Photochemoprevention of topical formulation containing purified fraction of Inga edulis leaves extract.

Natural antioxidants have attracted attention for their therapeutic use as photochemopreventive agents. Inga edulis leaves extract and its purified fraction have high polyphenolic content and high antioxidant capacity. In addition, they presented UV photostability and low citotoxicity in fibroblast cells. In this context, this study first aimed at development of topical formulation containing purified fraction of I. edulis extract and the evaluation of skin penetration of the compounds. Moreover, the photoprotective/photochemopreventive potential of the formulation containing I. edulis purified fraction were investigated in vitro and in vivo. The topical formulation containing 1% of the purified fraction of I. edulis increased the endogenous antioxidant potential of the skin, and vicenin-2 and myricetin compounds were able to penetrate the epidermis and dermis. Additionally, the purified fraction (25 and 50 mg/mL) showed a photoprotective effect against UVA and UVB radiation in L929 fibroblast cells. In vivo studies have shown that the formulation added with purified fraction provided an anti-inflammatory effect on the skin of animals after UVB exposure, since it was observed a reduction in MPO activity, IL-1ß and TNF-α cytokines, and CXCL1/KC chemokine concentrations. In conclusion, the purified fraction of I. edulis, rich in phenolic compounds, when incorporated in topical formulation, appears as an alternative to prevent skin damages induced by UV radiation, due to its antioxidant and anti-inflammatory properties.

Photoprotective effect of solid lipid nanoparticles of rutin against UVB radiation damage on skin biopsies and tissue-engineered skin.

Solid lipid nanoparticles (SLNs) containing rutin were prepared to enhance their photochemopreventive effect on the skin. SLNs were produced by the hot melt microemulsion technique. Two 3D skin models: ex vivo skin explants and 3D tissue engineering skin were used to evaluate the photochemopreventive effect of topical formulations containing rutin SLNs, against ultraviolet B (UVB) radiation, inducing sunburn cells, caspase-3, cyclobutane pyrimidine dimers, lipid peroxidation, and metalloproteinase formation. The rutin SLNs presented average size of 74.22 ± 2.77 nm, polydispersion index of 0.16 ± 0.04, encapsulation efficiency of 98.90 ± 0.25%, and zeta potential of -53.0 ± 1.61 mV. The rutin SLNs were able to efficiently protect against UVB induced in the analysed parameters in both skin models. Furthermore, the rutin SLNs inhibited lipid peroxidation and metalloproteinase formation. These results support the use of rutin SLNs as skin photochemopreventive agents for topical application to the skin.

Soybean extract modified by Aspergillus awamori stimulates a greater collagen-I synthesis in the intracellular matrix of human fibroblasts.

Aglycone isoflavones are estrogen-like bioactive compounds found in low amounts in soybean, which are increased by biotransformation processes. This study investigated two biotransformation processes of soybean extracts with Aspergillus awamori fungus, evaluating aglycone content and capability of stimulation of collagen-I deposition. Isoflavones were quantified via HPLC; cytotoxicity of biotransformed extracts toward mouse and human fibroblasts was evaluated via NRU and apoptosis/necrosis assays; and collagen-I deposition was measured through Western blot, immunofluorescence, and immunoassay. BSE-2 was the biotransformed soybean extract with the highest aglycone content and did not decrease viability or demonstrated cytotoxicity to either L929 or HDFa cells. BSE-2, at the optimal concentration of 1.33 µg/mL, increased substantially collagen-I amount in HDFa intracellular matrix compared to non-biotransformed soybean extract (NBSE) and immunoassay demonstrated that the extracellular deposition was mostly inhibited by BSE-2 concentrations, except at 1.33 µg/mL. Hence, biotransformed soybean extract by the enzymatic filtrate of Aspergillus awamori fungus demonstrated a high nutricosmetic potential, showing safeness and effective collagen-I augmentation.

Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 Variant.

Pathogenic variants of the ADGRG1 gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous ADGRG1 variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel ADGRG1 variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.

