Doctorat en sciences médicales / info:eu-repo/semantics/nonPublished

Essential hypertension (EH) is a risk factor for many cardiovascular disorders. Treatment of established EH, especially for prolonged control of this pathogenic process, represents a great challenge. Moreover, hypertension is considered an important risk factor for the development of many other diseases, e.g. erectile dysfunction. <p> Hemin and other heme derivatives, e.g. heme-L-lysinate (HLL) and heme-L-arginate, have been used extensively to upregulate expression of heme oxygenase (HO) and production of endogenous carbon monoxide (CO). Short-term hemin administration for 4-5 days has been shown to markedly decrease high blood pressure (BP) in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) or Sprague Dawley (SD) rats. This short-term therapy was effective in treating young, but not adult SHR. In the present study, hemin (15 mg/kg/day) was administered to 12-week old adult SHR through subcutaneously implanted osmotic minipumps for 3 consecutive weeks (the hemin protocol). Into the second week of the hemin protocol, BP of SHR was normalized from 203.2 ± 2.5 to 123.4 ±1.9 mmHg (n=20, p<0.001). There was no further decrease of BP in the remaining days of the hemin protocol. Normalization of BP in these treated SHR was maintained for 9 months after the removal of hemin pumps. <p>To further investigate the metabolic characteristics of hemin during hemin protocol administration, we attempted to monitor circulatory heme levels. A valid standard calibration curve was established using hemin or HLL in <i>in vitro</i> experiments. It was established that the basal serum level of heme was negligible in all rat strains prior to hemin protocol initiation. During the hemin protocol, serum heme level of all rats was significantly elevated; however, it quickly dropped to basal levels thereafter. <p>At the end of the 3-week hemin protocol, HO-1 expression, HO activity, soluble guanylyl cyclase (sGC) expression, and cyclic guanosine monophosphate (cGMP) content were all increased, but phosphodiesterase-5 (PDE-5) expression was down-regulated in the mesenteric arteries. The hemin protocol also reversed SHRs decreased arterial lumen size, and increased expression levels of vascular endothelial growth factor. These changes lasted 9 months after the hemin protocol. The hemin protocol did not cause hepatic or renal toxicity. Our study thus unmasks a novel hemin protocol that will not only normalize BP in SHR with established hypertension but, more importantly, also provide long-lasting anti-hypertension protection. Sustained upregulation of the HO-regulated signaling pathways and reversal of vascular remodeling in small peripheral vessels in treated SHR are among potential underlying mechanisms for the anti-hypertensive effect of the hemin protocol.<p>We further studied if the beneficial effects of hemin protocol on BP of SHR could be extended to improvement of their penile erection. Intracavernosal pressure changes after electrical stimulation of the cavernous nerve (CN) were monitored in adult SHR and age-matched normotensive SD rats after administration of either hemin or hydralazine. Expression levels of HO-1, HO-2, sGC, and PDE-5 in penile tissues were also examined. Frequency-dependent intracavernosal pressure (ICP) changes were reduced in adult SHR. Three weeks after hemin treatment, ICP responses to CN stimulations were significantly increased to the level of normotensive rats, which was linked to normalization of BP of hemin-treated SHR. Hydralazine-treated SHR experienced normalization of BP but not ICP after 3 weeks of treatment. Expression of HO-1 and sGC was upregulated and that of PDE-5 downregulated in hemin-treated SHR. Decreased ICP response in adult SHR can be improved through chronic hemin treatment of SHR. Prolonged upregulation of HO-1 and sGC as well as lowered expression of PDE-5 may account for normalization of erectile dysfunction in SHR subsequent to hemin treatment. <p>This thesis reports for the first time that 21-day hemin administration led to a 9-month normalization of high BP of adult SHR. These effects were mediated through sustained stimulation of the HO/CO system and its downstream effectors targets. Increased activity of HO-1 led to normalization of the abnormally high expression level of VEGF in peripheral mesenteric arteries of adult SHR. Subsequently, this resulted in reversal of the eutrophic remodeling of these arteries, which seems to be the priniciple determinant of the long-term normalization of BP observed for 9 months after stoppage of hemin treatment. The invention of hemin protocol offers a new therapeutic approach for the clinical management of established hypertension for a long duration.<p>Our study, for the first time, correlated changes in serum heme levels with BP levels after injection of hemin or HLL in normotensive and hypertensive rats. Application of this heme monitoring technology will also pave the way for clinical application of hemin therapy in treatment of EH.<p> Another intriguing finding in this thesis is that upregulation of HO-1, through the hemin protocol, led to improvement of abnormally low ICP encountered in adult SHR. Upregulation of HO-1 may represent a novel therapeutic approach to treat hypertension-related erectile dysfunction.

