Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The oxidative stress is envolved in several diseases, including neurological diseases. Centella asiatica is a medicinal plant which was has long been used to treat neurological disturbances in Ayurvedic medicine. The aim of this study was to evaluate the antioxidant potencial of different extracts of C.asiatica in vitro. Were quantified by High Performance Liquid Chromatograph (HPLC) the present compounds and examined the phenolic content of the infusion and fractions: ethyl acetate, n-butanol and dichlorometane. Furthermore, the ability of C.asiatica extracts as scavenger of DPPH., as well as, the antioxidant capacity it was analyzed, through the reduction of molybdenum (VI)(Mo6+) to molybidenum (V)(Mo5+). Finally, we determined the effect of the extracts on lipid peroxidation induced by quinolinic acid (QA) and sodium nitroprusside (SNP) in different regions of the rat brain (cerebral cortex, striatum and hippocampus). HPLC analysis showed that flavonoids, triterpene glycosides, tannins and phenolic acids were present in extracts of C.asiatica. The content of phenolic compounds showed that the ethyl acetate fraction is rich in these compounds, followed by dichloromethane fraction of butanol and of infusion. Moreover, with the first analyzes it was also found a higher antioxidant potential of ethyl acetate fraction as DPPH. radical scavenger. In agreement with in vitro assays, the ethyl acetate fraction showed the highest antioxidant effect by decreasing lipid peroxidation induced by AQ in cerebral cortex (IC50 = 11.82), striatum (IC50 = 13.91) and hippocampus (IC50 = 13. 55) from rat brain. However, when the pro-oxidant agent was NPS, potency of infusion, the ethyl acetate fraction and dichloromethane were not significantly different to the cortex and hippocampus, which highlighted a greater difference of action in the striatum between the infusion (IC50 = 16.12), the ethyl acetate (IC50 = 13.57) and dichloromethane (IC50 = 11.05) regarding the butanol fraction (IC50 = 47.94). In conclusion, the results demonstrated that the infusion of C.asiatica and other fractions exhibit antioxidant capacity in vitro, which is related to their phytochemical content. Thus, the therapeutic potential in neurological diseases of C. asiatica, could be associated with its antioxidant activity. / O estresse oxidativo está envolvido em várias patologias incluindo as doenças neurológicas. A Centella asiática é uma planta medicinal que tem sido muito utilizada para o tratamento de distúrbios neurológicos na medicina Ayurvédica. O objetivo do presente estudo foi avaliar o potencial antioxidante de diferentes extratos de C. asiática in vitro. Foi quantificado por cromatografia líquida de alta eficiência (CLAE) o conteúdo fenólico da infusão e das frações: acetato de etila, n-butanólica e diclorometano. Além disso, analisou-se a capacidade dos extratos de C. asiática como scavenger do radical DPPH., bem como, a capacidade antioxidante total através da redução do molibdênio (VI) (Mo6 +) a molibdênio (V) (Mo5 +). Finalmente, determinou-se o efeito dos extratos na peroxidação lipídica induzida por ácido quinolínico (AQ) e nitroprussiato de sódio (NPS), em diferentes regiões do cérebro de rato (córtex, estriado e hipocampo). A análise por CLAE revelou que flavonóides, glicosídeo triterpeno, taninos e ácidos fenólicos estavam presentes nos extratos de C. asiática. O teor de compostos fenólicos demonstrou que a fração acetato de etila é rica nestes compostos, seguida da fração diclorometano, da n-butanólica e por fim da infusão. Além disso, com as primeiras análises também verificamos um maior potencial antioxidante da fração acetato de etila como scavenger de radical DPPH.. Em acordo com as análises in vitro, a fração acetato de etila apresentou o maior efeito antioxidante através da diminuição da peroxidação lipídica induzidas por AQ em córtex (IC50=11,82), estriado (IC50=13,91) e hipocampo (IC50=13,55) de cérebro de rato. Por outro lado, quando o agente pró-oxidante foi NPS, a potência de infusão, das frações de acetato de etila e diclorometano não foram diferentes significativamente para córtex e hipocampo, sendo destacada uma maior diferença de ação no estriado, entre a infusão (IC50=16,12), a acetato de etila (IC50= 13,57) e a diclorometano (IC50= 11,05) em realção a fração butanólica (IC50 = 47,94). Em conclusão, os resultados encontrados demonstraram que a infusão e demais frações de C. asiática apresentam capacidade antioxidante in vitro, a qual está relacionada ao seu conteúdo fitoquímico. Assim, o potencial terapêutico de C. asiática em doenças neurológicas, poderia ser associado com a sua atividade antioxidante.