Evaluation of cell biomarkers as in vitro photoprotective assays for sunscreen formulations

Objectives: The aim of this study was to evaluate cellular indicators, which change with exposure to ultraviolet (UV) radiation and can be used as parameters for measuring sunscreens efficiency. Methods: Commercial strains of L929 and HaCaT cells (skin dermis and epidermis, respectively), from the cell bank of Rio de Janeiro, were exposed to different doses of UVA (350 nm) and UVB (309 nm) radiation. The evaluation of the photoprotective potential of sunscreens was analyzed with cell viability, lipid peroxidation and ROS generation tests. Samples of sunscreen with SPF values ranging from 15 to 60 were applied to a quartz plate superimposed on the top of a microplate containing the cell culture, and then the system was irradiated. Results: The viability and lipid peroxidation of the two cell lines remained unchanged after exposure to UVA radiation. When exposed to UVB radiation, the reduction in viability and the increase in lipid peroxides were dose-dependent, that is, they varied from 3.15% to 95.4%, and from 1.2 to 42.7 nM MDA/pg protein, respectively, both for the L929 strain. The dose of 0.5 J/cm2 reduced by 41.4%±1.67 the number of viable cells, and the dose of 30 J/cm2 promoted the oxidation of 42.7 nM of MDA/pg protein. These doses were selected to evaluate the photoprotective effectiveness of commercial sunscreens. Sunscreens exposed to UVB rays could prevent the loss of cell viability (viability remained around 100% for higher SPF) and the formation of lipid peroxides (30 to 80% reduction of peroxide levels). None of the two cell strains, submitted to UVB radiation, formed amounts of intracellular ROS in a dose-dependent manner. Under exposure to UVA radiation, only the HaCaT cell line produced the largest amounts of ROS in a dose-dependent manner. After treating these cells with photoprotective formulations (20 J/cm2), the researchers observed a reduction in the amount of ROS formed. Conclusions: The parameters of cell viability and lipid peroxidation were promising to evaluate the photoprotective capacity of sunscreens against UVB radiation. The generation of ROS expressed in the HaCaT strain can discriminate the photoprotective potential of formulations against UVA radiation, as sunscreens reduced the formation of ROS. These results suggest that in vitro tests that evaluate the damage caused to cells can predict cellular indicators of the photoprotective effectiveness of sunscreens and contribute to minimize these tests in the initial phase of product research and development.

Liquid crystalline nanodispersion functionalized with cell-penetrating peptides improves skin penetration and anti-inflammatory effect of lipoic acid after in vivo skin exposure to UVB radiation.

In this study, the development and the performance of a new targeted liquid crystalline nanodispersion (LCN) by the attachment of cell-penetrating peptides (CPP) onto their surfaces to improve skin delivery of lipoic acid (LA) were evaluated. For that, the synthesis and characterization of this new platform as well as its spatiotemporal analysis from in vitro and in vivo topical application were explored and extensively discussed in this paper. The TAT or D4 peptides were chosen as CPP due to specific target strategies by the charge grouping on the skin surface or target the overexpressed epidermal growth factor receptor (EGFR) of cell membrane of keratinocytes, respectively. Thus, the nanoparticle characterization results when taken together suggested that designed LCNs maintained their hexagonal phase structure, nanoscale particle size, and low polydispersity index even after drug, lipopolymers, and peptide additions, which are proved to be favorable for topical skin delivery. There were no statistical differences among the LCNs investigated, except for superficial charge of LCN conjugated with TAT which may have altered the LCN zeta potential due to cationic charge of TAT amino acid sequence compared with D4. The cumulative amounts of LA retained into the skin were determined to be even higher coming from the targeted LCNs. Moreover, the exogenous antioxidant application of the LA from the LCNs can prevent ROS damage, which was demonstrated by this study with the less myeloperoxidase (MPO) activity and decrease in cytokine levels (TNF-alpha and IL-1ß) generated by the oxidative stress modulation. Together, the data presented highlights the potential of these targeted LCNs, and overall, opens new frontiers for preclinical trials.

Apple Extract (Malus sp.) and Rutin as Photochemopreventive Agents: Evaluation of Ultraviolet B-Induced Alterations on Skin Biopsies and Tissue-Engineered Skin.

