Effect of a low-mineralized thermal spring water on skin barrier mechanical properties using atomic force microscopy.

The mineral content of thermal spring water (TSW) applied to the skin surface can directly influence the skin barrier. Indeed, our previous study showed that Avène TSW (ATSW), a low mineral content thermal spring water, protects the stratum corneum from dehydration compared to a mineral-rich TSW (MR-TSW) and maintains skin surface ultrastructure. While many TSWs have been recognized to have beneficial effects on skin, little is known about their localized and specific effects on skin barrier biomechanics at the nanometric scale. The aim of this study was to compare the effects of ATSW with a reference, MR-TSW, on the biomechanical barrier properties of the skin under homeostasis conditions using atomic force microscopy (AFM). AFM was used to obtain a precise nanomechanical mapping of the skin surface after three applications of both TSW. This provides specific information on the skin topographical profile and elasticity. The topographic profile of skin samples showed a specific compaction of the skin layers after application of MR-TSW, characterized by an increase of the total number of external skin layers, compared to non-treated samples. By contrast, ATSW did not modify the skin topographic profile. High-resolution force/volume acquisitions to capture the elastic modulus showed that it was directly correlated with skin rigidity. The elastic modulus strongly and significantly increased after MR-TSW application compared to non-treated skin. By contrast, applications of ATSW did not increase elastic modulus. These data demonstrate that applications of MR-TSW significantly modified skin barrier properties by increasing skin surface layer compaction and skin rigidity. By contrast, ATSW did not modify the topographical profile of skin explants nor induce mechanical stress at the level of the stratum corneum, indicating it does not disrupt the biophysical properties linked to skin surface integrity.

Characterization of the forehead skin microbiome in the early phase of acne.

BACKGROUND: The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. OBJECTIVES: To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. METHODS: The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. RESULTS: Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. CONCLUSION: Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.

Specific protection of sensitive skin against environmental stress by maintenance and improvement of barrier function.

BACKGROUND: Sensitive skin is a common condition that can severely impact quality of life. Several mechanisms are thought to be involved, including those affecting the skin barrier function, hydration and skin innervation. OBJECTIVES: To investigate the benefit of cream and balm formulations dedicated to sensitive skin and containing Aquaphilus dolomiae extract-G3 (ADE-G3) on skin barrier functions (lipid composition, pH, TEWL), as well as protective responses to dry and pollution stresses. METHODS: In vitro sensitized (using histamine) reconstructed human epidermis (RHE) were subjected to dehydration and pollution stress in the absence and presence of the formulations. Endpoint measurements included transepithelial electric resistance (TEER), stratum corneum protein expression and lipid contents. Clinical measurements included transepithelial water loss (TEWL), skin pH and the lipid index. RESULTS: When applied in cream and balm formulations, ADE-G3, increased the TEER in sensitized RHEs. In non-sensitized dehydrated RHEs, both formulations increased recovery of skin barrier integrity after dehydration, evident as a return of the ratios of filaggrin/profilaggrin and caspase-14/procaspase-14 to values measured in control non-stressed RHEs, as well as reducing the 'natural moisturizing factor' to control levels. In clinical studies performed on dry human skin, the formulations helped to maintain and improve the skin barrier function. This was evident as an intense and sustained moisturization (total lipids and lipid esters were increased), an increase in pH and a decrease in the TEWL by both formulations. When exposed to pollution stress by treating the models with benzo[a]pyrene and airborne particulate matter (PM10), application of both formulations prior to exposure attenuated the induction of CYP1A1, CYP1B1 and UGT1A7 expression, indicating a protective effect. CONCLUSIONS: ADE-G3 cream and balm formulations increased the hydration of the skin but also protected and improved the skin barrier integrity of sensitive skin exposed to dry and cold and airborne pollutant-induced stress environments.

Protective effect of Aquaphilus dolomiae extract-G1, ADE-G1, on tight junction barrier function in a Staphylococcus aureus-infected atopic dermatitis model.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease characterized by recurrent pruritic inflammatory skin lesions and defects of the skin barrier. Bacterial infection with Staphylococcus aureus contributes to increased severity of AD by compromising the barrier further. A microorganism component of Avène Thermal Spring Water, Aquaphilus dolomiae, is thought to contribute to some of its beneficial effects to skin, eg AD alleviation. AIMS: Here, we have investigated the effects of an extract of A. dolomiae, A. dolomiae extract-G1 (ADE-G1), on the structural barrier function of keratinocytes, tight junction (TJ) protein expression and the expression of several genes altered in AD patients. METHODS: An epidermal cell culture model mimicking the AD environment and phenotype was used, in which S. aureus-infected cell cultures of normal human epidermal keratinocytes were exposed to a proinflammatory environment. Endpoints measured included the transepithelial electrical resistance (TER) and immunohistological staining of the epidermal TJ proteins, claudin and occludin. Additional analysis was made of several genes known to be differentially regulated in skin from AD patients (C-C motif chemokine ligand 20 (CCL20), interleukin-8 (IL-8), S100 calcium binding protein A7 (S100A7), defensin beta 4 (DEFB4) and filaggrin). RESULTS: Aquaphilus dolomiae extract-G1 strongly increased TER in non-infected cells and provided protection against infection by overcoming the decrease in TER induced by the infection with S. aureus. In infected cells exposed to a pro-inflammatory environment - depicting AD-like conditions - TER protection by ADE-G1 was still observed. Gene expression analysis of infected and pro-inflammatory stimulated cells indicated that ADE-G1 modulated the inflammatory response (induced IL-8 and attenuated CCL20 expression), increased antimicrobial activities (induced DEFB4 and A100A7) and strengthened barrier function (restored filaggrin expression). CONCLUSIONS: ADE-G1 reinforces barrier function and strongly protects TJ barrier disruption induced by bacterial infection and inflammation.

