Die Forschung um die Optimierung der Insel-Transplantation nimmt in der Behandlung des Typ I Diabetes eine Vorreiterstellung ein. Nachdem im Zeitraum von drei Jahrzehnten Fortschritte im Bereich der Insel-Isolierung und Immunosuppression gemacht wurden, stehen wir heute am Beginn des klinischen Einsatzes dieser Technik an ausgewählten Patientengruppen. Ziel der vorliegenden Arbeit ist die umfassende Funktionsdiagnostik isolierter porziner mikroverkapselter Inseln. Mit Hilfe einer miniaturisierten Mikroperifusionskammer wurde der Einfluss des Kulturmediums, der IEQ-Zahl sowie der Mikroverkapselung auf die Insulinsekretion untersucht. Zusätzlich wurde die Insel-Vitalität den Perifusions- Parametern gegenübergestellt. Untersucht wurden zudem die dosisabhängige Stimulierbarkeit der Inseln mit Nährstoffen, Hormonen und Neuromediatoren unter normo- und hyperglykämischen Bedingungen und ihre Aktivierbarkeit bei anhaltender In-Vitro-Kultur. / The research towards an optimized transplantation of islet cells takes an outrider position in the future treatment of the typ I diabetes. After three decades of progress in the field of island isolation and immunosuppression, we face the beginning of the clinical application of this technology at selected groups of patients. A goal of this study was a comprehensive functional diagnostic of isolated microencapsulated porcine Islets of Langerhans. With a new miniaturized microperifusion chamber we studied the influence of the culture medium, IEQ numbers as well as the microencapsulation on the insulin secretion of the islet cells. Additionally the island vitality was correlated to functional parameters received during microperifusion. Besides this we qualitatively and quantitatively examined the dose-dependent stimulation of the islands with nutrients, hormones and neuromediators under normo and hyperglycaemic conditions as well as their function under prolonged in-vitro-culture.

O antígeno leucocitário humano (HLA)-G corresponde a uma molécula não clássica de classe I do complexo principal de histocompatibilidade. Segundo a literatura, tal molécula pode ser expressa em ambos os contextos patológico e fisiológico. Diversos autores têm apresentado evidências acerca do papel do HLA-G na tolerância imune do feto durante a gestação, bem como para o sucesso de alotransplantes. No entanto, até o momento, há poucas informações publicadas a respeito da expressão fisiológica dessa molécula nos diferentes órgãos humanos. Em acréscimo a isso, a participação do HLA-G em eventos fisiológicos é ainda um assunto controverso entre cientistas. Tendo em vista o exposto, o objetivo desse estudo foi investigar a expressão da proteína HLA-G em órgãos fetais durante o progredir da gestação, bem como em órgãos adultos. Trata-se de um estudo descritivo, comparativo, transversal e retrospectivo realizado com base na revisão de prontuários e análise de necropsias/biópsias de diferentes órgãos de fetos e adultos através do método de imunohistoquímica. Os resultados demonstraram a existência de diferença estatística significativa na imunomarcação da proteína HLA-G em glândulas adrenais (p= 0,0003), baço (p= 0,0276), coração (p= 0,0474), fígado (p= 0,0052), pulmões (p = 0,0367), rins (p = 0,0377) e timo (p= 0,0336) na comparação entre o primeiro e segundo trimestre gestacional; em glândulas adrenais (p= 0,0329), baço (p= 0,0095), pâncreas (p= 0,0009) e placenta (p= 0,0285) na comparação entre o segundo e terceiro trimestre gestacional; e no coração (p= 0,0304), fígado (p= 0,0055), pulmões (p= 0,0150) e rins (p= 0,0312) na comparação entre o terceiro trimestre gestacional e a fase adulta. Foi verificado um aumento na expressão do HLA-G fetal a partir do segundo trimestre gestacional em órgãos como glândulas adrenais, coração, fígado, rins, timo e pulmões. Entretanto, isso não foi uma constante, pois em outros, a exemplo do baço, pâncreas e placenta, não observouse essa tendência durante o mesmo período. Durante o terceiro trimestre gestacional e a fase adulta evidenciou-se valores mais elevados para a expressão do HLA-G nos rins, e valores bastante inferiores no fígado. A expressão fisiológica do HLA-G embora positiva em todos os órgãos avaliados, nos três trimestres gestacionais e/ou na fase adulta, apresentou diferenças na intensidade e localização nos diferentes órgãos e períodos. Os achados a partir dessa pesquisa certamente representam uma importante contribuição para um melhor entendimento do mecanismo gestacional, assim como da fisiologia do HLA-G em adultos, sobretudo no que concerne o estabelecimento da tolerância imunológica em transplante de órgãos / Human leukocyte antigen (HLA)-G is a nonclassical class I major histocompatibility complex molecule. According to the literature, this molecule can be expressed in both pathological and physiological contexts. Several authors have presented evidence about the role of HLA-G in the immune tolerance of the fetus during pregnancy, as well as for the success of allotransplants. However, until now, there are very few