The skin is exposed to the solar ultraviolet B (UVB) radiation, which leads to the formation of several types of skin damage responsible for cancer initiation and aging. Malus sp. is a genus of apples, which are a good source of polyphenolic compounds. Malus sp. and more precisely one of its components, rutin, have preventive effects on many diseases caused by reactive oxygen species. In addition, previous studies have suggested the topical usage of the extract as a cosmetic product to prevent skin damage caused by oxidative stress. In this study, we evaluated the efficacy of two topical formulations containing 1.25% of Malus sp. extract and the equivalent amount of rutin (0.75%). The photochemopreventive effect was assessed on two three-dimensional (3D) skin models, that is, ex vivo skin explants and 3D tissue-engineered skin to compare the models. Both formulations protected against the UVB-induced increase in sunburn cell formation, as well as caspase-3 activation and cyclobutane pyrimidine dimer formation in both skin models. Furthermore, the formulations inhibited the lipid peroxidation and the metalloproteinase formation induced by UVB radiation. The tissue-engineered skins and the skin explants provided effective tools to assess the UVB-induced damages. These results support use of the Malus sp. extract and rutin as skin photochemopreventive agents for topical application.

Yangambin and Epi-yangambin Isomers: New Purification Method from Ocotea fasciculata and First Cytotoxic Aspects Focusing on In Vivo Safety.

Ocotea fasciculata presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from Ocotea fasciculata, and (ii) an in vitro cytotoxicity study to estimate, for the first time, the LD50 values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium. The best condition for epimers isolation was achieved in normal-phase liquid chromatography. The lignan fraction (LF), previously obtained from the plant ethanolic extract, was purified yielding 17% and 29% of YAN and EPI-YAN, respectively. The in vitro study demonstrated that YAN and EPI-YAN were safe, and only at the highest concentration studied, a decrease on cell viability was observed. The estimated LD50 value was higher than 1612 mg/kg for both epimers. The LF, on the other hand, demonstrated an estimated LD50 of 422 mg/kg. Lignan cytotoxicity studies also evidenced that the higher cell viability was related to the higher concentration of fetal bovine serum as a source of albumin in medium. This is the first time the LD50 and safety of the isolated epimers were estimated, opening up great perspectives of success in in vivo studies.

Pharmacokinetics, Pharmacodynamics and Dermal Distribution of 5-Methoxypsoralen Based on a Physiologically Based Pharmacokinetic Model to Support Phytotherapy Using Brosimum gaudichaudii.

The treatment of vitiligo includes the combination of psoralens and ultraviolet type A exposure. Psoralens belong to a group of natural furanocoumarins that cause the skin to become sensitive temporarily to ultraviolet type A. The aim of this study was to develop a physiologically based pharmacokinetic model of 5-MOP from Brosimum gaudichaudii to support psoralen and ultraviolet type A therapy. A study of rats was used to establish and validate rat tissue distribution. The same chemical-specific parameters used in the rat model were also employed in the human model to project human pharmacokinetics. The highest exposures in the rats were in the brain and skin. Following a single dose of 1.2 mg/kg 5-MOP in humans, the model predicted a maximum concentration of 20 ng/mL and an area under the curve of 125 ng.h/mL, matching clinical results. The half-maximum melanogenesis concentrations in B16F10 cells were 29.5, 18.5, 11.5, and 6.5 ng/mL for synthetic 5-MOP, synthetic 5-MOP with ultraviolet type A, B. gaudichaudii alone, and B. gaudichaudii plus ultraviolet type A, respectively. Physiologically based pharmacokinetic model prediction in humans supported a once-every-two-day regimen for optimal melanin production. This type of framework can be applied to support strategies for dose selection and to investigate the impact of drugs on melanocyte recovery.

Obtainment of an enriched fraction of Inga edulis: identification using UPLC-DAD-MS/MS and photochemopreventive screening.

