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Eye & Contact Lens Jan 2005Human beta-defensin-2 (hBD-2) and cathelicidin LL-37 are salt-sensitive cationic antimicrobial peptides expressed by ocular surface epithelia. The goal of this study was...
PURPOSE
Human beta-defensin-2 (hBD-2) and cathelicidin LL-37 are salt-sensitive cationic antimicrobial peptides expressed by ocular surface epithelia. The goal of this study was to investigate the effect of preservative-free artificial tears on hBD-2 and LL-37 antimicrobial activity against Pseudomonas aeruginosa.
METHODS
P. aeruginosa was incubated with hBD-2 or LL-37 in the absence or presence (70% vol/vol) of different preservative-free artificial tears--Visine Tears (300 mOsm/kg), Tears Naturale Free (261 mOsm/kg), TheraTears (185 mOsm/kg), and Refresh Plus (325 mOsm/kg)--for 2 hours at 37 degrees C. In some experiments, P. aeruginosa was incubated with hBD-2 or LL-37 and Visine Tears or Tears Naturale Free with or without carboxymethylcellulose (0.5% vol/vol final concentration). Plates were inoculated with samples of each reaction mixture and then incubated for 24 hours at 37 degrees C.
RESULTS
Visine Tears and Tears Naturale Free had little or no effect on the antimicrobial activity of 100 microg/mL hBD-2 or LL-37. In the presence of Refresh Plus and TheraTears, the activity of 100 microg/mL hBD-2 or LL-37 was reduced by 90% to 100%. Carboxymethylcellulose, at a concentration comparable to that present in Refresh Plus, reduced the effectiveness of hBD-2 or LL-37 by 40% to 90% in the presence of Tears Naturale Free and Visine Tears.
CONCLUSION
Human beta-defensin-2 and cathelicidin LL-37 inhibit the growth of P. aeruginosa in vitro, but this activity is markedly reduced in the presence of Refresh Plus and TheraTears. These results suggest that carboxymethylcellulose-containing artificial tears may reduce the activity of the endogenously produced antimicrobial peptides.
Topics: Anti-Infective Agents; Antimicrobial Cationic Peptides; Carboxymethylcellulose Sodium; Humans; Ophthalmic Solutions; Preservatives, Pharmaceutical; Pseudomonas aeruginosa; Sodium Chloride; beta-Defensins; Cathelicidins
PubMed: 15665670
DOI: 10.1097/01.icl.0000146320.64438.8c -
BMC Ophthalmology Aug 2017The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the...
Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study.
BACKGROUND
The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients.
METHODS
A cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni's adjustment of p-values.
RESULTS
No significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls.
CONCLUSIONS
Compared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be aware that even PF formulations may lead to a mild ocular surface impairment.
Topics: Aged; Antihypertensive Agents; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Tolerance; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Microscopy, Confocal; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Tears; Time Factors; Timolol; Tonometry, Ocular; Treatment Outcome
PubMed: 28768500
DOI: 10.1186/s12886-017-0534-z -
Cells Apr 2023Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side...
Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side effects. We tested several types of preservatives such as phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea (IU), the composition of gluconolactone and sodium benzoate (GSB), diazolidinyl urea (DU), and two grapefruit essential oils, one of which was industrially produced and a second which was freshly distilled from fresh grapefruit peels. This study aimed to find the relationship between preservative concentration, cell growth, collagen secretion, and cell viability. We hypothesized that these products induced a decrease in collagen secretion from human dermal fibroblasts. Our research, for the first time, addressed the overall effect of other preservatives on skin extracellular matrix (ECM) by studying their effect on metalloproteinase-2 (MMP-2) activity. Except for cytotoxicity and contact sensitivity tests, there are no studies of their effect on skin ECM in the available literature. These studies show potential antimicrobial activity, especially from the compounds IU and DU towards reference bacteria and the compounds methyl paraben and propyl paraben against reference fungi. The MTS test showed that fibroblasts are more sensitive to the tested group of preservatives than keratinocytes, which could be caused by the differences between the cells' structures. The grapefruit oils exhibited the most cytotoxicity to both tested cell lines compared to all considered preservatives. The most destructive influence of preservatives on collagen synthesis was observed in the case of IU and DU. In this case, the homemade grapefruit oil turned out to be the mildest one. The results from a diverse group of preservatives show that whether they are natural or synthesized compounds, they require controlled use. Appropriate dosages and evaluation of preservative efficacy should not be the only aspects considered. The complex effect of preservatives on skin processes and cytotoxicity is an important topic for modern people.
