Orientador: Henrique Luiz Monteiro / Banca: Eduardo Kokubun / Banca: Alex Antonio Florindo / Resumo: A hipótese inicial do trabalho é a de que a maior prática de atividades físicas entre indivíduos diabéticos pode diminuir o custo total do tratamento do DM2 e suas complicações. Objetivo: Avaliar se pacientes diabéticos e com maior envolvimento com a prática de atividades físicas apresentam menor custo com medicamentos, consultas e exames médicos. Métodos: Trabalho transversal realizado junto a dois núcleos de saúde, na cidade de Bauru-SP. A casuística foi composta por 121 diabéticos tipo 2, de ambos os sexos, e com idade inferior a 75 anos. Foram analisados os prontuários clínicos dos pacientes (cálculo do custo), avaliada a presença de neuropatia, o estado nutricional, aferida a pressão arterial e aplicados questionários (atividade física, condição econômica e risco coronariano). A análise dos dados foi realizada após a divisão dos indivíduos em grupos de atividade física: Ativo, Moderadamente ativo e Sedentário. ANOVA one-way e ANOVA two-way avaliaram a interação da prática de atividades físicas e indicadores de custo médico. Para as variáveis categóricas, o teste qui-quadrado foi utilizado para verificar a existência de associações. As regressões linear e logística também foram aplicadas. Resultados: Neuropatia diabética aproximou-se dos 30% e diabéticos não acometidos representaram maiores custos para a saúde no que se refere às consultas com clínico geral. Diabéticos sedentários, quando comparados com ativos, apresentaram custo com clínico geral 63% maior (P= 0,012). Quando comparados com os não insulino-dependentes, os doentes que utilizam insulina apresentaram custos mais elevados para medicamentos (R$40.554,9±2976 vs R$2.454,4±216; p= 0,001) e consultas de enfermagem (R$8.064,8±487 vs R$6.147,9±208; p= 0,001). Entre os insulino-dependentes, a atividade física não exerceu efeito aparente sobre nenhuma das variáveis de custo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The initial hypothesis of this work is that the higher physical activity level among diabetic individuals may reduce the total cost treatment of DM2 and its complications. Objective: To analyze whether diabetics patients and with increased physical activity levels show lower cost with medicines, medical consultations and examination. Methods: A cross-sectional research conducted at two health centers in the city of Bauru - SP, Brazil. The sample consisted of 121 type 2 diabetic patients of both sexes and aged below 75 years. For this research we analyzed the clinical records of patients (calculating cost), evaluated the presence of neuropathy, assessed the nutritional status, measured blood pressure and applied questionnaires (physical activity, status economical and coronary risk). Data analysis was performed after the division of individuals into groups for physical activity: Active, Moderately active and Sedentary. One-way ANOVA and two-way ANOVA evaluated the interaction between practice of physical activities and indicators of medical cost. For categorical variables, the chi-square was used to verify the existence of associations. Logistic and linear regressions were also applied. Results: Diabetic neuropathy rate was approximately 30% and diabetic patients without its diagnosis presented higher costs for the health regarding consultations with the general practitioner. Sedentary diabetic subjects had 63% higher cost for general practitioner than active ones (p = 0.012). Diabetics insulin-dependent had higher costs for drugs (R$40.554,9±2976 vs R$2.454,4±216; p= 0,001) and nursing visits (R$8.064,8±487 vs R$6.147,9±208; p= 0,001) than those ones non-insulin-dependent. Among those using insulin, physical activity had no apparent effect on cost. The therapeutic scheme also influenced the cost, and diet increased the cost of treatment and exercise reduced it. Conclusion:... (Complete abstract click electronic access below) / Mestre

A neuropatia periférica diabética é caracterizada por hiperalgesia e alodínia. O receptor CB1 é o principal responsável pelo efeito dos canabinóides na via nociceptiva. A Hemopressina (Hp), é um agonista inverso do CB1, que induz antinocicepção. Neste trabalho investigamos o efeito do tratamento com Hp (2,5 mg/Kg, por 28 dias) sobre a neuropatia diabética de camundongos, induzido por estreptozotocina (200mg/kg). A Hp reverte a hipersensibilidade mecânica em camundongos com neuropatia diabética, sendo que este efeito é específico para o tratamento da nocicepção e envolve a participação de receptores CB1, astrócitos e microglia em nível espinal. A Hp também previne a desmielinização do nervo isquiático dos animais diabéticos, e auxilia na manutenção dos níveis do NGF. Ainda, a Hp participa no controle da sensibilidade ao estímulo térmico quente em animais KO MOR e participa do controle da sensibilidade mecânica de animais KO MOR diabéticos pelo aumento da dimerização de CB1-DOR na medula espinal. Revelando a Hp um candidato para fins terapêuticos. / Diabetic peripheral neuropathy is characterized by hyperalgesia and allodynia. CB1 receptors are primarily responsible for the effect of cannabinoids in nociceptive pathways. Hemopressin (Hp) is an inverse agonist of CB1, which induces antinociception. In this study we investigated the effects of treatment with Hp (2.5 mg / kg for 28 days) on mice subjected to diabetic neuropathy by streptozotocin (STZ - 200 mg/kg). Hp treatement reversed the mechanical hypersensitivity in mice with neuropathy diabetic, and this effect is specific for the treatment of nociception and involves the participation of CB1 receptors, astrocytes and microglia at the spinal level. Hp prevented demyelination of the sciatic nerve in diabetic animals, and assisted in mantaining the levels of NGF. Also, Hp participates in the control of heat sensitivity to thermal stimulus in KO MOR animals and participates in the control of mechanical sensitivity in KO MOR diabetics animals by the increase in CB1-DOR dimerization in the spinal cord. Revealing Hp as a candidate for therapeutic purposes.

