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Protein compartmentalization in the frame of a liquid-liquid phase separation is a key mechanism to optimize spatiotemporal control of biological systems. Such a compartmentalization process reduces the intrinsic noise in protein concentration due to stochasticity in gene expression. Employing Flory-Huggins solution theory, Avramov/Casalini's model, and the Grüneisen parameter, we unprecedentedly propose a cellular Griffiths-like phase (CGLP), which can impact its functionality and self-organization. The here-proposed CGLP is key ranging from the understanding of primary organisms' evolution to the treatment of diseases. Our findings pave the way for an alternative Biophysics approach to investigate coacervation processes.
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Unsaturated fatty acids (UFA) play a crucial role in central cellular processes in animals, including membrane function, development, and disease. Disruptions in UFA homeostasis can contribute to the onset of metabolic, cardiovascular, and neurodegenerative disorders. Consequently, there is a high demand for analytical techniques to study lipid compositions in live cells and multicellular organisms. Conventional analysis of UFA compositions in cells, tissues, and organisms involves solvent extraction procedures coupled with analytical techniques such as gas chromatography, MS and/or NMR spectroscopy. As a nondestructive and nontargeted technique, NMR spectroscopy is uniquely capable of characterizing the chemical profiling of living cells and multicellular organisms. Here, we use NMR spectroscopy to analyze Caenorhabditis elegans, enabling the determination of their lipid compositions and fatty acid unsaturation levels both in cell-free lipid extracts and in vivo. The NMR spectra of lipid extracts from WT and fat-3 mutant C. elegans strains revealed notable differences due to the absence of Δ-6 fatty acid desaturase activity, including the lack of arachidonic and eicosapentaenoic acyl chains. Uniform 13C-isotope labeling and high-resolution 2D solution-state NMR of live worms confirmed these findings, indicating that the signals originated from fast-tumbling lipid molecules within lipid droplets. Overall, this strategy permits the analysis of lipid storage in intact worms and has enough resolution and sensitivity to identify differences between WT and mutant animals with impaired fatty acid desaturation. Our results establish methodological benchmarks for future investigations of fatty acid regulation in live C. elegans using NMR.
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Caenorhabditis elegans , Ácidos Graxos Insaturados , Animais , Caenorhabditis elegans/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/análise , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Lipídeos/análise , Lipídeos/químicaRESUMO
BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.
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Transplante de Fígado , Soluções para Preservação de Órgãos , Preservação de Órgãos , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Preservação de Órgãos/métodos , Perfusão/métodos , Perfusão/instrumentação , Estudo de Prova de Conceito , Oxigênio , Fígado/cirurgia , Trifosfato de Adenosina , Idoso , Adulto , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Isquemia FriaRESUMO
Ash emission from volcanic eruptions affects the environment, society, and human health. This study shows the total concentration and lung bioaccessible fraction of eight potential toxic metal(loid)s in five Popocatépetl ashfall samples. Mineralogical phases and particle size distribution of the ashfall were analyzed by X-ray diffraction (XRD) and Scanning Electron Microscope (SEM) techniques, respectively. The bioaccessibility test of Gamble solution (GS) and Artificial Lysosomal Fluid (ALF) were conducted to simulate extracellular (pH 7) and intracellular (pH 4.5) conditions, respectively. The studied metal(loid)s showed the following total concentration (mg kg-1): 1.98 (As), 0.17 (Cd), 134.09 (Cr), 8.66 (Cu), 697.33 (Mn), 55.35 (Ni), 8.77 (Pb), and 104.10 (Zn). Geochemical indices suggested that some metal(loid)s are slightly enriched compared to the local soil background concentrations. Several mineralogical phases were identified in the collected ashfall deposits, such as plagioclase, pyroxene, and Fe-Ti oxide, among others. According to the risk assessment results, the non-carcinogenic risk related to ashfall exposure returns an HQ > 1 for children. In contrast, the estimation of carcinogenic risk was found to be within the tolerable limit. Metal(loid)s showed low bioaccessibility (< 30%) in GS and ALF, with the highest values found in ALF solution for As (12.18%) and Cu (7.57%). Despite their metal-bioaccessibility, our findings also showed that dominant ash particle size ranged between fine (< 2.5 µm) and extremely fine (< 1 µm), considered highly inhalable fractions. The results obtained in this work indicate that volcanic ashes are bioinsoluble and biodurable, and exhibit low bioaccessibility when in contact with lung human fluids.
