Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 583
Filtrar
1.
Reprod Domest Anim ; 59(7): e14671, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005009

RESUMO

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1-3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen-thawed in vivo-produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p < .02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B-mode and Doppler-mode did not significantly predict pregnancy rates on D35 (p < .6 and p < .5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p < .08 and p < .06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p > .05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation.


Assuntos
Transferência Embrionária , Progesterona , Útero , Feminino , Animais , Bovinos/fisiologia , Transferência Embrionária/veterinária , Gravidez , Útero/irrigação sanguínea , Útero/diagnóstico por imagem , Progesterona/sangue , Ultrassonografia/veterinária , Corpo Lúteo/fisiologia , Taxa de Gravidez , Sincronização do Estro , Resultado da Gravidez/veterinária
2.
Environ Pollut ; : 124513, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002751

RESUMO

Aquatic biota are exposed to toxic substances resulting from human activities, reducing environmental quality and can compromise the health of the organisms. This study aimed to employ Danio rerio as an environmental bioindicator, analyzing the effects of water from distinct urban aquatic environments. An active biomonitoring system was set up to compare the temporal dynamics of histological biomarkers for gill and liver and the patterns of non-protein thiols (NPSH) in muscle in specimens exposed for 3, 6, and 12 days. Three large urban basins in the city of Campo Grande (Midwest of Brazil) were selected. Two sites are in a very populous area (i.e Lagoa and Bandeira) and another on in an area with agricultural activities (i.e Anhanduí). All the streams displayed distinct qualitative characteristics. The presence of metals, including Mn, Zn, Fe, and Al, as well as pH, temperature, and dissolved oxygen, accounted for 38% of the variability (PC1), while total solids, conductivity, ammonia, nitrite, and explained 24 % (PC2). Degree tissue changes index (DTC) in gill and the concentration of NPSH increased in all streams during 3, 6 and 12 days of exposure. DTC in liver increases in all exposure times in most populous stream (i.e Lagoa and Bandeira). Histopathological evidence in the gill, including proliferation, desquamation, and necrosis of the primary lamellar epithelium; fusion and aneurysms in the secondary lamellar epithelium were observed after three days of exposure. Degenerative nuclear figures were noted in the liver after three days of exposure, followed by hepatocellular hypertrophy, lipidosis, and necrosis at twelve days. Our findings showing time-dependent effects of urban aquatic environments in histopathological (i.e DTC) and biochemical biomarkers in zebrafish. The biomonitoring model enabled a comparison of the temporal dynamics of various health markers, using zebrafish as bioindicator. Future studies might use this experimental model and biomarkers for environmental biomonitoring program.

3.
Theriogenology ; 226: 302-307, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38959840

RESUMO

The aim of this study was to evaluate the superestimulatory and superovulatory responses of cattle treated with corifollitropin-alpha, a long-acting human recombinant FSH (rhFSH). In the first and second experiments, we used Nelore (Bos indicus) heifers previously submitted to follicular wave suppression by active immunization against GnRH. In Experiment 1 (a dose-response study), heifers (n = 20) were randomly allocated into five groups, which received placebo (saline) or a single sc dose of 7.5, 15.0, 22.5 or 30.0 µg rhFSH. The heifers were subjected to daily ovarian scan and blood sampling during 11 days. We observed group, time, and group x time effects (P<0.0001) for both average follicle size and circulating FSH concentrations, with a strong correlation (R = 0.82, P<0.0001) between the area under curve (AUC) for both parameters. The peak concentration of FSH 24h after treatment and average follicle size at all timepoints, however, were similar (P>0.05) between groups 22.5 and 30.0 µg. In Experiment 2, heifers (n = 18) were allocated into three groups, which received (0h) either placebo (control), 25 µg rhFSH or 130 mg pFSH (Folltropin). There was no difference (P>0.05) in average follicle size at any moment, as well as in intrafollicular E2 at 120h or in plasma P4 seven days later between groups rhFSH and pFSH. In Experiment 3, cycling Nelore heifers (n = 20) were subjected to a wave synchronization protocol and superovulated (day 0) using a standard pFSH protocol (120 mg split in eight decreasing im doses) or with a single sc injection of 20 µg rhFSH. The number of follicles >7 mm on day 4 did not differ (P=0.4370). Heifers receiving rhFSH had greater average follicle size on day 4 (P=0.0005), ovulation rate (P<0.0001), and number of CL (P=0.0155), as well as a trend towards a greater number of ova (P=0.07) and viable embryos (P=0.0590). In Experiment 4, superovulation was induced with a single sc injection of 25 µg rhFSH in Girolando and Nelore cows and heifers (n = 20). None of the embryo yield endpoints differed between the two breeds (P>0.05). In conclusion, cattle superstimulation and superovulation can be successfully induced with a single dose of a long-acting rhFSH (corifollitropin-alpha).