Inga edulis is a fruit tree native from Central and South America. Different species of Inga have demonstrated high polyphenolic content and high antioxidant capacity. The oxidative stress significantly contributes to the development of several chronicle diseases, particularly age-related diseases. Therefore, photochemoprevention is an emerging interest in the use of naturally occurring antioxidants for their therapeutic use. A partial purification of the extract was carried out onto macroporous resin and the main components of I. edulis leaf extract and fraction were identified using UPLC-DAD-MS/MS as epicatechin, apigenin C-di-hexoside, myricetin-O-hexose-deoxyhexose, myricetin-O-deoxyhexose and vicenin-2, which was identified for the first time in I. edulis. Both extract and fraction presented high antioxidant capacity, the fraction exhibiting higher polyphenol and flavonoid contents and higher content of vicenin-2, suggesting that the fractioning process effectively resulted in the partial purification of the extract. The cytotoxicity and photostability were assessed in L929 fibroblast cells to evaluate whether I. edulis extract and fraction were suitable for topical application. The UVA and UVB irradiated extract and fraction did not decrease the antioxidant capacity and cell viability of L929 fibroblasts, demonstrating the photostability of the samples. The fractioning process successfully purified and enriched I. edulis extract, and both the extract and fraction are potential candidates to be safely incorporated in topical photochemopreventive formulations.

Cecropia obtusa extract and chlorogenic acid exhibit anti aging effect in human fibroblasts and keratinocytes cells exposed to UV radiation.

Cecropia obtusa is popularly used in the Amazonian region and exhibits antioxidant activity. Cosmetic formulations containing C. obtusa extract are commercially available for purchase; however, the chemical composition and the effects of the topical application of the extract are not described in the literature. Therefore, this study aimed to identify the main components of C. obtusa for the first time and to assess the anti aging effect in human fibroblasts and keratinocytes exposed to UVR. The main components in C. obtusa extract were identified by LC-DAD-MS/MS as chlorogenic acid (CGA), luteolin-C-hexoside, luteolin-C-hexose-O-deoxy-hexose, and apigenin-C-hexose-O-deoxy-hexose. C. obtusa extract and CGA decreased the metalloproteinase-1 and protein carbonyl levels and increased the collagen and hyaluronic acid contents. Overall, the extract exhibited better activity than CGA, and we demonstrated the ability of the extract to protect against the UV-induced increase in the pro inflammatory cytokines IL-1ß and IL-6, which are potential pathways of the antioxidant and anti aging effect. The chemical characterization added important data to broaden the knowledge related to C. obtusa, and the results suggest that the extract is a promising candidate to be incorporated in topical photochemoprotective formulations.

The extended production of UV-induced reactive oxygen species in L929 fibroblasts is attenuated by posttreatment with Arrabidaea chica through scavenging mechanisms.

Ultraviolet radiation (UVR) exposure causes various injurious effects to human skin by generating reactive oxygen species (ROS). Excessive ROS production can lead to oxidative stress which may damage cellular components like lipids and proteins and causing photoaging. The use of natural photochemopreventive agents with antioxidant properties is an important alternative to improve the effectiveness of sunscreens and reduce skin photodamage. A crude extract (CE) from the leaves of Arrabidaea chica underwent partition by a liquid-liquid method. The hexane fraction (FH), chloroform fraction (FC), and ethyl acetate fraction (FEA) were obtained. The antioxidant capacity of the CE, FH, FC, and FEA was studied in a cell-free system using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and the xanthine/luminol/xanthine oxidase system. The FC had the best antioxidant activity. We also evaluated the photochemoprotective effect of A. chica in protecting L929 fibroblasts against UV-A- and UV-B-induced cell damage. A. chica inhibited the extended production of ROS up to 3h. Posttreatment with the CE and FC attenuated UV-induced cell damage through scavenging mechanisms, including the quenching of intracellular ROS and mitochondrial O2- and preventing lipid peroxidation. These results suggest that A. chica may be a promising non-sunscreen photoprotector that can improve the effectiveness of commercial sunscreens.

A novel research model for evaluating sunscreen protection in the UV-A1.

