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The one-humped or the dromedarian camel is a pseudo-ruminant mammal, well adapted to the hot and dry climates of the desert. Its ability to withstand torrid heat and extreme desiccation is of paramount importance to its survival. The studies presented in this thesis were designed to investigate and document the effect of dehydration in the presence or absence of angiotensin II (Ang II) AT1 receptor blocker (losartan) on blood constituents, electrolytes, hormones, neurotransmitters as well as liver and kidney enzymes in a subset of dehydrated camels and to compare them with hydrated camels. Additionally, we studied the response of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) and revealed for the first time the cardiac storage form of BNP in the camel heart. Dehydration induced significant increments in packed cell volume (PCV), white blood cells (WBC), gamma glutamyl-transferase (GGT), serum sodium, creatinine and urea levels, and a doubling in plasma cortisol and arginine vasopressin (AVP) levels. At the same time dehydration caused significant decrease in body weights, plasma insulin like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), and a 50% decrement in ANP and BNP levels. Moreover, dehydration with and without losartan resulted in significant changes in stress hormones and anti-oxidants in plasma, liver and kidney homogenates. Losartan on one hand enhanced the effect of dehydration resulting in significant increases in sodium, creatinine and urea levels. In addition losartan raised the  binding affinity of Ang II AT2 receptors in the small intestine with 8-fold and with 16-fold for liver AT1 receptors, indicating that Ang II AT1 and AT2 receptor binding sites were present in camel's small intestine while only AT1 receptor binding sites were found in the camel liver. One the other hand losartan resulted in significant decrease in body weights impaired the rise in anti-diuretic hormone and reduced aldosterone level. Finally, we showed that the proBNP is the storage form of BNP in the camel heart.

Reproductive biology is a necessary element for the management of elasmobranch fisheries. Traditionally, characterization of elasmobranch reproduction has involved lethal sampling to examine gross reproductive structures and development of embryos. However, this method is counterproductive to the conservation of shark populations. One non-lethal alternative is the measurement of serum hormones, which often vary according to reproductive events. Radioimmunoassay (RIA) has been used to measure hormone concentrations in reproductive endocrinology, but can be problematic for researchers. Alternatively, chemiluminescence immunoassays (CLIA) are routinely used for measuring circulating hormone concentrations in low-volume, non-extracted human serum samples. However these assays have not been previously examined for use with elasmobranch blood. In the first component of this study, I examined whether CLIA was a suitable alternative for detecting seasonal profiles of these hormones in the bonnethead, Sphyrna tiburo. This was accomplished by collecting serum from sexually mature male (n = 35) and female (n = 32) bonnetheads , measuring reproductive organs for maturity and reproductive stage, and measuring concentrations of testosterone (T) in males, and 17β-estradiol (E2) and progesterone (P4) in females using RIA and CLIA. CLIA was successfully validated for use with shark serum by assessing parallelism and spike recovery. CLIA-derived measurements were significantly correlated with those obtained with RIA (r = 0.809, 0.773, and 0.908 for T, E2, and P4, respectively; p

[ES] Resumen Como pez de gran valor económico, procedente de una de las líneas de teleósteos más antiguas, con un ciclo de vida misterioso, un potencial de acuicultura excepcional, y con importancia cultural y actividades de pesca en casi todos los países de Europa, la anguila europea posee un enorme valor socioeconómico. Este valor se suma a la desgraciada situación actual en peligro crítico de población natural de anguilas europeas. Como el ciclo de vida de la anguila aún no se ha conseguido cerrar en cautiverio, si la especie se extingue en la naturaleza, no seremos capaces de recuperarla. El cierre del ciclo de vida de la anguila europea ha sido, por lo tanto, el objetivo final de varios estudios. Sin embargo, a pesar de una investigación científica sustancial, desde la década de 1930, varios aspectos de la maduración de la anguila, como el mecanismo que bloquea la maduración de la anguila en la etapa prepúber en cautiverio, aún no se conocen bien. Por lo tanto, es necesario ampliar nuestro conocimiento sobre la reproducción de la anguila para inducir mejores hipótesis y lograr un progreso sustancial. Para profundizar en este campo, esta tesis se realizó con el objetivo específico de desarrollar métodos innovadores para la inducción de la maduración de la anguila y