Η στεφανιαία νόσος αποτελεί ένα από τα πιο συχνά αίτια νοσηρότητας και θνητότητας στο γενικό πληθυσμό. Ένα μεγάλο ποσοστό από τους ασθενείς με στεφανιαία νόσο οδηγείται σε αγγειοπλαστική στεφανιαίων αρτηριών (PTCA) με ή χωρίς εμφύτευση stent, όταν η στένωση στο αγγείο είναι ≥ 70-75%. Παρά την πρόοδο στον τομέα της αγγειοπλαστικής, με τη χρήση των drug-eluting stents και την ελάττωση της επαναστένωσης σε ποσοστό <5-10%, το υψηλό ποσοστό (20-25%) επαναστένωσης παραμένει η Αχίλλειος πτέρνα στα συμβατικά, μεταλλικά(bare)stents. Η χρήση των drug-eluting stents περιορίζεται σε περιπτώσεις με επαναστένωση, σε σακχαροδιαβητικούς και σε υψηλού κινδύνου βλάβες για επαναστένωση. Τα μεγάλα ποσοστά όψιμης επαναστένωσης(≥ 9-10%) και το υψηλό κόστος τους, κάνουν ακόμα πιο επιτακτική την ανάγκη εντατικοποίησης της έρευνας προς την κατεύθυνση εντοπισμού παραγόντων σχετιζόμενων με την επαναστένωση. Σκοπός της εργασίας μας ήταν να διερευνήσει τον πιθανό ρόλο πολυμορφισμών γονιδίων στην υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών και εμφύτευση μεταλλικών stents. Συγκεκριμένα, εξετάσθηκε αναλυτικά ο γενετικός πολυμορφισμός των γονιδίων α2Β-αδρενεργικού υποδοχέα και της CETP(πρωτεΐνη μεταφοράς εστέρων χοληστερόλης). Η υπόθεση στηρίχτηκε στο γεγονός ότι σε μια σημαντική μελέτη 912 αρρένων Φινλανδών μέσης ηλικίας, αποδείχτηκε ότι ο D/D γονότυπος σε σχέση με τον I/D γονότυπο και τον I/I γονότυπο, εμφανίζει 2,5 φορές μεγαλύτερο κίνδυνο για οξέα στεφανιαία επεισόδια, συμπεριλαμβανομένου του εμφράγματος μυοκαρδίου. Η εκσεσημασμένη αγγειοσύσπαση, τόσο στην περιφέρεια, όσο και στις στεφανιαίες αρτηρίες μέσω του πολυμορφισμού του γονιδίου α2Β που θεωρείται πιθανό αίτιο για τα οξέα στεφανιαία επεισόδια, μαζί με το σημαντικό ρόλο του α2Β αδρενεργικού υποδοχέα στην υπερπλασία και μετανάστευση των λείων μυϊκών κυττάρων, πιθανόν να έχει μεγάλη συμβολή στη διεργασία της υποτροπής ισχαιμίας. Μελετήσαμε προοπτικά 96 Έλληνες που υπέστησαν επιτυχή PTCA και εμφύτευση stents, εκ των οποίων 81 ήταν άνδρες και 15 γυναίκες(μέση ηλικία ± σταθερά απόκλιση=57,7± 10,1 ετών, με όρια 37-76 ετών) που προσήλθαν με συμπτωματική στεφανιαία νόσο. Όλοι οι παραπάνω ασθενείς συμμετείχαν στη μελέτη μεταξύ των ετών 2001 και 2003 και παρακολουθήθηκαν κλινικά για 6-8 μήνες μετά από μια επιτυχή τεχνική διάνοιξης του αποφραγμένου αγγείου. Αμέσως μετά την PTCA και για ένα(1) μήνα οι ασθενείς έλαβαν ασπιρίνη(100-325mg/day) και κλοπιδογρέλη 75mg/day. Η εκτίμηση της υποτροπής ισχαιμίας βασίστηκε σε στατικό και δυναμικό σπινθηρoγράφημα θαλλίου στους 3 και 6-8 μήνες μετά την PTCA. Αιμοδυναμικά, σε όσους υπέστησαν νέα στεφανιογραφία μέχρι και τους 6-8 μήνες, η επαναστένωση ορίσθηκε ως ≥ 50% στένωση του αυλού του αγγείου στο σημείο όπου έγινε η αγγειοπλαστική. Εκτός από την ομάδα των ασθενών και μια ομάδα υγιών μαρτύρων 83 ατόμων, συμμετείχε στη μελέτη για σύγκριση της συχνότητας του γονότυπου. Το τελικό καταληκτικό σημείο για την παραπάνω μελέτη, ήταν η συχνότητα της υποτροπής ισχαιμίας στους 8 μήνες κλινικής παρακολούθησης. Υποτροπή ισχαιμίας και της επαναστένωσης ≥ 50% σε όσους υπεβλήθησαν σε νέα στεφανιογραφία, συνέβη σε 15 από τους 96 ασθενείς. Ας σημειωθεί ότι οι περισσότεροι ασθενείς (70/96) είχαν το φυσιολογικό γονότυπο με το αλληλόμορφο I, λιγότεροι ασθενείς (23/96) είχαν το Insertion/Deletion και μόλις 3/96 είχαν το Deletion/ Deletion γονότυπο. Από το γονοτυπικό group, υποτροπή ισχαιμίας παρουσιάσθηκε σε 11/70 για τον I/I, 3/23 για τον I/D γονότυπο και 1/3 για τον D/D γονότυπο. Δε βρέθηκε συσχέτιση μεταξύ πολυμορφισμού γονιδίου και υποτροπής ισχαιμίας στους ασθενείς μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Προηγούμενες μελέτες έχουν ερευνήσει τη συσχέτιση των πολυμορφισμών των γονιδίων της ACE, του AT1 υποδοχέα της αγγειοτενσίνης II και της CETP με την επαναστένωση μετά από αγγειοπλαστική. Εντούτοις, καμιά μελέτη δεν πραγματοποιήθηκε που να συγκρίνει τον α2Β-AR πολυμορφισμό και την υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Όπως αρχικά αναφέρθηκε, ο γονότυπος α2Β ευνοεί τη μετανάστευση των αγγειακών SMCs, επηρεάζει τη λειτουργία του Α.Ν.Σ. και συσχετίζει το α2Β-AR αλληλόμορφο D deletion με οξέα στεφανιαία επεισόδια. Όλα τα παραπάνω στοιχεία μπορεί να δικαιολογούν το ρόλο του α2Β-AR πολυμορφισμού στην υποτροπή ισχαιμίας και πιθανόν την επαναστένωση μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Βέβαια, η αρνητική συσχέτιση των πολυμορφισμών του α2Β-AR και της CETP ΤaqIB με την υποτροπή ισχαιμίας μετά από αγγειοπλαστική, μπορεί να θεωρηθεί προκαταρκτική, δεδομένου ότι συμμετείχε σχετικά μικρός αριθμός ασθενών συγκριτικά με μεγάλες πληθυσμιακές μελέτες και επειδή ο D/D γονότυπος δεν είναι ιδιαίτερα συχνός(για τη μελέτη των α2Β-AR). Όσον αφορά τη μελέτη με τη CETP, διερευνήσαμε τον πολυμορφισμό ΤaqIB που είναι μια σιωπηρή μετάλλαξη βάσης στο 277 νουκλεοτίδιο της CETP(η οποία μπορεί να αναγνωρισθεί με την περιοριστική ενδονουκλεάση ΤaqI), με την πιθανότητα υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Οι