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1.
Chempluschem ; : e202400025, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436967

RESUMO

Enzyme immobilization can offer a range of significant advantages, including reusability, and increased selectivity, stability, and activity. In this work, a central composite design (CCD) of experiments and response surface methodology (RSM) were used to study, for the first time, the L-asparaginase (ASNase) immobilization onto functionalized carbon xerogels (CXs). The best results were achieved using CXs obtained by hydrothermal oxidation with nitric acid and subsequent heat treatment in a nitrogen flow at 600 °C (CX-OX-600). Under the optimal conditions (81 min of contact time, pH 6.2 and 0.36 g/L of ASNase), an immobilization yield (IY) of 100 % and relative recovered activity (RRA) of 103 % were achieved. The kinetic parameters obtained also indicate a 1.25-fold increase in the affinity of ASNase towards the substrate after immobilization. Moreover, the immobilized enzyme retained 97 % of its initial activity after 6 consecutive reaction cycles. All these outcomes confirm the promising properties of functionalized CXs as support for ASNase, bringing new insights into the development of an efficient and stable immobilization platform for use in the pharmaceutical industry, food industry, and biosensors.

2.
Int J Rheum Dis ; 27(1): e14862, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37578016

RESUMO

Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is recommended for non-muscle-invasive bladder cancer after transurethral resection. BCG-associated musculoskeletal adverse events are rare. We report two cases of BCG reactive arthritis that were unusually severe and refractory. These describe two male patients who presented with polyarthritis after BCG exposure. Ultrasonography-guided glucocorticoid injections, high-dose systemic glucocorticoids and the institution of sulfasalazine were required for achievement of remission. Bacillus Calmette-Guérin reactive arthritis can present as polyarthritis of small and medium joints or as mono-oligoarthritis of asymmetrical ankles and knees, frequently associated with tenosynovitis and enthesitis. The mechanism by which BCG promotes arthralgia and arthritis is poorly understood. The most well-accepted theory is that the BCG antigens migrate to different peripheral tissues, including the joints. There is also a lack of knowledge regarding risk factors, with possible genetic factors playing a role. As the two presented cases show, BCG-induced reactive arthritis should be considered in the differential diagnosis of arthritis and refractory tenosynovitis in BCG-exposed patients.


Assuntos
Artrite Reativa , Vacina BCG , Tenossinovite , Neoplasias da Bexiga Urinária , Humanos , Masculino , Administração Intravesical , Artrite Reativa/induzido quimicamente , Artrite Reativa/diagnóstico , Artrite Reativa/tratamento farmacológico , Vacina BCG/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/diagnóstico
3.
Estud. pesqui. psicol. (Impr.) ; 23(4): 1180-1192, dez. 2023.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1537284

RESUMO

A construção dos eixos que compõem a chamada do Dossiê "Psicanálise e Política: a insistência do Real" provocou debate instigante entre os cinco editores deste número da Revista "Estudos e Pesquisa em Psicologia".


Assuntos
Política , Psicanálise
4.
Medicina (Ribeirao Preto, Online) ; 56(4)dez. 2023. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1538407

RESUMO

Background: Regular physical activity (PA) is essential for health maintenance and disease prevention. COV-ID-19 and its social isolation affected patients with cardiovascular (CV) disease. This is a scoping review aiming to map, analyze, and summarize the impacts caused by the isolation of the COVID-19 pandemic concerning PA and CV health in adults. Methods: The review was based on PRISMA-ScR. PubMed, PubMed Central, BVS/BIREME, Scopus, Web of Science, CINAHL, Brazilian Digital Library of Theses and Dissertations, and SciELO databases were selected to search. Two search phases were performed: May 2021 and March 2022. English-language full-text papers were included. Initially, the titles and abstracts of the retrieved documents were read and screened based on the research question. A third reviewer resolved disagreement through consensus meetings. An assessment form was adapted for data extraction. The study was registered in the Open Science Framework platform under the DOI https://doi.org/10.17605/OSF.IO/AH6P8. Results: 11 papers were included and demonstrated that regular PA could be challenging in social isolation environments. Most participants were moderately active and performed low-intensity PA. Confinement led to the limitation of everyday activities, nutritional disorders, and reduced PA, contributing to weight gain. Quarantine was associated with stress and depression, leading to an unhealthy diet (AU).


