Pharmacokinetics of Metformin in Combination With Sitagliptin in Adult Horses After Enteral Administration

© 2019. Elsevier. This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0 This document is the accepted version of a published work that appeared in final form in Journal of Equine Veterinary Science (JEVS) To access the final work, see DOI: https://doi.org/10.1016/j.jevs.2018.10.017Insulin dysregulation (ID) is a common metabolic disorder in horses. Recently, incretin hormone release has been suggested to be involved in ID in horses. In human medicine, metformin and sitagliptin are commonly used in combination for metabolic syndrome. This combination could be useful in treating ID in horses. However, no pharmacokinetics data have been reported in this species. The objective of the present study was to establish the plasma concentration–time profile and to derive pharmacokinetics data for a combination of metformin and sitagliptin in horses after enteral administration. Six healthy adult Purebred Spanish horses were used. A metformin (15 mg/kg) plus sitagliptin (1.5 mg/kg) preparation was administered by intragastric route (IG) as an enteral solution. Blood samples were collected from 0 to 48 hours after IG drug administration. Plasma concentrations of metformin and sitagliptin were measured using HPLC methods. The t½λz for metformin was 2.9 hours and for sitagliptin 21 hours. The Cmax was 442 ± 84 mg/L within 0.9 hours for metformin and 94 ± 14 mg/L within 1.3 hours for sitagliptin. No adverse effects were observed, and the combination of metformin and sitagliptin was well tolerated. Therefore, these results suggest that metformin plus sitagliptin might be a combination to consider in horses with ID. Additional studies are needed to establish the effectiveness and tolerance in equids affected by endocrine disorders

Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

Chronic kidney disease (CKD) comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident), continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT) becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed

Revisiting the Epipalaeolithic-Neolithic Transition in the Extreme NW of Africa : The Latest Results of the Chronological Sequence of the Cave of Kaf Taht el-Ghar (Tétouan, Morocco)

This study focuses on the chronostratigraphic sequence of the Cave of Kaf Taht el-Ghar (Dar Ben Karrich, Tétouan, Morocco) excavated in 2012 in the framework of the AGRIWESTMED research project. The broad sequence reveals a series of occupations ranging from the Pleistocene (Moroccan Aterian) to recent historical times. Our research identifies a rich Early Neolithic phase (sixth millennium cal BC) containing the earliest pottery and domesticated animal and plant remains in the western Maghreb. However, this Early Neolithic level is not an immediate successor of the last traces of the Epipalaeolithic hunter-gatherer occupation, which started at the end of the Younger Dryas (10,900-9700 cal BC). An abandonment phase, spanning more than a millennium, separated them. This hiatus appears to originate from a cold climatic event that began in the late seventh millennium cal BC (ca. 6200 BC) and ended around the mid-sixth millennium cal BC. La présente étude est centrée sur la séquence chronostratigraphique de la grotte de Kaf Taht el-Ghar (Dar Ben Karrich, Tétouan, Maroc), fouillée pour la dernière fois en 2012 dans le cadre du projet de recherche AGRIWESTMED. La séquence générale révèle une série d'occupations allant du Pléistocène (Atérien marocain) jusqu'aux temps historiques récents. Parmi les résultats les plus remarquables, on peut souligner l'identification d'une riche phase du Néolithique Ancien (6ème millénaire avant JC) contenant les plus anciens restes de poteries et de plantes et animaux domestiques datés au Maghreb occidental. Cette phase n'est. pas consécutive à l'occupation épipaléolithique, car il existe une nette rupture entre les deux phases, qui s'étend sur plus d'un millénaire. Cela semble coïncider en partie avec l'événement climatique froid de 6200 cal av. J.-C. Le début de l´ occupation épipaléolithique commencerait à son tour avec la fin du Dryas récent (10,900-9,700 cal av. J.-C.)

Population structure of an endemic fish Limia zonata (Cyprinodontiformes: Poeciliinae) in the Maimón River, Dominican Republic

The population structure of Limia zonata (Nichols, 1915) was studied in four locations in the Maimón River, Monseñor Nouel province, Dominican Republic. The sex and adult-juveniles ratio was calculated for all sampled localities. It was found that the sex ratio of L. zonata was significantly different from 1: 1 and is biased towards females (1.0: 1.6). Juvenile fish were more abundant and frequent than adults (69.3%). More than 800 fish were measured and weighed to analyze the frequency of size classes, morphometry and body condition. Ten size classes were distinguished that vary in frequency according to sex. Total length of the specimens ranged from 6.50 to 65.69 mm, while weight varied between 0.004 and 3.941 g. The morphology varied between sexes and a pronounced sexual dimorphism was found. All the morphometric variables studied showed a high level of association (r). The adjustment of the regression models (r2) of the morphometric relationships was between 85% and 99%. The relationship between the standard length and the total weight was reflected in the rates of growth. The Relative Condition Factor (Kn) demonstrated the good state of health of this fish population, but also variations between the sexes were detected

Reflections on the Other Side. A Southern Iberia Origin for the First Pottery Production of Northern Morocco?

