Essays in Empirical Corporate Finance and Banking

This dissertation studies topics in the areas of empirical corporate finance, banking, and financial intermediation. In the first chapter, entitled Personal Relationships in Loan Renegotiation: Evidence from Corporate Loans, I estimate the effect of personal relationships between a loan officer and a firm on the probability to renegotiate a loan and the outcomes of the renegotiation. To identify this effect, I exploit a bank reorganization in Greece in the mid-2010s, which allows me to identify two types of firms: one, those whose personal relationships with loan officers were discontinued and those whose relationships were not. This paper’s main conclusion is that personal relationships mitigate the cost of distress for the firm in a loan renegotiation. The firm is worse off following the interruption of its loan officer relationship, as it is less able to renegotiate, and the firm also receives tougher loan terms on renegotiated loans. The insights from the second chapter, entitled Lending Relationships and Moral Hazard in Loan Renegotiation, can have important policy implications related to the rise of nonperforming loans (NPLs). Many banks operating in countries that were hit by the 2010 European debt crisis, faced a significant rise in NPLs. This rise became one of the main challenges that banks face, as high levels of NPLs tie up bank capital and thus reduce profitability and increase funding costs. In the second chapter, I provide empirical evidence that banks, through efficient renegotiation and strong relationships with firms, can prevent loan defaults. This analysis suggests that firms with more distant lending relatioships are more likely to strategically delay a loan payment in order to efficiently trigger a loan renegotiation. This strategic behavior gives rise to the moral hazard phenomenon. In the third chapter, entitled Securing the Unsecured: Do stronger creditor rights affect firms’ access to credit?, I seek to understand whether stronger creditor rights influence firms’ capital structure and access to finance. To answer this question, I use the passage of an enforcement on cash assets reform in Croatia that aimed to increase the collection of the unsecured debt. To identify exogenous variation across firms affected more by the reform versus those that were not, I use a novel dataset on courts’ efficiency in dealing with the specific type of cases affected by the reform. The conclusion of the paper is that firms maintain higher leverage and have easier access to credit when creditor rights are stronger. The firms that benefit the most are medium size and have limited access to tangible assets. When firms are able to borrow more, they invest more in fixed assets

Fatty Acids Derived from Royal Jelly Are Modulators of Estrogen Receptor Functions

Royal jelly (RJ) excreted by honeybees and used as a nutritional and medicinal agent has estrogen-like effects, yet the compounds mediating these effects remain unidentified. The possible effects of three RJ fatty acids (FAs) (10-hydroxy-2-decenoic-10H2DA, 3,10-dihydroxydecanoic-3,10DDA, sebacic acid-SA) on estrogen signaling was investigated in various cellular systems. In MCF-7 cells, FAs, in absence of estradiol (E2), modulated the estrogen receptor (ER) recruitment to the pS2 promoter and pS2 mRNA levels via only ERβ but not ERα, while in presence of E2 FAs modulated both ERβ and ERα. Moreover, in presence of FAs, the E2-induced recruitment of the EAB1 co-activator peptide to ERα is masked and the E2-induced estrogen response element (ERE)-mediated transactivation is inhibited. In HeLa cells, in absence of E2, FAs inhibited the ERE-mediated transactivation by ERβ but not ERα, while in presence of E2, FAs inhibited ERE-activity by both ERβ and ERα. Molecular modeling revealed favorable binding of FAs to ERα at the co-activator-binding site, while binding assays showed that FAs did not bind to the ligand-binding pocket of ERα or ERβ. In KS483 osteoblasts, FAs, like E2, induced mineralization via an ER-dependent way. Our data propose a possible molecular mechanism for the estrogenic activities of RJ's components which, although structurally entirely different from E2, mediate estrogen signaling, at least in part, by modulating the recruitment of ERα, ERβ and co-activators to target genes

Plant derived and synthetic selective estrogen receptor modulators and their effects on estrogen related diseases

