RESUMO
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.
Assuntos
Glaucoma , Prostaglandinas F Sintéticas , Anti-Hipertensivos/toxicidade , Compostos de Benzalcônio/metabolismo , Compostos de Benzalcônio/toxicidade , Cloprostenol/metabolismo , Túnica Conjuntiva/metabolismo , Glaucoma/metabolismo , Humanos , Latanoprosta/toxicidade , Soluções Oftálmicas/toxicidade , Conservantes Farmacêuticos/metabolismo , Conservantes Farmacêuticos/toxicidade , Prostaglandinas F Sintéticas/toxicidade , TravoprostRESUMO
Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosal-containing influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 microgHg at birth, 30, 60 and 120 days, and 50 microgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 microgHg/kg b.w.) than from breastfeeding (0.266 microgHg/kg b.w.). While mothers showed a relative decrease (-57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant's hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.