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1.
Planta Med ; 90(5): 380-387, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38219731

RESUMO

In previous studies, we demonstrated that the ethanolic extract of Heliopsis longipes roots and its main alkamide, affinin, elicit a vasorelaxant effect through a mechanism involving activation of the gasotransmitter pathways and stimulation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels. However, it has not yet been demonstrated whether the EEH and affinin are capable of lowering high blood pressure. Therefore, the aim of the present study was to determine the effect of the oral administration of the EEH and affinin on the systolic blood pressure of NG-nitro-L-arginine methyl ester-induced hypertensive rats and to explore the participation of cannabinoid receptors and transient receptor potential channels in the mechanism of action of this alkamide. Our results showed that the ethanolic extract of H. longipes and affinin significantly lowered systolic blood pressure and induced an improvement in endothelial function, which is associated with increased serum nitric oxide levels. Inhibition of cannabinoid type 1 receptors by rimonabant (3 mg/kg), transient receptor potential ankyrin 1 channels by HC-030031 (8 mg/kg), and transient receptor potential vanilloid 1 channels by capsazepine (5 mg/kg) significantly decreased the antihypertensive effect induced by affinin, suggesting that the blood pressure-lowering effect of this alkamide involves activation of cannabinoid type 1 receptors and transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 channels.


Assuntos
Anti-Hipertensivos , Canabinoides , Alcamidas Poli-Insaturadas , Ratos , Animais , Anti-Hipertensivos/farmacologia , Receptores de Canabinoides , Anquirinas , Capsaicina , Extratos Vegetais/farmacologia , Canais de Cátion TRPV , Receptor CB1 de Canabinoide
2.
Toxicol Ind Health ; 40(3): 134-143, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38289205

RESUMO

Mercury is a ubiquitous environmental xenobiotic; the primary sources of exposure to this metal are artisanal gold mining and the direct production of mercury. In Mexico, artisanal mercury mining continues to be an important activity in different regions of the country. Exposure to mercury vapors releases can have severe health impacts, including immunotoxic effects such as alterations in cytokine profiling. Therefore, in the present work, we evaluated the inflammatory cytokines profile in the blood serum of miners exposed to mercury. A cross-sectional observational study was performed on 27 mining workers (exposed group) and 20 control subjects (nonexposed group) from central Mexico. The mercury urine concentration (U-Hg) was determined by atomic absorption spectrometry, and IL-2, IL-6, IL-8, IL-10, and TNF-α were measured using a Multiplex Assay. The results showed that the U-Hg in the miners had a median value of 552.70 µg/g creatinine. All cytokines showed a significant increase in the miner group compared with the control group, except for TNF-α. In addition, we observed a positive correlation between U-Hg concentration and cytokine levels. In conclusion, mercury exposure correlated with cytokine levels (considered acute inflammatory marker) in miners; therefore, workers exposed to this metal show an acute systemic inflammation that could lead to alterations in other organs and systems.


Assuntos
Mercúrio , Exposição Ocupacional , Humanos , Mercúrio/análise , Exposição Ocupacional/análise , Citocinas , Monitoramento Ambiental/métodos , Fator de Necrose Tumoral alfa , Estudos Transversais , Soro/química , Mineração , Ouro
3.
Fish Physiol Biochem ; 50(4): 1849-1860, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38985359

RESUMO

Classical assessments of new fish feeds are anthropocentric, focusing mainly on growth. Although this methodology is accurate, it does not consider the fish' perspective. This study aimed to investigate the behavioural responses and feed preferences of Nile tilapia (Oreochromis niloticus) and gilthead seabream (Sparus aurata) through a self-selection trial using self-feeders. Both species were offered three feeds: a control (PD) commercial-like feed and two diets (ORG1 and ORG2) formulated with different inclusions of alternative ingredients to address some of the current environmental concerns and/or ethical issues often associated with commercial formulations. Three groups of tilapia with an average weight of 163.0 g ± 4.3 g (mean ± SD) and four groups of seabreams with 174.7 g ± 27.0 g were tested. Tilapia exhibited a preference for ORG2 (46.5%), influenced by the sensory properties of the feed and post-ingestion signals. Seabream did not show a preference for any feed. These findings highlight the effectiveness of self-selection experiments in allowing fish to express their feeding behaviour and preferences. Therefore, this approach should be considered in the initial screening and design of new aquaculture feeds and ingredients.


