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Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania and is responsible for more than 1 million new cases and 70,000 deaths annually worldwide. Treatment has high costs, toxicity, complex and long administration time, several adverse effects, and drug-resistant strains, therefore new therapies are urgently needed. Synthetic compounds have been highlighted in the medicinal chemistry field as a strong option for drug development against different diseases. Organic salts (OS) have multiple biological activities, including activity against protozoa such as Leishmania spp. This study aimed to investigate the in vitro leishmanicidal activity and death mechanisms of a thiohydantoin salt derived from l-arginine (ThS) against Leishmania amazonensis. We observed that ThS treatment inhibited promastigote proliferation, increased ROS production, phosphatidylserine exposure and plasma membrane permeabilization, loss of mitochondrial membrane potential, lipid body accumulation, autophagic vacuole formation, cell cycle alteration, and morphological and ultrastructural changes, showing parasites death. Additionally, ThS presents low cytotoxicity in murine macrophages (J774A.1), human monocytes (THP-1), and sheep erythrocytes. ThS in vitro cell treatment reduced the percentage of infected macrophages and the number of amastigotes per macrophage by increasing ROS production and reducing TNF-α levels. These results highlight the potential of ThS among thiohydantoins, mainly related to the arginine portion, as a leishmanicidal drug for future drug strategies for leishmaniasis treatment. Notably, in silico investigation of key targets from L. amazonensis, revealed that a ThS compound from the l-arginine amino acid strongly interacts with arginase (ARG) and TNF-α converting enzyme (TACE), suggesting its potential as a Leishmania inhibitor.
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Arginina , Leishmania , Macrófagos , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio , Animais , Arginina/farmacologia , Arginina/química , Arginina/metabolismo , Camundongos , Humanos , Leishmania/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/parasitologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ovinos , Antiprotozoários/farmacologia , Antiprotozoários/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Eritrócitos/metabolismo , Linhagem Celular , Leishmania mexicana/efeitos dos fármacos , Leishmania mexicana/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting the joints, skin and entheses. Despite the importance of the topic, few studies have investigated the association between PsA and sexual function. The purpose of this study was to assess sexuality and the prevalence of sexual dysfunction (SD) in patients with PsA. METHODS: This was an observational, cross-sectional single-center study on 23 PsA patients (male=12; female=11) evaluated with 2 male questionnaires (MSQ= Male Sexual Quotient, and IIEF=International Index of Erectile Function) and 2 female questionnaires (FSQ= Female Sexual Quotient, and FSFI=Female Sexual Function Index) validated for Brazilian Portuguese, in order to determine changes in sexual function. Clinical parameters, musculoskeletal activity and skin activity were also analyzed to identify factors associated with SD. RESULTS: The mean age was 52.1±9.7 years (males) and 49.1±9.6 years (females). Clinically, the patients had low skin and peripheral joint disease activity or were in remission. The mean time of PsA was 10±6.2 years, and 65.2% had a steady sexual partner. The mean MSQ score was 75.8±16.8. The prevalence of SD was 91.7% in men (IIEF), with a predominance of mild SD. The mean FSQ score was 64.9±24.1. The prevalence of SD was 72.7% in women (FSFI), with low domain scores. Also, a significant association was found between female age and total and domain-specific FSFI scores. PASI (Psoriasis Area and Severity Index) and the general satisfaction domain (IIEF) were significantly correlated. CONCLUSION: This study found a high prevalence of SD in PsA patients. Age had a negative impact on female sexual function. Physicians need to be more aware of SD in this population to provide early multidisciplinary treatment and minimize the impact of the disease on the quality of life of patients and their partners.
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Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.
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Leishmaniasis is a disease caused by a protozoan of the genus Leishmania, affecting millions of people, mainly in tropical countries, due to poor social conditions and low economic development. First-line chemotherapeutic agents involve highly toxic pentavalent antimonials, while treatment failure is mainly due to the emergence of drug-resistant strains. Leishmania arginase (ARG) enzyme is vital in pathogenicity and contributes to a higher infection rate, thus representing a potential drug target. This study helps in designing ARG inhibitors for the treatment of leishmaniasis. Py-CoMFA (3D-QSAR) models were constructed using 34 inhibitors from different chemical classes against ARG from L. (L.) amazonensis (LaARG). The 3D-QSAR predictions showed an excellent correlation between experimental and calculated pIC50 values. The molecular docking study identified the favorable hydrophobicity contribution of phenyl and cyclohexyl groups as substituents in the enzyme allosteric site. Molecular dynamics simulations of selected protein-ligand complexes were conducted to understand derivatives' interaction modes and affinity in both active and allosteric sites. Two cinnamide compounds, 7g and 7k, were identified, with similar structures to the reference 4h allosteric site inhibitor. These compounds can guide the development of more effective arginase inhibitors as potential antileishmanial drugs.