In mammals, estrogens have multiple effects ranging from control of reproductive, brain and immune function. They are considered to promote breast and endometrial cancer, whereas the lack of estrogens, during menopause, is correlated with increased risk of osteoporosis, coronary heart disease and neurodegenerative diseases such as Alzheimer’s disease and depression. Estrogens exert their effect via their intracellular receptors ERa and ERß, which have been detected in tissue targets for the hormone.Recent data, based on in vitro and in vivo experiments, demonstrate that synthetic and plant derived compounds (phytoestrogens) exhibit estrogenic or antiestrogenic activity. Their selective (estrogenic or antiestrogenic) biological action is tissue-specific and these substances are widely known as Selective Estrogen Receptor Modulators or SERMs. Phytoestrogens are considered to have beneficial effects on human’s health as they act as anticancer agents, prevent osteoporosis and lower the risk for coronary diseases. On the other hand synthetic analogs, such as tamoxifen and raloxifen, are currently used therapeutically for the treatment of breast cancer and osteoporosis.In the present study, we examined the estrogenic or antiestrogenic effect of plant extracts derived from Greek flora {Sideritis euboea, Sideritis cladestina, Marticaria chamomilla, Pimpinella anisum and Onobrychis ebenoides) and of substances isolated from the above extracts (ebenfuran I, II and III) as well as synthetically produced (deoxybenzynes NF7, NF4 and isoflavones NF6). For this purpose, we used the appropriate in vitro assays and in vivo model : 1) estrogen receptor binding affinity (RBA) assay, in cytosol extracted from breast cancer tissue or breast cancer cell-line MCF-7 2) stimulation of the differentiation and mineralisation of osteoblastic cell culture (MC3T3-E1 and KS483) by histochemical staining for alkaline phosphatase and by measuring ALP activity 3) induction, like antiestrogens, of the insulin growth factor binding protein 3 (IGFBP-3) in MCF-7 breast cancer cells 4) proliferation of cervical adenocarcinoma (HeLa) cells by use of MTT assay 5) in vivo model of ovariectomised rats, that have been estrogen deprived for at least 7 months (osteoporosis model), in which we measured a. stimulation of uterus proliferation, using as biological marker the uterus weigh and progesterone receptor levels b. promotion of apoptosis in brain, by detecting apoptotic protein bax and c. control of the lipid profile, by measuring HDL, LDL and triglyceride levels in serum.Our results demonstrate that ebenfurans I and II show estrogen binding activity. Ebenfìiran II exhibits the highest antiestrogenic activity in breast cancer cells, no stimulatory or even inhibitory effect on cervix adenocarcinoma cells and positive effect on osteoblasts. Ebenfuran I exhibits antiestrogenic effect in breast cancer cells and inhibitory effect on HeLa cells. The synthetic deoxybenzynes NF7, NF6 and the isoflavone NF6 show high antiestrogenic activity in breast cells while they inhibit cell proliferation on cervix adenocarcinoma cell line. On the other hand, plant extracts S.euboea, S.cladestina, M.chamomilla, P. anisum act as antiestrogens in breast and as estrogens in osteoblasts, whereas at high concentrations they show stimulatory effect on cervix adenocarcinoma HeLa cells. In vivo study of Onobrychis ebenoides demonstate that it doesn’t stimulate uterus proliferation has no apoptotic effect in brain and shows beneficial effect on LDL profile in rat’s serum. However, O. ebenoides extract exhibits estrogenic activity in breast cancer MCF-7 cell line. In this study, the in vitro assays and in vivo model used represent suitable systems, that works very well in assessing the estrogenic or antiestrogenic effects on test compounds and can be used for future evaluation of proportional compounds. The substances and plant extracts tested exhibit a potential SERM-like profile and lead us to further investigate their properties in vitro and in vivo.Ο ρόλος των οιστρογόνων στη φυσιολογική λειτουργία, όχι μόνο του αναπαραγωγικού συστήματος της γυναίκας αλλά και των λοιπών συστημάτων του οργανισμού (π.