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1.
J Toxicol Environ Health A ; 87(7): 275-293, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38285019

RESUMO

Tithonia diversifolia is a perennial bushy plant found in South America with significant ethnopharmacological importance as an antimalarial, antidiabetic, antibacterial, and anticancer agent. The aim of the present study was to determine the cytotoxicity of the ethanolic extract from leaves of T. diversifolia (TdE) on human cancer cell lines (HCT-116, SNB-19, NCIH-460 and MCF-7), as well as the mechanism of action involved in cell death and cellular modulation of oxidative stress. The TdE exhibited significant activity with IC50 values ranging from 7.12 to 38.41 µg/ml, with HCT-116 being the most sensitive cell line. Subsequent experiments were conducted with HCT-116 cell line. TdE decreased the number of viable cells, followed by induction of apoptotic events, increase in mitochondrial membrane permeabilization, and enhanced G2/M phase of the cell cycle. Pro-oxidative effects including elevated acidic vesicular organelle formation, lipid peroxidation, and nitric oxide by-products, as well as reduced levels of intracellular glutathione and reactive oxygen species production were also observed following incubation with TdE, which may lead to DNA damage followed by apoptotic cell death. These results demonstrate the potential of TdE ethanolic leaf extraction for biological activity and enhance the importance of continuing to study natural sources of plants for the development of anticancer agents.


Assuntos
Antineoplásicos , Tithonia , Humanos , Extratos Vegetais/farmacologia , Células HCT116 , Estresse Oxidativo , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Etanol , Antineoplásicos/farmacologia , Folhas de Planta
2.
Chem Biodivers ; 21(7): e202400670, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38747034

RESUMO

Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MSE) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study's integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer.


Assuntos
Antineoplásicos Fitogênicos , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Metabolômica , Phyllanthus , Phyllanthus/química , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga
3.
J Med Virol ; 95(1): e28169, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36138495

RESUMO

The most widely used vaccines were messenger RNA (mRNA), viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use, and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after 6 months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection enhances the antibody response. We analyze the humoral response (spike [S] IgM for the SARS-CoV-2 and IgG for the S and nucleocapsid [N] proteins) in samples collected before the third dose and 6 months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG antispikes were stimulated mainly 30 days after the third dose (30d/3D), with a decline over time. The IgG anti-N was stimulated predominantly in 90d/3D and 180d/3D. The N IgG levels were 50 and 35 times higher in the positive polymerase chain reaction (PCR) group in 90d/3D and 180d/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180d/3D. The BNT162b2 boosted the S IgG levels, decreasing after 60 days. The booster shot induced IgM and IgG antibodies against spike protein. Infection after vaccination increased antibodies against protein N.


Assuntos
Formação de Anticorpos , COVID-19 , Humanos , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2/genética , Imunoglobulina G , Imunoglobulina M , Anticorpos Antivirais
4.
J Med Virol ; 95(8): e29055, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37641396

RESUMO

We investigated the impact of the fourth dose with ChAdOx1 nCoV-19 (AstraZeneca) in the humoral immune response to SARS-CoV-2 during a 9-month follow-up period in which Omicron was the predominant variant in Brazil. IgG for the SARS-CoV-2 spike protein (S) and nucleocapsid (N) proteins were analyzed in samples collected before and after the fourth dose. All participants were tested monthly for SARS-CoV-2 infection by RT-qPCR. The antibody response induced by the fourth dose of the coronavirus disease 2019 vaccine was evaluated and compared with the response induced by the second and third doses. The additional antibody response to the viral S protein after the fourth dose was smaller than those after the third vaccine dose. In contrast, an increase in the N IgG levels could be observed after the fourth dose compared to other vaccine doses. In the comparison of the antibody response before and after the fourth dose, an increase in both S-and-N IgG was noted, mainly in the positive qPCR group. We did not observe a significant decline in IgG levels after the fourth dose, as observed after the second and third doses, therefore, a sustained humoral response to both S and N proteins seems to be achieved.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Formação de Anticorpos , ChAdOx1 nCoV-19 , Brasil/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Imunoglobulina G
5.
Molecules ; 28(7)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37049771

RESUMO

Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-d]imidazole compounds were synthesized from ß-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104), intense fluorescence emissions in the blue region, and large Stokes shifts (20-103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-d]imidazoles showed IC50 between 8.71 and 29.92 µM against HL-60 cells. For HCT-116 cells, values for IC50 between 21.12 and 62.11 µM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-d]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Citotoxinas , Relação Estrutura-Atividade , Corantes Fluorescentes/farmacologia , Antineoplásicos/farmacologia , Imidazóis/farmacologia
6.
Bioorg Med Chem Lett ; 48: 128240, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34217828

RESUMO

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.


