Οι ομάδες των ορμονών που επηρεάζουν σημαντικά την αύξηση και την ανάπτυξη των παιδιών και των εφήβων, ανήκουν κυρίως στον άξονα της αύξησης και της αναπαραγωγής, στο σύστημα του stress και στο ανοσολογικό σύστημα. Η κορτιλόλη, η λεπτίνη και η IL-6 αποτελούν στρεσογόνους παράγοντες οι οποίοι συνδέονται με τη δυναμική της ανάπτυξης και ενηβωσης του ανθρώπινου οργανισμού. Εκτός από την επίδραση τον ορμονών, η ενήβωση και η αναπαραγωγή του φύλου μπορεί να επηρεαστεί από φαρμακολογικούς παράγοντες, όπως είναι η υδροκορτιζόνη, τα αναβολικά στεροειδή και τα οιστρογόνα. Η φυσική άσκηση είναι ένας τύπος φυσικού stress που προκαλεί πλήθος ορμονικών, μεταβολικών και ανοσολογικών αλλαγών ενώ οι αθλητές και οι αθλήτριες ρυθμικής και ενόργανης γυμναστικής εκτίθονται σε έντονους φυσικούς και ψυχολογικούς στρεσογόνους παράγοντες. Τα τελευταία χρόνια οι προσδιορισμοί στο σίελο προσελκύουν τεράστιο ενδιαφέρον (λόγω του ανώδυνου τρόπου συλλογής του σιέλου) και κυρίως χρησιμοποιούνται στην Ενδοκρινολογία για την παρακολούθηση των επιπέδων των στεροειδών ορμονών. Υλικά και Μέθοδοι: Μελετήθηκαν 142 αθλήτριες και 97 αθηλτές της ενόργανης γυμναστικής υψηλού αγωνιστικού επιπέδου καθώς και 107 αθλήτριες της ρυθμικής γυμναστικής. Ως ομάδα ελέγχου μελετήθηκαν 73 κορίτσια και 68 αγόρια, τα οποία δεν αθλούνταν. Η συλλογή των δειγμάτων έγινε χρησιμοποιώντας μια ειδικά σχεδιασμένη συσκευή συλλογής σιέλου (Salivette). Για τον προσδιορισμό της λεπτίνης στο σίελο χρησιμοποιήθηκε ραδιοανοσολογική μέθοδος ενώ για τον προσδιορισμό της κορτιζόλης η μέθοδος ηλεκτροχημειοφωταύγειας. Για την μέτρηση της IL-6 στο σίελο αναπτύχθηκε και επικυρώθηκε μέθοδος Elisa υψηλής ευαισθησίας. Αποτελέσματα: Οι αθήτριες της ρυθμικής και της ενόργανης γυμναστικής χαρακτηρίζονται από υψηλότερα επίπεδα κορτιζόλης στο σίελο (p<0,01) συγκριτικά με τους μάρτυρες και τους αθλητές της ενόργανης. Τόσο στους αθλητές όσο και στις αθλήτριες της ενόργανης γυμναστικής, οι απογευματινές τιμές κορτιζόλης (μετά από άσκηση) παραμένουν στα ίδια επίπεδα με τις πρωινές τιμές. Στις αθλήτριες της ενόργανης τα επίπεδα της IL-6 παρουσιάζουν τάση αύξησης και της λεπτίνης τάση μείωσης μετά από άσκηση, αν και οι μεταβολές αυτές δεν είναι στατιστικά σημαντικές. Η συλλογή του σιέλου είναι μια μη επεμβατική, ανώδυνη τεχνική που επιτρέπει την επαναλαμβανόμενη δειγματοληψία. Η ραδιοανοσολογικής μέθοδος είναι απλή και εύκολη για τον προσδιορισμό της λεπτίνης στο σίελο, ενώ η μέθοδος της ηλεκτροχημειοφωταύγειας αποτελεί αξιόπιστη επιλογή για τη μέτρηση της κορτιζόλης στο σίελο. Για τον προσδιορισμό της IL-6 στο σίελο απαιτείται η ανάπτυξη και η επικύρωση μεθόδου Elisa, λόγω του ότι ο σίελος επηρεάζει τη μέτρηση της συγκεκριμένης κυτοκίνης. Τόσο στις αθλήτριες όσο και στους αθλητές της ενόργανης γυμναστικής υψηλού αγωνιστικού επιπέδου, ο νυχθημερήσιος ρυθμός έκκρισης της κορτιζόλης καταργείται. Επίσης οι αθλήτριες της ενόργανης γυμναστικής χαρακτηρίζονται από υψηλότερες τιμές δεικτών stress συγκριτικά με τους αθλητές. / The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol, leptin and IL-6 in elite artistic and rytmic gymnasts. Design: The study included two hundred and forty-nine (249) Caucasian athletes (elite Gymnasts) -142 girls(aged 16.0 ± 1.6 years) and 97 boys (aged 16.8 ± 1.1 years) from 44 European countries, during theEuropean Championship of Gymnastics held in Volos-Greece on April 2006. One hundred and forty-one pubertal adolescents, who were recruited from public schools in Greece, not engaged in strenuous sports activities were used as controls (73 girls aged 16.0 ± 1.4 years and 68 boys aged 15.3 ±2.0 years). Methods: Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. Cortisol concentrations were measured using a chemmiluminesce method. Leptin and IL-6 concentrations were measured using RIA and ELISA methods. Acute stress was assessed using a questionnaire designed for the study. Results: No difference was found between morning and afternoon salivary cortisol levels in both male and female AG. Female AG presented higher levels of morning salivary cortisol than female controls (p<0.05). Both male and female AG had higher degree of psychological stress in comparison with controls . Female AG had higher morning and afternoon salivary cortisol levels and higher degree of stress than males. Conclusions: In elite AG the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AG presented higher levels of morning salivary cortisol and psychological stress compared to both male AG and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Head and neck cancer is one of the most common cancers worldwide. The current standard of care for head and neck cancer includes surgical resection of the tumor followed by chemoradiation. This targeted head and neck radiation causes dysfunction of the salivary glands, which leads to xerostomia, mucositis, dysphagia, dental caries, and malnutrition. These side effects greatly decrease patient quality of life and increase their financial responsibility. Current therapies available to ameliorate these negative side effects are expensive, only provide short-term relief, and many of them have negative side effects of their own. Therefore, another therapy is needed to prevent salivary gland dysfunction or restore its function following targeted head and neck radiation. Autophagy is a homeostatic cellular mechanism that could be targeted as a therapeutic mechanism in the salivary glands following targeted head and neck radiation. Autophagy is a catabolic process necessary to maintain cellular homeostasis. It has been shown to play a beneficial role in a variety of disease states including diabetes mellitus, obesity, and cancer. The role of autophagy in the response of cancerous tissue to radiation has been vastly studied. However, the role autophagy plays in normal tissue response to radiation remains poorly understood and much more research in this area is needed.Atg5^(f/f);Aqp5-Cre mice have a conditional knockout of Atg5, a gene necessary for autophagy, in the salivary glands. These mice have unchanged baseline levels of apoptosis, proliferation, and stimulated salivary flow rates when compared to wild-type mice. Therefore, they are a useful model to investigate the role of autophagy in the response of the salivary glands to targeted head and neck radiation. These Atg5^(f/f);Aqp5-Cre autophagy-deficient mice display increased radiosensitivity following targeted head and neck radiation. Furthermore, post-therapy use of CCI-779, a rapalogue and inducer of autophagy, allowed for restoration of salivary gland function following targeted head and neck radiation. Taken together, these results implicate autophagy as playing a beneficial role in normal salivary function following radiation. Therefore, autophagy could be utilized by normal salivary gland tissue following targeted head and neck radiation to maintain salivary gland function.