χ. καρδιαγγειακό, κεντρικό νευρικό και οστά) έχει αποτελέσει εκτενές πεδίο έρευνας τα τελευταία έτη. Τα οιστρογόνα έχουν συσχετιστεί με πολλές παθήσεις, όπως καρκίνο του μαστού και του ενδομήτριου, οστεοπόρωση, καρδιαγγειακά νοσήματα και νευροψυχικές διαταραχές, έτσι ώστε να μιλούμε για θεραπευτική χρήση των οιστρογόνων σε πολλές από αυτές τις παθήσεις. Παράλληλα, η θεραπεία ορμονικής υποκατάστασης με οιστρογόνα κατά τη διάρκεια της εμμηνόπαυσης κρίνεται απαραίτητη, προκειμένου να μειωθούν τα δυσμενή, για τη γυναίκα, αποτελέσματα της απουσίας των οιστρογόνων.Τα τελευταία χρόνια, έχει εξακριβωθεί ένας μεγάλος αριθμός ουσιών, φυσικών ή συνθετικών, που φαίνεται να έχουν οιστρογονική ή αντιοιστρογονική δράση, μέσω του υποδοχέα των οιστρογόνων ER σε in vitro και in vivo πειράματα. Ορισμένες από τις ουσίες αυτές είναι φυτικής προέλευσης (φυτοοιστρογόνα), και απαντώνται σε τρόφιμα ευρείας κατανάλωσης (π.χ. σόγια και δημητριακά), ενώ επιδημιολογικές μελέτες τις συνδέουν με προστατευτική δράση έναντι ορμονοεξαρτώμενων μορφών καρκίνου και οστεοπόρωση. Παράλληλα, έχουν συντεθεί αντίστοιχες ουσίες, όπως η ταμοξιφαίνη και η ραλοξιφαίνη, που χρησιμοποιούνται θεραπευτικά στον καρκίνο του μαστού και στην οστεοπόρωση. Οι ουσίες αυτές στο σύνολο τους ονομάζονται Εκλεκτικοί Τροποποιητές του Υποδοχέα Οιστρογόνων, καθώς η δράση τους είναι εκλεκτική και εξαρτάται από το είδος του ιστού και του υποδοχέα ER (ERa και ERß) με τον οποίο προσδένονται.Στην παρούσα διατριβή έγινε μια προσπάθεια να αξιολογηθούν, ως προς την οιστρογονική ή αντιοιστρογονική τους δράση σε διάφορα συστήματα, εκχυλίσματα, που παρασκευάζονται από φυτά της ελληνικής χλωρίδας (Sideritis euboea, Sideritis cladestina, Pimpinella anisum, Marticaria chamomilla και Onobrychis ebenoides), και καθαρές ουσίες που είτε έχουν απομονωθεί από τα φυτικά εκχυλίσματα (εμπενφουράνιο I, II και III), είτε έχουν παρασκευαστεί χημικά (δεοξυβενζοΐνες NF7, NF4 και ισοφλαβόνη NF6). Για το σκοπό αυτά χρησιμοποιήθηκαν οι κάτωθι πειραματικές διατάξεις : 1) Μελέτη της ικανότητας πρόσδεσης των ουσιών στον υποδοχέα οιστρογόνων ER σε κυτοσόλιο από δείγματα καρκίνου του μαστού και από κυτταροκαλλιέργειες καρκινικών κυττάρων μαστού MCF-7 2) Διερεύνηση της επίδρασης των υπό μελέτη ουσιών και εκχυλισμάτων στην αναστολή κυτταρικού πολλαπλασιασμού σε καρκινικά κύτταρα τραχήλου της μήτρας HeLa 3) Μελέτη της πιθανής οιστρογονικής ή αντιοιστρογονικής δράσης των υπό μελέτη ουσιών και εκχυλισμάτων σε καρκινικά κύτταρα μαστού MCF-7 (με δείκτη την IGFBP3 πρωτεΐνη) και σε οστεοβλάστες MC3T3-E1 και KS483 (με δείκτη την αλκαλική φωσφατάση) 4) In vivo μελέτη των εκχυλισμάτων σε μοντέλο ωοθηκεκτομηθέντων επίμυων (μοντέλο οστεοπόρωσης) και διερεύνηση της δράσης αυτών στην μήτρα (με δείκτη το βάρος μήτρας και τα επίπεδα υποδοχέων προγεστερόνης σε αυτήν), στον εγκέφαλο (με δείκτη την αποπτωτική πρωτεΐνη bax) και στο λιπιδιμικό προφίλ στο ορό των επίμυων (με ποσοτικό προσδιορισμό της FIDL, LDL και τριγλυκεριδίων).Τα αποτελέσματα έδειξαν ότι τα εμπενφουράνια έχουν την ικανότητα πρόσδεσης στον ER, με εξαίρεση το εμπενφουράνιο III. Το εμπενφουράνιο I έχει αντιοιστρογονική δράση στο μαστό και αναστέλλει τον πολλαπλασιασμό στα κύτταρα τραχήλου της μήτρας, ενώ το εμπενφουράνιο II παρουσιάζει αντιοιστρογονική δράση στο μαστό και οιστρογονική στα οστά και αναστέλλει τον κυτταρικό πολλαπλασιασμό στη μήτρα. Οι συνθετικές δεοξυβενζοΐνες NF7, NF4 και ισοφλαβόνη NF6 έχουν ικανότητα πρόσδεσης στον ER, με ταυτόχρονη οιστρογονική δράση στο μαστό και δυνατότητα αναστολής κυτταρικού πολλαπλασιασμού στη μήτρα. Όσον αφορά στα εκχυλίσματα S.euboea, S.cladestina, P.anisum, M.chamomïlla, δρουν ως αντιοιστρογόνα στο μαστό και ως οιστρογόνα στα οστά, αλλά επάγουν τον κυτταρικό πολλαπλασιασμό στη μήτρα, σε υψηλές όμως συγκεντρώσεις. Με βάση την in vivo μελέτη, το εκχύλισμα O.ebenoides δεν προκαλεί υπερπλασία της μήτρας, ούτε επάγει αποπτωτικούς μηχανισμούς στον εγκέφαλο. Παράλληλα, έχει ευεργετική επίδραση στο λιπιδιμικό προφίλ, καθώς δεν αυξάνει την LDL χοληστερόλη στον ορό του αίματος των επίμυων. Εντούτοις, στα in vitro πειράματα έδειξε οιστρογονική δράση στα κύτταρα μαστού.Οι πειραματικές διατάξεις, που αναπτύχθηκαν και χρησιμοποιήθηκαν στην παρούσα διατριβή, αποτελούν ένα αξιόπιστο σύστημα αξιολόγησης ουσιών και εκχυλισμάτων ως προς την οιστρογονική/αντιοιστρογονική δράση τους και μπορεί να χρησιμοποιηθούν στο μέλλον για ανάλογη μελέτη άλλων ουσιών. Όσον αφορά τις υπό μελέτη απομονωμένες ουσίες και εκχυλίσματα, η εκλεκτική δράση τους στα διάφορα συστήματα (μαστός, μήτρα, οστά) τα καθιστά πιθανούς Εκλεκτικούς Τροποποιητές του Υποδοχέα Οιστρογόνων ή SERM και παρουσιάζει ενδιαφέρον η περαιτέρω in vitro και in vivo μελέτη τους

