Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: OBJECTIVE: The aim of this study was to compare the accuracy of non-invasive brachial blood pressure measurements, using automated and manual devices, to invasive brachial intra-arterial blood pressure measurements in patients with preeclampsia, during acute severe hypertension. STUDY DESIGN: A prospective descriptive cross sectional study was conducted in the Obstetrics Critical Care Unit (OCCU) of Tygerberg Hospital. Pre-eclamptic patients with acute severe hypertension, who required the placement of brachial intra-arterial lines due to failed radial intra-arterial line placement, were included in the study. Both automated oscillometric and blinded manual aneroid sphygmomanometric blood pressures were recorded during hypertensive peaks and after stabilization of BP using intravenous Labetalol or Nepresol. These two noninvasive methods of blood pressure measurements were compared to brachial intraarterial blood pressure measurements. RESULTS: There was weak correlation between manual and intra-arterial SBP (r = 0.27, p = 0.048) for SBP≥160mmHg. The calculated mean difference between manual SBP compared to the intra-arterial SBP in this group was -23.19mmHg (+/- 19.40). There was moderate correlation between automated and intra-arterial SBP (r = 0.69, p < 0.05). The calculated mean difference between automated SBP compared to the intra-arterial SBP in this group was -16.85mmHg (+/- 11.58). CONCLUSION: This study of pre-eclamptic women demonstrated that both non-invasive methods of BP measurement were inaccurate measures of the true systolic intra-arterial BP and significantly underestimated SBP≥160mmHg when compared to brachial intra-arterial measurements. The SBP was also underestimated, to a lesser degree, for mild moderate hypertension. This study also demonstrated that direct invasive BP monitoring using the brachial artery is a safe method for accurate haemodynamic monitoring. We recommend the use of intra-arterial BP monitoring in pre-eclamptic women with acute severe hypertension. Radial arterial cannulation should be used as the first option and the brachial artery should be used if the first option fails. / AFRIKAANSE OPSOMMING: DOELWIT: Die doel van hierdie studie was om die akuraatheid van nie indringende bragiale bloeddruk metings, wat met outomatiese en manuele aparate geneem is, te vergelyk met bragiale intra-arteriele bloeddruk metings gedurend akute erge hipertensie in pasiente met pre-eklampsie, STUDIE ONTWERP: ʼn Prospektiewe beskrywende dwarssnit studie was in die Obstetriese Kritiese Sorg Eenheid (OCCU) van Tygerberg Hospitaal uit gevoer. Preeklamptiese pasiente met akute erge hipertensie, wat bragiale intra-arteriele lyne nodig gehad het, as gevolg van gefaalde radiale intra-arteriele lyn plasing, was in hierdie studie ingesluit. Beide outomatiese ossilometriese en geblinde aneroide sfigmomanometriese bloeddrukke, tydens hipertensiewe pieke en na stabilisering van bloeddrukke met binneaarse Labetalol of Nepresol, was aangeteken, Die twee nie indringende metodes van bloeddruk meting was met bragiale intra-arteriele bloeddruk metings vergelyk. RESULTATE: Daar was ʼn swak korrelasie tussen manuele en intra-arteriele sistoliese bloedrukke SBP (r = 0.27, p = 0.048) vir SBP≥160mmHg. Die berekende gemiddelde verskil tussen manuele SBP en intra-arteriele SBP was -23.19mmHg (+/- 19.40) in hierdie groep. Daar was ʼn matige korrelasie tussen outomatiese en intra-arteriele SBP (r = 0.69, p < 0.05). Die berekende gemiddelde verskil tussen outomaties SBP vergelyk met intra-arteriele SBP was -16.85mmHg (+/- 11.58) in hierdie groep. GEVOLGTREKKING: Hierdie studie van pre-eklamptiese vrouens, het getoon dat beide nie indringende metodes van bloeddruk meting, nie akurate metings van ware sistoliese intraarteriele bloeddruk is nie, en SBP≥160mmHg word aansienlik onderskat wanneer dit met bragiale intra-arteriele metings vergelyk word. Die SBP was ook tot ʼn minder mate onderskat vir matige hipertensie. Die studie het ook getoon dat die direkte bragiale intra-arteriele metode van bloeddruk monitering, ʼn veilige metode van hemodinamiese monitering is. Ons beveel die gebruik van intra-arteriele bloeddruk monitering aan, in preeklamptiese vrouens met akute erge hipertensie. Radiale arteriele kanulasie moet gebruik word as die eerste opsie en die bragiale arterie moet gebruik word as die eerste opsie faal.