Assuntos
Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante Humano , Ovário , Superovulação , Bovinos , Animais , Feminino , Superovulação/efeitos dos fármacos , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Foliculoestimulante Humano/farmacologia , Ovário/efeitos dos fármacos , Meia-Vida , Gravidez , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/administração & dosagem , Humanos
4.
Artigo em Inglês | MEDLINE | ID: mdl-39012306

RESUMO

BACKGROUND: Overweight and obesity are major public health issues with increasing incidence and prevalence, affecting more than 50% of the population in developed countries. Due to its complex pathophysiology and multifactorial etiology, disease understanding, diagnostic approach and management remain suboptimal. Together with a structured nutritional intervention and physical activity plan, pharmacological treatment has the potential to magnify weight loss and health related benefits. Liraglutide is one of the most effective and frequently prescribed weight loss medication. Its efficacy and safety have been demonstrated in randomized clinical trials, however, real world data in Portugal is scarce. The authors report on the experience of a University Hospital Endocrine Clinic in the management of patients with overweight and obesity with liraglutide on top of lifestyle intervention. The aim of the study was to evaluate the effectiveness of liraglutide in the management of overweight and obesity. METHODS: Retrospective, longitudinal observational study. Inclusion criteria were adult patients (>18 years old) with obesity (BMI>30 kg/m2) or overweight (≥27 kg/m2) with at least one obesity related co-morbidity (hypertension, dyslipidemia, obstructive sleep apnea, non-alcoholic fatty liver disease) with at least three months of liraglutide treatment. Diabetes diagnosis and prior bariatric surgery were exclusion criteria. Demographic and clinical variables were included and weight was recorded before and after at least 3 months of liraglutide treatment. RESULTS: One hundred forty-eight patients (85.8% females) with a mean age of 48.7±11.9 years were treated with liraglutide. Mean baseline BMI was 33.8±5.2 kg/m2 and median follow-up was 13 months. At the last appointment, 85.8% were still taking liraglutide. Among patients still taking liraglutide, mean weight loss was 7.6 kg (7.9%), with significantly greater losses in patients treated for more than 6 months (8.6kg vs. 6.2 kg, P=0.016). Patients with obesity lost significantly more weight than overweight patients (8.3 kg vs. 4.5 kg, P=0.028), despite similar treatment duration. The reasons for liraglutide withdrawal were gastrointestinal intolerance (7), medication cost (2), inefficacy (10) and physician instructions (1). CONCLUSIONS: The present study documents the long-term efficacy of liraglutide in the treatment of patients with overweight and obesity, with a low rate of drug withdrawal. Mean weight loss was significant and more evident from the 6th month of treatment on. Liraglutide, along with lifestyle intervention, is a good option for weight management in the majority of patients with obesity.