Assuntos
Ração Animal , Ciclídeos , Dieta , Dourada , Animais , Dourada/fisiologia , Ração Animal/análise , Ciclídeos/fisiologia , Dieta/veterinária , Aquicultura/métodos , Preferências Alimentares , Comportamento Alimentar
4.
Rev Panam Salud Publica ; 47: e29, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-36909806

RESUMO

Humanitarian crises can occur in places affected by chemical, physical, biological, and social threats, especially when these threats interact with each other and cause a syndemic. In order to avoid crises in these places, it is necessary to introduce mitigation measures that we have framed as "humanitarian scenarios". Due to their nature, implementation of these interventions requires the creation of multidisciplinary operational groups with a work strategy that integrates them into the affected community. In the case of the child population, the operational group was called the 'childhood risks in contaminated places' (CRCP) unit; contaminated places meaning localities impacted by chemical, physical, or biological threats. The strategy has six phases: (i) planning the survey and site visit; (ii) community involvement in identifying threats, vulnerabilities, and routes of exposure (the path of pollutants from their source to the receiving population), and in preparing joint work for the subsequent phases; iii) prioritization of risks identified through environmental monitoring and use of biomarkers of exposure and effects; iv) risk prevention through the creation of various 'capacities and alternatives for the prevention of syndemic threats'; (v) advocacy to implement these capacities and alternatives through risk communication and local training; and (vi) protection through measures that include telehealth, social progress, and innovation to improve health coverage. The strategy has been implemented in different contexts, and in some of them it has been enriched by analysis of respect for human rights.


Crises humanitárias podem ocorrer em locais afetados por ameaças químicas, físicas, biológicas e sociais, principalmente quando essas ameaças interagem entre si e causam uma sindemia. Para evitar as crises, é necessário introduzir nesses locais medidas de mitigação que enquadramos no termo "cenários humanitários". Por sua natureza, a implementação de tais ações de intervenção exige a formação de grupos operacionais multidisciplinares e de uma estratégia de trabalho que permita integrá-los à comunidade afetada. No caso da população infantil, o grupo operacional recebeu o nome de Unidade de Riscos Infantis em Áreas Contaminadas (na sigla em espanhol, RISC), ou seja, em locais impactados por ameaças químicas, físicas ou biológicas. A estratégia consiste nas seis fases a seguir: i) planejamento para o estudo e visita ao local; ii) participação da comunidade para identificar ameaças, vulnerabilidades e rotas de exposição (caminho que os contaminantes devem seguir desde a sua fonte até a população receptora), bem como para o trabalho conjunto nas fases seguintes; iii) priorização dos riscos identificados por meio do monitoramento ambiental e uso de biomarcadores de exposição e efeitos; iv) prevenção de riscos por meio da criação de diversas capacidades e alternativas para a prevenção diante de ameaças sindêmicas (CAPAS); v) promoção da implantação das CAPAS por meio da comunicação de riscos e capacitação local; e vi) proteção com medidas que incluem propostas de telessaúde, progresso social e inovação para melhorar a cobertura de saúde. A estratégia foi aplicada em diferentes contextos, em alguns dos quais foi enriquecida com uma análise do respeito pelos direitos humanos.

5.
J Therm Biol ; 113: 103544, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37055103

RESUMO

Ectothermic vertebrates, e.g. fish, maintain their body temperature within a specific physiological range mainly through behavioural thermoregulation. Here, we characterise the presence of daily rhythms of thermal preference in two phylogenetically distant and well-studied fish species: the zebrafish (Danio rerio), an experimental model, and the Nile tilapia (Oreochromis niloticus), an aquaculture species. We created a non-continuous temperature gradient using multichambered tanks according to the natural environmental range for each species. Each species was allowed to freely choose their preferred temperature during the 24h cycle over a long-term period. Both species displayed strikingly consistent temporal daily rhythms of thermal preference with higher temperatures being selected during the second half of the light phase and lower temperatures at the end of the dark phase, with mean acrophases at Zeitgeber Time (ZT) 5.37 h (zebrafish) and ZT 12.5 h (tilapia). Interestingly, when moved to the experimental tank, only tilapia displayed consistent preference for higher temperatures and took longer time to establish the thermal rhythms. Our findings highlight the importance of integrating both light-driven daily rhythm and thermal choice to refine our understanding of fish biology and improve the management and welfare of the diversity of fish species used in research and food production.