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Arginase , Inibidores Enzimáticos , Leishmania , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Arginase/antagonistas & inibidores , Arginase/química , Arginase/metabolismo , Leishmania/enzimologia , Leishmania/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Relação Quantitativa Estrutura-Atividade , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Sítio Alostérico , Antiprotozoários/farmacologia , Antiprotozoários/química , Domínio CatalíticoRESUMO
COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.
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COVID-19 , Proteases 3C de Coronavírus , Peptidomiméticos , Humanos , SARS-CoV-2/metabolismo , Peptidomiméticos/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Aminoácidos , Simulação de Dinâmica Molecular , Antivirais/farmacologia , Antivirais/químicaRESUMO
Abstract Objective The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Ceará (northeastern Brazil) over a period of five years. Results The mean age at diagnosis was 44.1 ± 16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the national average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing.
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Leucemia Mieloide Aguda , Prognóstico , LeucemiaRESUMO
The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.
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Antineoplásicos , Neoplasias da Mama , Naftoquinonas , Humanos , Feminino , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismo , Triazóis/farmacologia , Naftoquinonas/farmacologia , Proteínas Quinases Ativadas por AMP , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
INTRODUCTION: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. ethod: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies. The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of primary hemostasis and blood coagulation. The compounds that showed inhibition greater than 85% were submitted to the analysis of their potency by calculating the concentration required to inhibit 50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent with IC50 of 1.45 µM. Interestingly, this derivative inhibited more than 90% of platelet aggregation induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay, most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally, the compounds tested at 100 µM also showed no cytotoxic effects in HepG2 and Vero cells. RESULT: The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR, which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity. CONCLUSION: Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates for the development of novel antiplatelet agents.
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ABSTRACT BACKGROUND AND OBJECTIVES: The presence of central sensitization (CS) in people with chronic neck pain requires clarification, as does the possible disparities between genders. Therefore, this study aimed to evaluate the presence of CS in chronic neck pain according to gender. METHODS: Cross-sectional study with the participation of 260 adults (18-59 years old) with chronic neck pain, carried out between September 2022 and September 2023. Instruments were applied to collect sociodemographic profile, pain characteristics, cervical functional disability and presence of SC. The software SPSS 23.0 was used for comparative analyzes. RESULTS: Regarding disparities between genders, there were no differences in the intensity of pain and cervical functional disability (p=0.134 and p=0.277, respectively). However, SC was higher in women (43.5 ± 14.0; p=0.003). In females, CS was related to "pain interference" in the aspects of walking (r=0.311; p=0.001), relationships with people (r=0.309; p=0.001), appreciation of life (r=0.321; p= 0.001) and with cervical functional disability (r=0.570; p=0.001). In males, CS was related to "pain interference" in aspects such as general activity (r=0.311; p=0.008), mood (r=0.376; p=0.001), walking (r=0.313; p= 0.007), relationships with people (r=0.477; p=0.001), sleep (r=0.321; p=0.006), appreciation of life (r=0.427 p=0.001) and functional disability (r=0.667; p<0.001). CONCLUSION: Women with chronic neck pain showed a greater presence of CS, while CS in men was related to a variety of aspects that negatively affect life. Given this, differences between genders could be considered in the management of patients with chronic neck pain.