Assuntos
Antineoplásicos/farmacologia , Compostos Ferrosos/farmacologia , Aprendizado de Máquina , Metalocenos/farmacologia , Micro-Ondas , Simulação de Acoplamento Molecular , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/síntese química , Compostos Ferrosos/química , Humanos , Metalocenos/síntese química , Metalocenos/química , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
7.
Bioorg Med Chem Lett ; 53: 128419, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715305

RESUMO

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 µM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.


Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Naftoquinonas/farmacologia , Aminas/química , Aminas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/síntese química , Citotoxinas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Ácidos Picolínicos/química , Ácidos Picolínicos/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade
8.
Bioorg Med Chem Lett ; 30(20): 127469, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32768650

RESUMO

The pentacyclic triterpene 3ß,6ß,16ß-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC50 0.11-0.26 µg mL-1) when compared with its free form (IC50 1.07-1.44 µg mL-1). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Combretum/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Cápsulas , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-Atividade
9.
Toxicol Appl Pharmacol ; 380: 114692, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31356931

RESUMO

Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p < 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.


Assuntos
Acetamidas/uso terapêutico , Ansiolíticos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Acetamidas/farmacologia , Acetamidas/toxicidade , Adolescente , Adulto , Animais , Ansiolíticos/farmacologia , Ansiolíticos/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Camundongos , Adulto Jovem
10.
BMC Anesthesiol ; 18(1): 15, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29390969

RESUMO

BACKGROUND: Delirium is a common complication after cardiac surgery in older adult patients. However, risk factors and the influence of delirium on patient outcomes are not well established. We aimed to determine the incidence, predisposing and triggering factors of delirium following cardiac surgery. METHODS: One hundred seventy-three consecutive patients aged ≥60 years were studied. Patients' characteristics and two cognitive function assessment tests were recorded preoperatively. Perioperative variables were blood transfusion, orotracheal intubation time (OIT), renal dysfunction, and hypoxemia. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. The composite outcome consisted of death, infection, and perioperative myocardial infarction until hospital discharge or 30 days after surgery, and for up to 18 months. RESULTS: One hundred six patients (61.27%) were men and the age was 69.5 ± 5.8 years. EuroSCORE II index was 4.06 ± 3.86. Hypertension was present in 75.14%, diabetes in 39.88%, and 30.06% were illiterate. Delirium occurred in 59 patients (34.1%). Education level (OR 0.81, 0.71-0.92), hypertension (OR 2.73, 1.16-6.40), and mitral valve disease (OR 2.93, 1.32-6.50) were independent predisposing factors for delirium, and atrial fibrillation after surgery (OR 2.49, 1.20-5.20) represented the potential triggering factor. Delirium (OR 2.35, 1.20-4.58) and OIT ≥ 900 min (OR 2.50; 1.30-4.80) were independently associated with the composite outcome. CONCLUSIONS: In older adult patients submitted to cardiac surgery, delirium is a frequent complication that is associated with worst outcome. Independent risk factors for delirium included education level, hypertension, mitral valve disease, and atrial fibrillation after cardiac surgery.


Assuntos
Fibrilação Atrial/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Delírio/epidemiologia , Escolaridade , Doenças das Valvas Cardíacas/epidemiologia , Hipertensão/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
12.
Palliat Support Care ; 15(6): 628-637, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28166861