Introdução: A prática regular de atividade física (AF) é essencial para a manutenção da saúde e prevenção de doenças. A COVID-19 e seu isolamento social afetaram pacientes com doenças cardiovasculares (CV) na prática dessas atividades. Desta forma, realizou-se uma revisão de escopo com o objetivo de mapear, analisar e sintetizar os impactos causados pelo isolamento da pandemia de COVID-19 na realização de AF e na saúde CV em adultos. Métodos: A revisão foi baseada no PRISMA-ScR. Foram selecionadas para a pesquisa a PubMed, PubMed Central, BVS/BIREME, Scopus, Web of Science, CINAHL, Biblioteca Digital Brasileira de Teses e Dissertações e bases de dados SciELO. Duas fases de busca foram realizadas: maio de 2021 e março de 2022. Foram incluídos artigos que possuíam texto completo em inglês. Inicialmente, os títulos e resumos dos documentos recuperados foram lidos e triados com base na questão de pesquisa. Um terceiro revisor foi utilizado para avaliar os desacordos por meio de reuniões de consenso. Um formulário de avaliação foi adaptado para extração de dados. O estudo foi registrado na plataforma Open Science Framework sob o DOI https://doi.org/10.17605/OSF.IO/AH6P8. Resultados: 11 artigos foram incluídos neste estudo e demonstraram que a AF regular pode ser desafiadora em ambientes de isolamento social. A maioria dos participantes era moderadamente ativa e praticava AF de baixa intensidade. O confinamento levou à limitação das atividades cotidianas, distúrbios nutricionais e diminuição da AF, contribuindo para o ganho de peso. A quarentena foi associada ao estresse e à depressão, levando a uma dieta pouco saudável. Possíveis soluções apontam para a realização de AF domiciliar, considerando a saúde basal e o estado CV. Conclusão: A era pós-COVID-19 e suas consequências apontam para a necessidade de planejamento de estratégias que aumentem e mantenham a AF domiciliar como medida protetora para a população em geral, considerando saúde CV, recursos e espaço domiciliar (AU).


Assuntos
Humanos , Isolamento Social , Doenças Cardiovasculares , Comportamento Sedentário , COVID-19
5.
Syst Rev ; 12(1): 222, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993931

RESUMO

BACKGROUND: Medication adherence has a major impact on reducing mortality and healthcare costs related to the treatment of cardiovascular diseases and diabetes mellitus. Selecting the best patient-reported outcome measure (PROM) among the many available for this kind of patient is extremely important. This study aims to critically assess, compare and synthesize the quality of the measurement properties of patient-reported outcome measures to assess medication adherence among patients with cardiovascular diseases and/or type 2 diabetes mellitus. METHODS: This review followed the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines and was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). The searches were performed in Web of Science, SCOPUS, PubMed, CINAHL, EMBASE, LILACS, PsycINFO, and ProQuest (gray literature). RESULTS: A total of 110 records encompassing 27 different PROMs were included in the review. The included records were published between 1986 and 2023, most of which reported studies conducted in the United States and were published in English. None of the PROMs were classified in the category "a", thus being recommended for use due to the quality of its measurement properties. The PROMs that should not be recommended for use (category "c") are the MTA, GMAS, DMAS-7, MALMAS, ARMS-D, and 5-item questionnaire. The remaining PROMs, e.g., MMAS-8, SMAQ, MEDS, MNPS, ARMS-12, MGT, MTA-OA, MTA-Insulin, LMAS-14, MARS-5, A-14, ARMS-10, IADMAS, MAQ, MMAS-5, ProMAS, ARMS-7, 3-item questionnaire, AS, 12-item questionnaire, and Mascard were considered as having the potential to be recommended for use (category "b"). CONCLUSION: None of the included PROMs met the criteria for being classified as trusted and recommended for use for patients with cardiovascular diseases and/or type 2 diabetes mellitus. However, 21 PROMs have the potential to be recommended for use, but further studies are needed to ensure their quality based on the COSMIN guideline for systematic reviews of PROMs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019129109.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Qualidade de Vida , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , Psicometria
6.
Sports (Basel) ; 11(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37505622

RESUMO

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition that emerges in childhood and its symptoms continue through adulthood. The Adult Developmental Coordination Disorders/Dyspraxia Checklist was the first instrument used to screen adults with possible DCD. The psychometric characteristics of the Uzbek version of the scale were explored. An independent translation of the questionnaire from the original version into the Uzbek language was made. The sample comprised 301 Uzbekistan adults, aged between 17 and 42 years old (M = 20.66; SD = 2.26). Analyses were performed using R software (4.1.0). Descriptive analysis, exploratory factor analysis, and evidence of reliability in terms of internal consistency were assessed using the psych package (2.1.6), intraclass correlation coefficients were assessed using the irr package (0.84.1), and weighted Kappa were assessed using vcd package (1.4-10). To analyse the factor structure of the ADC scale, when applied to an Uzbekistan sample, exploratory factor analysis (EFA) was performed. In the Uzbek version, a one-factor structure was identified, and moderated psychometric properties were found, which makes it a possible alternative to the original scale when applied to adults. This Uzbek version reduces respondents' fatigue since it is smaller than the original one. More studies are needed to confirm the cut-off scores of this new version.