5.
Sao Paulo Med J ; 142(6): e2023349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38896746

RESUMO

BACKGROUND: Congenital Anomalies of the Upper Limb (CAUL) are a group of structural or functional abnormalities that develop during intrauterine life and can lead to limb dysfunction. OBJECTIVES: To analyze the prevalence of congenital anomalies of the upper limbs in Brazil and assess maternal and neonatal variables. DESIGN AND SETTING: A cross-sectional, descriptive study was conducted on congenital upper limb malformations among live births across Brazil. METHODS: The study spanned from 2010 to 2019. Data were sourced from the Department of Informatics of the Unified Health System (DATASUS) and the Live Birth Information System (SINASC) portal. Analyses focused on the information reported in field 41 of the Live Birth Declaration Form entered into the computerized system. RESULTS: The most common anomaly in Brazil was supernumerary fingers, classified as ICD-Q69.0, affecting 11,708 children, with a prevalence of 4.02 per 10,000 live births. Mothers aged over 40 years had a 36% higher prevalence of having children with CAUL than mothers under 40 years old (OR = 1.36; 95% CI 1.19-1.56). Newborns weighing ≥ 2,499 g were 2.64 times more likely to have CAUL compared to those weighing ≥ 2,500 g (OR = 2.64; 95% CI 2.55-2.73). CONCLUSION: There was an observed increase in the reporting of CAUL cases over the decade studied. This trend serves as an alert for health agencies, as understanding the prevalence of CAUL and its associated factors is crucial for preventive medicine.


Assuntos
Deformidades Congênitas das Extremidades Superiores , Humanos , Brasil/epidemiologia , Estudos Transversais , Prevalência , Feminino , Recém-Nascido , Masculino , Adulto , Deformidades Congênitas das Extremidades Superiores/epidemiologia , Adulto Jovem , Idade Materna , Extremidade Superior
6.
J Xenobiot ; 14(2): 772-797, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38921653

RESUMO

Substituted phenethylamines including 2C (2,5-dimethoxyphenethylamines) and NBOMe (N-(2-methoxybenzyl)phenethylamines) drugs are potent psychoactive substances with little to no knowledge available on their toxicity. In the present in vitro study, we explored the mechanisms underlying the neurotoxicity of six substituted phenethylamines: 2C-T-2, 2C-T-4, 2C-T-7 and their corresponding NBOMes. These drugs were synthesized and chemically characterized, and their cytotoxicity (0-1000 µM) was evaluated in differentiated SH-SY5Y cells and primary rat cortical cultures, by the NR uptake and MTT reduction assays. In differentiated SH-SY5Y cells, mitochondrial membrane potential, intracellular ATP and calcium levels, reactive oxygen species production, and intracellular total glutathione levels were also evaluated. All the tested drugs exhibited concentration-dependent cytotoxic effects towards differentiated SH-SY5Y cells and primary rat cortical cultures. The NBOMe drugs presented higher cytotoxicity than their counterparts, which correlates with the drug's lipophilicity. These cytotoxic effects were associated with mitochondrial dysfunction, evident through mitochondrial membrane depolarization and lowered intracellular ATP levels. Intracellular calcium imbalance was observed for 2C-T-7 and 25T7-NBOMe, implying a disrupted calcium regulation. Although reactive species levels remained unchanged, a reduction in intracellular total GSH content was observed. Overall, these findings contribute to a deeper understanding of these drugs, shedding light on the mechanisms underpinning their neurotoxicity.

7.
Methods Mol Biol ; 2796: 157-184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38856901

RESUMO

Kir channels are potassium (K+) channels responsible for the mechanism of inward rectification, which plays a fundamental role in maintaining the resting membrane potential. There are seven Kir subfamilies, and their opening and closing mechanism is regulated by different regulatory factors. Genetically inherited defects in Kir channels are responsible for several rare human diseases, and for most of them, there are currently no effective therapeutic treatments. High-resolution structural information is not available for several members within the Kir subfamilies. Recently, our group achieved a significant breakthrough by utilizing cryo-EM single-particle analysis to elucidate the first structure of the human Kir2.1 channel. We present here the data processing protocol of the cryo-EM data of the human Kir2.1 channel, which is applicable to the structural determination of other ion channels by cryo-EM single-particle analysis. We also introduce a protocol designed to assess the structural heterogeneity within the cryo-EM data, allowing for the identification of other possible protein structure conformations present in the collected data. Moreover, we present a protocol for conducting all-atom molecular dynamics (MD) simulations for K+ channels, which can be incorporated into various membrane models to simulate different environments. We also propose some methods for analyzing the MD simulations, with a particular emphasis on assessing the local mobility of protein residues.


