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1.
Clin Microbiol Rev ; 37(2): e0012423, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38775460

RESUMO

SUMMARYThis narrative review and meta-analysis summarizes a broad evidence base on the benefits-and also the practicalities, disbenefits, harms and personal, sociocultural and environmental impacts-of masks and masking. Our synthesis of evidence from over 100 published reviews and selected primary studies, including re-analyzing contested meta-analyses of key clinical trials, produced seven key findings. First, there is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Second, masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect. Third, respirators are significantly more effective than medical or cloth masks. Fourth, mask mandates are, overall, effective in reducing community transmission of respiratory pathogens. Fifth, masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation. Sixth, while there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably D/deaf people) are disadvantaged when others are masked. Finally, there are risks to the environment from single-use masks and respirators. We propose an agenda for future research, including improved characterization of the situations in which masking should be recommended or mandated; attention to comfort and acceptability; generalized and disability-focused communication support in settings where masks are worn; and development and testing of novel materials and designs for improved filtration, breathability, and environmental impact.


Assuntos
COVID-19 , Máscaras , Infecções Respiratórias , SARS-CoV-2 , Humanos , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/transmissão , COVID-19/prevenção & controle , COVID-19/transmissão , Dispositivos de Proteção Respiratória/normas
2.
Rev Physiol Biochem Pharmacol ; 184: 121-157, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35266054

RESUMO

Chitosan is a natural polysaccharide widespread in nature. It has many unique and attractive properties for the pharmaceutical field: it is biodegradable, safe, hypoallergenic, biocompatible with the body, free of toxicity, with proven anticholesterolemic, antibacterial, and antimycotic action. In this review we highlighted the physical, chemical, mechanical, mucoadhesive, etc. properties of chitosan to be taken into account when obtaining various pharmaceutical forms. The methods by which the pharmaceutical forms based on chitosan are obtained are very extensive, and in this study only the most common ones were presented.


Assuntos
Quitosana , Humanos , Quitosana/química , Preparações Farmacêuticas
3.
Mass Spectrom Rev ; 43(3): 560-609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37503656

RESUMO

The role of mass spectrometry (MS) has become more important in most application domains in recent years. Pharmaceutical analysis is specific due to its stringent regulation procedures, the need for good laboratory/manufacturing practices, and a large number of routine quality control analyses to be carried out. The role of MS is, therefore, very different throughout the whole drug development cycle. While it dominates within the drug discovery and development phase, in routine quality control, the role of MS is minor and indispensable only for selected applications. Moreover, its role is very different in the case of analysis of small molecule pharmaceuticals and biopharmaceuticals. Our review explains the role of current MS in the analysis of both small-molecule chemical drugs and biopharmaceuticals. Important features of MS-based technologies being implemented, method requirements, and related challenges are discussed. The differences in analytical procedures for small molecule pharmaceuticals and biopharmaceuticals are pointed out. While a single method or a small set of methods is usually sufficient for quality control in the case of small molecule pharmaceuticals and MS is often not indispensable, a large panel of methods including extensive use of MS must be used for quality control of biopharmaceuticals. Finally, expected development and future trends are outlined.


Assuntos
Produtos Biológicos , Descoberta de Drogas , Desenvolvimento de Medicamentos , Produtos Biológicos/química , Espectrometria de Massas/métodos , Preparações Farmacêuticas
4.
Mol Cell Proteomics ; 22(6): 100559, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37105363

RESUMO

The 2nd CASMS conference was held virtually through Gather. Town platform from October 17 to 21, 2022, with a total of 363 registrants including an outstanding and diverse group of scientists at the forefront of their research fields from both academia and industry worldwide, especially in the United States and China. The conference offered a 5-day agenda with an exciting scientific program consisting of two plenary lectures, 14 parallel symposia, and 4 special sessions in which a total of 97 invited speakers presented technological innovations and their applications in proteomics & biological mass spectrometry and metabo-lipidomics & pharmaceutical mass spectrometry. In addition, 18 invited speakers/panelists presented at 3 research-focused and 2 career development workshops. Moreover, 144 posters, 54 lightning talks, 5 sponsored workshops, and 14 exhibitions were presented, from which 20 posters and 8 lightning talks received presentation awards. Furthermore, the conference featured 1 MCP lectureship and 5 young investigator awardees for the first time to highlight outstanding mid-career and early-career rising stars in mass spectrometry from our society. The conference provided a unique scientific platform for young scientists (i.e., graduate students, postdocs and junior faculty/investigators) to present their research, meet with prominent scientists, and learn about career development and job opportunities (http://casms.org).