Assuntos
Ciclídeos , Tilápia , Animais , Peixe-Zebra , Ciclídeos/fisiologia , Temperatura , Ritmo Circadiano/fisiologia
6.
J Sci Food Agric ; 103(13): 6491-6499, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37221944

RESUMO

BACKGROUND: Tilapia (Oreochromis spp.) in the form of frozen fillets is one of the fishes with the highest commercial production levels worldwide. However, protein denaturation, membrane rupture, and lipid oxidation are commonly observed in fillets when stored at standard commercial freezing temperatures for long periods. This study proposes, for the first time, the use of maltodextrin and state diagrams to define processing strategies and suitable storage temperatures for fresh and dehydrated tilapia fillets. Differential scanning calorimetry (DSC) was used to study the effect of maltodextrin weight fractions ( W MD ) of 0, 0.4, and 0.8 on the thermal transitions of tilapia fillets as a function of solid mass fractions ( W s ). RESULTS: The glass transition temperature curve ( T g vs . W s ) and characteristic parameters of maximal freeze concentration ( T g ' , T m ' , W s ' ) of tilapia increased significantly with the addition of maltodextrin. Using developed state diagrams, freezing and storage temperatures of -22 °C, -15 °C, and -10 °C (P < 0.05) for long-term preservation were defined for tilapia fillets produced with W MD of 0, 0.4, and 0.8. CONCLUSION: Maltodextrin is an excellent alternative as a cryoprotectant and drying aid to increase the thermal parameters of tilapia fillets by achieving frozen storage temperatures above the standard commercial freezing temperature of -18 °C. © 2023 Society of Chemical Industry.


Assuntos
Tilápia , Animais , Tilápia/metabolismo , Temperatura , Temperatura Baixa , Polissacarídeos/metabolismo
7.
Toxicol Mech Methods ; 33(3): 233-238, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36093949

RESUMO

Atrazine (ATZ) is part of a group of herbicides called triazines. ATZ is widely used in agricultural areas of Mexico, commonly used for the selective control of weeds in corn and sorghum crops. The exposure to ATZ can have serious human health effects since its use was associated with the development of cutaneous melanoma in an epidemiological study. The aim of this study was to evaluate the expression of maturation and apoptotic markers in primary skin cultures exposed to ATZ. The primary skin cultures were exposed to 0.1, and 10 µM ATZ with or without ultraviolet (UV) radiation and the expression of maturation and apoptotic markers were evaluated by RT-qPCR. We observed a significant increase in all the melanocyte maturation markers in cells exposed to ATZ with or without UV, with SOX-9 and FAK (melanoblast markers) being the highest. Also, the expression of BCL-2 (anti-apoptotic marker) was the most increased gene in cells exposed to ATZ with or without UV. Low concentrations of ATZ and UV radiation induce genetic changes associated with the development of immature melanocytes and activate mechanisms associated with the inhibition of apoptosis characteristics of malignant cell transformation, which will allow proposing new therapeutic targets and generating new restrictions or care in farmers exposed to pesticides such as the ATZ.


Assuntos
Atrazina , Herbicidas , Melanoma , Humanos , Apoptose , Atrazina/toxicidade , Herbicidas/toxicidade , Melanócitos , Melanoma/induzido quimicamente , Melanoma/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia
8.
Nephrology (Carlton) ; 27(6): 484-493, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35289974

RESUMO

AIM: Evaluate the expression of exomiRs-126, -146, and -155 in urinary exosomes of patients with T2DM and diabetic kidney disease to establish a predictive classification model with exomiRs and clinical variables in order to determine their contribution to DKD. METHODS: The study group included 92 subjects: 64 patients diagnosed with T2DM subclassified into two groups with albuminuria (T2DM with albuminuria, n = 30) and without albuminuria (TD2M, n = 34) as well as 28 healthy, non-diabetic participants. Exosomes were isolated from urine and identified by TEM and flow cytometry. Profile expression of exomiRs-126, -146 and -155 was evaluated by RT-qPCR. Data were analysed by permutational multivariate analysis of variance (PERMANOVA), similarity percentage (SIMPER), principal coordinate analysis (PCO), and canonical analysis of principal coordinates (CAP). RESULTS: T2DM patients with and without albuminuria showed higher levels of miR-155 and miR-146 compared with controls. In addition, T2DM patients with albuminuria presented a significant increase in miR-126 contrasted to controls and patients without albuminuria. PCO analysis explained 34.6% of the total variability of the data (PERMANOVA; p < .0001). Subsequently, SIMPER analysis showed that miR-146, miR-155, and miR-126 together, with some clinical parameters, contributed to 50% of the between-group significance. Finally, the CAP analysis developed showed a correct classification of 89.01% with the analysed parameters. CONCLUSION: A platform using a combination of clinical variables and exomiRs could be used to classify individuals with T2D as risk for developing DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , MicroRNAs , Albuminúria/etiologia , Albuminúria/genética , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo
9.
Geophys Res Lett ; 48(4): 2020GL090700, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34511659

