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1.
Biomedicines ; 12(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38255214

ABSTRACT

The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

2.
Biomedicines, v. 12, n. 1, p. 109, jan. 2024
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5239

ABSTRACT

The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

3.
Rev Bras Ortop (Sao Paulo) ; 58(6): e952-e956, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38077764

ABSTRACT

Vertebral hemangioma is a benign vascular tumor that is usually asymptomatic and is discovered incidentally on imaging. When symptomatic, the most frequent presentation occurs in the form of vague back pain of insidious onset and, in rare cases, may be associated with root or spinal compression, causing sensory and motor deficits. The authors report the case of a 33-year-old man, previously healthy, with a diagnosis of thoracic spine hemangioma at multiple levels, in the sternum, in the scapula and in the costal arches; all lesions were symptomatic, and surgical intervention was required; one of the lesions at the thoracic spine level evolved with spinal compression and acute neurological deficit, requiring urgent surgical intervention. Intraosseous hemangiomas represent < 1% of all bone tumors, having few reports of multifocal presentation in the axial and appendicular skeleton. In the literature review, no other case of aggressive multifocal intraosseous hemangioma with this presentation was found, including associated neurological symptoms in the same case.

4.
Cancers (Basel) ; 15(22)2023 Nov 09.
Article in English | MEDLINE | ID: mdl-38001606

ABSTRACT

Breast cancer is the most common cancer in women, the so-called "Triple-Negative Breast Cancer" (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings.

5.
Rev. bras. ortop ; 58(6): 952-956, 2023. graf
Article in English | LILACS | ID: biblio-1535618

ABSTRACT

Abstract Vertebral hemangioma is a benign vascular tumor that is usually asymptomatic and is discovered incidentally on imaging. When symptomatic, the most frequent presentation occursinthe formofvague back painofinsidiousonset and,inrare cases, maybeassociated with root or spinal compression, causing sensory and motor deficits. The authors report the case of a 33-year-old man, previously healthy, with a diagnosis of thoracic spine hemangio-ma at multiple levels, in the sternum, in the scapula and in the costal arches; all lesions were symptomatic,and surgicalinterventionwas required; oneof thelesionsatthe thoracicspine level evolved with spinal compression and acute neurological deficit, requiring urgent surgical intervention. Intraosseoushemangiomas represent<1%ofall bonetumors, having few reports of multifocal presentation in the axial and appendicular skeleton. In the literature review, no other case of aggressive multifocal intraosseous hemangioma with this presentation was found, including associated neurological symptoms in the same case.


Resumo O hemangioma vertebral, um tumor vascular benigno, geralmente é assintomático e descoberto incidentalmente em exames de imagem. Quando sintomático, a apresentação mais frequente ocorre sob a forma de dorsalgia vaga de início insidioso e, em raros casos, pode estar associadoa compressão radicularoumedular, causando déficit sensitivo emotor. Osautores relatamocasodeumhomemde33anos, previamentehígido, com diagnósticos de hemangioma na coluna torácica em múltiplos níveis, no esterno, na escápula e nos arcos costais; todas as lesões eram sintomáticas e houve necessidade de intervenção cirúrgica, sendo que uma das lesões ao nível da coluna torácica evoluiu com compressão medular e déficit neurológico agudo, com necessidade de intervenção cirúrgica de urgência. Os hemangiomas intraósseos representam<1% detodosostumores ósseos,eaapresentação multifocal no esqueleto axial e apendicular apresenta poucos relatos. Na revisão bibliográfica, não foi encontrado outro caso dehemangioma intraósseo multifocal agressivo com tal apresentação, inclusive com sintomas neurológicos associados em um mesmo caso.


Subject(s)
Humans , Male , Adult , Spinal Diseases , Bone Diseases/drug therapy , Hemangioma
6.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5166

ABSTRACT

Breast cancer is the most common cancer in women, the so-called “Triple-Negative Breast Cancer” (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings.