Essential hypertension (EH) is a risk factor for many cardiovascular disorders. Treatment of established EH, especially for prolonged control of this pathogenic process, represents a great challenge. Moreover, hypertension is considered an important risk factor for the development of many other diseases, e.g. erectile dysfunction. <p> Hemin and other heme derivatives, e.g. heme-L-lysinate (HLL) and heme-L-arginate, have been used extensively to upregulate expression of heme oxygenase (HO) and production of endogenous carbon monoxide (CO). Short-term hemin administration for 4-5 days has been shown to markedly decrease high blood pressure (BP) in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) or Sprague Dawley (SD) rats. This short-term therapy was effective in treating young, but not adult SHR. In the present study, hemin (15 mg/kg/day) was administered to 12-week old adult SHR through subcutaneously implanted osmotic minipumps for 3 consecutive weeks (the hemin protocol). Into the second week of the hemin protocol, BP of SHR was normalized from 203.2 ± 2.5 to 123.4 ±1.9 mmHg (n=20, p<0.001). There was no further decrease of BP in the remaining days of the hemin protocol. Normalization of BP in these treated SHR was maintained for 9 months after the removal of hemin pumps. <p>To further investigate the metabolic characteristics of hemin during hemin protocol administration, we attempted to monitor circulatory heme levels. A valid standard calibration curve was established using hemin or HLL in <i>in vitro</i> experiments. It was established that the basal serum level of heme was negligible in all rat strains prior to hemin protocol initiation. During the hemin protocol, serum heme level of all rats was significantly elevated; however, it quickly dropped to basal levels thereafter. <p>At the end of the 3-week hemin protocol, HO-1 expression, HO activity, soluble guanylyl cyclase (sGC) expression, and cyclic guanosine monophosphate (cGMP) content were all increased, but phosphodiesterase-5 (PDE-5) expression was down-regulated in the mesenteric arteries. The hemin protocol also reversed SHRs decreased arterial lumen size, and increased expression levels of vascular endothelial growth factor. These changes lasted 9 months after the hemin protocol. The hemin protocol did not cause hepatic or renal toxicity. Our study thus unmasks a novel hemin protocol that will not only normalize BP in SHR with established hypertension but, more importantly, also provide long-lasting anti-hypertension protection. Sustained upregulation of the HO-regulated signaling pathways and reversal of vascular remodeling in small peripheral vessels in treated SHR are among potential underlying mechanisms for the anti-hypertensive effect of the hemin protocol.<p>We further studied if the beneficial effects of hemin protocol on BP of SHR could be extended to improvement of their penile erection. Intracavernosal pressure changes after electrical stimulation of the cavernous nerve (CN) were monitored in adult SHR and age-matched normotensive SD rats after administration of either hemin or hydralazine. Expression levels of HO-1, HO-2, sGC, and PDE-5 in penile tissues were also examined. Frequency-dependent intracavernosal pressure (ICP) changes were reduced in adult SHR. Three weeks after hemin treatment, ICP responses to CN stimulations were significantly increased to the level of normotensive rats, which was linked to normalization of BP of hemin-treated SHR. Hydralazine-treated SHR experienced normalization of BP but not ICP after 3 weeks of treatment. Expression of HO-1 and sGC was upregulated and that of PDE-5 downregulated in hemin-treated SHR. Decreased ICP response in adult SHR can be improved through chronic hemin treatment of SHR. Prolonged upregulation of HO-1 and sGC as well as lowered expression of PDE-5 may account for normalization of erectile dysfunction in SHR subsequent to hemin treatment. <p>This thesis reports for the first time that 21-day hemin administration led to a 9-month normalization of high BP of adult SHR. These effects were mediated through sustained stimulation of the HO/CO system and its downstream effectors targets. Increased activity of HO-1 led to normalization of the abnormally high expression level of VEGF in peripheral mesenteric arteries of adult SHR. Subsequently, this resulted in reversal of the eutrophic remodeling of these arteries, which seems to be the priniciple determinant of the long-term normalization of BP observed for 9 months after stoppage of hemin treatment. The invention of hemin protocol offers a new therapeutic approach for the clinical management of established hypertension for a long duration.<p>Our study, for the first time, correlated changes in serum heme levels with BP levels after injection of hemin or HLL in normotensive and hypertensive rats. Application of this heme monitoring technology will also pave the way for clinical application of hemin therapy in treatment of EH.<p> Another intriguing finding in this thesis is that upregulation of HO-1, through the hemin protocol, led to improvement of abnormally low ICP encountered in adult SHR. Upregulation of HO-1 may represent a novel therapeutic approach to treat hypertension-related erectile dysfunction.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2002 / Typescript (photocopy)

Visuals play an important role in the healthcare field; students learning anatomy and physiology, patient education materials, and public infographics all rely on the effective communication of textual material in graphic form. The goal of this thesis is to contribute visual material that takes the form of signaling pathways and comparison of different disorder states as material for use in the university setting. In order to produce reliable visuals, a literature review was completed.