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Erupções Vulcânicas , Medição de Risco , Humanos , México , Disponibilidade Biológica , Tamanho da Partícula , Pulmão/metabolismo , Pulmão/química , Monitoramento Ambiental/métodos , Microscopia Eletrônica de Varredura , Metais/análise , Difração de Raios X , Exposição Ambiental , Poluentes Atmosféricos/análiseRESUMO
OBJECTIVE: To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). ANIMALS: 6 adult University owned horses. METHODS: Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1ß, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-ß1) using immunoassays. Plasma was evaluated for drug concentrations. RESULTS: No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). CLINICAL RELEVANCE: Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted.
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4-Butirolactona , Anti-Inflamatórios não Esteroides , Citocinas , Peptídeos e Proteínas de Sinalização Intercelular , Fenilbutazona , Plasma Rico em Plaquetas , Sulfonas , Animais , Cavalos/sangue , 4-Butirolactona/análogos & derivados , 4-Butirolactona/administração & dosagem , 4-Butirolactona/farmacologia , Citocinas/sangue , Sulfonas/administração & dosagem , Sulfonas/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Fenilbutazona/administração & dosagem , Fenilbutazona/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Administração Oral , Masculino , Estudos Cross-Over , FemininoRESUMO
Resumo Fundamento Não houve evidência científica sobre o tratamento inicial com solução salina hipertônica (SSH) na insuficiência cardíaca agudamente descompensada (ICAD). Objetivos Este estudo avaliou o impacto do uso de SSH junto com um diurético de alça (DA) como o primeiro tratamento diurético para ICAD, com foco na função renal, níveis de eletrólitos e resultados clínicos. Métodos Neste estudo retrospectivo de caso-controle, 171 pacientes adultos (93 mulheres/78 homens) com ICAD foram incluídos entre 1º de janeiro de 2022 e 31 de dezembro de 2022. Os pacientes foram alocados em dois grupos: combinação inicial de SSH+DA e DA padronizada. O desfecho primário foi piora da função renal (PFR). A hospitalização por IC e a mortalidade por todas as causas foram avaliadas durante 6 meses de acompanhamento. O nível de significância adotado na análise estatística foi de 5%. Resultados Os grupos exibiram semelhanças nas características basais. Diurese significativamente maior no 1º dia (3975 [3000-5150] vs. 2583 [2000-3250], p=0,001) e natriurese na 2ª hora (116,00 [82,75-126,00] vs. 131,75-140,00] vs. 94,00-103,25] vs. 99,00 [96,00-103,00], p=0,295), TFG (48,50 [29,75-72,50 vs. 50,00[35,50-63,50, p=0,616) e creatinina (1,20 [0,90-1,70] vs. 1,20 [1,00-1,50], p=0,218) permaneceu estável no grupo SSH combinado inicial quando comparado ao grupo DA padronizado (Cl-: 102,00[99,00-106,00] vs. 98,00[95,00-103,00], p=0,001, TFGe: 56,00 [41,00-71,00] vs. 55,00[35,00-71,00], p=0,050, creatinina: 1,10[0,90-1,40] vs. 1,20 [0,90-1,70], p=0,009). A piora da função renal (16,1% vs. 35,5%, p = 0,007) e o tempo de internação hospitalar (4 dias [3-7] vs. 5 dias [4-7], p = 0,004) foram menores na combinação inicial SSH+DA em comparação com o DA padronizado. A mortalidade hospitalar, a hospitalização por IC e a mortalidade por todas as causas foram semelhantes entre os dois grupos. Conclusão SSH como terapia inicial, quando combinada com DA, pode proporcionar uma diurese segura e eficaz sem prejudicar a função renal na ICAD. Portanto, a SSH pode levar a um menor tempo de internação hospitalar para esses pacientes.