Assuntos
Microscopia Crioeletrônica , Simulação de Dinâmica Molecular , Canais de Potássio Corretores do Fluxo de Internalização , Microscopia Crioeletrônica/métodos , Canais de Potássio Corretores do Fluxo de Internalização/química , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Humanos , Conformação Proteica
8.
Pharmaceutics ; 16(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38931832

RESUMO

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases' progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

9.
Chemosphere ; 361: 142515, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38830460

RESUMO

The catalytic performance of modified hydroxyapatite nanoparticles, Ca10-xFex-yWy(PO4)6(OH)2, was applied for the degradation of methylene blue (MB), fast green FCF (FG) and norfloxacin (NOR). XPS analysis pointed to the successful partial replacement of Ca by Fe. Under photo-electro-Fenton process, the catalyst Ca4FeII1·92W0·08FeIII4(PO4)6(OH)2 was combined with UVC radiation and electrogenerated H2O2 in a Printex L6 carbon-based gas diffusion electrode. The application of only 10 mA cm-2 resulted in 100% discoloration of MB and FG dyes in 50 min of treatment at pH 2.5, 7.0 and 9.0. The proposed treatment mechanism yielded maximum TOC removal of ∼80% and high mineralization current efficiency of ∼64%. Complete degradation of NOR was obtained in 40 min, and high mineralization of ∼86% was recorded after 240 min of treatment. Responses obtained from LC-ESI-MS/MS are in line with the theoretical Fukui indices and the ECOSAR data. The study enabled us to predict the main degradation route and the acute and chronic toxicity of the by-products formed during the contaminants degradation.


Assuntos
Eletrodos , Peróxido de Hidrogênio , Ferro , Azul de Metileno , Nanopartículas , Poluentes Químicos da Água , Catálise , Peróxido de Hidrogênio/química , Ferro/química , Azul de Metileno/química , Nanopartículas/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Norfloxacino/química , Durapatita/química , Corantes/química , Processos Fotoquímicos , Raios Ultravioleta
10.
BMC Oral Health ; 24(1): 641, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816807

RESUMO

BACKGROUND: Different processing techniques are employed to obtain poly (methyl methacrylate) (PMMA) with consistent surface quality in terms of topography and tribological function. The purpose of this research is to evaluate its influence on the surface height distribution. METHODS: In this research, samples of conventional and CAD/CAM acrylic resins were prepared. The following surface roughness parameters were extracted from the profilometric readings: arithmetic mean roughness (Pa), skewness (Psk) and kurtosis (Pku). Profilometric profiles were additionally obtained. RESULTS: The average roughness (Pa) with the conventional technique was significantly higher compared to CAD/CAM (t = 4.595; P < 0.001). Heat-cured resins presented the highest mean Pa (F = 6.975; P = 0.06). Heat-cured and milled resins show lower coefficient variation (CV) values, indicating more consistent surface finishing. The surface profiles revealed distinct characteristics in terms of skewness and kurtosis. CONCLUSIONS: The surface processing method, chemical composition and resin type significantly influence the surface finishing of the resin. The CAD/CAM resins exhibited superior results in terms of surface arithmetic mean roughness (Pa). However, heat-cured resin revealed to present the better surface consistency.


Assuntos
Resinas Acrílicas , Desenho Assistido por Computador , Teste de Materiais , Polimetil Metacrilato , Propriedades de Superfície , Resinas Acrílicas/química , Polimetil Metacrilato/química , Materiais Dentários/química , Humanos , Temperatura Alta
11.
Anim Reprod Sci ; 266: 107491, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754337

RESUMO

The aims of this study were to determine anti-müllerian hormone (AMH) cutoff values for selecting Gir (Bos taurus indicus) oocyte donors and estimate the impact of using AMH concentrations as a selection criterion. In Exp. 1, Gir heifers (n=120) were sampled for AMH analysis and submitted to ovum pick-up and in vitro embryo production (OPU-IVEP). AMH cutoff values were calculated using ROC analysis or, alternatively, by the successive exclusion of heifers with the lowest AMH values. The correlations between AMH and OPU-IVEP outcomes were significant (P<0.001), though low or moderate (r= 0.34-0.52). We estimated an improvement (P<0.05) after the use of AMH cutoff values to select donors of +15.3% for total oocyes, +19.4% for viable COC, and +23.4% for blastocysts. This selection pressure, however, led to the exclusion of 32.8%, 37.9%, and 50.0% of the initial potential donors, respectively. In Exp. 2, we analyzed data from OPU-IVEP sessions of 658 Gir donors with known genomic values for predicted transmitting ability for milk (GPTAm) and age at first calving (GPTAafc). The selection based on the number of oocytes recovered had no effect (P>0.05) on the average GPTAm nor GPTAafc values of the remaining donors. In summary, plasma AMH ≥700 pg/mL is a cutoff value that can be used to select Gir heifers with a greater potential as oocyte donors. Nevertheless, this selection leads to the exclusion of up to 50% of potential donors. Finally, exclusion of poor responders had no effect on mean genomic estimates for milk production or age at first calving in the selected subset of donors.