A eletromiografia de superfície (EMGs) é atualmente muito utilizada para diversos fins, em especial por ser um método não invasivo, com o objetivo de verificar a atividade elétrica neuromuscular em diversas doenças e/ou lesões que venham afetar esse sistema. E também as modificações, os efeitos e a especificidade do exercício e/ou treinamento físico na função neuromuscular. Em relação às diversas doenças potencialmente capazes de causar alterações nas propriedades teciduais e fisiológicas do sistema neuromuscular, destaca-se o Diabetes Mellitus Tipo II (DM tipo II). O principal objetivo do presente estudo foi estudar a resposta do sinal eletromiográfico frente ao exercício resistido agudo do tipo Leg Press 45° dos músculos reto femoral (RF), vasto medial (VM), vasto lateral (VL) e bíceps femoral (BF), em indivíduos portadores de DM tipo II. Participaram deste estudo 10 indivíduos portadores de DM tipo II (GD) e 10 indivíduos saudáveis (GC), na faixa etária de 50 a 60 anos. Não foram observadas diferenças significativas (p \'< OU =\' 0,05) para idade (55,3±6,1 vs 55,5±5,7) e estatura (1,7±0,1 vs 1,7±0,1) entre o GD e GC. Entretanto houve diferenças estatística significativas entre GD e GC para os valores de massa corporal (92,9±7,6 vs 84,2±13,8) e Índice de Massa Corpórea (IMC) (32,07±1,7 vs 27,8±2,5). Em relação à análise do sinal eletromiográfico foram observadas diferenças em relação ao recrutamento muscular ao longo do movimento de \"Leg Press\" destacando-se que para o GD o músculo mais ativo foi o RF seguido do VL, já para o GC foi o VL seguido do VM, e quanto aos valores de slope do RMS não houve diferença quanto ao músculo BF para ambos os grupos demonstrando valores positivos, porém para os músculos RF, VM e VL houve diferença entre os GC e GD. Resultados estes que podem estar associados a alterações do sistema neuromuscular, desencadeadas pela resistência insulínica ao tecido muscular e modificações metabólicas causadas pelo DM tipo II. / Surface electromyography (sEMG) is currently widely used for various purposes, especially for being a noninvasive method, in order to check the electrical activity in various neuromuscular diseases and / or injuries that may affect this system. And also changes the effects and specificity of exercise and / or exercise training on neuromuscular function. Regarding the various diseases that can potentially cause changes in tissue properties and physiological neuromuscular system, there is the Type II Diabetes Mellitus (DM type II). The main objective of this study was to study the response of the electromyographic signal against acute resistance exercise like \"Leg Press\" 45 ° of the rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF), in individuals with type II DM. The study included 10 individuals with type II DM (GD) and 10 healthy individuals (CG), aged 50-60 years. There were no significant differences (p \'< OU =\' 0.05) for age (55.5±5.7 vs 55.3±6.1) and height (1.7±0.1 vs 1.7±0.1) between the GC and GD. However there were statistically significant differences between GC and GD values for body mass (84.2±13.8 vs 92.9±7.6) and body mass index (BMI) (27.8±2.5 vs 32,0±1.7). Regarding the analysis of the electromyographic signal differences were observed in relation to muscle recruitment during the movement \"Leg Press\" highlighting that for GD muscle was the most active followed by VL RF, since the CG was followed VL VM, and the values of the RMS slope there was no difference in BF for both groups demonstrating positive values, but to the muscles RF, VM and VL was no difference between the GC and GD. These results that may be associated with changes in the neuromuscular system, triggered by insulin resistance to muscle tissue and metabolic changes caused by diabetes mellitus type II.