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No description available.

Contexto: O exercício físico faz parte do tratamento do diabetes mellitus tipo 2 (DM2), doença que possui maior prevalência na população idosa. Maior foco tem sido dado ao efeito do treinamento de força no controle glicêmico, sendo que menor número de estudos tem como desfecho primário parâmetros neuromusculares, em idosos com DM2. Objetivo: Avaliar os efeitos de um programa de treino de força nos parâmetros neuromusculares de idosos com DM2, em relação à um grupo controle. Delineamento: ensaio clínico randomizado, com dois grupos, intervenção (GI) e controle (GC). Métodos: Quarenta e quatro participantes foram alocados nos dois grupos: GI (n=22), que realizou treinamento de força três vezes por semana, durante 12 semanas; GC (n=22), que realizou uma sessão semanal de alongamento, durante 12 semanas. O treinamento de força foi composto por 11 exercícios, com 2-3 séries de 12-10 repetições e intensidade de 15 a 12 repetições máximas. O desfecho primário do estudo foi a qualidade muscular, por tensão específica e eco intensidade, que foi avaliada antes e após as 12 semanas, assim como os demais desfechos secundários. Os dados foram análises tanto pela intenção de tratar (ITT), como pela análise por protocolo (PP), baseado em 70% ou mais de comparecimento as seções. As comparações foram realizadas com Equação de Estimação Generalizadas e ANOVA de duas vias com medidas repetidas, para as análises ITT e PP, respectivamente. Resultados: Não houve modificação (p≥0,05) da qualidade muscular avaliada por eco intensidade ou por tensão específica, no GI e GC, para ambas as análises. Foram encontradas melhorias (p≤0,05) na força máxima dinâmica para o GI e GC na análise ITT e apenas para o GI na análise PP. Não foi encontrada diferença (p≥0,05) na força máxima isométrica, no GI e GC, em ambas as análises. Na análise ITT não foram encontradas melhorias (p≥0,05) no desempenho dos testes funcionais, para ambos os grupos, enquanto na análise PP houve redução (p≤0,05) no tempo de realização do teste timed up and go e subir escada no GC, e nos testes de sentar e levantar da cadeira e subir escada para o GI. Para a espessura muscular do quadríceps femoral houve aumento (p≤0,05) dos valores para o GI, mas não para o GC, em ambas as análises. Em relação a gordura visceral, não houve modificação dos valores em ambos os grupos com a análise ITT, mas houve redução (p≤0,05) com a análise PP, para os dois grupos. Os valores de hemoglobina glicada reduziram para o GI e aumentaram (p≤0,05) para o GC na análise PP, mas não foram encontradas diferenças (p≥0,05) para a análise ITT. Redução (p≤0,05) dos níveis de triglicerídeos foi encontrada para o GI, mas não para o GC, em ambas as análises. Conclusões: o programa de treino de força proposto no presente estudo foi capaz de melhorar a força dinâmica e a espessura muscular de idosos com DM2 no período de 12 semanas, mas não causou modificações significativas na qualidade muscular durante esse período, mostrando que para alguns parâmetros neuromusculares talvez seja necessário período maior de treinamento nessa população. / Context: Physical exercise is a cornerstone of diabetes mellitus type 2 (DM2) treatment, a disease that has a higher prevalence in the elderly population. Greater focus has been given to the effects of strength training on glycemic control, and a lower number of studies has investigated neuromuscular parameters as a primary endpoint in elderly with DM2. Objective: To evaluate the effects of a strength training program on the neuromuscular parameters of elderly patients with DM2, in relation to a control group. Design: Randomized clinical trial with intervention (GI) and control (CG) groups. Methods: Forty-four participants were randomized to both groups: GI (n= 22), which underwent strength training three times a week for 12 weeks, and GC (n = 22), which performed a weekly stretching session for 12 weeks. Strength training was composed of 11 exercises, with 2-3 sets of 12-10 repetitions and was set the intensity of 15 to 12 maximal repetitions. The primary outcome of the study was muscle quality measured by specific tension and eco intensity, evaluated before and after 12 weeks, as well as the other secondary outcomes. Data was analyzed by both, intention-to-treat (ITT) and per protocol (PP) analysis (based on 70% or more attendance sections). The comparisons were performed with Generalized Estimation Equation and two-way ANOVA with repeated measurements for ITT and PP analyzes, respectively. Results: No change (p≥0.05) in muscle quality assessed by echo intensity or by specific tension were found in GI and GC, in both analyzes. Increase (p≤0.05) in maximum dynamic strength was found for GI and GC in ITT analyze, but only for GI in PP analyze. No difference in maximum isometric force (p≥0.05) was found for GI and GC in both analysis. In the ITT analysis, there were no improvements (p≥0.05) in functional tests performance in both groups, whereas in the PP analysis reduction (p≤0.05) was found in the timed up and go and climb stairs tests in the GC, and in the sit to stand and climb stairs tests in the GI. Quadriceps femoris muscle thickness increased (p≤0.05) in GI in both analyzes, but not for GC. No difference was found for visceral fat, in both groups in the ITT analysis, but there was a reduction (p≤0.05) in the PP analysis for both groups, with no difference between groups. Glycated hemoglobin values was reduced (p≤0.05) in GI and significantly increased in GC in PP analysis, but no differences were found in ITT. Reduction (p≤0.05) in triglyceride levels was found in GI, but not in GC, in both analyzes. Conclusions: The strength training program used in this study was able to improve dynamic strength and muscle thickness of elderly patients with DM2 in the 12-week period, but it was not able to induce significant changes in muscle quality, indicating that for some neuromuscular parameters it may be required a longer period of training for this population.