Assuntos
Espectrometria de Massas , Sociedades Científicas , Humanos , China , Preparações Farmacêuticas , Proteômica , Estados Unidos
5.
BMC Genomics ; 25(1): 130, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302916

RESUMO

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Relógios Circadianos/genética , Análise da Randomização Mendeliana , Comorbidade , Estudo de Associação Genômica Ampla , Peptidase 7 Específica de Ubiquitina , Proteínas Argonautas
6.
BMC Plant Biol ; 24(1): 765, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39123105

RESUMO

The present study focused on the physiological and biochemical aspects of Tricleocarpa fragilis, red seaweed belonging to the phylum Rhodophyta, along the South Andaman coast, with particular attention given to its symbiotic relationships with associated flora and fauna. The physicochemical parameters of the seawater at the sampling station, such as its temperature, pH, and salinity, were meticulously analyzed to determine the optimal harvesting period for T. fragilis. Seaweeds attach to rocks, dead corals, and shells in shallow areas exposed to moderate wave action because of its habitat preferences. Temporal variations in biomass production were estimated, revealing the highest peak in March, which was correlated with optimal seawater conditions, including a temperature of 34 ± 1.1 °C, a pH of 8 ± 0.1, and a salinity of 32 ± 0.8 psu. GC‒MS analysis revealed n-hexadecanoic acid as the dominant compound among the 36 peaks, with major bioactive compounds identified as fatty acids, diterpenes, phenolic compounds, and hydrocarbons. This research not only enhances our understanding of ecological dynamics but also provides valuable insights into the intricate biochemical processes of T. fragilis. The established antimicrobial potential and characterization of bioactive compounds from T. fragilis lay a foundation for possible applications in the pharmaceutical industry and other industries.


Assuntos
Rodófitas , Alga Marinha , Rodófitas/fisiologia , Rodófitas/metabolismo , Alga Marinha/fisiologia , Alga Marinha/metabolismo , Água do Mar/química , Ecossistema , Biomassa , Ácidos Graxos/metabolismo , Simbiose/fisiologia , Animais
7.
J Pediatr ; : 114251, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39181319

RESUMO

OBJECTIVES: To compare the number and incidence of Kawasaki disease (KD) patients in years 2 through 4 of the coronavirus disease 2019 (COVID-19) pandemic, and determine the impact of 3 years of implementation infection control measures and their subsequent relaxation on the epidemiology of KD in Japan. STUDY DESIGN: We conducted a population-based, cohort study including consecutive KD patients in Kobe City between 2021 and 2023. We compared the incidence of KD cases, in relation to timing of infection control measures, as well as infectious disease cases based on a regional surveillance system. Data from a previous 2016 through 2020 study were used for comparison. RESULTS: A total of 566 children with KD were identified during the study period. During the infection control period in 2021 to 2022, the incidence of KD remained low compared with the pre-pandemic level (281.3 and 327.5/100,000 children aged 0-4 years in 2021to 2022 and 2016 through 2019, respectively), but a recovery trend began in the 0-1-year age group. During the relaxation period in 2023, the incidence of KD increased across a wide age range, reaching the highest recorded in Japan (426.7/100,000 children aged 0-4 years), and the median age of onset increased to age 30 months. The resurgence of KD coincided with the patterns for multiple infectious diseases in 2023. The seasonality of KD observed before the pandemic was altered. CONCLUSIONS: KD resurged in 2023 after relaxation of the prolonged COVID-19 pandemic restrictions in Japan. This phenomenon coincided with the rise of multiple infectious diseases, and supports the pathogenesis of KD being triggered by infectious agents.