The increased depth of castellated beams presents stability problems, specifically during erection. During erection the castellated beam must support the weight of an erector and self-weight until the continuous bracing of the floor deck is in place. The stability of the unbraced member is based on its resistance to lateral-torsional buckling. The cross-sectional properties that are related to lateral-torsional buckling, such as out-of-plane bending, warping constant, and torsional constant were calculated using three different approaches to model the unique geometry of castellated beams. These properties were used in various lateral-torsional buckling solutions to determine which procedure should be used to check for this mode of failure. Two specimens were tested to evaluate the results of the analytical unbraced length determination process. The tests results were used to better model the contribution of the web-to-column flange double angle connection on the stability of the castellated beam. / Master of Science

A busca por melhorias de produtividade na indústria da construção civil é fundamental para garantia do crescimento sustentável do setor. Nesse sentido, o uso de estruturas de aço na construção de edifícios aparece como uma alternativa interessante às tradicionais estruturas em concreto armado. Essa dissertação tem por objetivo o estudo da produtividade da mão de obra e de equipamentos de içamento na montagem de estruturas de aço para edifícios de múltiplos pavimentos, buscando comprovar a hipótese de que essa produtividade varia em conjunto com alguns fatores que podem ser identificados e que essa variação pode ser quantificada. A pesquisa foi realizada segundo metodologia de Estudo de Caso, sendo que cinco obras compuseram o estudo. Como resultados, observa-se que produtividade potencial da mão de obra variou entre 3,33 e 8,23 Hh/peça ou 11,8 e 33,8 Hh/t e que a produtividade potencial dos equipamentos variou entre 0,38 e 0,53 Eqh/peça ou 1,84 e 2,29 Eqh/t, além de terem se encontrado correlações significativas entre os fatores tonelada/peça, disponibilidade do equipamento de içamento e quantidade relativa de pilares e os indicadores de produtividade. / The search for productivity gains in the construction industry is critical to ensure the sustainable growth of the sector. The use of steel structures for buildings appears as an interesting alternative to the traditional concrete structures. This research aims to study labor productivity and lifting equipments productivity in the erection of steel structures for multistory buildings, trying to prove the hypothesis that productivity indicators are correlated with some identifiable factors and that its variation can be quantified. The research was conducted as a Case Study, in which five construction sites were considered. As a result, it was observed that labor productivity ranged between 3,33 and 8,23 man-hour/piece or 11,8 and 33,8 man-hour/t, and that the equipments productivity ranged between 0,38 and 0,53 equipment-hour/piece or 1,84 and 2,29 equipment-hour/t, and it was found significant correlations between the factors tons per piece, equipment availability and relative number of columns and the productivity indicators.

There has been full of inefficiency and waste in current operation method of steel structure industries. This study hopes to utilize Toyota Just-in-time Production System for fabrication of steel structure to eliminate current each waste during the production process. The main purpose of this study is take case company as an example to discuss the following respects: 1.The current production process of steel structure industries. 2.The application of Toyota Just-in-time Production System in the steel structure fabrication. This study first introduces the framework of Toyota Just-in-time Production System to apprehend its spirit and then explains the concept and advantage of Toyota Just-in-time Production System explicitly. Also, this study compares Toyota Just-in-time Production System with current production method of steel structure industries. Second, according to the glancing of related document reference, this study discusses the application method and its profit for Toyota Just-in-time Production System in the manufacturing industries. As there are significant differences in structure or operation method between steel structure industries and manufacturing industries, thus this study utilizes gradual erection plan to match Toyota Just-in-time Production System during the period of fabrication process plan to eliminate the distinction between these two industries besides explaining the necessary rationalized operation when leading Toyota Just-in-time Production System in. Having visited the production line and made mutual communication with operation chief, this study has found the current problems existing in production management in case company. According to this discovery, this study uses bridge production line and built-up H section production line as pilot implementation to discuss the possible question and solution policy for Toyota Just-in-time Production System concept applied in steel structure fabrication so as to frame the procedures and criterion of Toyota Just-in-time Production System in fabrication of steel structure and also to evaluate its profit.