Made available in DSpace on 2015-03-26T13:40:03Z (GMT). No. of bitstreams: 1 texto completo.pdf: 532553 bytes, checksum: afb4fdf0d2eec084cc5b732167b89c7d (MD5) Previous issue date: 2014-02-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Seeds frequently encounter biotic and abiotic stress that adversely affects growth, development, or productivity. The objective of this work was to investigate the effect of nitric oxide (NO) like protective agent in sesame seeds submitted to different stresses. Therefore, two experiments were conducted. In the first one, sesame seeds were placed in soaked substrate with water or with different concentrations of cadmium chloride and cadmium chloride plus sodium nitroprusside (SNP) in the following treatments: 1) water (control), 2) +200 μM of SNP, 3) 800 μM of CdCl2, 4) 800 μM of CdCl2 +200 μM of SNP, 5) 600 μM of CdCl2, 6) 600 μM of CdCl2 +200 μM of SNP, 7) 400 μM of CdCl2 and 8) 400 μM of CdCl2 +200 μM of SNP. Were done the following determinations: germination (G), first count of germination (PC), speed germination index (IVG), hipocotyl length (CH), radicle length (CR), dry mass of hipocotyl (MSH) and dry mass of radicle (DMR) and imbibition curve. It were quantified the activity of antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and total peroxidase (POX). It was adopted the completely randomized design with five replicates. The data were submitted to variance analysis and the means obtained for treatments were compared by Tukey test at 5% of significance. The means obtained in treatments with and without SNP were compared by F test at 5% and the times of imbibition by Tukey test at 5%. For the realization of imbibition curve was realized a polynomial regression fit 3. In the second experiment, sesame seeds were placed in soaked substrate with water or with different concentrations of PEG 6000 and PEG 6000 plus SNP in the following treatments: 1) water (control), 2) +200 μM of SNP, 3) 0,1MPa, 4) -0,1MPa +200 μM of SNP, 5) - 0,2MPa, 6) -0,2MPa +200 μM of SNP, 7) -0,3MPa and 8) -0,3MPa, +200 μM of SNP. The same determinations done in experiment one, was made in the experiment two. Both stress caused the reduction of germination and vigor, being the highest concentrations, the most harmful to sesame seeds. NO was able to minimize the damage caused by the stresses, reversing partially all the biochemical parameters evaluated, what provides higher and faster germination, beyond the higher initial development of xiii seedlings. Cadmium and PEG 6000 provoked less absorption and less gain of mass in higher concentrations in relation to water, and an extension of Phase II. In relation to the antioxydative system, there was an increaseof enzymatic activity in period of 0 to 24 houras, showing the organization of the antioxidant system with the sesame seeds over time. Was observed that in higher potentials and in solutions more concentrated, the activity enzymatic was higher, what suggest detoxifying activity of these molecules in seeds submitted to water deficit and solution of cadmium more strict. The use of SNP, increased the activity of antioxidative enzymes, evidencing an efficient of elimination of EROs formed. / Sementes estão frequentemente expostas a diversos estresses bióticos e abióticos