όροι Β1 και Β2 αντίστοιχα χρησιμοποιήθηκαν για να δηλώσουν την ύπαρξη ή μη της περιοριστικής περιοχής (site) της ΤaqIB. Το Β2 αλληλόμορφο σχετίζεται με αυξημένα επίπεδα HDL και ελαττωμένα επίπεδα CETP, τόσο σε υγιείς όσο και σε άτομα με στεφανιαία νόσο(μοιάζει με ήπιας μορφής ανεπάρκεια CETP). Αντίθετα το Β1 αλληλόμορφο σχετίζεται με ελαττωμένα επίπεδα HDL και με αυξημένα επίπεδα και δραστηριότητα CETP. Επειδή η ΤaqIB σχετίζεται με χαμηλά επίπεδα HDL και αυξημένο κίνδυνο για CHD(επηρεάζοντας το μεταβολισμό των λιποπρωτεϊνών), μπορεί να συμμετέχει στην παθοφυσιολογία της υποτροπής ισχαιμίας μετά από αγγειοπλαστική. Μελετήσαμε 204 ασθενείς από το έτος 2001 έως και το 2003 με την προοπτική να διερευνηθεί η συσχέτιση ΤaqIB στον Ελλαδικό πληθυσμό με την πιθανότητα υποτροπής ισχαιμίας μετά από αγγειοπλαστική σε άτομα που φέρουν τον παραπάνω γονότυπο. Η συχνότητα της ΤaqIB(54%) ήταν παρόμοια με τη συχνότητα του πολυμορφισμού σε μια ομάδα 35 υγιών μαρτύρων. Το αποτέλεσμα από αυτή τη μελέτη δεν αποδεικνύει ότι ο ΤaqIB πολυμορφισμός στο γονίδιο της CETP είναι σημαντικός προγνωστικός παράγων για εκτίμηση του κινδύνου υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών. Συμπερασματικά, η υποτροπή ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών οφείλεται σε έναν πολύπλοκο μηχανισμό και σε ένα πολυπαραγοντικό φαινόμενο. Μπορεί οι πολυμορφισμοί του α2Β και της CETP, να μην αναδείχθηκαν ως ανεξάρτητοι παράγοντες υποτροπής ισχαιμίας μετά από αγγειοπλαστική στεφανιαίων αρτηριών, αλλά σε συνδυασμό με άλλους πολυμορφισμούς γονιδίων και υπό την επίδραση συγκεκριμένων περιβαλλοντικών παραγόντων, είναι πολύ πιθανόν να συμμετέχουν στην παραπάνω διεργασία της υποτροπής ισχαιμίας και κατ’επέκταση της επαναστένωσης μετά από PTCA. / Coronary heart disease is one of the most common causes of morbidity and mortality in the population. A great percent of the patients with coronary heart disease may undergo percutaneous coronary angioplasty (PTCA) with or without the implantation of stents, mainly when the stenosis of the vessel is ≥ 70-75%. Despite the progress made with the introduction of drug-eluting stents and the reduction of the restenosis rate up to 5%-10%, the Achillean heel of the angioplasty using bare metal stents, is the restenosis rate which is 20%-25% of all cases. The use of drug-eluting stents is limited in cases with restenosis, in patients with diabetes mellitus and in high-risk for restenosis lesions. The great percent of late restenosis(≥ 9-10%) and the high price of drug-eluting stents, make more urgent the necessity for more intense research on the identification of the exact factors involved in the pathophysiology of restenosis. The primary objective of our study is to define the role of gene polymorphisms in the recurrence of ischaemia after PTCA and the implantation of the stents. Virtually, we scrutinely examined the role of the genetic polymorhisms of α2Badrenergic receptor and the CETP(Cholesteryl Ester Transfer Protein)-TaqIB polymorphism. Our assumption was based on the conclusion drawn by a study conducted in Finnish patients, which showed that D/D genotype confers 2,5 increase in the risk for acute coronary events(including acute myocardial infarction). The intense vasoconstriction properties of the α2Badrenergic polymorphism both on the coronary arteries and the periphery is considered to be the primary cause of the acute coronary events. The aforementioned statement with the significant role of α2B adrenergic receptor α2B-AR on the hyperplasia and mainly the migration of smooth muscle cells, probably correlates well with the pathophysiology of the recurrence of ischaemia after PTCA. We conducted a genetic association/prospective follow-up study in 96 Greek coronary artery disease patients undergoing coronary angioplasty and stent implantation. 81 patients were men and 15 women(mean age ± standard deviation=57,7± 10,1 years, ranges 37-76 years old) who presented with symptomatic CAD. All patients were enrolled in the study between 2001 and 2003 and were followed-up clinically for 6-8 months after an initially successful procedure. Post-angioplasty and for one (1) month following the procedure, all the patients received aspirin(100-325mg/day) and clopidogrel(75mg/day). Assessment of recurrence of ischaemia was based on positive thallium stress testing(at least moderate defect to the distribution of the culprit lesion of the vessel which was revascularised). Hemodynamically, restenosis was defined as ≥50% narrowing of the vessel at the point where angioplasty was performed. In addition to the patient group, a control group of totally 83 asymptomatic individuals were included in the study for comparison of the frequency of the genotype. The final end-point of the current study was the incidence of restenosis at 8 months of clinical follow-up. Recurrence of ischaemia (including restenosis rate ≥50% to the patients who underwent coronary