aumentar el conjunto de conocimientos sobre los procesos europeos de maduración de la anguila. Los procedimientos hormonales utilizados actualmente para la maduración sexual de la anguila artificial probablemente no induzcan el proceso natural de maduración. Por lo tanto, esta tesis ha evaluado el potencial de las hormonas recombinantes específicas de la anguila para inducir un proceso de maduración más natural. Este estudio específico mostró que la espermatogénesis completa y la espermiación se pueden inducir con gonadotropinas específicas de anguila recombinante; sin embargo, la calidad del gameto resultante es aún inferior a los resultados de los protocolos establecidos. Sin embargo, la utilización de hormonas recombinantes tiene un gran potencial para futuras implementaciones. Además, el experimento de gonadotropina recombinante ha generado nuevos detalles sobre el efecto de las gonadotropinas homólogas en el eje BPG de las anguilas europeas. Trabajos previos han llevado a la hipótesis de que un tratamiento térmico adecuado puede reducir o reemplazar parcialmente los tratamientos hormonales estándar para la maduración sexual de la anguila europea, o puede mejorar la calidad y / o cantidad de gametos. En esta tesis, se probó el efecto de varios regímenes térmicos en el eje BPG de machos de anguila europeos prepúberes, sin administración de hormonas. Los resultados muestran claramente que un tratamiento de agua de mar fría durante 2 semanas (10 ° C) afecta el eje BPG de los machos de anguila europeas. Los resultados específicos incluyeron un aumento en la sincronización de espermatogonias, niveles elevados de testosterona y 11-ketotestosterona en plasma, agrupamiento de muestras de transcriptomas del eje BPG del grupo tratado con agua de mar fría y posiblemente niveles aumentados de la proteína subunidad ß de la hormona luteinizante de la hipófisis. Los genes transcritos diferencialmente incluyeron varios genes, procesos y vías interesantes, que parecen estar involucrados en la maduración "natural" temprana de la anguila y que pueden ser biomarcadores adecuados para las distintas etapas de este proceso. Para un análisis adecuado de los datos transcriptómicos, se creó un transcriptoma de anguila europea de novo. Se demostró que este transcriptoma de novo posee una superior integridad al genoma de anguila europea disponible y, por lo tanto, es una herramienta útil para el análisis adicional de genes específicos. Un análisis de este transcriptoma reveló un gran número de pares de genes parálogos, que mostraron una baja divergencia entre secuencias sinónimas. Entre las hipótesis potenciales sobre e / [CAT] Com a espècie de renom culinari que pertany a un dels llinatges teleostis més antics, amb un cicle vital misteriós, un potencial d'aqüicultura excepcional, i una tradició pesquera a gairebé tots els països d'Europa, l'anguila europea posseeix un enorme valor socioeconòmic. No obstant això, aquest valor només fa que augmentar la preocupació de la seva població, que actualment es troba catalogada com "en perill crític d'extinció". Atès que el cicle de vida de les anguiles encara no ha estat tancat en captivitat, l'espècie no serà salvable en el cas que s'extingeixi en estat natural, per la qual cosa tancar el cicle de vida d'aquesta espècie ha estat l'objectiu final de diversos grups d'investigació durant els últims anys.. No obstant això, i malgrat la investigació científica de qualitat duta a terme des de la dècada de 1930, encara hi han diversos aspectes de la maduració de les anguiles -com el mecanisme que bloqueja la maduració sexual de l'anguila a l'etapa pre-puberal en captivitat- que son poc coneguts en l'actualitat. Per tal d'ampliar els coneixements sobre la reproducció de les anguiles i aconseguir un progrés substancial, aquesta tesi es va dur a terme amb l'objectiu específic de desenvolupar mètodes innovadors per a la inducció de la maduració de l'anguila europea, a més de afegir-hi el coneixement en els processos de maduració bàsics d'aquesta espècie. Els procediments hormonals utilitzats actualment per a la maduració artificial de l'anguila europea no acaben d'induir el procés de maduració natural tal i com probablement es dóna a la natura. Doncs, en primer lloc, aquesta tesi va avaluar el potencial d'hormones recombinants específiques d'anguila europea per induir un procés de maduració molt més natural. Aquest estudi específic va mostrar que mitjançant estes gonadotropines específiques d'anguila europea és possible induir l'espermatogènesi i l'espermiació completes. Tot i que els resultats van mostrar que la qualitat dels gamets va ser inferior als resultats que generen els protocols establerts fins ara amb un altre tipus d'hormones (generalment d'origen humà), la utilització d'hormones recombinants específiques es presenta amb un gran potencial per a la seva implementació futura en la inducció de la maduració sexual de l'anguila europea, ja que l'estudi va generar noves idees sobre