The human stomach is a complex organ with sophisticated function. – The control of delivery of nutrients to the small intestine is tightly regulated, and the patterns and determinants of the associated processes are numerous, complex and interrelated. The presence of nutrients in the small intestine stimulates the release of a number of gastrointestinal hormones, including glucagon-like peptide-1 (GLP-1). Exogenous GLP-1 reduces fasting and postprandial glucose concentrations, and this is thought to be via a slowing of gastric emptying (GE). The effects of endogenous GLP-1 on GE and glycaemia were evaluated using exendin(9-39), a GLP-1 antagonist, in healthy subjects, in a randomised, placebo-controlled study, in Chapter 5. Exendin(9-39) increased postprandial glycaemia through an acceleration of GE; these findings support the putative role of GLP-1 as an enterogastrone. The capacity to measure GE has greatly increased the understanding of normal and disordered gastric physiology. 30 – 50 % of patients with longstanding diabetes have delayed GE. Scintigraphy remains the ‘gold standard’ in the measurement of GE, however, it is associated with a radiation burden. Recently, three-dimensional (3D) ultrasonography was validated against scintigraphy in healthy subjects. In Chapter 6, GE was measured concurrently by 3D ultrasonography and scintigraphy in patients with diabetic gastroparesis, and good correlation and agreement was found between both techniques. Glycaemic control represents one of the main pathogenetic factors of diabetic gastroparesis. Hyperglycaemia slows, while hypoglycaemia accelerates, GE in healthy subjects and patients with uncomplicated type 1 diabetes. Chapter 7 reports a study investigating the effects of insulin-induced hypoglycaemia vs. euglycaemia on GE in longstanding type 1 diabetes. Hypoglycaemia accelerated GE of a mixed solid/liquid meal; the magnitude of this acceleration was greater when GE during euglycaemia was slower. In contrast to glucose, the effects of intravenous (iv) fructose (used widely in the diabetic diet) on GE are less well understood. The comparative effects of iv fructose, glucose and saline on GE and antropyloroduodenal motility in healthy males are reported in Chapter 8. Compared with saline, fructose infusion was associated with a slowing of GE and suppression of antral waves, the magnitude of which was comparable to glucose. Treatment for the management of gastroparesis is currently suboptimal and there is a need for novel prokinetic agents. Itopride has demonstrated prokinetic activity in dogs. The effects of itopride on GE, glycaemia and upper gastrointestinal symptoms were studied in patients with longstanding diabetes in a randomised, placebo-controlled trial (Chapter 9). There was a trend for itopride to accelerate both solid and liquid GE. 48 % of patients had delayed solid and/or liquid GE on placebo, and in this group, itopride accelerated liquid, but not solid, GE. Autonomic neuropathy represents another pathogenetic factor of diabetic gastroparesis, and delayed GE is more prevalent in patients with autonomic dysfunction. There is evidence that C-peptide improves autonomic nerve function (ANF) in type 1 diabetes. The effects of C-peptide on GE and ANF were studied in patients with longstanding type 1 diabetes in randomised, placebo-controlled design, in Chapter 10. C-peptide had no effect on solid or liquid GE, or ANF. Gastroparesis, particularly in patients with diabetes, represents an important clinical problem. The studies presented in this thesis have provided fundamental insights into the measurement and determinants of gastric motor function and postprandial glycaemia, and treatment of gastroparesis, however, further studies which assess the complex pathogenesis and pathophysiology of gastroparesis, and which include a larger cohort of patients, are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1456472 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

