Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (M.C.S.)--Carleton University, 2005. / Includes bibliographical references (p. 115-123). Also available in electronic format on the Internet.

Dissertation (Ph.D.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 104 pages. Includes vita. Includes bibliographical references.

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Ο σκοπός της παρούσας μελέτης ήταν να εξετάσει τον ρόλο της ταξόλης (paclitaxel) και της καρβοπλατίνης σε σχέση με τις παραμέτρους του ανοσοποιητικού συστήματος σε ασθενείς πάσχοντες από μη μικροκυτταρικό καρκίνο του πνεύμονα και από καρκίνο των ωοθηκών· πριν, κατά τη διάρκεια και μετά από χημειοθεραπεία και η επίδραση που είχε ο ανωτέρω συνδυασμός φαρμάκων στην συνολική επιβίωση των ασθενών. Υλικό και Μέθοδος: Εξετάσθηκαν 24 ασθενείς με μη-μικροκυτταρικό καρκίνο του πνεύμονα και 20 με καρκίνο των ωοθηκών (όλοι μεταστατικοί), όπου χωρίστηκαν σε δύο ομάδες με κριτήριο την επιβίωση και που εν συνεχεία τους χορηγήθηκε συνδυασμός καρβοπλατίνης και ταξόλης για έξι θεραπευτικούς κύκλους. Ομάδα Α. Ασθενείς με καλή επιβίωση (>12 μήνες για μη-μικροκυτταρικό καρκίνο του πνεύμονα, >30 μήνες για καρκίνο των ωοθηκών) Ομάδα Β. Ασθενείς με «φτωχή» επιβίωση (<12 μήνες για μη-μικροκυτταρικό καρκίνο του πνεύμονα, <18 μήνες για καρκίνο των ωοθηκών) Την ίδια χρονική περίοδο εξετάσθηκαν οι λεμφοκυτταρικοί υποπληθυσμοί (CD3, CD4, CD8, CD56, CD34) καθώς και οι κυτταροκίνες ιντερλευκίνη-3 (IL-3) και ιντερφερόνη-γ (IFN-γ), σε σχέση με την ποιότητα ζωής και το προσδόκιμο επιβίωσης κατά την διάρκεια της χημειοθεραπευτικής αγωγής. Η στατιστική ανάλυση των αποτελεσμάτων έγινε με την μέθοδο ANOVA. Αποτελέσματα: Από την εξαγωγή των αποτελεσμάτων παρατηρήθηκε μία στατιστικώς σημαντική διαφορά ανάμεσα στις τιμές των λεμφοκυτταρικών 207 υποπληθυσμών CD4 και CD4/CD8 μετά από χημειοθεραπεία μεταξύ των δύο ομάδων ασθενών Α και Β (p=0,001 και p=0,006). Αυτό σημαίνει ότι η περαιτέρω αύξηση του αριθμού των βοηθητικών Τ-λεμφοκυττάρων (T-helper) μετά από χημειοθεραπεία συμβάλλει θετικά στο προσδόκιμο επιβίωσης. Επιπροσθέτως, στατιστικώς ενδιαφέρων σε σημείο που να μπορούμε να μιλήσουμε και για προγνωστικό παράγοντα, ήταν η διαφορά ανάμεσα στις τιμές της ιντερφερόνης-γ μεταξύ των ομάδων Α και Β πριν και μετά τη χημειοθεραπεία (p=0,039 και p=0,027, αντιστοίχως). Οι ασθενείς με υψηλές τιμές ιντερλευκίνης-3 παρουσίαζαν επίσης χαμηλή τοξικότητα. Συμπεράσματα: Στην παρούσα μελέτη η προσπάθεια μας επικεντρώθηκε στο να καταδείξουμε την επίδραση που ασκείται, από την χρήση του συνδυασμού καρβοπλατίνης-ταξόλης, στους λεμφοκυτταρικούς υποπληθυσμούς και στις κυτταροκίνες καθώς και την επιρροή που ασκούν και τα δύο αυτά στοιχεία του ανοσοποιητικού συστήματος στο προσδόκιμο επιβίωσης και στην εν γένει ποιότητα ζωής. / The aim of the present study was to exam the role of Paclitaxel (Taxane) and Carboplatin in the parameters of the immune system in patients with non-smallcell lung cancer and in patients with ovarian cancer before, during and after chemotherapy treatment, and the effect of this combination in the overall survival of the patients. Methods: 24 patients with non-small-cell lung cancer (NSCLC) and 20 patients with ovarian cancer (all in stage IIIb-IV) were treated with a combination of paclitaxel and carboplatin for six treatment cicles and they were separated into two groups in terms of survival. GROUP (A). Long survival (>12 months for NSCLC, >30 months for ovarian Ca) GROUP (B). Long survival (<12 months for NSCLC, <18 months for ovarian Ca) At the same time we combined the relevant parameters (CD3, CD4, CD8, CD56, CD34, IL-3, IFN-γ) with the quality of life during treatment with chemotherapy. The results were analyzed using ANOVA system. Results: We observed a significant statistical difference between the values of CD4 and CD4/CD8 after chemotherapy between group A and group B (p=0,001 and p=0,006). This means that the