Medical devices biocompatibility assessment on HCE: Evidences of delayed cytotoxicity of preserved compared to preservative free eye drops.

A multiple endpoint analysis (MEA) approach on human reconstructed corneal epithelium (HCE) model has been applied to assess the biocompatibility (cytotoxicity and irritation potential) of medical devices (MD): ophthalmology literature clearly shows the need to better assess these products to exclude any potential chronic damage to the ocular surface. Preserved eye drops (Artelac Multidose, Optive multidose and Artelac Rebalance Multidose) and the same without preservative (Artelac Edo, Optive Unidose, Artelac Rebalance Unidose) and Thealoz Duo were tested after acute (24 h + 16 h post incubation) and repeated (2 applications/day for 72 h) exposure using BAK 0.01% as positive control on HCE. Cellular viability, trans-epithelial electrical resistance measurements, LDH release and occludin gene expression were evaluated for each product to discriminate the potential toxicity of preservatives. The BAK 0.01% toxicity on HCE was confirmed following both exposures. The analysis of the same parameters reveals that the 72 h exposure was suitable to identify toxicity and damages to the ocular surface even for 'soft' preserved MD. The results confirm the reliability, sensitivity and predictivity of the MEA on HCE in detecting subclinical signs of cellular toxicity: 'soft' preservatives resulted toxics suggesting that delayed toxicity should be integral part of the biocompatibility assessment of ophthalmic formulations intended for long-term use.

Facial contact dermatitis and the irritant potential of mobile phone screens.

A teenager with atopic dermatitis presented with a 12-month history of recurrent, pruritic, round and polygonal patches on her face. Patch tests using the European standard series (including nickel, chromium, and cobalt chloride), a plastic and glue series of allergens, polyester components, and personal and environmental products in contact with the patient were conducted. For the patient and 3 of 14 healthy volunteers, positive reactions were observed to the patient's mobile phone touchscreen (TS), an extract solution from the TS, and a non-TS phone of another brand. Accordingly, the patient's dermatitis disappeared when contact with mobile phone screens was avoided.

Oral tissue irritants in toothpaste: a case report.

In this case, an adolescent patient presented with multiple, asymptomatic ulcerated lesions- resembling aphthous ulcerations- located in the oral cavity. The etiology of these lesions appeared to be associated with soft tissue irritants found in the patient's toothpaste. This report highlights the need to rule out known oral irritants in dentifrices for patients who present with oral ulcerations.

Safety assessment of trimoniums as used in cosmetics.

Quaternary ammonium salts, including alkyl chain, alkanol, and polymer derivatives (trimoniums) are used in cosmetics mainly as surfactant-cleansing agents, hair-conditioning agents, and antistatic agents.  The Cosmetic Ingredient Review Expert Panel reviewed the relevant animal and human data and noted gaps in the available safety data for some of the trimomiums.  The available data on many of the trimoniums are sufficient, however, and similar structural activity relationships, functions in cosmetics, and cosmetic product usage supported extending these data to the entire group.  These ingredients were determined to be safe in the present practices of use and concentration when formulated to be nonirritating.

Rinsing with alcohol-free or alcohol-based chlorhexidine solutions after periodontal surgery. A double-blind, randomized, cross-over, pilot study.