RESUMO JUSTIFICATIVA E OBJETIVOS: A presença de sensibilização central (SC) em pessoas com dor cervical crônica carece de esclarecimentos, bem como as possíveis disparidades entre os sexos. Portanto, objetivou-se avaliar a presença de SC na dor cervical crônica de acordo com o sexo. MÉTODOS: Estudo transversal com a participação de 260 adultos (18-59 anos) com dor cervical crônica, realizado entre setembro de 2022 e setembro de 2023. Foram aplicados instrumentos para coletar perfil sociodemográfico, características da dor, incapacidade funcional da cervical e presença de SC. Para análises comparativas foi utilizado o SPSS 23.0. RESULTADOS: Nas disparidades entre os sexos, não houve diferenças na intensidade da dor e incapacidade funcional cervical (p=0,134 e p=0,277, respectivamente). No entanto, a SC foi mais elevada nas mulheres (43,5 ± 14,0; p=0,003). No sexo feminino, a SC apresentou relação com a "interferência da dor" nos aspectos: caminhar (r=0,311; p=0,001), relacionamento interpessoal (r=0,309; p=0,001), apreciação da vida (r=0,321; p=0,001) e com incapacidade funcional da cervical (r=0,570; p=0,001). Já no sexo masculino, a SC teve relação com a "interferência da dor" em aspectos como atividade geral (r=0,311; p=0,008), humor (r=0,376; p=0,001), caminhar (r=0,313; p=0,007), relacionamento interpessoal (r=0,477; p=0,001), sono (r=0,321; p=0,006), apreciação da vida (r=0,427 p=0,001) e incapacidade funcional (r=0,667; p<0,001). CONCLUSÃO: Mulheres com dor cervical crônica mostraram maior presença da SC, enquanto nos homens a SC esteve relacionada a uma variedade de aspectos que afetam negativamente a vida. Diante disso, as diferenças entre os sexos poderiam ser consideradas no gerenciamento de pacientes com dor cervical crônica.
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ABSTRACT The Removable Partial Denture stands as an effective rehabilitation choice for patients who have undergone partial maxillectomy surgery due to maxillary tumors, involving the partial surgical removal of the maxillary bone. Removable partial denture are meticulously designed to restore masticatory, phonetic, and aesthetic functions, thereby contributing significantly to enhancing self-esteem and aiding patients in resuming social activities. During the patient's history-taking phase, it is of paramount importance to assess the patient's overall health, psychological state, expectations, and limitations. Ensuring regular follow-ups is imperative to prevent complications and to guarantee the durability of the prosthesis. Prosthetic planning constitutes a critical phase and can pose challenges, especially in achieving proper retention, stability, and suitable supports. Factors such as the defect size, the number of remaining teeth, and the amount of remaining bone structures can influence the treatment prognosis. It is crucial to emphasize that lack of adequate planning can lead to rehabilitation failures, resulting in discomfort, compromised functionality, and even potential harm to the patient's health. In this context, this study aims to present a successful clinical case of a patient who underwent partial maxillectomy and was rehabilitated through a Removable Partial Denture fixed with clasps on the entire left upper hemi-arch. This case vividly illustrates the importance of a personalized approach to prosthetic rehabilitation in patients with partial maxillectomy, taking into account the specificities of each case and highlighting the necessity of interdisciplinary collaboration to achieve satisfactory outcomes.
RESUMO A prótese parcial removível é uma opção eficaz de reabilitação para pacientes que passaram por cirurgia de maxilectomia parcial em decorrência de tumores maxilares, ou seja, remoção cirúrgica parcial do osso maxilar. A prótese parcial removível deve ser projetada para recuperar as funções mastigatória, fonética e estética, contribuindo assim na melhoria da autoestima e ajudando o paciente a retornar às atividades sociais. Durante a anamnese, é de grande importância verificar o estado geral e psicológico do paciente, suas expectativas e limitações, garantir o acompanhamento frequente para evitar complicações e garantir a durabilidade da prótese. O planejamento protético é uma etapa crítica e pode apresentar desafios, especialmente na obtenção de retenção, estabilidade e suportes adequados. Fatores como o tamanho do defeito, o número de dentes remanescentes e a quantidade de estruturas ósseas remanescentes podem interferir no prognóstico do tratamento. É importante ressaltar que a falta de planejamento pode levar a falhas na reabilitação, resultando em desconforto, má funcionalidade e até mesmo danos à saúde do paciente. Nesse contexto, o presente trabalho tem como objetivo apresentar um caso clínico de sucesso de uma paciente que foi submetida a uma maxilectomia parcial e reabilitada por meio de uma prótese parcial removível fixada por grampos em todo o hemiarco superior esquerdo. Este caso ilustra a importância de uma abordagem personalizada para a reabilitação protética em pacientes com maxilectomia parcial, considerando as particularidades de cada caso e a colaboração interdisciplinar para a obtenção de resultados satisfatórios.