The majority of a bridge designer’s time is spent ensuring strength and serviceability limit states are satisfied for the completed structure under various dead and live loads. Anecdotally, the profession has done an admirable job designing safe bridges, but engineering the construction process by which bridges get built plays a lesser role in the design offices. The result of this oversight is the complete collapse of a few large bridges as well as numerous other serviceability failures during construction. According to the available literature there have been only a few attempts to monitor a full-scale bridge in the field during the entire construction process. Another challenge for engineers is the lack of analysis tools available which predict the behavior of the bridge during the intermediate construction phases. During construction, partial bracing is present and the boundary conditions can vary significantly from the final bridge configuration. The challenge is magnified for complex bridge geometries such as curved bridges or bridges with skewed supports. To address some of the concerns facing engineers a three span curved steel I-girder bridge was monitored throughout the entire construction process. Field studies collected data on the girder lifting behavior, partially constructed behavior, and concrete deck placement behavior. Additional analytical studies followed using the field measurements to verify the finite element models. Finally, conclusions drawn from the physical and analytical testing were utilized to derive equations that predicted behavior, and analysis tools were developed to provide engineers with solutions to a wide range of construction related problems. This dissertation describes the development of two design tools, UT Lift and UT Bridge. UT Lift is a macro-enabled Excel spreadsheet that predicts the behavior of curved I-girders during lifting. The derivation of the equations necessary to accomplish these calculations and the implementation are described in this dissertation. UT Bridge is a PC-based, user-friendly, 3-D finite element program for I-girder bridges. The basic design philosophy of UT Bridge aims to allow an engineer to take the information readily available in a set of bridge drawings and easily input the necessary information into the program. A straight or curved I-girder bridge with any number of girders or spans can then be analyzed with a robust finite element analysis for either the erection sequence or the concrete deck placement. The development of UT Bridge as well as the necessary element formulations is provided in this dissertation. / text

Orientador: Edson Antunes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade ce Ciencias Medicas / Made available in DSpace on 2018-08-13T10:46:39Z (GMT). No. of bitstreams: 1 Pena_ClesioBorges_M.pdf: 779579 bytes, checksum: aeca20777087c88ff1ca05b3acc4316c (MD5) Previous issue date: 2009 / Resumo: A ereção peniana envolve a interação da estimulação neural do músculo liso do corpo cavernoso bem como liberação neuro-humoral de fatores contráteis e relaxantes do endotélio. A cascata de sinalização óxido nítrico (NO)/(GMPc) é o evento mais importante e efetivo no mecanismo de ereção peniana. Nesta última década, diversos inibidores de fosfodiesterase tipo 5 (PDE5) foram desenvolvidos e aprovados para o tratamento da disfunção erétil. Estes fármacos atuam inibindo a ação da PDE5 sobre o GMPc, que modula respostas fisiológicas em vários tecidos, como o relaxamento do músculo liso do corpo cavernoso. Dentre os inibidores de PDE5, são atualmente comercializados o sildenafil, tadalafil, vardenafil e o carbonato de lodenafil, sendo este último sintetizado no Brasil. Os objetivos deste trabalho foram: 1. Avaliar a eficácia do carbonato de lodenafil na função erétil de ratos, usando a técnica de pressão intracavernosa (ICP); 2. Avaliar o possível sinergismo entre o treinamento físico e o inibidor de PDE5 carbonato de lodenafil; e 3. Avaliar o efeito do carbonato de lodenafil, isoladamente, ou em associação com o treinamento físico na ICP de ratos submetidos (ou não) ao tratamento crônico com L-NAME. Ratos Wistar machos foram anestesiados com uretana (1,2 g/ Kg) por via intraperitonial. A seguir foi realizada uma traqueostomia para facilitar a respiração do animal, e a artéria carótida foi canulada para o monitoramento contínuo da pressão arterial média (MAP). Uma cânula provida de agulha foi inserida no corpo cavernoso esquerdo para registro da ICP, usando-se transdutores de pressão. A cavidade abdominal foi aberta