l'efecte de les gonadotropines l'eix BPG de l'anguila europea. En segon lloc, i treballant amb la hipòtesi que un tractament tèrmic adequat pot reduir o substituir parcialment els tractaments hormonals estàndards per a la maduració sexual de l'anguila europea, en aquesta tesi es va provar l'efecte de diversos règims tèrmics (sense administració d'hormones) en l'eix BPG dels mascles europeus pre-puberals amb l'objectiu de millorar la qualitat i / o quantitat dels gamets. Els resultats mostraren clarament que un tractament d'aigua de mar de 2 setmanes a baixa temperatura (10 °C) va afectar l'eix BPG dels mascles europeus d'anguila. Resultats més específics van mostrar un augment de la sincronització de les espermatogonies, elevats nivells plasmàtics de testosterona i 11-ketotestosterona, una agrupació de mostres de transcriptoma de l'eix BPG del grup tractat amb aigua de mar freda i, possiblement, un augment dels nivells de la proteïna de la subunitat ß de la hormona luteinitzant de la hipofisi. Els gens transcrits diferencials van al·ludir a diversos gens, processos i vies interessants, que semblen estar implicats en la maduració inicial de l'anguila "natural" i podrien resultar biomarcadors adequats per a les etapes d'aquest procés. No obstant això, es necessiten estudis addicionals per avaluar el potencial dels biomarcadors d'aquests gens i, de manera complementària, comprovar si un pre-tractament d'aigua de mar freda pot millorar la resposta de les anguiles europees a un tractament hormonal artificial, com suggereixen els resultats. Finalment, amb l'objectiu / [EN] As an expensive fish from one of the most ancient teleost lineages, with a mysterious life cycle, exceptional aquaculture potential, and cultural associations and fishing activity in almost every country in Europe, the European eel possess huge socioeconomic value. This value only adds to the misfortune of the current critically endangered state of the wild European eel population. As the eel lifecycle has not yet been closed in captivity, the species will not be salvable if it went extinct in the wild. Closing the life-cycle of the European eel has thus been the ultimate objective of several studies. However, despite the substantial scientific investigation, since the 1930s, several aspects of eel maturation, such as the mechanism which blocks eel sexual maturation at the pre-pubertal stage in captivity, is still poorly understood. Therefore, it is necessary to broaden our knowledge of eel reproduction to induce better hypotheses and therethrough achieve substantial progress. In order to further this field, this thesis was conducted with the specific objective of developing innovative methods for induction of eel maturation and add to the pool of knowledge of European eel maturation processes. The hormonal procedures currently used for artificial eel sexual maturation are probably not inducing the natural maturation process. Therefore, this thesis has evaluated the potential of eel specific recombinant hormones to induce a more natural maturation process. This specific study showed that full spermatogenesis and spermiation can be induced with recombinant eel specific gonadotropins; however, the resulting gamete quality is still inferior to the results of established protocols. Nevertheless, the utilization of recombinant hormones holds a large potential for future implementation. Furthermore, the recombinant gonadotropin experiment has generated novel insights into the effect of homologous gonadotropins on the BPG axis of European eels. Previous work has led to the hypothesis that the right thermal environmental treatment may reduce or partially replace the standard hormonal treatments for sexual maturation of European eel, or may improve gamete quality and/or quantity. In this thesis, the effect of various thermal regimes was tested on the BPG axis of pre-pubertal European eel males, without administration of hormones. The results clearly show that a 2 week cold (10 °C) seawater treatment effects the BPG-axis of European eel males. Specific results included an increase in the synchronization of spermatogonial cells, elevated testosterone and 11-ketotestosterone plasma levels, clustering of BPG-axis transcriptome samples from the cold seawater treated group and possibly increased levels of pituitary luteinizing hormone ß-subunit protein. Differentially transcribed genes alluded to several interesting genes, processes, and pathways, which appears to be involved in early "natural" eel maturation and may prove to be suitable biomarkers for the stages of this process. In order for proper analysis of the transcriptomic data, a de novo European eel transcriptome was assembled. This de novo transcriptome was proven to have superior completeness to the available European eel genome and is thus a useful tool for further analysis of specific genes. An analysis of this transcriptome revealed a large number of paralog gene pairs, which showed low synonymous sequence divergence. Among the potential hypothesis regarding the origin of these paralog gene pairs, the hypothesis of a 4R whole genome duplication is among the most parsimonious. Several of these duplicated genes were involved in reproduction and the onset of puberty. Regardless of the origin, further analysis of these genes may reveal eel specific adaptations, which could help to better understand the exceptional reproductive system of eels. / Rozenfeld, C. (2019). Development of innovative methods for induction of European eel (Anguilla anguilla) spermatogenesis [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/125697 / TESIS