Assuntos
Hormônio Antimülleriano , Fertilização in vitro , Animais , Hormônio Antimülleriano/sangue , Bovinos/sangue , Bovinos/fisiologia , Feminino , Fertilização in vitro/veterinária , Técnicas de Cultura Embrionária/veterinária , Oócitos/fisiologia , Doação de Oócitos/veterinária , Recuperação de Oócitos/veterinária , Recuperação de Oócitos/métodos , Transferência Embrionária/veterinária
12.
ACS Pharmacol Transl Sci ; 7(5): 1637-1649, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751615

RESUMO

Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O-methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver. There is a knowledge gap concerning which mechanisms and chemical properties govern the toxicity of nitrocatechol-based COMT inhibitors. Using a vast array of cell-based assays, we found that tolcapone-induced toxicity is caused by direct interference with mitochondria that does not depend on bioactivation by P450. Our findings also suggest that (a) lipophilicity is a key property in the toxic potential of nitrocatechols; (b) the presence of a carbonyl group directly attached to the nitrocatechol ring seems to increase the reactivity of the molecule, and (c) the presence of cyano moiety in double bond stabilizes the reactivity decreasing the cytotoxicity. Altogether, the fine balance between lipophilicity and the chemical nature of the C1 substituents of the nitrocatechol ring may explain the difference in the toxicological behavior observed between tolcapone and entacapone.

13.
PLOS Glob Public Health ; 4(5): e0003061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709753

RESUMO

Men who have sex with men (MSM) and transgender women (TW) are disproportionally affected by HIV infection. This cross-sectional study evaluated the HIV-1/2 prevalence, risk factors and HIV molecular features of MSM and TW from Midwest Brazil. Four hundred and thirty participants (278 MSM and 152 TW) from Mato Grosso do Sul, Brazil, were interviewed and tested for HIV-1/2 infection between November 2011 and September 2013. Participants who were assigned male at birth, older than 18 years old and self-declared as MSM or TW were recruited from LGBT+ associations, as well as public (parks, square, streets, etc) and private [nightclubs, saunas, brothels, etc] places. The prevalence of HIV-1 was 14.4% (9.0% among MSM and 24% among TW; p<0.001). The factor independently associated with HIV-1 infection among MSM was being 30 years-old or older. Among TW, having suffered sexual coercion, lifetime syphilis infection and hepatitis C virus exposure were associated with HIV-1 infection. Phylogenetic analyses classified 65% sequences as subtype B and 35% as possible recombinants. All but one recombinant sample were from TW individuals. High HIV-1 prevalences were observed in both groups, highlighting the urgent need to devise specific HIV interventions targeting these key populations. Notably, TWs are more vulnerable to HIV infection, which was associated with sexual violence and co-infection with other STIs. With regard to MSM, being 30 years old or older was significanty associated to HIV, reinforcing the idea that MSM are less exposed [or exposed later] to STIs than TWs, although MSM are clearly more vulnerable than the general population.

14.
Acta Med Port ; 37(5): 379-385, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38577868

RESUMO

Gender dysphoria is defined as a condition characterized by mental suffering associated with the incongruence between one's experienced gender and their birth-assigned sex. Gender as a construct and gender dysphoria as a condition in need of multidisciplinary intervention have developed as swiftly as their visibility in society, making it mandatory to promote the literacy and education of all healthcare professionals in this area. This article aims to review information based on scientific evidence on people with gender dysphoria and its clinical approach, while contributing to a safe, inclusive, and non-discriminatory practice of healthcare.