7.
Front Med (Lausanne) ; 9: 860813, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847785

RESUMO

Psoriatic arthritis (PsA) is a phenotypically heterogeneous chronic inflammatory disease associated to type I major histocompatibility complex alleles whose complex pathogenesis is still not completely understood. The psoriatic synovium shares general features of chronic inflammation with rheumatoid arthritis (RA) and other arthritis, such as hyperplasia of the intimal lining layer, sublining influx of inflammatory cells and neoangiogenesis, but recognizing disease-specific histopathologic findings may help in diagnosis and definition of therapeutic targets. Available literature reports conflicting data regarding the extension of lining hyperplasia, that does not allow depiction from RA. Sublining inflammatory cells consist of T and B cells and macrophages, plasma cells, mast cells and follicular dendritic cells, with a higher amount of overall T, mast cell and IL-17 producing CD8+ T lymphocytes and lower proportion of plasma cells when compared to the rheumatoid synovium. The amount of synovium IL17+ CD8+ T cells correlates positively to measures of disease activity. Lymphoid follicles with characteristics of germinal centers have been identified, similar to the ones described in RA. Neoangiogenesis is more prominent in PsA but can also be an outstanding feature in some RA samples, and different molecules involved in the process appear to have different influence in each disease. IL-17 and IL-22 expression in the synovium does not allow depiction between diseases. Among other cytokines and molecules likely implicated in disease physiopathology, only IL-35 is demonstrated to be reduced in PsA when compared to RA.

8.
ARP Rheumatol ; 1(2): 183-184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35810380

RESUMO

An immunosuppressed 72 year-old woman presented with bilateral hand-fingers tenderness and increased circumference. Serum leukocyte and neutrophil counts were slightly raised and C-reactive protein moderately increased. On ultrasound there was flexor tenosynovitis of the 3rd right and 1st to 4th left hand-fingers and left common flexor tendon sheet. Candida albicans was isolated in synovial fluid cultures and the symptoms resolved with fluconazole. This is the first case reporting bilateral Candida tenosynovitis of the hand, highlighting the possible role of concealed hematogenous spread of opportunistic microorganisms in atypical clinical manifestations in immunocompromised patients.


Assuntos
Tenossinovite , Idoso , Candida albicans , Feminino , Dedos , Mãos/diagnóstico por imagem , Humanos , Tendões , Tenossinovite/tratamento farmacológico
9.
BioTech (Basel) ; 11(2)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35822783

RESUMO

L-asparaginase (ASNase) is an aminohydrolase currently used in the pharmaceutical and food industries. Enzyme immobilization is an exciting option for both applications, allowing for a more straightforward recovery and increased stability. High surface area and customizable porosity make carbon xerogels (CXs) promising materials for ASNase immobilization. This work describes the influence of contact time, pH, and ASNase concentration on the immobilization yield (IY) and relative recovered activity (RRA) using the Central Composite Design methodology. The most promising results were obtained using CX with an average pore size of 4 nm (CX-4), reaching IY and RRA of 100%. At the optimal conditions (contact time 49 min, pH 6.73, and [ASNase] 0.26 mg·mL-1), the ASNase-CXs biocomposite was characterized and evaluated in terms of kinetic properties and operational, thermal, and pH stabilities. The immobilized ASNase onto CX-4 retained 71% of its original activity after six continuous reaction cycles, showed good thermal stability at 37 °C (RRA of 91% after 90 min), and was able to adapt to both acidic and alkaline environments. Finally, the results indicated a 3.9-fold increase in the immobilized ASNase affinity for the substrate, confirming the potential of CXs as a support for ASNase and as a cost-effective tool for subsequent use in the therapeutic and food sectors.