With the publication of the famous Erdős-Ko-Rado Theorem in 1961, intersection problems became a popular area of combinatorics. A family of combinatorial objects is t-intersecting if any two of its elements mutually t-intersect, where the latter concept needs to be specified separately in each instance. This thesis is split into two parts; the first is concerned with intersecting injections while the second investigates intersecting posets. We classify maximum 1-intersecting families of injections from {1, ..., k} to {1, ..., n}, a generalisation of the corresponding result on permutations from the early 2000s. Moreover, we obtain classifications in the general t>1 case for different parameter limits: if n is large in terms of k and t, then the so-called fix-families, consisting of all injections which map some fixed set of t points to the same image points, are the only t-intersecting injection families of maximal size. By way of contrast, fixing the differences k-t and n-k while increasing k leads to optimal families which are equivalent to one of the so-called saturation families, consisting of all injections fixing at least r+t of the first 2r+t points, where r=|_ (k-t)/2 _|. Furthermore we demonstrate that, among injection families with t-intersecting and left-compressed fixed point sets, for some value of r the saturation family has maximal size . The concept that two posets intersect if they share a comparison is new. We begin by classifying maximum intersecting families in several isomorphism classes of posets which are linear, or almost linear. Then we study the union of the almost linear classes, and derive a bound for an intersecting family by adapting Katona's elegant cycle method to posets. The thesis ends with an investigation of the intersection structure of poset classes whose elements are close to the antichain. The overarching theme of this thesis is fixing versus saturation: we compare the sizes and structures of intersecting families obtained from these two distinct principles in the context of various classes of combinatorial objects.

INTRODUÇÃO: O ronco acomete grande parte da população e o seu tratamento é um desafio, pois existem muitas opções terapêuticas e esta escolha deve ser individualizada. Entre vários procedimentos palatais para tratamento do ronco e da apneia do sono, a injeção roncoplástica (IR) surgiu como uma alternativa econômica para alguns casos selecionados. OBJETIVOS: Avaliar os resultados da IR no tratamento do ronco, comparando o oleato de etanolamina 5% e o etanol 50%. Além disso, descrever uma metodologia de aplicação própria e analisar seus resultados clínicos, complicações, medidas palatais por ressonância magnética (RM) e parâmetros polissonográficos. MÉTODOS: estudo clínico, duplo cego e randomizado, realizado de 2007 a 2010. Foram incluídos adultos roncadores com índice de apneia-hipopneia (IAH) <15. Critérios de exclusão: cirurgia palatal pregressa, IMC>35, obstrução nasal ou faríngea > 50% da via aérea, deformidade crânio-facial, gestação, ausência de acompanhante de quarto, alergia ou comorbidade grave. Sessões ambulatoriais de IR foram realizadas no palato mole (três pontos), máximo de três sessões, com quatro semanas de intervalo mínimo. Os pacientes foram divididos em dois grupos: um recebeu oleato de etanolamina 5% (A) e o outro, etanol 50%(B). A intensidade do ronco foi aferida por escala visual-analógica de 10cm (EVA). Foram analisados outros parâmetros clínicos, como sonolência e dor, além de RM e polissonografias. RESULTADOS: Dos 22 pacientes incluídos neste estudo (A=9 / B=13), 19 (86,4%) apresentaram diminuição importante ou desaparecimento do ronco. A intensidade de ronco (EVA) decresceu nos dois grupos: de 8,0 para 3,0 no Grupo A (p=0,007) e de 8,0 para 3,0 no Grupo B (p=0,001). A escala de sonolência de Epworth diminui de 8,0 para 6,0 no Grupo A (p=0,05) e de 11,0 para 5,0 no Grupo B (p=0,005). A dor durante o procedimento, aferida em EVA, foi de 4,0 nos dois Grupos. Nos dias subseqüentes, a dor foi de 3,5 no Grupo A e 2,0 no Grupo B, sem diferença entre os grupos. Na amostra geral, o tempo médio para retorno a alimentação foi de 2,0 dias e a melhora do ronco ocorreu em 14,0 dias. Não foram observadas complicações graves. Vinte e um pacientes apresentaram afta palatal, mas nenhum desenvolveu fístula. Das medidas realizadas por RM, a espessura palatal reduziu de 0,9 para 0,8 cm (p=0,34), o comprimento palatal diminuiu de 3,7 para 3,4 cm (p=0,02) e a área palatal foi de 2,8 para 2,5 cm2 (p=0,29). Nas