The human stomach is a complex organ with sophisticated function. – The control of delivery of nutrients to the small intestine is tightly regulated, and the patterns and determinants of the associated processes are numerous, complex and interrelated. The presence of nutrients in the small intestine stimulates the release of a number of gastrointestinal hormones, including glucagon-like peptide-1 (GLP-1). Exogenous GLP-1 reduces fasting and postprandial glucose concentrations, and this is thought to be via a slowing of gastric emptying (GE). The effects of endogenous GLP-1 on GE and glycaemia were evaluated using exendin(9-39), a GLP-1 antagonist, in healthy subjects, in a randomised, placebo-controlled study, in Chapter 5. Exendin(9-39) increased postprandial glycaemia through an acceleration of GE; these findings support the putative role of GLP-1 as an enterogastrone. The capacity to measure GE has greatly increased the understanding of normal and disordered gastric physiology. 30 – 50 % of patients with longstanding diabetes have delayed GE. Scintigraphy remains the ‘gold standard’ in the measurement of GE, however, it is associated with a radiation burden. Recently, three-dimensional (3D) ultrasonography was validated against scintigraphy in healthy subjects. In Chapter 6, GE was measured concurrently by 3D ultrasonography and scintigraphy in patients with diabetic gastroparesis, and good correlation and agreement was found between both techniques. Glycaemic control represents one of the main pathogenetic factors of diabetic gastroparesis. Hyperglycaemia slows, while hypoglycaemia accelerates, GE in healthy subjects and patients with uncomplicated type 1 diabetes. Chapter 7 reports a study investigating the effects of insulin-induced hypoglycaemia vs. euglycaemia on GE in longstanding type 1 diabetes. Hypoglycaemia accelerated GE of a mixed solid/liquid meal; the magnitude of this acceleration was greater when GE during euglycaemia was slower. In contrast to glucose, the effects of intravenous (iv) fructose (used widely in the diabetic diet) on GE are less well understood. The comparative effects of iv fructose, glucose and saline on GE and antropyloroduodenal motility in healthy males are reported in Chapter 8. Compared with saline, fructose infusion was associated with a slowing of GE and suppression of antral waves, the magnitude of which was comparable to glucose. Treatment for the management of gastroparesis is currently suboptimal and there is a need for novel prokinetic agents. Itopride has demonstrated prokinetic activity in dogs. The effects of itopride on GE, glycaemia and upper gastrointestinal symptoms were studied in patients with longstanding diabetes in a randomised, placebo-controlled trial (Chapter 9). There was a trend for itopride to accelerate both solid and liquid GE. 48 % of patients had delayed solid and/or liquid GE on placebo, and in this group, itopride accelerated liquid, but not solid, GE. Autonomic neuropathy represents another pathogenetic factor of diabetic gastroparesis, and delayed GE is more prevalent in patients with autonomic dysfunction. There is evidence that C-peptide improves autonomic nerve function (ANF) in type 1 diabetes. The effects of C-peptide on GE and ANF were studied in patients with longstanding type 1 diabetes in randomised, placebo-controlled design, in Chapter 10. C-peptide had no effect on solid or liquid GE, or ANF. Gastroparesis, particularly in patients with diabetes, represents an important clinical problem. The studies presented in this thesis have provided fundamental insights into the measurement and determinants of gastric motor function and postprandial glycaemia, and treatment of gastroparesis, however, further studies which assess the complex pathogenesis and pathophysiology of gastroparesis, and which include a larger cohort of patients, are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1456472 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Contexto: O exercício físico faz parte do tratamento do diabetes mellitus tipo 2 (DM2), doença que possui maior prevalência na população idosa. Maior foco tem sido dado ao efeito do treinamento de força no controle glicêmico, sendo que menor número de estudos tem como desfecho primário parâmetros neuromusculares, em idosos com DM2. Objetivo: Avaliar os efeitos de um programa de treino de força nos parâmetros neuromusculares de idosos com DM2, em relação à um grupo controle. Delineamento: ensaio clínico randomizado, com dois grupos, intervenção (GI) e controle (GC). Métodos: Quarenta e quatro participantes foram alocados nos dois grupos: GI (n=22), que realizou treinamento de força três vezes por semana, durante 12 semanas; GC (n=22), que realizou uma sessão semanal de alongamento, durante 12 semanas. O treinamento de força foi composto por 11 exercícios, com 2-3 séries de 12-10 repetições e intensidade de 15 a 12 repetições máximas. O desfecho primário do estudo foi a qualidade muscular, por tensão específica e eco intensidade, que foi avaliada antes e após as 12 semanas, assim como os demais desfechos secundários. Os dados foram análises tanto pela intenção de tratar (ITT), como pela análise por protocolo (PP), baseado em 70% ou mais de comparecimento as seções. As comparações foram realizadas com Equação de Estimação