8.
J Med Virol ; 96(8): e29855, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39119991

RESUMO

Non-pharmaceutical interventions (NPIs) implemented to control SARS-CoV-2 have significantly influenced the activity of respiratory pathogens. This study investigated epidemiological changes among hospitalized patients with respiratory syncytial virus (RSV) before (2017-2019) and during (2020-2022) the COVID-19 pandemic in Hangzhou, China. We also examined viral load distribution across demographic and temporal variables. Nasopharyngeal swabs were collected and RSV loads were quantified using reverse transcriptase polymerase chain reaction (RT-qPCR). RSV epidemic characteristics, seasonal dynamics, and viral load distributions were compared between pre- and pandemic years. General linear models were employed to assess associations between viral loads and age. Among 19 742 cases, 1576 and 2092 tested positive during the pre- and pandemic years, respectively. From February to July 2020, the implementation of NPIs led to the cessation of RSV circulation. However, after these measures were relaxed, RSV cases resurged over two consecutive seasons during the pandemic, notably affecting older children compared to those in the pre-pandemic years (1.00 years, IQR: 0.50-2.00 vs. 0.58 years, IQR: 0.27-1.00, p < 0.001). Specifically, in 2021-2022, an off-season resurgence of RSV began earlier (mid-June), lasted longer (40 weeks), and involved more positive cases (1238 cases) than both 2020-2021 and pre-pandemic years. Viral load distribution demonstrated a clear age-related relationship in both pre- and pandemic years, with younger children consistently showing higher viral loads, independently of gender and season (all p-values for trends <0.001). These findings highlight the impact of NPIs on RSV epidemiology and underscore the need to prioritize RSV infection prevention in younger children from the perspective of viral load.


Assuntos
COVID-19 , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , SARS-CoV-2 , Estações do Ano , Carga Viral , Humanos , China/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , COVID-19/epidemiologia , COVID-19/virologia , Lactente , Pré-Escolar , Masculino , Feminino , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Criança , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Hospitalização/estatística & dados numéricos , Recém-Nascido , Criança Hospitalizada/estatística & dados numéricos , Adolescente , Nasofaringe/virologia
9.
Electrophoresis ; 45(1-2): 55-68, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37495859

RESUMO

Separation and identification of chiral molecules is a topic widely discussed in the literature and of fundamental importance, especially in the pharmaceutical and food fields, both from industrial and laboratory points of view. Several techniques are used to carry out these analyses, but high-performance liquid chromatography is often the "gold standard." The high costs of chiral columns, necessary for this technique, led researchers to look for an alternative, and capillary electrophoresis (CE) is a technique capable of overcoming some of the disadvantages of liquid chromatography, often providing comparable results in terms of sensitivity and robustness. We addressed this topic, already widely discussed in the literature, providing an overview of the last 6 years of the most frequent and recent applications of CE. To make the manuscript more effective, we decided to divide it into paragraphs that represent the main field of application, from enantioseparation in complex matrices (pharmacokinetic studies or toxicological dosage of drugs, analysis of environmental pollutants, and analyses of foods) to quality control analyses on pharmaceutical formulas. About these, which are the fields of most meaningful use, we mentioned some of the most innovative and performing methods, with a look to the future on the application of new materials used, such as chiral selectors, that can make these types of analyses accessible to all, reducing cost, time, and excessive use of toxic solvents.