RESUMO

OBJECTIVE: Dignity therapy (DT) is a brief form of psychotherapy developed for patients living with a life-limiting illness that has demonstrated efficacy in treating several dimensions of end-of-life psychological distress. Our aim was to determine the influence of DT on demoralization syndrome (DS), the desire for death (DfD), and a sense of dignity (SoD) in terminally ill inpatients experiencing a high level of distress in a palliative care unit. METHOD: A nonblinded phase II randomized controlled trial was conducted with 80 patients who were randomly assigned to one of two groups: the intervention group (DT + standard palliative care [SPC]) or the control group (SPC alone). The main outcomes were DS, DfD, and SoD, as measured according to DS criteria, the Desire for Death Rating Scale, and the Patient Dignity Inventory (PDI), respectively. All scales were assessed at baseline (day 1) and at day 4 of follow-up. This study is registered with http://www.controlled-trials.com/ISRCTN34354086. RESULTS: Of the 80 participants, 41 were randomized to DT and 39 to SPC. Baseline characteristics were similar between the two groups. DT was associated with a significant decrease in DS compared with SPC (DT DS prevalence = 12.1%; SPC DS prevalence = 60.0%; p < 0.001). Similarly, DT was associated with a significant decrease in DfD prevalence (DT DfD prevalence = 0%; SPC DfD prevalence = 14.3%; p = 0.054). Compared with participants allocated to the control group, those who received DT showed a statistically significant reduction in 19 of 25 PDI items. SIGNIFICANCE OF RESULTS: Dignity therapy had a beneficial effect on the psychological distress encountered by patients near the end of life. Our research suggests that DT is an important psychotherapeutic approach that should be included in clinical care programs, and it could help more patients to cope with their end-of-life experiences.


Assuntos
Pessoalidade , Psicoterapia/normas , Estresse Psicológico/terapia , Assistência Terminal/normas , Adaptação Psicológica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Prevalência , Psicometria/instrumentação , Psicometria/métodos , Psicoterapia/instrumentação , Psicoterapia/métodos , Qualidade de Vida/psicologia , Estatísticas não Paramétricas , Estresse Psicológico/complicações , Inquéritos e Questionários , Assistência Terminal/métodos , Doente Terminal/psicologia
13.
Molecules ; 21(7)2016 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-27384551

RESUMO

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-ß-lapachone (NßL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NßL on PLGA. Finally, the cytotoxic activity of NßL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.


Assuntos
Benzofuranos/administração & dosagem , Cápsulas , Preparações de Ação Retardada , Portadores de Fármacos , Ácido Láctico , Naftoquinonas/administração & dosagem , Ácido Poliglicólico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Benzofuranos/química , Cápsulas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração Inibidora 50 , Ácido Láctico/química , Masculino , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Naftoquinonas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Neoplasias da Próstata , Análise Espectral Raman
14.
J Affect Disord ; 346: 182-191, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37949241

RESUMO

BACKGROUND: Dietary fatty acids are related to the development of several inflammatory-related diseases, which may include depression. So, the association between fatty acids, culinary oils and fat intake and depression in highly educated Brazilians was evaluated. METHODS: Multicenter cross-sectional study using baseline data from the Cohort of Universities of Minas Gerais. The diagnosis of depression was self-reported, and the daily intake of fatty acids was assessed using a 144-item food frequency questionnaire (FFQ). RESULTS: A total of 7157 participants (68.83 % women) with a median age of 33 years were included. The prevalence of depression was 12.60 % (N = 902). In the adjusted analyses, it was observed that individuals with the highest intake of omega-6 fatty acids (n-6) (OR: 1.36, 95 % CI 1.11-1.67) had a higher prevalence of depression. This increased n-6 intake was identified as a risk factor for depression only among male participants, while among overweight participants, higher n-6 intake was also positively associated with depression. Conversely, a higher ratio of polyunsaturated to monounsaturated and saturated fatty acids (PM/S) was also found to be positively associated with depression, but this association was observed only among non-overweight participants. No associations were found between the consumption of culinary oils or fats and depression. LIMITATIONS: Cross-sectional design limits the assessment of causality. The use of the FFQ can make estimates more difficult. CONCLUSION: Higher consumption of n-6, and higher PM/S ratios were associated with depression, and individual factors can interfere. The mental health care policies should include specific nutritional strategies.


Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Depressão/epidemiologia , Prevalência , Brasil/epidemiologia , Estudos Prospectivos , Óleos
15.
J Med Virol ; 85(4): 563-74, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23417613

RESUMO

Progression towards AIDS can vary from 5 to 10 years from the establishment of the primary infection by HIV-1 to more than 10 years in the complete absence of antiretroviral therapy. Several factors can contribute to the outcome of HIV infection, including host genetic and viral replicating characteristics. Historically, nef-deleted viral genomes have been associated with disease progression. Therefore, the lentiviral Nef protein is regarded as a progression factor. The objective of this work was to characterize the nef gene from a group of treatment naive patients infected with HIV-1 for more than 10 years. These patients were classified as long-term non-progressors, elite controller, and slow-progressors according to clinical and laboratorial data. A premature stop codon within the nef gene leading to the expression of a truncated peptide was observed on samples from the elite controller patient. For the slow-progressor patients, several degrees of deletions at the C-terminal of Nef were observed predicting a loss of function of this protein. The vif gene was characterized for these patients and a rare mutation that predicts a miss localization of the Vif protein to the nucleus of infected cells that could prevent its function as an APOBEC neutralization factor was also observed. These data indicate the importance of the HIV accessory proteins as factors that contribute to the outcome of AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/genética , HIV-1/patogenicidade , Mutação , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Progressão da Doença , Humanos
16.
Psychosomatics ; 54(5): 451-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23465741