published data regarding the physiological expression of this molecule in different human organs. Moreover, the role of HLA-G in physiological events is still a controversial subject among scientists. In view of the above, the objective of this study was to investigate the expression of HLA-G protein in fetal organs during the progression of gestation, as well as in adult organs. This was a descriptive, comparative, cross-sectional and retrospective study based on the review of medical records and immunohistochemical analysis of different organs of fetuses and adult people. The results showed a statistically significant difference in the immunostaining of HLA-G protein in adrenal glands (p = 0.0003), spleen (p = 0.0276), heart (p = 0.0474), liver (p = 0.0367), kidneys (p = 0.0377) and thymus (p = 0.0336) in the comparison between the first and second gestational trimesters; in adrenal glands (p = 0.0329), spleen (p = 0.0095), pancreas (p = 0.0009) and placenta (p = 0.0285) in the comparison between the second and third gestational trimesters; and in the heart (p = 0.0304), liver (p = 0.0055), lungs (p = 0.0150) and kidneys (p = 0.0312) in the comparison between the third gestational trimester and the adult phase. An increase of fetal HLA-G expression was observed from the second gestational trimester in organs such as adrenal glands, heart, liver, kidneys, thymus and lungs. However, this was not a constant finding, since in other organs including spleen, pancreas and placenta, this trend was not observed during the same period. During the third gestational trimester and the adult phase, higher values for HLA-G expression in the kidneys and much lower values in the liver were observed. Although the physiological expression of HLA-G has been positive in all evaluated organs (in the three gestational trimesters and/or in adulthood), it showed differences in its intensity and location in the different organs and periods. The findings from this research certainly represent an important contribution to a better understanding of the gestational mechanism, as well as on the physiology of HLA-G in adults, especially regarding the establishment of immunological tolerance in organ transplantation

MMed thesis - Faculty of Health Sciences / The field of organ and tissue transplantation has necessitated an improved understanding of their associated pathophysiological pathways. Specific areas of interest involve the changes that follow ischaemia and derangement’s that accompany organ and tissue storage, reperfusion injury and the “no-reflow” phenomenon. Strategies have been devised to manipulate and modify these processes, improving tissue and organ survival and function. These have involved the use of preservation solutions. Although most research involves organ transplantation, these principles have been translated and applied to various tissues, surgical flaps and microvascular replantations. These studies have generally used the skin flap as their model with little knowledge regarding muscle flaps, the most vulnerable to the ischaemic process. This study targets the use of one such preservation system and uses skeletal muscle as its tissue model. The vascular anatomy of the rectus femoris muscle in the New Zealand white rabbit was studied anatomically and radiologically and thus described. The isolated rectus femoris muscle flap was harvested and perfused in-vitro with cooled, oxygenated University of Wisconsin solution (UWS) using a pulsatile renal perfusion pump. UWS was selected as it contains vital additives important in cryopreservation of organs. Monitoring of various physiological parameters was performed. The muscle was examined at 0, 4, 8, 12, 18 and 24 hours of extra-corporeal perfusion using warm and cold, non-perfused controls. The contralateral muscle served as the control. End-points were the percentage of muscle survival, as determined by a new grading system of muscle ischaemia, based on 3 light and 7 electron microscopic criteria. The overall percentage of muscle survival (combined light and electron microscopy scores) resulted in approximately 58% survival at 24 hours for the perfused muscle versus 31% for the cold stored muscle. The stored muscle had the same survival rate at 12 hours as did the perfused muscle at 24 hours. For all time periods beyond 4 to 8 hours, perfused muscle showed statistically improved survival rates compared to the stored muscle. Eight hours appears to be a crucial point beyond which survival in muscle deteriorates to a much greater degree without perfusion. Questions remain as to which method of preservation yields the best survival benefit and, as yet, there is no “ideal” perfusate. The future involves manipulating perfusion solutions and trying to arrest or reverse established warm ischaemia. Success of free tissue transfers and replantations of musclecontaining body parts may be enhanced. These techniques may also allow us to effectively store previously harvested flaps and eventually, to enter the realm of “banked” allograft tissue flaps.