further increase of T-helper cells after chemotherapy has a better prognosis concerning survival. In addiction, statistically interesting, which we may call a prognostic factor, was the difference in values of IFN-γ between individuals of groups and B before and after chemotherapy (p=0,039 and p=0,027, respectively). Patients with high IL-3 had little chance of toxicity. Conclusions: In the current study we tried to demonstrate the effects from the use of the combination of carboplatin-paclitaxel in the whole population of Tcells/ cytokines and the reaction of them in the quality of life.

Η λεπτίνη, μια ορμόνη που ρυθμίζει την όρεξη έχει βρεθεί να ενισxύει την τύπου 1 ανοσολογική απόκριση και να αναστέλλει την παροδική ανοσοπάρεση που παρατηρείται στα ζώα με έλλειψη λεπτίνης ή στους ανθρώπους που υποφέρουν από εγγενή ή φυσιολογική έλλειψη λεπτίνης. Οι ασθενείς που υποφέρουν από β-θαλασσαιμία έχει παρατηρηθεί ότι έχουν έλλειψη λεπτίνης, ένα φαινόμενο που αποδίδεται κυρίως στην υπερφόρτωση με σίδηρο και τις πολλαπλές ενδοκρινοπάθειες που συνοδεύουν αυτή τη νόσο. Ο σκοπός της μελέτης μας ήταν να καθοριστούν τα επίπεδα λεπτίνης και φερριτίνης του ορού των ασθενών που υποφέρουν από μείζονα β-θαλασσαιμία και να διερευνηθεί η επίδραση της λεπτίνης στην Th1 (IL-2, IFN-γ ) και Th2 (IL-4, IL-10) έκκριση κυτταροκινών από περιφερικά Τ κύτταρα που απομονώθηκαν από ασθενείς και controls. Τα δείγματα αίματος προήλθαν από143 ασθενείς και 58 υγιείς κατά αντιστοιχία ηλικίας και ΒΜΙ (δείκτη μάζας σώματος). Από όλους τους ασθενείς το μόνο γκρουπ που έδειξε μια ασθενή θετική συσχέτιση μεταξύ ΒΜΙ και λεπτίνης ήταν αυτό των ενήλικων γυναικών που λάμβαναν θεραπεία ορμονικής υποκατάστασης. Μια αρνητική συσχέτιση λεπτίνης και φεριττίνης παρατηρήθηκε σε όλους τους ασθενείς. Η ανασυνδυασμένη λεπτίνη όταν προστέθηκε στα Τ κύτταρα των controls δεν επηρέασε σημαντικά την έκκριση της IFN-, IL-2 ή της IL-4 ενώ μείωσε ελαφρώς την έκκριση της IL-10. Στα Τ-κύτταρα των ασθενών η ανσυνδυασμένη λεπτίνη οδήγησε στην έκκριση μόνο της IFN-γ. Οι ομόζυγοι θαλασσαιμικοί ασθενείς λαμβάνουν πολλαπλές μεταγγίσεις και χρειάζονται μια ισχυρή Th1 ανσολογική απόκριση για να χειριστούν αποτελεσματικά την συνεχή έκθεση σε παθογόνα. Η ικανότητα της λεπτίνης να αλλάζει την έκφραση των κυτταροκινών στους ασθενείς με θαλασσαιμία προς έναν ευνοϊκό γι’ αυτούς τύπου 1 φαινότυπο θα μπορούσε να ληφθεί υπόψη για τον σχεδιασμό νέων θεραπευτικών σχημάτων. / Leptin, a hormone that regulates appetite, has been shown to enhance the type 1 immune response and reverse the partial immunoparesis observed in leptin-deficient animals or humans suffering from congenital or physiological leptin deficiency. Patients suffering from -thalassemia have also been reported to be leptin deficient, a phenomenon attributed mainly to the iron overload and multiple endocrinopathies that accompany this disease. The purpose of our study was to determine the serum leptin and ferritin levels of patients suffering from -thalassemia major and investigate the effect of leptin on Th1 (IL-2, IFN- ) and Th2 (IL-4, IL-10) cytokine secretion patterns of peripheral blood T-cells isolated from thalassemic patients and controls. Blood samples were drawn from 143 patients and 58 age- and Body Mass Index-matched controls. From all the patients, the only group that showed a week positive correlation between BMI and leptin values was this of adult females that were treated with sex hormones. A negative correlation of leptin and ferritin levels was observed in all patients. Recombinant leptin (rleptin) added alone to control T-cells did not significantly influence IFN-, IL-2 or IL-4 production whereas it weakly induced IL-10 secretion. In patients’ T-cells, rleptin induced IFN- secretion only. Homozygous thalassemic patients receive multiple blood transfusions and need a strong Th1 immune response to cope with the resulting exposure to pathogens. Leptin’s ability to skew the cytokine secretion pattern in thalassemic patients towards a beneficial for them Th1 phenotype, could be taken into consideration for the design of new therapeutics.

