This work presents the possibility of using a synthetic membrane for pretracing mucosal penetration studies. The permeability of two types of membranes, porcine oral mucosa and a synthetic Nuclepore membrane, to water was compared. Moreover, the water permeability of membranes modified with waterproofing formulations was measured to study their ability to protect against the penetration of viruses, toxins, etc. A very good correlation was obtained between the transmucosal water loss (TMWL) values of the artificial membrane and the mucosa. These results support the possible use of this synthetic membrane in the screening of the water permeability of formulations. In addition, studies of the permeation of different actives, drugs and biocides through the two membranes were carried out, and these results were compared with their skin permeation data. The synthetic membrane does not seem to discern between compounds in terms of permeability, which could be due to the lack of lipids in the composition of this synthetic membrane. Therefore, Nuclepore alone cannot be used as a model for the release of actives. Additionally, the permeation of caffeine through intact or modified membranes incorporating waterproofing formulations was also studied. In this case, similar permeation profiles through the synthetic membrane and mucosa were found. The results from these assays should lend support to the use of this synthetic membrane when screening formulations to be applied in oral penetration studies.

The permeability of the oral or nasal mucosa is higher than that of the skin. Mucosa permeability depends mainly on the thickness and keratinization degree of the tissues. Their permeability barrier is conditioned by the presence of certain lipids. This work has the main aim of reinforcing the barrier effect of oral mucosa with a series of formulations. Sixty-three initial formulations were evaluated for transmembrane water loss, with 16 formulations selected to test on sublingual mucosa. In vitro release tests of caffeine, ibuprofen, dexamethasone and ivermectin were carried out on porcine skin, mucosa and modified mucosa in order to compare the effectiveness of the formulations. A similar permeation profile was obtained in the different membranes: caffeine > ibuprofen ~ dexamethasone > ivermectin. The most efficient formulation was a liposomal formulation composed of lipids that are present in the skin stratum corneum. Impermeability provided by this formulation was really notable mainly for the low molecular weight compounds, decreasing their permeability coefficient between 40-80%. The reinforcement of the barrier function of mucosa provides a reduction or prevention of the permeation of different actives such as viruses, contaminants, toxins, etc.

We present an attempt to estimate the long-term changes of Relative Sea Level (RSL) and the different factors contributing to such trends on a local and regional scale using a statistical linear model. The time series analysed correspond to 17 tide-gauges grouped in three different areas: the northern and western Atlantic coasts of the Iberian Peninsula, the Canary Islands, and the southern and eastern coasts of the Iberian Peninsula and Balearic Islands. The analysis was performed for two periods: 1948-2019, using tide-gauge data, and 1993-2019, using both tide-gauge and altimetry data for comparison. The trends for the period 1948-2019 ranged between 1.09 0.14 (Canary Islands) and 2.05 0.21 mm/yr, for the northern and western Atlantic Iberian Peninsula. Altimetry data during the period 1993-2019 yielded quite homogeneous results for all the locations and regions, ranging between 2.7 0.4 and 3.0 0.3 mm/yr. On the contrary, the results obtained from tide-gauge data for this recent period showed a large dispersion, very likely due to local effects or even levelling or instrumental errors. Nevertheless, when the results were averaged for each area, the observed trends were comparable to the altimetry results, with values of 2.3 0.8, 2.7 0.5 and 2.8 0.8 mm/yr for the three regions of study. A stepwise forward linear regression has been used to relate the observed RSL variability to the atmospheric forcing and the thermosteric and halosteric components of the sea level. Surprisingly, the thermosteric and halosteric contributions were not significantly correlated to the observed RSL in many cases, and consequently the steric, the total addition of mass, the mass of salt, and the freshwater contributions to the observed sea level trends could not be reliably estimated. This result seems to be the consequence of the scarcity of temperature and salinity data. This hypothesis is confirmed by the exception of L’Estartit tide-gauge. This location is close to a well sampled region. In this case, the atmospheric variables and the thermosteric and halosteric terms explained the 80 % of the observed RSL variance and the contributions of these terms could be estimated. The freshwater contribution for this location was between 1.3 and 1.4 mm/yr, consistent with recent estimations of the contributions of glaciers and Greenland and Antarctica Ice Sheets. These results highlight the importance of monitoring programs and routine sampling for the determination of the different factors contributing to the sea level variability.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.