Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity.

Purpose: The purpose of this study was to investigate the effect of sodium hyaluronate (SH) on benzalkonium chloride (BAK)-induced toxicity in the ocular surface epithelium and corneal nerves. Methods: Ocular surface epithelial cells from Balb/c mice were cultured with 0.1% to 0.4% SH and 0.001% to 0.01% BAK and their metabolic activity, viability, and wound repair capacity were assessed in vitro. Following a controlled corneal wound, re-epithelialization and recovery of epithelial barrier function and mechanosensitivity were measured in Balb/c mice treated with 0.4% SH 3 times/day and 0.01% BAK twice daily for 3 weeks. Nerve morphology was assessed by confocal microscopy of corneal whole mounts. Results: Whereas BAK exposure reduced metabolic activity, viability, and wound repair ability of ocular epithelial cells in vitro, pretreatment with SH ameliorated BAK toxicity in a concentration-dependent manner. The highest SH concentration partially reversed the effects of 0.01% BAK in vitro and increased the corneal healing rate of BAK-exposed mice. Although all corneal wounds closed after 4 days, continuous SH treatment improved corneal barrier dysfunction 18 days after wounding and accelerated the recovery of corneal mechanical sensitivity to baseline levels in BAK-exposed mice. SH treatment also increased corneal nerve density in the wounded area after 3 weeks. Conclusions: SH mitigates BAK-associated ocular epithelial and neurotoxicity in a concentration-dependent manner. Translational Relevance: Commercially available, high-concentration SH formulations may have added benefits in treating BAK-associated ocular surface toxicity.

In vitro exposure of porcine spermatozoa to methylparaben, and propylparaben, alone or in combination adversely affects sperm quality.

Parabens (PBs) are widely used in the cosmetic, pharmaceutical, and food industries as preservatives of products. Because of its great use, humans and other organisms are highly exposed daily. However, little is known about the effect of PBs on male infertility. Therefore, the aim of the present study was to evaluate the effect of methylparaben (MePB) and propylparaben (PrPB), alone or in combination, on the physiological characteristics of pig in vitro exposed sperm to different concentrations (0, 200, 500, and 700 µM) for viability, motility, and acrosome integrity evaluation and (0, 200, 500, 700, 1000, and 2000 µM) for DNA fragmentation index evaluation, after 4 h of exposure. The results showed that sperm viability decreased after exposure to MePB from the concentration of 500 µM. In the PrPB and mixture groups, viability decreased at all concentrations except for the control. The decrease in viability of sperm exposed to PrPB was greater than that of the mixture and MePB groups. Sperm motility decreased in all the experimental groups exposed to PBs, at all concentrations, except for the control group. Acrosome integrity was not decreased in the MePB group; however, in the PrPB group, it decreased at a concentration of 200 µM and in the mixture at 500 µM. All groups exhibited DNA damage at different concentrations, except for the control group. Additionally, the effect of PBs on sperm quality was concentration-dependent. The results demonstrated that MePB and PrPB alone or in combination can have adverse effects on sperm quality parameters. MePB had lower toxicity than did both PrPB and the mixture. The mixture did not have an additive effect on any of the parameters evaluated. This could partially explain the link between PB exposure and infertility.

Theory of Planned Behavior applied to the choice of food with preservatives by owners and for their dogs.

