TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level

Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine N-acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied. Several experiments were undertaken to verify the adequate time to reach the maximal effect by using the TRPV4 agonist GSK1016790A, together with a dose–response study. An increase of 2.4 folds in AANAT was seen after 18 h of incubation with 10 nM of GSK1016790A (p < 0.001, n = 6). This increment was verified by antagonist assays. In summary, AANAT levels and therefore melatonin synthesis change after TRPV4 channel stimulation. Using this cell model together with human ciliary body tissue it is possible to suggest that AANAT plays an important role in pathologies related to intraocular pressure

Effect of nutritional supplement based on melatonin on the intraocular pressure in normotensive subjects

Purpose: To evaluate the effect of a new nutritional supplement based on melatonin on the intraocular pressure (IOP) in normotensive subjects. Patients and methods: A short-term prospective study was designed. Sixty-seven normotensive subjects were recruited. Patients were divided into two groups. The daily group (DG) (n = 18) was instructed to take the supplement between 22:00 and 23:00 (before sleeping) for 3 consecutive days. IOP was measured from 10.00 to 11.00 am the day before treatment and during the 3 days of experiment. The acute group (AG) (n = 49) was instructed to take the supplement after the second measure (11.00) of the second day. IOP was measured 1 h and just before the intake of the supplement and 1 and 2 h after. All measurements in this group were taken 1 day before without any supplement (control) and the day of experiment. Results: The DG group showed a significant decrease in IOP after supplement intake in all days of experiment, from 14.9 ± 3.4 mm Hg to 13.8 ± 2.9 mm Hg after 3 days of experiment (p value < 0.001). For AG, IOP did not change during the control day; however, a reduction of 1 mm Hg was found 2 and 3 h after supplement intake, from 15.7 ± 2.5 mm Hg to 14.7 ± 2.5 mm Hg and 15.1 ± 2.7 mm Hg, respectively, being statistically significant (p value < 0.001). Conclusion: The supplement based on melatonin was able to reduce the IOP in normotensive subjects after 2 h of intake. Moreover, the daily intake showed a reduction in IOP during the 3 days of experiment

Comparison of Intraocular Pressure before and after Laser In Situ Keratomileusis Refractive Surgery Measured with Perkins Tonometry, Noncontact Tonometry, and Transpalpebral Tonometry

Purpose. To compare the intraocular pressure (IOP) before and after Laser In Situ Keratomileusis (LASIK), measured by Diaton, Perkins, and noncontact air pulse tonometers. Methods. Fifty-seven patients with a mean age of 34.88 were scheduled for myopia LASIK treatment. Spherical equivalent refraction (SER), corneal curvature (K), and central corneal thickness (CCT) and superior corneal thickness (SCT) were obtained before and after LASIK surgery. IOP values before and after surgery were measured using Diaton, Perkins, and noncontact air pulse tonometers. Results. The IOP values before and after LASIK surgery using Perkins tonometer and air tonometers were statistically significant (). However, no significant differences were found () for IOP values measured with Diaton tonometer. CCT decreases significantly after surgery () but no statistical differences were found in SCT (). Correlations between pre- and postsurgery were found for all tonometers used, with and for the air pulse tonometer, and for Perkins, and and for Diaton. Conclusion. Transpalpebral tonometry may be useful for measuring postsurgery IOP after myopic LASIK ablation because this technique is not influenced by the treatment

Unravelling the vertebrate scavenger assemblage in the Gobi Desert, Mongolia

Despite the essential role that vertebrate scavengers play in ecosystems, most studies have been conducted in Europe and North America, and there is a lack of information on vertebrate scavengers in vast regions of the world. Our aim was to describe the functioning and composition of the unknown vertebrate scavenger assemblage in the Gobi Desert, Mongolia, and determine how carcass size and habitat type affect species composition and carrion use. We monitored carcasses with camera traps and we also conducted observation points to survey the raptor community and identify the proportion of raptor species making use of the carcasses. We recorded eight vertebrate scavenger species (five birds and three mammals) by camera trap and seven raptors at observation points. Over half of the raptor species recorded at the observation points were also found feeding on carrion. The two most threatened species were only recorded in the mountain habitat. Furthermore, scavenger abundance and consumption rates were higher at large carcasses. This study highlights the importance of scavenging by raptors and other vertebrate scavengers for carrion elimination in ecosystems with extreme climatic conditions.AOT, JMPG, ZMR, LNA and ESG were supported by Generalitat Valenciana (SEJI/2018/024), ZMR and LNA also by contracts co-funded by the Generalitat Valenciana and the European Social Fund (APOSTD/2019/016 and ACIF/2019/056, respectively), and JASZ by funds from the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (RTI 2018-099609-B-C21)

Expression of Melatonin and Dopamine D Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension

Background: Experiments in the late nineties showed an inverse relationship in the eye levels of melatonin and dopamine, thereby constituting an example of eye parameters that are prone to circadian variations. The underlying mechanisms are not known but these relevant molecules act via specific cell surface dopamine and melatonin receptors. This study investigated whether these receptors formed heteromers whose function impact on eye physiology. We performed biophysical assays to identify interactions in heterologous systems. Particular heteromer functionality was detected using Gi coupling, MAPK activation, and label-free assays. The expression of the heteroreceptor complexes was assessed using proximity ligation assays in cells producing the aqueous humor and human eye samples. Dopamine D receptors (DRs) were identified in eye ciliary body epithelial cells. We discovered heteromers formed by DR and either MT (MTR) or MT (MTR) melatonin receptors. Heteromerization led to the blockade of DR-Gi coupling and regulation of signaling to the MAPK pathway. Heteromer expression was negatively correlated with intraocular hypertension. Conclusions: Heteromers likely mediate melatonin and dopamine actions in structures regulating intraocular pressure. Significant expression of DR-MTR and DR-MTR was associated with normotensive conditions, whereas expression diminished in a cell model of hypertension. A clear trend of expression reduction was observed in samples from glaucoma cases. The trend was marked but no statistical analysis was possible as the number of available eyes was 2