Topics: Humans; Parabens; Matrix Metalloproteinase 2; Preservatives, Pharmaceutical; Cosmetics; Allergens
PubMed: 37048149
DOI: 10.3390/cells12071076 -
Journal of Pharmaceutical Sciences Jun 2021Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual...
Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics.
Topics: Excipients; Micelles; Polysorbates; Preservatives, Pharmaceutical; Surface-Active Agents
PubMed: 33387597
DOI: 10.1016/j.xphs.2020.12.030 -
BioMed Research International 2013The treatment goals for glaucoma are lowering the intraocular pressure and preservation of vision. Topical hypotensive drops are the standard form of therapy which is... (Review)
Review
The treatment goals for glaucoma are lowering the intraocular pressure and preservation of vision. Topical hypotensive drops are the standard form of therapy which is often associated with some symptoms of toxicity, ocular inflammation, allergy, or ocular surface disease (OSD). OSD is a common comorbidity in glaucoma patients, and its prevalence with glaucoma increases with age. Use of topical treatment could additionally increase symptoms of OSD mostly due to preservatives added to multidose medication bottles used to reduce the risk of microbial contamination. This toxicity has been particularly associated with BAK, the most commonly used preservative which damages conjunctival and corneal epithelial cells and significantly aggravates OSD symptoms. OSD adversely affects patients' quality of life causing discomfort and problems with vision which in turn may result in noncompliance, lack of adherence, and eventually visual impairment. In the management of glaucoma patients OSD symptoms should not be overlooked. If they are present, topical glaucoma treatment should be adapted by decreasing the amount of drops instilled daily, using BAK-free or preservative-free medication and lubricants if necessary. Awareness of the presence and importance of OSD will in turn improve patients' adherence and compliance and thus ultimately the preservation of long-term vision.
Topics: Administration, Topical; Aged; Antihypertensive Agents; Eye; Glaucoma; Humans; Intraocular Pressure; Male; Preservatives, Pharmaceutical; Treatment Outcome
PubMed: 24224176
DOI: 10.1155/2013/696328 -
Journal of the European Academy of... Jun 2022Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans.
BACKGROUND
Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans.
OBJECTIVES
To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet.
PATIENTS AND METHODS
Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019.
RESULTS
Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol-positive patients, compared to benzyl alcohol-negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases.
CONCLUSIONS
Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful.
Topics: Allergens; Benzyl Alcohol; Dermatitis, Allergic Contact; Humans; Patch Tests; Perfume; Preservatives, Pharmaceutical; Reproducibility of Results; Retrospective Studies
PubMed: 35080274
DOI: 10.1111/jdv.17968 -
Physiological Research Nov 2018Parabens are a group of chemicals used as preservatives in the food, cosmetic and pharmaceutical industries. They are known to possess estrogenic effects, and therefore...
Parabens are a group of chemicals used as preservatives in the food, cosmetic and pharmaceutical industries. They are known to possess estrogenic effects, and therefore have been classified as endocrine disruptors. In addition to the classical endocrine organs, other tissues have endocrine activity, including adipose tissue. Several chemicals are known to cause obesogenic effects, and parabens are currently being studied in this context. The aim of this study was to investigate the possible connections of paraben exposure and obesity. Blood plasma from 27 healthy women was collected during their menstrual cycle. Basal anthropometric measures, levels of parabens (methylparaben, ethylparaben and propylparaben), adipokines (adiponectin, adipsin, leptin, resistin and visfatin) and hormones affecting energy balance and metabolic health (c-peptide, ghreline, GIP, GLP-1, glucagon, insulin, PAI-1) were measured. A Kolmogorov-Smirnov test showed higher methylparaben and propylparaben levels in women with BMI 25-34.9 compared to those with BMI 18.5-24.9. Plasma levels of methylparaben as well as the sum of parabens were positively associated with the plasma adipsin levels. Negative associations for methylparaben were found for glucagon, leptin and PAI-1. In accordance with other experimental studies we observed important associations of methylparaben and hormones affecting energy balance and metabolic health, indicating its obesogenic potential.
Topics: Adipokines; Adult; Energy Metabolism; Female; Food Preservatives; Humans; Obesity; Parabens; Preservatives, Pharmaceutical
PubMed: 30484673
DOI: 10.33549/physiolres.934004 -
Korean Journal of Ophthalmology : KJO Jun 2024To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in...