Generalizadas e ANOVA de duas vias com medidas repetidas, para as análises ITT e PP, respectivamente. Resultados: Não houve modificação (p≥0,05) da qualidade muscular avaliada por eco intensidade ou por tensão específica, no GI e GC, para ambas as análises. Foram encontradas melhorias (p≤0,05) na força máxima dinâmica para o GI e GC na análise ITT e apenas para o GI na análise PP. Não foi encontrada diferença (p≥0,05) na força máxima isométrica, no GI e GC, em ambas as análises. Na análise ITT não foram encontradas melhorias (p≥0,05) no desempenho dos testes funcionais, para ambos os grupos, enquanto na análise PP houve redução (p≤0,05) no tempo de realização do teste timed up and go e subir escada no GC, e nos testes de sentar e levantar da cadeira e subir escada para o GI. Para a espessura muscular do quadríceps femoral houve aumento (p≤0,05) dos valores para o GI, mas não para o GC, em ambas as análises. Em relação a gordura visceral, não houve modificação dos valores em ambos os grupos com a análise ITT, mas houve redução (p≤0,05) com a análise PP, para os dois grupos. Os valores de hemoglobina glicada reduziram para o GI e aumentaram (p≤0,05) para o GC na análise PP, mas não foram encontradas diferenças (p≥0,05) para a análise ITT. Redução (p≤0,05) dos níveis de triglicerídeos foi encontrada para o GI, mas não para o GC, em ambas as análises. Conclusões: o programa de treino de força proposto no presente estudo foi capaz de melhorar a força dinâmica e a espessura muscular de idosos com DM2 no período de 12 semanas, mas não causou modificações significativas na qualidade muscular durante esse período, mostrando que para alguns parâmetros neuromusculares talvez seja necessário período maior de treinamento nessa população. / Context: Physical exercise is a cornerstone of diabetes mellitus type 2 (DM2) treatment, a disease that has a higher prevalence in the elderly population. Greater focus has been given to the effects of strength training on glycemic control, and a lower number of studies has investigated neuromuscular parameters as a primary endpoint in elderly with DM2. Objective: To evaluate the effects of a strength training program on the neuromuscular parameters of elderly patients with DM2, in relation to a control group. Design: Randomized clinical trial with intervention (GI) and control (CG) groups. Methods: Forty-four participants were randomized to both groups: GI (n= 22), which underwent strength training three times a week for 12 weeks, and GC (n = 22), which performed a weekly stretching session for 12 weeks. Strength training was composed of 11 exercises, with 2-3 sets of 12-10 repetitions and was set the intensity of 15 to 12 maximal repetitions. The primary outcome of the study was muscle quality measured by specific tension and eco intensity, evaluated before and after 12 weeks, as well as the other secondary outcomes. Data was analyzed by both, intention-to-treat (ITT) and per protocol (PP) analysis (based on 70% or more attendance sections). The comparisons were performed with Generalized Estimation Equation and two-way ANOVA with repeated measurements for ITT and PP analyzes, respectively. Results: No change (p≥0.05) in muscle quality assessed by echo intensity or by specific tension were found in GI and GC, in both analyzes. Increase (p≤0.05) in maximum dynamic strength was found for GI and GC in ITT analyze, but only for GI in PP analyze. No difference in maximum isometric force (p≥0.05) was found for GI and GC in both analysis. In the ITT analysis, there were no improvements (p≥0.05) in functional tests performance in both groups, whereas in the PP analysis reduction (p≤0.05) was found in the timed up and go and climb stairs tests in the GC, and in the sit to stand and climb stairs tests in the GI. Quadriceps femoris muscle thickness increased (p≤0.05) in GI in both analyzes, but not for GC. No difference was found for visceral fat, in both groups in the ITT analysis, but there was a reduction (p≤0.05) in the PP analysis for both groups, with no difference between groups. Glycated hemoglobin values was reduced (p≤0.05) in GI and significantly increased in GC in PP analysis, but no differences were found in ITT. Reduction (p≤0.05) in triglyceride levels was found in GI, but not in GC, in both analyzes. Conclusions: The strength training program used in this study was able to improve dynamic strength and muscle thickness of elderly patients with DM2 in the 12-week period, but it was not able to induce significant changes in muscle quality, indicating that for some neuromuscular parameters it may be required a longer period of training for this population.