que prejudicam o seu crescimento, desenvolvimento e produtividade. O objetivo desse trabalho foi investigar o efeito do óxido nítrico (ON) como agente protetor em sementes de gergelim (Sesamum indicum L.) submetidas à diferentes estresses. Para tanto, foram conduzidos dois experimentos. No primeiro, as sementes foram semeadas em substrato umedecido com água ou com diferentes concentrações de cloreto de cádmio (CdCl2) e cloreto de cádmio acrescido de nitroprussiato de sódio (SNP) nos seguintes tratamentos: 1) água (controle), 2) +200 μM de SNP, 3) 800 μM de CdCl2, 4) 800 μM de CdCl2 +200 μM de SNP, 5) 600 μM de CdCl2, 6) 600 μM de CdCl2 +200 μM de SNP, 7) 400 μM de CdCl2 e 8) 400 μM de CdCl2 +200 μM de SNP. As seguintes determinações foram feitas: germinação (G), primeira contagem de germinação (PC), índice de velocidade de germinação (IVG), comprimento de hipocótilo (CH) e radícula (CR), massa seca de hipocótilo (MSH) e radícula (MSR), curva de embebiçao, além da quantificação da atividade das enzimas antioxidativas, superóxido dismutase (SOD), catalase (CAT), ascorbato peroxidase (APX) e peroxidases totais (POX). O delineamento estatístico utilizado foi o inteiramente casualizado com cinco repetições. Os dados foram submetidos à análise de variância (ANOVA) e as médias obtidas para os tratamentos foram comparadas pelo teste Tukey a 5% de significância. As médias obtidas nos tratamentos com e sem SNP foram comparadas pelo teste F a 5% de significância e os tempos de embebição na análise das atividades das enzimas, também pelo teste Tukey a 5%. Para a realização da curva de embebição realizou-se regressão com ajuste polinomial de grau 3. No segundo experimento, as sementes de gergelim foram semeadas em substrato umedecido com água ou em diferentes concentrações de polietileno glicol (PEG 6000) e PEG 6000 acrescido de SNP nos seguintes tratamentos: 1) água (controle), 2) +200 μM de SNP, 3) 0,1Mpa, 4) -0,1MPa +200 μM de SNP, 5) - 0,2MPa, 6) -0,2MPa +200 μM de SNP, -7) 0,3MPa e 8) -0,3MPa, +200 μM de SNP. As mesmas determinações e análises estatísticas do primeiro experimento foram realizadas. Conclui-se que ambos os estresses causaram a redução da germinação e do vigor, sendo Xi as maiores concentrações as mais prejudiciais às sementes de gergelim. O ON foi capaz de amenizar os danos causados pelos estresses invertendo parcialmente todos os parâmetros fisiológicos avaliados, o que proporcionou maior e mais rápida germinação além de maior desenvolvimento inicial das plântulas. O cádmio e o PEG 6000 provocaram menor absorção e menor ganho de massa nas maiores concentrações em relação à água assim como um prolongamento da Fase II da embebição. Em relação ao sistema antioxidante, houve aumento da atividade enzimática no período de 0 a 24 horas, demonstrando organização do sistema antioxidante nas sementes de gergelim com o decorrer do tempo. Observou-se que nos maiores potenciais e nas soluções mais concentradas, a atividade enzimática foi maior, o que sugere atividade desintoxicante dessas moléculas em sementes submetidas ao déficit hídrico e solução de cádmio mais rigorosa. O uso do SNP, de maneira geral, aumentou a atividade das enzimas antioxidantes, evidenciando um eficiente sistema de eliminação das espécies reativas de oxigênio formadas.