Thesis advisor: Thomas Chiles / Thesis advisor: James Kim / The purpose of this thesis is to describe some of the research I conducted in Dr. Markmann’s laboratory at Massachusetts General Hospital in the field of transplantation immunology. The first portion provides background information on the immune system and its different components, eventually providing an in-depth look at regulatory T cells, and their role in transplant immunology. The second portion of the thesis is dedicated to my experiments. This part presents the materials and methods used, the previous findings that led to my experiments, the data analysis and results, and a conclusive discussion. The research I did that is included in this thesis pertains to regulatory T cells. It is believed that a potential pathway to prolonging allograft survival is to drive antigen-specific CD4+Foxp3- T cells to convert to CD4+Foxp3+ T cells. I studied the effects of retinoic acid (RA) and anti-CD45RB treatment on Foxp3 expression in CD4+ T cells. These studies were done using different lines of transgenic mice that provided models of antigen-specificity. My in vitro data demonstrated that RA is capable of boosting TGF-β-mediated Foxp3 upregulation in a synergistic manner and that anti-CD45RB is also able to increase Foxp3 expression. In vivo RA experiments were inconclusive, and due to some misfortune and time constraints in vivo anti-CD45RB experiments were not conducted. Research funded by the following sources: 2R56AI048820, 5R01AI057851, and 5K01DK079207. / Thesis (BS) — Boston College, 2011. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Biology.

A literatura apresenta vários artigos que estudam o tipo e a frequência de alterações bucais em pessoas transplantadas renais, mas é escassa em pesquisas que proporcionem evidências científicas sobre o risco de tratamento odontológico invasivo induzir infecção local ou à distância em receptores de transplante. A escassez de estudos que abordam manejo clínico em procedimentos odontológicos invasivos em pacientes transplantados reflete o empirismo e a falta de homogeneidade nas recomendações das equipes transplantadoras em relação ao manejo odontológico ideal do indivíduo receptor de transplante renal. Este volume apresenta um compilado de três trabalhos científicos que abordaram manejo do indivíduo transplantado renal e a avaliação do desfecho clínico após procedimentos odontológicos invasivos. As pesquisas foram executadas no Centro de Atendimento a Pacientes Especiais (CAPE) da Faculdade de Odontologia da USP. Todas tiveram aprovação do comitê de ética em pesquisa. A primeira pesquisa buscou conhecer, por meio de questionário, as condutas dos cirurgiões dentistas frente ao tratamento odontológico de pacientes transplantados renais. O segundo estudo avaliou retrospectivamente a incidência de complicações após exodontias em pacientes transplantados renais, realizadas no CAPE, por diferentes dentistas, que foram precedidas ou não por antibioticoterapia profilática. O terceiro estudo teve por objetivo avaliar a reparação alveolar após extrações de dentes erupcionados de forma prospectiva, em pacientes transplantados e controles, sem receberem antibioticoterapia profilática. Os resultados mostraram que a maioria dos dentistas entrevistados se sentem inseguros em realizar tratamento odontológico em pacientes transplantados renais e prescrevem antibiótico profilático excessivamente, e com posologia empírica. Foi constatado por meio do estudo retrospectivo que o uso ou não de antibiótico profilático antes de exodontias em indivíduos transplantados renais não afeta o desfecho pós-operatório. Por fim, os resultados do terceiro estudo evidenciaram que não há diferença na epitelização e no reparo alveolar pós-exodôntico entre indivíduos transplantados renais e não transplantados, quando submetidos à exodontias simples, sem o uso de antibiótico profilático. / The literature presents several papers regarding type and frequency of oral manifestations in renal transplant recipients, but there is a lack of studies that give scientific evidence about the risk of invasive dental treatment to induce local or distant site infection in renal transplant individuals. The lack of studies that focus on clinic management in invasive dental procedures reflects the empiricism and lack of standardization on the recommendations given by the