Women's advice to healthcare professionals regarding breastfeeding : "offer sensitive individualized breastfeeding support"- an interview study

Background The World Health Organization recommends exclusive breastfeeding for 6 months followed by continued breastfeeding with complementary food up to 2 years of age or beyond. Few women achieve this recommendation in Sweden, and they often stop breastfeeding earlier than they would like. Investigating women's advice to healthcare professionals is important for the provision of optimal breastfeeding support. The aim of this study was to explore women's advice to healthcare professionals regarding support for continuing to breastfeed for at least 6 months. Methods This investigation used an exploratory study design, and a purposive sample of women was recruited between 2015 and 2016 through social media platforms. The work is a follow-up of an earlier study exploring women's perceptions of the factors that assisted them in breastfeeding for at least 6 months. Telephone interviews were conducted with 139 Swedish women who reported that they had breastfed for at least 6 months. Women were asked the question, "Do you have any advice that you would like to give to healthcare professionals regarding breastfeeding support?". The data were analysed using content analysis. Results The theme, "Professionals need to offer women sensitive, individualized breastfeeding support to promote a positive breastfeeding experience", describes the women's advice based on five categories: 1) providing evidence-based care, 2) preparing expectant parents during pregnancy, 3) creating a respectful and mutual dialogue, 4) offering individual solutions to breastfeeding problems, and 5) offering practical support. Conclusions This study highlights the importance of professionals providing evidence-based breastfeeding support in a sensitive and individualized manner. This consideration is an important prerequisite to strengthening women's self-confidence and assisting them in reaching their breastfeeding goals, which may enhance the positive nature of their breastfeeding experience