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-01-05T10:19:14Z No. of bitstreams: 1 lucianadonascimentocampissi.pdf: 2290736 bytes, checksum: f85ace5a49af039ecef38e258539073a (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2017-01-31T10:34:04Z (GMT) No. of bitstreams: 1 lucianadonascimentocampissi.pdf: 2290736 bytes, checksum: f85ace5a49af039ecef38e258539073a (MD5) / Made available in DSpace on 2017-01-31T10:34:04Z (GMT). No. of bitstreams: 1 lucianadonascimentocampissi.pdf: 2290736 bytes, checksum: f85ace5a49af039ecef38e258539073a (MD5) Previous issue date: 2016-08-12 / A detecção precoce do diabetes mellitus e suas complicações constituem verdadeiros desafios para a saúde pública. Em um sistema público organizado hierarquicamente como o SUS (níveis primário, secundário e terciário) temos na Atenção Primária a entrada no sistema de saúde. Logo torna-se fundamental que o rastreio do DM e suas complicações sejam efetivos, de modo a evitar perdas funcionais e aposentadorias precoces. Uma das complicações mais temíveis do diabetes mellitus é a neuropatia diabética, condição altamente prevalente e responsável por cerca de 70% dos casos de amputação não-traumática. Assim, o rastreio da neuropatia diabética pode reduzir os impactos pessoais, familiares e sociais dessa condição crônica. Objetivo: elaborar um teste de triagem simples e de fácil aplicação para detecção precoce da neuropatia diabética pelo enfermeiro da Atenção Primária à Saúde. Método: Estudo transversal no qual foram avaliados 269 prontuários de pacientes diabéticos atendidos no Centro Hiperdia/Juiz de Fora-MG. Foram tabulados dados demográficos, clínicos e neurológicos da população avaliada no período de 2010 a 2014. Resultados: Sessenta e dois por cento dos diabéticos eram do sexo feminino; a média idade foi de 58,7 anos e o Índice de Massa Corporal teve média de 30,6; o tempo médio de diagnóstico do diabetes mellitus foi de 11,5 anos e a hemoglobina glicada (HbA1c) foi igual a 9,1 %. Queimação nos pés (64,9%), parestesia (83,8%), dormência (73%) e dor neuropática (54,1%) foram os sintomas mais prevalentes. Os sintomas foram preditores ruins para o diagnóstico de neuropatia diabética provável. Por outro lado, as alterações das sensibilidades térmica e dolorosa e a ausência do reflexo Aquileu foram as anormalidades mais frequentemente relacionadas com a presença de neuropatia diabética. / Early detection of diabetes mellitus and its complications are real challenges for Public Health. In a public system hierarchically organized as SUS (primary, secondary and tertiary levels), primary care is the entry into the health system. It is essential the effective screening of DM and its complications to avoid functional loss and early retirements. One of the most feared complications of diabetes mellitus is the diabetic neuropathy, a highly prevalent condition that accounts for about 70% of the cases of non-traumatic amputation. Therefore, the screening of diabetes mellitus can reduce personal, social and familial impacts of this chronic condition. Objective: to develop a screening test of simple application for early detection of diabetes mellitus by the nurse in primary care. Method: a cross-sectional study was made with data of 269 subjects based on medical records of diabetic patients attended at Hiperdia Center/Juiz de Fora-MG. Demographic, clinical and neurological data of the population evaluated between January of 2010 to December of 2014 were statistically analyzed. Results: sixty-two percent were female; the average age was 58.7 years and body mass index average was of 30.6 kg/cm2; the average time of diagnosis of diabetes mellitus was 11.5 years and glycated hemoglobin (HbA1c) was 9.1%. Burning sensation in the feet (64.9%), paresthesia (83.8%), numbness (73%) and neuropathic pain (54.1%) were the most prevalent symptoms, but the symptoms were bad predictors for the diagnostic of probable diabetic neuropathy. On the other hand, abnormalities of thermal sensitivity and pain as well as the absence of ankle jerk reflex were most often related to the presence of diabetic neuropathy.