Many pet owners make food choices for their pets that are similar to those they make for themselves, and food characteristics such as the presence of preservatives can influence this decision. The Theory of Planned Behavior (TPB) is a tool used to predict intentions and behavior and can be an important indicator for the pet food industry. The aim of this study was to investigate pet owner behavior regarding food with or without preservatives, based on the behavior prediction of TPB. A questionnaire was distributed with questions related to direct (attitude, subjective norms, and perceived behavioral control) and indirect (behavioral beliefs, normative beliefs, and intentions) measures for the analysis of TPB. For the statistical analysis the structural equation modeling (SEM) was used. The correlation between owner behavior and the behavior imposed on their dog's diet was evaluated by paired T test or paired Wilcoxon test according to variables' adherence or not to normality, respectively. A total of 1,021 answers were evaluated after the inclusion and exclusion criteria were applied. The results indicated that TPB was effective in predicting the intentions (r2 = 0.58 for dogs and r2 = 0.59 for owners) and behavior (r2 = 0.58 for dogs and r2 = 0.57 for owners) regarding the intake of diets without preservatives. It was observed that owners are more concerned with the diet of their dogs than their own and they believe that the intake of preservatives can be prejudicial to the health of their dogs (p<0.001). However, owners trust more in pet food manufacturers than human food manufacturers (p<0.001). Therefore, it can be concluded that TPB can be an important tool to understand consumer behavior towards their dog food, and that the industry should intensify its approach on safety of preservatives in pet food, since many owners still believe they can be prejudicial to dogs.

Evidence on Neurotoxicity after Intrauterine and Childhood Exposure to Organomercurials.

Although the molecular mechanisms underlying methylmercury toxicity are not entirely understood, the observed neurotoxicity in early-life is attributed to the covalent binding of methylmercury to sulfhydryl (thiol) groups of proteins and other molecules being able to affect protein post-translational modifications from numerous molecular pathways, such as glutamate signaling, heat-shock chaperones and the antioxidant glutaredoxin/glutathione system. However, for other organomercurials such as ethylmercury or thimerosal, there is not much information available. Therefore, this review critically discusses current knowledge about organomercurials neurotoxicity-both methylmercury and ethylmercury-following intrauterine and childhood exposure, as well as the prospects and future needs for research in this area. Contrasting with the amount of epidemiological evidence available for methylmercury, there are only a few in vivo studies reporting neurotoxic outcomes and mechanisms of toxicity for ethylmercury or thimerosal. There is also a lack of studies on mechanistic approaches to better investigate the pathways involved in the potential neurotoxicity caused by both organomercurials. More impactful follow-up studies, especially following intrauterine and childhood exposure to ethylmercury, are necessary. Childhood vaccination is critically important for controlling infectious diseases; however, the safety of mercury-containing thimerosal and, notably, its effectiveness as preservative in vaccines are still under debate regarding its potential dose-response effects to the central nervous system.

Conservação de peças anatômicas em cloreto de sódio: um estudo com produto de fecundação / Conservation of anatomical parts in sodium chloride: a study with fertilization product / Conservación de partes anatómicas en cloruro sódico: un estudio con producto de fertilización

Introdução: Os materiais de origem humana geralmente são conservados em formaldeído, para possibilitar o estudo da anatomia humana, tal conservante possui baixo custo e boa fixação, contudo é toxico. Diante do exposto é necessário, o estudo de outros métodos de conservação, menos prejudiciais, como a solução de NaCl 30%. Objetivo: Comparar a conservação de peças anatômicas em solução de NaCl à 30% e formaldeído a 10%. Método: Pesquisa experimental, exploratória e descritiva, realizada com dois produtos de abortamento, no laboratório de anatomia de uma universidade pública, no estado do Paraná/BR. Foi realizada fixação em solução de formol 10%, em seguida uma amostra foi lavado em água corrente e armazenado em solução de NaCl à 30%. Após 6 meses da conservação em solução salina, foram coletadas amostras, estas foram submetidas a análise de crescimento bacteriano. Avaliou-se tonalidade e turgor cutâneo, odor e peso, bem como crescimento bacteriano. O estudo seguiu os preceitos éticos (CAAE: 53740121.9.0000.9247). Resultados: Foram realizadas observações após 24h, 7, 30, 60, 90 e 180 dias. O feto em solução de NaCl não possui odor, e diminuição do turgor da pele. Ambas a amostras não apresentaram crescimento bacteriano. Considerações finais: A solução de NaCl a 30% desidrata a pele, mas não altera significativamente a forma e estrutura, ainda não possui odor e nem toxicidade, o que garante benefícios a saúde de quem os manipula, bem como tal concentração de NaCl inibe de forma efetiva o crescimento bacteriano nos tecidos e na própria solução, se demostrando eficaz na conservação.