PURPOSE
To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in treatments-naive patients with primary open-angle glaucoma (POAG).
METHODS
This was a retrospective, real-world clinical practice setting study that included 107 eyes of 107 subjects with POAG who had never been treated for glaucoma. All subjects were received PF tafluprost/timolol FC once daily. Intraocular pressure (IOP) levels were documented for each eye at the untreated baseline and up to 6 months after the initiation of medical treatment. All adverse events, including ocular and systemic adverse reactions, were recorded. Additionally, the reasons for medication discontinuations were thoroughly documented.
RESULTS
A total of 32 POAG patients with high-baseline IOP (>21 mmHg) and 75 with normal-baseline IOP were included in the study. The subjects' baseline mean age was 62.4 ± 8.7 years (range, 26.0-85.0 years); among them, 42 were female (39.3%). Mean IOP at baseline for all patients was 18.6 ± 4.3 mmHg. The mean IOP at 6 months was 12.6 ± 4.7 mmHg, representing a significant decrease compared to the baseline (-32%, p < 0.001). In POAG patients with high-baseline IOP, mean IOP was significantly lowered from 28.0 ± 5.7 mmHg at baseline to 18.0 ± 5.5 mmHg (-35%, p < 0.001); in patients with normal-baseline IOP, from 14.6 ± 3.4 mmHg at baseline to 10.3 ± 4.1 mmHg (-29%, p < 0.001). PF tafluprost/timolol FC was well-tolerated and safe. After 6 months, 97.2% of all patients remained on therapy.
CONCLUSIONS
In this real-world observational study, once-daily treatment with PF tafluprost/timolol FC demonstrated clinically relevant and statistically significant efficacy, as well as safety and good tolerability, in treatment-naive patients diagnosed with POAG.
Topics: Humans; Glaucoma, Open-Angle; Female; Male; Retrospective Studies; Intraocular Pressure; Middle Aged; Prostaglandins F; Timolol; Adult; Aged; Treatment Outcome; Ophthalmic Solutions; Preservatives, Pharmaceutical; Drug Combinations; Antihypertensive Agents; Follow-Up Studies; Tonometry, Ocular; Aged, 80 and over; Dose-Response Relationship, Drug
PubMed: 38665112
DOI: 10.3341/kjo.2024.0021 -
International Journal of Molecular... Nov 2022In recent years, personal care products (PCPs) have surfaced as a novel class of pollutants due to their release into wastewater treatment plants (WWTPs) and receiving... (Review)
Review
In recent years, personal care products (PCPs) have surfaced as a novel class of pollutants due to their release into wastewater treatment plants (WWTPs) and receiving environments by sewage effluent and biosolid-augmentation soil, which poses potential risks to non-target organisms. Among PCPs, there are preservatives that are added to cosmetics for protection against microbial spoilage. This paper presents a review of the occurrence in different environmental matrices, toxicological effects, and mechanisms of microbial degradation of four selected preservatives (triclocarban, chloroxylenol, methylisothiazolinone, and benzalkonium chloride). Due to the insufficient removal from WWTPs, cosmetic preservatives have been widely detected in aquatic environments and sewage sludge at concentrations mainly below tens of µg L. These compounds are toxic to aquatic organisms, such as fish, algae, daphnids, and rotifers, as well as terrestrial organisms. A summary of the mechanisms of preservative biodegradation by micro-organisms and analysis of emerging intermediates is also provided. Formed metabolites are often characterized by lower toxicity compared to the parent compounds. Further studies are needed for an evaluation of environmental concentrations of preservatives in diverse matrices and toxicity to more species of aquatic and terrestrial organisms, and for an understanding of the mechanisms of microbial degradation. The research should focus on chloroxylenol and methylisothiazolinone because these compounds are the least understood.
Topics: Animals; Sewage; Preservatives, Pharmaceutical; Cosmetics
PubMed: 36430973
DOI: 10.3390/ijms232214495 -
International Journal of Environmental... Jan 2023Although the molecular mechanisms underlying methylmercury toxicity are not entirely understood, the observed neurotoxicity in early-life is attributed to the covalent... (Review)
Review
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.
Topics: Humans; Thimerosal; Methylmercury Compounds; Preservatives, Pharmaceutical; Mercury; Vaccines; Neurotoxicity Syndromes; Sulfhydryl Compounds
PubMed: 36673825
DOI: 10.3390/ijerph20021070