Archaeological works in Morocco (the Spanish-Moroccan team) were funded by a European Research Council Advanced Grant AGRIWESTMED (Origins and spread of agriculture in the western Mediterranean region) coordinated by L.P.-CH. Processing works were performed thanks to a IJCI-2016-27812 -Spanish Ministry of Science, Innovation and Universities-Universidad de Granada, Juan de la Cierva-Incorporacion Agreement (2016, by RMMS), and by funding provided in the framework of project "Archaeobiology of the Neolithic of the Southern Iberian Peninsula" (NeArqBioSI) A-HUM-460-UGR18 by Consejeria de Economia, Conocimiento, Empresas y Universidad. FEDER Programme - Andalusian CouncilGranada University. Finally, G. Perez-Jorda has carried out this research within the grant CIDEGENT/2019/00, funded by the Generalitat Valenciana.This work is a starting point for rethinking the role of the Iberian Peninsula in the neolithisation of northern Morocco. It focuses on the similarities and divergences between the first pottery productions and their decorations in both territories. This relationship is supported by the existence of an accurate chronological gradation between the first evidence of Neolithisation in Iberian Peninsula and that of northern Morocco which suggests a north–south direction. We also present arguments on the possible links between the early ceramics from the north of Morocco and those from the south of Iberia, providing a first approach to an issue that will need to be carefully analysed in future research.European Research Council Advanced Grant AGRIWESTMED (Origins and spread of agriculture in the western Mediterranean region)Consejeria de Economia, Conocimiento, Empresas y Universidad A-HUM-460-UGR18FEDER Programme - Andalusian CouncilGranada UniversityGeneralitat Valenciana European Commission General Electric CIDEGENT/2019/0

Analysis of extreme rainfall in the Ebre Observatory (Spain)

The relationship between maximum rainfall rates for time intervals between 5 min and 24 h has been studied from almost a century (1905-2003) of rainfall data registered in the Ebre Observatory (Tarragona, Spain). Intensity-duration-frequency (IDF) curves and their master equation for every return period in the location have been obtained, as well as the probable maximum precipitation (PMP) for all the considered durations. In particular, the value of the 1-day PMP has resulted to be 415 mm, very similar to previous estimations of this variable for the same location. Extreme rainfall events recorded in this period have been analyzed and classified according to their temporal scale. Besides the three main classes of cases corresponding to the main meteorological scales, local, mesoscale, and synoptic, a fourth group constituted by complex events with high-intensity rates for a large range of durations has been identified also, indicating the contribution of different scale meteorological processes acting together in the origin of the rainfall. A weighted intensity index taking into account the maximum rainfall rate in representative durations of every meteorological scale has been calculated for every extreme rainfall event in order to reflect their complexity

Analysis of synoptic patterns in relationship with severe rainfall events in the Ebre Observatory (Catalonia)

The study has obtained a classification of the synoptic patterns associated with a selection of extreme rain episodes registered in the Ebre Observatory between 1905 and 2003, showing a return period of not less than 10 years for any duration from 5 min to 24 h. These episodes had been previously classified in four rainfall intensity groups attending to their meteorological time scale. The synoptic patterns related to every group have been obtained applying a multivariable analysis to three atmospheric levels: sea-level pressure, temperature, and geopotential at 500 hPa. Usually, the synoptic patterns associated with intense rain in southern Catalonia are featured by low-pressure systems advecting warm and wet air from the Mediterranean Sea at the low levels of the troposphere. The configuration in the middle levels of the troposphere is dominated by negative anomalies of geopotential, indicating the presence of a low or a cold front, and temperature anomalies, promoting the destabilization of the atmosphere. These configurations promote the occurrence of severe convective events due to the difference of temperature between the low and medium levels of troposphere and the contribution of humidity in the lowest levels of the atmosphere.Peer ReviewedPostprint (author's final draft

Analysis of extreme rainfall in the Ebre Observatory (Spain)