polissonografias, o IAH variou de 6,9 para 5,0 no Grupo A (p=0,89) e de 5,2 para 6,3 no Grupo B (p=0,22), enquanto a saturação mínima de O2 e os microdespertares não apresentaram alterações estatisticamente significantes. CONCLUSÕES: A IR mostrou resultados favoráveis no tratamento do ronco, porém não houve diferença entre os grupos que receberam oleato de etanolamina 5% e etanol 50%. Nossa metodologia de aplicação reproduziu as taxas de sucesso de outros estudos, sem apresentar casos de fístula palatal ou complicações graves. As aferições por RM evidenciaram redução do comprimento palatal após as injeções. Não foram observadas alterações das variáveis polissonográficas após o procedimento / BACKGROUND: Snoring affects a significant portion of the population and the treatment is a challenge, because there are many options and the choice should be individualized. Among various palatal procedures for the treatment of snoring and sleep apnea, the injection snoreplasty (IS) has emerged as an economic alternative for selected cases. OBJECTIVES: To evaluate IS in the snoring treatment, comparing 5% ethanolamine oleate and 50% ethanol. Also, to describe a distinct method of injection and analyze its clinical results, complications, palatal measures by resonance imaging (MRI), and polysomnographic parameters. METHODS: Clinical, double-blind, randomized trial conducted from 2007 to 2010. Adult snorers with apneahypopnea index (AHI) <15 were included. Exclusion criteria: previous palatal surgery, BMI> 35, pharyngeal or nasal obstruction> 50% of the airway, craniofacial deformity, pregnancy, lack of room partner, allergy or severe comorbidity. IS outpatient sessions were held in the soft palate (three points), maximum of three sessions, with at least four weeks apart. Patients were randomized into two groups: 5% ethanolamine oleate (A) or 50% ethanol (B). The intensity of snoring was measured by visual-analogue scale of 10 cm (VAS). Other clinical parameters were analyzed, such as sleepiness and pain, as well as MRI and polysomnography. RESULTS: Of 22 patients enrolled in this study (A = 9 / B = 13), 19 (86.4%) showed significant reduction or disappearance of snoring. The snoring loudness (VAS) decreased in both groups: 8.0 to 3.0 in Group A (p=0.007) and 8.0 to 3.0 in Group B (p=0.001). The Epworth Sleepiness Scale decreased from 8.0 to 6.0 in Group A (p=0.05) and from 11.0 to 5.0 in Group B (p=0.005). The pain during the procedure, measured by VAS, was 4.0 in both Groups. On subsequent days, the pain was 3.5 in Group A and 2.0 in Group B, with no difference between groups. In the overall sample, the mean time to return to regular nourishing was 2.0 days and the improvement of snoring occurred in 14.0 days. There were no serious complications. Twenty-one patients had palatal ulcer, but none developed fistula. On the MRI measurements, the palatal thickness reduced from 0.9 to 0.8 cm (p=0.34), the palatal length decreased from 3.7 to 3.4 cm (p=0.02) and the palatal area decreased from 2.8 to 2.5 cm2 (p=0.29). On polysomnography, the AHI ranged from 6.9 to 5.0 in Group A (p=0.89) and from 5.2 to 6.3 in Group B (p=0.22), while the lowest O2 saturation and arousals showed no statistically significant changes. CONCLUSIONS: IS showed favorable results in the treatment of snoring, but with no difference between the groups receiving 5% ethanolamine oleate and 50% ethanol. Our own methodology reproduced the success rates of other studies, without cases of palatal fistula or severe complications. Measures by MRI showed a reduction of the palatal length after the injections. There were no changes in polysomnographic variables after the procedure

Durante a injeção intracitoplasmática de espermatozoides (ICSI) seleciona-se um espermatozoide móvel e morfologicamente normal para injeção em ovócito maduro. Evidências recentes indicam que mesmo espermatozoides aparentemente normais podem ocultar defeitos em nível molecular. O principal objetivo deste trabalho foi a descrição de um novo método capaz de selecionar espermatozoides maduros a partir de amostras não processadas em procedimento de ICSI. Em um estudo comparativo e prospectivo testou-se uma gota estendida modificada. A \"gota estendida com mecanismo contracorrente\" - GEMC foi montada em uma placa de ICSI padrão a partir de seis gotas de meio de cultivo (10 ?L). O posicionamento e união precisa das gotas deram origem a dois reservatórios e um canal, resultando em um fluxo de líquido através do canal. A adição de uma solução de