1. Investigación

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in -cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.

Objective: The study aimed to quantitatively evaluate the elution of methylmethacrylate from CAD-CAM manufactured removable complete dentures (RCDs) using high performance liquid chromatography (HPLC). Methods: Thirty-two RCDs were manufactured following either the CNC-milling (Milled: n=8) or the 3D-printing (n=24) protocols. The 3D-printed dentures were further categorized into three groups based on their postproduction rinsing cycles [Extended wash cycle (EWC), Standard wash cycle (SWC), and SWC with an additional Dur´econ coating (SWC2)]. HPLC was used to evaluate the methylmethacrylate concentrations (MMCs) eluted from the dentures in each group for different time periods (1, 2, 4, 8, and 24 hours). Mean and standard deviations were calculated for the MMCs; data was verified for normal distribution, ANOVA and post hoc tests were applied for statistical analyses (⍺=0.05). Results: The HPLC revealed that all the denture groups recorded some amounts of MMCs, with significant differences [F (3, 31) = 23.646, p<0.0001]. The milled denture group had the highest MMCs at 24 hours when compared to the EWC (p<0.0001), SWC (p=0.001), and SWC2 (p<0.0001) denture groups. SWC had a higher MMC than EWC (p=0.032) and SWC2 (p=0.015). No differences were found in MMCs when comparing EWC and SWC2 (p=0.989). Conclusion: Methylmethacrylate concentrations were significantly lower in 3D-printed RCDs than in milled RCDs when using the resins employed in this study. Furthermore, the MMCs can be further decreased in 3D-printed RCDs when coated with an additional thin protective layer (Dur´econ) by following the manufacturerrecommended rinsing protocol or when an extended isopropanol wash cycle is adopted.

In recent years, the use of 3D printing technologies in orthopedic surgery has markedly increased, as they offer the possibility of printing personalized prostheses. The work presented in this article is a preliminary study of a research project which aims to manufacture customized spacers containing antibiotics for use in joint replacement surgery. The objective of this work was to design and print different 3D constructs to evaluate the use of different materials, their properties after the process of 3D printing, such as resistance, and the release kinetics of drugs from the constructs. Different designs and different materials were analyzed to obtain a 3D construct with suitable properties. Our design takes advantage of the micropores created between the layers of the 3D printed filaments to release the contained drug. Using polylactic acid (PLA) we were able to print cylindrical structures with interconnected micropores and a hollow chamber capable of releasing methylene blue, which was selected as a model drug. The final PLA 3D construct was printed with a 10% infill. The physical and technological characteristics, morphological changes at body temperature and interaction with water were considered to be acceptable. The PLA 3D printed constructs were found to have sufficient strength to withstand a force of 500 kg. The results obtained allow to continue research in this project, with the aim of manufacturing prostheses containing a reservoir of antibiotics or other drugs in their interior for their subsequent controlled release.

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of e cient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug di usion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies di erences. Micelles of Pluronic F68 (3–4 nm) and Soluplus (52–59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation e ciency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen’s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the di erences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the di usion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen’s egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the di erent antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 C in darkness and it is not an irritant to the eye. The di usion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.

Introducción: El deterioro cognitivo (DC) es una enfermedad que aumenta con la edad. Es importante conocer los factores protectores y de riesgo de esta enfermedad. Metodología: Estudio observacional realizado a 729 personas mayores de 65 años en 13 farmacias comunitarias durante dos años. Se recogieron datos demográficos (sexo, edad, nivel de estudios) y de estilos de vida (afición a la lectura, realización de pasatiempos, horas de televisión) y para el cribaje de los pacientes se realizaron los test SPMSQ (Short-Portable Mental State Questionaire) de Pfeiffer y Mini-Mental State Examination (MMSE) versión NORMADERM. También se realizó una revisión bibliográfica del tema. Resultados: Se detectó un 17,6% de DC. Se encontró una asociación estadísticamente significativa como protección frente al DC con la afición a la lectura y el nivel de estudios. No se encontró asociación con las horas de televisión (TV) ni con la realización de pasatiempos. La revisión bibliográfica aportó más factores protectores y de riesgo. Discusión: Con nuestros datos podemos afirmar que tanto la reserva cognitiva (años de estudio) como la estimulación cognitiva (horas de lectura) protegen del DC. Sobre los demás datos obtenidos no se han encontrado coincidencias, por lo que sería necesario aumentar el tamaño muestral para poder realizar una comparación más eficaz. Conclusiones: El nivel educativo bajo es un factor de riesgo de DC, mientras que estudios superiores serían un factor preventivo. La lectura es un factor protector de DC. / Introduction: Cognitive Dysfunction (CD) is a disease that increases with age. It is important to know the protective and risk factors for this disease. Methodology: Observational study carried out on 729 people over 65 years of age in community 13 pharmacies for two years. Demographic data were collected (sex, age, level of studies) and lifestyles (love of reading, hobbies such as crossword puzzles or sudokus etc, TV hours), and the SPMSQ (Short-Portable Mental State Questionaire) test of Pfeiffer and Mini- Mental State Examination (MMSE) were carried out to check the patient’s CD. A bibliographic review of the subject was also conducted. Results: 17.6% of CD was detected. A statistically significant association was found as a protection against CD with a love of reading and the level of studies. No association was found with TV hours or hobbies. The literature review provided more protective and risk factors. Discussion: With our data we can affirm that both cognitive reserve (years of study) and cognitive stimulation (hours of reading) protect from CD. No coincidences were found on the other data obtained, so it would be necessary to increase the sample size in order to make a more effective comparison. Conclusions: Low educational level is a risk factor for CD while higher education would be a preventive factor. Reading is a protective factor of CD.