Assuntos
Disforia de Gênero , Humanos , Disforia de Gênero/diagnóstico , Disforia de Gênero/terapia , Disforia de Gênero/psicologia , Masculino , Feminino
15.
ACS Appl Mater Interfaces ; 16(17): 21522-21533, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647198

RESUMO

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson's disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug's short half-life and toxicity. This work aims to use PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks. Using the nanoprecipitation method, tolcapone-loaded nanoparticles with a DLC% of 5.7% were obtained (EE% of 47.0%) and subjected to a lyophilization optimization process to obtain a final shelf-stable formulation. Six different cryoprotectants in concentrations up to 10% (w/v) were tested. A formulation of PLGA nanoparticles with 3% hydroxypropyl-ß-cyclodextrin (HPßCD) as a cryoprotectant (PLGA-HP@Tolc), presenting sub-200 nm sizes and low polydispersity (PdI < 0.200) was selected. Cytotoxicity assays, namely, MTT and SRB, were used to study the metabolic activity and cell density of tolcapone and PLGA-HP@Tolc-treated cells. In both assays, a hepatocarcinoma cell line (HepG2) growing in glucose or glucose-free media (galactose-supplemented medium) was used. The results demonstrated that the treatment with the PLGA-HP@Tolc formulation led to a decrease in cytotoxicity in comparison to free tolcapone-treated cells in both media tested. Moreover, the elected formulation also counteracted ATP-depletion and excessive ROS production induced by tolcapone. The results suggest that HPßCD might have a dual function in the formulation: cryoprotectant and anticytotoxic agent, protecting cells from tolcapone-induced damage. Using an in vitro COMT inhibition assay, the PLGA-HP@Tolc formulation demonstrated to inhibit COMT as efficiently as free tolcapone. Overall, the results suggest that tolcapone-loaded PLGA NPs could be an interesting alternative to free tolcapone, demonstrating the same in vitro efficacy in inhibiting COMT but with a safer cytotoxic profile.


Assuntos
Nanopartículas , Polietilenoglicóis , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tolcapona , Nanopartículas/química , Nanopartículas/toxicidade , Tolcapona/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Polietilenoglicóis/química , Células Hep G2 , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Inibidores de Catecol O-Metiltransferase/química , Inibidores de Catecol O-Metiltransferase/farmacologia , Tamanho da Partícula , Crioprotetores/química , Crioprotetores/farmacologia , Sobrevivência Celular/efeitos dos fármacos
16.
Enferm. glob ; 23(74): 1-13, abr.2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-232278

RESUMO

Objetivo: Verificar la asociación entre los niveles de ansiedad y depresión en participantes de un Programa Multidisciplinario para el Tratamiento de la Obesidad, con variables antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y aptitud física relacionada con la salud. Método: Estudio cuantitativo, correlacional, transversal, realizado con adultos participantes del Programa Multidisciplinario de Tratamiento de la Obesidad en un municipio del Noroeste de Paraná. Para la recolección de datos se aplicaron medidas antropométricas en julio de 2021; composición corporal; parámetros bioquímicos y hemodinámicos; pruebas de aptitud física relacionadas con la salud; y escala para evaluar los niveles de ansiedad y depresión. Resultados: Participaron del estudio 116 individuos, 87,94% mujeres, 12,06% hombres, con una edad media de 40 años. Hubo una correlación positiva considerable entre la hemoglobina y el hematocrito; colesterol total y LDL; glucosa y HbA1C1; peso e IMC; peso y perímetro abdominal; peso y circunferencia de la cintura; IMC y perímetro abdominal; IMC y perímetro de cintura; así como ansiedad y depresión. Conclusión: Los niveles de ansiedad y depresión de los participantes de Programa Multidisciplinario para el Tratamiento de la Obesidad no se correlacionaron significativamente con las variables de medición antropométricas; composición corporal; parámetros bioquímicos y hemodinámicos; y pruebas de evaluación de la aptitud física relacionadas con la salud. (AU)