7.
Biomed Pharmacother ; 153: 113398, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36076530

ABSTRACT

Triple-negative breast cancer is the most aggressive subtype of breast cancer, with worse clinical evolution and tumor-free survival, leading to the need to develop new effective therapies for its control. The present study evaluated the action of tumor-penetrating peptide BR2 associated with 2-aminoethyl dihydrogen phosphate (2-AEH2P) on triple-negative breast tumor cells. Cell viability was evaluated by the MTT colorimetric method, mitochondrial electrical potential, and proteins involved in cell proliferation and death control were evaluated by flow cytometry and structural and morphological analysis by confocal microscopy. The results obtained showed that the peptide BR2 and the association 2-AEH2P + BR2 promoted significant cytotoxicity in tumor lines, compared to 2-AEH2P alone. In addition, the association 2-AEH2P + BR2 promoted tumor cells arrest in the G0/G1 phases. Interestingly, both treatments modulated the expression of markers CD44, CD34, CD24, cyclin D1, and Bcl-2, increased p21, Bax, and released cytochrome c. The association proved to be more effective, providing modulation of proteins involved in cell death and senescence, more pronounced cytotoxicity for tumor cells compared to normal cells, and the reduction of markers related to aggressiveness profile, progression, and tumor metastasis.


Subject(s)
Triple Negative Breast Neoplasms , Apoptosis , Cell Line, Tumor , Cell Proliferation , Humans , Phosphates , Triple Negative Breast Neoplasms/pathology
8.
Biomed Pharmacother, v. 153, 113398, set. 2022
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-4472

ABSTRACT

Triple-negative breast cancer is the most aggressive subtype of breast cancer, with worse clinical evolution and tumor-free survival, leading to the need to develop new effective therapies for its control. The present study evaluated the action of tumor-penetrating peptide BR2 associated with 2-aminoethyl dihydrogen phosphate (2-AEH2P) on triple-negative breast tumor cells. Cell viability was evaluated by the MTT colorimetric method, mitochondrial electrical potential, and proteins involved in cell proliferation and death control were evaluated by flow cytometry and structural and morphological analysis by confocal microscopy. The results obtained showed that the peptide BR2 and the association 2-AEH2P + BR2 promoted significant cytotoxicity in tumor lines, compared to 2-AEH2P alone. In addition, the association 2-AEH2P + BR2 promoted tumor cells arrest in the G0/G1 phases. Interestingly, both treatments modulated the expression of markers CD44, CD34, CD24, cyclin D1, and Bcl-2, increased p21, Bax, and released cytochrome c. The association proved to be more effective, providing modulation of proteins involved in cell death and senescence, more pronounced cytotoxicity for tumor cells compared to normal cells, and the reduction of markers related to aggressiveness profile, progression, and tumor metastasis.

9.
Biomed Pharmacother, v. 142, 112054, out. 2021
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3936

ABSTRACT

The main obstacle in the treatment of cancer patients has been resistance to multiple drugs, leading to the need to develop molecules with a higher specificity target. The liposomal formulation DODAC/2-AEH2P has antitumor potential, inducing apoptosis in several tumor types. Human chronic myeloid leukemia K-562 and K-562 Lucena (MDR+) cells were treated with the DODAC carrier and the liposomal formulation 2-AEH2P. Viability, cell cycle phases, apoptosis, marker expression and mitochondrial potential were analyzed. Significant reduction in viability was observed for all treatments. Changes in the distribution of the cell cycle phases and expression of markers involved in the apoptosis pathways were observed. Reduction of the mitochondrial electrical potential mediated by Bcl-2, being regulated by the reduction of the MTCH2 protein linked to the progression of myeloid leukemia and an increase in the pro-apoptotic proteins Bad and Bax, dependent on p53. This study demonstrated a significant therapeutic potential through apoptotic effects in leukemic cells, regardless of the molecular resistance profile (MDR+).

10.
Biomolecules ; 10(9)2020 08 25.
Article in English | MEDLINE | ID: mdl-32854282

ABSTRACT

Corn cob is an agricultural byproduct that produces an estimated waste burden in the thousands of tons annually, but it is also a good source of xylan, an important bioactive polysaccharide. Silver nanoparticles containing xylan (nanoxylan) were produced using an environmentally friendly synthesis method. To do this, we extracted xylan from corn cobs using an ultrasound technique, which was confirmed by both chemical and NMR analyses. This xylan contained xylose, glucose, arabinose, galactose, mannose, and glucuronic acid in a molar ratio of 50:21:14:9:2.5:2.5, respectively. Nanoxylan synthesis was analyzed using UV-vis spectroscopy at kmax = 469 nm and Fourier transform infrared spectroscopy (FT-IR), which confirmed the presence of both silver and xylan in the nanoxylan product. Dynamic light scattering (DLS) and atomic force microscopy (AFM) revealed that the nanoxylan particles were ~102.0 nm in size and spherical in shape, respectively. DLS also demonstrated that nanoxylan was stable for 12 months and coupled plasma optical emission spectrometry (ICP-OES) showed that the nanoxylan particles were 19% silver. Nanoxylan reduced Leishmania amazonensis promastigote viability with a half maximal inhibitory concentration (IC50) value of 25 µg/mL, while xylan alone showed no effective. Additionally, nanoxylan exhibited antifungal activity against Candida albicans (MIC = 7.5 µg/mL), C. parapsilosis (MIC = 7.5 µg/mL), and Cryptococcus neoformans (MIC = 7.5 µg/mL). Taken together, these data suggest that it is possible to synthesize silver nanoparticles using xylan and that these nanoxylan exert improved antileishmanial and antifungal activities when compared to the untreated polysaccharide or silver nitrate used for their synthesis. Thus, nanoxylan may represent a promising new class of antiparasitic agents for use in the treatment of these microorganisms.