Introduction: The materials of human origin are usually preserved in formaldehyde, to enable the study of human anatomy, this preservative has low cost and good fixation, however it is toxic. Therefore, it is necessary to study other less harmful preservation methods, such as 30% NaCl solution. Objective: To compare the preservation of anatomical specimens in 30% NaCl solution and 10% formaldehyde solution. Method: Experimental, exploratory and descriptive research, carried out with two abortion products, in the anatomy laboratory of a public university, in the state of Paraná/BR. Fixation in 10% formaldehyde solution was performed, after which a sample was washed in running water and stored in a 30% NaCl solution. After 6 months of preservation in saline solution, samples were collected and submitted to bacterial growth analysis. Skin tone and turgor, odor, weight, and bacterial growth were evaluated. The study followed the ethical precepts (CAAE: 53740121.9.0000.9247). Results: Observations were made after 24h, 7, 30, 60, 90 and 180 days. The fetus in NaCl solution had no odor, and decreased skin turgor. Both samples showed no bacterial growth. Final considerations: The 30% NaCl solution dehydrates the skin, but does not alter significantly the shape and structure, and also has no odor or toxicity, which guarantees health benefits to those who handle them, and such concentration of NaCl inhibits effectively the bacterial growth in the tissues and in the solution itself, proving to be effective in conservation.

Introducción: Los materiales de origen humano suelen conservarse en formol, para posibilitar el estudio de la anatomía humana, este conservante tiene bajo coste y buena fijación, sin embargo es tóxico. Por ello, es necesario estudiar otros métodos de conservación menos nocivos, como la solución de NaCl al 30%. Objetivo: Comparar la conservación de especímenes anatómicos en solución de NaCl al 30% y en solución de formaldehído al 10%. Método: Investigación experimental, exploratoria y descriptiva, realizada con dos abortos, en el laboratorio de anatomía de una universidad pública, en el estado de Paraná/BR. Fue realizada fijación en solución de formaldehído al 10%, después de lo cual la muestra fue lavada en agua corriente y almacenada en solución de NaCl al 30%. Tras 6 meses de conservación en solución salina, se recogieron las muestras y se sometieron a análisis de crecimiento bacteriano. Se evaluaron el tono y la turgencia de la piel, el olor, el peso y el crecimiento bacteriano. El estudio siguió los preceptos éticos (CAAE: 53740121.9.0000.9247). Resultados: Las observaciones se realizaron después de 24h, 7, 30, 60, 90 y 180 días. El feto en solución de NaCl no tenía olor, y la turgencia de la piel disminuyó. Ambas muestras no mostraron crecimiento bacteriano. Consideraciones finales: La solución de NaCl al 30% deshidrata la piel, pero no altera significativamente la forma y estructura, además no tiene olor ni toxicidad, lo que garantiza beneficios para la salud de quienes los manipulan, y dicha concentración de NaCl inhibe eficazmente el crecimiento bacteriano en los tejidos y en la propia solución, demostrando ser eficaz en la conservación.

A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK. METHODS: Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide. RESULTS: The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe. CONCLUSIONS: The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Comparison of Different Temperature Conditions for Microbial Enumeration of Aspergillus brasiliensis in the Preservative Efficacy Test.

The preservative efficacy test is an important method for assessing the antimicrobial effect of cosmetic products. In this study, the optimum conditions for the efficient microbial enumeration of Aspergillus brasiliensis were investigated. Cosmetic products, inoculated with A. brasiliensis spore suspensions, were cultivated at 22.5°C, 32.5°C, or 40°C and the detection rate and the number of colonies were determined using the pour culture method. There was no difference in the viable counts of visible colonies among different temperature conditions. However, the viable counts after 3 days of culture were significantly greater for the cultures maintained at 32.5°C or 40°C compared with those maintained at 22.5°C. This effect was attenuated in products containing fatty acids, which could inhibit fungal growth. Overall, these results demonstrate that cultivating A. brasiliensis at 32.5°C reduces the time required for enumeration in the preservative efficacy test. Thus, the results of this study are expected to help improve and expedite microbiological quality control in the cosmetic industry.