angiography) occurred in 15 of the 96 patients. In note, the majotiy of patients (70/96) had the Insertion/Insertion genotype, fewer patients (23/96) had the Insertion/Deletion genotype and only 3/96 had the Deletion /Deletion genotype. With regard to to the genotype groups , restenosis was found in 11/70 for I/I, 3/23 for I/D and 1/3 for the D/D genotype. No association between gene polymorphisms and recurrence of ischaemia was detected to the patients who underwent coronary angioplasty. Previous studies have investigated the association between gene polymorhisms of angiotensin-converting enzyme(ACE), the AT1 receptor for angiotensin II and cholesteryl ester transfer protein (CETP) with restenosis in patients after coronary angioplasty. However, no study has been performed to involve the α2B-AR polymorphism with recurrence of ischaemia after percutaneous angioplasty of coronary vessels. As it was initially mentioned, α2B genotype promotes the migration of vascular SMCs, influences the function of autonomic nervous system and the α2B-AR deletion variant is associated with acute coronary events. All these data might correlate the role of α2B-AR polymorphism with the recurrence of ischaemia and probably with the restenosis after an angioplasty of coronary vessels. Nevertheless, the negative findings of our study might be considered preliminary, taking into account the small number of patients that were studied and the rarity of the Deletion/Deletion(D/D) genotype. As far as the CETP study, we investigated the TaqIB polymorphism, which is a silent base change affecting the 277th nucleotide and can be identified by the restriction endonuclease TaqI, with the chance of recurrence of ischaemia after PTCA. The terms B1 and B2 are used to denote the presence and absence, respectively, of the TaqI restriction site. The B2 allele has been associated with increased HDL levels and decreased CETP levels and activity in both patients with CHD and healthy subjects(resembling a mild form of CETP deficiency). On the other hand, the B1 allele has been associated with decreased HDL levels and increased CETP levels and activity. Due to the fact that TaqIB is associated with decreased HDL levels and increased risk for CHD, affecting the lipoprotein metabolism might be involved in the pathophysiology of reccurence of ischaemia after PTCA. We studied 204 patients between 2001 and 2003 with the primary objective to investigate the frequency of TaqIB and possible association with reccurence of ischaemia after PTCA in the patients who have this genotype. The frequency of TaqIB was 54% similar to the frequency of the polymorphism in a group of 35 healthy controls. The results from this study does not indicate that the TaqIB polymorphism at the CETP gene locus is a significant predictor for assessing the risk of reccurence of ischaemia after PTCA. As a conclusion, reccurence of ischaemia after PTCA is due to a complicated mechanism and to a multifactoral phenomenon. Virtually, we didn’t find any correlation of α2ΒAR polymorphism and CETP TaqIB with reccurence of ischaemia, especially as causitive factors, but based on their role in the pathophysiology, under certain circumstances, especially with the cooperation of other genes, these polymorphisms can not be definitely excluded in the reccurence of ischaemia and the restenosis after PTCA.

Terepthalic acid bis-(2-thiophen-3-yl-ethyl)ester (TATE) was synthesized through the reaction of 2-thiophen-3-yl-ethanol and terepthaloyl chloride. Electrochemical behavior of the TATE and TATE in the presence of thiophene were studied by cyclic voltammetry (CV). The chemical structure of monomer is characterized via Nuclear Magnetic Resonance Spectroscopy (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Homopolymer of TATE was synthesized by galvanostatic and potentiostatic methods, and copolymerization of TATE with thiophene was achieved via potentiostatic method. Both homopolymer (PTATE) and copolymer [P(TATE-co-Th)] were characterized by various techniques including cyclic voltammetry, FTIR, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermal Gravimetry Analysis (TGA) and UV-VIS Spectrophotometer. Conductivities of samples were measured by four probe technique. Electronic band gap of polymers measured as the onset of the &amp / #960 / -&amp / #960 / * transition using spectroelectrochemical analysis and colorimetry studies were investigated. Dual type polymer electrochromic devices (ECDs) based on PTATE, P(TATE-co-Th) and poly(3,4-ethylenedioxythiophene) (PEDOT) have been constructed. Spectroelectrochemistry, switching ability and stability of the devices were investigated by UV-Vis Spectrophotometer and Cyclic Voltammetry.

The master thesis deals actual tendencies and approaches to film and audiovisual education in Czech Republic and personal pedagogical experience of students and graduates of the Film and TV School of Academy of Performing Arts in Prague.