Submitted by SERGIO MANUEL RUGELES REYES null (smrugelesr@gmail.com) on 2018-01-04T14:31:39Z No. of bitstreams: 1 Dissertacao FINAL FINAL.pdf: 839997 bytes, checksum: 1ff42407d98ebf9f8e9ead2312027554 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-01-05T10:00:57Z (GMT) No. of bitstreams: 1 rugelesreyes_sm_me_jabo.pdf: 839997 bytes, checksum: 1ff42407d98ebf9f8e9ead2312027554 (MD5) / Made available in DSpace on 2018-01-05T10:00:57Z (GMT). No. of bitstreams: 1 rugelesreyes_sm_me_jabo.pdf: 839997 bytes, checksum: 1ff42407d98ebf9f8e9ead2312027554 (MD5) Previous issue date: 2017-10-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A deficiência de zinco atinge um terço da população mundial e uma estratégia para solucionar essa problemática é a biofortificação agronômica de hortaliças. A rúcula tem ganhado notoriedade nos últimos anos devido às suas propriedades nutricionais e boa aceitação pelos consumidores. Em razão do incremento no seu consumo, torna-se uma hortaliça folhosa com alto potencial para estudos de biofortificação agronômica com zinco, porém, ainda são poucas as pesquisas feitas a respeito. Assim, em um solo com alto teor do micronutriente, objetivou-se avaliar o efeito de aplicações foliares de zinco, em diferentes épocas, sobre parâmetros fisiológicos, produtivos e nutricionais de rúcula ‘Folha larga’, visando à biofortificação agronômica. O experimento foi instalado na UNESP, câmpus Jaboticabal e foram avaliados dois fatores: dose de Zn (0,5; 1 e 1,5 kg ha-1 de Zn) e épocas de aplicação (15 dias após a emergência - DAE, 20 DAE, 25 DAE, 15 e 20 DAE e 15, 20 e 25 DAE) mais um controle, que não recebeu aplicação de zinco. Observou-se que não houve efeito dos fatores nem da interação nas variáveis fisiológicas, assim como na altura, área foliar e massa fresca da parte aérea. Doses de Zn afetaram os teores de N, Mn e P, enquanto para Cu e Fe não foram encontrados efeitos significativos. Verificou-se que com aplicação de 1,5 kg ha-1 de Zn, feita aos 25 DAE, obteve-se maior teor de Zn nas folhas de rúcula, representando incremento de 279% em relação ao controle, denotando a efetividade de aplicações foliares de zinco como estratégia de biofortificação em rúcula. / Zinc deficiency affects a third of the world population and a strategy to solve this problem is agronomic biofortification of vegetables. Arugula has gained importance in recent years due to its nutritional properties and good acceptance by consumers. Due to the increase in its consumption, it becomes a leafy vegetable with high potential for studies of agronomic biofortification with zinc, however, few researches have been done about them. Thus, in a soil with high micronutrient content, the objective was to evaluate the effect of foliar zinc applications, at different times, on physiological, productive and nutritional parameters of 'Broad Leaf' arugula, aiming at agronomic biofortification. The experiment was realized at UNESP, Jaboticabal Campus and two factors were evaluated: Zn dose (0.5, 1 and 1.5 kg ha-1 of Zn) and times of application (15 days after emergence - DAE, 20 DAE, 25 DAE, 15 and 20 DAE, and 15, 20 and 25 DAE) plus one control, which did not receive zinc application. It was observed that there was no effect of the factors or the interaction in the physiological variables, as well as in the height, leaf area and fresh mass of the aerial part. Doses of Zn affected the contents of N, Mn and P, whereas for Cu and Fe no significant effects were found. It was verified that with the application of 1.5 kg ha-1 of Zn, realized at 25 DAE, a higher Zn content was obtained in the arugula leaves, representing an increase of 279% in relation to the control, showing the effectiveness of foliar applications of zinc as a biofortification strategy in arugula.