PVP (polivinilpirrolidona) gerou um gradiente de viscosidade no final do circuito. Amostras seminais foram obtidas de 40 pacientes inférteis. Cada amostra seminal foi dividida em 4 alíquotas: uma alíquota para o processamento por centrifugação em gradiente de densidade (CGD), uma alíquota para a GEMC utilizando amostras não processadas, uma alíquota para a GEMC utilizando amostras processadas e uma alíquota para controle. Nos grupos GEMC uma média de 200 espermatozoides foram consecutivamente coletados, sem seleção, no reservatório de captura utilizando-se uma micropipeta de injeção como no procedimento convencional de ICSI. A morfologia espermática foi avaliada e demonstrou melhora, comparando-se com os controles, em todos os tratamentos utilizados. A imaturidade da cromatina foi avaliada utilizando-se o teste do azul de anilina. Em relação à imaturidade, 100% dos homens obtiveram melhores resultados tanto após o preparo por CGD quanto utilizando o método GEMC. Isto se refletiu em uma redução das formas imaturas de 28.65 ± 8.97% no sêmen fresco para 17.29 ± 7.72% após processamento por CGD (P < 0.01). Uma redução ainda maior nas formas imaturas foi obtida após o método GEMC quando comparado com o processamento por CGD: 0.89 ± 1.31% (P < 0.01) utilizando-se sêmen fresco e 1.05 ± 1.63% (P < 0.01) utilizando-se amostras processadas. Um novo método unindo seleção e captura de espermatozoides em um mesmo procedimento de ICSI foi descrito e testado. O método GEMC seleciona espermatozoides de forma fácil e permite o uso direto de amostras não processadas em procedimentos de ICSI. Este método seleciona espermatozoides maduros com mais eficiência do que o processamento por CGD. Novos estudos são necessários para se analisar o impacto do método nas taxas de fertilização, desenvolvimento embrionário, gravidez, implantação e abortamento / During intracytoplasmic sperm injection (ICSI) a motile spermatozoon with normal morphology is visually selected for insemination of an oocyte. Recent evidence indicates that even though the sperm appears morphologically normal, a possibility of defects at the molecular level still exists. The main objective of this work was to describe a novel approach capable of selecting mature spermatozoa from unprocessed semen sample in a one-step ICSI procedure. A modified extended drop was tested in a prospective comparative study. The \"Gota Estendida com Mecanismo Contracorrente - GEMC\" (Positive Rheotaxis Extended Drop - PRED) was assembled on a standard ICSI dish and consisted of six culture medium droplets (10 ?L). The precise merging of the drops created two reservoirs and a channel therefore the fluid flew through the channel. The addition of a PVP solution created a viscosity gradient in the final sector of the circuit. Semen samples were taken from 40 subfertile men. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), one aliquot for GEMC using fresh semen, one aliquot for GEMC using processed semen and one aliquot for the control. In GEMC a mean of 200 spermatozoa were collected consecutively, without selection, from the outlet reservoir with an injecting pipette as for conventional ICSI procedure. Sperm morphology was assessed and resulted in improvement compared to controls in all treatments. Chromatin immaturity was assessed using aniline blue assay. Regarding to chromatin immaturity, 100% of men had better results after DGC preparation and GEMC approach. This was reflected in a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC processed semen (P < 0.01). An even greater reduction was achieved after GEMC approach showing a mean of 0.89 ± 1.31% uncondensed chromatin compared to DGC processed sample (P < 0.01). A novel one-step ICSI approach joining sperm selection and recovery was developed and tested. This GEMC approach can select sperm easily and permits the direct use of native semen in ICSI. This approach can select sperm with lower chromatin immaturity than DGC method. Further studies need to access its relation to fertilization, embryo development, pregnancy, implantation and miscarriage rates