RESUMO

The Atmosphere-Space Interactions Monitor measures Terrestrial Gamma-Ray Flashes (TGFs) simultaneously with optical emissions from associated lightning activity. We analyzed optical measurements at 180-230, 337, and 777.4 nm related to 69 TGFs observed between June 2018 and October 2019. All TGFs are associated with optical emissions and 90% of them are at the onset of a large optical pulse, suggesting that they are connected with the initiation of current surges. A model of photon delay induced by cloud scattering suggests that the sources of the optical pulses are from 0.7 ms before to 4.4 ms after the TGFs, with a median of -10 ± 80 µs, and 1-5 km below the cloud top. The pulses have rise times comparable to lightning but longer durations. Pulse amplitudes at 337 nm are ∼3 times larger than at 777.4 nm. The results support the leader-streamer mechanism for TGF generation.

10.
Saudi Pharm J ; 29(11): 1258-1266, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34819787

RESUMO

Hawthorn (Crataegus spp.) has been used for the treatment of several heart diseases and hypertension. The studies carried out on several hawthorn species have led to the development of standardized extracts useful in the cure of mild chronic cardiac diseases. In Mexico, the most common Crataegus species are C. mexicana and C. gracilior. Decoctions prepared from the fruits and leaves of these species have been employed to the treat respiratory diseases, tachycardia and to improve coronary blood flow. Considering that to date there are no reports of the use of Mexican Crataegus species to treat cardiovascular diseases, we propose an analytical method to obtain a quantified extract of Crataegus mexicana leaves for the development of a standardized extract with therapeutic value in cardiovascular diseases as an alternative source to the extracts obtained from Crataegus species of European and Asian origin. Therefore, the aim of this study was to obtain an extract prepared from C. mexicana leaves with the highest vasodilator activity to select the optimal chemical marker to stablish and validate a reversed-phase high-performance liquid chromatography (RPHPLC-DAD) analytical method for obtaining a quantified extract with vasodilator effect. The results obtained from the analytical method validation, which was carried out according to the guidelines stablished in the Eurachem Guide and the ICH guidelines proved that the RPHPLC-DAD method we developed was specific, precise, accurate, and showed good linearity over the concentration range of 3 - 21 µg/ml for (-)-epicatechin and rutin, which were selected as chemical markers.

11.
Appl Opt ; 58(29): 8002-8006, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31674353

RESUMO

We present the main parameters, design features, and optical characterization of the GrAnada LIghtning Ultrafast Spectrograph (GALIUS): a portable, ground-based spectrographic system intended for analysis of the spectroscopic signature of lightning. It has been designed to measure the spectra of the light emitted from natural and triggered lightning and artificial electrostatic discharges at recording speeds up to 2.1 Mfps. It includes a set of four interchangeable grisms covering different spectral ranges (from 375 nm to 854.5 nm) with spectral resolutions from 0.29 nm to 0.76 nm. A set of 10 collector lenses allows the recording of the spectrum of electrostatic discharges and lightning in different scenarios.

12.
Int J Mol Sci ; 20(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480481

RESUMO

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.


Assuntos
Anticarcinógenos/uso terapêutico , Bifidobacterium longum , Neoplasias Colorretais/terapia , Licopeno/uso terapêutico , Probióticos/uso terapêutico , Administração Oral , Animais , Anticarcinógenos/administração & dosagem , Bifidobacterium longum/fisiologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Licopeno/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Probióticos/administração & dosagem , Receptor IGF Tipo 1/análise
13.
Molecules ; 24(5)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862086

RESUMO

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H2S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H2S/KATP signaling pathways and blockade of α1-adrenoceptors and L-type voltage-dependent Ca2+ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H2S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Isoxsuprina/química , Isoxsuprina/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Vasodilatadores/química , Vasodilatadores/farmacologia , Trifosfato de Adenosina/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/química , Bloqueadores dos Canais de Cálcio/química , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Triagem em Larga Escala , Humanos , Sulfeto de Hidrogênio/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Óxido Nítrico/metabolismo , Bibliotecas de Moléculas Pequenas , Fluxo de Trabalho
14.
BMC Cancer ; 18(1): 1056, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382908