Made available in DSpace on 2014-06-11T19:30:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-10-26Bitstream added on 2014-06-13T20:21:11Z : No. of bitstreams: 1 abreu_js_dr_jabo.pdf: 580857 bytes, checksum: 7cd4b8b96649d30421df9e3fae023302 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O sistema imune é dividido em duas partes que se complementam: o sistema imune inato (não específico) e o adquirido (específico). O sistema imune inato é considerado como a primeira linha de defesa e inclui barreiras físicas (pele e muco) e componentes celulares e moleculares (macrófagos, células killer e fatores solúveis de imunidade, como lisozima, proteínas do sistema complemento, peptídeos antimicrobianos, entre outros). No processo de criação, o sistema imune dos peixes pode ser prejudicado por vários fatores, mas efeitos benéficos podem ser observados com o uso de substâncias conhecidas como imunoestimulantes. Dentre os imunoestimulantes estudados, os glicanos vêm sendo amplamente utilizados como importantes indutores de mecanismos não específicos de defesa. Em algumas espécies de peixes tropicais, como o pacu (Piaractus mesopotamicus) e matrinxã (Brycon amazonicus), estudos observaram o papel da vitamina C como imunoestimulante avaliando a hematologia dos peixes como indicador das alterações imunológicas. O número de leucócitos e de trombócitos é considerado importante indicador de seu estado de saúde. Entretanto, não são conhecidos estudos que avaliem outros parâmetros imunológicos bem como os efeitos do glicano nas respostas imunológicas inatas de peixes tropicais. O pacu, por ser uma espécie onívora, de fácil cultivo e adaptada a ampla variedade de alimentos, tem grande importância na piscicultura brasileira e por esta razão foi escolhido como modelo experimental nesta pesquisa. O objetivo deste trabalho foi testar, inicialmente, técnicas para avaliação de alguns mecanismos inatos de defesa (atividade respiratória de leucócitos e concentração e atividade de lisozima) nesta 37 espécie tropical, cujos resultados são apresentados no capítulo 2 desta tese. Este estudo registrou essas respostas imunes inatas no pacu... / The immune system is divided in two parts that complement each other: the specific and non-specific immune system. The non-specific immune system is the primary defence line and includes natural barriers (skin and mucus) and cellular and molecular components (macrophages, natural killer cells, immune soluble factors, like lysozyme, complement, antimicrobials peptides, among others). In all farming, the immune system of fish may be damaged by many factors, but the benefic effects may be observed using immunostimulants. It has been of common knowledge that glucans are the most known of them and are being used like nonspecific defence mechanisms stimulants. In some tropical fish species, such as pacu (Piaractus mesopotamicus) and matrinxã (Brycon amazonicus), studies evaluated vitamin C effect as immunostimulant, considerating the fish hematology as immune alterations indicator. The leucocytes and trombocytes number is considerated an important health indicator. However, there are no studies evaluating different immune parameters and the glucan effect in innate immune response of tropical fish. The pacu is an omnivore specie of great importance to Brazilian fish farming. For this reason, it was chosen as experimental model in this research. The aim of this work was to test some techniques for evaluation of some defence innate mechanisms (burst oxidative and lysozyme) in this tropical specie, whose results are showed in chapter 2 of this work. This research recorded these immune responses of pacu and established adequate methodologies for its determination. After, this study evaluated the effect of glucan, administered to intraperitoneal injection and incorporated in the diet, in stimulation of some immune systems components of pacu. Besides, it was also verified 39 the stress responses after the capture of pacu fed with diets supplemented with glucan ...(Complete abstract, click electronic access below)