O trabalho tem como objetivo determinar a influencia da concentração de monoestearato de sorbitano, componente do núcleo oleoso das nanocápsulas, na cinética de liberação do éster etílico de indometacina a partir de nanocápsulas de poli(ε-caprolactona) (PCL). Com este propósito o éster etílico de indometacina foi associado a cada sistema e sua hidrólise alcalina foi realizada para simular uma condição sink. A velocidade de consumo do éster etílico de indometacina foi menor conforme o aumento da concentração do monoestearato de sorbitano. O tempo de meia-vida do consumo do éster etílico de indometacina associado as nanocápsulas foi relacionado com a concentração do monoestearato de sorbitano, sendo maior, enquanto maior a concentração do monoestearato. O mecanismo de liberação foi determinado como sendo transporte anômalo. Foi observada uma relação linear direta entre o aumento da concentração do monoestearato de sorbitano e a concentração de partículas nas suspensões de nanocápsulas (R2=0,9711). Mistura de outras nanopartículas que não as nanocápsulas, foram observadas e caracterizadas. O fluxo difusional do éster a partir das nanocápsulas foi determinado e diminuiu significativamente com o aumento da concentração do monoestearato, devido a mudanças na viscosidade do núcleo das nanocápsulas com o aumento da concentração do monoestearato de sorbitano. Por fim, os resultados demonstraram que o principal fator que contribui para o retardo no tempo para o consumo do éster etílico de indometacina é a relação direta entre a concentração do monoestearato de sorbitano e a permeabilidade das nanocápsulas (R=0,9894). / The aim of this work was to evaluate the influence of the sorbitan monoestearate concentration, one of the components of the oil core of the nanocapsules, in the release kinetic of the indomethacin ethyl ester-loaded poli(ε-caprolactone) nanocapsules. In this way, the indomethacin ethyl ester was entrapped within each system and its alkaline hydrolysis was carried out to simulate a sink condition. The rate for the indomethacin ethyl ester consumption decreased with the increase in sorbitan monostearate concentrations. The indomethacin ethyl ester half-live was related to the sorbitan monostearate concentration, increasing as the sorbitan monostearate concentration increased. The drug release mechanism was determined as anomalous transport. Linear correlations were obtained between the increase in the sorbitan monostearate concentration and the particles concentration in the suspensions (R2 = 0.9711). Mixture of different nanoparticles that are not nanocapsules were observed by density gradient and characterized. The indomethacin ethyl ester fluxes from the nanocapsules were determined and presented a decrease of the flux as the sorbitan monostearate concentration increased. This result was related to changes in the oil core viscosity caused by the variation of the sorbitan monostearate concentration. Finally, the results demonstrated that the main factor that contributes for the delaying in the time for the indometahcin ethyl ester consumption was the direct relation between the sorbitan monostearate concentration and the apparent permeability of the nanocapsules (R2 = 0.9894).

O trabalho tem como objetivo determinar a influencia da concentração de monoestearato de sorbitano, componente do núcleo oleoso das nanocápsulas, na cinética de liberação do éster etílico de indometacina a partir de nanocápsulas de poli(ε-caprolactona) (PCL). Com este propósito o éster etílico de indometacina foi associado a cada sistema e sua hidrólise alcalina foi realizada para simular uma condição sink. A velocidade de consumo do éster etílico de indometacina foi menor conforme o aumento da concentração do monoestearato de sorbitano. O tempo de meia-vida do consumo do éster etílico de indometacina associado as nanocápsulas foi relacionado com a concentração do monoestearato de sorbitano, sendo maior, enquanto maior a concentração do monoestearato. O mecanismo de liberação foi determinado como sendo transporte anômalo. Foi observada uma relação linear direta entre o aumento da concentração do monoestearato de sorbitano e a concentração de partículas nas suspensões de nanocápsulas (R2=0,9711). Mistura de outras nanopartículas que não as nanocápsulas, foram observadas e caracterizadas. O fluxo difusional do éster a partir das nanocápsulas foi determinado e diminuiu significativamente com o aumento da concentração do monoestearato, devido a mudanças na viscosidade do núcleo das nanocápsulas com o aumento da concentração do monoestearato de sorbitano. Por fim, os resultados demonstraram que o principal fator que contribui para o retardo no tempo para o consumo do éster etílico de indometacina é a relação direta entre a concentração do monoestearato de sorbitano e a permeabilidade das nanocápsulas (R=0,9894). / The aim of this work was to evaluate the influence of the sorbitan monoestearate concentration, one of the components of the oil core of the nanocapsules, in the release kinetic of the indomethacin ethyl ester-loaded poli(ε-caprolactone) nanocapsules. In this way, the indomethacin ethyl ester was entrapped within each system and its alkaline hydrolysis was carried out to simulate a sink condition. The rate for the indomethacin ethyl ester consumption decreased with the increase in sorbitan monostearate concentrations. The indomethacin ethyl ester half-live was related to the sorbitan monostearate concentration, increasing as the sorbitan monostearate concentration increased. The drug release mechanism was determined as anomalous transport. Linear correlations were obtained between the increase in the sorbitan monostearate concentration and the particles concentration in the suspensions (R2 = 0.9711). Mixture of different nanoparticles that are not nanocapsules were observed by density gradient and characterized. The indomethacin ethyl ester fluxes from the nanocapsules were determined and presented a decrease of the flux as the sorbitan monostearate concentration increased. This result was related to changes in the oil core viscosity caused by the variation of the sorbitan monostearate concentration. Finally, the results demonstrated that the main factor that contributes for the delaying in the time for the indometahcin ethyl ester consumption was the direct relation between the sorbitan monostearate concentration and the apparent permeability of the nanocapsules (R2 = 0.9894).