Contexto: O exercício físico faz parte do tratamento do diabetes mellitus tipo 2 (DM2), doença que possui maior prevalência na população idosa. Maior foco tem sido dado ao efeito do treinamento de força no controle glicêmico, sendo que menor número de estudos tem como desfecho primário parâmetros neuromusculares, em idosos com DM2. Objetivo: Avaliar os efeitos de um programa de treino de força nos parâmetros neuromusculares de idosos com DM2, em relação à um grupo controle. Delineamento: ensaio clínico randomizado, com dois grupos, intervenção (GI) e controle (GC). Métodos: Quarenta e quatro participantes foram alocados nos dois grupos: GI (n=22), que realizou treinamento de força três vezes por semana, durante 12 semanas; GC (n=22), que realizou uma sessão semanal de alongamento, durante 12 semanas. O treinamento de força foi composto por 11 exercícios, com 2-3 séries de 12-10 repetições e intensidade de 15 a 12 repetições máximas. O desfecho primário do estudo foi a qualidade muscular, por tensão específica e eco intensidade, que foi avaliada antes e após as 12 semanas, assim como os demais desfechos secundários. Os dados foram análises tanto pela intenção de tratar (ITT), como pela análise por protocolo (PP), baseado em 70% ou mais de comparecimento as seções. As comparações foram realizadas com Equação de Estimação Generalizadas e ANOVA de duas vias com medidas repetidas, para as análises ITT e PP, respectivamente. Resultados: Não houve modificação (p≥0,05) da qualidade muscular avaliada por eco intensidade ou por tensão específica, no GI e GC, para ambas as análises. Foram encontradas melhorias (p≤0,05) na força máxima dinâmica para o GI e GC na análise ITT e apenas para o GI na análise PP. Não foi encontrada diferença (p≥0,05) na força máxima isométrica, no GI e GC, em ambas as análises. Na análise ITT não foram encontradas melhorias (p≥0,05) no desempenho dos testes funcionais, para ambos os grupos, enquanto na análise PP houve redução (p≤0,05) no tempo de realização do teste timed up and go e subir escada no GC, e nos testes de sentar e levantar da cadeira e subir escada para o GI. Para a espessura muscular do quadríceps femoral houve aumento (p≤0,05) dos valores para o GI, mas não para o GC, em ambas as análises. Em relação a gordura visceral, não houve modificação dos valores em ambos os grupos com a análise ITT, mas houve redução (p≤0,05) com a análise PP, para os dois grupos. Os valores de hemoglobina glicada reduziram para o GI e aumentaram (p≤0,05) para o GC na análise PP, mas não foram encontradas diferenças (p≥0,05) para a análise ITT. Redução (p≤0,05) dos níveis de triglicerídeos foi encontrada para o GI, mas não para o GC, em ambas as análises. Conclusões: o programa de treino de força proposto no presente estudo foi capaz de melhorar a força dinâmica e a espessura muscular de idosos com DM2 no período de 12 semanas, mas não causou modificações significativas na qualidade muscular durante esse período, mostrando que para alguns parâmetros neuromusculares talvez seja necessário período maior de treinamento nessa população. / Context: Physical exercise is a cornerstone of diabetes mellitus type 2 (DM2) treatment, a disease that has a higher prevalence in the elderly population. Greater focus has been given to the effects of strength training on glycemic control, and a lower number of studies has investigated neuromuscular parameters as a primary endpoint in elderly with DM2. Objective: To evaluate the effects of a strength training program on the neuromuscular parameters of elderly patients with DM2, in relation to a control group. Design: Randomized clinical trial with intervention (GI) and control (CG) groups. Methods: Forty-four participants were randomized to both groups: GI (n= 22), which underwent strength training three times a week for 12 weeks, and GC (n = 22), which performed a weekly stretching session for 12 weeks. Strength training was composed of 11 exercises, with 2-3 sets of 12-10 repetitions and was set the intensity of 15 to 12 maximal repetitions. The primary outcome of the study was muscle quality measured by specific tension and eco intensity, evaluated before and after 12 weeks, as well as the other secondary outcomes. Data was analyzed by both, intention-to-treat (ITT) and per protocol (PP) analysis (based on 70% or more attendance sections). The comparisons were performed with Generalized Estimation Equation and two-way ANOVA with repeated measurements for ITT and PP analyzes, respectively. Results: No change (p≥0.05) in muscle quality assessed by echo intensity or by specific tension were found in GI and GC, in both analyzes. Increase (p≤0.05) in maximum dynamic strength was found for GI and GC in ITT analyze, but only for GI in PP analyze. No difference in maximum isometric force (p≥0.05) was found for GI and GC in both analysis. In the ITT analysis, there were no improvements (p≥0.05) in functional tests performance in both groups, whereas in the PP analysis reduction (p≤0.05) was found in the timed up and go and climb stairs tests in the GC, and in the sit to stand and climb stairs tests in the GI. Quadriceps femoris muscle thickness increased (p≤0.05) in GI in both analyzes, but not for GC. No difference was found for visceral fat, in both groups in the ITT analysis, but there was a reduction (p≤0.05) in the PP analysis for both groups, with no difference between groups. Glycated hemoglobin values was reduced (p≤0.05) in GI and significantly increased in GC in PP analysis, but no differences were found in ITT. Reduction (p≤0.05) in triglyceride levels was found in GI, but not in GC, in both analyzes. Conclusions: The strength training program used in this study was able to improve dynamic strength and muscle thickness of elderly patients with DM2 in the 12-week period, but it was not able to induce significant changes in muscle quality, indicating that for some neuromuscular parameters it may be required a longer period of training for this population.