Integrated approaches to testing and assessment as a tool for the hazard assessment and risk characterization of cosmetic preservatives.

The safety assessment of cosmetic products is based on the safety of the ingredients, which requires information on chemical structures, toxicological profiles, and exposure data. Approximately 6% of the population is sensitized to cosmetic ingredients, especially preservatives and fragrances. In this context, the aim of this study was to perform a hazard assessment and risk characterization of benzalkonium chloride (BAC), benzyl alcohol (BA), caprylyl glycol (CG), ethylhexylglycerin (EG), chlorphenesin (CP), dehydroacetic acid (DHA), sodium dehydroacetate (SDH), iodopropynyl butylcarbamate (IPBC), methylchloroisothiazolinone and methylisothiazolinone (MCI/MIT), methylisothiazolinone (MIT), phenoxyethanol (PE), potassium sorbate (PS), and sodium benzoate (SB). Considering the integrated approaches to testing and assessment (IATA) and weight of evidence (WoE) as a decision tree, based on published safety reports. The hazard assessment was composed of a toxicological matrix correlating the toxicity level, defined as low (L), moderate (M), or high (H) and local or systemic exposure, considering the endpoints of skin sensitization, skin irritation, eye irritation, phototoxicity, acute oral toxicity, carcinogenicity, mutagenicity/genotoxicity, and endocrine activity. In a risk assessment approach, most preservatives had a margin of safety (MoS) above 100, except for DHA, SDH, and EG, considering the worst-case scenario (100% dermal absorption). However, isolated data do not set up a safety assessment. It is necessary to carry out a rational risk characterization considering hazard and exposure assessment to estimate the level of risk of an adverse health outcome, based on the concentration in a product, frequency of use, type of product, route of exposure, body surface location, and target population.

Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial.

Purpose: To evaluate the efficacy of a preservative free sodium hyaluronate/chondroitin sulfate ophthalmic solution (SH/CS-PF) in patients with dry eye disease (DED).Methods: This was a randomized phase IV, multicentric, prospective, double-blind clinical trial. Intent-to-treat (ITT) and per-protocol (PP) analyses were performed. Patients were assigned to receive either SH/CS-PF, Systane® Ultra (PEG/PG) or Systane® Ultra PF (PEG/PG-PF) for 90 days. A total of 326 patients were included in the ITT, and 217 in the PP analysis. Efficacy endpoints were goblet cell density, Nelson's grades (conjunctival impression cytology), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and Schirmer's test. Other parameters included were tolerability, measured by the ocular symptomatology; and safety, measured through corneal staining, intraocular pressure, visual acuity and adverse events.Results: In the ITT, there was a significant increase in mean goblet cell density in all treatments compared with their baseline (28.4% vs 21.4% and 30.8%), without difference between arms (p = .159). Eyes exposed to SH/CS-PF, PEG/PG and PEG/PG-PF showed Grade 0-I squamous metaplasia (85.5%, 87.9% and 93.2%, respectively). Similar improvements were observed for TBUT (1.24 ± 2.3s vs 1.27 ± 2.4s and 1.39 ± 2.3s) and OSDI scores at day 90 (-8.81 ± 8.6 vs -7.95 ± 9.2 and -8.78 ± 9.8), although no significant intergroup difference was found. Schirmer's test also presented improvement compared to baseline (1.38 ± 4.9 vs 1.50 ± 4.7 and 2.63 ± 5.9), with a significantly higher variation for PEG/PG-PF. There were no significant differences between treatments for any tolerability and safety parameter, nor between ITT and PP analyses for any outcome.Conclusions: The topical application of SH/CS-PF is as effective, safe and well tolerated as that of PEG/PG or PEG/PG-PF. The results suggest that SH/CS-PF may lead to normalization of clinical parameters and symptom alleviation in patients treated for DED.