RESUMO

BACKGROUND: Colorectal cancer is the third most common cancer worldwide; and in 40% of all cases, KRAS4b-activating mutations occur. KRAS4b is transported by phosphodiesterase-6δ (PDEδ) to the plasma membrane, where it gets activated. PDEδ downregulation prevents redistribution and activation of KRAS4b. Thus, targeting the KRAS4b-PDEδ complex is a treatment strategy for colorectal cancer. METHODS: Using docking and molecular dynamics simulations coupled to molecular mechanics, the generalized born model and solvent accessibility (MMGBSA) approach to explore protein-ligand stability, we found that the compound ((2S)-N-(2,5-diclorofenil)-2-[(3,4-dimetoxifenil)metilamino]-propanamida), termed C19, bound and stabilized the KRAS4b-PDEδ complex. We investigated whether C19 decreases the viability and proliferation of colorectal cancer cells, in addition to knowing the type of cell death that it causes and if C19 decreases the activation of KRAS4b and their effectors. RESULTS: C19 showed high cytotoxicity in the colorectal cancer cell lines HCT116 and LoVo, with a stronger effect in KRAS-dependent LoVo cells. Importantly, C19 significantly decreased tumor size in a xenograft mouse model and showed lower side effects than 5-fluorouracil that is currently used as colorectal cancer treatment. CONCLUSIONS: Mechanistically, the cytotoxic effect was due to increased apoptosis of tumor cells and decreased phosphorylation of Erk and Akt. Therefore, our results suggest that C19 may serve as a promising new treatment for colorectal cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/química , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Camundongos , Modelos Moleculares , Conformação Molecular , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/química , Transdução de Sinais , Relação Estrutura-Atividade , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Vet Pathol ; 55(3): 457-461, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402207

RESUMO

A 1-month-old Purebred Spanish Horse (PSH) foal presented with progressive hepatic failure culminating in death. Hepatic lesions were consistent with congenital hepatic fibrosis (CHF). Genetic studies in the PKHD1 gene in the affected foal revealed that it was heterozygous for the 2 previously described single-nucleotide polymorphisms (SNPs) linked to CHF in Swiss Franches-Montagnes (SFM) horses. In addition, 2 novel mutations were detected, the foal being homozygous for one of them and heterozygous for the other. Genetic studies in a healthy PSH population ( n = 35) showed a 3-fold higher genotypic frequency for PKHD1 SNP g.49,630,834G>A and a 5-fold higher genotypic frequency for PKHD1 SNP g.49,597,760A>T compared with those reported for SFM horses. SNPs in the PKHD1 gene in CHF-affected SFM horses might not fully explain the CHF observed in the PSH. Other mutations in the PKHD1 gene could play a more important role in the PSH.


Assuntos
Doenças Genéticas Inatas/veterinária , Doenças dos Cavalos/congênito , Cirrose Hepática/veterinária , Receptores de Superfície Celular/metabolismo , Animais , Evolução Fatal , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/patologia , Genótipo , Doenças dos Cavalos/genética , Doenças dos Cavalos/patologia , Cavalos , Fígado/patologia , Cirrose Hepática/congênito , Cirrose Hepática/genética , Cirrose Hepática/patologia , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética
16.
Molecules ; 23(6)2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29912156

RESUMO

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4'-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4'-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4'-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.


Assuntos
Músculo Liso/irrigação sanguínea , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , GMP Cíclico/metabolismo , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Medicina Tradicional , México , Estrutura Molecular , Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Ratos , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Vasodilatação , Vasodilatadores/química
17.
Lung ; 195(2): 185-191, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28236261