The use of a broad spectrum sunscreen is considered one of the main and most popular measures for preventing the damaging effects of ultraviolet radiation (UVR) on the skin. In this study we have developed a novel in vitro method to assess sunscreens efficacy to protect calcineurin enzyme activity, a skin cell marker. The photoprotective efficacy of sunscreen products was assessed by measuring the UV-A1 radiation-induced depletion of calcineurin (Cn) enzyme activity in primary neonatal human dermal fibroblast (HDFn) cell lysates. After exposure to 24J/cm2 UV-A1 radiation, the sunscreens containing larger amounts of UV-A1 filters (brand B), the astaxanthin (UV-A1 absorber) and the Tinosorb® M (UV-A1 absorber) were capable of preventing loss of Cn activity when compared to the sunscreens formulations of brand A (low concentration of UV-A1 filters), with the Garcinia brasiliensis extract (UV-B absorber) and with the unprotected cell lysate and exposed to irradiation (Irradiated Control - IC). The Cn activity assay is a reproducible, accurate and selective technique for evaluating the effectiveness of sunscreens against the effects of UV-A1 radiation. The developed method showed that calcineurin activity have the potential to act as a biological indicator of UV-A1 radiation-induced damages in skin and the assay might be used to assess the efficacy of sunscreens agents and plant extracts prior to in vivo tests.

Photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves against UVB-induced oxidative stress in fibroblasts and hairless mice.

Ultraviolet B (UVB) irradiation increases the risk of various skin disorders, leading to inflammation and oxidative stress and thereby increasing the risk of skin photoaging and carcinogenesis. The use of photochemoprotectors such as natural products with antioxidant and anti-inflammatory properties represents a strategy for preventing UVB-induced skin damage. We investigated the photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves (BCF) on fibroblasts and hairless mice exposed to UVB radiation. The mixture of phenolic compounds in BCF prevented the decrease in reduced glutathione (GSH) levels in fibroblast cultures induced by UVB radiation more than some of their individual standards ((+)-catechin (CAT), epigallocatechin gallate and quercetin 3-O-ß-d-glucopyranoside). Prepared gel formulations increased skin antioxidant activity, and BCF components and the CAT standard were retained in the HRS/J hairless mice epidermis 2h after application. Topical treatment with the BCF or CAT formulations (1%) significantly reduced the decrease in GSH levels and decreased myeloperoxidase activity and the secretion of pro-inflammatory cytokines IL-1ß and IL-6 induced by UVB radiation (P<0.05), indicating that both BCF and CAT had anti-inflammatory effects. BCF inhibited UVB-induced metalloproteinase (MMP)-9 secretion/activity, whereas CAT had no effect on MMP-9 activity in the skin of treated animals. These results therefore suggest that BCF can be used as a photochemoprotective agent and antioxidant in the prevention/treatment of inflammation and oxidative stress of the skin induced by UVB radiation.

The role of soybean extracts and isoflavones in hormone-dependent breast cancer: aromatase activity and biological effects.

Estrogen receptor-positive (ER+) breast cancer is the most common cause of cancer death in women worldwide. Nowadays, the relationship between soya diet and breast cancer is controversial due to the unknown role of its isoflavones, genistein (G) and daidzein (D). In this work, we investigated not only the anti-tumor properties of a soybean extract (NBSE) but also whether the biotransformation of extract (BSE) by the fungus Aspergillus awamori increased its effectiveness. The BSE showed a stronger anti-aromatase activity and anti-proliferative efficacy in ER+ aromatase-overexpressing breast cancer cells. D and G were weak aromatase inhibitors, but inhibited cancer cell growth, being G the isoflavone that contributed to the BSE-induced effects. This work demonstrated that the biotransformation increased the anti-aromatase activity and the anti-tumoral efficacy of soybean extract in breast cancer cells. Moreover, it elucidated the potential use of soya in the prevention and/or treatment of ER+ breast cancer.

RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase.