Propylparaben Reduces the Long-Term Consequences in Hippocampus Induced by Traumatic Brain Injury in Rats: Its Implications as Therapeutic Strategy to Prevent Neurodegenerative Diseases.

BACKGROUND: Severe traumatic brain injury (TBI), an important risk factor for Alzheimer's disease, induces long-term hippocampal damage and hyperexcitability. On the other hand, studies support that propylparaben (PPB) induces hippocampal neuroprotection in neurodegenerative diseases. OBJECTIVE: Experiments were designed to evaluate the effects of subchronic treatment with PPB on TBI-induced changes in the hippocampus of rats. METHODS: Severe TBI was induced using the lateral fluid percussion model. Subsequently, rats received subchronic administration with PPB (178 mg/kg, TBI+PPB) or vehicle (TBI+PEG) daily for 5 days. The following changes were examined during the experimental procedure: sensorimotor dysfunction, changes in hippocampal excitability, as well as neuronal damage and volume. RESULTS: TBI+PEG group showed sensorimotor dysfunction (p < 0.001), hyperexcitability (64.2%, p < 0.001), and low neuronal preservation ipsi- and contralateral to the trauma. Magnetic resonance imaging (MRI) analysis revealed lower volume (17.2%; p < 0.01) and great damage to the ipsilateral hippocampus. TBI+PPB group showed sensorimotor dysfunction that was partially reversed 30 days after trauma. This group showed hippocampal excitability and neuronal preservation similar to the control group. However, MRI analysis revealed lower hippocampal volume (p < 0.05) when compared with the control group. CONCLUSION: The present study confirms that post-TBI subchronic administration with PPB reduces the long-term consequences of trauma in the hippocampus. Implications of PPB as a neuroprotective strategy to prevent the development of Alzheimer's disease as consequence of TBI are discussed.

The application of pharmaceutical quality by design concepts to evaluate the antioxidant and antimicrobial properties of a preservative system including desferrioxamine.

BACKGROUND: The purpose of the present study was to investigate the antioxidant and antimicrobial activities of a conventional preservative system containing desferrioxamine mesylate (DFO) and optimize the composition of the system through mathematical models. METHODS: Different combinations of ethylenediaminetetraacetic acid (EDTA), sodium metabisulfite (SM), DFO and methylparaben (MP) were prepared using factorial design of experiments. The systems were added to ascorbic acid (AA) solution and the AA content over time, at room temperature and at 40 °C was determined by volumetric assay. The systems were also evaluated for antioxidant activity by a fluorescence-based assay. Antimicrobial activity was assessed by microdilution technique and photometric detection against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus brasiliensis. A multi-criteria decision approach was adopted to optimize all responses by desirability functions. RESULTS: DFO did not extend the stability of AA over time, but displayed a better ability than EDTA to block the pro-oxidant activity of iron. DFO had a positive interaction with MP in microbial growth inhibition. The mathematical models showed adequate capacity to predict the responses. Statistical optimization aiming to meet the quality specifications of the ascorbic acid solution indicated that the presence of DFO in the composition allows to decrease the concentrations of EDTA, SM and MP. CONCLUSION: DFO was much more effective than EDTA in preventing iron-catalyzed oxidation. In addition, DFO improved the inhibitory response of most microorganisms tested. The Quality by Design concepts aided in predicting an optimized preservative system with reduced levels of conventional antioxidants and preservatives, suggesting DFO as a candidate for multifunctional excipient.

In vivo demonstration of immunologic cross-reactivity to octylisothiazolinone in patients primarily and strongly sensitized to methylisothiazolinone.

