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1.
Animal ; 18(3): 101084, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367312

RESUMO

Procedures such as transport and marketing can subject animals to water and feed deprivation and impair animal health and performance. Maintaining the mineral status of animals under these conditions can bring benefits to health and performance. The use of hydroxychloride mineral sources can improve mineral status, nutrient digestibility and performance. Two studies were conducted to investigate how the supplementation of 02 trace mineral sources of Cu and Zn and 48-hour water/feed deprivation would affect the performance and metabolism of grass-fed beef cattle. In the first study, 20 castrated and rumen-canulated Nellore steers (BW = 350 ±â€¯132 kg; 20 m) were distributed in individual pens, in a 2 × 2 factorial arrangement: supplemental Cu and Zn sources from inorganic vs hydroxychloride (HTM) and 48-hours deprivation (WFD) vs unrestricted (WFU) access to water and feed. The 57d of study was divided into two periods: (1) Adaptation from -21d to -1d and (2) evaluation from 0d to 36d. Interaction between deprivation × period was detected (P < 0.05) for digestibility of DM (DMD), organic matter (OMD), neutral detergent fiber (NDFD), and acid detergent fiber (ADFD). Deprivation increased DMD, OMD, NDFD, and ADFD immediately after the deprivation period (3-5d), but impaired digestibility at longer periods such as 11-13d and 32-34d. DM (DMI) and nutrient intake (P = 0.075), as well as NDFD were higher in HTM. Several ruminal parameters were affected by deprivation: short-chain fatty acids concentration decreased, while rumen pH increased (deprivation × time; P < 0.05); decreased propionate, butyrate and increased isobutyrate, isovalerate, and valerate in WFD (deprivation × time; P < 0.05), respectively. In the second study, eighty-four intact Nellore males (BW = 260 ±â€¯35 kg) were blocked by BW and randomly assigned to Urochloa brizantha cv. Marandu paddocks for 131d in a 2 × 2 factorial arrangement. Liver Cu was higher in WFU/HTM animals (mineral × deprivation; P < 0.05). Interaction between deprivation × period (P < 0.05) was detected for BW and average daily gain (ADG). On 2d and 12d after deprivation, WFD increased ADG and recovered the BW lost. In conclusion, water and feed deprivation imposed in these trials were able to impact several nutrient digestibility and ruminal fermentation parameters in short- and long-term. Performance was not affected by the studied factors. Furthermore, supplementation with sources of Cu and Zn hydroxychloride increased Cu in the liver and tended to increase DMI and NDFD.


Assuntos
Cobre , Zinco , Masculino , Bovinos , Animais , Suplementos Nutricionais , Dieta/veterinária , Água/metabolismo , Detergentes/metabolismo , Digestão , Minerais/metabolismo , Fermentação , Ração Animal/análise , Rúmen/metabolismo
2.
Theriogenology ; 215: 78-85, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016304

RESUMO

During in vitro maturation (IVM) cumulus-oocyte complexes (COCs) are exposed to conditions that can trigger oxidative stress, thus, reducing oocyte maturation and viability. Aiming to mitigate these detrimental conditions, the effects of IVM medium supplementation with anethole have been tested. Anethole, also known as trans-anethole (1-methoxy-4 [1-propenyl]-benzene), is a naturally occurring phenylpropanoid with various pharmacological properties, including antioxidant effects. However, no study has examined anethole effect on goat COCs during IVM. Thus, the aim of this study was to evaluate the effects of different anethole concentrations on oocyte maturation, oxidative stress, and in vitro development of caprine embryos after parthenogenetic activation. Goat COCs were selected and randomly distributed into the following treatments: TCM-199+ medium (control), or TCM-199+ medium supplemented with 30 µg/mL (AN30); 300 µg/mL (AN300) or 2000 µg/mL (AN2000) of anethole. After IVM, part of the COCs was chosen for oocyte viability and chromatin configuration, intracellular reactive oxygen species levels, and mitochondrial membrane potential assessment. Another part of COCs was parthenogenetically activated, and presumptive zygotes were cultured for 7 days. Results demonstrated that anethole at 30 µg/mL increased oocyte maturation and cleavage rates when compared to the other treatments (P < 0.05), as well as oocyte viability and in vitro embryo production when compared to the control treatment (P < 0.05). Additionally, treatment with anethole at 2000 µg/mL decreased oocyte nuclear maturation and cleavage rates when compared to other treatments (P < 0.05) and embryo production if compared to control and AN30 treatments (P < 0.05). Moreover, anethole at 2000 µg/mL increased mitochondrial membrane potential when compared to the other treatments (P < 0.05). In conclusion, anethole exerts a concentration-dependent effect during goat COCs IVM. For a more desirable outcome of oocyte viability and maturation, and in vitro embryo production, the use of anethole at 30 µg/mL is recommended.