12.
Mar Drugs ; 19(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34822494

RESUMO

Bioactive lipidic compounds of microalgae, such as polyunsaturated fatty acids (PUFA) and carotenoids, can avoid or treat oxidation-associated conditions and diseases like inflammation or cancer. This study aimed to assess the bioactive potential of lipidic extracts obtained from Gloeothece sp.-using Generally Recognized as Safe (GRAS) solvents like ethanol, acetone, hexane:isopropanol (3:2) (HI) and ethyl lactate. The bioactive potential of extracts was assessed in terms of antioxidant (ABTS•+, DPPH•, •NO and O2•assays), anti-inflammatory (HRBC membrane stabilization and Cox-2 screening assay), and antitumor capacity (death by TUNEL, and anti-proliferative by BrdU incorporation assay in AGS cancer cells); while its composition was characterized in terms of carotenoids and fatty acids, by HPLC-DAD and GC-FID methods, respectively. Results revealed a chemopreventive potential of the HI extract owing to its ability to: (I) scavenge -NO• radical (IC50, 1258 ± 0.353 µg·mL-1); (II) inhibit 50% of COX-2 expression at 130.2 ± 7.4 µg·mL-1; (III) protect 61.6 ± 9.2% of lysosomes from heat damage, and (IV) induce AGS cell death by 4.2-fold and avoid its proliferation up to 40% in a concentration of 23.2 ± 1.9 µg·mL-1. Hence, Gloeothece sp. extracts, namely HI, were revealed to have the potential to be used for nutraceutical purposes.


Assuntos
Cianobactérias , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Organismos Aquáticos , Compostos de Bifenilo , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Picratos
13.
Syst Rev ; 10(1): 202, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238365

RESUMO

BACKGROUND: The pharmacological treatment of cardiovascular diseases and type 2 diabetes mellitus reduces the risk of cardiovascular events.; however, most patients do not adhere to the treatment. There are several self-reported measures for assessing medication adherence. Identifying the instruments with the best psychometric evidence is essential for selecting an accurate measure. The aim of this study is to critically assess, compare and synthesize the quality of the measurement properties of patient-reported outcome measures to access medication adherence among patients with cardiovascular diseases and/or type 2 diabetes mellitus. METHODS: This protocol is reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. The following databases will be searched: Web of Science, SCOPUS, PubMed, CINAHL, EMBASE, LILACS, PsycINFO and ProQuest. DISCUSSION: This review will provide a detailed assessment of the measurement properties of self-reported medication adherence instruments in patients with cardiovascular diseases and/or type 2 diabetes mellitus to support clinical practice and research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019129109.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Adesão à Medicação , Metanálise como Assunto , Psicometria , Revisões Sistemáticas como Assunto
14.
Healthcare (Basel) ; 9(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208830

RESUMO

Artificial intelligence (AI)-based solutions have revolutionized our world, using extensive datasets and computational resources to create automatic tools for complex tasks that, until now, have been performed by humans. Massive data is a fundamental aspect of the most powerful AI-based algorithms. However, for AI-based healthcare solutions, there are several socioeconomic, technical/infrastructural, and most importantly, legal restrictions, which limit the large collection and access of biomedical data, especially medical imaging. To overcome this important limitation, several alternative solutions have been suggested, including transfer learning approaches, generation of artificial data, adoption of blockchain technology, and creation of an infrastructure composed of anonymous and abstract data. However, none of these strategies is currently able to completely solve this challenge. The need to build large datasets that can be used to develop healthcare solutions deserves special attention from the scientific community, clinicians, all the healthcare players, engineers, ethicists, legislators, and society in general. This paper offers an overview of the data limitation in medical predictive models; its impact on the development of healthcare solutions; benefits and barriers of sharing data; and finally, suggests future directions to overcome data limitations in the medical field and enable AI to enhance healthcare. This perspective is dedicated to the technical requirements of the learning models, and it explains the limitation that comes from poor and small datasets in the medical domain and the technical options that try or can solve the problem related to the lack of massive healthcare data.

15.
BMC Cancer ; 21(1): 359, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823840

RESUMO

BACKGROUND: Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. METHODS: For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. RESULTS: In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. CONCLUSION: In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/genética , Mucina-2/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Adulto Jovem
16.
J Clin Med ; 10(3)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494396

RESUMO

Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach-SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography-Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overrepresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell-cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer's and Parkinson's, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.