transplant team regarding the ideal dental management of the renal transplant recipient. This volume presents a compilation of three scientific papers that approach the management of renal transplant recipient and the assessment of clinical outcomes after invasive dental procedures. The researches were performed at the Special Care Dentistry Center (SCDC), of School of Dentistry, University of Sao Paulo. All studies had ethical approval. The first study sought to know, through a questionnaire, the conducts of dentists regarding dental treatment on renal transplant recipients. The second was a retrospective study, that assessed post-operative complications following dental extractions performed at SCDC, that was preceded or not by antibiotic prophylaxis. The third was a prospective study, which assessed the socket healing after dental extractions of erupted teeth, on renal transplant recipients and control individuals, without antibiotic prophylaxis. The results show that most dentists interviewed feel insecure on performing dental treatment on renal transplanted patients as these practitioners prescribe prophylactic antibiotics excessively and based on empirical therapeutic posology. It was verified through the retrospective study that the antibiotic prophylactic prescription or non-prescription preceding an invasive dental procedure does not affect the post-operative outcome for renal transplant recipients. Finally, the results of the third study evidenced that there is no difference in post-extraction epithelization and thus healing between renal transplant recipients and non-transplanted individuals, without using antibiotic prophylaxis.

Introdução: A neutropenia febril (NF) é um evento adverso intrínseco ao transplante de células-tronco hematopoiéticas (TCTH), decorrente da mielossupressão ocasionada pelo procedimento, que impacta de modo importante na morbidade e na mortalidade do paciente. Objetivos: Analisar os pacientes submetidos ao TCTH quanto a ocorrência de NF. Método: Coorte retrospectiva conduzida com 61 pacientes submetidos ao TCTH no Hospital de Clínicas da Universidade Estadual de Campinas. Foram extraídos dados relativos a características basais dos pacientes, procedimento de TCTH, tempo de internação e desfecho clínico para determinar os fatores associados à NF. As variáveis independentes foram idade, sexo, comorbidades, diagnóstico, tipo de transplante, regime de condicionamento, fonte das células, nº de CD34, tempo de enxertia, escore de risco pré-TCTH do EBMT, SAPSII. A NF foi definida de acordo com o Common Terminology Criteria for Adverse Events (CTC/AE) v4.0, considerando o desfecho dicotômico, a duração em dias, a data da ocorrência, o grau e a análise de sobrevida. Os dados foram analisados por meio de testes paramétricos e não paramétricos, dependendo do nível de mensuração das variáveis e utilizaram-se Kaplan-Meier e regressão logística. Para todas as análises considerou-se nível de significância de 5%. Resultados: A incidência de NF nos pacientes submetidos ao TCTH foi de 78,7%, com duração média de 8,3 dias, sem diferença significativa entre os tipos de transplantes (p=0,176). Não foram encontrados fatores de risco para a NF, porém, os pacientes submetidos ao transplante autólogo (p=0,022) e ao regime de condicionamento mieloablativo (p=0,026) apresentaram menor sobrevida para este evento adverso. Os pacientes que utilizaram ventilação mecânica (p=0,052), que necessitaram do uso de drogas vasoativas (p=0,012) e que foram a óbito (OR=9,66; p=0,052), apresentaram NF em sua totalidade. Conclusão: A incidência de NF foi expressiva e, ainda que não tenham sido identificados fatores associados a ela, os pacientes submetidos ao regime NMA e TCTH alogênico apresentaram maior sobrevida para o surgimento de NF. Estes achados relativos a sobrevida podem subsidiar o enfermeiro na proposição de intervenções, visando evitar complicações infecciosas decorrentes da NF. / Introduction: Febrile neutropenia (FN) is an intrinsic adverse event to hematopoietic stem cell transplantation (HSCT), due to the myelosuppression caused by the procedure, which has an important impact on patient morbidity and mortality. Objectives: To analyze the patients submitted to HSCT regarding the occurrence of FN. Method: Retrospective cohort with 61 patients submitted to HSCT at Hospital de Clínicas, State University of