Assuntos
Cabras , Técnicas de Maturação in Vitro de Oócitos , Animais , Feminino , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Cabras/fisiologia , Oócitos/fisiologia , Suplementos Nutricionais , Células do Cúmulo
3.
Braz J Biol ; 83: e274635, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37851772

RESUMO

This study evaluated the insecticidal activity of crude extracts from Enterolobium contortisiliquum (Vell.) seeds on eggs and larvae of A. aegypti, and also verified the phytochemical profile and the presence of lectins in the extract. The 0.15 M NaCl saline solution was used as the extracting substance. For tests with eggs and larvae, the crude extract was used in its raw form (RCE) and boiled at 100º C for 5 min (BCE). Concentrations of 4.68; 9.37; 18.75; 28.13; 37.13 and 46.89 mg/mL, with distilled water as a negative control. Assays were performed in triplicate. The results were subjected to analysis of variance, Tukey's test and Log-Probit analysis to determine LC50 and LC90. BCE showed better results on eggs than RCE, managing to prevent the hatching of larvae in 81.66% ± 10.40 of treated eggs, at a concentration of 46.89 mg/mL. The LC50 and LC90 were set at 35.95 and 52.67 mg/mL, respectively. In tests with larvae, concentrations of 46.89 and 37.13 mg/mL, for RCE and BCE, caused 100% mortality in 24 hours of exposure. Larval mortality at the other concentrations increased with exposure time extending to 48 h. RCE, at 48 h exposure is the most promising extract on larvae (E = 72.77%, LC90 = 10.86 mg/mL). In RCE, the presence of lectins and secondary metabolites: flavonoids, xanthones and phenols, were detected. The results demonstrate the potential of E. contortisiliquum seed extracts with ovicidal and larvicidal action on A. aegypti.


Assuntos
Aedes , Anopheles , Fabaceae , Inseticidas , Animais , Inseticidas/farmacologia , Solução Salina/análise , Extratos Vegetais/química , Sementes , Larva , Compostos Fitoquímicos/análise , Lectinas/análise
4.
Artigo em Inglês | MEDLINE | ID: mdl-37172801

RESUMO

High-fat diet-induced obesity detrimentally affects brain function by inducing chronic low-grade inflammation. This neuroinflammation is, at least in part, likely to be mediated by microglia, which are the main immune cell population in the brain. Microglia express a wide range of lipid-sensitive receptors and their activity can be modulated by fatty acids that cross the blood-brain barrier. Here, by combining live cell imaging and FRET technology we assessed how different fatty acids modulate microglia activity. We demonstrate that the combined action of fructose and palmitic acid induce Ikßα degradation and nuclear translocation of the p65 subunit nuclear factor kB (NF-κB) in HCM3 human microglia. Such obesogenic nutrients also lead to reactive oxygen species production and LynSrc activation (critical regulators of microglia inflammation). Importantly, short-time exposure to omega-3 (EPA and DHA), CLA and CLNA are sufficient to abolish NF-κB pathway activation, suggesting a potential neuroprotective role. Omega-3 and CLA also show an antioxidant potential by inhibiting reactive oxygen species production, and the activation of LynSrc in microglia. Furthermore, using chemical agonists (TUG-891) and antagonists (AH7614) of GPR120/FFA4, we demonstrated that omega-3, CLA and CLNA inhibition of the NF-κB pathway is mediated by this receptor, while omega-3 and CLA antioxidant potential occurs through different signaling mechanisms.