BACKGROUND: Notwithstanding that concomitant exposure to different isothiazolinone derivatives may result in concomitant sensitization, clinical and animal studies have suggested cross-reactivity between these derivatives, notably between methylisothiazolinone (MI) and octylisothiazolinone (OIT). OBJECTIVE: To investigate if patients sensitized to MI show cross-reactions to OIT and/or to benzisothiazolinone (BIT) by applying the concept of the re-test method. PATIENTS AND METHODS: From March to October 2019 consecutive patients were patch tested with MI 0.2% aqueous in duplicate at the two lower corners of both shoulder blades. Patients sensitized to MI, but not to OIT 0.1% petrolatum (pet.) nor to BIT 0.1% pet., were re-tested, 2 months later, with the latter two derivatives at the skin sites where the MI reactions had fully disappeared. RESULTS: Of 116 patients, 15 (13%) were sensitized to MI, eight of these not sensitized to BIT nor to OIT. Of these, seven patients, all (very) strongly sensitized to MI, were re-tested: five patients showed positive patch test reactions to OIT 0.1% pet.; one patient to OIT 0.1% pet. and BIT 0.1% pet.; and one other patient showed no reactions. CONCLUSION: This study suggests that patients primarily and strongly sensitized to MI may show immunologic cross-reactions to OIT, and to a far lesser extent to BIT.

Toxicity of thimerosal in biological systems: Conformational changes in human hemoglobin, decrease of oxygen binding capacity, increase of protein glycation and amyloid's formation.

Thimerosal (TH), an organomercurial compound, is used as a preservative in vaccines and cosmetics. Its interaction with human hemoglobin (Hb) was investigated under physiological conditions using biophysical and biological assays, aiming to evaluate hazardous effects. TH interacts spontaneously with Hb (stoichiometry 2:1, ligand-protein), preferably by electrostatic forces, with a binding constant of 1.41 × 106 M-1. Spectroscopic data allows to proposing that TH induces structural changes in Hg, through ethylmercury transfer to human Hb-Cys93 residues, forming thiosalicylic acid, which, in turn, interacts with the positive side of the amino acid in the Hb-HgEt adduct chain. As a consequence, inhibition of Hb-O2 binding capacity up to 72% (human Hb), and 50% (human erythrocytes), was verified. Dose-dependent induction of TH forming advanced glycation end products (AGE) and protein aggregates (amyloids) was additionally observed. Finally, these results highlight the toxic potential of the use of TH in biological systems, with a consequent risk to human health.

High rate of sensitization to Kathon CG, detected by patch tests in patients with suspected allergic contact dermatitis.

BACKGROUND: Kathon CG, a combination of methylchloroisothiazolinone and methylisothiazolinone, is widely used as preservative in cosmetics, as well in household cleaning products, industrial products such as paints and glues. It has emerged as an important sensitizing agent in allergic contact dermatitis. OBJECTIVES: This study evaluated the reactivity to this substance in patients subjected to patch tests at the Dermatology Institute in Bauru, São Paulo from 2015 to 2017 and its correlation with other preservatives, the professional activity and location of the lesions. METHODS: The patients were submitted to standard series of epicutaneous tests, standardized by the Brazilian Group Studies on Contact Dermatitis. RESULTS: Out the 267 patients tested, 192 presented positivity to at least one substance and 29 of the patients (15.10%) presented reaction to Kathon CG, with predominance of the female gender (n=27); main professional activity associated with Kathon CG sensibilization was cleaning (17.24%), followed by aesthetic areas (13.79%) and health care (10.34%). The most prevalent sensitizations among the substances tested were nickel sulphate (56.3%), followed by cobalt chloride (23.4%), neomycin (18.2%), potassium dichromate (17.7%), thimerosal (14.5%), formaldehyde (13.2%), paraphenylenediamine (9.3%), and fragrance mix (8.3%). STUDY LIMITATIONS: We do not have data from patients that were submitted to patch test a decade ago in order to confront to current data and establish whether or no sensitization to Kathon CG has increased. CONCLUSION: High positivity to Kathon CG corroborates the recent findings in the literature, suggesting more attention to concentration of this substance, used in cosmetics and products for domestic use.