Abstract Background There was no scientific evidence about the initial treatment of hypertonic saline solution (HSS) in acutely decompensated heart failure (ADHF). Objectives This study assessed the impact of using HSS along with a loop diuretic (LD) as the first diuretic treatment for ADHF, focusing on renal function, electrolyte levels, and clinical outcomes. Methods In this retrospective case-control study, 171 adult patients (93 females/78 males) with ADHF were included between January 1, 2022, and December 31, 2022. Patients were allocated into two groups: upfront combo HSS+LD and standardized LD. The primary endpoint was worsening renal function (WRF). Hospitalization for HF and all-cause mortality were evaluated during 6 months of follow-up. The significance level adopted in the statistical analysis was 5%. Results The groups exhibited similarities in baseline characteristics.A significantly higher diuresis on the 1st day (3975 [3000-5150] vs. 2583 [2000-3250], p=0.001) and natriuresis on the 2nd hour (116.00 [82.75-126.00] vs. 68.50 [54.00-89.75], p=0.001) in the initial upfront combo HSS+LD were found in comparison with the standardized LD.When compared to the standardized LD, the utilization of HSS led to an increase in serum Na+ (137.00 [131.75-140.00] vs. 140.00 [136.00-142.25], p=0.001 for upfront combo HSS, 139.00 [137.00-141.00] vs. 139.00 [136.00-140.00], p=.0470 for standardized LD), while chloride (99.00 [94.00-103.25] vs. 99.00[96.00-103.00], p=0.295), GFR (48.50 [29.75-72.50 vs. 50.00 [35.50-63.50, p=0.616), and creatinine (1.20 [0.90-1.70] vs. 1.20 [1.00-1.50], p=0.218) remained stable in the upfront combo HSS group when compared to standardized LD group (Cl-: 102.00 [99.00-106.00] vs. 98.00 [95.00-103.00], p=0.001, eGFR: 56.00 [41.00-71.00] vs. 55.00 [35.00-71.00], p=0.050, creatinine:1.10 [0.90-1.40] vs. 1.20 [0.90-1.70], p=0.009). Worsening renal function (16.1% vs 35.5%, p=0.007), and length of stay in the hospital (4 days [3-7] vs. 5 days [4-7], p=0.004) were lower in the upfront combo HSS+LD in comparison with the standardized LD. In-hospital mortality, hospitalization for HF, and all-cause mortality were similar between the two groups. Conclusion HSS as an initial therapy, when combined with LD, may provide a safe and effective diuresis without impairing renal function in ADHF. Therefore, HSS may lead to a shorter length of stay in the hospital for these patients.
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The change in the corrosion activities of SS304 and the carbon steel A36 were studied during their exposure for 30 days to hybrid pumice-Portland cement extract (CE), to simulate the concrete-pore environment. The ionic composition and the initial pH (12.99) of the CE were influenced by the reduction of Portland cement (PC) content, volcanic pumice oxides and alkaline activators. Because of the air CO2 dissolution, the pH decreased and maintained a constant value ≈ 9.10 (established dynamic ionic equilibrium). The CE promoted the passivation of both steels and their free corrosion potential (OCP) reached positive values. On the surfaces, Fe and Cr oxides were formed, according to the nature of the steel. Over the time of exposure, the presence of chloride ions in the pumice caused a localized pitting attack, and for carbon steel, this fact may indicate an intermediate risk of corrosion. The chloride effect was retarded by the accumulation of SO42- ions at the steel surfaces. Based on electrochemical impedance (EIS), the polarization resistance (Rp) and the thickness of the passive layers were calculated. Their values were compared with those previously reported for the steels exposed to CEs of Portland and supersulfated cements, and the hybrid cement was considered as a PC "green" alternative.
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The banana tree circle (BTC) is a low-cost system for local greywater management, using a natural treatment and disposal process, providing additional resource recovery benefits. However, there are no standard design criteria for BTC that would allow for quality control of its efficiency and sustainability, and little is currently known about the full-scale performance of BTC. Based on the scoping literature review of 31 documents in the scientific database and eight documents from grey literature, a standard design model was proposed for the BTC technology based on the concept of water balance, greywater flows, rain, infiltration, and evapotranspiration. The first two steps of the BTC design were determining the areas required for infiltration and evapotranspiration. A cylindrical form trench, the soil percolation rate, and the hydraulic loading rate were considered for the infiltration area. The banana trees' evapotranspiration rate was taken into consideration for the evapotranspiration area. The proposed model was applied in a case study where we used a trench with 0.8 m depth and 1.5 m diameter. This study proposes a standard design criterion for the BTC based on environmental factors, and the scoping of the literature provides the basis for future studies to evaluate its environmental sustainability.