FundaÃÃo de Amparo à Pesquisa do Estado do Amazonas / Os efeitos dos triterpenos pentaciclicos &#61537;-amirina e &#61538;-amirina, isolados a partir da resina de Protium heptaphyllum March. (Burseraceae), foram testados preliminarmente em modelos de nocicepÃÃo oral, sendo que &#61538;-amirina apresentou significantes efeitos antinociceptivos, norteando a pesquisa com este isolado na investigaÃÃo de seus efeitos em modelos de dor orofacial induzida por capsaicina ou formalina e na dor induzida por capsaicina na cÃrnea de camundongos; na dor tÃrmica (testes de imersÃo de cauda em Ãgua quente e placa quente); e na nocicepÃÃo visceral induzida por Ãcido acÃtico 0,6%. Camundongos Swiss machos (n = 8 / grupo) foram prÃ-tratados com &#946;-amirina (10, 30 e 100 mg / kg, v.o.), morfina (5 mg / kg, s.c.) ou controle (Ãgua destilada + 0,05% de Tween 80, v.o.), uma hora antes de capsaicina (20 &#61549;L, 1,5 &#61549;g) ou formalina (20&#61549;L/animal) serem administradas na vibrissa direita. &#946;-amirina tambÃm foi avaliada em teste comportamental relacionado à dor, desta vez por aplicaÃÃo tÃpica de capsaicina na conjuntiva do camundongo (âeye wiping testâ). Neste teste foi medido o tempo, em segundos, que o animal passou âlimpandoâ o olho durante um perÃodo de 10 minutos. O triterpenÃide demonstrou principalmente um efeito antinociceptivo dose-independente em todos os modelos de nocicepÃÃo testados. Na dor orofacial induzida por capsaicina, &#61538;-amirina (30 e 100 mg/kg) e morfina foram mais eficazes na reduÃÃo da resposta nociceptiva. Nestas doses, as reduÃÃes foram de 81 e 90% para &#61538;-amirina e 97% para morfina, respectivamente. No modelo de dor orofacial, a nocicepÃÃo produzida pela capsaicina à acompanhada por um aumento na resposta tÃrmica localizada (que foi mensurada por termometria), e reduzida significantemente pelo prÃ-tratamento dos animais com &#61538;-amirina ou L-NAME, um inibidor da NOS. Em animais diabÃticos, a capsaicina injetada na vibrissa promoveu um menor grau de nocicepÃÃo orofacial comparada com os nÃo-diabÃticos. No teste da formalina, morfina e &#946;-amirina apresentaram antinocicepÃÃo significativa reversÃvel nas duas fases por naloxona. No entanto, &#946;-amirina (30 mg/kg) inibiu a segunda fase com maior eficiÃncia. Os valores de DE50 para &#946;-amirina e morfina foram 16,44 mg/kg (LC 10,0-38,41) e 3 mg/kg (LC 2,5-5,0) na primeira fase e 43,37 mg/kg (LC 30,52-39,30) e 3 mg/kg (LC 2,5-5,0) na segunda fase, respectivamente. A co-administraÃÃo de &#946;-amirina e morfina, em seus respectivos nÃveis de dose de DE50, nÃo apresentou qualquer efeito aditivo ou potencializador antinociceptivo. No entanto, as combinaÃÃes das doses DE25 e DE12,5 apresentaram uma antinocicepÃÃo comparÃvel ao efeito combinado da DE50, sugerindo que atravÃs da utilizaÃÃo de &#946;-amirina, a dose analgÃsica de morfina poderia ser minimizada para evitar a sua alta dose e os efeitos colaterais associados. &#946;-amirina tambÃm foi eficaz em aumentar o limiar de dor tÃrmica no teste da imersÃo da cauda (mais nÃo no teste placa quente) e, na reduÃÃo das contorÃÃes induzidas por Ãcido acÃtico. A antinocicepÃÃo produzida por &#946;-amirina, foi significativamente bloqueada em animais prÃ-tratados com os respectivos antagonistas vermelho de rutÃnio (2 mg/kg, s.c.) e naloxona (1 mg/kg, i.p.), indicando o envolvimento de receptores da capsaicina (TRPV1) e opiÃides em seu mecanismo. No teste da formalina, de forma similar à morfina, &#946;-amirina bloqueou significativamente a inibiÃÃo da ingestÃo alimentar associada a dor. Assim como morfina, &#946;-amirina apresentou aÃÃo inibitÃria sobre o trÃnsito intestinal, efeito esse revertido pelo prÃ-tratamento com antagonista opiÃide nÃo seletivo, naloxona. Estes dados sugerem que &#946;-amirina apresenta um potencial antinociceptivo comparÃvel à analgesia perifÃrica produzida pela morfina, evidencia