The final publication is available at Springer via http://dx.doi.org/10.1007/s00704-015-1476-0Relationship between maximum rainfall rates for time intervals between 5 minutes and 24 hours has been studied from almost a century (1905-2003) of rainfall data registered in the Ebre Observatory (Tarragona, Spain). Intensity-duration-frequency (IDF) curves and its master equation for every return period in the location have been obtained, as well as the probable maximum precipitation (PMP) for all the considered durations. In particular, the value of the 1-day PMP has resulted 415 mm, very similar to previous estimations of this variable for the same location. Extreme rainfall events recorded in this period have been analyzed and classified according to their temporal scale. Besides the three main classes of cases corresponding to the main meteorological scales, local, mesoscale and synoptic, a fourth group constituted by complex events with high intense rates for a large range of durations has been identified also, indicating the contribution of different scale meteorological processes acting together in the origin of the rainfall. A weighted intensity index taking into account the maximum rainfall rate in representative durations of every meteorological scale has been calculated for every extreme rainfall event in order to reflect their complexity.Peer ReviewedPostprint (published version

La decoración cerámica en el Neolítico de Kaf Taht el-Ghar (Tetuán, Marruecos). Campaña AGRIWESTMED 2012

Presentamos el estudio de los restos cerámicos de la fase neolítica de Kaf Taht el-Ghar (Mechrouha, Tetuán, Marruecos), enfocado principalmente en el análisis de técnicas y patrones decorativos. Ello cuenta con el interés añadido de corresponder, en su fase antigua, a las cerámicas asociadas a las primeras evidencias de agricultura y ganadería en el Magreb Occidental, encuadradas en el tercer cuarto del VI milenio cal AC. En dichas decoraciones dominan impresiones variadas, en particular las realizadas con concha estriada y lisa, peine y de cypraea. El uso de tales técnicas podría incluir estas primeras producciones cerámicas dentro del mundo impresso-cardial de la Europa mediterránea centro-occidental. A una fase avanzada, atribuida al Neolítico Medio, corresponde un conjunto de cerámicas con fuertes analogías y conexiones con la denominada Achakar Ware, de rasgos técnico-estilísticos marcadamente diferenciados. Entre estos se cuenta el uso de engobe colorante y la aplicación de impresiones con roulette cordada, lo que parece relacionar estas ultimas producciones con tradiciones propias del actual territorio del Sahara.Here we present the study of the pottery remains from the Neolithic phase of Kaf Taht el-Ghar (Mechrouha, Tetouan, Morocco), focused on the analysis of decorative patterns and techniques. In its early phase, its association with the first evidence of agriculture and livestock in the western Maghreb, framed in the third quarter of the 6th millennium BC, is noteworthy. A variety of impressions are dominant in the decorations, those made with striated and smooth shells, combs, and cowry. The use of these techniques could include these first ceramic productions within the impressa-cardial complex of central-western Mediterranean Europe. An advanced phase, assigned to the Middle Neolithic, includes a group of ceramics with strong analogies and connections with the so-called Ashakar Ware, of notably different technical and stylistic features. These include the use of coloured slip and the application of roulette-corded impressions, suggesting a link with former traditions specific to the Sahara territory

Pottery decoration in the Neolithic of Kaf Taht el-Ghar (Tetouan, Morocco). AGRIWESTMED Works 2012

Here we present the study of the pottery remains from the Neolithic phase of Kaf Taht el-Ghar (Mechrouha, Tetouan, Morocco), focused on the analysis of decorative patterns and techniques. In its early phase, its association with the first evidence of agriculture and livestock in the western Maghreb, framed in the third quarter of the 6th millennium BC, is noteworthy. A variety of impressions are dominant in the decorations, those made with striated and smooth shells, combs, and cowry. The use of these techniques could include these first ceramic productions within the impressa-cardial complex of central-western Mediterranean Europe. An advanced phase, assigned to the Middle Neolithic, includes a group of ceramics with strong analogies and connections with the so-called Ashakar Ware, of notably different technical and stylistic features. These include the use of coloured slip and the application of roulette-corded impressions, suggesting a link with former traditions specific to the Sahara territory.Presentamos el estudio de los restos cerámicos de la fase neolítica de Kaf Taht el-Ghar (Mechrouha, Tetuán, Marruecos), enfocado principalmente en el análisis de técnicas y patrones decorativos. Ello cuenta con el interés añadido de corresponder, en su fase antigua, a las cerámicas asociadas a las primeras evidencias de agricultura y ganadería en el Magreb Occidental, encuadradas en el tercer cuarto del VI milenio cal AC. En dichas decoraciones dominan impresiones variadas, en particular las realizadas con concha estriada y lisa, peine y de cypraea. El uso de tales técnicas podría incluir estas primeras producciones cerámicas dentro del mundo impresso-cardial de la Europa mediterránea centro-occidental. A una fase avanzada, atribuida al Neolítico Medio, corresponde un conjunto de cerámicas con fuertes analogías y conexiones con la denominada Achakar Ware, de rasgos técnico-estilísticos marcadamente diferenciados. Entre estos se cuenta el uso de engobe colorante y la aplicación de impresiones con roulette cordada, lo que parece relacionar estas ultimas producciones con tradiciones propias del actual territorio del Sahara