The aim of this randomized, double-blind, cross-over pilot study was to evaluate the effect on plaque formation and patient experience of rinsing after periodontal surgery using chlorhexidine solution with or without alcohol. Twenty patients refrained from tooth brushing after surgery and used two mouth rinses.Ten patients used alcohol-based (AB) 0.1% and another ten used alcohol-free (AF) 0.12% chlorhexidine (CHX). Sutures were removed after 2 weeks and teeth were cleaned; thereafter, the two groups shifted solution. Plaque at operated teeth was recorded at 2 and 4 weeks (Quigley-Hein Index). Patient experience was assessed with a visual analogue scale (0-10). Mean (SD) plaque indices at 2 and 4 weeks were 1.0 (0.8) and 1.1 (1.0) for AB CHX and 1.1 (0.7) and 0.8 (0.7) for AF CHX, respectively (no significant differences between solutions). At 2 weeks, between-group differences in taste experience of the solutions differed non-significantly: 6.1 (2.8) for AB and 6.0 (2.3) for AF. At 4 weeks, values were 4.6 (2.5) for AB and 6.9 (3.3) for AF-patients tended to prefer AF (p = 0.050). Taste change over the study period was equal for both groups: -37 (3.3) for AB and 3.4 (2.3) for AF at 2 weeks and slightly higher at 4 weeks 4.9 (2.8) and 4.5 (2.5) for AB and AF, respectively. Smarting was low in both groups: 2.2 (3.2) and 1.3 (2.2) for AB and 1.0 (1.5) and 1.9 (2.0) for AF at 2 and 4 weeks, respectively. To conclude, alcohol-free and alcohol-based chlorhexidine showed the same plaque inhibitory effect in periodontal patients after periodontal surgery. Both rinses were well tolerated by the patients.

The environment, the airway, and the athlete.

OBJECTIVE: To review the interaction of environmental factors with host conditions, including atopy, the potential resulting impaired upper and lower airway function, and diagnostic and therapeutic considerations in the athlete. DATA SOURCES: OVID, MEDLINE, and PubMed searches were performed cross-referencing the keywords asthma, athlete, atopy, bronchospasm, exercise, pollution, and rhinitis. STUDY SELECTION: Articles were selected based on relevance to the subject matter. RESULTS: Recent studies have yielded significant advances in our understanding of how intrinsic and extrinsic factors can potentially result in impaired function of the airways of athletes. Extrinsic factors include environmental exposure to temperature, humidity, aeroallergens, irritants, and pollution. Intrinsic factors include atopy, allergic rhinitis, asthma, and anatomical variants. These intrinsic and extrinsic factors can affect both the athlete's quality of life and athletic performance. However, uncertainty remains regarding relative contributions of these factors in explaining the high degree of bronchospasm seen in various populations of athletes with and without asthma, and no consensus exists regarding the most appropriate diagnostic and therapeutic modalities. CONCLUSIONS: Great variability exists in the presentation, laboratory findings, diagnostic maneuvers, and response to therapeutic measures among populations of athletes in different sports and among individuals. An improved understanding of the unique exposures faced by athletes in different disciplines, of the available tests for pursuing the appropriate diagnosis, and of the available therapies will allow the allergist to provide clinical improvement and allow the athlete to find relief and achieve his/her full potential.

Contact Dermatitis in Construction Workers in Northeastern Italian Patch Test Database Between 1996 and 2016.

BACKGROUND: Contact dermatitis in construction workers (CWs) is frequent due to the widespread exposure to sensitizing substances and irritating agents and the wet and cold working conditions. OBJECTIVE: Our objectives were to evaluate contact dermatitis characteristics among CWs who underwent patch test in northeastern Italy and to identify related allergens. METHODS: Seven hundred ninety-five CWs were studied and their data were compared to 2.099 male white-collar workers. The associations between patch test results and occupations were assessed by multivariate logistic regression analysis. Incidence data were calculated from 1996 to 2016. RESULTS: CWs with confirmed occupational dermatitis presented an increased risk to be sensitized to potassium dichromate [OR 3.1 (95%IC 2.0-4.8)], to thiurams [OR 8 .6 (95%IC 4.0-18.4)], and to epoxy resins [OR 12.7 (95%IC 6.1-26.4)]. Sensitization to chromate decreased significantly after 2004, following EU regulation of chromate content in concrete, while sensitization to epoxy resins and thiurams increased. The overall incidence of occupational contact dermatitis in CWs decreased significantly. CONCLUSION: Our study demonstrated the effectiveness of EU regulations in reducing chromate sensitization in CWs and the overall incidence of occupational contact dermatitis. However, sensitization to other haptens is increasing, though improvement of protective measures is compulsory.

Risk factors for corneal inflammatory and mechanical events with extended wear silicone hydrogel contact lenses.