expondo o nervo cavernoso esquerdo, localizado na região dorso-lateral da próstata. Um eletrodo bipolar de platina conectado a um estimulador foi posicionado sobre o nervo cavernoso. Estimulações elétricas do nervo cavernoso (pulso de 1 ms, 45 s, 6 V) a diferentes freqüências (2, 4, 6, 8 e 10 Hz) foram aplicadas. As alterações de pressão foram registradas em sistema PowerLab de aquisição de dados. A administração da droga foi realizada pela veia jugular. O treinamento físico teve duração de oito semanas, em sessões de uma hora por dia, cinco dias por semana. O grupo que recebeu L-NAME fez um treinamento físico preventivo de quatro semanas, e no início da quinta semana o L-NAME passou a ser administrado na dose aproximada de 10 mg/rato/dia, durante 4 semanas. Observamos que o treinamento físico em animais normotensos não alterou a pressão arterial média nem a pressão intracavernosa. O tratamento crônico com L-NAME aumentou a pressão arterial média nos animais sedentários. No entanto, este aumento foi atenuado nos animais submetidos ao treinamento físico. O L-NAME aboliu a resposta erétil (valores de ICP) nos animais sedentários. O treinamento físico não foi capaz de prevenir ou atenuar a queda da pressão intracavernosa induzida pelo L-NAME. O carbonato de lodenafil se mostrou eficaz em promover aumento da pressão intracavernosa tanto em animais sedentários bem como em treinados, no entanto, não houve sinergismo entre o treinamento físico e o carbonato de lodenafil. Adicionalmente, a associação entre treinamento físico e carbonato de lodenafil não foi eficaz em restaurar os valores de ICP em animais tratados com L-NAME. / Abstract: Penile erection involves an interaction between neural stimulation of the corpus cavernosum smooth muscle and neurohumoral contractile and relaxing factors released from the endothelium. The nitric oxide (NO)/cGMP pathway is the most important and effective mechanism of penile erection. In the last decade, phosphodiesterase 5 (PDE5) inhibitors were developed and approved for treating erectile dysfunction. These compounds inhibit the PDE5, which deactivates the cGMP, responsible by several physiological responses in many tissues, such as the relaxation of the corpus cavernosum smooth muscle. To date, 4 PDE5 inhibitors are commercially available, sildenafil, tadalafil, vardenafil and lodenafil carbonate, the last one being synthesized in Brazil. The aim of this work was: 1) to evaluate the efficacy of lodenafil carbonate in rat erectile function, measured by the intracavernous pressure (ICP); 2) to evaluate whether the erectile responses of lodenafil carbonate are potentiated in exercised rats; and 3) to evaluate the effects of lodenafil carbonate, only, or associated to physical exercise in the ICP, in rats submitted (or not) to chronic treatment with L-NAME. Male Wistar rats were anesthetized with urethane (1.2 g/Kg, i.p.). It was performed a tracheotomy to allow the animal to breath, and the carotid artery was cannulated to continuously measure the mean arterial pressure (MAP). A needle coupled to a cannula was inserted in the left corpus cavernosum to measure ICP. The abdominal cavity was open and the cavernous nerve was exposed. A platinum bipolar electrode was placed on the cavernous nerve and connected to an electric stimulator. Electrical field stimulation of the cavernous nerve (pulses of 1 ms, 45 s, 6 V) under different frequencies (2, 4, 6, 8 e 10 Hz) were applied. Changes in the MAP and ICP were registered in a Powerlab¿ data acquisition system. Drugs were administered via jugular vein. The physical training program consisted in 60 min/day of running, 5 days/week and lasted eight weeks. In the group exercised which received L-NAME (10 mg/rat/day), LNAME administration started after the fourth week of training, during 4 weeks further. We observed that the physical training did not alter MAP and ICP in normotensive rats. Chronic L-NAME administration increased the MAP in sedentary rats. However, this increase was attenuated in trained rats. L-NAME administration blunted the increase in the ICP in sedentary rats and exercise was not able to prevent or attenuate this decrease in the ICP induced by L-NAME. Lodenafil carbonate was efficient in promote an increase in the ICP in both sedentary and trained animal. However, there was no synergism between lodenafil carbonate and exercise in producing increase in the ICP. Additionally, association between exercise and lodenafil carbonate was not able to restore the ICP in L-NAMEtreated animal. / Mestrado / Mestre em Farmacologia