Campinas. Data were extracted on the baseline information of patients, HSCT procedure, time of hospitalization and clinical outcome to determine the factors associated with FN. The independent variables were age, gender, comorbidities, diagnosis, type of transplantation, conditioning regime, cell source, CD34 number, grafting time, pre-HSCT risk score of EBMT, SAPSII. The FN was defined according to the Common Terminology Criteria for Adverse Events (CTC / AE) v4.0, considering the dichotomous outcome, duration in days, date of occurrence, degree and survival analysis. Data were analyzed using parametric and non-parametric tests, depending on the level of measurement of the variables and Kaplan-Meier and logistic regression were used. A significance level of 5% was considered for all analyzes. Results: The incidence of FN in patients submitted to HSCT was 78.7%, with an average duration of 8.3 days, with no significant difference between the types of transplants (p = 0.176). No risk factors were found for FN, however, patients submitted to autologous transplantation (p = 0.022) and myeloablative conditioning (p = 0.026) presented lower survival rates for this adverse event. Patients who used mechanical ventilation (p = 0.052), who required the use of vasoactive drugs (p = 0.012) and who died (OR = 9.66, p = 0.052) presented FN in their entirety. In addition, the occurrence of FN had an association with longer hospitalization time (p = 0.003). Conclusion: The incidence of FN was significant. Although no associated factors were identified, patients submitted to NMA and allogeneic HSCT presented a higher survival rate for the onset of FN. These findings regarding survival can subsidize the nurse in proposing interventions, in order to avoid infectious complications due to FN.

La protéostase cellulaire représente l'ensemble des mécanismes régulant la production, le repliement, le transport et la dégradation des protéines dans la cellule afin de maintenir son homéostasie. La protéostase cellulaire est fréquemment altérée dans les cellules tumorales, pouvant induire une accumulation de protéines mal repliées. En réponse à cette accumulation, la cellule met en place une réponse physiologique adaptative appelée "Unfolded Protein Response" (UPR). Dans la 1ère partie de l'étude nous avons montré que le sorafénib, i.e. le traitement de référence du carcinome hépatocellulaire (CHC) avancé, altérait la protéostase tumorale et inhibait l'initiation de la traduction des protéines. Nous avons cherché des outils permettant de mesurer l'altération de la protéostase tumorale chez les patients en s'intéressant à la régulation des marqueurs tumoraux sériques par la protéostase cellulaire. Dans la deuxième partie de l'étude, nous avons exploré un potentiel rôle de l'UPR dans la tumorigénèse des carcinomes à cellules rénales (RCC) post-transplantation. L'incidence des RCC est largement augmentée chez les patients transplantés en comparaison à la population générale. Bien que la carcinogénèse du RCC soit multifactorielle, la prise chronique de traitements immunosuppresseurs tels que la ciclosporine (CsA) semble impliquée dans ce processus. Nous avons montré in vitro que la CsA pouvait altérer la protéostase tumorale et induire l'UPR. Cette induction semble liée à l'agressivité des RCC dans ce contexte / Cellular proteostasis is the process regulating the production, folding, trafficking and degradation of proteins within the cell in order to maintain its homeostasis. Cellular proteostasis is frequently altered in tumor cells, leading to an accumulation of unfolded proteins. In response to this accumulation, the cell activates an adaptive physiological response called "Unfolded Protein Response" (UPR). In the first part of the study we showed that sorafenib, i.e. the standard of care for advanced hepatocellular carcinoma (HCC), altered tumor proteostasis and inhibited the initiation of protein translation. We looked for tools to measure the alteration of tumor proteostasis in patients by focusing on the regulation of serum tumor markers by cellular proteostasis. In the second part of the study, we explored a potential role of UPR in tumorigenesis of post-transplant renal cell carcinoma (RCC). The incidence of RCC is greatly increased in transplant patients compared to the general population. Although carcinogenesis of RCC is multifactorial, chronic intake of immunosuppressive drugs such as ciclosporin (CsA) appears to be involved in this process. We showed in vitro that CsA alters tumor proteostasis and induce UPR. This induction seemed linked to the aggressiveness of the RCC in this context