Assuntos
Ácidos Graxos Ômega-3 , NF-kappa B , Humanos , NF-kappa B/metabolismo , Ácidos Graxos/metabolismo , Microglia/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Inflamação/metabolismo
5.
Food Chem ; 410: 135319, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634564

RESUMO

The tomato processing industry is one of the world's most important markets. This industry aims to optimise production, minimise energy costs and waste streams while ensuring high-quality products. This sector produces substantial amounts of by-products frequently disposed of as waste rather than reintroducing them with a new intent into the supply chain. However, these by-products are rich in bioactive compounds (BC), including carotenoids, fibre, which exhibit antioxidant, anti-inflammatory and chemopreventive properties, and cardiovascular protection. Reusing these compounds is favourable to reducing the environmental impact and enables the development of added-value products with various possible uses such as food and feed additives, nutraceuticals, cosmeceuticals, etc. This review summarises relevant issues towards the recovery and valorisation of BC from industrial tomato by-products within a circular economy context.


Assuntos
Solanum lycopersicum , Humanos , Carotenoides/análise , Antioxidantes , Manipulação de Alimentos , Suplementos Nutricionais
6.
Clin Pharmacol Ther ; 112(3): 605-614, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35355249

RESUMO

PF-06835919 is a first-in-class ketohexokinase inhibitor (KHKi), recently under development for the treatment of metabolic and fatty liver diseases, which inhibited organic anion transporting polypeptide (OATP)1B1 in vitro and presented drug-drug interaction (DDI) risk. This study aims to investigate the dose-dependent effect of KHKi on OATP1B in vivo activity. We performed an open-label study comparing pharmacokinetics of atorvastatin (OATP1B probe) dosed alone (20 mg single dose) and coadministered with two dose strengths of KHKi (50 and 280 mg once daily) in 12 healthy participants. Additionally, changes in exposure of coproporphyrin-I (CP-I), an endogenous biomarker for OATP1B, were assessed in the atorvastatin study (1.12-fold and 1.49-fold increase in area under the plasma concentration-time profile (AUC) with once-daily 50 and 280 mg, respectively), and a separate single oral dose study of KHKi alone (100-600 mg, n = 6 healthy participants; up to a 1.80-fold increase in AUC). Geometric mean ratios (90% confidence interval) of atorvastatin AUC following 50 and 280 mg KHKi were 1.14 (1.00-1.30) and 1.54 (1.37-1.74), respectively. Physiologically-based pharmacokinetic modeling of CP-I plasma exposure following a single dose of KHKi predicted in vivo OATP1B inhibition from about 13% to 70% over the 100 to 600 mg dose range, while using the in vitro inhibition potency (1.9 µM). Model-based analysis correctly predicted "no-effect" (AUC ratio < 1.25) at the low dose range and "weak" effect (AUC ratio < 2) on atorvastatin pharmacokinetics at the high dose range of KHKi. This study exemplified the utility of biomarker-informed model-based approach in discerning even small effects on OATP1B activity in vivo, and to project DDI risk at the clinically relevant doses.


Assuntos
Frutoquinases , Atorvastatina , Biomarcadores , Interações Medicamentosas , Frutoquinases/metabolismo , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Medição de Risco
7.
Environ Res ; 209: 112868, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35143803

RESUMO

A fruit processing wastewater was submitted to different advanced oxidation processes, namely, electro-Fenton (EF), electrochemical oxidation (EO), activated persulfate (PS), and combined EF/PS. The performance of the treatment processes, at different experimental conditions, regarding organic load removal, biodegradability increment, toxicity reduction, and specific energy consumption (Esp), was evaluated. At the experimental conditions studied, EO led to the treated solutions with the highest biodegradability increment, from 0.24 to 0.48, and toxicity reduction towards Daphnia magna, from 5.8 to 1.5 toxic units, without requiring the addition of chemicals. Nevertheless, the highest chemical oxygen demand (COD) removals were obtained for EF and combined EF/PS treatments. For the electrochemical processes, an increase in COD removal rate with applied current density (j) was observed. However, the increase in j substantially raised the Esp. In PS treatment, COD removals above 80% were only achieved for high amounts of added persulfate and iron, which led to less biodegradable and more toxic solutions. Combined EF/PS attained the lowest Esp values, mainly due to the conductivity increase originated by the persulfate and iron salts addition. Besides the disadvantage of the chemicals added, this combined treatment led to treated solutions with very acidic pH and significant iron content.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Análise da Demanda Biológica de Oxigênio , Frutas/química , Peróxido de Hidrogênio , Oxirredução , Eliminação de Resíduos Líquidos , Águas Residuárias/química , Águas Residuárias/toxicidade , Poluentes Químicos da Água/análise
8.
Mol Neurobiol ; 58(11): 5971-5985, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34432265