A presente Tese tem por objetivo estudar alguns aspectos das interações água-detergente que são importantes para o entendimento das propriedades fisico-químicas da própria micela. além das interações que ocorrem na pseudo-fase micelar. Estas interações foram estudadas utilizando-se duas técnicas: RMN de 1H, para avaliar o efeito de micelas aquosas iônicas, zwitteriônicas e não-iônicas sobre a estrutura da água; e o estudo cinético da hidrólise espontânea de um éster do ácido carbônico, para determinar a reatividade cinética desta água além de, possivelmente, esclarecer alguns aspectos da questão da penetração da água na micela. Foi determinado o efeito da concentração do detergente e a presença de deutério no solvente sobre os deslocamentos químicos dos prótons da água. Foi usada a seguinte série de detergentes: dodecilsulfato de sódio (SOS, aniônico), dodecilbenzenossulfonato de sódio (SDBS, aniônico), perfluoroctanoato de sódio (SPFO, aniônico), cloreto de cetiltrimetilamônio (CTACl, catiônico), éter octilfenil(9,5)polioxietilênico (TX-100) e dodecildimetilamônio-3-propanossulfonato (DDAPS, zwitteriônico). O deslocamento químico dos prótons da água. depende linearmente da concentração de detergente e os coeficientes angulares das retas são sinsíveis à concentração de deutério no solvente. A partir destas correlações foram calculados os fatores de fracionamneto deutério/prótio,&#966; cujas magnitudes dão uma idéia quantitativa do efeito do detergente sobre a estrutura da água. Para averiguar a origem micelar do fracionamento observado, foram determinados também os fatores de fracionamento para compostos modelos. Estes são constituídos de cadeias carbônicas curtas que não formam agregados mas que possuem os mesmos grupos hidrofílicos dos detergentes. Foram usados os seguintes compostos como modelos: butilsulfato de sódio (modelo para SDS), p-tolouenossulfonato de sódio (modelo para SDBS), perfluorobutirato de sódio (modelo para SPFO) e brometo de butiltrimetilamônio (modelo para CTACl). Os resultados obtidos mostram que estes compostos perturbam pouco a estrutura água e são diminuidores da sua estrutura. Os detergentes, com a excessão de DDAPS e TX-100, claramente aumentam a estrutura da água devido a efeitos eletrorrestritivos. Interações inter e intramoleculares entre os íons do DDAPS resultam numa neutralização interna das cargas e explicam o seu pequeno efeito (aumento) sobre a estrutura do solvente. Nao é fácil oferecer uma explicação simples para a diminuição da estrutura da água na presença de TX-100, pois existe a interferência de fatores cujos efeitos sobre o fracionamento não podem ainda ser avaliados. Entre estes destacamos o enrolamento das cadeias oxietilênicas do detergente. a presença de água fisicamente presa entre estas cadeias e o fato de que a distruibição das moléculas de água entre as unidades de oxietileno não é homogênea. Foram determinadas as constantes de velocidade, os parâmetros de ativação e o efeito isotópico cinético do solvente para a hidrólise independente do pH de carbonato de bis(2,4-dinitrofenila) , na presença de SDS, CTABr, CTACl, TX-100 de cetildimetilamônio-3-propanossulfonato (HDAPS) . O efeito micelar foi analisado em termos da transferência do éster do seio aquoso para água micelar, e do efeito salino acoplado a fatores eletrostáticos das micelas iônicas. Como modelo para o efeito da transferência do meio, a reação foi estudada em misturas de água e acetonitrila. O efeito salino foi avaliado estudando a reação em presença de alguns dos compostos-modelo acima mencionados. Houve mudanças marcantes na entropia e na entalpia de ativação da reação somente em presença de grandes quantidades de acetonitrila no solvente (fração molar de 0,55 a 0,90). O efeito salino foi pequeno. Todos os detergentes, especialmente o SDS, diminuiram velocidade da reação devido a fatores entálpicos desfavoráveis. Para ter uma idéia do sítio da solubilização do éster nas micelas usadas, estudamos o efeito de acetato e decanoato de p-nitrofenila (compostos usados como modelo para CDNF), sobre os deslocamentos químicos dos grupos de cada detergente. Os resultados mostram que o sítio de solubilização destes ésteres não está predominantemente na região da superfície da micela. Os ésteres movimentam-se rapidamente (em relação à escala do tempo da RMN), em todo volume da micela. Efetuamos um cálculo simples mostrando que a penetração da água até os primeiros dois grupos metilênicos pode dar origem a um volume hidratado da micela de mais de 50%. Uma consideração dos parâmetros de ativação, dos resultados de RMN de 1H e do significado do cálculo do volume micelar efetuado, nos levou a concluir que nossos dados cinéticos podem ser explicados sem a necessidade de assumir uma micela extensivamente hidratada, como por exemplo aquela proposta pelo modelo de aglomeração poros (porous cluster model). / Study of micelle-water interactions is relevant to the physical chemistry of the micelle itself, and for a better understanding of the interactions occuring therein. In the present thesis two aspects of these interactions were studied: the effect of the organized assembly on the structure of water at the micellar interface, and on the kinetic reactivity of water as probed by examining the pH-independent (spontaneous) hydrolysis of a carbonate ester. The effect of the following surfactants on the structure of water was studied: sodium dodecylsulphate (SDS, anionic) sodium dodecylbenzene sulphonate (SDBS, anionic), sodium perfluorooctanoate (SPFO, anionic), cetyltrimethylammonium chloride (CTACl, cationic), polyoxyethylene (9.5) octylphenyl ether (TX-100, nonionic), dodecyldimethylammonio-3-propane sulphonate (DDAPS, zwitterionic). The dependence of the chemical shift of the water protons on the surfactant concentration, and on the deuterium content of the solvent was used to calculate the deuterium/protium fractionation factor, &#966;. The magnitude of the latter (relative to unity, the fractionation factor for bulk water) gives a quantitative idea of the solvent structure perturbation by the micellar pseudophase. In order to ascertain that the observed D/H fractionation is micelle-induced, the fractionation factors for model compounds were also determined. These were short-chain, i.e., non-aggregating compounds bearing the same head-groups as the surfactants. The following model compounds were used: sodium butylsulphate (model for SDS), sodium p-toluenesulphonate (model for SDBS), sodium perfluorobutyrate (model for SPFO) and butyltrimethylammonium