Sammanfattning  Bakgrund: Njurtransplantation är en av de främsta behandlingarna vid njursvikt, som resulterar i både positiva och negativa effekter för patienten.    Syftet: Syftet med denna uppsats var att ta reda hur mottagaren upplever sin hälsorelaterade livskvalitet (HRQoL), fysiskt, psykiskt och socialt, efter en njurtransplantation. Metod: En litteraturöversikt där tio artiklar av kvantitativ karaktär valdes ut för att sedan granskas och analyseras.Databaserna som användes var PubMed, CINAHL, MEDLINE, Cochrane och PsycInfo.Katie Erikssons omvårdnadsteori användes som teoretisk referensram. Resultat: Studiens resultat delades upp i psykisk livskvalitet, fysisk livskvalitet och social livskvalitet. Flertalet patienter rapporterade om försämrad fysisk livskvalitet relaterat till de bieffekter som de immunsuppressiva läkemedlen medför. Studien indikerar dock på att patientens HRQoL påverkas av dess förväntningar innan transplantationen, då de som hade lägre förväntningar uppgav en högre skattad livskvalitet efter transplantationen. Patienter uppgav att de kände sig friare i jämförelse med dialyspatienter, främst då de inte är bundna till dialysbehandling. Den psykiska livskvaliteten upplevdes som förbättrad i jämförelse än innan operationen, då patienterna rapporterade den psykiska stressen som mindre. Många upplevde känsla av oro över både de efterföljande sjukdomarna som en njurtransplantation kan medföra, men även över transplantavstötning. De patienter som hade högre inkomst rapporterade högre social livskvalitet jämfört med de som hade det sämre ställt, efter en njurtransplantation.  Slutsats: Patienterna rapporterade ett varierande resultat av hur de upplever sin HRQoL efter njurtransplantation. Den fysiska livskvaliteten var den som var mest försämrad, i och med de biverkningar som läkemedlen medför. Generellt upplevde dock flertalet av patienterna en förbättrad HRQoL i jämförelse med innan transplantationen. För att minska patientens lidande har sjuksköterskan en mycket viktig roll. / Abstract  Background: Kidney transplantation is one of the primary treatments for renal disease, which results in both positive and negative effects for the patient.  Aim: The aim of this review was to find out how the recipient of the kidney experiences his or her health-related quality of life (HRQoL), physically, mentally and socially, after a kidney transplantation. Method: A systematic review where ten quantitative studies were elected to be reviewed and analyzed. The data bases that has been used is PubMed, CINAHL, MEDLINE, Cochrane and PsycInfo. The nursing theory of Katie Eriksson was used as a theoretical reference. Results: The result of the study was divided in physical, mental and social quality of life (QoL). Multiple patients reported that they experienced worse physical HRQoL related to the side effects of the immunosuppressant medication. Although, the study indicates that the patients HRQoL is affected by the high expectations before the transplantation, where the patients with lower expectations reported a higher score of experienced HRQoL after the kidney transplantation. Patients also stated that they felt more free in comparison with patients undergoing dialysis since they are not bound to go to any dialysis treatments. The experienced mental QoL after the operation was better than before because of less mental stress. The diseases that a kidney transplantation can lead to, along with the worry of transplant rejection was stated as a concern among a lot of the patients. The patients with a higher income reported a better experienced social QoL, after kidney transplantation, compared to the patients with lower socioeconomic status.  Conclusion: The patients reported varying results about the experienced HRQoL after a kidney transplantation. The psysical QoL was stated as the most impaired, mainly because of the side effects of the immunosuppressants. However, the majority of the patients generally experienced an improved HRQoL in comparison with their life before the transplantation. It is a big part of the nursing role to decrease the suffering of the patient.