Subject(s)
Antifungal Agents/chemical synthesis , Antiprotozoal Agents/chemical synthesis , Metal Nanoparticles/chemistry , Silver/chemistry , 3T3 Cells , Animals , Antifungal Agents/chemistry , Antiprotozoal Agents/chemistry , Candida albicans/drug effects , Candida parapsilosis/drug effects , Cryptococcus neoformans/drug effects , Drug Stability , Dynamic Light Scattering , Excipients/chemistry , Excipients/isolation & purification , Green Chemistry Technology/methods , Humans , Leishmania mexicana/drug effects , Metal Nanoparticles/ultrastructure , Mice , Microbial Sensitivity Tests , Particle Size , Reducing Agents/chemistry , Reducing Agents/isolation & purification , Spectrophotometry , Xylans/chemistry , Xylans/isolation & purification , Xylans/ultrastructure , Zea mays/chemistry
11.
Molecules ; 25(9)2020 Apr 28.
Article in English | MEDLINE | ID: mdl-32354047

ABSTRACT

The genus Gracilaria synthesizes sulfated polysaccharides (SPs). Many of these SPs, including those synthesized by the edible seaweed Gracilaria birdiae, have not yet been adequately investigated for their use as potential pharmaceutical compounds. Previous studies have demonstrated the immunomodulatory effects of sulfated galactans from G. birdiae. In this study, a galactan (GB) was extracted from G. birdiae and evaluated by cell proliferation and antioxidant tests. GB showed no radical hydroxyl (OH) and superoxide (O2-) scavenging ability. However, GB was able to donate electrons in two further different assays and presented iron- and copper-chelating activity. Urolithiasis affects approximately 10% of the world's population and is strongly associated with calcium oxalate (CaOx) crystals. No efficient compound is currently available for the treatment of this disease. GB appeared to interact with and stabilize calcium oxalate dihydrate crystals, leading to the modification of their morphology, size, and surface charge. These crystals then acquired the same characteristics as those found in healthy individuals. In addition, GB showed no cytotoxic effect against human kidney cells (HEK-293). Taken together, our current findings highlight the potential application of GB as an antiurolithic agent.


Subject(s)
Antioxidants/chemistry , Calcium Oxalate/antagonists & inhibitors , Gracilaria/chemistry , Polysaccharides/chemistry , Calcium/chemistry , Calcium Oxalate/chemistry , Cell Survival , Chelating Agents/pharmacology , Copper/chemistry , Drug Design , Electrons , Galactans/chemistry , HEK293 Cells , Humans , Hydrolysis , Hydroxyl Radical , Ions , Iron/chemistry , Kidney/drug effects , Monosaccharides/chemistry , Oxygen/chemistry , Proteins , Seaweed/chemistry , Superoxides/chemistry
12.
Mar Drugs ; 17(1)2018 Dec 21.
Article in English | MEDLINE | ID: mdl-30577590