Critically ill patients often exhibit abnormal glycaemia that can lead to severe complications and potentially death. In critically ill adults, hyperglycaemia is a common problem that has been associated with increased morbidity and mortality. In contrast, critically ill infants often suffer from hypoglycaemia, which may cause seizures and permanent brain injury. Further complicating the matter, both of these conditions are diagnosed by blood glucose (BG) measurements, often taken several hours apart, and, as a result, these conditions can remain poorly managed or go completely undetected. Emerging ‘continuous’ glucose monitoring (CGM) devices with 1-5 minute measurement intervals have the potential to resolve many issues associated with conventional intermittent BG monitoring. The objective of this research was to investigate and develop methods and models to optimise the clinical use of CGM devices in critically ill patients. For critically ill adults, an in-silico study was conducted to quantify the potential benefits of introducing CGM devices into the intensive care unit (ICU). Mathematical models of CGM error characteristics were implemented with existing, clinically validated, models of the insulin-glucose regulatory system, to simulate the behaviour of CGM devices in critically ill patients. An alarm algorithm was also incorporated to provide a warning at the onset of predicted hypoglycaemia, allowing a virtual dextrose intervention to be administered as a preventative measure. The results of the in-silico study showed a potential reduction in nurse workload of approximately 75% and a significant reduction in hypoglycaemia, while also providing insight into the optimal rescue dose size and resulting dynamics of glucose recovery. During 2012, ten patients were recruited into a pilot clinical trial of CGM devices in critical care with a primary goal of assessing the reliability of CGM devices in this environment, with a specific interest in the effects of CGM device type and sensor site on sensor glucose (SG) data. Results showed the mean absolute relative difference of SG data across the cohort was between 12-24% and CGM devices were capable of monitoring some patients with a high degree of accuracy. However, certain illnesses, drugs and therapies can potentially affect sensor performance, and one particular set of results suggested severe oedema may have affected sensor performance. A novel and first of its kind metric, the Trend Compass was developed and used to assesses trend accuracy of SG in a mathematically precise fashion without approximation, and, importantly, does so independent of glucose level or sensor bias, unlike any other such metrics. In this analysis, the trend accuracy between CGM devices was typically good. A recent hypothesis suggesting that glucose complexity is associated with mortality was also investigated using the clinical CGM data. The results showed that complexity results from detrended fluctuation analysis (DFA) were influenced far more by CGM device type than patient outcome. In addition, the location of CGM sensors had no significant effect on complexity results in this data set. Thus, while this emerging analytical method has shown positive results in the literature, this analysis indicates that those results may be misleading given the impact of technology outweighing that of physiology. This particular result helps to further delineate the range of potential applications and insight that CGM devices might offer in this clinical scenario. In critically ill infants, CGM devices were used to investigate hypoglycaemia during the first 48 hours after birth. More than 50 CGM data sets were obtained from several studies of CGM in infants at risk of hypoglycaemia at the Waikato hospital neonatal ICU (NICU). In light of concerns regarding CGM accuracy, particularly during the first few hours of monitoring and/or at low BG levels, an alternative, novel calibration scheme was developed to increase the reliability of SG data. The recalibration algorithm maximised the value of very accurate calibration BG measurements from a blood gas analyser (BGA), by forcing SG data to pass through these calibration BG measurements. Recalibration increased all metrics of hypoglycaemia (number, duration, severity and hypoglycaemic index) as the factory CGM calibration was found to be reporting higher values at low BG levels due to its least squares calibration approach based on the assumption of a less accurate calibration glucose meter. Thus, this research defined new calibration methods to directly optimise the use of CGM devices in this clinical environment, where accurate reference BG measurements are available. Furthermore, this work showed that metrics such as duration or area under curve were far more robust to error than the typically used counted-incidence metrics, indicating how clinical assessment may have to change when using these devices. The impact of errors in calibration measurements on metrics used to classify hypoglycaemia was also assessed. Across the cohort, measurement error, particularly measurement bias, had a larger effect on hypoglycaemia metrics than delays in entering calibration measurements. However, for patients with highly variable glycaemia, timing error can have a significantly larger impact on output SG data than measurement error. Unusual episodes of hypoglycaemia could be successfully identified using a stochastic model, based on kernel density estimation, providing another level of information to aid decision making when assessing hypoglycaemia. Using the developed algorithms/tools, with CGM data from 161 infants, the incidence of hypoglycaemia was assessed and compared to results determined using BG measurements alone. Results from BG measurements showed that ~17% of BG measurements identified hypoglycaemia and over 80% of episodes occurred in the first day after birth. However, with concurrent BG and SG data available, the SG data consistently identified hypoglycaemia at a higher rate suggesting the BG measurements were not capturing some episodes. Duration of hypoglycaemia in SG data varied from 0-10+%, but was typically in the range 4-6%. Hypoglycaemia occurred most frequently on the first day after birth and an optimal measurement protocol for at risk infants would likely involve CGM for the first week after birth with frequent intermittent BG measurements for the first day. Overall, CGM devices have the potential to increase the understanding of certain glycaemic abnormalities and aid in the diagnosis/treatment of other conditions in critically ill patients. This research has used a range of prospective and retrospective clinical studies to develop methods to further optimise the use of CGM devices within the critically ill clinical environment, as well as delineating where they are less useful or less robust. These latter results clearly define areas where clinical practice needs to adapt when using these devices, as well as areas where device makers could target technological improvements for best effect. Although further investigations are required before these devices are regularly implemented in day-to-day clinical practice, as an observational tool they are capable of providing useful information that is not currently available with conventional intermittent BG monitoring.

