Impacto da gordura abdominal e resistência à insulina na hipertensão arterial em mulheres não-obesas

OBJECTIVE: To evaluate the impact of abdominal fat and insulin resistance on arterial hypertension of non-obese women. METHODS:Thirty-five non-obese women (NO), age 35-68 years were studied, and divided into two groups according to the presence of hypertension (BP > 140 x 90 mmHg) ( HT = hypertensive; NT = normotensive). Leptin measurement and oral glucose tolerance test (OGTT) to assess insulin were performed in these patients. A CT-scan was used to evaluate visceral (VF) and subcutaneous abdominal fat (SCF). The Central fat distribution index (CDI) was proposed to evaluate the impact of subcutaneous abdominal fat on central fat distribution in hypertensive patients. RESULTS: When compared to NT-NO (n = 17) group, HT-NO (n = 18) showed higher blood pressure levels (systolic and diastolic), greater VF area (84.40 ± 55.70 versus 37.50 ± 23.00 cm²; p = 0.036), greater SCF area (174.30 ± 83.00 versus 79.80 ± 27.40 cm²; p = 0.030), higher HOMAr index (1.59 ± 0.72 versus 0.93 ± 0.48 mmol.mU/L²; p = 0.006), higher CDI index (12.67 ± 7.04 versus 6.19 ± 2.57 cm²/kg) and higher leptin level (19.1 ± 9.6 versus 7.4 ± 3.5 ng/mL; p = 0.028). CONCLUSIONS: Arterial hypertension in non-obese women is associated with insulin resistance, central fat distribution and higher leptin levels.OBJETIVO: Avaliar o impacto da gordura abdominal e resistência à insulina na hipertensão arterial em mulheres não-obesas. MÉTODOS: Foram estudadas 35 mulheres não obesas (NO), com idade entre 35 e 68 anos, separadas em dois grupos de acordo com a presença de hipertensão arterial (PA > 140 x 90 mmHg) (HT = hipertenso; NT = normotenso). A leptina foi dosada e um OGTT realizado. Um corte tomográfico foi usado para avaliar a gordura visceral (VF) e subcutânea abdominal (SCF). O índice de distribuição central de gordura (CDI) foi proposto para avaliar o impacto da gordura subcutânea abdominal na distribuição central de gordura em pacientes hipertensas. RESULTADOS: Quando comparado ao grupo NT-NO (n = 17), o grupo HT-NO (n = 18) mostrou maiores níveis de pressão arterial (sistólica e diastólica), maior área de gordura visceral (84.40 ± 55.70 versus 37.50 ± 23.00 cm²; p = 0.036), maior área de gordura subcutânea abdominal (174.30 ± 83.00 versus 79.80 ± 27.40 cm²; p = 0.030), maior HOMAr (1.59 ± 0.72 versus 0.93 ± 0.48 mmol.mU/L²; p = 0.006), maior índice CDI (12.67 ± 7.04 versus 6.19 ± 2.57 cm²/kg) e maior nível de leptina (19.1 ± 9.6 versus 7.4 ± 3.5 ng/mL; p = 0.028). CONCLUSÕES: A hipertensão arterial em mulheres não obesas está associada à resistência à insulina, distribuição central de gordura e altos níveis de leptina.Universidade Federal de São Paulo (UNIFESP) Departamento de EndocrinologiaUNIFESP, Depto. de EndocrinologiaSciEL

Antecedentes del estudio metabólico de MDPV y metilona. Propuesta de un modelo de biotransformación a través de hongos del género Cunninghamella