Assuntos
Eletroforese Capilar , Eletroforese Capilar/métodos , Cromatografia Líquida , Estereoisomerismo , Cromatografia Líquida de Alta Pressão , Preparações Farmacêuticas
10.
Insect Mol Biol ; 33(5): 516-533, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38864655

RESUMO

Many species are threatened by climate change and must rapidly respond to survive in changing environments. Epigenetic modifications, such as DNA methylation, can facilitate plastic responses by regulating gene expression in response to environmental cues. Understanding epigenetic responses is therefore essential for predicting species' ability to rapidly adapt in the context of global environmental change. Here, we investigated the functional significance of different methylation-associated cellular processes on temperature-dependent life history in seed beetles, Callosobruchus maculatus Fabricius 1775 (Coleoptera: Bruchidae). We assessed changes under thermal stress in (1) DNA methyltransferase (Dnmt1 and Dnmt2) expression levels, (2) genome-wide methylation and (3) reproductive performance, with (2) and (3) following treatment with 3-aminobenzamide (3AB) and zebularine (Zeb) over two generations. These drugs are well-documented to alter DNA methylation across the tree of life. We found that Dnmt1 and Dnmt2 were expressed throughout the body in males and females, but were highly expressed in females compared with males and exhibited temperature dependence. However, whole-genome methylation did not significantly vary with temperature, and only marginally or inconclusively with drug treatment. Both 3AB and Zeb led to profound temperature-dependent shifts in female reproductive life history trade-off allocation, often increasing fitness compared with control beetles. Mismatch between magnitude of treatment effects on DNA methylation versus life history effects suggest potential of 3AB and Zeb to alter reproductive trade-offs via changes in DNA repair and recycling processes, rather than or in addition to (subtle) changes in DNA methylation. Together, our results suggest that epigenetic mechanisms relating to Dnmt expression, DNA repair and recycling pathways, and possibly DNA methylation, are strongly implicated in modulating insect life history trade-offs in response to temperature change.


Assuntos
Besouros , Metilação de DNA , Epigênese Genética , Reprodução , Animais , Besouros/genética , Besouros/fisiologia , Feminino , Reprodução/genética , Temperatura , Masculino , Citidina/análogos & derivados , Citidina/farmacologia , Mudança Climática
11.
Br J Psychiatry ; 224(6): 198-204, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38235531

RESUMO

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Reino Unido , Masculino , Idoso , Feminino , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade
12.
Crit Rev Toxicol ; : 1-15, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093553

RESUMO

Embryofetal development (EFD) studies are performed to characterize risk of drugs in pregnant women and on embryofetal development. In line with the ICH S5(R3) guideline, these studies are generally conducted in one rodent and one non-rodent species, commonly rats and rabbits. However, the added value of conducting EFD studies in two species to risk assessment is debatable. In this study, rat and rabbit EFD studies were evaluated to analyze the added value of a second species. Information on rat and rabbit EFD studies conducted for human pharmaceuticals submitted for marketing authorization to the European Medicines Agency between 2004 and 2022 was collected from the database of the Dutch Medicines Evaluation Board, along with EFD studies conducted for known human teratogens. In total, 369 compounds were included in the database. For 55.6% of the compounds similar effects were observed in rat and rabbit EFD studies. Discordance was observed for 44.6% of compounds. Discordance could often be explained based on occurrence of maternal toxicity or the compound's mechanism of action. For other compounds, discordance was considered of limited clinical relevance due to high exposure margins or less concerning EFD toxicity. For 6.2%, discordance could not be explained and was considered clinically relevant. Furthermore, for specific therapeutic classes, concordance between rat and rabbit could vary. In conclusion, in many cases the added value of conducting EFD studies in two species is limited. These data could help identify scenarios in which (additional) EFD studies could be waived or create a weight-of-evidence model to determine the need for (additional) EFD studies.

13.
Mol Pharm ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141824

RESUMO

This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B3) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC50 values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC50 parameter was determined against a model representative of crustaceans─Artemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.