PURPOSE: To identify risk factors for contact lens-related corneal inflammatory events and mechanical events in wearers of silicone hydrogel lenses on a 30-night extended wear (EW) schedule in India. METHODS: An interventional study with 188 subjects wearing silicone hydrogel lenses bilaterally on a 30-night EW schedule. Subjects were dispensed with lenses and reviewed at scheduled visits up to 6 months of EW. Multivariate logistic regression, after adjusting for within subject correlation, was used to develop the statistical model. RESULTS: Occupations in non-ideal environments were found to predispose a lens wearer to inflammatory events (p = 0.003). Wearers in the non-ideal group, who had varying degrees of exposure to ocular irritants in their work environment had highest incidence of inflammatory events (19.2%). Wearers in a controlled, ideal environment had lowest levels of events (3.3%). Students occupied a position between the two groups (9.3%). Inflammatory rate was higher among wearers with increased microbial contamination of lenses (p = 0.002). Wearers with an inflammatory event had mean colony forming unit of 1.97 log compared with mean colony forming unit of 1.45 log in group with no inflammatory event. Corneal vascularization was associated with the development of inflammatory events (p = 0.001) with 50% of wearers with vascularization experiencing events compared with 7.6% of subjects with no vascularization. Reduced lens movement was associated with inflammatory events with subjects more likely to develop inflammatory events compared with those wearers with optimal lens movement (p = 0.027). CONCLUSIONS: A multitude of factors, including environmental influences, lens contamination, ocular characteristics, and lens fit, contributes to the development of inflammatory events, information that is of clinical relevance to practitioners worldwide. Occupational environment was also a contributory factor, confirming that a duty of clinicians is to ascertain the nature of the work environment of lens wearers (and potential wearers) and to balance the needs of the wearer with the potential risks.

A review of the safety of tooth bleaching.

UNLABELLED: This article considers the safety of tooth bleaching based on a Medline search of clinical, animal and in vitro studies between 1986 and 2007. CLINICAL RELEVANCE: Bleaching is the least invasive option for improving tooth colour compared to alternatives such as crowns and veneers. However, no dental procedure is without risk and the clinician should be aware of the safety issues and adverse effects of tooth bleaching so that patients can be fully informed.

Contact stomatitis.

Contact stomatitis occurs in up to 10% of the population. Mechanical or chemical irritation, ill-fitting dentures, and dental fillings can induce irritant contact stomatitis. Type I hypersensitivity and type IV hypersensitivity to dental products and foods are frequently responsible for the allergic types of contact stomatitis. We review the causal agents of contact stomatitis, the differential diagnoses, diagnostic testing, and potential treatment.

Clinical trial evaluating two peroxide whitening strips used by teenagers.

Double-blind clinical research was conducted to compare the clinical response of a thin, concentrated peroxide whitening strip (relative to a marketed control) among a teenage population with preceding safety and efficacy data. Informed consent and child assent was obtained from 48 teens, 13-17 years of age. After baseline measurements were taken, subjects were divded randomly into two groups, one using a thin 10% hydrogen peroxide whitening strip, the other using a 6.5% hydrogen peroxide strip with a thicker gel layer. Strip use was 30 minutes twice per day for 22 days on the maxillary arch, followed by 22 days on the mandibular arch. Efficacy was measured objectively based on L*a*b* color change from digital images taken every 11 days, where L* indicates lightness and b* indicates blue-to-yellow shade. The mean age was 15.1 (+/-1.5) years. Relative to baseline, both strip groups experienced significant (p < 0.0001) color improvement for yellowness (deltab*) and lightness/brightness (deltaL*) beginning at the first visit (Day 11). Continued use resulted in significant color improvement through Day 22. Groups did not differ significantly (p > 0.33) with respect to combined deltab* or deltaL* at end-of-treatment. Tooth sensitivity and oral irritation represented the most common adverse events. No subject discontinued early due to a treatment-related adverse event. Teenagers who used either 10% hydrogen peroxide gel or 6.5% hydrogen peroxide gel whitening strips twice a day for 44 days saw significant tooth whitening without serious adverse events.