<p>Balans redoks potencijala u živoj ćeliji predstavlja imperativ održavanja zdravog fenotipa, i u&nbsp;krajnjem, njenog preživljavanja. Nitrozativni stres može ozbiljno naru&scaron;iti ćelijsku redoks&nbsp;homeostazu i, u kombinaciji sa oksidativnim stresom, uticati na ćelijsku proliferaciju i&nbsp;diferencijaciju, a u nekim slučajevima i na aktivaciju maligne transformacije&nbsp;U ovom radu ispitivani su efekti donora NO natrijum-nitroprusida na dve ćelijske linije u&nbsp;kulturi: transformisane&nbsp; ćelije mi&scaron;ijih fibroblasta (L929) i maligne&nbsp; ćelije humane&nbsp;eritroleukemije (K562). Natrijum- nitroprusid (SNP) je fotoreativan molekul sa veoma&nbsp;kratkim poluživotom koji izaziva koncentraciono - zavisnu proliferaciju ili inhibiciju<br />ćelijskog rasta in vitro.NO izaziva različite efekte u zavisnosti od eksperimentalnog modela,&nbsp;svoje relativne koncentracije kao i okruženja u kojem nastaje. Ispitivanja mogućnosti direktne&nbsp;transformacije azot oksida u redoks aktivne vrste kao &scaron;to su nitrozonijum katjon (NO⁺) i&nbsp;nitroksil anjon (NO^-/HNO) i direktni efekti tih redoks potomaka u ćeliji tek su u začetku. U&nbsp;na&scaron;im eksperimentima, kori&scaron;ćenjem donora NO - natrijum nitroprusida (SNP) i dve vrste&nbsp;superoksid dismutaza, CuZn-SOD i Mn-SOD, stvorili smo uslove generisanja vi&scaron;e vrsta&nbsp;signalnih molekula i ispitali odgovor transfomisanih (L929) i malignih (K562) ćelija na njih.&nbsp;Rezultati eksperimenata pokazuju da izabrani parametri (količina slobodnih tiolnih grupa i&nbsp;glutationa) mogu biti relevantni za praćenje efekata egzogenog azot oksida i njegovih redoks&nbsp;potomaka kod različitih, transformisanih i malignih ćelijskih linija.</p> / <p>The redox potential balance in the living cell isthe imperative of continuation of healthy phenotype, and subsequently of its survival. Nitrosative stress may seriously damage cell&#39;s redox homeostasis, and in combination with oxidative stress may influence cell proliferation and differentiation, in some cases even activation of malignant transformation. This paper investigates effects of sodium nitroprusside as&nbsp; NO donor on two cell lines in culture: transformed cells of mice fibroblasts (L929) and malignant cells of human eritroleukemia (K562). The sodium nitroprusside(SNP)&nbsp; is a photo reactive molecule with very short half-life, causing concentration- dependant proliferation or inhibition of cell growth in vitro.The NO causes different effects depending on experimental model, its relative concentration and environment&nbsp; where it is formed. Investigations of possibility of direct transformation from nitrogen oxide to redox-active species as nitrosonium cation (NO+) and nitroxyl anion (NO &minus;/HNO), as well as direct effects ofthose redox descendants within the cell are only in beginning. In our experiments,by using sodium nitroprusside (SNP) as NO donor and&nbsp; two kind of superoxide dismutase, CuZn-SOD and Mn-SOD, we created conditions to generate several kinds of signal molecules and investigated reaction of transformed (L929) and malignant (K562) cells tothose. Results of experiments are showing the parameters chosen (amount of free thiol groups and glutathione) may be relevant in measuring the effect of exogenous nitrate oxideand its redox descendants in different,&nbsp; both transformed and malignant cell lines.</p>

High blood pressure, also called hypertension is one of the most common worldwide diseases afflicting humans and is a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease. If blood pressure is controlled and oscillations in the hemodynamic variables are reduced, patients experience fewer complications after surgery. In clinical practice, this is usually achieved using manual drug delivery. Given that different patients have different sensitivity and reaction time to drugs, determining manually the right drug infusion rates may be difficult. This is a problem where automatic drug delivery can provide a solution, especially if it is designed to adapt to variations in the patient’s conditions. This research work presents an investigation into the development of abnormal blood pressure (hypertension) controllers for postoperative patients. Control of the drugs infusion rates is used to simultaneously regulate the hemodynamic variables such as the Mean Arterial Pressure (MAP) and the Cardiac Output (CO) at the desired level. The implementation of optimal control system is very essential to improve the quality of patient care and also to reduce the workload of healthcare staff and costs. Many researchers have conducted studies earlier on modelling and/or control of abnormal blood pressure for postoperative patients. However, there are still many concerns about smooth transition of blood pressure without any side effect. The blood pressure is classified in two categories: high blood pressure (Hypertension) and low blood pressure (Hypotension). The hypertension often occurred