14.
Mol Pharm ; 21(7): 3121-3143, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38814314

RESUMO

Environmental impacts of the industrial revolution necessitate adoption of sustainable practices in all areas of development. The pharmaceutical industry faces increasing pressure to minimize its ecological footprint due to its significant contribution to environmental pollution. Over the past two decades, pharmaceutical cocrystals have received immense popularity due to their ability to optimize the critical attributes of active pharmaceutical ingredients and presented an avenue to bring improved drug products to the market. This review explores the potential of pharmaceutical cocrystals as an ecofriendly alternative to traditional solid forms, offering a sustainable approach to drug development. From reducing the number of required doses to improving the stability of actives, from eliminating synthetic operations to using pharmaceutically approved chemicals, from the use of continuous and solvent-free manufacturing methods to leveraging published data on the safety and toxicology, the cocrystallization approach contributes to sustainability of drug development. The latest trends suggest a promising role of pharmaceutical cocrystals in bringing novel and improved medicines to the market, which has been further fuelled by the recent guidance from the major regulatory agencies.


Assuntos
Cristalização , Desenvolvimento de Medicamentos , Desenvolvimento de Medicamentos/métodos , Preparações Farmacêuticas/química , Indústria Farmacêutica/métodos , Humanos , Química Farmacêutica/métodos
15.
Mol Pharm ; 21(2): 916-931, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38235686

RESUMO

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.


Assuntos
Curcumina , Nanofibras , Preparações Farmacêuticas , Curcumina/química , Ritonavir , Sistemas de Liberação de Medicamentos , Polímeros/química , Liberação Controlada de Fármacos , Nanofibras/química
16.
Mol Pharm ; 21(6): 2949-2959, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38685852

RESUMO

Crystallization is a widely used purification technique in the manufacture of active pharmaceutical ingredients (APIs) and precursor molecules. However, when impurities and desired compounds have similar molecular structures, separation by crystallization may become challenging. In such cases, some impurities may form crystalline solid solutions with the desired product during recrystallization. Understanding the molecular structure of these recrystallized solid solutions is crucial to devise methods for effective purification. Unfortunately, there are limited analytical techniques that provide insights into the molecular structure or spatial distribution of impurities that are incorporated within recrystallized products. In this study, we investigated model solid solutions formed by recrystallizing salicylic acid (SA) in the presence of anthranilic acid (AA). These two molecules are known to form crystalline solid solutions due to their similar molecular structures. To overcome challenges associated with the long 1H longitudinal relaxation times (T1(1H)) of SA and AA, we employed dynamic nuclear polarization (DNP) and 15N isotope enrichment to enable solid-state NMR experiments. Results of solid-state NMR experiments and DFT calculations revealed that SA and AA are homogeneously alloyed as a solid solution. Heteronuclear correlation (HETCOR) experiments and plane-wave DFT structural models provide further evidence of the molecular-level interactions between SA and AA. This research provides valuable insights into the molecular structure of recrystallized solid solutions, contributing to the development of effective purification strategies and an understanding of the physicochemical properties of solid solutions.


Assuntos
Isótopos de Carbono , Cristalização , Espectroscopia de Ressonância Magnética , Isótopos de Nitrogênio , Ácido Salicílico , ortoaminobenzoatos , Espectroscopia de Ressonância Magnética/métodos , Ácido Salicílico/química , Cristalização/métodos , Isótopos de Nitrogênio/química , ortoaminobenzoatos/química , Isótopos de Carbono/química , Soluções/química , Estrutura Molecular
17.
Psychooncology ; 33(7): e6369, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38960607

RESUMO

OBJECTIVE: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis. METHODS: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. RESULTS: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis. CONCLUSION: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.


Assuntos
Serviços de Saúde Mental , Neoplasias da Próstata , Psicotrópicos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/terapia , Idoso , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Psicotrópicos/uso terapêutico , Austrália do Sul , Idoso de 80 Anos ou mais , Saúde Mental , Transtornos Mentais/epidemiologia , Transtornos Mentais/tratamento farmacológico , Sistema de Registros , Análise de Séries Temporais Interrompida , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos
18.
Extremophiles ; 28(2): 21, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38532228