a exploraÃÃo desta para o desenvolvimento de um analgÃsico nÃo-opiÃide Ãtil na farmacoterapia de patologias do trigÃmeo e visceral. / The effects of pentacyclic triterpene &#946;-amiryn and &#946;-amyrin, isolated from resin of Protium heptaphyllum March. (Burseraceae), were preliminarily showed significant tested in models of nociception oral, and antinociceptives effects, guiding the search with this isolate in the investigation of their effects in models of orofacial pain induced by capsaicin or formalin and against capsaicin-induced corneal pain; thermal pain (tail immersion test in hot water and hot-plate) and in acetic acid 0,6%-induced visceral nociception in mice. Male Swiss mice (n = 8 per group) were pre-treated with &#946;-Amyrin (10, 30, and 100 mg/kg, p.o.), morphine (5 mg/kg, s.c.) or vehicle (distlled water + 0,05% Tween 80), one hour before the capsaicin (20 &#956;l, 1.5 &#956;g) or formalin (20 &#956;l, 1.5%) injection into the right vibrissa. &#946;-Amyrin was also assessed on pain-related behavioral test (Eye-wiping) by topical application of capsaicin (20 &#956;l, 1.5 &#956;g) on to the mouse conjuctiva and the time (sec) that the animal spent in eye wiping was determined during a 10 min period. The triterpenoid demonstrated mostly a dose-unrelated antinociception in all the test models of nociception. Against the orofacial pain induced by capsaicin, &#946;-Amyrin (30 e 100 mg/kg, p.o.) and morphine showed greater potency in reducing the nociceptive response. At the doses employed, the reductions were 81 and 90% to &#946;-Amyrin and 97% for the morphine, respectively. Capsaicin nociception in orofacial test is accompanied by a localized thermal flare (measured by thermometry), which was significantly diminished by pretreatment of animals with &#946;-Amyrin or L-NAME, an NOS inhibitor. In four weeks diabetic mice, capsaicin injected into vibrissa pad demonstrated a lesser degree of orofacial nociception compared to non-diabetics. In formalin test, both morphine and &#946;-Amyrin showed significant naloxone reversible antinociception in both phases. However, &#946;-Amyrin inhibited the second phase response, more prominently, at 30 mg/kg. The caliculated ED50 values for &#946;-Amyrin and morphine were 16,44 mg/kg (CL 10,0 - 38,41) and 3 mg/kg (CL 2,5 - 5,0) in the first phase and 43,37 mg/kg (CL 30,52 - 39,30) and 3 mg/kg (CL 2,5 - 5,0) in the second phase, respectively. Co-administration of &#946;-Amyrin and morphine at their respective ED50 dose levels failed to demonstrate any additive or potentiating effect on anti-nociception. However, at ED25 and ED12.5 dose-combinations exhibited an antinociception that equalled their ED50 combination effect, suggesting that by the use of &#946;-Amyrin, the analgesic dose of morphine could be minimised to avoid its high-dose-associated side-effects. Similar to morphine, &#946;-Amyrin significantly blocked the pain-related suppression of food intake in formalin test. &#946;-Amyrin (30 and 100 mg/kg was also effective in increasing the thermal pain threshold in hot-water tail immersion test (but not in hot-plate test), and in reducing the acetic acid-induced writhes. The antinociception produced by 30 mg/kg &#946;-Amyrin was significantly blocked in animals pre-treated with the respective antagonists capsazepine (5 mg/kg, s.c.), and naloxone (1 mg kg/kg, i.p.), indicating the involvement of capsaicin (TRPV1) and opioid receptors in its mechanism. Like morphine, &#946;-Amyrin showed an inhibitory effect on intestinal transit, an effect reversed by pretreatment with nonseletive opiÃide antagonist, naloxona. These data indicate that &#946;-Amyrin has the antinociceptive potential comparable to peripheral analgesia produced by morphine that could be explored further on its suitability in developing a non-opioid analgesic useful in pharmacotherapy of trigeminal and visceral pathologies.