RESUMO

The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system to the pathogenesis of multiple sclerosis (MS). Here, we examined the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also investigated if the treatment with pramipexole (PPX)-a dopamine D2/D3 receptor-preferring agonist-would be able to prevent EAE-induced motor and mood dysfunction, as well as its underlying mechanisms of action. We report that D2R immunocontent is upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontents in lymph nodes and the oxidative damage in the spinal cord and striatum of EAE animals were significantly increased during the chronic phase. Also, during the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. Surprisingly, therapeutic treatment with PPX failed to inhibit the progression of EAE. Of note, PPX treatment inhibited EAE-induced depressive-like while failed to inhibit anhedonic-like behaviors. We observed that PPX treatment downregulated IL-1ß levels and increased BNDF content in the spinal cord after EAE induction. Herein, we show that a D2/D3 receptor-preferred agonist mitigated EAE-induced depressive-like behavior, which could serve as a new possibility for further clinical trials on treating depressive symptoms in MS patients. Thus, we infer that D2R participates in the crosstalk between CNS and immune system during autoimmune and neuroinflammatory response induced by EAE, mainly in the acute and chronic phase of the disease.


Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Anedonia/efeitos dos fármacos , Anedonia/fisiologia , Animais , Axônios/patologia , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Corpo Estriado/metabolismo , Depressão/etiologia , Depressão/prevenção & controle , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/psicologia , Feminino , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Estresse Oxidativo , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/genética , Pramipexol/farmacologia , Pramipexol/uso terapêutico , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistas , Método Simples-Cego , Medula Espinal/metabolismo , Medula Espinal/patologia
9.
J Appl Microbiol ; 130(1): 61-75, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32654270

RESUMO

AIM: To evaluate the antifungal activity of extracts of Chamaecostus cuspidatus against Candida and Trichophyton species. METHODS AND RESULTS: Crude ethanol extracts of leaves, stems and rhizomes were prepared and evaluated for antimicrobial activity. Only the rhizomes extract (RE) showed antifungal activity but had no inhibitory effect against bacteria (Staphylococcus aureus and Escherichia coli). The RE was then submitted to liquid-liquid partition with hexane (Hex), dichloromethane, chloroform, ethyl acetate and water. The Hex fraction (Hex Fr) from the RE was found to have the best antifungal effect. Three known saponins were isolated from the Hex Fr, of which two (dioscin and aferoside A) showed good antifungal activity. In addition, Hex Fr and the two bioactive compounds had no antibacterial effect, but exhibited fungicidal activity, caused significant changes in the morphology of the fungal cells and showed anti-Candida albicans biofilm activity. Finally, the bioactive plant products presented greater selectivity for fungal cells over normal human cells. CONCLUSIONS: The rhizomes of C. cuspidatus have bioactive saponins that function as effective antifungals against Candida and Trichophyton species, and have antibiofilm activity against C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: Chamaecostus cuspidatus REs may have potential clinical application towards the management of superficial mycoses caused by Candida and Trichophyton species.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Saponinas/farmacologia , Trichophyton/efeitos dos fármacos , Zingiberales/química , Antifúngicos/química , Antifúngicos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rizoma/química , Saponinas/química , Saponinas/isolamento & purificação
10.
Molecules ; 25(9)2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32397593

RESUMO

The possibility of obtaining a carmine or pink color on ordinary cooked ham by applying natural dyes from three plant species, namely red radish (Raphanus sativus L.), hibiscus (Roselle sabdariffa L.) and red beetroot (Beta vulgaris L.), was investigated. The extracts were evaluated for the stability at physical-chemical parameters and subjected to cytotoxicity assays in the gastric cell line AGS Encapsulation of the extracts in soybean lecithin liposomes and maltodextrin microcapsules was performed. Lyophilized extracts before and after encapsulation in maltodextrin were applied in the formulation of ordinary cooked ham and used in a pilot scale of production. The color of cooked ham samples from different assays was evaluated visually and by colorimetry. The results suggest that the coloration of ordinary cooked ham obtained with extracts of red beetroot is very promising for future applications in this type of meat product.