RESUMO

PURPOSE: It remains unclear whether there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. Subclinical carotid atherosclerosis is a predictor of future cardiovascular events. Exacerbations increase all-cause mortality in COPD, and exacerbation-like episodes have been described in subjects without COPD. Our objectives were as follows: (1) to confirm the independent association between COPD and carotid atherosclerosis and (2) to asses the possible relationship between COPD exacerbations or exacerbation-like episodes and a higher risk of atherosclerosis. METHODS: 127 COPD subjects and 80 control subjects with smoking history were studied. Carotid ultrasound examination was carried out in all subjects. Univariate and multivariate logistic regression analyses were performed in order to assess the relationship between both COPD diagnosis and previous COPD exacerbations (or exacerbation-like episodes in non-COPD subjects) and the presence of carotid atherosclerosis. RESULTS: The prevalence of carotid atherosclerosis was higher in COPD group (65.3 vs. 47.5%, p = 0.01; OR 2.18, 95% CI 1.23-3.88, p < 0.01). Diagnosis of COPD was not independently associated with atherosclerosis, after adjusting for potential confounders. Neither COPD exacerbations nor exacerbation-like episodes in control subjects were associated with a higher risk of atherosclerosis. CONCLUSION: There is a higher prevalence of carotid atherosclerosis in COPD than in control smokers or ex-smokers, but the differences seem to be related to shared risk factors. We have not found evidence for an increased risk of atherosclerosis associated with COPD exacerbations or exacerbation-like events. Further longitudinal studies should be carried out to confirm these findings.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Exacerbação dos Sintomas , Idoso , Doenças Assintomáticas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar/epidemiologia
18.
An Acad Bras Cienc ; 89(2): 1243-1250, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28489192

RESUMO

This study aimed to investigate pirarucu's (Arapaima gigas) ability to trigger a self-feeding system to regulate protein intake between two standard diets that contained 39% and 49% of crude protein. The same system allowed the evaluation of daily feeding and locomotor activity rhythms. Eighteen fish (654.44±26.85g) were distributed into six 250 L tanks (3 fish/tank). Fish had free access to both diets (39% vs. 49% protein) by feeders (2 per tank), adapted to be activated by fish themselves. This system was connected to a computer system. After an adaptation period, fish learned to activate feeders and the mean food intake recorded was 2.14% of their body weight on a daily basis. Fish showed feeding (72.48%) and locomotor (72.49%) activity predominantly during the daytime, and daily variations of choice between diets, but fixed a protein intake feeding target at 44.53%. These results should be considered when discussing feeding behavior, feeding schedules and diet intake regulations.


Assuntos
Ração Animal , Regulação do Apetite/fisiologia , Proteínas Alimentares/administração & dosagem , Comportamento Alimentar/fisiologia , Peixes/metabolismo , Análise de Variância , Animais , Ritmo Circadiano/fisiologia , Proteínas Alimentares/metabolismo , Locomoção/fisiologia , Atividade Motora/fisiologia , Valores de Referência , Fatores de Tempo
19.
Int J Mol Sci ; 18(1)2017 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-28117739

RESUMO

Heliopsis longipes roots have been widely used in Mexican traditional medicine to relieve pain, mainly, toothaches. Previous studies have shown that affinin, the major alkamide of these roots, induces potent antinociceptive and anti-inflammatory activities. However, the effect of H. longipes root extracts and affinin on the cardiovascular system have not been investigated so far. In the present study, we demonstrated that the dichloromethane and ethanolic extracts of H. longipes roots, and affinin, isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. Affinin-induced vasorelaxation was partly dependent on the presence of endothelium and was significantly blocked in the presence of inhibitors of NO, H2S, and CO synthesis (NG-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG), and chromium mesoporphyrin (CrMP), respectively); K⁺ channel blockers (glibenclamide (Gli) and tetraethyl ammonium (TEA)), and guanylate cyclase and cyclooxygenase inhibitors (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and indomethacin (INDO), respectively). Our results demonstrate, for the first time, that affinin induces vasodilation by mechanisms that involve gasotransmitters, and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.


Assuntos
Amidas/isolamento & purificação , Amidas/farmacologia , Asteraceae/química , Epoprostenol/metabolismo , Gasotransmissores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Amidas/química , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , AMP Cíclico/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Indometacina/farmacologia , Masculino , Cloreto de Metileno , Modelos Biológicos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Alcamidas Poli-Insaturadas , Canais de Potássio/metabolismo , Ratos Wistar
20.
Appl Opt ; 55(23): 6436-42, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27534491

RESUMO

We present the main parameters, design features, and optical characterization of the Granada Sprite Spectrograph and Polarimeter (GRASSP), a ground-based spectrographic system intended for the analysis of the spectroscopic signature of transient luminous events (TLEs) occurring in the mesosphere of the Earth. It has been designed to measure the spectra of the light emitted from TLEs with a mean spectral resolution of 0.235 nm and 0.07 nm/px dispersion in the wavelength range between 700 and 800 nm.

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