A retrospective evaluation of 56 patients with oral burning and limited clinical findings.

This study retrospectively evaluated the charts of 56 patients who had been referred to an oral medicine clinic between 1995 and 2004 with oral burning and limited clinical findings. Of the 56 patients, 35 had a final diagnosis of essential burning mouth disorder (EBMD). Five patients with EBMD had a family history of diabetes and two had been diagnosed with late-onset diabetes. Other oral burning diagnoses included sialoadenitis (burning lips syndrome), irritation or allergic reactions to triclosan, diabetic neuropathy, subclinical oral candidiasis, nutritional deficiency/neuropathy, and a drug reaction to an ACE inhibitor (scalded mouth syndrome) that resulted in oral burning.

Clinical features of cinnamon-induced contact stomatitis.

Cinnamon flavoring agents are known to act on the mucosa as irritants or sensitizers. The objective of this study was to report on clinical and histologic features important in the diagnosis of cinnamon-induced contact stomatitis. We examined 37 past cases of contact stomatitis and identified clinical signs and symptoms and possible causes. The most common cause in the 37 cases was toothpaste; other causes were chewing gum and foods. Although various clinical findings were observed, some characteristics were evident. The most commonly affected site was the gingiva, which showed diffuse or generalized erythema and epithelial sloughing. It is important to identify the causative agents of such a disorder by understanding characteristic signs and symptoms and conducting an appropriate inquiry.

In vivo skin penetration of macromolecules in irritant contact dermatitis.

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where tmin was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, tmin was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin.

Role of macromolecules in the safety of use of body wash cosmetics.

One of the most challenging problems related to the use of surfactants in body wash cosmetics is their potential to cause skin irritations. Surfactants can bind with proteins, remove lipids from the epidermal surface, contribute to the disorganization of liquid crystal structures in the intercellular lipids, and interact with living skin cells. These processes can lead to skin irritations and allergic reactions, and impair the epidermal barrier function. The present study is an attempt to assess the effect of polymers and hydrolysed proteins present in the formulations of model body wash cosmetics on product properties. Special attention was given to the safety of use of this product type. The study examined three macromolecules: polyvinylpyrrolidone (PVP), hydrolysed wheat protein (HWP) and polyvinylpyrrolidone/hydrolysed wheat protein crosspolymer (PVP/HWP). The addition of the substances under study was found to improve the foaming properties of body wash cosmetics, increase their stability during storage, and contribute significantly to an improvement in the safety of product use by reducing the irritant potential. The strongest ability to reduce the skin irritation potential was determined for the formula enriched with the PVP/HWP crosspolymer.

Clinical and forensic signs related to chemical burns: a mechanistic approach.

This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis.

Practical prevention of vaginal and rectal transmission of HIV by adapting the oral defense: use of commercial lubricants.

HIV is transmitted to 6.4 million human beings per year and the majority of these transmissions are sexual. Condoms are highly effective and are recommended as the primary preventive. However, the fact that there are millions of sexual transmissions each year indicates that many people do not use condoms and that additional preventives are needed. The mechanisms of natural prevention of oral transmission by saliva may be adaptable to the susceptible vagina and rectum. The objective of our study was to reduce the sexual transmission of HIV by mimicking saliva's targeting of the transmitting infected leukocytes and any cell-free HIV in seminal fluid. The previously recommended anti-HIV topical microbicide, nonoxynol-9, has not prevented HIV transmission in humans, probably because it causes mucosal irritation and attracts CD4(+) cells. To identify effective preparations that are nonirritating, we studied the anti-HIV activity of commercially available, over-the-counter (OTC) lubricants and vaginal preparations that are judged safest by the U.S. Food and Drug Administration (FDA), and are nonirritating. The effect of OTC preparations on both the production of HIV by infected leukocytes and cell-free HIV suspended in seminal fluid was measured under simulated in vivo conditions. We surveyed 22 OTC vaginal preparations and excluded those with low inhibitory activity and those that were inhibitory but likely to be irritating. Three included preparations are highly active against both HIV-infected leukocytes suspended in seminal fluid and active against cell-free HIV, under in vitro conditions that simulate in vivo conditions. Since the preparations identified here as anti-HIV substances have the advantages of being widely available, inexpensive, acceptable, in the safest U.S. FDA category, and may be used by recipient women or men, they should be tested in clinical trials to help prevent sexual transmission of HIV.