High rate of sensitization to Kathon CG, detected by patch tests in patients with suspected allergic contact dermatitis

Abstract Background: Kathon CG, a combination of methylchloroisothiazolinone and methylisothiazolinone, is widely used as preservative in cosmetics, as well in household cleaning products, industrial products such as paints and glues. It has emerged as an important sensitizing agent in allergic contact dermatitis. Objectives: This study evaluated the reactivity to this substance in patients subjected to patch tests at the Dermatology Institute in Bauru, São Paulo from 2015 to 2017 and its correlation with other preservatives, the professional activity and location of the lesions. Methods: The patients were submitted to standard series of epicutaneous tests, standardized by the Brazilian Group Studies on Contact Dermatitis. Results: Out the 267 patients tested, 192 presented positivity to at least one substance and 29 of the patients (15.10%) presented reaction to Kathon CG, with predominance of the female gender (n = 27); main professional activity associated with Kathon CG sensibilization was cleaning (17.24%), followed by aesthetic areas (13.79%) and health care (10.34%). The most prevalent sensitizations among the substances tested were nickel sulphate (56.3%), followed by cobalt chloride (23.4%), neomycin (18.2%), potassium dichromate (17.7%), thimerosal (14.5%), formaldehyde (13.2%), paraphenylenediamine (9.3%), and fragrance mix (8.3%). Study limitations: We do not have data from patients that were submitted to patch test a decade ago in order to confront to current data and establish whether or no sensitization to Kathon CG has increased. Conclusion: High positivity to Kathon CG corroborates the recent findings in the literature, suggesting more attention to concentration of this substance, used in cosmetics and products for domestic use.

Thimerosal-containing vaccines and deficit in child development: Population-based study in southern Brazil.

BACKGROUND: The discussion on the safety of thimerosal-containing vaccines (TCVs) and their impact on child development it́s very relevant. METHODS: This is a cohort study with mother-child dyads who received prenatal care in the Unified Health System. The domains of motor, cognitive and language development were evaluated in children between 24 and 36 months of age. Data on vaccination were obtained through the child's immunization record. A linear regression analysis was carried out considering possible confounders. RESULTS: In bivariate analyses, motor and language development were associated with TCVs (p < 0.05). However, in the multivariate analysis, this association was not maintained (p > 0.05). These results indicate that the use of TCVs is not associated with child development. The importance of this study is summarized in transmitting relevant information regarding public health, based on reliable data.

Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review / Eficácia do uso de colírios sem preservativos comparados com colírios com preservativos no tratamento do olho seco: uma revisão sistemática

ABSTRACT This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.

RESUMO Esta revisão sistemática teve como objetivo avaliar a eficácia do uso de lágrimas artificiais sem conservantes em comparação com lubrificantes preservados no tratamento do olho seco na Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). As bases de dados online foram pesquisadas (LILACS, EMBASE, MEDLINE e CENTRAL) desde o início até abril de 2018; referências de artigos incluídos também foram pesquisadas. Foram utilizados os seguintes descritores: lubrificantes OU lágrimas artificiais OU lágrimas artificiais, lubrificantes E olho seco OU síndrome do olho seco OU síndromes, olho seco OU olhos secos. Dos 2028 resultados de busca eletrônica, 29 artigos completos foram recuperados, e quatro foram considerados relevantes. O número de participantes desses estudos variou de 15 e 76. A meta-análise foi possível para as seguintes variáveis: escore de desfecho dos sintomas de acordo com o Índice de Doença da Superfície Ocular - Allergan (OSDI), taxa de secreção lacrimal pelo teste de Schirmer, taxa de evaporação lacrimal usando o teste de tempo de ruptura do filme lacrimal, queimação, sensação de corpo estranho e fotofobia. Nenhuma diferença estatisticamente significativa foi observada entre os dois grupos, e nenhum efeito adverso foi atribuído às intervenções. Evidências provando que as lágrimas artificiais sem conservantes são mais eficazes do que as lágrimas artificiais preservadas estão faltando.