RESUMO

BACKGROUND: Desire for death (DFD) within the context of palliative care has become a prominent medical issue and remains the subject of much controversy. METHODS: Cross-sectional study designed to assess the prevalence and associated demographic, physical, psychiatric, and psychosocial factors for DFD in patients with advanced disease. RESULTS: Seventy-five terminally ill patients were included in the analyses in a 28-month period. The prevalence of DFD was 20% (95% CI [11.7-30.8]). No statistical differences were observed between patients with and without DFD with respect to sex, age, race, education, religion, type of family, medical diagnosis, and medication. There were associations between DFD and being married/cohabitating (OR = 4.0; 95% CI [1.21-13.29]) and being socially isolated (OR = 0.3; 95% CI [0.06-0.98]). Significant positive correlations were found between moderate to severe Edmonton Symptom Assessment Scale (ESAS) scores and DFD for tiredness (OR = 10.1; 95% CI [1.57 ± inf]) and drowsiness (OR = 6.0; 95% CI [1.77-20.37]). DFD was also correlated with depression (DSM-IV criteria: OR = 5.5; 95% CI [1.56-19.47]; Hospital and Anxiety Depression Scale (HADS) depression subscale ≥11: OR = 8.6; 95% CI [1.33 ± inf]). In exact multivariate regression analyses predicting DFD, three independent factors emerged: marital status (OR = 5.3; 95% CI [1.16-29.89]); HADS depression sub-scale score ≥11 (OR = 8.3; 95% CI [1.11 ± inf]); drowsiness (OR = 5.8; 95% CI [1.29-32.85]). DISCUSSION: Prevalence of DFD was high in this sample of patients. Identifying factors associated with DFD could help provide medical and social interventions capable of diminishing suffering in terminal ill patients.


Assuntos
Depressão/psicologia , Suicídio Assistido/psicologia , Doente Terminal/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Fatores de Risco , Fases do Sono , Isolamento Social/psicologia
17.
Pharmacology ; 91(3-4): 153-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23392332

RESUMO

Tramadol is a central-acting analgesic associated with nausea and vomiting. Clinical studies have demonstrated that glucocorticoids have analgesic and antiemetic effects when administered perioperatively. The aim of this study is to test the hypothesis that coadministration of tramadol and dexamethasone decreases both postoperative pain and tramadol requirement by patient-controlled analgesia (PCA). Forty female patients undergoing thyroidectomy under general anesthesia were enrolled in a double-blind randomized controlled study and allocated to receive dexamethasone 4 mg i.v. (dexamethasone group, n = 20) or saline (control group, n = 20). At 0, 1, 2, 4 and 22 h of PCA, tramadol consumption and pain were evaluated. Although pain (numerical rating scale 0-10) was significantly lower in the dexamethasone group compared to the control group (2.9 ± 1.4 vs. 3.8 ± 1.2, p = 0.02) at the beginning of PCA, tramadol demand was not significantly different. Although the results herein show a possible beneficial effect of a preoperative single low dose of dexamethasone on postoperative pain, the hypothesis that this corticosteroid decreases tramadol requirement is not supported.


Assuntos
Analgésicos Opioides/administração & dosagem , Antieméticos/administração & dosagem , Dexametasona/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Tramadol/administração & dosagem , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Náusea/prevenção & controle , Tireoidectomia , Vômito/prevenção & controle
18.
Palliat Support Care ; 11(6): 481-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23506744