A Uncaria tomentosa (U. tomentosa), popularmente conhecida como \"Unha-de-gato\", é uma planta medicinal nativa das Américas, mundialmente empregada devido às suas atividades anti-inflamatórias e imunomodulatórias. O consumo desta planta ocorre não apenas na forma in natura, mas principalmente como fitoterápico, sendo muitas vezes utilizada de forma indiscriminada pela população. Apesar de vários estudos revelarem as propriedades terapêuticas da U. tomentosa, poucos são os trabalhos que empregam protocolos estabelecidos por agências regulamentadoras internacionais, para a avaliação dos possíveis efeitos tóxicos e imunotóxicos deste fitoterápico. Assim, o propósito do presente estudo foi verificar se a administração de um extrato seco de U. tomentosa, comercialmente disponível no mercado, poderia ocasionar efeitos tóxicos e imunotóxicos em ratos após 90 dias de tratamento. Para isso, 40 ratos Wistars machos foram tratados oralmente com as doses de 15, 75 ou 150 mg/kg de extrato seco de U. tomentosa comercialmente disponível no mercado, contendo teores de alcaloides de acordo com aqueles valores preconizados em literatura. No final do período experimental, os animais foram submetidos à eutanásia para realização de avaliações bioquímicas, hematológicas, histopatológicas, análise de órgãos linfoides e não-linfoides, avaliação das respostas imunes inata, inflamatória e humoral, bem como teste para determinação de reação de hipersensibilidade do tipo IV. Os resultados revelaram aumento nos níveis de ALT dos animais tratados com a dose de 75 mg/kg, e redução nos índices glicêmicos de ratos tratados com 75 e 150 mg/kg de U. tomentosa. Entretanto, somente os ratos tratados com a maior dose exibiram discreta vacuolização centro-lobular hepática; assim, somente os dados de ALT não são sugestivos de efeitos hepáticos adversos da U. tomentosa após um longo período de tratamento. A redução nos índices sanguíneos de glicose dos ratos, após tratamento com a U. tomentosa, podem representar importante risco para seres humanos diabéticos, susceptíveis ao desenvolvimento de hipoglicemia e que fazem uso da U. tomentosa para outros propósitos. Em conclusão, estes estudos demonstraram que, apesar de a U. tomentosa não promover efeitos tóxicos e imunotóxicos, o uso prolongado da mesma, a altas doses, pode promover redução dos índices glicêmicos. / Uncaria tomentosa (U. tomentosa), commonly known as \"Cat\'s claw\", is a native medicinal plant from America, it is employed worldwide for its anti-inflammatory and immunomodulatory activities. The consumption of this plant occurs not only in natura, but mainly as a phytotherapic, used indiscriminately by the population. Although many researchers revealed the therapeutic properties of U. tomentosa, few studies employing established protocols by international regulatory agencies for the evaluation of the possible toxic and immunotoxic effects of this herbal medicine. Thus, the purpose of the present study was to verify if the dry extract of U. tomentosa could promote toxic and/or immunotoxic effects in rats following 90 days of treatment. For this, forty male rats were orally treated with 15, 75 or 150mg/kg of dry extract of U. tomentosa, commercially available, containing levels of alkaloids according to those values recommended in the literature. At the end of experimental period, the rats were killed for the evaluation of the biochemistry, haematology, histopathology, status of the lymphoid and non-lymphoid organs, evaluation of innate, inflammatory and humoral immune responses, as well as a test to determine the delayed type hypersensitivity. The results revealed an increase in the levels of ALT in the animals treated with 75mg/kg and a reduction in the glycaemic levels of rats treated with 75 and 150mg/kg of U. tomentosa. However, only rats treated with the higher dose showed a slight centrilobular hepatic vacuolation; thus, ALT data alone are not suggestive of a hepatic adverse effect of U. tomentosa following long-term treatment. The reduction in blood glucose levels of the rats, could represent an important risk for diabetic humans, who are susceptible to the development of hypoglycaemia and who might use U. tomentosa for purposes other than anti-diabetes. In conclusion, these studies demonstrated that, while U. tomentosa has no immunotoxic effect, long-term U. tomentosa treatment at high doses can promote reduction in glycemic levels.