ABSTRACT

In this study, sulfated polysaccharide-rich extracts were isolated from 22 tropical seaweeds (4 red, 11 brown, and 7 green) found in northeastern Brazil, and evaluated for the role of anticoagulant agents. Fifteen of the extracts showed anticoagulant activity, including all the extracts from green seaweeds. Udotea flabellum (a green seaweed) extract was the most potent, requiring an amount of only 3 µg to double the plasma coagulation time in the activated partial thromboplastin time test. A similar result was obtained with 1 µg of heparin. Two sulfated homogalactans with anticoagulant activity, F-I (130 kDa) and F-II (75 kDa), were isolated from this extract using several bio-guided purification steps. Their anticoagulant activity, as well as properties related to antitumor activity (anti-proliferative, anti-adhesive, and anti-migratory), were accessed. Their anticoagulant activities were close to that of heparin. We found that F-I and F-II (0.5⁻10 µg/mL) were not able to directly inhibit thrombin. In the presence of anti-thrombin, F-I (0.5 µg/mL) was more effective than heparin (0.5 µg/mL) in inhibiting thrombin, while F-II showed similar effects as heparin. F-I and F-II also inhibited B16-F10 (murine melanoma cells) adhesion, migration, and proliferation on a fibronectin-coated surface, but not on laminin- or collagen I-coated surfaces. Except for the antiproliferative activity, the other effects of F-I and F-II were eliminated upon their desulfation (~50%), indicating that the degree of sulfation is not as important for F-I and F-II anti-proliferative activity as the sulfation position. Taken together, the results provide strong evidence for the potential utility of sulfated galactans from U. flabellum, making these compounds an interesting option for future investigations that aim to design new anticoagulant/antitumor agents.


Subject(s)
Anticoagulants/pharmacology , Antineoplastic Agents/pharmacology , Chlorophyta/chemistry , Plant Extracts/pharmacology , Seaweed/chemistry , Animals , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Brazil , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Galactans/chemistry , Galactans/isolation & purification , Galactans/pharmacology , Heparin/pharmacology , Mice , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Sulfates/chemistry , Sulfates/isolation & purification , Sulfates/pharmacology , Thrombin/antagonists & inhibitors
13.
PLoS One ; 12(11): e0187013, 2017.
Article in English | MEDLINE | ID: mdl-29190741

ABSTRACT

BACKGROUND: An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS) becomes attractive. OBJECTIVE: We tested the hypothesis that two preoperative active(a)-tDCS sessions compared with sham(s)-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS) at rest and during walking (primary outcomes)]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10) during Conditioned Pain Modulation (CPM-task), disability related to pain (DRP) and analgesic consumption (secondary outcomes). Also, we assessed if the brain derived neurotrophic factor (BDNF) in the cerebral spinal fluid (CSF) after tDCS could predict the intervention's effect on the DRP. METHODS: It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old) who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each) of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S). RESULTS: A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001). At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68) while during walking was 1.67cm (95%CI = 1.05 to 2.28). A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001), produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21) and higher function of descending pain modulatory system (DPMS) during CPM-task. CONCLUSION: A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02360462.


Subject(s)
Hallux Valgus/surgery , Neuronal Plasticity , Pain, Postoperative/therapy , Preoperative Care , Transcranial Direct Current Stimulation , Adult , Brain-Derived Neurotrophic Factor/cerebrospinal fluid , Chronic Pain , Double-Blind Method , Female , Humans , Middle Aged , Pain, Postoperative/metabolism , Prospective Studies
14.
J Stroke Cerebrovasc Dis ; 26(10): 2256-2263, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28642017

ABSTRACT

BACKGROUND AND PURPOSE: Demonstration of an improvement process of quality indicators in stroke care is essential to obtain certification as a primary stroke center (PSC). Our aim was to evaluate factors that influence temporal trends in quality indicators of ischemic stroke (IS) in a Brazilian hospital. METHODS: We evaluated patients discharged with IS from a tertiary hospital from January 2009 to December 2013. Ten predefined performance measures selected by the Get With the Guidelines-Stroke program were assessed. We also compared 5 quality indicators available from a secondary community hospital for the first year of the series to those found in the tertiary hospital. RESULTS: We evaluated 551 patients at the tertiary stroke center (median age 77.0 years [interquartile range 64.0-84.0]; 58.4% were men). The quality indicators that improved with time were the use of cholesterol-lowering therapy (P = .02) and stroke education (P = .04). The median composite perfect care did not consistently improve throughout the period (P = .13). After a multivariable adjustment, only thrombolytic treatment (odds ratio [OR] 2.06, P < .01), dyslipidemia (OR 2.03, P < .01), and discharge in a Joint Commission International's (JCI) visit year (OR 1.8, P < .01) remained as predictors of a perfect care index of 85% or higher. The quality indicators with worse performance (anticoagulation for atrial fibrillation and cholesterol reduction) were similar in the tertiary and secondary community hospitals. CONCLUSIONS: We found a significant improvement in some quality indicators across the years in a PSC located in Latin America. The overall perfect care measure did not improve and was influenced by being discharged in a JCI visit year, having dyslipidemia, and having undergone thrombolytic treatment.