The thesis is a study of the effects of radiation on the salivary glands in an experimental and a clinical study. Irradiation is a cornerstone in the management of head and neck cancer and is as other modalities of cancer treatment, afflicted with adverse reactions. An optimal radiotherapy regime is limited by the sensitivity of the normal tissues with regard to early and late effects. In certain cases the early effects can be so troublesome that it will cause interruption in the irradiation and questioning of the curative intention. Although DNA is the lethal target, other parts of the cell have been proposed as sensitive targets to irradiation. Different in vitro secretory models and quantitative morphological characterization and immunohistochemical evaluation of neuropeptides were performed in rat salivary glands after irradiation. The irradiation was given unilaterally or bilaterally once a day for a five-day schedule with 6 MV photons (total dose 20, 30, 35, 40, 45 Gy) or a two fractions regime in five days with a total dose of 24 or 32 Gy. The contralateral gland served as a control for unilaterally treated animals and parallel analyses were done 10 days or 180 days following the last irradiation dose. An early, dose-dependent effect of fractionated irradiation on noradrenaline-stimulated potassium fluxes (86Rb+ fluxes) was demonstrated. In contrast, the exocytotic amylase release displayed no obvious alterations, and morphologically no changes were seen. Regarding late effects (180 days) the noradrenaline-stimulated electrolyte secretion was decreased at least for the higher doses of irradiation. Amylase content and loss of acini was also dose-dependently decreased. At 10 days after bilateral irradiation there was a marked increase in the expression of the neuropeptides substance P, leu-enkephalin and bombesin in the ganglionic cells associated with the submandibular glands and in nerve fibers of the glandular parenchyme. In addition, a clinical prospective evaluation of 25 patients was performed before, during radiotherapy and 6, 12 and 18 months after the end of treatment. A great interindividual variation in the recovery was demonstrated with regard to salivary flow rate. Irradiation doses about 40-50 Gy caused generally reversible changes; sometimes salivary secretion was almost completely restored 6-18 months after the end of radiotherapy. Doses exceeding 65 Gy induced almost irreversible alterations. Even if DNA is the target for the lethal effect of irradiation, other constituents, such as the cell membrane or neuropeptide expression can be significantly affected by irradiation and cause important physiological changes. / <p>S. 1-43: sammanfattning, s. 47-164: 6 uppsatser</p> / digitalisering@umu

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / "July 1998." Typescript. Vita. Includes bibliographical references (leaves 145-165). Also available on the Internet.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--University of Göteborg, 1983. / Extra t.p. with thesis statement inserted. Includes the author's five published papers. Includes bibliographical references.

Thesis (Ph.D. in Cell and Developmental Biology) -- University of Colorado, 2005. / Typescript. Includes bibliographical references (leaves 155-180). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (p. 135-151).