RESUMO

Antarctica harbors a microbial diversity still poorly explored and of inestimable biotechnological value. Cold-adapted microorganisms can produce a diverse range of metabolites stable at low temperatures, making these compounds industrially interesting for biotechnological use. The present work investigated the biotechnological potential for antimicrobial and antitumor activity of filamentous fungi and bacteria isolated from marine sediment samples collected at Deception Island, Antarctica. A total of 89 microbial isolates were recovered from marine sediments and submitted to an initial screening for L-glutaminase with antitumoral activity and for antimicrobial metabolites. The isolates Pseudogymnoascus sp. FDG01, Pseudogymnoascus sp. FDG02, and Penicillium sp. FAD33 showed potential antiproliferative action against human pancreatic carcinoma cells while showing no toxic effect on non-tumor cells. The microbial extracts from unidentified three bacteria and four filamentous fungi showed antibacterial activity against at least one tested pathogenic bacterial strain. The isolate FDG01 inhibited four bacterial species, while the isolate FDG01 was active against Micrococcus luteus in the minimal inhibitory concentration of 0.015625 µg mL -1. The results pave the way for further optimization of enzyme production and characterization of enzymes and metabolites found and reaffirm Antarctic marine environments as a wealthy source of compounds potentially applicable in the healthcare and pharmaceutical industry.


Assuntos
Ascomicetos , Fungos , Humanos , Regiões Antárticas , Ascomicetos/metabolismo , Sedimentos Geológicos/microbiologia , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias/metabolismo , Preparações Farmacêuticas/metabolismo
19.
Ann Behav Med ; 58(1): 37-47, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37648242

RESUMO

BACKGROUND: To control infections, behavioral non-pharmaceutical interventions (NPIs) such as social distancing and hygiene measures (masking, hand hygiene) were implemented widely during the COVID-19 pandemic. At the same time, adherence to NPIs has also been implied in an increase in mental health problems. However, the designs of many existing studies are often poorly suited to disentangle complex relationships between NPI adherence, mental health symptoms, and health-related cognitions (risk perceptions, control beliefs). PURPOSE: To separate between- and temporal within-person associations between mental health, health-related cognitions, and NPI adherence. METHODS: Six-month ecological momentary assessment (EMA) study with six 4-day assessment bouts in 397 German adults. Daily measurement of adherence, mental health symptoms, and cognitions during bouts. We used dynamic temporal network analysis to estimate between-person, as well as contemporaneous and lagged within-person effects for distancing and hygiene NPIs. RESULTS: Distinct network clusters of mental health, health cognitions, and adherence emerged. Participants with higher control beliefs and higher susceptibility were also more adherent (between-person perspective). Within-person, similar findings emerged, additionally, distancing and loneliness were associated. Lagged findings suggest that better adherence to NPIs was associated with better mental health on subsequent days, whereas higher loneliness was associated with better subsequent hygiene adherence. CONCLUSIONS: Findings suggest no negative impact of NPI adherence on mental health or vice versa, but instead suggest that adherence might improve mental health symptoms. Control beliefs and risk perceptions are important covariates of adherence-both on between-person and within-person level.


Adhering to COVID protective behaviors might be less detrimental for mental health than some previous claims: Over 6 months in 2021­2022, adults from Germany who adhered to COVID protection recommendations (mask-wearing, hand hygiene, social distancing) on any one day reported better mental health the following days.


Assuntos
COVID-19 , Higiene das Mãos , Adulto , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias/prevenção & controle , Saúde Mental
20.
Br J Clin Pharmacol ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155240

RESUMO

Older adults are at risk of adverse drug events during transition of care from hospital to community, thus optimal communication about medications at discharge is essential. Standardization of medication discharge plan (MDP) is lacking. This study aimed to (1) create a standardized MDP for older adults using consensus-based principles, (2) create a short-version MDP and (3) generate a practical guide. Modified Delphi was used to establish consensus on guiding principles for the MDP. Additionally, participants were asked about guiding principles deemed most essential, patient prioritization, the format and mode of transmission of the MDP. Twenty-six guiding principles reached consensus, with 17 prioritized for a short-version MDP. The practical guide includes explanations of the guiding principles, criteria for patient selection and recommendations on the format and mode of transmission. The results of this study will assist implementation of MDPs when older adults are discharged from hospital.

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