Diabetes mellitus affects more than 382 million people worldwide and an estimated 30-50% of patients develop some form of neuropathy. Patients typically present with sensory symptoms including hypersensitivity/pain and/or loss of somatosensation. In diabetic neuropathy, the longest nerves of the peripheral nervous system (PNS) show the worst pathology and symptoms are typically felt in the distal extremities. The cause of this apparent length-dependent pathology remains unknown. Through comprehensive integration of untargeted proteomic and metabolomic analyses of the PNS in the streptozotocin rat model of diabetes, we showed that bioenergetic pathways were more dysfunctional in the distal sciatic nerve (SN) than the lumbar 4/5 dorsal root ganglia (DRG) and cranial trigeminal ganglia (TG). Whilst glucose levels increased in all tissues in diabetes, there was extensive upregulation of proteins involved in mitochondrial oxidative phosphorylation in the distal SN compared to healthy age/weight-matched controls which was not evident in the proximal DRG or TG. There were significant changes in lipid metabolites in the SN, a phenomenon which is less apparent in the DRG and not evident in the TG. We investigated the therapeutic potential of copper chelation with triethylenetetramine to reverse such changes and whilst copper chelation prevented nerve conduction velocity deficits, it did not alter aberrant nerve metabolism. To further understand the functional deficits in diabetic neuropathy, we performed in vivo microelectrode recordings from the TG and the thalamic ventral posteromedial (VPM) nucleus in control and diabetic rats in response to precise whisker stimulation. Recordings from the TG showed that the tuning of the primary afferents to graded stimuli is preserved in diabetes. Furthermore, we found that neurons within the VPM showed increased spontaneous activity in diabetes, but maintained tuning to graded whisker stimulation in their evoked firing rate. Thus, the cranial TG appear to be relatively unaffected by diabetes at a biochemical or physiological level, but diabetes may lead to pathophysiological changes within the thalamus which could alter somatosensory processing. Despite a global metabolic insult in diabetes, the molecular consequences are not consistent throughout the nervous system. We show that metabolic dysfunction occurs specifically in regions known to be more affected in neuropathy. Due to such a focal dysfunction, aberrant oxidative phosphorylation in the sciatic nerve may be a key driver to the distal pathogenesis of diabetic neuropathy.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2016-05-18T14:21:17Z No. of bitstreams: 1 Mozania Reis de Matos.pdf: 2867660 bytes, checksum: ba235c77e42996f7aa6a0a4de5a2c5cd (MD5) / Made available in DSpace on 2016-05-18T14:21:17Z (GMT). No. of bitstreams: 1 Mozania Reis de Matos.pdf: 2867660 bytes, checksum: ba235c77e42996f7aa6a0a4de5a2c5cd (MD5) Previous issue date: 2015-03-03 / In practical prevention , the instruments that extend self-care are welcome. Added to this the stimulus promotion, health education and the interdisciplinary care. The Patient Interpretation of Neuropaty (PIN), is a questionnaire of Interpretation of neuropathy by patient, developed and validated in the USA and in England (UK). By means of this instrument, the patient makes the self-evaluation of your foot and health care to be carried out with it, aiming at the prevention of ulcer diabetic foot. Thus, the aim of the present study is to translate and validate the questionnaire of interpretation of neuropathy for the Portuguese and assess the degree of understanding of the patients on the questions of (PIN). Participated in this study 100 patients at the outpatient clinic of foot insensitive of the Institute of Orthopedics and Traumatology, University of Sao Paulo. Were used parametric and non-parametric tests in the analysis of data.The values obtainedwith the BrazilianversionPINare verysimilar to the valuesof the original versions, theUSAandtheUK.We think it isa valuabletool providingthe patientobserveneuropathicchangesthat increase the risk of ulcers on the feet. The questionnairetranslated and validatedfor the Portuguese language, soit seemsto be a reliableandapplicabletool to evaluate theself-careof the patientat the same timethat allows thehealthcare professionalto designeffective measuresforprevention ofdiabetic footulcer, resulting in a betterprognosisandquality of life ofdiabetes patientswithND. / Nas práticas de prevenção, os instrumentos que ampliem o autocuidado são bem vindos. Soma-se a isto o estimulo a promoção, a educação em saúde e o atendimento interdisciplinar. O PatientInterpretationofNeuropaty (PIN), é um questionário de Interpretação da Neuropatia pelo Paciente, desenvolvido e validado nos USA e na Inglaterra(UK). Por meio deste instrumento o paciente faz a auto avaliação do seu pé e dos cuidados de saúde a serem realizados com ele, visando à prevenção da úlcera de pé diabético. Sendo assim o presente estudo tem como objetivo traduzir e validar o questionário de interpretação da neuropatia para o português e avaliar o grau de compreensão dos pacientes sobre as indagações do (PIN). Participaram deste estudo 100 pacientes do ambulatório de pé insensível do Instituto de Ortopedia e Traumatologia da Universidade de São Paulo. Foram usados testes paramétricos e não paramétricos na análise de dados. Os valores obtidos com a versão Brasileira do PIN são muito semelhantes aos valores das versões originais, dos USA e da U.K. Julgamos ser um instrumento valioso que propicia ao paciente observar alterações neuropáticas que aumentam o risco de úlcera nos pés. O questionário traduzido e validado para a língua portuguesa, parece assim ser um instrumento confiável e aplicável paraavaliar o autocuidado do paciente,ao mesmo tempo quepermite ao profissional de saúde desenhar medidas efetivas para prevenção da úlcera de pé diabético,ocasionando um melhor prognostico e qualidade de vida dos portadores de diabetes com ND.