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Modelos Teóricos , Musa , Conservação dos Recursos Naturais/métodos , Eliminação de Resíduos Líquidos/métodos , ÁrvoresRESUMO
Rhodamines constitute a class of dyes extensively investigated and applied in various contexts, primarily attributed to their high luminescence quantum yield. This study delves into the impact of aggregation on the thermal and optical properties of Rhodamine 6G (R-6G) solutions in distilled water. Examined properties encompass thermal diffusivity (D), temperature coefficient of the refractive index (dn/dT), fluorescence quantum efficiency (η), and energy transfer (ET). These parameters were assessed through thermal lens (TL) and conventional absorption and emission spectroscopic techniques. The dimerization of R-6G solutions was revisited, revealing that an increase in R-6G concentration alters the features of absorption and emission spectra due to dimer formation, resulting in unexpected behavior of η. Consequently, we introduce a novel model for the fraction of absorbed energy converted into heat (φ), which accounts for emissions from both monomers and dimers. Employing this model, we investigate and discuss the concentration-dependent behaviors of η for monomers (ηm) and dimers (ηd). Notably, our findings demonstrate that ηm values necessitate ηd = 0.2, a relatively substantial value that cannot be disregarded. Additionally, applying the Förster theory for dipole-dipole electric ET, we calculate microparameters for ET between monomers (CDD) and monomer-dimer (CDA). Critical ranges for ET in each case are quantified. Microparameter analysis indicates that ET between monomer-monomer and monomer-dimer species of R-6G dissolved in distilled water holds significance, particularly in determining ηm. These results bear significance, especially in scenarios involving high dye concentrations. While applicable to R-6G in water, similar assessments in other media featuring aggregates are encouraged.
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OBJECTIVE: Strategies to increase readiness to change may enhance community-based substance use treatment outcomes. This study evaluated the effect of solution-focused brief therapy (SFBT) on readiness to change and substance use compared to treatment as usual (TAU) in a Brazilian community-based substance use treatment center. METHODS: One hundred two adults (M = 36.79, SD = 10.29) were quasi-randomized into SFBT or TAU groups. Assessments were completed at baseline, post-test, and 1-month follow-up. The primary outcome was the changes in readiness to change at post-test and 1-month follow-up. The secondary outcome was the change in substance use at 1-month follow-up. RESULTS: Through Quade non-parametric analysis of covariance (ANCOVA), both groups decreased tobacco, alcohol, and cocaine/crack use at 1-month follow-up, but SFBT had greater reductions in alcohol use (p = .05). ANCOVA analysis demonstrated no differences between groups on readiness to change at any time point. However, among participants who used multiple substances (n = 59), SFBT showed higher readiness to change at post-test (p = .05). CONCLUSIONS: These findings strengthen the evidence that SFBT holds promise for positive community-based substance use treatment outcomes.
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INTRODUCTION: Severe mental disorders can cause significant and lasting distress for patients and their families and generate high costs through the need for care and loss of productivity. This study tests DIALOG+, an app-based intervention to make routine patient-clinician meetings therapeutically effective. It combines a structured evaluation of patient satisfaction with a solution-focused approach. METHODS: We conducted a qualitative study, based on a controlled clinical trial, in which 9 psychiatrists and 18 patients used DIALOG+ monthly over a six-month period. Semi-structured interviews were used to explore the experiences of participants and analysed in an inductive thematic analysis focusing on the feasibility and effects of the intervention in the Colombian context. RESULTS: Experiences were grouped into five overall themes: a) impact of the intervention on the consultation and the doctor-patient relationship; b) impact on patients and in promoting change; c) use of the supporting app, and d) adaptability of the intervention to the Colombian healthcare system. CONCLUSIONS: DIALOG+ was positively valued by most of the participants. Participants felt that it was beneficial to the routine consultation, improved communication and empowered patients to take a leading role in their care. More work is required to identify the patient groups that most benefit from DIALOG+, and to adjust it, particularly to fit brief consultation times, so that it can be rolled out successfully in the Colombian healthcare system.
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Assistência Ambulatorial , Transtornos Mentais , Satisfação do Paciente , Relações Médico-Paciente , Humanos , Colômbia , Transtornos Mentais/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Assistência Ambulatorial/organização & administração , Assistência Ambulatorial/métodos , Aplicativos Móveis , Entrevistas como Assunto , Pesquisa Qualitativa , Comunicação , Índice de Gravidade de Doença , Adulto JovemRESUMO
Formic acid is utilized to induce esterification and chemical gelatinization in starch, particularly in the fabrication of electrospun fibers for nanomaterial production. This study investigated the impact of different concentrations (15, 20, 25, and 30 %) of cassava starch and formic acid as a solvent on the characteristics of the resultant polymeric solutions and electrospun fibers. Morphology, size distribution, thermogravimetric properties, diffraction patterns, and relative crystallinity were evaluated for the electrospun fibers. The amylose content of starch varied from 16.5 to 23.7 %, decreasing with esterification, achieving a degree of substitution of approximately 0.93. The solution-rheology exhibited elastic behavior, with viscosity increasing as starch concentration increased, hindering the fabrication of fibers at 25 and 30 % starch. Successful electrospun fibers were formed using 15 % and 20 % starch, displaying homogeneous morphologies with mean diameters of 165 nm and 301 nm, respectively. Esterification influenced thermogravimetric properties, leading to fibers with reduced degradation temperatures and mass loss compared to native starches. The electrospun fibers presented an amorphous structure, indicating a drastic reduction in relative crystallinity from 35.2 % in native starch to 8.5 % for esterified starches. This study highlights the intricate relationship between starch concentration, esterification, and solution viscosity, affecting the electrospinnability and properties of starch-polymeric solutions.