Introduction: Achilles tendinopathy can be a chronic disabling condition. Sclerosing injections under ultrasonographic guidance is one method to treat Achilles tendinopathy. Initially good results have later been questioned. Surgery is another treatment option that has been questioned because of varying reported success rate. Aim: We aimed to assess patient- reported outcome in patients suffering from Achilles tendinopathy, treated with sclerosing injections and/or surgery during a 6 ½ year- period. Method: After review of patient records, the Self-reported foot and ankle score (SEFAS) together with an in-house satisfaction questionnaire were mailed to the patients. A SEFAS score of 48 represents normal foot/ankle function. Results: 97 patients (53 women, 44 men, 104 tendons) were included. 69 patients (41 women, 28 men, 75 tendons) returned the questionnaires. The SEFAS values (median and range) were 37.5 (13-48) in patients treated with sclerosing therapy, 42 (15-48) in patients treated surgically and 47 (19-48) in patients that received both treatments. A greater proportion of surgically treated patients were satisfied (90% vs 50%), experienced symptom improvement and were able to return to the previous level of activity. Complications following surgery were wound infections (n=3) and deep vein thrombosis (n=3), two with pulmonary embolism. Following sclerosing injection, there was one complete Achilles tendon rupture. Conclusion: Sclerosing injections seems to be a safe treatment and a positive outcome in 50% of patients might be sufficient to use this therapy in selected patients with Achilles tendinopathy. However, surgical treatments seem more effective but are associated with more severe complications.

INTRODUÇÃO: O ronco acomete grande parte da população e o seu tratamento é um desafio, pois existem muitas opções terapêuticas e esta escolha deve ser individualizada. Entre vários procedimentos palatais para tratamento do ronco e da apneia do sono, a injeção roncoplástica (IR) surgiu como uma alternativa econômica para alguns casos selecionados. OBJETIVOS: Avaliar os resultados da IR no tratamento do ronco, comparando o oleato de etanolamina 5% e o etanol 50%. Além disso, descrever uma metodologia de aplicação própria e analisar seus resultados clínicos, complicações, medidas palatais por ressonância magnética (RM) e parâmetros polissonográficos. MÉTODOS: estudo clínico, duplo cego e randomizado, realizado de 2007 a 2010. Foram incluídos adultos roncadores com índice de apneia-hipopneia (IAH) <15. Critérios de exclusão: cirurgia palatal pregressa, IMC>35, obstrução nasal ou faríngea > 50% da via aérea, deformidade crânio-facial, gestação, ausência de acompanhante de quarto, alergia ou comorbidade grave. Sessões ambulatoriais de IR foram realizadas no palato mole (três pontos), máximo de três sessões, com quatro semanas de intervalo mínimo. Os pacientes foram divididos em dois grupos: um recebeu oleato de etanolamina 5% (A) e o outro, etanol 50%(B). A intensidade do ronco foi aferida por escala visual-analógica de 10cm (EVA). Foram analisados outros parâmetros clínicos, como sonolência e dor, além de RM e polissonografias. RESULTADOS: Dos 22 pacientes incluídos neste estudo (A=9 / B=13), 19 (86,4%) apresentaram diminuição importante ou desaparecimento do ronco. A intensidade de ronco (EVA) decresceu nos dois grupos: de 8,0 para 3,0 no Grupo A (p=0,007) e de 8,0 para 3,0 no Grupo B (p=0,001). A escala de sonolência de Epworth diminui de 8,0 para 6,0 no Grupo A (p=0,05) e de 11,0 para 5,0 no Grupo B (p=0,005). A dor durante o procedimento, aferida em EVA, foi de 4,0 nos dois Grupos. Nos dias subseqüentes, a dor foi de 3,5 no Grupo A e 2,0 no Grupo B, sem diferença entre os grupos. Na amostra geral, o tempo médio para retorno a alimentação foi de 2,0 dias e a melhora do ronco ocorreu em 14,0 dias. Não foram observadas complicações graves. Vinte e um pacientes apresentaram afta palatal, mas nenhum desenvolveu fístula. Das medidas realizadas por RM, a espessura palatal reduziu de 0,9 para 0,8 cm (p=0,34), o comprimento palatal diminuiu de 3,7 para 3,4 cm (p=0,02) e a área palatal foi de 2,8 para 2,5 cm2 (p=0,29). Nas polissonografias, o IAH variou de 6,9 para 5,0 no Grupo A (p=0,89) e de 5,2 para 6,3 no Grupo B (p=0,22), enquanto a saturação mínima de O2 e os microdespertares não apresentaram alterações estatisticamente significantes. CONCLUSÕES: A IR mostrou resultados favoráveis no tratamento do ronco, porém não houve diferença entre os grupos que receberam oleato de etanolamina 5% e etanol 50%. Nossa metodologia de aplicação reproduziu as taxas de sucesso de outros estudos, sem apresentar casos de fístula palatal ou complicações graves. As aferições por RM evidenciaram redução do comprimento palatal após as injeções. Não foram observadas alterações das variáveis polissonográficas após o procedimento / BACKGROUND: Snoring affects a significant portion of the population and the treatment