Assuntos
Beta vulgaris/química , Betalaínas/análise , Culinária/métodos , Produtos da Carne/normas , Extratos Vegetais/análise , Carne de Porco/normas , Betacianinas/análise , Betacianinas/química , Betacianinas/toxicidade , Betalaínas/química , Betalaínas/isolamento & purificação , Betalaínas/toxicidade , Cápsulas/química , Linhagem Celular , Cor , Colorimetria , Corantes/química , Corantes/isolamento & purificação , Hibiscus/química , Humanos , Lecitinas/química , Lipossomos/química , Espectrometria de Massas , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Polissacarídeos/química , Raphanus/química , Glycine max/química
11.
J Ethnopharmacol ; 251: 112571, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31935494

RESUMO

BACKGROUND: Senecio biafrae is a medicinal plant widely used in traditional medicine to cure female infertility. Some effects have been pharmacologically demonstrated on immature female rats but in vivo and in vitro investigations are still necessary for determining its mechanism of action. The aim of the present study was to evaluate the estrogenic and FSH-like effects of the plant extracts and fractions on some fertility parameters in immature female rats and on in vitro survival and growth of swine preantral follicles. METHODS: 21-23 days old female Wistar rats orally received extracts and fractions of S. biafrae at 0, 8 and 64 mg/kg doses over 20 days. The LH, FSH, estradiol and progesterone serum levels were evaluated as well as the ovarian cholesterol, uterus and ovaries masses and proteins. The numbers of follicles at different developmental stages were recorded in ovarian cortexes after histology. Slices of swine ovarian cortexes were cultured along 1 or 7 days in alpha-minimum essential medium (α-MEM) and fixed for morphological analysis of preantral follicles. The fresh control, cultured control (CIV control) and different Senecio biafrae-treated ovarian fragments were analyzed for preantral follicles development. Treatments that showed the best follicle growth in culture were submitted to AgNOR test. The aqueous and MeOH/CH2Cl2 extracts as well as the ethyl acetate and hexane fractions of S. biafrae were submitted to the HPLC for analysis of polyphenolic secondary metabolites. RESULTS: Ovarian and uterine proteins were significantly high (p < 0.01) in animals treated with the two dosages of ethyl acetate and n-butanol fractions. The same result was recorded with uterine proteins in animals treated with the hexane fraction. The FSH level significantly dropped with all ethanolic extract doses and with the 64 mg/kg dosage of the methanol/methylene chloride (MeOH/CH2Cl2) extract while LH was reduced (p < 0.01) in almost all the treated groups. Estradiol level was significantly increased (p < 0.001) in the three groups receiving the extracts, but reduced (p < 0.001) in the three groups receiving the fractions of the plant. The progesterone level increased with almost all the treated groups. Primary and secondary follicles augmented (p < 0.01) in MeOH/CH2Cl2 extract and n-butanol fraction while tertiary follicles increased with the same extract and the ethyl acetate fraction (p < 0.05). Treatments with aqueous and ethanolic extracts as well as ethyl acetate fraction led to a significant increase (p < 0.05) in the number of morphologically normal follicles after 7 days of culture as compared to the CIV control. The number of AgNOR dots per follicle was significantly low (p < 0.05) in all cultured groups as compared to the fresh control, except the ethyl acetate 2.8 ng/ml dosage. The same observation was done with AgNOR dots per cell in the 2.8 ng/ml dosage aqueous extract-treated fragments. The phenolic compounds mainly encountered in the plant, independently of the extract or fraction are apigenin, eugenol and rutin. CONCLUSION: Extracts and fractions of S. biafrae have an important FSH-like effect which induces follicular survival and growth.