Orientador: José Antonio Dell'Aqua Junior / Banca: Marco Antonio Alvarenga / Banca: Silvia Ferrari / Resumo: A indução de múltiplas ovulações nas espécies domésticas é de extrema importância para a melhoria dos resultados e custos de biotécnicas como a transferência de embriões, inseminação com sêmen de baixa fertilidade, transferência de oócitos, entre outras. Este estudo teve como objetivo determinar se a sulpirida poderia induzir multiplas ovulações em éguas. Dezessete éguas foram aleatoriamente utilizadas nos dois grupos experimentais. No grupo de éguas tratadas com sulpirida 1mg/kg (IM) a cada 12 horas, o protocolo foi iniciado apenas em éguas que alcançaram um folículo de 24 mm ± 2mm de diâmetro e um segundo folículo ≥ 20 ± 2 mm de diâmetro. No grupo controle, utilizou-se o mesmo protocolo de início do tratamento porém as éguas foram tratadas com solução salina 0,9% (IM) a cada 12 horas. Em ambos os grupos, se durante as avaliações ultrassonográficas era verificado crescimento folicular concomitante de dois ou mais folículos, o tratamento perdurava até quando o menor folículo atingisse no mínimo 33 mm de diâmetro. Neste momento a ovulação foi induzida com 1500 UI de hCG. A inseminação artificial foi realizada 24 horas após a indução, e os embriões foram coletados no oitavo dia após a primeira ovulação. As variáveis estudadas foram analisadas utilizando o teste t de Student e teste exacto de Fisher. No grupo tratado, 35% das éguas tiveram mais que uma ovulação e uma média de 1,4 ovulações por ciclo enquanto que no grupo controle apenas 11% das éguas tiveram mais que uma ovulação e uma média de 1,1 ovulações por ciclo. No grupo tratado com sulpirida o tempo de início do tratamento até a primeira ovulação foi de 3,9 ± 0,9 dias enquanto que no grupo controle foi de 4,9 ± 1,0 (P<0,001). A administração da Sulpirida durante o desenvolvimento folicular, estimulou a atividade ovariana e não contribuiu para um aumento significativo nas taxas de duplas ou triplas ... / Abstract: The induction of multiple ovulations in domestic species is of extreme importance to provide improvements of results and costs of biotechnologies such as embryo transfer, artificial insemination with poor quality semen, oocyte transfer among others. This study aimed to determine if sulpiride could induce multiple ovulations in mares. Seventeen mares randomly passed the two experimental groups. In the group of mares treated with sulpiride 1mg/kg (IM) every 12 hours, the protocol was initiated only in mares that have achieved a follicle of 24 mm ± 2 mm in diameter and a second follicle ≥ 20 ± 2 mm in diameter. In the control group, were used the same protocol, but the mares were treated with 0.9% saline solution (IM) every 12 hours. During the ultrasound evaluation if was observed the follicular growth the treatment even when the lower follicle reached at least 33 mm in diameter. At this time the ovulation was induced with 1500 IU of hCG. Artificial insemination was performed 24 hours after ovulation induction, and the embryos were collected on the eighth day after the first ovulation. The variables were analyzed using Student's t Fisher's exact test and test. In group treated, 35% of the mares had more than one ovulation and ovulation an average of 1.4 per cycle while in control group only 11% of the mares had more than one ovulation and ovulation an average of 1.1 per cycle. In the group treated with sulpiride the time of the treatment beginning to the first ovulation was 3,9 ± 0.9 days whereas the control group was 4.9 ± 1.0 (P<0,001). Administration of Sulpiride during follicular development stimulated ovarian activity but did not contribute to a significant increase in the rates of double or triple ovulations, however some mares had a higher incidence of multiple ovulations when subjected to the proposed protocol, suggesting that further studies should be conducted for clarification of these results / Mestre