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O estudo objetivou mapear as estratégias utilizadas para o trabalho colaborativo em equipes de Saúde da Família (eSF) inseridas na Atenção Primária à Saúde (APS), em um município do norte de Minas. Trata-se de um estudo qualitativo, com a proposta metodológica da Cartografia. Os dados foram produzidos em quatro eSF por meio de observação participante, questionário de identificação, diário cartográfico, entrevista semiestruturada individual e grupo focal. A análise do discurso e o rastreio cartográfico possibilitaram a construção de duas categorias temáticas e um mapa cartográfico. Alcançou-se que as estratégias, consideradas linhas de fuga, permitem transformações existenciais no trabalho em equipe, pois originam nascentes em solos cristalizados, pensamentos problematizadores, subjetividade e interações disciplinares. Concluiu-se que as linhas duras não devem ser eliminadas do trabalho em equipe, pois coexistem nessa realidade, e o que importa é como são vivenciadas nas relações.(AU)
El objetivo del estudio fue mapear las estrategias utilizadas para el trabajo colaborativo en equipos de Salud de la Familia (eSF), inseridas en la Atención Primaria de la Salud, en un municipio del Norte de Minas Gerais. Se trata de un estudio cualitativo, con la propuesta metodológica de la Cartografía. Los datos se produjeron en cuatro eSF, por medio de observación participativa, cuestionario de identificación, diario cartográfico, entrevista semiestructurada individual y grupo focal. El análisis del discurso y el rastreo cartográfico posibilitaron la construcción de dos categorías temáticas y un mapa cartográfico. Se vio que las estrategias, consideradas líneas de fuga, permiten transformaciones en el trabajo en equipo, puesto que originan manantiales en suelos cristalizados, pensamientos problematizadores, subjetividad e interacciones disciplinarias. Se concluyó que las líneas duras no deben eliminarse del trabajo en equipo, puesto que coexisten en esta realidad y lo que importa es cómo se experimentan en las relaciones.(AU)
The study aimed to map the strategies used for collaborative work in Family Health Teams (FHT), inserted in Primary Health Care, in a municipality in the North of Minas. This is a qualitative study, with the methodological proposal of Cartography. Data were produced in four FHT, through participant observation, identification questionnaire, cartographic diary, semi-structured individual interview and focus group. Discourse analysis and mapping screening enabled the construction of two thematic categories and a cartographic map. It was reached that the strategies, considered lines of flight, allow existential transformations in teamwork, since they originate springs in crystallized soils, problematizing thoughts, subjectivity, and disciplinary interactions. It was concluded that hard lines should not be eliminated from teamwork, for they coexist in this reality, and what matters is how they are experienced in relationships.(AU)
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The aim is to present validity evidence of the Brazilian-Portuguese Recovery Experience Questionnaire (REQ-PB) by applying a procedure to decentering cross-cultural scales translation and adaptation. First, we had a phase with bilingual experts, which assessed different criteria of translation quality. In sequence, we conducted the replication of the original research to achieve validity indicators in the Brazilian context. We carried out both Confirmatory Factor Analysis (to find structural validity indicators) and correlations with various external variables (to find convergent validity indicators). Step 1 showed promising results of decentering translation. In step 2 participated 164 workers and the CFA confirmed the four-factor model: psychological detachment from work, relaxation, mastery experience, and control over leisure time. The convergent validity showed a significant correlation with external variables. The REQ-PB showed adequate psychometric properties and may explain and compare empirical evidence of the recovery topic. We concluded that we have a good quality scale to be used in future research and integrated with other constructs to support interventions.
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Etnicidade , Atividades de Lazer , Humanos , Brasil , Portugal , Inquéritos e Questionários , Psicometria , Reprodutibilidade dos Testes , Comparação TransculturalRESUMO
BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.
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Ibuprofeno , Sulfonamidas , Humanos , Disponibilidade Biológica , Ibuprofeno/química , Ibuprofeno/farmacocinética , Células CACO-2 , Solubilidade , SuspensõesRESUMO
OBJECTIVES: to improve an instrument that measures postpartum women's satisfaction with obstetric care. METHODS: action research, developed from a preliminary version of an instrument prepared by nurse-midwives working in public services in the Federal District. The analysis of the results of application of instrument carried out in a pilot test, analysis of evidence of instrument validity, literature review, focus group with the instrument's developers and interview with the target audience were carried out. RESULTS: factorial analysis showed three existing factors in the construct. Seven nurses participated, discussing the instrument reformulation, and 20 mothers reported their perceptions about the care received during childbirth, generating five thematic units. FINAL CONSIDERATIONS: instrument improvement occurred through item and response scale reconstruction and reorganization, in addition to application of a pre-test with the target population, resulting in an instrument composed of 13 items.