Assuntos
Ovário/efeitos dos fármacos , Extratos Vegetais/farmacologia , Senécio , Animais , Colesterol/metabolismo , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ovário/metabolismo , Progesterona/sangue , Ratos Wistar , Suínos
13.
J Pharmacol Exp Ther ; 372(3): 308-319, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31879375

RESUMO

Within the drug pharmacokinetics (PK)-absorption, distribution, metabolism, and excretion (ADME) research community, investigators regularly generate in vitro data sets using appropriately vendor-sourced and processed human tissue. Such data enable drug screening, the generation of kinetic parameters, extrapolation of in vitro to in vivo, as well as the modeling and simulation of drug PK. Although there are large numbers of manuscripts describing studies with deceased organ donor tissue, relatively few investigators have published studies utilizing living donor tissue biopsy samples. After a review of the available literature, it was possible to find publications describing the use of tissue biopsy samples to determine enzyme inhibition ex vivo, the study of genotype-phenotype associations, the evaluation of tissue expression profiling following an inducer, and assessment of correlations between tissue expression profiles and in vivo-derived trait measures (e.g., biomarker plasma levels and probe drug PK). Some reports described multiple single-tissue biopsies, whereas others described single multiple-organ biopsies. It is concluded that biopsy-derived data can support modeling exercises (as input data and when validating models) and enable the assessment of organ-specific changes in enzyme and transporter profiles resulting from drug interactions, disease (e.g., metabolic disease, fibrosis, inflammation, cancer, infection), age, pregnancy, organ impairment, and genotype. With the emergence of multiorgan axes (e.g., microbiome-gut-liver-kidney) and interest in remote sensing (interorgan communication), it is envisioned that there will be increased demand for single- and multiorgan tissue biopsy data to support hypothesis testing and PK-ADME model building. SIGNIFICANCE STATEMENT: Based on a review of the literature, it is apparent that profiling of human tissue biopsy samples is useful in support of pharmacokinetics (PK)-absorption, distribution, metabolism, and excretion (ADME)-related studies. With conventional tissue biopsy as precedent, it is envisioned that researchers will turn to less invasive "liquid biopsy" methods in support of ADME-related studies (e.g., profiling of plasma-derived tissue-specific nanovesicles). Generation of such multiorgan liquid biopsy data in larger numbers of subjects and at multiple study time points will provide a rich data set for modeling purposes.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Fígado/enzimologia , Proteínas de Membrana Transportadoras/metabolismo , Modelos Biológicos , Preparações Farmacêuticas/metabolismo , Biópsia , Humanos , Taxa de Depuração Metabólica , Preparações Farmacêuticas/sangue , Farmacocinética , Distribuição Tecidual
14.
Oxid Med Cell Longev ; 2019: 5316984, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772706

RESUMO

Advanced maternal age is associated with higher infertility rates, pregnancy-associated complications, and progeny health issues. The ovary is considered the main responsible for these consequences due to a continuous decay in follicle number and oocyte quality. Intracellular imbalance between oxidant molecules and antioxidant mechanisms, in favour of the former, results in oxidative stress (OS) that is believed to contribute to ovarian ageing. This work is aimed at evaluating whether an age-related increase in ovarian OS, inflammation, and fibrosis may contribute to tissue dysfunction and whether specific antioxidant supplementation with a NADPH oxidase inhibitor (apocynin) could ameliorate them. Mice aged 8-12 weeks (reproductively young) or 38-42 weeks (reproductively aged) were employed. Aged mice were divided into two groups, with one receiving apocynin (5 mM) in the drinking water, for 7 weeks, upon which animals were sacrificed and their ovaries collected. Ovarian structure was similar at both ages, but the ovaries from reproductively aged mice exhibited lipofuscin deposition, enhanced fibrosis, and a significant age-related reduction in primordial and primary follicle number when compared to younger animals. Protein carbonylation and nitration, and markers of OS were significantly increased with age. Moreover, mRNA levels of inflammation markers, collagens, metalloproteinases (MMPs), and tissue inhibitor MMPs (TIMPs) were upregulated. Expression of the antifibrotic miRNA29c-3p was significantly reduced. Apocynin supplementation ameliorated most of the age-related observed changes, sometimes to values similar to those observed in young females. These findings indicate that there is an age-related increase in OS that plays an important role in enhancing inflammation and collagen deposition, contributing to a decline in female fertility. Apocynin supplementation suggests that the imbalance can be ameliorated and thus delay ovarian ageing harmful effects.


Assuntos
Acetofenonas/uso terapêutico , Ovário/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Acetofenonas/farmacologia , Idoso , Animais , Suplementos Nutricionais , Feminino , Humanos , Camundongos , Gravidez
15.
Mucosal Immunol ; 12(1): 188-199, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30279515

RESUMO

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-ß via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-ß)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.