Subject(s)
Brain Ischemia/therapy , Disease Management , Quality Improvement/trends , Stroke/therapy , Aged , Aged, 80 and over , Brain Ischemia/blood , Brazil , Cholesterol/blood , Female , Hospitals, Community , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Patient Education as Topic , Stroke/blood , Tertiary Care Centers , Thrombolytic Therapy , Time Factors , Treatment Outcome
15.
Nanomaterials (Basel) ; 8(1)2017 Dec 25.
Article in English | MEDLINE | ID: mdl-29295570

ABSTRACT

In this study, we aimed to synthesize silver nanoparticles containing fucans from Dictyota mertensii (Martius) Kützing using an environmentally friendly method and to characterize their structure as well as antiproliferative, immunomodulatory, and antibacterial effects. Fucan-coated silver nanoparticles (FN) were characterized by Fourier-transform infrared analysis, dynamic light scattering, zeta potential, atomic force microscopy, energy dispersive X-ray spectroscopy, and inductively coupled plasma emission spectrometry. They were evaluated for their effect on cell viability, minimum inhibitory bactericidal concentration, and release of nitric oxide and cytokines. The FN were successfully synthesized using an environmentally friendly method. They were size-stable for 16 months, of a spherical shape, negative charge (-19.1 mV), and an average size of 103.3 ± 43 nm. They were able to inhibit the proliferation of the melanoma tumor cell line B16F10 (60%). In addition, they had immunomodulatory properties: they caused an up to 7000-fold increase in the release of nitric oxide and cytokines (IL-10; IL-6 and TNF-α) up to 7000 times. In addition, the FN showed inhibitory effect on Gram-positive and -negative bacteria, with MIC values of 50 µg/mL. Overall, the data showed that FN are nanoparticles with the potential to be used as antitumor, immunomodulatory, and antibacterial agents.

16.
Acta méd. (Porto Alegre) ; 38(2): [7], 2017.
Article in Portuguese | LILACS | ID: biblio-883714

ABSTRACT

Objetivos: Avaliar as lesões mais frequente do joelho. Este é local de acometimento de grande número de patologias, tanto agudas quanto crônicas, sendo queixa nesta região anatômica motivo frequente de atendimento e assunto amplo a ser debatido. Assim, uma forma de compreender algumas patologias que acometem o joelho é revisar as afecções mais frequentes conforme a faixa etária. Métodos: Foram revisados seis artigos que abordam as patologias mais frequentes desta região, conforme cada faixa etária. Resultados: Na criança, cita-se a doença de Osgood-Schlatter, osteocondrite dissecante e menisco discóide; já no adulto, as lesões ligamentares e meniscais assumem papel de destaque e no idoso, a osteoartrose do joelho équeixa importante deste grupo de pacientes. De modo geral, o raio-x é o primeiro exame a ser solicitado, de maneira complementar a uma anamnese e exame físico detalhados. O tratamento é definido pelo ortopedista. Medidas gerais como repouso articular, gelo, elevação do membro e imobilização podem ser orientadas até que o paciente consulte o especialista. Conclusões: As lesões de joelho são queixas frequentes e podem ter diversas etiologias, sendo o trauma a mais frequente. Dividir o tema por faixa etária facilita ao examinador direcionar a história e o exame físico.


Aims: Evaluate the mains injuries of the knee. This is a frequent site of injuries with a large amount of pathologies, as much as acute injuries as well as chronic injuries, what makes this anatomic region a frequent motivation for consultation and an extensive subject for debate. Thereby one way of understanding some of these pathologies that involves the knee is reviewing the affections more frequent by age. Methods: Six studies that evaluate the most frequent knee injuries were reviewed, according to each age range. Results: On childhood, Osgood-Schlatter disease, osteochondritis dissecans and discoid meniscus; On adulthood, the ligaments and meniscus injuries become the centerpiece; On the elderly patient osteoarthritis has a main part on the complains. Radiography is the first complementary exam requested, on a general waybeing used to complement the physical examination and the history. Definitive treatment is given by the orthopedist, general measures as joint rest, ice, elevation of the limb and immobilization can be orientated by any doctor until the patient consult a specialist. Conclusions: Knee injuries are frequents and can have multiple etiologies, being trauma the most frequent. Divide by age range makes it easier for the examiner to direct the history and physical examination.


Subject(s)
Knee Injuries , Meniscus , Ligaments
17.
Int J Mol Sci ; 17(8)2016 Aug 19.
Article in English | MEDLINE | ID: mdl-27548151

ABSTRACT

Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.