Infection with human immunodeficiency virus type 1 (HIV-1) results in a wide range of immunologic and hematopoietic abnormalities. The overall goal of this dissertation was directed toward obtaining a better understanding of the interactions of HIV-1 and myeloid cells in relation to the pathogenesis of AIDS. The human myelomonocytic cell line, HL-60, was used as a model system to determine if HIV-1 infects myeloid progenitor cells and subsequently, if infection affects their differentiation. HL-60 cells and the human prototypic T cell line, H9 were infected with three different HIV-l isolates (IIIB, PM213, and NL4-3) which are known to infect T cells. All three isolates productively infected both H9 and HL-60 cells; however, HIV-1 antigen expression and cytopathicity was delayed by approximately 15 days in infected HL-60 cells compared H9 cells. To examine the effect of HIV-l infection on myeloid differentiation, chronically infected HL-60 cells and clonal lines derived from them were induced to differentiate into either granulocytes by treatment with dimethyl formamide (DMF) or into monocytes by treatment with phorbol l2-myristate 13 acetate (PMA). By both cellular morphology and function, approximately the same percentage of treated, HIV-infected HL-60 cells differentiated into either granulocytes or monocytes as treated, control HL-60 cells. Taken together, these results indicate that HIV-1 infection does not affect the morphological or functional differentiation of HL-60 cells. In an effort to understand the differences in the regulation of HIV-l infection in myeloid versus T cells, the life cycle of NL4-3 was examined in HL-60 cells and H9 cells. Initially, NL4-3 replication was restricted in HL-60 cells compared to H9 cells. This restriction was overcome 15 days after infection by the generation of a viral isolate, NL4-3(M). NL4-3(M), harvested during the lytic phase of NL4-3 infection of HL-60 cells, caused cell death approximately 8 days after infection in both H9 and HL-60 cells. Although measurements of viral entry kinetics demonstrated that the timing of entry of NL4-3 and NL4-3(M) in HL-60 cells and NL4-3 in H9 cells was similar, a quantitative polymerase chain reaction (PCR) analysis of newly reverse transcribed NL4-3 DNA in H9 and HL-60 cells revealed that NL4-3 infected H9 cells and NL4-3(M) infected HL-60 cells contain consistently higher amounts of newly reverse transcribed DNA than NL4-3 infected HL-60 cells. The delay in NL4-3 replication in HL-60 cells was further amplified by inefficient spread of the virus throughout the HL-60 culture as measured by RNA production and DNA integration suggesting that another step in the viral life cycle after reverse transcription was also restricted. These results suggest that the efficiency of NL43 replication in HL-60 cells is restricted at several steps in the viral life cycle. Further, these restrictions are overcome by the generation of a viral variant, NL4-3(M), which efficiently replicates in myeloid cells. The tropism of NL4-3(M) was further characterized by testing its growth in monocyte-derived macrophages (MDM). Unlike NL4-3, NL4-3(M) productively infected MDM cultures. The ability of NL4-3(M) to infect macrophages was conferred by the envelope gene. This was demonstrated by the ability of the recombinant virus, NL4-3envA, which contains the envelope of NL4-3(M) in the context of the NL4-3 genome, to infect and replicate in MDM cultures. The envelope gene of NL4-3(M), however, did not confer ability to rapidly kill HL-60 cells. Together, these findings demonstrate that viral determinants controlling entry into MDM are different trom the determinants controlling the cytopathic phenotype in HL-60 cells.