Assuntos
Colite/imunologia , Neoplasias Colorretais/imunologia , Doenças Inflamatórias Intestinais/imunologia , Ácidos Linoleicos Conjugados/metabolismo , Macrófagos/imunologia , PPAR gama/metabolismo , Linfócitos T/imunologia , Ácido Aminossalicílico/metabolismo , Animais , Carcinogênese , Células Cultivadas , Colite/induzido quimicamente , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR gama/genética , Fator de Crescimento Transformador beta/metabolismo
16.
J Appl Toxicol ; 38(10): 1323-1335, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29785833

RESUMO

Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee. Glycine amidation was predominant in human, minipig, hamster and rabbit, while taurine amidation was predominant in mice, rat and dogs. BA profiles consisted primarily of tri-OH BAs in hamster, rat, dog and mice, di-OH BAs in human, rabbit and minipig, and mono-OH BA in chimpanzee. BA profiles comprised primarily hydrophilic and less toxic BAs in mice, rat, pig and hamster, while it primarily comprised hydrophobic and more toxic BAs in human, rabbit and chimpanzee. Therefore, the hydrophobicity index was lowest in minipig and mice, while it was highest in rabbit, monkey and human. Glucuronidation and glutathione conjugation were low in all species across all BAs. Total concentration of BAs in urine was up to 10× higher and more hydrophilic than plasma in most species. This was due to the presence of more tri-OH, amidated, sulfated and primary BAs, in urine compared to plasma. In general, BA profiles of chimpanzee and monkeys were most similar to human, while minipig, rat and mice were most dissimilar to human.


Assuntos
Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/urina , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Especificidade da Espécie , Animais , Cães , Avaliação Pré-Clínica de Medicamentos , Humanos , Macaca fascicularis , Macaca mulatta , Mesocricetus , Camundongos Endogâmicos C57BL , Pan troglodytes , Coelhos , Ratos Sprague-Dawley , Suínos
17.
J Anim Physiol Anim Nutr (Berl) ; 102(2): 514-524, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28691242

RESUMO

Consumption of a second meal of colostrum with high quality could contribute to the intestinal epithelium development, especially if there is poor supply of colostrum just after birth. The effect of a second colostrum meal was evaluated on histomorphometry of the intestinal mucosa of newborn Holstein calves fed with high- and low-quality first colostrum. Seventy-two calves were fed with a first colostrum meal with high (HFM, close to 100 mg/ml) or low (LFM, close to 30 mg/ml) IgG concentration. At 12 hr of life, three treatments of second colostrum feeding were applied to the calves either fed high or low first colostrum: calves fed with low (LOW-close to 30 mg/ml) or high (HIGH-close to 100 mg/ml) IgG concentration; and colostrum enriched with lyophilized bovine colostrum with high IgG concentration (ENRICHED-higher than 120 mg/ml), resulting in six groups. Intestinal samples were collected after 24 and 72 hr of life. In the distal jejunum and ileum, LOW showed higher villus height than ENRICHED (p < .05). In the distal jejunum, greater villus perimeter was observed in the LOW compared to ENRICHED at 24 hr (p < .05). In ileum, LFM showed higher villus perimeter compared to HFM (p < .05). LOW showed the highest villus height-to-crypt depth ratio in the medium and distal jejunum and ileum, p < .05. ENRICHED and HFM showed decreased muscle layer thickness in the proximal and distal jejunum respectively (p < .05). The results reveal that the high concentration of total solids, crude protein, IgG and IGF-I of colostrum with high quality worsened the absorptive area, but may have stimulated the activity of cell division in intestinal crypts. Considering the present results, bovine colostrum enriched with lyophilized bovine colostrum stimulates intestinal epithelium renewal of Holstein calves in the first days of life.


Assuntos
Ração Animal/análise , Animais Recém-Nascidos , Bovinos , Colostro/química , Mucosa Intestinal/efeitos dos fármacos , Animais , Alimentos Fortificados , Liofilização
18.
J Wound Care ; 26(11): 692-695, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29131751

RESUMO

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.


