Identification of prognostic biomarkers for antibiotic associated nephrotoxicity in cystic fibrosis.

BACKGROUND: Our objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation. METHODS: We populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents. We translated candidate biomarkers to a CF cohort via analysis of urine collected prior to, during and two weeks after antibiotics and patients were followed for a median of 3 years after antibiotic use. RESULTS: Polymyxin E treatment resulted in a statistically significant increase in the pro-apoptotic Fas gene relative to control in RNAseq of MPS: fold-change = 1.63, FDR q-value = 7.29 × 10-5. Effluent analysis demonstrated an acute rise of soluble Fas (sFas) concentrations that correlated with cellular injury. In 16 patients with CF, urinary sFas concentrations were significantly elevated during antibiotic treatment, regardless of development of AKI. Over a median of three years of follow up, we identified seven cases of incident chronic kidney disease (CKD). Urinary sFas concentrations during antibiotic treatment were significantly associated with subsequent development of incident CKD (unadjusted relative risk = 2.02 per doubling of urinary sFas, 95 % CI = 1.40, 2.90, p < 0.001). CONCLUSIONS: Using an ex-vivo MPS, we identified a novel biomarker of proximal tubule epithelial cell injury, sFas, and translated these findings to a clinical cohort of patients with CF.

Microphysiological systems in absorption, distribution, metabolism, and elimination sciences.

The use of microphysiological systems (MPS) to support absorption, distribution, metabolism, and elimination (ADME) sciences has grown substantially in the last decade, in part driven by regulatory demands to move away from traditional animal-based safety assessment studies and industry desires to develop methodologies to efficiently screen and characterize drugs in the development pipeline. The past decade of MPS development has yielded great user-driven technological advances with the collective fine-tuning of cell culture techniques, fluid delivery systems, materials engineering, and performance enhancing modifications. The rapid advances in MPS technology have now made it feasible to evaluate critical ADME parameters within a stand-alone organ system or through interconnected organ systems. This review surveys current MPS developed for liver, kidney, and intestinal systems as stand-alone or interconnected organ systems, and evaluates each system for specific performance criteria recommended by regulatory authorities and MPS leaders that would render each system suitable for evaluating drug ADME. Whereas some systems are more suitable for ADME type research than others, not all system designs were intended to meet the recently published desired performance criteria and are reported as a summary of initial proof-of-concept studies.

Influence of vegetable oils in the rheology, texture profile and sensory properties of cosmetic formulations based on organogel.

OBJECTIVE: The knowledge about how ingredients in formulation can influence the texture profile is an important factor on the development of a cosmetic product. In this context, the aim of this work was to evaluate the effect of vegetable oils in the texture profile, rheological and sensorial properties of cosmetic formulations based on organogel. METHODS: Four organogel-based emulsions were developed and supplemented or not with sunflower, macadamia or olive oils. Analyses of rheological behaviour, texture profile and sensory properties were performed. RESULTS: The vegetable oils added to formulation did not alter the pseudoplastic rheological behaviour, but increased the area of hysteresis and reduced the work of shear of the formulations. In addition, the sunflower seed oil increased the consistency index and all texture parameters while the macadamia oil reduced firmness and consistency. The cosmetic formulation based on organogel containing the sunflower seed oil showed the highest score on sensory evaluation. CONCLUSION: The vegetable oils affected the rheology behaviour, texture profile and sensory properties of the formulations under study. However, the influence of sunflower oil in organogel-based cosmetic formulation was more pronounced considering texture profile and the response perceived by subjects in the sensorial analysis.

OBJECTIF: Les connaissances sur la manière dont les ingrédients d'une formulation peuvent influencer la texture constituent un facteur important dans la conception d'un produit cosmétique. Dans ce contexte, l'objectif de ce travail était d'évaluer l'effet des huiles végétales sur la texture, les propriétés rhéologiques et sensorielles des formulations cosmétiques à base d'organogel. MÉTHODES: Quatre émulsions à base d'organogels ont été préparées et enrichies ou non d'huiles de tournesol, de macadamia ou d'olive. Le comportement rhéologique, la texture et les propriétés sensorielles ont été analysés. RÉSULTATS: Les huiles végétales ajoutées à la formulation n'ont pas altéré le comportement rhéologique pseudoplastique, mais ont augmenté la surface du cycle d'hystérésis et réduit l'effet lissant des formulations. En outre, l'huile de tournesol a augmenté l'indice d'onctuosité et tous les paramètres de la texture, tandis que l'huile de macadamia a réduit la fermeté et l'onctuosité. La formulation cosmétique à base d'organogel contenant l'huile de tournesol a obtenu le meilleur score lors de l'évaluation sensorielle. CONCLUSION: Les huiles végétales ont affecté le comportement rhéologique, la texture et les propriétés sensorielles des formulations étudiées. Cependant, l'influence de l'huile de tournesol dans la formulation des cosmétiques à base d'organogel était plus prononcée compte tenu de la texture et de la réaction perçue par les sujets lors de l'analyse sensorielle.