Gene therapy by RNA interference (RNAi) is a post-transcriptional silencing process that can suppress the expression of a particular gene and it is a promising therapeutic approach for the treatment of many severe diseases, including cutaneous disorders. However, difficulties related to administration and body distribution limit the clinical use of small interfering RNA (siRNA) molecules. In this study, we proposed to use nanocarriers to enable siRNA application in the topical treatment of skin disorders. A siRNA nanodispersion based on liquid crystalline phase and composed of monoolein (MO), oleic acid (OA) and polyethylenimine (PEI) was developed and its physicochemical properties, efficiency of complexation and carrier/siRNA stability were assessed. Subsequently, cell viability, cellular uptake, in vitro skin irritation test using reconstructed human epidermis (RHE) and in vitro IL-6 knockdown in psoriasis skin model were evaluated. The results showed that the liquid crystalline nanodispersion is a promising topical delivery system for administration of siRNA, being able to overcome the limitations of the route of administration, as well those resulting from the characteristics of siRNA molecules. The formulation was effective at complexing the siRNA, presented high rate of cell uptake (∼90%), increased the skin penetration of siRNA in vitro, and did not cause skin irritation compared with Triton-X (a moderate irritant), resulting in a 4-fold higher viability of reconstructed human epidermis and a 15.6-fold lower release of IL-1α. A single treatment with the liquid crystalline nanodispersion carrying IL-6 siRNA for 6h was able to reduce the extracellular IL-6 levels by 3.3-fold compared with control treatment in psoriasis skin model. Therefore, liquid crystalline nanodispersion is a suitable nanocarrier for siRNA with therapeutic potential to suppress skin disease-specific genes. This study also highlights the applicability of reconstructed skin models in pharmaceutical field to evaluate the performance of delivery systems without the use of animal models.

O processo de supervisão em ensino clínico. Perspectiva dos estudantes e enfermeiros / The Monitoring Process in Clinical Teaching. Perspective from Students and Nurses / El proceso de supervisión en la enseñanza clínica. Perspectiva de los estudiantes y de los enfermeros

Introdução: O grande desafio que se coloca hoje à formação em enfermagem prende-se com o processo de (re) construção de saberes dos estudantes em ensino clínico onde a supervisão assume particular relevância. Objetivo: Conhecer a perceção dos enfermeiros tutores sobre a supervisão de estudantes de enfermagem em ensino clínico e conhecer a perceção dos estudantes de enfermagem sobre a supervisão em ensino clínico realizada pelos enfermeiros tutores, com a finalidade de contribuir com propostas para a praxis da supervisão. Metodo: Paradigma qualitativo, descritivo-exploratório. Participaram quinze estudantes de enfermagem e seis enfermeiros tutores, o instrumento de recolha de dados foi a entrevista semiestruturada, utilizando-se a análise de conteúdo segundo Bardin (1) no tratamento dos dados. Resultados: Os principais resultados revelam que os participantes concebem e percebem supervisão como processo de acompanhamento sistemático e orientação, potenciador do desenvolvimento de competências pessoais e profissionais, recorrendo a estratégias favorecedoras de reflexão. As dificuldades e necessidades dos enfermeiros tutores, relacionam-se com a formação em supervisão e maior disponibilidade para este processo. Os estudantes de enfermagem sugerem que os enfermeiros possuam conhecimento sobre alguns aspetos processuais de formação em ensino clínico e façam uma supervisão efetiva. As estratégias e conceção de supervisão destes participantes são coerentes com a finalidade preconizada para a supervisão de estudantes em ensino clinico, no entanto, emergem constrangimentos ao processo de supervisão. Conclusões: Parece-nos fundamental investir na formação em supervisão tal como numa gestão organizacional que possibilite a disponibilidade necessária para obter maior qualidade e segurança neste processo.

Introduction: The challenge nursing education faces today is related to the process of (re)construction of knowledge by students in clinical training, where supervision is important. Objective: To know the perception of nurses tutors on the supervision of nursing students in clinical teaching and the perception of nursing students on clinical teaching supervision carried out by tutor nurses. Method: Qualitative, descriptive and exploratory paradigm. Fifteen nursing students and six tutor nurses participated. The data collection instrument was a semi - structured interview, with a subsequent content analysis according to Bardin. Results: It was revealed that participants conceive supervision as a process of systematic support and guidance, enhancing the development of personal and professional skills for those who resorted to strategies which favored reflection. The difficulties and needs of tutors nurses are training in supervision and greater availability for this process. Nursing students suggest that nurse tutors are aware of some procedural aspects of training in clinical teaching and make an effective supervision. Strategies and monitoring design of these participants are consistent with the purpose of supervising students in clinical teaching; however, limitations arise in the monitoring process. Conclusions: It seems essential to invest in training as an organizational procedure that allows the availability necessary to achieve a higher quality in the process.