Subject(s)
Antioxidants/chemistry , Dextrans/chemistry , Animals , Antioxidants/pharmacology , Cell Proliferation/drug effects , Dextrans/pharmacology , Leuconostoc mesenteroides/chemistry , Lipid Peroxidation/drug effects , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Molecular Weight , Nitric Oxide/metabolism , RAW 264.7 Cells
18.
Clinics (Sao Paulo) ; 69(4): 241-6, 2014.
Article in English | MEDLINE | ID: mdl-24714831

ABSTRACT

OBJECTIVE: Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings. METHODS: We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS). RESULTS: A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76). CONCLUSIONS: Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Ischemic Attack, Transient/etiology , Risk Assessment/methods , Stroke/etiology , Age Factors , Aged , Aged, 80 and over , Atrial Fibrillation/physiopathology , Brazil , Echocardiography , Female , Humans , Ischemic Attack, Transient/physiopathology , Male , Middle Aged , Monitoring, Physiologic/methods , Multivariate Analysis , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Stroke/physiopathology , Tertiary Care Centers
19.
Clinics ; 69(4): 241-246, 4/2014. tab, graf
Article in English | LILACS | ID: lil-705783

ABSTRACT

OBJECTIVE: Atrial fibrillation is a common arrhythmia that increases the risk of stroke by four- to five-fold. We aimed to establish a profile of patients with atrial fibrillation from a population of patients admitted with acute ischemic stroke or transient ischemic attack using clinical and echocardiographic findings. METHODS: We evaluated patients consecutively admitted to a tertiary hospital with acute ischemic stroke or transient ischemic attack. Subjects were divided into an original set (admissions from May 2009 to October 2010) and a validation set (admissions from November 2010 to April 2013). The study was designed as a cohort, with clinical and echocardiographic findings compared between patients with and without atrial fibrillation. A multivariable model was built, and independent predictive factors were used to produce a predictive grading score for atrial fibrillation (Acute Stroke AF Score-ASAS). RESULTS: A total of 257 patients were evaluated from May 2009 to October 2010 and included in the original set. Atrial fibrillation was diagnosed in 17.5% of these patients. Significant predictors of atrial fibrillation in the multivariate analysis included age, National Institutes of Health Stroke Scores, and the presence of left atrial enlargement. These predictors were used in the final logistic model. For this model, the area under the receiver operating characteristic curve was 0.79. The score derived from the logistic regression analysis was The model developed from the original data set was then applied to the validation data set, showing the preserved discriminatory ability of the model (c statistic = 0.76). CONCLUSIONS: Our risk score suggests that the individual risk for atrial fibrillation in patients with acute ischemic stroke can be assessed using simple data, including age, National Institutes of Health Stroke Scores at admission, and the presence of left atrial enlargement. .


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Ischemic Attack, Transient/etiology , Risk Assessment/methods , Stroke/etiology , Age Factors , Atrial Fibrillation/physiopathology , Brazil , Echocardiography , Ischemic Attack, Transient/physiopathology , Multivariate Analysis , Monitoring, Physiologic/methods , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Stroke/physiopathology , Tertiary Care Centers
20.
Antioxidants (Basel) ; 3(4): 730-44, 2014 Nov 04.
Article in English | MEDLINE | ID: mdl-26785237

ABSTRACT

Polyporus dermoporus mushroom, native to Brazil, is produced under natural conditions in the unexplored reserve of Mata da Estrela-Rio Grande do Norte-RN. These mushrooms were delipidated with chloroform:methanol (2:1 v/v), extracted with water at 100 °C, and fractionated with ethanol (one and three volumes) and then centrifuged. The ethanol precipitation showed a high total sugar level of 64.8% and 1% of protein. This precipitate contained a high glucan level, characterized by chemical methods and by NMR of (13)C and ¹H and spectroscopy. The (13)C NMR spectrum of these mushroom extracts showed the presence of ß-glucose by a signal at 103.25 ppm. Studies with these glucans were made to elucidate antioxidant and anti-inflammatory activities. This extract of glucans inhibited the lipid peroxidation (42.9%) and superoxide radicals (83.3%) at 67 µg/mL. However, the inhibition of hydroxyl radical by the extract of this mushroom was 96% at 267 µg/mL. The action of this extract on induced pleurisy showed a 92.5% and 68.7% reduction in polymorphonuclears cells and nitric oxide, respectively, at 30 mg/kg. The glucans reduced the croton oil-induced ear edema by 65.6% at 30 mg/kg.

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