Protective properties of Avène Thermal Spring Water on biomechanical, ultrastructural and clinical parameters of human skin.

BACKGROUND: Thermal Spring Water (TSW) has been recognized to have beneficial effects on skin; however, the mechanisms underlying these are not completely elucidated. AIMS: We compared the effects of Avène TSW with mineral-rich (MR) TSW on the biomechanical properties of the skin using mechanistic ex vivo assays and clinical studies. METHODS: Ex vivo studies included the effect of both TSWs on the structure of the surface of human skin explants using scanning electron microscopy (SEM); mineral elemental content on the skin surface using SEM coupled to energy dispersing X-ray spectroscopy; and the stress properties of the stratum corneum (SC) when exposed to dehydration. Human clinical studies were conducted to compare the soothing effect of TSWs after a dermatological chemical peeling of face skin and to evaluate the overall sensitive scale of consumers using Avène TSW for 7 days. RESULTS: Both TSWs preserved surface skin ultrastructure; however, crystals formed from MR-TSW were needle-like and formed small grains, present in clusters heterogeneously spread over the surface. Needle crystals were mainly composed of calcium, while small clusters were mainly composed of sulphur. By contrast, Avène TSW-formed crystals composed of sodium and chlorine only were regular in shape and homogeneously distributed across the skin surface. Peak stress of SC layers was increased by MR-TSW, whereas Avène TSW showed a comparatively reduced effect on dehydration and stress. The difference in the two TSW types was reflected in clinical findings comparing postpeeling redness after TSW application. Avène TSW significantly decreased postpeeling redness, while MR-TSW increased it. The overall sensitive scale of consumers was decreased by 47% using Avène TSW for 7 days. CONCLUSIONS: Avène TSW decreases postpeeling redness and soothes sensitive skin in human volunteers. Mechanistic studies suggested that differences in biomechanical effects could be linked to differences in calcium content of the TSW.

Optical coherence tomography: An efficient imaging method for the visualization of human epidermis orientation.

Recently, it has been shown that epidermal sheets taken from suction blisters are very appropriate skin samples for Multi-Photon (MP) microscopy. However, we observed that image quality was much better when the sample was visualized through the basale side. Thus, the epidermis orientation needs to be controlled before MP imaging. We observed that the use of standard laboratory binoculars led to a high rate of false results. In this context, we showed that optical coherence tomography provided clear images of the epidermis orientation without loss of sample integrity and thus represents an effective technique before slide sealing and MP analysis.

[Mild cognitive impairment: a prevalence and sociodemographic factors study in the city of Córdoba, Argentina]. / Deterioro cognitivo leve: estudio de prevalencia y factores sociodemográficos en la ciudad de Córdoba, Argentina.

INTRODUCTION: The increase in life expectancy and the significant growth in the population of the elderly have generated an interest in secondary prevention of different diseases, especially from the age of 50. In Argentina, those over 65 represent 10% of the total population, what makes important to research into their mental health. A trans-sectional descriptive study has been carried out in four neuropsychology services in the city of Cordoba, within the framework of a campaign assessing memory for people over 50. SUBJECTS AND METHODS: In three months, 418 volunteers took part, with an average age of 64.24 years and 12.76 years of instruction, mostly belonging to a urban environment (80%). They were administered Folstein's Minimental State, neuropsychological tests and behavioral measures in two work sessions. RESULTS: The majority was found to have normal performances (75.6%, n = 316) at both behavioral and neuropsychological levels. A lower percentage was found at the borders of normality (8.6%, n = 36). 9.1% (n = 38) of those studied were found to have an amnesiac type of mild cognitive impairment, and 4.5% (n = 19) a multidomain type of deterioration. In sum, about 13.6% of people have a greater chance of developing dementia in coming years. CONCLUSION: The socio-demographic variables that most influence cognitive state appear to be the female gender, age higher than 65 years, lower levels of instruction, fewer children and fewer siblings.

[Assessment of the nutritional status of elderly patients treated at a home-hospital unit]. / Evaluación del estado nutricional de los pacientes mayores atendidos en una unidad de hospitalización a domicilio.

GOALS: To establish the nutritional status of our elderly patients, assess the usefulness of the various anthropometric and biochemical parameters as markers of malnutrition and to determine which of the variables studied have the greatest correlation with malnutrition. SCOPE: Home Hospital Unit of the Arnau de Vilanova Teaching Hospital in Lerida. PATIENTS: 57 patients > or = 60 years. Mean admission to our unit: 12.1 days. VARIABLES: Age, sex, groups by treatment complexity, associated pathology, diagnosis, reason for admission, duration of stay in hospital, surgery performed, complications during the stay at the Home Hospital Unit, weight, height, PCT, AC, BMI, albumin, haemoglobin and RTL. RESULTS: Patients of great age present lower levels of serum albumin (p < 0.005), total proteins (p < 0.001), transferrin (p < 0.03), haemoglobin (p < 0.02) and RTL (p < 0.04) than "younger" elderly patients. Serum albumin and haemoglobin are lower in patients in a complicated post-surgical condition (p < 0.04 and p < 0.02, respectively) and this group is the one with the longest stays (p < 0.001). Those patients with hypoalbuminaemia (74.1%) present lower PCT and RTL (p < 0.02) and a longer stay in hospital (p < 0.01) than those with normal levels of albumin in blood. Patients with anaemia (63.3%) present a lower RTL (p < 0.01) and a greater hospitalization time than those without anaemia. Total proteins (p < 0.0001), albumin (p < 0.004), transferrin (p < 0.003) and RTL (p < 0.005) correlate negatively with age. Albumin (p < 0.001), haemoglobin (p < 0.006) and RTL (p < 0.0001) present a negative correlation with length of hospital stay. CONCLUSION: The prevalence of global malnutrition is high (51% moderate-severe). The nutritional status worsens with age. The length of hospitalization increases gradually with age, with deteriation in the nutritional status and with complexity of the treatment provided.

Intraparenchymal injection of bone marrow mesenchymal stem cells reduces kidney fibrosis after ischemia-reperfusion in cyclosporine-immunosuppressed rats.

Ischemia-reperfusion and immunosuppressive therapy are a major cause of progressive renal failure after kidney transplantation. Recent studies have shown that administration of bone marrow mesenchymal stem cells (MSCs) improves kidney functional recovery in the acute phase of post ischemia-reperfusion injury. In the present study, we used an original model of renal ischemia-reperfusion in immunosuppressed rats (NIRC) to investigate the effects of bone marrow MSCs on progression of chronic renal failure and the mechanisms potentially involved. Left renal ischemia-reperfusion (IR) was induced in unilateral nephrectomized Lewis rats. After IR, rats were treated daily with cyclosporine (10 mg/kg SC) for 28 days. MSCs were injected into the kidney at day 7 after IR. At day 28 after IR, kidneys were removed for histomorphological, biochemical, and gene expression analysis. The effect of conditioned media from MSCs on epithelial-mesenchymal transition was studied in vitro on HK2 cells. Our results show that, as compared to untreated NIRC rats, rats treated by intrarenal injection of MSCs 7 days after IR displayed improvement in renal function, reduction of interstitial fibrosis, and decrease in chronic tubule injury. These effects were associated with a decrease in interstitial α-SMA accumulation and MMP2 activity, markers of fibroblast/fibroblast-like cell activation, and renal remodeling, respectively. Finally, experiments in vitro showed that MSC-conditioned medium prevented epithelial-mesenchymal transition induced by TGF-ß in HK2 cells. In conclusion, our results show that, in immunosuppressed animals, a single intrarenal administration of MSCs reduced renal fibrosis and promoted the recovery of renal function.

Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ.

Mesenchymal stem cells (MSCs) may be used as a cell source for cell therapy of solid organs due to their differentiation potential and paracrine effect. Nevertheless, optimization of MSC-based therapy needs to develop alternative strategies to improve cell administration and efficiency. One option is the use of alginate microencapsulation, which presents an excellent biocompatibility and an in vivo stability. As MSCs are hypoimmunogenic, it was conceivable to produce microparticles with [alginate-poly-L-lysine-alginate (APA) microcapsules] or without (alginate microspheres) a surrounding protective membrane. Therefore, the aim of this study was to determine the most suitable microparticles to encapsulate MSCs for engraftment on solid organ. First, we compared the two types of microparticles with 4 × 10(6) MSCs/ml of alginate. Results showed that each microparticle has distinct morphology and mechanical resistance but both remained stable over time. However, as MSCs exhibited a better viability in microspheres than in microcapsules, the study was pursued with microspheres. We demonstrated that viable MSCs were still able to produce the paracrine factor bFGF and did not present any chondrogenic or osteogenic differentiation, processes sometimes reported with the use of polymers. We then proved that microspheres could be implanted under the renal capsule without degradation with time or inducing impairment of renal function. In conclusion, these microspheres behave as an implantable scaffold whose biological and functional properties could be adapted to fit with clinical applications.