Introducción: El desafío que enfrenta hoy la educación de enfermería se relaciona con el proceso de (re)construcción de conocimientos de los estudiantes en la formación clínica, donde la supervisión es importante. Objetivo: conocer la percepción de los enfermeros tutores sobre la supervisión de estudiantes de enfermería en enseñanza clínica y la percepción de los estudiantes de enfermería sobre la supervisión en enseñanza clínica realizada por los enfermeros tutores. Método: Paradigma cualitativo, descriptivo-exploratorio. Participaron quince estudiantes de enfermería y seis enfermeros tutores. El instrumento de recolección de datos fue la entrevista semiestructurada, con análisis de contenido según Bardin en el tratamiento de los datos. Resultados: Se reveló que los participantes conciben la supervisión como proceso de acompañamiento sistemático y orientación, potenciador del desarrollo de aptitudes personales y profesionales, que recurrieron a estrategias favorecedoras de reflexión. Las dificultades y necesidades de los enfermeros tutores son la formación en supervisión y mayor disponibilidad para este proceso. Los estudiantes de enfermería sugieren que los enfermeros tutores tengan conocimiento de algunos aspectos de procedimiento de la formación en la enseñanza clínica y hacer una supervisión efectiva. Las estrategias y el diseño de la supervisión de estos participantes son consistentes con la finalidad de la supervisión de los estudiantes en la enseñanza clínica; sin embargo, surgen limitaciones en el proceso de supervisión. Conclusiones: Parece esencial invertir en la formación como una gestión organizativa que permite la disponibilidad necesaria para lograr una mayor calidad en el proceso.

Efectos de la desnutrición calórico-proteica temprana en el estado nutricional y atributos del síndrome metabólico en una cohorte de adultos jóvenes / Effect of early protein-calorie malnutrition on nutritional status and attributes of the metabolic syndrome in young adults

Introducción: estudios consistentes durante los últimos años han caracterizado la relación entre la desnutrición calórico-proteica (DCP) y el desarrollo de enfermedades no transmisibles en la adultez, como el Síndrome Metabólico (SM). Objetivo: analizar la relación entre SM en la adultez y la DCP durante los primeros 1.000 días de vida en una cohorte de adultos recientemente generada en Curicó, Chile. Material y métodos: se analizaron 49 sujetos adultos jóvenes que durante sus primeros dos años de vida sufrieron desnutrición calórico-proteica moderada a severa mediante la realización de antropometría, medición de la presión arterial y exámenes de laboratorio. Se determinó la prevalencia del SM y la carga de sus atributos. Resultados: se obtuvo una prevalencia de SM del 14,3% sin diferencias significativas por género, con una asociación directa y notable entre la carga de SM, el índice de masa corporal (IMC), el índice cintura/talla, presión arterial y niveles plasmáticos de glicemia y triglicé- ridos (TG), y una asociación inversa con colesterol HDL. Conclusión: la presión arterial sistólica y el valor plasmático de TG representaron los factores de riesgo más importantes del SM en esta cohorte. No se encontró asociación entre la DCP en los 1.000 primeros días de vida y el SM en la adultez (AU)

Background: during recent years consistent studies have characterized the relationship between moderate and severe protein-calorie malnutrition and the appearance of non-communicable diseases in adulthood like metabolic syndrome (MS). Aim: to analyze the relationship between moderate and severe protein-calorie malnutrition during the first 1 000 days of life and the MS in a cohort of adults from Curicó, Chile. Material and methods: we studied 49 young adults who had suffered moderate to severe protein-calorie malnutrition during their first two years of life. Anthropometry, blood pressure measurement and laboratory tests were performed, and the burden of MS attributes was determined. Results: the prevalence of MS was 14.3% with no significant differences by gender, showing a direct and significant association between burden of MS and body mass index, waist / height index, blood pressure, plasma levels of glucose and triglyceride, and an inverse association with HDL. Conclusion: systolic blood pressure and plasma level of triglyceride represented the most important risk factors for SM in this cohort. We found no association between the presence of protein-calorie malnutrition and MS (AU)