is a challenge, because there are many options and the choice should be individualized. Among various palatal procedures for the treatment of snoring and sleep apnea, the injection snoreplasty (IS) has emerged as an economic alternative for selected cases. OBJECTIVES: To evaluate IS in the snoring treatment, comparing 5% ethanolamine oleate and 50% ethanol. Also, to describe a distinct method of injection and analyze its clinical results, complications, palatal measures by resonance imaging (MRI), and polysomnographic parameters. METHODS: Clinical, double-blind, randomized trial conducted from 2007 to 2010. Adult snorers with apneahypopnea index (AHI) <15 were included. Exclusion criteria: previous palatal surgery, BMI> 35, pharyngeal or nasal obstruction> 50% of the airway, craniofacial deformity, pregnancy, lack of room partner, allergy or severe comorbidity. IS outpatient sessions were held in the soft palate (three points), maximum of three sessions, with at least four weeks apart. Patients were randomized into two groups: 5% ethanolamine oleate (A) or 50% ethanol (B). The intensity of snoring was measured by visual-analogue scale of 10 cm (VAS). Other clinical parameters were analyzed, such as sleepiness and pain, as well as MRI and polysomnography. RESULTS: Of 22 patients enrolled in this study (A = 9 / B = 13), 19 (86.4%) showed significant reduction or disappearance of snoring. The snoring loudness (VAS) decreased in both groups: 8.0 to 3.0 in Group A (p=0.007) and 8.0 to 3.0 in Group B (p=0.001). The Epworth Sleepiness Scale decreased from 8.0 to 6.0 in Group A (p=0.05) and from 11.0 to 5.0 in Group B (p=0.005). The pain during the procedure, measured by VAS, was 4.0 in both Groups. On subsequent days, the pain was 3.5 in Group A and 2.0 in Group B, with no difference between groups. In the overall sample, the mean time to return to regular nourishing was 2.0 days and the improvement of snoring occurred in 14.0 days. There were no serious complications. Twenty-one patients had palatal ulcer, but none developed fistula. On the MRI measurements, the palatal thickness reduced from 0.9 to 0.8 cm (p=0.34), the palatal length decreased from 3.7 to 3.4 cm (p=0.02) and the palatal area decreased from 2.8 to 2.5 cm2 (p=0.29). On polysomnography, the AHI ranged from 6.9 to 5.0 in Group A (p=0.89) and from 5.2 to 6.3 in Group B (p=0.22), while the lowest O2 saturation and arousals showed no statistically significant changes. CONCLUSIONS: IS showed favorable results in the treatment of snoring, but with no difference between the groups receiving 5% ethanolamine oleate and 50% ethanol. Our own methodology reproduced the success rates of other studies, without cases of palatal fistula or severe complications. Measures by MRI showed a reduction of the palatal length after the injections. There were no changes in polysomnographic variables after the procedure

Objetivos: Fator de crescimento de hepatócito (HGF) é um polipeptídeo multifuncional, envolvido na embriogênese e regeneração tecidual, com intensa atividade antifibrótica. Os objetivos do presente estudo foram avaliar os efeitos da injeção e reinjeção do HGF coincidindo com seu pico de ação sobre a densidade de colágeno, densidade de vasos, processo inflamatório na lâmina própria e espessura média do epitélio das pregas vocais escarificadas de coelhos. Métodos: Catorze coelhos foram submetidos à injúria em ambas as pregas vocais, subdivididos em grupos 1 e 2. Nos animais do grupo 1 injetou-se HGF nas pregas vocais direitas e nos animais do grupo 2 o HGF foi injetado bilateralmente, sendo reinjetado nas pregas vocais direitas 10 dias após, coincidindo com seu pico de ação. As pregas vocais esquerdas funcionaram como controle, e as laringes foram avaliadas respectivamente aos 30 e 40 dias, através de análise histológica. Resultados: Nossos resultados demonstraram menor densidade de colágeno nas pregas vocais direitas em relação aos controles em ambos os grupos (p=0,018). Densidade de vasos foi maior nas pregas vocais direitas dos animais do grupo 2 (p=0,018); a espessura média do epitélio e o processo inflamatório avaliado na lâmina própria mostraram diferenças estatisticamente não-significantes. Conclusões: A injeção do HGF promoveu menor densidade de colágeno na lâmina própria e a reinjeção levou à menor densidade de colágeno e maior densidade de vasos em pregas vocais escarificadas de coelhos / Objectives: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays various roles in embryogenesis and tissue