RESUMO

OBJECTIVE: Dignity therapy (DT) is a short-term psychotherapy developed for patients living with a life-limiting illness. Our aim was to determine the influence of DT on symptoms of depression and anxiety in people with a life-threatening disease with high level of distress, referred to an inpatient palliative care unit. METHOD: This was an open-label randomized controlled trial. Sixty terminally ill patients were randomly assigned to one of two groups: intervention group (DT+ standard palliative care [SPC]) or control group (SPC alone). The main outcomes were symptoms of depression and anxiety, measured with the Hospital Anxiety and Depression Scale, assessed at baseline, day 4, day 15, and day 30 of follow-up. RESULTS: Of the 60 participants, 29 were randomized to DT and 31 to SPC. Baseline characteristics were similar between the two groups. DT was associated with a significant decrease in depressive symptoms at day 4 and day 15 (mean = -4.46, 95% CI, -6.91-2.02, p = 0.001; mean= -3.96, 95% CI, -7.33 to -0.61; p = 0.022, respectively), but not at day 30 (mean = -3.33, 95% CI, -7.32-0.65, p = 0.097). DT was also associated with a significant decrease in anxiety symptoms at each follow-up (mean= -3.96, 95% CI, -6.66 to -1.25, p = 0.005; mean= -6.19, 95% CI, -10.49 to -1.88, p = 0.006; mean = -5.07, 95% CI, -10.22 to -0.09, p = 0.054, respectively). SIGNIFICANCE OF RESULTS: DT appears to have a short-term beneficial effect on the depression and anxiety symptoms that often accompany patients at the end of their lives. Future research with larger samples compared with other treatments is needed to better understand the potential benefits of this psychotherapy.


Assuntos
Ansiedade/prevenção & controle , Depressão/prevenção & controle , Neoplasias/terapia , Cuidados Paliativos/métodos , Pessoalidade , Psicoterapia Breve/métodos , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Assistência Terminal/métodos , Doente Terminal/psicologia
19.
Nat Prod Res ; 37(11): 1892-1896, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36083632

RESUMO

The Senna genus has a wide diversity of species, with an interesting chemical composition of secondary metabolites and applications as medicine. The folk medicine, mainly in developing countries, uses species of Senna to treat seizures, epilepsy and constipation. Though the recognized bioactivity, some Brazilian native species of Senna remain unexplored, such as Senna cearensis, a native species of Caatinga. This is the first report about the bioactivity of the flowers of S. cearensis Afr. Fern., a native species of northeast Brazil. In this communication, flavonoids and catechins are identified in S. cearensis flowers and the chemical composition is linked with its antioxidant, anticholinesterase, and cytotoxic activities. By UPLC-QTOF, some compounds that belong to the class of flavonoids were identified. They are: catechin, epigallocatechin, guibourtinidol-(4α-8)-catechin, and cassiaflavan-(Cat)-epicatechin. The cytotoxic activity is more noticeable for the HL60 (leukemia) cell line with a cell growth inhibition (GI%) of 81.65 ± 5.65.


Assuntos
Antineoplásicos , Catequina , Gleiquênias , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/farmacologia , Inibidores da Colinesterase/farmacologia , Catequina/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flores
20.
Mol Immunol ; 163: 13-19, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37717421

RESUMO

Understanding COVID-19 exposure differences among Healthcare Workers (HCWs) across various healthcare units is crucial for their protection and effective management of future outbreaks. However, comparative data on COVID-19 among HCWs in different healthcare units are scarce in Brazil. This study evaluated the relationship between SARS-CoV-2 infection and workplaces in HCWs from three distinct healthcare settings in Brazil. It also examined COVID-19 symptom dynamics reported by them. The cohort comprised 464 HCWs vaccinated with two doses of CoronaVac and a BNT162b2 booster from different institutions: Primary Health Care Units (PHCUs), Emergency Care Units (ECUs), and Hospitals. Participants answered a questionnaire and underwent blood collection at various time points after vaccinations. RT-PCR data and post-vaccination antibody responses were utilized as indicators of SARS-CoV-2 infection. We found that most infected HCWs worked in ECUs, where positive RT-PCR percentages were higher compared to PHCUs and Hospitals. ECUs also showed the highest seropositivity and antibody levels, especially after the first CoronaVac dose. The second dose of CoronaVac diminished the differences in the antibody levels among HCWs from ECUS, PHCUs, and Hospitals, indicating the benefit of the second dose to equalize the antibody levels between previously exposed and unexposed persons. Moreover, COVID-19 symptoms appeared to evolve over time.


Assuntos
COVID-19 , Saúde Pública , Humanos , Brasil/epidemiologia , Vacina BNT162 , SARS-CoV-2 , Pessoal de Saúde , Anticorpos Antivirais
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