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Formiatos , Manihot , Amido , Manihot/química , Esterificação , Formiatos/química , Amido/química , Viscosidade , Amilose/química , Reologia , TermogravimetriaRESUMO
OBJECTIVE: Evaluate the color and translucency of a nanoceramic resin subjected to hygiene practices and immersion in coffee over time. MATERIALS AND METHODS: Specimens (n = 80, HT and LT, 0.5-mm thick) of a nanoceramic resin were obtained and were divided in groups according to the simulated oral hygiene: no intervention (NT), brushing with an electric brush and water (BN), brushing with an electric brush and toothpaste for 10 s (BT), and immersion in mouthwash for 30 s (MW). Oral hygiene practices were repeated after staining in coffee solution for 15, 48, 336, 1440, 8640, and 35,040 min. Spectral wavelengths were recorded with a spectrophotometer at each time. ∆E00, ∆L', ∆C', ∆H', and TP00 were calculated by CIEDE2000 and were evaluated by 2-way ANOVA, repeated measures ANOVA, and Tukey's HSD test (α = 0.05). RESULTS: ANOVA showed significance among factors for ΔE00 (p < 0.05), with higher ΔE00 for NT-HT (11.7) and NT-LT (11.2). After T6 (2-year simulation), the lowest values were found for BT-HT (5.3) and BT-LT (4.9). All groups showed a reduction in lightness and translucency and increased chroma and hue. However, the smallest variations were found in the BT groups (p < 0.05). CONCLUSIONS: Brushing with toothpaste effectively minimized the color change of NCRs caused by coffee staining. CLINICAL SIGNIFICANCE: Oral hygiene practices, such as brushing with toothpaste, might be important to minimize staining of nanoceramic resin restorations, especially in patients who frequently consume coffee.
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Café , Cor , Higiene Bucal , Cerâmica/química , Humanos , Espectrofotometria , Escovação Dentária , Cremes Dentais/químicaRESUMO
Background: Myocardial protection is crucial for successful cardiac surgery, as it prevents heart muscle damage that can occur during the procedure. Prolonged hypoxia without proper protection can lead to adenosine triphosphate consumption, microvilli loss, blister formation, and edema. Custodiol, del Nido, and modified del Nido are single-dose cardioplegic solutions with proven safety and significance in modern surgery. While each has been independently assessed for patient outcomes, limited research directly compares them. This study aims to compare their myocardial protection using histological analysis. Methods: In a double-blind clinical trial, at least 90 patients will be randomly assigned to receive one of the three cardioplegic solutions. Myocardial biopsies will be collected before cardiopulmonary bypass and 15 minutes after reperfusion. The surgical, anesthetic and perfusion techniques will be the same for all patients, following the Institution's standard protocols. Discussion: The ideal cardioplegic solution does not exist, and its selection remains challenging for surgeons. In modern surgical practice, understanding the behavior of these solutions and the ischemic tissue damage caused during induced cardiac arrest allows for safer surgical procedures. The results of this clinical trial can help in understanding the behavior of cardioplegic solutions and their tissue effects. Thus, by selecting the best cardioplegic solution, ischemic damage can be minimized, enhancing the effectiveness of this essential technique in cardiac procedures. The study may aid in implementing clinical protocols in several institutions, aiming to choose the solution with a superior myocardial protection profile, increasing safety, and reducing expenses. Trial Registration: Brazilian Clinical Trials Registry (ReBEC, http://ensaiosclinicos.gov.br/): RBR-997tqhh. Registered: January 26th, 2022.