Assuntos
Pé Diabético/terapia , Hidrogéis/uso terapêutico , Oxigenoterapia Hiperbárica , Ferida Cirúrgica/terapia , Idoso , Amputação Cirúrgica , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pé Diabético/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Dedos do Pé/cirurgia , Cicatrização
19.
Theriogenology ; 89: 226-234, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28043356

RESUMO

The aim of this study was to investigate the effect of three concentrations of anethole (30, 300, and 2000 µg/mL) on survival, antrum formation, follicular diameter, and oocyte maturation in the caprine species. The study also evaluated the effects of anethole on transcripts of ICAM-1, CAV-1, TIMP-2, and PAI-1 genes and levels of reactive oxygen species (ROS) in isolated goat preantral ovarian follicles before and after in vitro culture for 18 days. Preantral follicles were isolated from goat ovaries and individually cultured in alpha minimum essential medium modified (α-MEM+), defined as the control treatment, α-MEM+ supplemented with ascorbic acid at a concentration of 100 µg/mL (AA), or α-MEM+ supplemented with three different concentrations of anethole (30, 300, 2000 µg/mL) for a period of 18 days. Treatments were named as α-MEM+, AA, AN30, AN300, and AN2000, respectively. After culture, the follicles were opened, the cumulus oocytes complex (COCs) were removed and matured in vitro. The walls of the follicles were used for the quantitation of mRNA by quantitative real-time polymerase chain reaction. Finally, the medium collected at the end of culture was used for the measurements of ROS. After 18 days of culture, the AA treatment showed the percentage of intact follicles and follicular diameter significantly higher compared with the other treatments. However, daily growth rate, antrum formation, and also oocyte diameter were similar among the treatments. In addition, compared with AA, the rate of oocytes for in vitro maturation (diameter ≥ 110 µm) and the meiosis resumption rate were significantly higher in the treatments AN30 and AN2000, respectively. When assessing gene related to remodeling of the basement membrane, significant differences in mRNA levels for ICAM-1, CAV-1, TIMP-2, and PAI-1 were observed in comparison with Day 0, i.e., in the noncultured control. In addition, the ROS from Day 12, all treatments with the addition of anethole have significantly lower values of ROS than α-MEM+ and AA. In conclusion, the addition of anethole to the in vitro culture medium was able to improve the development of goat preantral follicles by reducing concentrations of ROS and increasing the percentage of oocytes able to resume meiosis.


Assuntos
Anisóis/farmacologia , Cabras/fisiologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Folículo Ovariano/crescimento & desenvolvimento , Derivados de Alilbenzenos , Animais , Feminino , Técnicas de Maturação in Vitro de Oócitos/métodos , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
BMC Pediatr ; 16(1): 199, 2016 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-27912735

RESUMO

BACKGROUND: Providing an early, additional measles vaccine (MV) at 4.5 months of age has been shown to reduce child mortality in low-income countries. We studied the effects on growth at 9 and 24 months of age. METHODS: A randomized controlled trial was conducted in Guinea-Bissau from 2003-2007 including 6,648 children. Children were randomized 1:1:1 to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months (group C) Data on anthropometrics were obtained at enrolment at 4.5 months of age and again at 9 and 24 months of age. Analyses were stratified by sex, season of enrolment, and neonatal vitamin A supplementation (NVAS) status, as all these factors have been shown to modify the effect of early MV on mortality. RESULTS: Overall there was no effect of early MV on anthropometry at 9 months. At 24 months children who had received early MV had a significantly larger mid-upper-arm-circumference (MUAC/in cm) (Difference = 0.08; 95% CI (0.02;0.14)) compared with children in the control group; this effect was most pronounced among girls (0.12 (0.03;0.20)). The effect of early MV on MUAC remained significant in the dry season and in girls who received placebo rather than NVAS. CONCLUSION: Early MV was associated with a larger MUAC particularly in girls. These results indicate that a two-dose measles vaccination schedule might not only reduce child mortality but also improve growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT00168558 . Registered September 9, 2005, retrospectively registered.


Assuntos
Estatura , Desenvolvimento Infantil , Esquemas de Imunização , Vacina contra Sarampo , Sarampo/prevenção & controle , Aumento de Peso , Feminino , Seguimentos , Guiné-Bissau , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estações do Ano , Fatores Sexuais
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