regeneration and exhibits marked antifibrotic activity. The present study sought to assess the effects of HGF injection and reinjection coinciding with its peak of activity on collagen density, vessel density, inflammatory reaction in the lamina propria, and mean epithelial thickness in the injured rabbit vocal fold. Methods: Fourteen rabbits were subdivided into two groups and underwent scarring of both vocal folds. Animals in group 1 received HGF injections into the right vocal fold, whereas those in group 2 received bilateral HGF injections and a single reinjection into the right vocal fold 10 days after the first, to coincide with the peak of HGF activity. The left vocal folds served as controls in both groups. Histological assessment of laryngeal specimens was performed at 30 and 40 days respectively. Results: In both groups, collagen density was lower in the right vocal folds than in the left (control) folds (p=0.018). Vessel density was higher in the right vocal folds in group 2 (p=0.018). Differences were found in mean epithelial thickness and inflammatory reaction in the lamina propria, but did not reach statistical significance. Conclusions: In the scarred rabbit vocal fold, HGF injection is associated with decreased collagen density in the lamina propria, whereas reinjection after 10 days produces decreased collagen density and higher vessel density

Objetivos: Fator de crescimento de hepatócito (HGF) é um polipeptídeo multifuncional, envolvido na embriogênese e regeneração tecidual, com intensa atividade antifibrótica. Os objetivos do presente estudo foram avaliar os efeitos da injeção e reinjeção do HGF coincidindo com seu pico de ação sobre a densidade de colágeno, densidade de vasos, processo inflamatório na lâmina própria e espessura média do epitélio das pregas vocais escarificadas de coelhos. Métodos: Catorze coelhos foram submetidos à injúria em ambas as pregas vocais, subdivididos em grupos 1 e 2. Nos animais do grupo 1 injetou-se HGF nas pregas vocais direitas e nos animais do grupo 2 o HGF foi injetado bilateralmente, sendo reinjetado nas pregas vocais direitas 10 dias após, coincidindo com seu pico de ação. As pregas vocais esquerdas funcionaram como controle, e as laringes foram avaliadas respectivamente aos 30 e 40 dias, através de análise histológica. Resultados: Nossos resultados demonstraram menor densidade de colágeno nas pregas vocais direitas em relação aos controles em ambos os grupos (p=0,018). Densidade de vasos foi maior nas pregas vocais direitas dos animais do grupo 2 (p=0,018); a espessura média do epitélio e o processo inflamatório avaliado na lâmina própria mostraram diferenças estatisticamente não-significantes. Conclusões: A injeção do HGF promoveu menor densidade de colágeno na lâmina própria e a reinjeção levou à menor densidade de colágeno e maior densidade de vasos em pregas vocais escarificadas de coelhos / Objectives: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays various roles in embryogenesis and tissue regeneration and exhibits marked antifibrotic activity. The present study sought to assess the effects of HGF injection and reinjection coinciding with its peak of activity on collagen density, vessel density, inflammatory reaction in the lamina propria, and mean epithelial thickness in the injured rabbit vocal fold. Methods: Fourteen rabbits were subdivided into two groups and underwent scarring of both vocal folds. Animals in group 1 received HGF injections into the right vocal fold, whereas those in group 2 received bilateral HGF injections and a single reinjection into the right vocal fold 10 days after the first, to coincide with the peak of HGF activity. The left vocal folds served as controls in both groups. Histological assessment of laryngeal specimens was performed at 30 and 40 days respectively. Results: In both groups, collagen density was lower in the right vocal folds than in the left (control) folds (p=0.018). Vessel density was higher in the right vocal folds in group 2 (p=0.018). Differences were found in mean epithelial thickness and inflammatory reaction in the lamina propria, but did not reach statistical significance. Conclusions: In the scarred rabbit vocal fold, HGF injection is associated with decreased collagen density in the lamina propria, whereas reinjection after 10 days produces decreased collagen density and higher vessel density