La (±)-3,4-metilendioxipirovalerona (MDPV) y la (±)-3,4-metilenedioximetilcatinona (metilona) son algunos de los derivados sintéticos de catinonas más frecuentemente encontrados en productos que se comercializan como “sales de baño” y que hoy en día se emplean como drogas de abuso. Los reportes de casos fatales por consumo de estas sustancias aumentan cada día, y aunque existen algunos estudios farmacológicos y toxicológicos, no son claros los mecanismos de acción y los efectos causados por su consumo recreativo. La implementación de sistemas que permitan conocer el metabolismo de estas drogas en humanos y el diseño de métodos analíticos para su detección son ahora objeto de investigación. Este artículo presenta una revisión bibliográfica acerca de los estudios de biotransformación para MDPV y metilona empleando modelos in vitro con microsomas hepáticos humanos, fracciones celulares S9 y modelos in vivo con animales de experimentación y posterior análisis de los metabolitos que hay hasta la fecha. Las técnicas analíticas utilizadas para el análisis de metabolitos incluyen cromatografía líquida acoplada a detector selectivo de masas (LC-MS o LC-MS/MS) o la formación de derivados acetilados o sililados para su posterior análisis por cromatografía de gases acoplada a detector selectivo de masas (GC-MS). Además, se incluye una propuesta para el estudio del metabolismo para metilona y MDPV a través de hongos del género Cunninghamella.(±)-3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylendioxymethylcathi-none (methylone) are some of the most frequent synthetic derivatives of cathinones found in commercial products known as "Bath salts" and which today are used as drugs of abuse. Reports on fatal cases involving the consumption of these substances are raising and although there are some pharmacological and toxicological studies, their action mechanisms and effects due recreational consumption are not very well understood. The implementation of systems that allows the understanding of the metabolism of these drugs in humans and the design of analytical methods for their detection is now the subject of research. This paper shows a bibliographical review of the studies conducted on the biotransformation of methylone and MDPV using in vitro models with human hepatic microsomes, cell fractions S9 and in vivo models in animals with posterior analysis of the obtained metabolites. The analytical techniques used for the analysis of the metabolites include liquid chromatography coupled with mass spectrometry (LC-MS or LC-MS/MS) or the formation of acetylated or dimethyl silylated derivatives for their posterior analysis by gas chromatography (GC-MS). A proposal for the study of the metabolisms of methylone and MDPV through the fungus of the genera Cunninghamella is also included

Antecedentes del estudio metabólico de MDPV y metilona. Propuesta de un modelo de biotransformación a través de hongos del género Cunninghamella

La (±)-3,4-metilendioxipirovalerona (MDPV) y la (±)-3,4-metilenedioximetilcatinona (metilona) son algunos de los derivados sintéticos de catinonas más frecuentemente encontrados en productos que se comercializan como “sales de baño” y que hoy en día se emplean como drogas de abuso. Los reportes de casos fatales por consumo de estas sustancias aumentan cada día, y aunque existen algunos estudios farmacológicos y toxicológicos, no son claros los mecanismos de acción y los efectos causados por su consumo recreativo. La implementación de sistemas que permitan conocer el metabolismo de estas drogas en humanos y el diseño de métodos analíticos para su detección son ahora objeto de investigación. Este artículo presenta una revisión bibliográfica acerca de los estudios de biotransformación para MDPV y metilona empleando modelos in vitro con microsomas hepáticos humanos, fracciones celulares S9 y modelos in vivo con animales de experimentación y posterior análisis de los metabolitos que hay hasta la fecha. Las técnicas analíticas utilizadas para el análisis de metabolitos incluyen cromatografía líquida acoplada a detector selectivo de masas (LC-MS o LC-MS/MS) o la formación de derivados acetilados o sililados para su posterior análisis por cromatografía de gases acoplada a detector selectivo de masas (GC-MS). Además, se incluye una propuesta para el estudio del metabolismo para metilona y MDPV a través de hongos del género Cunninghamella.(±)-3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylendioxymethylcathi-none (methylone) are some of the most frequent synthetic derivatives of cathinones found in commercial products known as "Bath salts" and which today are used as drugs of abuse. Reports on fatal cases involving the consumption of these substances are raising and although there are some pharmacological and toxicological studies, their action mechanisms and effects due recreational consumption are not very well understood. The implementation of systems that allows the understanding of the metabolism of these drugs in humans and the design of analytical methods for their detection is now the subject of research. This paper shows a bibliographical review of the studies conducted on the biotransformation of methylone and MDPV using in vitro models with human hepatic microsomes, cell fractions S9 and in vivo models in animals with posterior analysis of the obtained metabolites. The analytical techniques used for the analysis of the metabolites include liquid chromatography coupled with mass spectrometry (LC-MS or LC-MS/MS) or the formation of acetylated or dimethyl silylated derivatives for their posterior analysis by gas chromatography (GC-MS). A proposal for the study of the metabolisms of methylone and MDPV through the fungus of the genera Cunninghamella is also included