Objetivo: Verificar associação entre níveis de ansiedade e depressão de participantes de um Programa Multiprofissional de Tratamento da Obesidade, com variáveis antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; e aptidão física relacionada à saúde. Método: Estudo transversal, realizado com adultos que participaram do programa em município do Noroeste do Paraná. Para a coleta de dados, aplicou-se em julho de 2021, avaliações de medidas antropométricas; composição corporal; parâmetros bioquímicos e hemodinâmicos; testes de aptidão física relacionada à saúde; e escala para avaliar os níveis de ansiedade e depressão. Resultados: Participaram do estudo 116 indivíduos, sendo 87,94% do sexo feminino, 12,06% do sexo masculino, com média de idade de 40 anos. Houve correlação positiva entre hemoglobinas e hematócritos; colesterol total e LDL; glicose e HbA1C1; peso, IMC e circunferências abdominal e de cintura; além de ansiedade e depressão. Conclusão: Os níveis de ansiedade e depressão não apresentaram correlação significativa com as variáveis estudadas. (AU)


Objective: To verify the association between levels of anxiety and depression of participants in a Multidisciplinary Program for the Treatment of Obesity, with anthropometric variables; body composition; biochemical and hemodynamic parameters; and health-related physical fitness. Method: Quantitative, correlational, cross-sectional study carried out with adults who participated in the Multidisciplinary Program for the Treatment of Obesity in a municipality in the Northwest of Paraná. For data collection, anthropometric measurements were applied in July 2021; body composition; biochemical and hemodynamic parameters; health-related physical fitness tests; and scale to assess levels of anxiety and depression. Results: 116 individuals participated in the study, 87.94% female, 12.06% male, with a mean age of 40 years. There was a considerable positive correlation between hemoglobin and hematocrit; total and LDL cholesterol; glucose and HbA1C1; weight and BMI; weight and abdominal circumference; weight and waist circumference; BMI and abdominal circumference; BMI and waist circumference; as well as anxiety and depression. Conclusion:The levels of anxiety and depression of the participants of the Multidisciplinary Program for the Treatment of Obesity did not present a significant correlation with the variables of anthropometric measurements; body composition; biochemical and hemodynamic parameters; and health-related physical fitness assessment tests. (AU)


Assuntos
Humanos , Adulto , Obesidade , Ansiedade , Depressão , Composição Corporal , Hemodinâmica , Aptidão Física , Estudos Transversais
17.
Zebrafish ; 21(3): 265-273, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38386543

RESUMO

In fish species, heterochromatinization is one process that could trigger sex chromosome differentiation. The present article describes a nascent XX/XY sex chromosome system evidenced by heterochromatin accumulation and microsatellite (GATA)8 in Hypostomus albopunctatus from two populations of the Paraná River basin. The specimens of H. albopunctatus from the Campo and Bossi Rivers share the same karyotype. The species exhibits 74 chromosomes (8m+14sm +16st +36a, fundamental number = 112). The C-banding technique suggests male heterogamety in H. albopunctatus, where the Y-chromosome is morphologically like the X-chromosome but differs from it for having long arms that are entirely heterochromatic. Double fluorescence in situ hybridization (FISH) with 18S and 5S rDNA probes confirmed the Ag-nucleolus organizer region sites in a single pair for both populations, and minor rDNA clusters showed interpopulational variation. FISH with the microsatellite (GATA)8 probe showed a dispersed pattern in the karyotype, accumulating these sequences of sex chromosomes of both populations. FISH with microsatellite (CGC)10 probe showed interpopulational variation. The absence of differentiated sex chromosomes in H. albopunctatus is described previously, and a new variant is documented herein where XY chromosomes can be seen in an early stage of differentiation.


Assuntos
Peixes-Gato , Heterocromatina , Animais , Peixes-Gato/genética , Heterocromatina/genética , Heterocromatina/metabolismo , Masculino , Feminino , Hibridização in Situ Fluorescente , Cromossomos Sexuais/genética , Cromossomo Y/genética , Repetições de Microssatélites , Cariótipo
18.
Conserv Physiol ; 12(1): coad106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38293639