Title: Evaluation of selected postural stability parameters of diabetic patients Objectives: The main objective of this thesis is to describe the level of postural stability using the selected parameters in diabetes mellitus type 2 and to try to find a relationship between the severity of disease. We also want to compare the level of postural stability for such an illness with respect to the values of selected parameters of the healthy population. Methods: It is a descriptive study. The theoretical part was the basis of the processing problems of diabetes mellitus, with a focus on neuropathy. After that we evaluate data of selected parameters of postural stability in diabetes mellitus type 2. The second part involves the experiment, which refers to the evaluation of this issue in terms of posturographic analysis. A group of 30 type 2 diabetic patients were divided according to their diabetologist disease severity into 4 groups. A control group of healthy subjects included a sample of 7 probands. The patient group was composed of 18 men and 12 women, whose average age was 62.63 ± 15.55 years, average weight 91.17 ± 19.97 kg, who were subjected to measurement using a pressure plate FootScan (RScan International, Belgium). Results: We managed to prove, that subjects with diabetic neuropathy have...

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My PhD research studies, described in this thesis, were designed to document the temporal development of mechanical allodynia, a hallmark symptom of painful diabetic neuropathy (PDN), as well as opioid hyposensitivity using two different rat models of diabetes mellitus (DM). Specifically, the studies were conducted using the streptozotocin (STZ)-diabetic rat model of chemically-induced Type 1 diabetes in two different rat strains, as well as the Zucker Diabetic Fatty (ZDF) rat genetic model of Type 2 diabetes. Additionally, a longitudinal investigation of the effect of basal insulin replacement therapy to restore euglycaemia from 7-days post-STZ administration, on the development of mechanical allodynia in the hindpaws of the STZ-diabetic Wistar rat model of PDN, was conducted. The studies herein also included a longitudinal study to document the temporal development of mechanical allodynia and opioid hyposensitivity in the ZDF rat, which also examined the influence of dietary composition on the time course for the development of mechanical allodynia in the hindpaws, together with opioid hyposensitivity in these animals. In the final section of this thesis, the experiments were designed to examine possible mechanisms that may contribute to the development of opioid hyposensitivity in ZDF diabetic rats. These experiments involved the quantification of opioid receptor messenger ribonucleic acid (mRNA) gene expression as well as μ-opioid receptor (MOP-r) functional responses in tissues collected from 29-wk old diabetic ZDF rats relative to 7-wk old pre-diabetic control ZDF animals. In Chapter One, diabetes mellitus and more specifically its longterm complication, PDN, the focus of this doctoral research program, has been reviewed. Specifically, possible pathogenic mechanisms underlying mechanical allodynia, the relevant diabetic rodent models of PDN, use of insulin replacement therapy in diabetic rodents and its impact on hallmark symptoms of PDN, role of opioid pharmacology, the comparative efficacy of opioids in the treatment of PDN, and possible mechanisms that may underpin the development of opioid hyposensitivity in PDN, including the impact of altered excitatory neurotransmitters, have been reviewed. In Chapter Two, a preliminary study was conducted to investigate the efficacy of 4-wks treatment with Linplants (subcutaneous (s.c.) sustained-release bovine insulin implants) alone and in combination with ActRapid® (s.c. human insulin; 0.05 U to 3.5 U/100 g/day) with respect to glycaemic control in STZ-diabetic Wistar rats, and on acute diabetes characteristics for a 5-wk post-STZ administration period. Briefly, STZ-diabetic rats were divided into three groups: (1) rats which received no insulin treatment, (2) rats which were implanted with one s.c. Linplant at Day 7 post-STZ administration, and (3) rats which received one s.c. Linplant plus a once-daily injection of ActRapid® once diabetes was confirmed at 7-days post-STZ administration. The findings were that following implantation of a single Linplant at Day 7 post-STZ administration, euglycaemia was achieved in 50% of STZ-diabetic rats, with glycaemic control maintained for up to 4-wks post-implantation. Furthermore, once-daily injection of ActRapid™ to animals whose blood glucose levels (BGLs) were not well-controlled through use of Linplants alone, failed to achieve euglycaemia. It is possible that the ActRapid™ doses administered were not sufficient to achieve euglycaemia, and that increasing the doses may provide more effective glycaemic control. However, doubling the mean ActRapid™ dose from 1.63 (+ 0.3) U administered at Day 28 to 2.56 (+ 0.6) U administered at Day 34 post-STZ administration effectively only reduced BGLs by 1.3 mM to 11.6 + 1.6 mM. This suggests that although administering additional large doses of