Introdução: O transplante cardíaco exerce um papel relevante no tratamento da insuficiência cardíaca grave. Dentro dos desfechos desfavoráveis a seus resultados, a falência primária do enxerto é reconhecida, como condição de gravidade e mortalidade elevada. Os fatores implicados no aparecimento da falência primária do enxerto ainda não são bem esclarecidos e sua relevância é pouco estudada. Objetivo: Observar se há associação entre hipernatremia do doador e de outras variáveis com o desenvolvimento da falência primária do enxerto (FPE). Métodos: Foram avaliados, retrospectivamente, 200 pacientes submetidos à cirurgia de Transplante Cardíaco Ortotópico (TxC) no Instituto Dante Pazzanese de Cardiologia (IDPC), no período entre 01/01/2001 e 31/12/2010, sendo cotado os níveis de sódio sérico no doador. Além disto, foram avaliados outros fatores relacionados ao doador, ao receptor e ao procedimento cirúrgico. Após a identificação de que o sódio sérico do doador estava elevado no grupo de receptores com FPE, um ponto de corte foi obtido pela curva ROC. O nível de significância dos testes foi de 5%. Um modelo de regressão logística múltipla foi ajustado para avaliar os efeitos de fatores e covariáveis presentes na FPE. Resultados: Entre os pacientes que desenvolveram falência primária do enxerto, a média do sódio sérico foi de 162,0 mEq/l contra 153,6 mEq/l dos que não apresentaram FPE. O valor de corte pela curva ROC foi de 159 mEq/l. Houve diferença significativa (p< 0,03) entre os dois grupos com aumento de ocorrência de falência primária do enxerto nos pacientes que receberam órgãos oriundos de doadores com sódio sérico >159mEq/l. A outra variável que apresentou valor significativo (p=0,04) foi o tabagismo do doador. Conclusão: Com base nesses achados, observou-se que existe associação entre a elevação do sódio sérico do doador com o desenvolvimento de falência primária do enxerto, após o transplante cardíaco. / Introduction: Cardiac transplantation has a role in the treatment of severe heart failure. Within the unfavorable outcomes to their results, the primary graft failure is recognized as a condition of severity and high mortality. The factors involved in the onset of primary graft failure are still unclear and their relevance is poorly studied. Objective: Observe if there is an association between donor hypernatremia and other variables with the development of primary graft failure (PGF). Methods: We retrospectively evaluated 200 patients who underwent surgery for orthotropic heart transplantation (HT) at the Instituto Dante Pazzanese de Cardiologia (IDPC) in the period between 01/01/2001 and 12/31/2010, and evaluated the serum sodium levels in the donor. Furthermore, we assessed other factors related to the donor, the recipient and the surgical procedure. After identification that the donor serum sodium was higher in the group of receivers with PGF, a cutoff point was obtained by ROC curve. The level of significance of the tests was 5%. A multiple logistic regression model was fitted to assess the effects of factors and covariates present in PGF. Results: Among patients who developed primary graft failure, the mean serum sodium was 162.0 mEq/l versus 153.6 mEq/l of which showed no PGF. The cutoff value for the ROC curve was 159 mEq/l. There was an important difference (p <0.03) between the two groups with increased incidence of primary graft failure in patients who received organs from donors with serum sodium> 159 mEq/l. The other variable that showed a significant value (p = 0.04) was smoking from the donor. Conclusion: Based on these findings, we observed that there is an association between elevated serum sodium from the donor with the development of primary graft failure after heart transplantation.