[EFFECT OF EARLY PROTEIN-CALORIE MALNUTRITION ON NUTRITIONAL STATUS AND ATTRIBUTES OF THE METABOLIC SYNDROME IN YOUNG ADULTS]. / EFECTOS DE LA DESNUTRICIÓN CALÓRICO-PROTEICA TEMPRANA EN EL ESTADO NUTRICIONAL Y ATRIBUTOS DEL SÍNDROME METABÓLICO EN UNA COHORTE DE ADULTOS JÓVENES.

BACKGROUND: during recent years consistent studies have characterized the relationship between moderate and severe protein-calorie malnutrition and the appearance of non-communicable diseases in adulthood like metabolic syndrome (MS). AIM: to analyze the relationship between moderate and severe protein-calorie malnutrition during the first 1 000 days of life and the MS in a cohort of adults from Curicó, Chile. MATERIAL AND METHODS: we studied 49 young adults who had suffered moderate to severe protein-calorie malnutrition during their first two years of life. Anthropometry, blood pressure measurement and laboratory tests were performed, and the burden of MS attributes was determined. RESULTS: the prevalence of MS was 14.3% with no significant differences by gender, showing a direct and significant association between burden of MS and body mass index, waist / height index, blood pressure, plasma levels of glucose and triglyceride, and an inverse association with HDL. CONCLUSION: systolic blood pressure and plasma level of triglyceride represented the most important risk factors for SM in this cohort. We found no association between the presence of protein-calorie malnutrition and MS.

Introducción: estudios consistentes durante los últimos años han caracterizado la relación entre la desnutrición calórico-proteica (DCP) y el desarrollo de enfermedades no transmisibles en la adultez, como el Síndrome Metabólico (SM). Objetivo: analizar la relación entre SM en la adultez y la DCP durante los primeros 1.000 días de vida en una cohorte de adultos recientemente generada en Curicó, Chile. Material y métodos: se analizaron 49 sujetos adultos jóvenes que durante sus primeros dos años de vida sufrieron desnutrición calórico-proteica moderada a severa mediante la realización de antropometría, medición de la presión arterial y exámenes de laboratorio. Se determinó la prevalencia del SM y la carga de sus atributos. Resultados: se obtuvo una prevalencia de SM del 14,3% sin diferencias significativas por género, con una asociación directa y notable entre la carga de SM, el índice de masa corporal (IMC), el índice cintura/talla, presión arterial y niveles plasmáticos de glicemia y triglicéridos (TG), y una asociación inversa con colesterol HDL. Conclusión: la presión arterial sistólica y el valor plasmático de TG representaron los factores de riesgo más importantes del SM en esta cohorte. No se encontró asociación entre la DCP en los 1.000 primeros días de vida y el SM en la adultez.

Redox-Active Profile Characterization of Remirea maritima Extracts and Its Cytotoxic Effect in Mouse Fibroblasts (L929) and Melanoma (B16F10) Cells.

Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima's biological actions are available and there are no reports regarding the redox-active profile of this plant. In this study, we examined the total phenolic content of Remirea maritima hydroalcoholic (RMHA) extracts, redox properties against different reactive species generated in vitro and their cytotoxic effect against fibroblasts (L929) and melanoma (B16F10) cells. Total reactive antioxidant potential index (TRAP) and total antioxidant reactivity (TAR) results revealed that RMHA at all concentrations tested showed significant antioxidant capacity. RMHA was also effective against hydroxyl radical formation, reduction of Fe3+ to Fe2+ and in scavenging nitric oxide (NO) radicals. In vitro, the level of lipid peroxidation was reduced by RMHA extract and the data showed significant oxidative damage protection. The RMHA cytotoxicity was evaluated by a neutral red assay in fibroblast (L929) and melanome (B16F10) cells. The obtained results showed that the RMHA (40 and 80 µg/mL, respectively) reduced 70% of the viable cells. In conclusion, this study represents the first report regarding the antioxidant and anti-proliferative potential of R. maritima against B16F10 melanoma cells.