Massive amounts of 13 C-depleted carbon rapidly entered the ocean more than once during the early Paleogene, providing a geological framework for understanding future perturbations in carbon cycling, including ocean acidification. To assess the number of events and their impact on deep-sea carbonate accumulation, I have studied carbonate ooze units of the upper Paleocene-lower Eocene, which were deposited on a subsiding flank of the East Pacific Rise (ODP Site 1215). From this record several proxies were used to ascertain changes in carbonate dissolution: carbonate content, foraminiferal test fragmentation, and planktic/benthic foraminiferal ratio. Based on these analyses, 1 observe that carbonate preservation generally increased from the late Paleocene (56 Ma) through the early Eocene (51.5 Ma), after which it became poor to negligible. This trend was punctuated by four short-term intervals characterized by carbonate dissolution and pronounced negative d 18 O and d 13 C excursions. It is inferred that these were anomalously warm periods (hyperthermals) caused by massive and relative fast 13 C-depleted carbon injections. These correspond to the PETM (∼55.5 Ma), H1/ETM-2 (∼53.7 Ma), I1 (∼53.2 Ma), and K/X (∼52.5 Ma) events. I also calculated carbonate, planktic, and benthic foraminiferal mass accumulation rates for the Site 1215. These were used to comprehensively examine the history of carbonate accumulation in the equatorial Pacific Ocean throughout the early Paleogene. I deduce that in the long-term (>10 5 yr) the lysocline and calcite compensation depth (CCD) generally deepened between 55.4 and 51.5 Ma; but rapidly (≤10 5 yr) shoaled and subsequently overcompensated during and after the four intervals of massive carbon injection. Planktic foraminiferal assemblages found in the record of Site 1215 follow a predicted pattern for selective dissolution. Species of Acarinina are preferentially preserved over Morozovella, which are preferentially preserved over Subbotina, Igorina and Globanomalina. A tiny and previously overlooked species, Praetenuitella antica n.sp, is formally described in this manuscript. This species is also resistant to dissolution. The findings of this study provide firm constraints to model the short and long-term carbon cycle dynamics during the early Paleogene

Biopharmaceuticals, including proteins, DNA and vaccines, are one of the fastest growing segments of the overall pharmaceutical market. While the hypodermic injection, the most common delivery method for these molecules, is effective, it also has limitations, including low patient compliance, need for medically trained personnel and biohazardous sharps after delivery. The overall goal of this thesis was to develop a new delivery system for biopharmaceuticals, based on dissolving polymer microneedles, which is effective and more patient compliant than the hypodermic needle. Microneedles are microscopic needles that are large enough to insert into the skin to deliver drugs effectively, while being short enough to avoid the pain causing nerves deep in the skin. An additional benefit of polymer microneedles is that the needles completely dissolve in the skin, leaving behind no biohazardous sharps. There are significant material and fabrication issues that must be overcome in the development of this new device. The first part of this thesis focused on the development of a new fabrication process, based on in situ photopolymerization, for the creation of polymer microneedles. These microneedles were shown to successfully insert into the skin, dissolving within a minute to deliver the encapsulated cargo, and retain full activity of encapsulated proteins. Next, we applied the microneedle technology to the delivery of the influenza virus. We found that the reformulation process required to encapsulate the influenza virus in polymer microneedles did not affect the antigenicity or immunogenicity of the virus. In addition, we used coated metal microneedles to successfully immunize mice with the influenza virus, verifying the delivery capabilities of a microneedle system. Finally, we used the dissolving polymer microneedles to successfully immunize mice with the influenza virus, resulting in full protection against lethal challenge after one immunization. This immune response was equivalent to the control intramuscular injection. In conclusion, we have developed dissolving polymer microneedles as an effective and patient compliant delivery system for biopharmaceuticals. This system could be especially applicable to mass immunization efforts or home use, since it can be self-administered and allows for easy disposal with no biohazardous sharps.