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Satisfação do Paciente , Período Pós-Parto , Gravidez , Feminino , Humanos , Parto , Mães , Parto Obstétrico , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Abstract The aim is to present validity evidence of the Brazilian-Portuguese Recovery Experience Questionnaire (REQ-PB) by applying a procedure to decentering cross-cultural scales translation and adaptation. First, we had a phase with bilingual experts, which assessed different criteria of translation quality. In sequence, we conducted the replication of the original research to achieve validity indicators in the Brazilian context. We carried out both Confirmatory Factor Analysis (to find structural validity indicators) and correlations with various external variables (to find convergent validity indicators). Step 1 showed promising results of decentering translation. In step 2 participated 164 workers and the CFA confirmed the four-factor model: psychological detachment from work, relaxation, mastery experience, and control over leisure time. The convergent validity showed a significant correlation with external variables. The REQ-PB showed adequate psychometric properties and may explain and compare empirical evidence of the recovery topic. We concluded that we have a good quality scale to be used in future research and integrated with other constructs to support interventions.
Resumo O objetivo é apresentar evidências da validade do Questionário de Experiência de Restauro em português brasileiro (REQ-PB) por meio da aplicação de um procedimento de descentralização para tradução e adaptação de escalas transculturais. Inicialmente, tivemos uma fase com especialistas bilíngues que avaliaram a qualidade da tradução utilizando diferentes critérios. Na sequência, realizamos a replicação da pesquisa original para alcançar os indicadores de validade no contexto brasileiro. Efetuamos tanto a análise fatorial confirmatória (para encontrar indicadores de validade estrutural) quanto correlações com variáveis externas (para encontrar indicadores de validade convergentes). O passo 1 mostrou resultados promissores na tradução descentralizada. No passo 2, participaram 164 trabalhadores e a análise fatorial confirmatória confirmou o modelo de quatro fatores: distanciamento psicológico do trabalho, relaxamento, experiência de domínio e controle do tempo livre. A validade convergente mostrou uma correlação significativa com variáveis externas. O REQ-PB mostrou propriedades psicométricas adequadas capazes de explicar e comparar evidências empíricas do tópico de restauro. Em resumo, a escala pode ser utilizada em pesquisas futuras e integrada aoutros construtos para orientar intervenções.
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PURPOSE: To investigate the combinations of variables that comprise the biopsychosocial model domains to identify clinical profiles of risk and protection of second anterior cruciate ligament injury. METHODS: One hundred and forty-five patients for return-to-sport testing after anterior cruciate ligament (ACL) reconstruction (ACLR) were contacted, and 97 were deemed eligible. All were evaluated between 6 and 24 months and followed up for 2 years. Participants answered the International Knee Documentation Committee (IKDC) and Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI), performed the postural stability assessment using the Biodex Balance System, and assessed muscle strength at 60° and 300°/s on the isokinetic dynamometer. Personal factors (age, gender, body mass index), body structures (graft type and concomitant injuries), and environmental factors (time between surgery and evaluation) were also collected. The participants were asked about the occurrence of a second ACL injury and return to sport after 2 years of follow-up. Classification and regression tree (CART) analysis was used to determine predictors of a second ACL injury. The receiver operating characteristic (ROC) curve was performed to verify the accuracy of the CART analysis, in addition to the sensitivity, specificity, and relative risk (RR) of the model. RESULTS: Of the initial 97 participants, 88 (89.8%) responded to follow-up and 14 (15.9%) had a second ACL injury (11 graft ruptures and three contralateral ACL). CART analysis identified the following variables as predictors of second ACL injury: return to sport, hamstring strength symmetry at 300°/s, ACL-RSI score, hamstrings/quadriceps ratio at 60°/s, and body mass index (BMI). CART correctly identified 9 (64.3%) of the 14 participants who were reinjured and 71 (95.9%) of the 74 participants who were not. The total correct classification was 90.9%. The area under the ROC curve was 0.88 (95% CI 0.72-0.99; p < 0.001), and the model showed a sensitivity of 75% (95% CI 42.8-94.5), specificity of 93.4% (95% CI 85.3-97.8), and RR of 15.9 (95% CI 4.9-51.4; p < 0.0001). CONCLUSION: The combination of hamstring strength symmetry, hamstring/quadriceps ratio (body functions); return to sport (activity and participation); psychological readiness; and BMI (personal factors) could identify three clinical risk profiles for a second ACL injury with good accuracy. LEVEL OF EVIDENCE: IV.