Transdermal nicotine suppresses cutaneous inflammation.

BACKGROUND: Cigarette smoking significantly alters the inflammatory response in the skin following application of irritants and rubefacients. The mechanism of this effect is unknown. There are thousands of components in cigarette smoke that may be pharmacologically important, but there is evidence to suggest that nicotine may play an important role in the observed effect on the inflammatory process. DESIGN: This was an interventional study to assess cutaneous responsiveness to different stimuli after transdermal nicotine administration in volunteer subjects. Cutaneous testing was performed at baseline and at weeks 2 and 4 (the end) of the study. SETTING: The department of Dermatology, University Hospital of Wales, Cardiff. PARTICIPANTS: Ten lifelong nonsmokers were recruited for the study. INTERVENTION: Nicotine patches were applied daily for 1 month. MAIN OUTCOME MEASURES: The following tests were performed: application of 2 times the minimal irritancy dose of sodium lauryl sulfate, irradiation with 2 times the minimal erythema dose of UV-B, measurement of cutaneous vasodilation following application of ethyl and hexyl nicotinate, and reactive hyperemia following arterial occlusion. RESULTS: There was a significant reduction in the cutaneous inflammatory response to sodium lauryl sulfate (P < .001) and irradiation with UV-B (P < .003) and a reduction in reactive hyperemia (P < .03) after 2 weeks of treatment, which returned values to normal at 4 weeks. There was no change in blood flow following application of topical nicotinates. CONCLUSIONS: Nicotine administration via a transdermal delivery system suppresses the cutaneous inflammatory response to sodium lauryl sulfate and UV-B, as well as triggers a transient suppression of reactive hyperemia following arterial occlusion. The apparent anti-inflammatory effects of smoking cigarettes can therefore only partially be explained as a long-term effect of nicotine.

Differential effects of noxious conditioning stimulation of the cheek by capsaicin on human sensory and inhibitory masseter reflex responses evoked by tooth pulp stimulation.

In this study, we investigated whether selective activation of nociceptive primary afferent fibers by capsaicin would induce modulations on tooth-pulp-evoked sensory or inhibitory masseter reflex responses in healthy human subjects. The contribution of central N-methyl-D-aspartate (NMDA) receptor mechanisms in capsaicin-induced effects on sensory or reflex responses was evaluated by dextromethorphan, an NMDA-receptor antagonist. The inhibitory masseter reflex was evoked by electrical stimulation (constant current, single pulses) of the upper incisor while the subject was biting at 10% of his maximal force. The sensation of the tooth pulp stimulation was evaluated by visual analogue scale (VAS). The magnitude, duration, and the the latency of the reflex were determined by bite force measurements. The inhibitor masseter reflex could be induced by non-painful tooth pulp stimulation, and the inhibition was enhanced as a function of increasing stimulus intensity. Capsaicin (1%) applied topically to the skin of the cheek produced a spontaneous burning pain sensation. During capsaicin treatment, the VAS ratings for the sensation induced by tooth pulp stimulation were significantly reduced, whereas no significant changes were found in the tooth-pulp-induced masseter reflex responses. Double-blind treatment with dextromethorphan at a dose of 100 mg (= the highest does without side-effects) had no effect on sensory or reflex responses. These data indicate that noxious stimulation of the facial skin by capsaicin induces differential effects on tooth-pulp-evoked sensory and inhibitory masseter reflex responses: Sensory responses are strongly attenuated, while masseter reflex responses are not significantly changed. Dextromethorphan at a clinically applicable dose does not influence tooth-pulp-evoked sensory or reflex responses or their modulation by capsaicin. Furthermore, the lack of modulation of the masseter reflex response by capsaicin differs from the capsaicin-induced enhancement of a nocifensive limb flexion reflex described earlier.