INTRODUÇÃO: Consumo de álcool na gestação é um sério problema de saúde pública envolvendo grande risco de embriotoxicidade e teratogenicidade fetal. Exposição fetal ao álcool causa liberação de glicocorticóides (GC) pela suprarrenal como conseqüência da ativação do eixo hipotálamo-hipófise-adrenal (HPA). Cortisol é o principal glicocorticóide endógeno capaz de interferir na atividade orgânica, influenciando a retroinibição do eixo HPA. Álcool consumido na gravidez pode alterar indiretamente o desenvolvimento fetal ao perturbar as interações hormonais normais dos eixos hipotálamo-pituitária-adrenal (HPA), hipotálamo-hipófise-tireoidal (HPT), hipotálamo-hipófise-gonadal (HPG), entre mãe e feto. OBJETIVOS: Comparar dosagens de cortisol salivar em crianças em idade escolar, com e sem histórico prévio de exposição intrauterina ao álcool, e sua relação com risco materno para Fetal Alcohol Spectrum Disorder (FASD) e intensidade do uso de álcool na gestação. METODOLOGIA: Amostra foi constituída de 76 pares de crianças e mães, de doze a treze anos de idade. Para análise do cortisol, foi coletada saliva e feitas análises por radioimunoensaio. RESULTADOS: Em relação à caracterização da amostra em função do risco materno se obteve significância para \"mãe praticante de religião\" (X²: 5,60; p=0,01). Associação significativa foi observada entre T-ACE positivo (Tolerance, Annoyed,Cut Down e Eye-Opener) na produção do Cortisol Awaking Response (CAR) e ritmo circadiano em função do sexo da criança (F: 9,26; p=0,003). Diferença significativa foi observada nas análises de níveis de cortisol em função do risco materno para FASD onde as análises de variância (t-tests) do cortisol ao despertar foram encontradas para \"CID positivo\" (Clasificação Internacional de doenças) (t:-2,659; p=0,01) e para cortisol aos 30 minutos depois de despertar em função de uso de álcool na gestação (t: -2,03 ; p=0,05). Em relação aos níveis de cortisol em função do uso de álcool na gestação, se obteve diferenças significativas para o cortisol aos 30 minutos depois de despertar (t: -2,03; p=0,05). Foram observadas diferenças significativas (p<0,01) para seguintes variáveis: níveis de cortisol em função do risco materno para FASD, álcool na gestação versus escore AUDIT (Alcohol Use Disorder Identification Test); Álcool na gestação versus T-ACE; Níveis de cortisol ao despertar versus Níveis de cortisol aos 30 min depois de despertar; Níveis de cortisol aos 30 min depois do despertar versus níveis de cortisol aos 60 min depois de despertar e Níveis de cortisol aos 60 min depois de despertar versus escore do AUDIT. As variáveis, álcool na gestação versus diagnóstico pelo CID, níveis de cortisol ao despertar versus escore do TACE, apresentaram significância (p=0,01). As análises com níveis de cortisol ao despertar versus níveis de cortisol aos 60 min depois de despertar; níveis de cortisol ao despertar versus escore do AUDIT-total; níveis de cortisol aos 30 min depois do despertar versus escore do T-ACE apresentaram significância estatística (respectivamente, p=0,03, p=0,04 e p=0,05). Em relação à avaliação da qualidade do sono em crianças com exposição pré-natal ao álcool por sexo, obteve-se significância para resistência em ir para a cama, para as meninas (p=0,01) e nas análises de correlação se observou diferenças significativas para ansiedade do sono versus níveis de cortisol salivar às 23 horas (p=0,01) e escore do SRQ total versus perturbação respiratória do sono (p=0,02). DISCUSSÃO: Se obteve uma associação entre uso de álcool na gestação e produção de cortisol salivar nos filhos, porém outras variáveis inerentes às mães podem influenciar no desenvolvimento do HPA e na produção de cortisol na pré-adolescência. CONCLUSÃO: Estes resultados podem contribuir para o melhor entendimento da fisiopatologia subjacente às manifestações clínicas de crianças expostas ao álcool durante a gestação e a fundamentar planos de prevenção para evitar que mulheres grávidas consumam álcool na gestação. / INTRODUCTION: Alcohol consumption during pregnancy is a serious public health problem, as it involves great risk related to fetal embryotoxicity and teratogenicity. Fetal alcohol exposure causes the release of glucocorticoids (GC) by the adrenal as consequence of activation of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol is the major endogenous glucocorticoid able to interfere with the organic activity, influencing retroinhibition of HPA axis. Furthermore, alcohol consumed during pregnancy can alter fetal development indirectly by disrupting the normal hormonal interactions of the hypothalamic-pituitary-adrenal axis (HPA), hypothalamic-pituitarytireoidal (HPT), and hypothalamic-pituitary-gonadal (HPG) between mother and fetus. OBJECTIVES: The objective of this research was to compare the measurements of salivary cortisol in school age children with and without previous history of intrauterine exposure to alcohol, and their relationship to maternal risk for Fetal Alcohol Spectrum Disorder (FASD) and the intensity of alcohol use during pregnancy. METHODOLOGY: The study sample consisted of 76 pairs of children and their mothers, between twelve and thirteen years old. For analysis of cortisol, saliva was collected and analyzes were made by radioimmunoassay method. RESULTS: Results show that, in relation to the characterization of the sample as a function of maternal risk for FASD, significance was obtained for the variable mother religious practice versus score of TACE (Tolerance, Annoyed,Cut Down e Eye-Opener) (X²: 5.60, p=0.01). Statistically significant association was observed between the covariate T-ACE and production of CAR (Cortisol Awaking Response) and circadian rhythm versus sex of the child (F: 9.26, p=0.003). Significant differences were also observed in the analysis of cortisol levels as a function of maternal risk for FASD for the test analysis of variance (t-tests) of cortisol after awakening versus \"negative CID\" and \"positive CID\" (International Clasification of Diseases) (t:-2.659; p=0.01) and cortisol at 30 minutes after awakening versus alcohol use during pregnancy (t:-2.03, p=0.05). In relation to cortisol levels due to the use of alcohol during pregnancy, significant differences were obtained for cortisol at 30 minutes after awakening versus alcohol use during pregnancy (t:-2.03, p=0.05). Significant differences (p<0.01) were found for variables: - cortisol levels as a function of maternal risk for FASD; - alcohol during pregnancy versus score of AUDIT (Alcohol Use Disorder Identification Test); - alcohol in pregnancy versus T-ACE; - cortisol levels after awakening versus cortisol levels at 30 min after awakening; - cortisol levels at 30 min after awakening versus cortisol levels at 60 min after awakening and cortisol levels at 60 min after awakening versus score of AUDIT. Analyses of alcohol during pregnancy versus mother diagnose CID (harmful use or dependence), and cortisol levels after awakening versus score of T-ACE showed significance (p=0.01). The analyses of cortisol levels at 60 min after awakening; cortisol levels after awakening versus AUDIT-total; cortisol levels at 30 min after awakening versus score of T-ACE were significant (respectively, p=0.03, p=0.04 and p=0.05). Regarding the assessment of sleep quality in children with prenatal exposure to alcohol by sex, significance was obtained for resistance to going to bed for female children (p=0.01) and through the analysis of correlation was observed significant results for anxiety sleep versus salivary cortisol levels at 23 hours (p=0.01) and score of mother SRQ total versus respiratory sleep disorder (p=0.02). DISCUSSION: An association was found between alcohol use during pregnancy and salivary cortisol in children of women who consumed alcohol during pregnancy, however other variables inherent to mothers could act in the development of the HPA and the production of cortisol in preadolescence. CONCLUSION: These results can contribute to a better understanding of the pathophysiology underlying the clinical manifestations of children exposed to alcohol during pregnancy and to establish a prevention plan to ensure that pregnant women do not consume alcohol during pregnancy.

<p>Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS.</p><p>Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, <i>a</i>) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg⁶Phe⁷, <i>b</i>) the levels of the tachykinin substance P (SP), <i>c</i>) the density of the SP neurokinin 1 (NK1) receptor, <i>d</i>) the level of the SP metabolite SP_1-7that frequently exerts opposite effects to SP, <i>e</i>) the SP_1-7generating enzyme substance P endopeptidase (SPE) and finally, <i>f</i>) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.</p>

Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS. Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, a) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7, b) the levels of the tachykinin substance P (SP), c) the density of the SP neurokinin 1 (NK1) receptor, d) the level of the SP metabolite SP1-7 that frequently exerts opposite effects to SP, e) the SP1-7 generating enzyme substance P endopeptidase (SPE) and finally, f) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.