar flexors and dorsiflexors with regard to peak torque, average power, and total work. CONCLUSIONS: Endoscopic-assisted Achilles tendon reconstruction with free hamstring tendon autograft for chronic ruptures of the Achilles tendon showed good to excellent results in all patients. Isokinetic testing showed a nonsignificant deficit between the involved and uninvolved sides at 2 years' follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic cases series.


Assuntos
Tendão do Calcâneo/cirurgia , Endoscopia/métodos , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Tendões/transplante , Tendão do Calcâneo/patologia , Adulto , Autoenxertos , Doença Crônica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ruptura/cirurgia , Transplante Autólogo , Resultado do Tratamento
19.
Front Bioeng Biotechnol ; 12: 1355133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558793

RESUMO

Harnessing solar energy is one of the most important practical insights highlighted to mitigate the severe climate change (CC) phenomenon. Therefore, this study aims to focus on the use of hybrid solar dryers (HSDs) within an environmentally friendly framework, which is one of the promising applications of solar thermal technology to replace traditional thermal technology that contributes to increasing the severity of the CC phenomenon. The HSD, based on a traditional electrical energy source (HSTEE) and electrical energy from photovoltaic panels (HSPVSE), was evaluated compared to a traditional electrical (TE) dryer for drying some medicinal and aromatic plants (MAPs). This is done by evaluating some of the drying outputs, energy consumed, carbon footprint, and financial return at 30, 40, and 50°C. The best quality of dried MAP samples in terms of essential oil (EO, %) and microbial load was achieved at 40°C. The HSTEE dryer has reduced energy consumption compared to the TE dryer by a percentage ranging from 37% to 54%. The highest CO2 mitigated ratio using the HSTEE dryer was recorded in thyme, marjoram, and lemongrass samples, with values ranging from 45% to 54% at 30, 40, and 50°C. The highest financial return obtained from energy consumption reduction and carbon credit footprint was achieved at 50°C, with values ranging from 5,313.69 to 6,763.03 EGP/year (EGP ≈ 0.0352 USD) when coal was used as a fuel source for the generation of electricity. Moreover, the HSPVSE dryer achieved a 100% reduction in traditional energy consumption and then reduced CO2 emissions by 100%, which led to a 100% financial return from both energy reduction and carbon credit. The highest financial returns were observed at 50°C, with values ranging from 13,872.56 to 15,007.02, 12,927.28 to 13,984.43, and 11,981.99 to 12,961.85 EGP/year (EGP ≈ 0.0352 USD) for coal, oil, and natural gas, respectively. The HS dryers show potential for environmental conservation contribution; furthermore, earning money from energy savings and carbon credit could help improve the living standards and maximize benefits for stakeholders.

20.
Naunyn Schmiedebergs Arch Pharmacol ; 397(7): 5193-5205, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38252300

RESUMO

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities.


Assuntos
Antioxidantes , Apoptose , Raios gama , Ácido Hialurônico , Compostos Organofosforados , Estresse Oxidativo , Protetores contra Radiação , Ubiquinona , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Raios gama/efeitos adversos , Camundongos , Compostos Organofosforados/farmacologia , Masculino , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Antioxidantes/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ácido Hialurônico/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/metabolismo , Nanopartículas , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Intestinos/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação
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