bromide (model for CTACl). The following conclusions were drawn from the determined fractionation factors: whereas the short-chain compounds perturb the structure of water only slightly, and are usually water structure breakers, the presence of the micelles clearly enhances the structure of the solvent. Exceptions are zwitterionic DDAPS (marginal structure enhancement) and nonionic TX-100 (water structure decrease). The behavior of the zwitterionic surfactant was explained based on the negligible electrostrictive effect of the micelle due to inter and intramolecular interactions between the head-ions. A simple rationale for the case of TX-100 is not easy because of can complicate such interpretation: the followino factors that coiling of the oxyethylene chains, physical trapping of water between the chains, noneven distribution of the water molecules along the oxyethylene chains. Rate constants, activation parameters, solvent kinetic isotope effect were determined for the pH-independent hydrolysis of 2,4-dintrophenyl carbonate in the presence of SDS, CTABr, CTACl. TX-100 and cetyldimethylammonio-3-propane sulphonate (HDAPS). The micellar effect was analyzed in terms of a transfer Effect, a salt and an electrostatic effect. The first refers to the transfer of the ester form bulk water to \"micellar\" water, and was mimicked by studying the reaction in water-acetonitrile mixtures. Salt effect was evaluated by conducting the hydrolysis in the presence some of the above mentioned short-chain compounds. For the reaction in aqueous acetonitrile the entropy and enthalpy of activation showed sizable changes only at high mole fraction (0.55 to 0.90) of the organic solvent. Salt effect was negligible. The tested detergents, specially SDS, slow the reaction rate due to unfavorable enthalpy. The solubilization site of the ester in the micelles was assesed by 1H NMR. using p-nitrophenyl acetate and decanoate as models. This study showed that the ester in the micelles is not localized at, or very near, to the micelle/water interface, but is rapidly moving (on the NMR time-scale) all over the micellar volume. Analysis of the obtained activation parameters, coupled with the 1H NMR data, and with the result of simple geometric calculation led us to conclude that deep water penetration in the micelle (e.g ., according to the porous cluster model) is not essential to rationalize our data.

Made available in DSpace on 2014-12-17T15:01:19Z (GMT). No. of bitstreams: 1 MiguelASN.pdf: 491289 bytes, checksum: be60500500779f6a3fd87b90108feb8c (MD5) Previous issue date: 2002-09-27 / The developments in formulating drilling fluids to apply in petroleum fields are based on new technologies and environmental challenges, where the technical performance of a developed drilling fluid is used to produce a minimum environmental impact, showing great economy in costs. It is well known that the potential use of oil-based drilling fluids is limited because these fluids when discharged in the sea do not disperse as much as water-based ones and may form waterproof films in the seabed, having a profound effect on plants and animals living in this environment. The current works have been made in investigating fluids called pseudofluids, which are synthetic ester-based, n-paraffin-based and other fluids formed from inverse emulsion. In this research the principal parameters involved in inverse emulsion process were studied, in laboratory scale, using esters as main component. Others commercial drilling fluids were used as comparative samples, as well as samples from laboratory and field where these drilling fluids are being applied. Concentrations of emulsifier and organophilic clay, which are viscosity donor, were varied to verify the influence of these parameters, in different oil/water ratios (55/45, 60/40, 65/35, 70/30, and 75/25). The salt concentration (NaCl) is an indicative parameter of stability and activity of an esterbased fluid. In this research the salt concentration was varied in 10,000, 20,000, and 50,000 ppm of NaCl. Some rheological properties of the produced fluids were studied, such as: initial gel, plastic viscosity, yield point, and apparent viscosity. Through the obtained rheological measures, the existence of two systems could be verified: fluid and flocculated. It could be noticed that the systems were influenced, directly, by the oil/water ratio and emulsifier, organophilic clay and NaCl concentrations. This study showed the viability to use an ester obtained from a regional vegetable product baba?u coconut oil to obtain an efficient and environmental safe drilling fluid / O desenvolvimento atual e futuro, em campos de petr?leo, baseia-se em novas tecnologias e desafios ao meio ambiente, onde se utiliza principalmente a performance t?cnica de um fluido de perfura??o que produza o m?nimo impacto ambiental, mostrando ainda, uma ?tima economia nos custos desses desenvolvimentos. Sabe-se que o potencial de continuidade de fluidos de perfura??o a base de ?leo est? limitado e, por conseguinte, o avan?o ambiental tem sido na investiga??o de fluidos chamados pseudo-fluidos, ou seja, fluidos sint?ticos base ?ster, ?ster, n-parafina e outros fluidos de emuls?o inversa, os quais est?o em estudo. Neste trabalho estudou-se em n?vel de laborat?rio as principais vari?veis envolvidas no processo de emuls?o inversa usando ?steres como componente principal, utilizando-se amostras comparativas de outros fabricantes, como tamb?m amostras provenientes de laborat?rio e de campo onde est?o sendo utilizados estes fluidos de perfura??o. As concentra??es de emulsificante ou argila organof?lica, que ? doadora de viscosidade, foram variadas para verificar a influ?ncia destes par?metros a diferentes raz?es ?leo/?gua (55/45, 60/40, 65/35, 70/30 e 75/25), mantendo-se constante os demais componentes do fluido. A concentra??o do sal, que ? um par?metro indicador de estabilidade e da atividade em fluido a base ?ster, foi variada em 10.000, 20.000 e 50.000 ppm de NaCl. Algumas propriedades reol?gicas dos fluidos assim produzidos foram estudadas, tais como: gel inicial, viscosidade pl?stica, limite de escoamento e viscosidade aparente. A partir das medidas reol?gicas obtidas, p?de-se verificar a exist?ncia de dois sistemas: fluido e floculado. P?de-se perceber que os resultados obtidos foram influenciados diretamente pela raz?o ?leo/?gua e pelas concentra??es do emulsificante, da argila organof?lica e do NaCl. Este estudo consolidou importantes conhecimentos que abrir?o portas para o sucesso de novas pesquisas, tornando-se fundamental a viabiliza??o de coloc?-lo posteriormente no mercado de trabalho do Brasil