Analysis of in vivo absorption of didanosine tablets in male adult dogs by HPLC

AbstractDidanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28°C. For an isocratic run, the flux was 1.0mL/min, detection was at 250nm and injected volume was 20μL. The method was selective and linear for concentrations between 50 and 5000ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at −20°C for one month after three freeze–thaw cycles, and for 24h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs

Ontologies and Unified Modeling Language: an approach to representation of domains of knowledge

This article emphasizes the use of Unified Modeling Language, UML in the specification of models based on ontologies in the representation of domains of knowledge, emphasizing the importance of semantic and of treatment of standardized language so the knowledge of the domain can be organized and shared. Finally, this article aims to establish a connection between the themes: the object oriented modeling and ontologies.Este artigo destaca o uso da Unified Modeling Language, UML na especificação de modelos baseados em ontologias na representação de domínios de conhecimento, enfatizando a importância da semântica e do tratamento da linguagem padronizada para que o conhecimento do domínio possa ser organizado e compartilhado. Finalmente, este artigo tem como objetivo estabelecer uma conexão entre as temáticas: modelagem orientada a objetos e ontologias

Thymus zygis subsp. zygis an endemic portuguese plant: phytochemical profiling, antioxidant, anti-proliferative and anti-inflammatory activities

Thymus zygis subsp. zygis is an endemic Portuguese plant belonging to the Thymus zygis species. Although T. zygis is commonly used as a condiment and as a medicinal herb, a detailed description of the polyphenol composition of hydroethanolic (HE) and aqueous decoction (AD) extracts is not available. In this work, we describe for the first time a detailed phenolic composition of Thymus zygis subsp. zygis HE and AD extracts, together with their antioxidant, anti-proliferative and anti-inflammatory activities. Unlike other Thymus species, T. zygis subsp. zygis extracts contain higher amounts of luteolin-(?)-O-hexoside. However, the major phenolic compound is rosmarinic acid, and high amounts of salvianolic acids K and I were also detected. T. zygis subsp. zygis extracts exhibited significant scavenging activity of ABTS+, hydroxyl (•OH), and nitric oxide (NO) radicals. Regarding the anti-proliferative/cytotoxic effect, tested against Caco-2 and HepG2 cells, the AD extract only slightly reduced cell viability at higher concentrations (IC50 > 600 µg/mL, 48 h exposure), denoting very low toxicity, while the HE extract showed a high anti-proliferative effect, especially at 48 h exposure (IC50 of 85.01 ± 15.10 μg/mL and 82.19 ± 2.46 μg/mL, for Caco-2 and HepG2, respectively). At non-cytotoxic concentrations, both extracts reduced the nitric oxide (NO) release by lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (at 50 μg/mL, HE and AD extracts inhibited NO release in ~89% and 48%, respectively). In conclusion, the results highlight the non-toxic effect of aqueous extracts, both resembling the consumption of antioxidants in foodstuff or in functional food. Furthermore, the HE extract of T. zygis subsp. zygis is a source of promising molecules with antioxidant, anti-inflammatory and anticancer activities, highlighting its potential as a source of bioactive ingredients for nutraceutical and pharmaceutical industries.This work was supported by the INTERACT project–“Integrative Research in Environment, Agro-Chains and Technology”, no. NORTE-01-0145- FEDER-000017, in its line of research entitled ISAC, co-financed by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020). By funds from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, under the projects UIDB/04033/2020 (CITAB), UIDB/00616/2020 (CQ-VR) and UIDB/04469/2020 (CEB). FCT is also acknowledged for the grant to C.M.G. (SFRH/BD/145855/2019).info:eu-repo/semantics/publishedVersio