Considerando que o diabetes experimental altera a morfologia e função das glândulas salivares de ratos, o objetivo deste estudo foi analisar o efeito da irradiação com laser em baixa intensidade no metabolismo das glândulas parótidas (GP) e submandibulares (GSM) de ratas diabéticas, assim como analisar a glicemia destes animais. Ratas Wistar com aproximadamente 195 g foram divididas em diabéticas (D) e controles (C), e subdivididas de acordo com a dose de irradiação recebida: C-D0 (0 J/cm2), C-D5 (5 J/cm2), C-D10 (10 J/cm2), C-D20 (20 J/cm2). O diabetes foi induzido por injeção de estreptozotocina 60 mg/kg p.c., e confirmado após 72 h, através da glicemia. Vinte e nove dias após a indução, as ratas receberam a irradiação de acordo com o grupo a qual pertenciam. O laser de diodo (Ecco Fibras®), 660nm, foi utilizado nas áreas correspondentes às GP e GSM. Após 24 h, as ratas foram eutanasiadas e as glândulas removidas para posterior análise iônica, histológica e bioquímica de concentração total de proteína, atividade das enzimas catalase, peroxidase e amilase. Além disso, análise glicêmica também foi realizada. Análise de variância e teste de Tukey revelaram diminuição da glicemia nos grupos D5 e D20 (p<0,05), assim como diminuição na atividade da enzima catalase, nestas mesmas dosagens, nas GP e GSM para valores similares às ratas não-diabéticas (p>0,05), sendo que para as GSM, a dose de 10 J/cm2 também se mostrou efetiva. Análise histológica demonstrou acúmulo de lipídeos nas GP dos animais diabéticos, sendo que para os grupos que receberam irradiação, este acúmulo foi reduzido. Com base nos resultados, podemos concluir que a irradiação com laser vermelho nas GP e GSM altera a atividade enzimática da catalase, assim como altera a concentração de glicose sangüínea e o acúmulo de lipídeos. Com isto, mais estudos devem ser realizados objetivando continuar as análises de parâmetros antioxidantes, assim como, análise glicêmica, uma vez que a hiperglicemia e alterações no sistema antioxidante são diretamente relacionadas às complicações do diabetes. / Considering that experimental diabetes alters rat salivary gland morphology and function, the aim of this study was to evaluate the effect of laser irradiation (LI) on the glycaemic state and some biochemical parameters of the parotid glands (PG) and submandibulary glands (SMG) in diabetic and non diabetic rats, which were divided into 8 groups: D0/5/10/20 and C0/5/10/20, respectively. Diabetes was induced by administration of streptozotocin (60 mg/kg) and confirmed later by the glycaemia results. Twenty-nine (29) days after the induction, the PG and SMG of groups D-C5, D-C10 and D-C20, were irradiated with 5, 10 and 20 J/cm2 of laser diode (660nm/100mW) respectively. On the following day, the rats were euthanized and the blood glucose determined. The PG and SMG were removed and total protein concentration and amylase, peroxidase and catalase activities were performed, as well as, ionic and histological analysis. The analysis of the results (ANOVA and Tukey tests) revealed a decrease in the glycaemia level for groups D5 and D20 (p<0.05). In addition, diabetic rats showed higher catalase and peroxidase activities than non diabetic groups, without radiation. The doses of 5 and 20 J/cm2 decreased catalase activity, of PG and SMG, of diabetic groups to non diabetic values (p<0.05). Moreover, the dose of 10 J/cm2 also was effective to SMGs. Histological analysis showed accumulation of lipids droplets on parotid glands of diabetic animals. However, the lipid droplets quantity was lower in comparison with that observed to non irradiated diabetic animals. The results of the present study suggest that the classical organs which control glycaemia should also be analyzed after being irradiated with LI, once hyperglycaemia and alterations of the antioxidant system are the main causes of diabetes complications.