O trabalho tem como objetivo determinar a influencia da concentração de monoestearato de sorbitano, componente do núcleo oleoso das nanocápsulas, na cinética de liberação do éster etílico de indometacina a partir de nanocápsulas de poli(ε-caprolactona) (PCL). Com este propósito o éster etílico de indometacina foi associado a cada sistema e sua hidrólise alcalina foi realizada para simular uma condição sink. A velocidade de consumo do éster etílico de indometacina foi menor conforme o aumento da concentração do monoestearato de sorbitano. O tempo de meia-vida do consumo do éster etílico de indometacina associado as nanocápsulas foi relacionado com a concentração do monoestearato de sorbitano, sendo maior, enquanto maior a concentração do monoestearato. O mecanismo de liberação foi determinado como sendo transporte anômalo. Foi observada uma relação linear direta entre o aumento da concentração do monoestearato de sorbitano e a concentração de partículas nas suspensões de nanocápsulas (R2=0,9711). Mistura de outras nanopartículas que não as nanocápsulas, foram observadas e caracterizadas. O fluxo difusional do éster a partir das nanocápsulas foi determinado e diminuiu significativamente com o aumento da concentração do monoestearato, devido a mudanças na viscosidade do núcleo das nanocápsulas com o aumento da concentração do monoestearato de sorbitano. Por fim, os resultados demonstraram que o principal fator que contribui para o retardo no tempo para o consumo do éster etílico de indometacina é a relação direta entre a concentração do monoestearato de sorbitano e a permeabilidade das nanocápsulas (R=0,9894). / The aim of this work was to evaluate the influence of the sorbitan monoestearate concentration, one of the components of the oil core of the nanocapsules, in the release kinetic of the indomethacin ethyl ester-loaded poli(ε-caprolactone) nanocapsules. In this way, the indomethacin ethyl ester was entrapped within each system and its alkaline hydrolysis was carried out to simulate a sink condition. The rate for the indomethacin ethyl ester consumption decreased with the increase in sorbitan monostearate concentrations. The indomethacin ethyl ester half-live was related to the sorbitan monostearate concentration, increasing as the sorbitan monostearate concentration increased. The drug release mechanism was determined as anomalous transport. Linear correlations were obtained between the increase in the sorbitan monostearate concentration and the particles concentration in the suspensions (R2 = 0.9711). Mixture of different nanoparticles that are not nanocapsules were observed by density gradient and characterized. The indomethacin ethyl ester fluxes from the nanocapsules were determined and presented a decrease of the flux as the sorbitan monostearate concentration increased. This result was related to changes in the oil core viscosity caused by the variation of the sorbitan monostearate concentration. Finally, the results demonstrated that the main factor that contributes for the delaying in the time for the indometahcin ethyl ester consumption was the direct relation between the sorbitan monostearate concentration and the apparent permeability of the nanocapsules (R2 = 0.9894).

Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In this study we identified the contaminants present in mixtures of methyl and ethyl esters of samples obtained from alternative sources of triacylglycerols, such as: Frying oil (OF), Cottonseed oil (OSA), Scum sludge (EE), Trap grease (GCG). The esters content (TE) of the samples were determined by gas chromatography with flame ionization detector (GC-FID) according to methodology NBR 15764. The samples presented TE below 96.5% (m/m), minimum percentage established by the National Agency of Petroleum, Natural Gas and Biofuels (ANP) to characterize the mixtures as Biodiesel. The identification of fatty acids methyl or ethyl esters (FAME or FAEE) in the mixtures were performed by gas chromatography/mass spectrometry (GC/MS), observing the presence of linear unsaturated esters with eighteen carbon atoms. By thermogravimetric profile, it was observed that the OF and OSA samples presented higher contamination by compounds of high molecular mass, approximately 12.00% (m/m), corroborating TE results. Reports in the literature indicate the processes of oxidative degradation or hydrolysis as being responsible for the origin of contaminants in these types of matrices, reinforced by the values of peroxide index obtained around 196.00 meq kg-1. By the easy ambiente sonic-spray ionization mass spectrometry technique (EASI-MS), in positive mode, it was possible to attribute the presence of dimers, confirmed by m/z 625, 673 and 689 ions, in addition to diacylglycerols (DAG) and triacylglycerols (TAG). The EE and GCG samples presented higher acid values around 28.00 mg KOH g-1 with higher contamination by free fatty acids (FFA). The FFA profile was determined by EASI-MS, in negative mode, and confirmed by derivatization of the samples with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and posterior GC/MS analysis. The identified FFAs comprised a range of six to eighteen carbon atoms with the majority presence of palmitic, linoleic, oleic and stearic acid. In the optimization of the open column chromatography method (CC) for the gravimetric determination of ester and contaminant content in the esters mixtures, the use of the chromatographic column with a 6 mm internal diameter and the use of hexane:dichloromethane (7:3) to elute the esters, and the use of ethyl ether:acetonitrile (8:2) to elute the contaminants were ideal conditions obtained in the optimization of the CC method. The optimized method of CC was applied in all the samples of this work, and the apolar fraction obtained and representative of the esters had esters contents above 96.5% (m/m). / Neste trabalho foram identificados os contaminantes presentes em amostras de misturas de ésteres metílicos e etílicos obtidos a partir de fontes alternativas de triacilgliceróis, tais como: óleo residual de fritura (OF), óleo da semente de algodão (OSA), escuma de esgoto (EE), gordura da caixa de gordura (GCG). O teor de ésteres (TE) das amostras foram determinados por cromatografia gasosa com detector de ionização por chama (GC-FID) conforme a metodologia NBR 15764. As amostras apresentaram TE abaixo de 96,5% (m/m), percentual mínimo estabelecido