Impact of percentage and particle size of sugarcane biochar on the sorption behavior of clomazone in Red Latosol

Biochar is a carbonaceous material that has excellent potential as a fertilizer and soil conditioner. However, there is a lack of information concerning the effects of the amount and particle size of this pyrogenic material on the soil sorption capacity. In this work, evaluation was made of changes in clomazone (CMZ) sorption in a Red Latosol following soil conditioning using different percentages (0.25, 0.5, and 1% w/w) of sugarcane biochar in three particle sizes (<106, 106-508, and 508-610 μm). The conditioned soils presented apparent sorption coefficients (Kd) up to 1300 times higher than that of pure soil, besides changes in the behavior of CMZ sorption. The biochar particle size and percentage influenced sorption of the herbicide as well as its retention in the amended soil during desorption processes. Both sorption and desorption Freundlich constants were linearly correlated with the external surface area of the biochar present in the soil

Current State-of-Art and New Trends on Lipid Nanoparticles (SLN and NLC) for Oral Drug Delivery

Lipids and lipid nanoparticles are extensively employed as oral-delivery systems for drugs and other active ingredients. These have been exploited for many features in the field of pharmaceutical technology. Lipids usually enhance drug absorption in the gastrointestinal tract (GIT), and when formulated as nanoparticles, these molecules improve mucosal adhesion due to small particle size and increasing their GIT residence time. In addition, lipid nanoparticles may also protect the loaded drugs from chemical and enzymatic degradation and gradually release drug molecules from the lipid matrix into blood, resulting in improved therapeutic profiles compared to free drug. Therefore, due to their physiological and biodegradable properties, lipid molecules may decrease adverse side effects and chronic toxicity of the drug-delivery systems when compared to other of polymeric nature. This paper highlights the importance of lipid nanoparticles to modify the release profile and the pharmacokinetic parameters of drugs when administrated through oral route

Sucupira oil-loaded nanostructured lipid carriers (NLC): lipid screening, factorial design, release profile, and cytotoxicity

Essential oils are odorant liquid oily products consisting of a complex mixture of volatile compounds obtained from a plant raw material. They have been increasingly proven to act as potential natural agents in the treatment of several human conditions, including diabetes mellitus (DM). DM is a metabolic disorder characterized by chronic hyperglycemia closely related to carbohydrate, protein and fat metabolism disturbances. In order to explore novel approaches for the management of DM our group proposes the encapsulation of sucupira essential oil, obtained from the fruits of the Brazilian plants of the genus Pterodon, in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS). Encapsulation was performed by hot high-pressure homogenization (HPH) technique and the samples were then analyzed by dynamic light scattering (DLS) for mean average size and polydispersity index (PI) and by electrophoretic light scattering (ELS) for zeta potential (ZP), immediately after production and after 24 h of storage at 4 °C. An optimal sucupira-loaded NLC was found to consist of 0.5% (m/V) sucupira oil, 4.5% (m/V) of Kollivax® GMS II and 1.425% (m/V) of TPGS (formulation no. 6) characterized by a mean particle size ranging from 148.1 ± 0.9815 nm (0 h) to 159.3 ± 9.539 nm (at 24 h), a PI from 0.274 ± 0.029 (0 h) to 0.305 ± 0.028 (24 h) and a ZP from −0.00236 ± 0.147 mV (at 0 h) to 0.125 ± 0.162 (at 24 h). The encapsulation efficiency and loading capacity were 99.98% and 9.6%, respectively. The optimized formulation followed a modified release profile fitting the first order kinetics, over a period of 8 h. In vitro cytotoxicity studies were performed against Caco-2 cell lines, for which the cell viability above 90% confirmed the non-cytotoxic profile of both blank and sucupira oil-loaded NLC.This work was financed through the projects M-ERA-NET/0004/2015-PAIRED, UIDB/04469/2020 (CEB strategic fund) and PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund), receiving financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio