Human skin responses to environmental pollutants: A review of current scientific models.

Whatever the exposure route, chemical, physical and biological pollutants modify the whole organism response, leading to nerve, cardiac, respiratory, reproductive, and skin system pathologies. Skin acts as a barrier for preventing pollutant modifications. This review aims to present the available scientific models, which help investigate the impact of pollution on the skin. The research question was "Which experimental models illustrate the impact of pollution on the skin in humans?" The review covered a period of 10 years following a PECO statement on in vitro, ex vivo, in vivo and in silico models. Of 582 retrieved articles, 118 articles were eligible. In oral and inhalation routes, dermal exposure had an important impact at both local and systemic levels. Healthy skin models included primary cells, cell lines, co-cultures, reconstructed human epidermis, and skin explants. In silico models estimated skin exposure and permeability. All pollutants affected the skin by altering elasticity, thickness, the structure of epidermal barrier strength, and dermal extracellular integrity. Some specific models concerned wound healing or the skin aging process. Underlying mechanisms were an exacerbated inflammatory skin reaction with the modulation of several cytokines and oxidative stress responses, ending with apoptosis. Pathological skin models revealed the consequences of environmental pollutants on psoriasis, atopic dermatitis, and tumour development. Finally, scientific models were used for evaluating the safety and efficacy of potential skin formulations in preventing the skin aging process or skin irritation after repeated contact. The review gives an overview of scientific skin models used to assess the effects of pollutants. Chemical and physical pollutants were mainly represented while biological contaminants were little studied. In future developments, cell hypoxia and microbiota models may be considered as more representative of clinical situations. Models considering humidity and temperature variations may reflect the impact of these changes.

Relevance of Lipid-Based Products in the Management of Dry Eye Disease.

Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.

The comparative cytotoxic effects of different local anesthetics on a human neuroblastoma cell line.

BACKGROUND: Although local anesthetics (LAs) are generally accepted as being safe, incidental neuronal damage has been reported for all LAs in humans. Therefore, in this study, we compared the dose corresponding to 50% cell lethality (LD50) of articaine, lidocaine, mepivacaine, bupivacaine, prilocaine, and ropivacaine in human neuroblastoma cells. METHODS: Undifferentiated SH-SY5Y cells were exposed for 20 minutes to different concentrations of each LA. Metabolic activity of viable cells was assessed by a cell viability test with a tetrazolium dye (WST-1) followed by optical density quantification. LD50 was determined by extrapolation of curve response. RESULTS: As expected, all LAs induced cell death in a concentration-dependent manner. The bupivacaine, lidocaine, prilocaine, mepivacaine, articaine, and ropivacaine LD50 were 0.95 ± 0.08, 3.35 ± 0.33, 4.32 ± 0.39, 4.84 ± 1.28, 8.98 ± 2.07, and 13.43 ± 0.61 mM, respectively, after 20 minutes of incubation on SH-SY5Y cells. Ropivacaine LD50 was significantly different from the bupivacaine, lidocaine, mepivacaine, and prilocaine LD50 (all P ≤ 0.009). No significant difference was obtained between ropivacaine and articaine LD50 and between prilocaine, lidocaine, and mepivacaine LD50. Articaine LD50 was significantly different from lidocaine LD50 (P = 0.03). Bupivacaine LD50 was significantly lower compared with all LAs (all P ≤ 0.003). CONCLUSIONS: LA neurotoxicity was tested in a validated in vitro model SH-SY5Y, a human neuroblastoma cell line. Three groups of LAs were identified in terms of toxicity: (1) the less (ropivacaine, articaine); (2) medium (mepivacaine, prilocaine, lidocaine); and (3) the high (bupivacaine). Among dental anesthetics, articaine is the least neurotoxic in SH-SY5Y cells.

Use of a new retrograde filling material (Biodentine) for endodontic surgery: two case reports.

Mineral trioxide aggregate (MTA) is considered at the present time as the gold standard for root-end filling in endodontic surgery. However, this biocompatible material presents several drawbacks such as a long setting time and handling difficulties. The aim of this article is to present a new commercialized calcium silicate-based material named Biodentine with physical improved properties compared to MTA in a clinical application. Two endodontic microsurgeries were performed by using specific armamentarium (microsurgical instrumentation, ultrasonic tips) under high-power magnification with an operatory microscope. Biodentine was used as a root-end filling in order to seal the root canal system. The two cases were considered completely healed at 1 year and were followed for one more year. The 2-year follow-up consolidated the previous observation with absence of clinical symptoms and radiographic evidence of regeneration of the periapical tissues.

Clinical evaluation of the performance and safety of a new dentine substitute, Biodentine, in the restoration of posterior teeth - a prospective study.

OBJECTIVES: A multicentric randomized, 3-year prospective study was conducted to determine for how long Biodentine, a new biocompatible dentine substitute, can remain as a posterior restoration. MATERIALS AND METHODS: First, Biodentine was compared to the composite Z100®, to evaluate whether and for how long it could be used as a posterior restoration according to selected United States Public Health Service (USPHS)' criteria (mean ± SD). Second, when abrasion occurred, Biodentine was evaluated as a dentine substitute combined with Z100®. RESULTS: A total of 397 cases were included. This interim analysis was conducted on 212 cases that were seen for the 1-year recall. On the day of restoration placement, both materials obtained good scores for material handling, anatomic form (0.12 ± 0.33), marginal adaptation (0.01 ± 0.10) and interproximal contact (0.11 ± 0.39). During the follow-up, both materials scored well in surface roughness (≤1) without secondary decay and post-operative pain. Biodentine kept acceptable surface properties regarding anatomic form score (≤1), marginal adaptation score (≤2) and interproximal contact score (≤1) for up to 6 months after placement. Resistance to marginal discoloration was superior with Biodentine compared to Z100®. When Biodentine was retained as a dentine substitute after pulp vitality control, it was covered systematically with the composite Z100®. This procedure yielded restorations that were clinically sound and symptom free. CONCLUSIONS: Biodentine is able to restore posterior teeth for up to 6 months. When subsequently covered with Z100®, it is a convenient, efficient and well tolerated dentine substitute. CLINICAL RELEVANCE: Biodentine as a dentine substitute can be used under a composite for posterior restorations.

A comparative study of a preservative-free latanoprost cationic emulsion (Catioprost) and a BAK-preserved latanoprost solution in animal models.

PURPOSE: Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free latanoprost 0.005% cationic emulsion (Catioprost(®)), and a BAK-preserved latanoprost 0.005% solution (Xalatan(®)), were compared. METHODS: The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed. RESULTS: Both the preservative-free and BAK-preserved latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free latanoprost cationic emulsion. CONCLUSIONS: In animal models, a preservative-free latanoprost cationic emulsion was as effective as Xalatan(®) for lowering IOP with an improved ocular tolerance profile.

Comparison of the ocular tolerability of a latanoprost cationic emulsion versus conventional formulations of prostaglandins: an in vivo toxicity assay.

PURPOSE: Using an established rabbit toxicological model, this in vivo study compared the ocular cytotoxicity of four topical intraocular pressure (IOP)-lowering agents: the commercial benzalkonium chloride (BAC)-containing solutions of 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost (containing 0.02%, 0.015%, and 0.005% BAC, respectively), and 0.005% latanoprost in a new cationic emulsion (LCEm) formulation. METHODS: Thirty adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 microl of sterile phosphate-buffered saline (PBS) along with each formulation was applied onto rabbit eyes 15 times at 5 min intervals. The ocular surface changes were investigated using slit-lamp examination, corneal in vivo confocal microscopy (IVCM) for cornea, limbus, conjunctiva/conjunctiva-associated lymphoid tissue (CALT) investigations, and conjunctival imprints for cytology and flow cytometry (FCM) analyses. RESULTS: Antiglaucoma eye drops induced an ocular surface cytotoxicity primarily related to the concentration of their common BAC preservative ((0.02%BAC+)latanoprost> (0.015%BAC+)travoprost> (0.005%BAC+)bimatoprost). LCEm did not induce any obvious signs of toxicity on the rabbit ocular surface with results similar to those of PBS; moreover, the conjunctiva/CALT and cornea had almost normal aspects. CONCLUSIONS: These in vivo and ex vivo toxicological procedures performed in an acute stress model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous eye drop solutions. The new formulation, LCEm, was well tolerated without inducing ocular surface damage or CALT activation. The cationic emulsion of latanoprost will most likely have fewer long-term adverse effects on the ocular surface than formulations containing toxic preservative BAC and may improve long-term tolerance over BAC-containing antiglaucomatous topical treatments.