17.
Pharmaceutics ; 12(8)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751818

RESUMO

The development of printable hydrogel inks for extrusion-based 3D printing is opening new possibilities to the production of new and/or improved pharmaceutical forms, specifically for topical application. Alginate and starch are natural polysaccharides that have been extensively exploited due to their biocompatibility, biodegradability, viscosity properties, low toxicity, and relatively low cost. This research work aimed to study the physicochemical and release kinetic effects of starch incorporation in alginate-based 3D hydrogel patches for topical delivery using a quality by design approach. The incorporation of a pregelatinized starch is also proposed as a way to improve the properties of the drug delivery system while maintaining the desired quality characteristics. Critical material attributes and process parameters were identified, and the sensitivity and adequacy of each parameter were statistically analyzed. The impact of alginate, starch, and CaCl2·2H2O amounts on relevant quality attributes was estimated crosswise. The amount of starch revealed a synergetic impact on porosity (p = 0.0021). An evident increase in the size and quantity of open pores were detected in the as printed patches as well as after crosslinking (15.6 ± 5.2 µm). In vitro drug release studies from the optimized alginate-starch 3D hydrogel patch, using the probe Rhodamine B, showed an initial high burst release, followed by a controlled release mechanism. The results obtained also showed that the viscoelastic properties, printing accuracy, gelation time, microstructure, and release rates can be modulated by varying the amount of starch added to the system. Furthermore, these results can be considered an excellent baseline for future drug release modulation strategies.

18.
An Acad Bras Cienc ; 92(2): e20191445, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785428

RESUMO

Sildenafil is a potent selective inhibitor of phosphosdiesterase-5 previously used in erectile dysfunction and subsequently approved in 2005 for pulmonary arterial hypertension treatment. Since oral administration of sildenafil shows pharmacokinetic problems with mean absolute bioavailability of 41%, the goal of this work was to develop a novel sildenafil self-emulsifying drug delivery system (SEDDS) for oral absorption improvement and management of dosage. One pharmaceutical solution and four SEDDS containing sildenafil were successfully obtained and SEDDS formed O/W nanoemulsion with droplet size less than 300 nm. The stability studies evidenced that the SEDDS containing 3.3% w/w of sildenafil yielded the best results. The safety of 2-pyrrolidone/isobutanol in oral formulations was assessed in mice and no lethality was achieved in the placebo groups with LD50 of 490 mg/Kg for SEDDS II-3.3, suggesting it as a safe excipient for humans. Therewithal, in silico studies using PBPK models provided the pharmacokinetic profile of sildenafil SEDDS. Subsequently, in silico evaluation indicated that the sildenafil SEDDS droplet size influenced its bioavailability, enhancing absorption, assuring a good pharmacokinetic profile. These findings suggest that the formulations developed here presented the potential to enhance drug oral absorption with the possibility to control drug dosage as they are liquid pharmaceutical formulations.


Assuntos
Hipertensão Arterial Pulmonar , Animais , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Emulsões , Humanos , Camundongos , Citrato de Sildenafila
19.
Acta Reumatol Port ; 45(1): 7-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32572015

RESUMO

Pain is a common feature of most rheumatic diseases and it is often the main reason for the patient to seek for a clinical appointment. Chronic pain has a major impact on patient's quality of life, being frequently associated with functional incapacity, sleep and mood disorders. This leads to absenteeism and heavy consumption of health resources, both representing huge burdens on national economy. Managing musculoskeletal pain is pivotal but can be challenging. The use of the available pharmaceutical armamentarium should be parsimonious. Opioids are strong analgesic drugs that mostly act through their agonist action on µ-receptors in the central nervous system. Opioid-related side effects are not negligible and are mediated through both central and peripheral opioid receptors. The use of opioids is well established in the treatment of oncologic pain but their role in the management of musculoskeletal pain is still controversial. Inflammatory rheumatic diseases, osteoarthritis, osteoporotic fractures, chronic low back pain and fibromyalgia represent diverse major rheumatic conditions that frequently lead to chronic pain. In order to standardize and optimize management of musculoskeletal chronic pain in these prevalent diseases, the Portuguese Rheumatology Society elaborated this position paper. The objectives were: a) to define the importance of pain assessment and classification; b) to guide patient selection, appropriate choice of opioids, their management, and raise awareness of their adverse effects; c) to review the existent data on possible indications of opioid therapy on rheumatic diseases.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Musculoesquelética/tratamento farmacológico , Medição da Dor/métodos , Doenças Reumáticas/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/diagnóstico , Esquema de Medicação , Redução da Medicação/métodos , Fibromialgia/tratamento farmacológico , Humanos , Dor Lombar/tratamento farmacológico , Dor Musculoesquelética/diagnóstico , Osteoartrite/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Seleção de Pacientes , Portugal , Reumatologia , Sociedades Médicas
20.
Cancers (Basel) ; 12(2)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093282

RESUMO

Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6- cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs.

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