after cardiac surgery, and the hypotension occurred during cardiac surgery. To achieve the optimal control solution for these abnormal blood pressures, many methods are proposed, one of the common methods is infusing the drug related to blood pressure to maintain it at the desired level. There are several kinds of vasodilating drugs such as Sodium Nitroprusside (SNP), Dopamine (DPM), Nitro-glycerine (NTG), and so on, which can be used to treat postoperative patients, also used for hypertensive emergencies to keep the blood pressure at safety level. A comparative performance of two types of algorithms has been presented in chapter four. These include the Internal Model Control (IMC), and Proportional-Integral-Derivative (PID) controller. The resulting controllers are implemented, tested and verified for three sensitivity patient response. SNP is used for all three patients’ situation in order to reduce the pressure smoothly and maintain it at the desire level. A Genetic Algorithms (GAs) optimization technique has been implemented to optimise the controllers’ parameters. A set of experiments are presented to demonstrate the merits and capabilities of the control algorithms. The simulation results in chapter four have demonstrated that the performance criteria are satisfied with the IMC, and PID controllers. On the other hand, the settling time for the PID control of all three patients’ response is shorter than the settling time with IMC controller. Using multiple interacting drugs to control both the MAP and CO of patients with different sensitivity to drugs is a challenging task. A Multivariable Model Reference Adaptive Control (MMRAC) algorithm is developed using a two-input, two-output patient model. Because of the difference in patient’s sensitivity to the drug, and in order to cover the wide ranges of patients, Model Reference Adaptive Control (MRAC) has been implemented to obtain the optimal infusion rates of DPM and SNP. This is developed in chapters five and six. Computer simulations were carried out to investigate the performance of this controller. The results show that the proposed adaptive scheme is robust with respect to disturbances and variations in model parameters, the simulation results have demonstrated that this algorithm cannot cover the wide range of patient’s sensitivity to drugs, due to that shortcoming, a PID controller using a Neural Network that tunes the controller parameters was designed and implemented. The parameters of the PID controller were optimised offline using Matlab genetic algorithm. The proposed Neuro-PID controller has been tested and validated to demonstrate its merits and capabilities compared to the existing approaches to cover wide range of patients. / Libyan Ministry of Higher Education scholarship

No description available.

We study the properties of photoinduced metal–nitrosyl linkage isomers in sodium nitroprusside (SNP) as a function of particle size. By embedding the molecular complex at various concentrations into mesopores of silica xerogels the size of the particles can be adjusted. The ground state is characterized by X-ray diffraction, absorption and infrared spectroscopy. The physical properties of the photoswitched molecules were analysed by steady-state low-temperature absorption, infrared spectroscopy and by nanosecond transient absorption spectroscopy. The electronic structure as well as the activation energies of the metastable linkage isomers are independent of the particle size down to single isolated molecules, indicating that the SNP complexes are quasi-free inside the pores of the gel. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos &#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04&#61693;. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular. / Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (&#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos &#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04&#61693;. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular. / Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (&#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function.

We study the properties of photoinduced metal–nitrosyl linkage isomers in sodium nitroprusside (SNP) as a function of particle size. By embedding the molecular complex at various concentrations into mesopores of silica xerogels the size of the particles can be adjusted. The ground state is characterized by X-ray diffraction, absorption and infrared spectroscopy. The physical properties of the photoswitched molecules were analysed by steady-state low-temperature absorption, infrared spectroscopy and by nanosecond transient absorption spectroscopy. The electronic structure as well as the activation energies of the metastable linkage isomers are independent of the particle size down to single isolated molecules, indicating that the SNP complexes are quasi-free inside the pores of the gel. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.