Adrenergic‐melatonin receptor complexes control ion homeostasis and intraocular pressure and their disruption contributes to hypertensive glaucoma

Background and Purpose: Often, glaucoma courses with elevated eye hydrostatic pression, which is regulated by endogenous melatonin. Via α1‐adrenoceptor activation, phenylephrine increases cytoplasmic [Ca2+] that is detrimental in glaucoma. The aims of the paper were i) elucidating the role of melatonin receptors in humour production and intraocular pressure (IOP) maintenance and ii) identifying glaucoma relevant melatonin‐adrenergic interactions. Experimental approach: Biophysical and proximity ligation assays were performed to identify interactions in heterologous systems, in cell lines and in human eyes. Gs/Gi/Gq signaling was investigated in heterologous systems and cells producing the aqueous humour. IOP was determined in a mice model of glaucoma. Retinography and topically pharmacological treatment were performed in control and in glaucomatous mice. Key Results: α1‐adrenergic and melatonin receptors form functional complexes in which the C‐terminal tail of the adrenergic receptor play a relevant role. Remarkably, activation of α1‐adrenoceptors in the complex did not lead to cytosolic Ca2+ increases, suggesting Gs instead of Gq coupling. The number of complexes significantly decreased in models of glaucoma and, more importantly, in human samples of glaucoma patients. The results led to hypothesize that melatonin, a hypotensive agent, plus blockade of α1‐adrenergic receptors could normalize pressure in glaucoma. Remarkably, co‐instillation of melatonin and prazosin, an α1‐adrenergic receptor antagonist, resulted in long‐term decreases in IOP in a well‐established animal model of glaucoma. Conclusions & Implications: The findings are instrumental to understand the physiological function of melatonin in the eye and its potential to address eye pathologies by targeting melatonin receptors and their complexes

COSMOS: the dialysis scenario of CKD-MBD in Europe

Background Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. Methods COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. Results The haemodialysis population in Europe is an aged population (mean age 64.8 ± 14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3 ± 14.3 versus 66.0 ± 13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. Conclusions The COSMOS baseline results show important differences across Europe in the management of CKD-MB

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Scavenging in the Anthropocene: Human impact drives vertebrate scavenger species richness at a global scale

Understanding the distribution of biodiversity across the Earth is one of the most challenging questions in biology. Much research has been directed at explaining the species latitudinal pattern showing that communities are richer in tropical areas; however, despite decades of research, a general consensus has not yet emerged. In addition, global biodiversity patterns are being rapidly altered by human activities. Here, we aim to describe large‐scale patterns of species richness and diversity in terrestrial vertebrate scavenger (carrion‐consuming) assemblages, which provide key ecosystem functions and services. We used a worldwide dataset comprising 43 sites, where vertebrate scavenger assemblages were identified using 2,485 carcasses monitored between 1991 and 2018. First, we evaluated how scavenger richness (number of species) and diversity (Shannon diversity index) varied among seasons (cold vs. warm, wet vs. dry). Then, we studied the potential effects of human impact and a set of macroecological variables related to climatic conditions on the scavenger assemblages. Vertebrate scavenger richness ranged from species‐poor to species rich assemblages (4–30 species). Both scavenger richness and diversity also showed some seasonal variation. However, in general, climatic variables did not drive latitudinal patterns, as scavenger richness and diversity were not affected by temperature or rainfall. Rainfall seasonality slightly increased the number of species in the community, but its effect was weak. Instead, the human impact index included in our study was the main predictor of scavenger richness. Scavenger assemblages in highly human‐impacted areas sustained the smallest number of scavenger species, suggesting human activity may be overriding other macroecological processes in shaping scavenger communities. Our results highlight the effect of human impact at a global scale. As speciesrich assemblages tend to be more functional, we warn about possible reductions in ecosystem functions and the services provided by scavengers in human‐dominated landscapes in the Anthropocene

Functional biogeography of vertebrate scavengers drives carcass removal across biomes

Resumen del trabajo presentado en el XVI Congreso Nacional de la AEET 2023: la ecología en una biosfera humanizada, celebrado en Almería entre el 16 y el 20 de octubre de 2023.Vertebrate scavengers play a crucial role in food web stability and cycling of organic matter and nutrients. However, the global factors that influence their functional biogeography and impact on ecosystem functioning at regional and local levels remain poorly understood. We aim to address this challenge by analyzing a global dataset covering 49 regions in all inhabited continents, including information on 1,847 locally monitored carcasses and 204 vertebrate scavenger species along with their functional traits. We investigate the importance of biogeographical (spatial), environmental and anthropogenic factors in structuring vertebrate scavengers¿ functional trait composition, diversity and abundance. Additionally, we investigate how these biodiversity attributes affect carcass removal at regional and local scales. Our results show that the functional trait composition of assemblages across studied regions was primarily explained by latitude and lon¬gitude, suggesting a strong biogeographical signature. In addition, while functional richness remained unexplained, scavenger abundance responded to both environmental and spatial factors. Further, we found that carcass removal was mainly driven by functional composition, but with the relative importance of particular functional traits varying from local to regional scales. At the local scale, carcass removal was positively related to large carnivorous species with large home ranges, while at the regional scale, carcass removal was better explained by the presence of vultures, other raptors and diurnal birds. Our study provides a better understanding of the factors controlling the func¬tional biogeography of terrestrial vertebrates and their role in maintaining essential ecological functions and services.Peer reviewe