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Currently, gonadotropin products (follicle stimulating hormone, FSH, and luteinizing hormone, LH) used in animal reproduction are produced by extraction and purification from abattoir-derived pituitary glands. This method, relying on animal-derived materials, carries the potential risk of hormone contamination and pathogen transmission. Additionally, chorionic gonadotropins are extracted from the blood of pregnant mares (equine chorionic gonadotropin; eCG) or the urine of pregnant women (human chorionic gonadotropin; hCG). However, recent advancements have introduced recombinant gonadotropins for assisted animal reproduction therapies. The traditional use of FSH for superovulation has limitations, including labor requirements and variability in superovulation response, affecting the success of in vivo (SOV) and in vitro (OPU/IVEP) embryo production. FSH treatment for superstimulation before OPU can promote the growth of a homogenous follicular population and the recovery of competent oocytes suitable for IVEP procedures. At present, a single injection of a preparation of long-acting bovine recombinant FSH (rFSH) produced similar superovulation responses resulting in the production of good-quality in vivo and in vitro embryos. Furthermore, the treatment with eCG at FTAI protocol has demonstrated its efficacy in promoting follicular growth, ovulation, and P/AI, mainly in heifers and anestrous cows. Currently, treatment with recombinant glycoproteins with eCG-like activity (r-eCG) have shown promising results in increasing follicular growth, ovulation, and P/AI in cows submitted to P4/E2 -based protocols. Bovine somatotropin (bST) is a naturally occurring hormone found in cows. Recombinant bovine somatotropin (rbST), produced through genetic engineering techniques, has shown potential in enhancing reproductive outcomes in ruminants. Treatment with rbST has been found to improve P/IA, increase donor embryo production, and enhance P/ET in recipients. The use of recombinant hormones allows to produce non-animal-derived products, offering several advantages in assisted reproductive technologies for ruminants. This advancement opens up new possibilities for improving reproductive efficiency and success rates in the field of animal reproduction.
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Metabolic syndrome (MetS) and obesity represent a public health problem worldwide. Bioelectrical impedance analysis (BIA) is a practical and effective way of evaluating body composition, especially abdominal fat. Liraglutide, a GLP-1 analog, reduces body weight and improves cardiometabolic parameters. In this prospective non-randomized intervention study, we evaluated the effect of 6 months of treatment with liraglutide (n = 57) on the clinical, laboratory and BIA findings of adult sex-stratified patients diagnosed with obesity and MetS, compared to a control group receiving sibutramine (n = 46). The groups were statistically similar with regard to the age of females (p = 0.852) and males (p = 0.657). Almost all anthropometric and BIA variables were higher in the treatment group than in the comparative group (p < 0.05). Abdominal circumference (AC) decreased significantly more in the treatment group. In males, body weight and fat mass also decreased (p < 0.05). Liraglutide treatment was associated with a greater reduction in trunk fat mass (FMT) (p < 0.05). AC and FMT were strongly correlated (rho = 0.531, p < 0.001) in the treatment group. In the multiple regression analysis, liraglutide treatment remained independently associated with FMT. Treatment with liraglutide for 6 months promoted weight loss, improved cardiometabolic and inflammatory parameters and led to a significant reduction in FMT correlated with AC in obese MetS patients of both sexes.
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Doenças Cardiovasculares , Síndrome Metabólica , Masculino , Adulto , Feminino , Humanos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Impedância Elétrica , Estudos Prospectivos , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/diagnóstico , Peso CorporalRESUMO
Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the Schistosoma genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from Myrciaria floribunda leaves as a molluscicidal and cercaricidal agent against Biomphalaria glabrata mollusks and Schistosoma mansoni cercariae. The Myrciaria floribunda essential oil from leaves showed nerolidol, ß-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% (w/w) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The Myrciaria floribunda nanoemulsion showed LC50 values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in Biomphalaria glabrata embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for Schistosoma mansoni cercariae after 2 h. In addition, a survival of 80% was observed in Danio rerio, and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of Myrciaria floribunda leaves may be a promising alternative for schistosomiasis control.