pela Agência Nacional do Petróleo, Gás Natural e Biocombustíveis (ANP) para se caracterizar as misturas como Biodiesel. A identificação dos ésteres metílicos ou etílicos de ácidos graxos (FAME ou FAEE) nas misturas foram realizadas por cromatografia em fase gasosa/espectrometria de massas (GC/MS), observando a presença majoritária de ésteres lineares insaturados com dezoito átomos de carbono. Pelo perfil termogravimétrico, foi observado que as amostras OF e OSA apresentaram maior contaminação por compostos de alta massa molecular, aproximadamente 12,00% (m/m), corroborando o TE. Relatos na literatura apontam os processos de degradação oxidativa ou de hidrólise como sendo os responsáveis pela origem de contaminantes nestes tipos de matrizes, reforçados pelos valores de índice de peróxidos obtidos em torno de 196,00 meq kg-1. Pela técnica de ionização ambiente por sonic-spray (EASI-MS), em modo positivo, foi possível atribuir a presença majoritária de dímeros, confirmados pelos íons de m/z 625, 673 e 689, além de diacilgliceróis (DAG) e triacilgliceróis (TAG). As amostras EE e GCG apresentaram maiores índices de acidez em torno de 28,00 mg KOH g-1 com maiores contaminações por ácidos graxos livres (FFA). O perfil dos FFA foi determinado por EASI-MS, em modo negativo, e confirmado por derivatização das amostras com N,Obis( trimetilsilil)trifluoracetamida (BSTFA) e análise por GC/MS. Os FFA identificados abrangeram uma faixa de seis a dezoito átomos de carbono com a presença majoritária do ácido palmítico, linoleico, oleico e esteárico. Na otimização do método de cromatografia em coluna aberta (CC) para determinação do teor de ésteres e de contaminantes em amostras de misturas de ésteres, o uso da coluna cromatográfica com diâmetro interno de 6 mm, e o uso de hexano:diclorometrano (7:3) para eluição dos ésteres, e o uso de éter etílico:acetonitrila (8:2) para eluição dos contaminantes foram as condições ideais obtidas na otimização do método de CC. O método otimizado de CC foi aplicado em todas as amostras deste trabalho, e a fração apolar obtida e representativa dos ésteres apresentaram teores de ésteres acima de 96,5% (m/m).

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study aimed to characterize chemically biodiesel derived from waste oils and fats, and also optimize the methodology for determining the ester content. The methyl biodiesel were obtained from residual frying oil, sewage scum, grease trap, cottonseed oil and oils from the Annonacia family of plants, more specifically the Annona salzmannii, vepretorum and squamosa species. We also investigated the potencial to produce biodiesel from oils obtained from exotic plants like Annona salzmannii, vepretorum and squamosa species. The tested ethyl biodiesel was produced from residual frying oil. The curves TG/DTG of biodiesel samples showed mass losses by evaporation and decomposition of esters. Infrared spectra showed high intensity of absorption bands (1739-1770 cm-1) attributed to C=O stretching ester; confirmed by C-O ester stretch (1247-1034 cm-1). For most samples of biodiesel tested the acid value was in accordance with the limit established by ANP. The study ester content was determined by gas chromatography using the external and internal standardization, using the esters C17:0 and C18:1 as standards. The method with PTV injection, heptane and external standardization using the standard C18:1 showed the best repeatability (0.62%) and reproducibility (3.00%), both with a correlation coefficient of r2= 0.9991. The results of the esters content obtained from the samples showed values between 75 and 93%. Using the method with classical column using silica as adsorbent was observed an increase in the ester content of the samples, reaching the value required by legislation. The comprehensive two-dimensional chromatography has been used in proving the absence of co-eluting compounds that would compromise the determination of the ester content. The supercritical method, using ethanol, proved to be an effective process for alternative raw materials. High conversion rates were obtained (~93%) employing a raw material with a high content of free fatty acids. We observed that with increasing temperature there is a reduction in ester content and that using hexane as co-solvent there was high yield in ester content. / Este trabalho teve como objetivo caracterizar quimicamente o biodiesel derivado de óleos e gorduras residuais e oleaginosas, e também otimizar a metodologia para a determinação do teor de éster. Os biodiesel metílicos foram obtidos a partir de óleo residual de fritura, de escuma de esgoto, gordura de caixa de gordura, óleo de algodão e óleos obtidos de plantas da família Annona, mais especificamente das espécies Anonna salzmannii, vepretorum e squamosa. O biodiesel etílico testado foi produzido a partir de óleo residual de fritura. As curvas de TG/DTG das amostras de biodiesel mostraram perdas de massas características da evaporação e da decomposição de ésteres. Os espectros de infravermelho apresentaram bandas de absorção de alta intensidade em (1739-1770 cm-1) atribuída ao estiramento C=O de éster; confirmado pelo estiramento C O de éster (1247-1034 cm-1). Para a maior parte das amostras de biodísel testadas o índice de acidez esteve dentro dos limites estabelecidos pela ANP. O estudo do teor de ésteres foi determinado através de cromatografia a gás, utilizando a padronização interna e externa, empregando os ésteres C17:0 e C18:1 como padrões. O método com injeção PTV, heptano e padronização externa usando o padrão C18:1 foi o que apresentou melhor repetibilidade (0,62%) e reprodutibilidade (3,00%), ambos com coeficiente de correlação de r2= 0,9991. Os resultados dos teores de ésteres obtidos a partir amostras apresentaram valores entre 75 e 93%. Utilizando o método de coluna clássica com sílica como adsorvente foi observado um aumento no teor de éster das amostras, atingindo valor exigido pela legislação. A cromatografia bidimensional abrangente foi empregada na comprovação da ausência de co-eluição de compostos que comprometem a determinação de teor ésteres nos biodiesel. O método supercrítico, empregando o etanol, mostrou-se um processo eficaz para matérias-primas alternativas. Foram obtidas elevadas taxas de conversões (~93%) empregando uma matéria-prima com um alto teor de ácidos graxos livres. Foi possível notar que com o aumento de temperatura houve uma redução no teor de éster e que utilizando hexano como co-solvente houve rendimento elevado no teor de éster.