Topical application and oral supplementation of peptides in the improvement of skin viscoelasticity and density.

BACKGROUND: The combination of oral supplementation and topical formulations to the improvement of skin conditions has been proposed as an innovative approach to obtain effective treatments. However, studies comparing the effectiveness of each type of treatments are still in lack. This way, the objective of this work was to evaluate the clinical efficacy of a dermocosmetic formulation with di- and tripeptides, as well the effects of an oral supplementation based on hydrolyzed collagen through biophysical and skin imaging techniques. METHODS: Sixty healthy female subjects, aged between 40 and 50 years, were enrolled, being separated in 3 groups: topical formulation, oral supplementation, and oral placebo. The stratum corneum water content, skin viscoelasticity, dermis echogenicity, and skin pores parameters were evaluated. RESULTS: The group with the topical formulation showed a significant increase in the stratum corneum water content and skin elasticity after 28-day period and also acted in the dermis echogenicity after 90 days with the formulation with peptides. The oral supplementation acted on skin elasticity and presented a more pronounced effect on dermis echogenicity, reducing skin pores after 90-day period. CONCLUSION: The obtained results with oral supplementation and topical application of hydrolyzed proteins were considered complementary in the improvement of general skin conditions, acting in different mechanisms.

Chemical Analysis and Evaluation of Antioxidant, Antimicrobial, and Photoprotective Activities of Schinopsis brasiliensis Engl. (Anacardiaceae).

Schinopsis brasiliensis Engl. is a native plant of Caatinga which has high concentrations of compounds capable of absorbing ultraviolet light, suggesting its potential application for the development of sunscreen preparations. After its identification and collection, this vegetable drug was submitted to a physicochemical analysis through the preparation of ethanolic extract. The phytochemical screening and analysis of extracts were carried out by high-performance liquid chromatography (HPLC) evaluation. The antioxidant activity of the extract was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and ß-carotene bleaching test. Inhibitory hemolytic activity and morphological deformation of erythrocytes induced by H2O2 were also demonstrated and the antimicrobial activity was analyzed by the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) method. For the in vitro determination of the sun protection factor (SPF), the spectrophotometric method was used. From the analyses carried out with this species, this plant showed significant results for the antioxidant and antimicrobial activities, as well as sunscreen action. Important flavonoids were identified. These data are an important step for the development of new photoprotective cosmetic with Caatinga species, revealing importance and representing another incentive for the preservation of the species involved and analyzed in the study.

Development and Evaluation of Photoprotective O/W Emulsions Containing Hydroalcoholic Extract of Neoglaziovia variegata (Bromeliaceae).

Neoglaziovia variegata is a Bromeliaceae plant species widely found in Brazil with several pharmacological properties, including photoprotective activity. Although herbal-based active ingredients have been applied in cosmetic products, especially for skin treatment, its application in sunscreen formulations remains unexplored. The aim of this work is to evaluate the photoprotective effect of cosmetic formulations containing hydroalcoholic extract of N. variegata (Nv-HA). Initially, the phenolic and flavonoid total content of Nv-HA were determined. The photoprotective activity of Nv-HA was subsequently assessed using a spectrophotometric method. Nv-HA was incorporated in O/W emulsions in the presence or absence of synthetic filters and their photoprotective efficacy was evaluated by spectrophotometric SPF determination. Finally, the stability study of the formulations was performed through the freezing/defrosting method. Nv-HA showed significant phenolic and flavonoids content (61.66 ± 5.14 mg GAE/g and 90.27 ± 5.03 mg CE/g, resp.). Nv-HA showed SPF values of 5.43 ± 0.07 and 11.73 ± 0.04 for the concentrations of 0.5 and 1.0% (v/v), respectively. It was verified that Nv-HA potentiated the photoprotective effect of formulations containing only synthetic filters. Furthermore, the formulations have remained stable at the end of the preliminary stability study. According to the results, it was concluded that Nv-HA can be used as a chemical filter in cosmetic formulations.