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OBJECTIVE: To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). ANIMALS: 6 adult university-owned horses. METHODS: For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was repeated using a crossover design. For the second phase, following at least a 2-week washout period, the study protocol was repeated with phenylbutazone (1 g) or firocoxib (57 mg) administered orally. Plasma was collected 6 hours after administration for evaluation of drug concentrations, and APS and PRP were analyzed for concentrations of drug, platelets, leukocytes, and several growth factors and cytokines (PDGF, fibroblast growth factor, TGF-ß1, IL-1ß, IL-10, IL-6, IL-8, and tumor necrosis factor-α) before and 6 hours after administration of NSAIDs using immunoassays. RESULTS: There were no significant differences in concentrations of cytokines or growth factors before or after administration of any NSAID. There were significant differences in concentrations of leukocytes and platelets based on both product and time. NSAID concentrations in plasma were not significantly different from concentrations in APS and PRP. CLINICAL RELEVANCE: These results help guide clinicians on the appropriate use of these NSAIDs in conjunction with the processing of APS and PRP, which is unlikely to significantly alter the final product after single-dose administration.
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Anti-Inflamatórios não Esteroides , Citocinas , Cavalos , Plasma Rico em Plaquetas , Animais , 4-Butirolactona/administração & dosagem , 4-Butirolactona/efeitos adversos , 4-Butirolactona/análogos & derivados , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Citocinas/sangue , Citocinas/metabolismo , Cavalos/sangue , Cavalos/metabolismo , Cetoprofeno/administração & dosagem , Cetoprofeno/efeitos adversos , Fenilbutazona/administração & dosagem , Fenilbutazona/efeitos adversos , Plasma Rico em Plaquetas/metabolismo , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Distribuição AleatóriaRESUMO
There is a growing emphasis on seeking stabilizing agents with minimal transformation, prioritizing environmentally friendly alternatives, and actively contributing to the principles of the circular economy. This research aimed to assess the stability of a novel spray-dried hydrocolloid from high Andean algae when introduced into an aqueous solution. Nostoc sphaericum freshwater algae were subject to atomization, resulting in the production of spray-dried hydrocolloid (SDH). Subsequently, suspension solutions of SDH were meticulously prepared at varying pH levels and gelling temperatures. These solutions were then stored for 20 days to facilitate a comprehensive evaluation of their stability in suspension. The assessment involved a multifaceted approach, encompassing rheological analysis, scrutiny of turbidity, sedimentation assessment, ζ-potential, and measurement of particle size. The findings from these observations revealed that SDH exhibits a dilatant behavior when in solution, signifying an increase in with higher shear rate. Furthermore, it demonstrates commendable stability when stored under ambient conditions. SDH is emerging as a potential alternative stabilizer for use in aqueous solutions due to its easy extraction and application.
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Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.
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Neoplasias Ósseas , Osteossarcoma , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Animais , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Eliminação Renal , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Osteossarcoma/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Endotoxin contamination is a threat to the safety of pharmaceutical products, especially parenteral drugs. Any sterile and/or pyrogen-free pharmaceutical product requires regulatory specifications to ensure safe patient use. This study covers the performance evaluation study of an endotoxin quantitation commercial kit by recombinant Factor C (rFC), Endozyme II® Go, for 0.9% sodium chloride injection. The samples were spiked with endotoxin solutions between 0.0005 and 10 EU/mL and tested by the rFC kit to evaluate precision, accuracy, detection and quantification limits, linearity, and robustness. Each of the six points was assayed at least five times.The relative standard deviation for precision testing ranged from 1.9 to 8.3%. The recovery accuracy values of endotoxin were between 61% and 125% for the range from 0.005 to 10 EU/mL. The results demonstrated that the rFC method allows endotoxin quantification with accuracy, precision, specificity, and linearity for the range of 0.005 and 10 EU/mL for 0.9% sodium chloride injection. (AU)
A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral. (AU)
Assuntos
Técnicas In Vitro , Endotoxinas , Solução Salina , Cloreto de SódioRESUMO
In this work, we propose a novel approach for extracting Cu and Ni from vegetable oils (which can be expanded to other metals). The method is based on the transference of the analytes to an aqueous acid phase due to the disruption of a three-component solution. The extraction was carried out in two steps. In the first step, a three-component solution was prepared comprising the sample, 1-octanol, and HNO3 solution. Next, the homogeneous system was disrupted by adding 1.0 mL of deionized water, and two phases were formed. The aqueous extract deposited in the bottom of the flask was collected with a micropipette, and Cu and Ni were determined by graphite furnace atomic absorption spectrometry (GF AAS). The developed method presented limits of quantification (LOQ) of 0.25 and 0.17 ng g-1 for Cu and Ni, respectively, and was successfully applied in the analysis of eleven oil samples from different origins.