RESUMO

The Pace-of-Life syndrome proposes that behavioural, physiological and immune characteristics vary along a slow-fast gradient. Urbanization poses several physiological challenges to organisms. However, little is known about how the health status of frogs is affected by urbanization in the Tropics, which have a faster and more recent urbanization than the northern hemisphere. Here, we analysed a suite of physiological variables that reflect whole organism health, reproduction, metabolic and circulatory physiology and leukocyte responses in Leptodactylus podicipinus. Specifically, we tested how leukocyte profile, erythrocyte morphometrics and germ cell density, as well as somatic indices and erythrocyte nuclear abnormalities differ throughout the adult life span between urban and rural populations. We used Phenotypic Trajectory Analysis to test the effect of age and site on each of the multivariate data sets; and a Generalised Linear Model to test the effect of site and age on nuclear abnormalities. Somatic indices, erythrocyte nuclear abnormalities, erythrocyte morphometrics and leukocyte profile differed between populations, but less so for germ cell density. We found a large effect of site on nuclear abnormalities, with urban frogs having twice as many abnormalities as rural frogs. Our results suggest that urban frogs have a faster pace of life, but the response of phenotypic compartments is not fully concerted.

19.
Biomed Pharmacother ; 171: 116108, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218079

RESUMO

Metastasis is the leading cause of cancer-related deaths. Despite this relevance, there is no specific therapy targeting metastasis. The interaction of the tumor cell with platelets, forming microemboli is crucial for successful hematogenous dissemination. Heparin disrupts it by a P-selectin-mediated event. However, its clinical use for this purpose is hindered by the requirement of high doses, leading to anticoagulant-related side effects. In this study, we obtained a low-anticoagulant heparin through the fractionation of a pharmaceutical bovine heparin. This derivative was referred to as LA-hep and we investigated its efficacy in inhibiting metastases and explored its capacity of suppressing the interaction between tumor cells and platelets. Our data revealed that LA-hep is as efficient as porcine unfractionated heparin in attenuating lung metastases from melanoma and colon adenocarcinoma cells in an assay with a single intravenous administration. It also prevents platelet arrest shortly after cell injection in wild-type mice and suppresses melanoma-platelets interaction in vitro. Moreover, LA-hep blocks P-selectin's direct binding to tumor cells and platelet aggregation, providing further evidence for the role of P-selectin as a molecular target. Even in P-selectin-depleted mice which developed a reduced number of metastatic foci, both porcine heparin and LA-hep further inhibited metastasis burden. This suggests evidence of an additional mechanism of antimetastatic action. Therefore, our results indicate a dissociation between the heparin anticoagulant and antimetastatic effects. Considering the simple and highly reproducible methodology used to purify LA-hep along with the data presented here, LA-hep emerges as a promising drug for future use in preventing metastasis in cancer patients.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Melanoma , Humanos , Animais , Bovinos , Camundongos , Heparina/farmacologia , Anticoagulantes/farmacologia , Selectina-P/metabolismo , Melanoma/patologia , Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Plaquetas/metabolismo , Preparações Farmacêuticas/metabolismo , Metástase Neoplásica/patologia
20.
Zebrafish ; 21(1): 39-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38285204

RESUMO

Eigenmannia is a highly diverse genus within the Sternopygidae family, comprising 30 species. Due to its complex taxonomy, molecular analyses have been crucial for species delimitation within this group. Therefore, the present study presents a genetic analysis using sequences of the mitochondrial gene cytochrome c oxidase subunit 1 (COI) in specimens previously identified through alpha taxonomy as E. correntes (with unpublished data), E. virescens, and E. trilineata, originating from various locations within the Upper Paraná and Paraguay River basins in Brazil. The molecular data confirm the taxonomic complexity of the genus, as individuals morphologically identified as E. virescens and E. trilineata shared the same haplotype (H52). Furthermore, the results of the species delimitation tests suggest that specimens morphologically identified as E. virescens belong to the species E. trilineata. In addition, samples morphologically identified as E. correntes may correspond to more than one Operational Taxonomic Units (OTUs). Furthermore, the intraspecific Kimura-2-parameter (K2P) distances within the different studied populations are significant. This study has contributed valuable information about genetic diversity in Eigenmannia, emphasizing the importance of using integrative analyses to resolve taxonomic conflicts within the group. It also supports biogeographical studies and assists in biodiversity conservation efforts.


Assuntos
Gimnotiformes , Humanos , Animais , Gimnotiformes/genética , Brasil , Rios , Paraguai , Peixe-Zebra , Filogenia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...