ActRapid™ to STZ-diabetic rats may eventually achieve euglycaemia, this method would presumably not be a more efficient method in achieving euglycaemia compared with the use of dosage-adjustable s.c. Linplants. Group (1) STZ-diabetic rats which were not treated with insulin developed diabetic signs including polydipsia, hyperphagia, decreased rate of body weight gain, and mechanical allodynia. Group (2) rats in which insulin treatment from 7-days post-STZ administration restored euglycaemia and reversed polydipsia and hyperphagia, were protected against the development of mechanical allodynia and reduced weight gain for the 5-wk study duration, while rats from Group (3) with incomplete glycaemic control developed levels of polydipsia, hyperphagia, reduced weight gain and mechanical allodynia intermediate between rats in Groups (1) and (2). These findings collectively suggest a direct correlation between the level of glycaemic control and the extent to which mechanical allodynia, a defining symptom of PDN, develops. In Chapter Three, the findings from the preliminary 5-wk study in Chapter Two were used to design a 24-wk longitudinal study of the temporal development of mechanical allodynia and opioid hyposensitivity in STZ-diabetic Wistar rats for comparison with the findings of a similar study previously undertaken by our laboratory using STZ-diabetic Dark Agouti rats (Nielsen et al, 2007). Additionally, this study examined the effects of tight glycaemic control achieved through the use of insulin implants as a means of potentially preventing the development of mechanical allodynia and opioid hyposensitivity for up to 24 weeks in STZ-diabetic Wistar rats. Briefly, STZ-diabetic rats were divided into 3 groups: (1) non-insulin treated STZ-diabetic Dark Agouti rats to provide comparison data with our laboratory’s previously published data in this rat strain (Nielsen et al, 2007), (2) non-insulin treated STZ-diabetic Wistar rats to examine possible between-species differences, and (3) STZ-diabetic Wistar rats which were treated with adjustable-dose s.c. Linplants from Day 7 post-STZ administration to maintain euglycaemia for the remainder of the 24-wk study period. In this 24-wk longitudinal study in STZ-diabetic rats, body weight, 24-hr water intake, paw withdrawal thresholds (PWTs) and BGLs were monitored at fortnightly intervals in all animals in order to document possible temporal changes in the development of diabetic signs and mechanical allodynia in the hindpaws respectively. STZ-diabetic rats underwent 6-wkly opioid antinociceptive testing, using single bolus doses of each of morphine and oxycodone with a 2-3 day washout period between individual opioids in order to assess the potential influence of both diabetes and glycaemic control on opioid potency in these animals. The findings demonstrate that non-insulin treated STZ-diabetic rats of both strains exhibited a decreased rate of body weight gain and polydipsia, as well as progressive development of mechanical allodynia in the hindpaws and loss of morphine potency. Importantly, STZ-diabetic Wistar rats which were treated with insulin to maintain euglycaemia from Day 7 post-STZ administration failed to develop these diabetic symptoms for the duration of the 24-wk study period, highlighting the importance of chronic hyperglycaemia in the development of mechanical allodynia and morphine hyposensitivity in the STZ-diabetic rodent model of PDN. The research described in Chapter Four involved a 22-wk longitudinal study of the development of diabetes and its longterm sensory nerve complications, viz mechanical allodynia and opioid hyposensitivity, in the ZDF rodent model of Type 2 diabetes commencing at 7-wks of age. This study also examined the influence of four different diets fed to separate groups of ZDF rats from 7-wks age, on the time course for the development of diabetes, mechanical allodynia in the hindpaws and opioid hyposensitivity in these animals. Briefly, ZDF rats were sub-divided into four dietary groups, each of which was fed one of the four following diets for 22-wks commencing at 7-wks of age, viz: (a) Purina 5008™, (b) a domestically-produced rat chow of similar composition to Purina 5008 (termed Purina Composition diet), (c) a Diabetogenic diet, or (d) Standard Rat Chow. All rats underwent once-fortnightly measurement of BGLs, body weight, 24-hr water intake, and measurement of PWTs in the hindpaws. Additionally, ZDF rats underwent opioid antinociceptive testing, similar to that previously described for STZ-diabetic rats (Chapter Three), to investigate the influence of diabetes and dietary composition on the antinociceptive potency of single bolus doses of morphine and oxycodone administered at 6-weekly intervals over a 22-wk study period. The afore-mentioned data were compared with the respective data obtained from the pre-diabetic control group of ZDF rats that were euthanised at 7-wks of age prior to the development of hyperglycaemia. The results demonstrate that the ZDF rat develops mechanical allodynia in the hindpaws and opioid hyposensitivity in a temporal fashion, in a manner similar to that previously documented for the STZ-diabetic Wistar rat model of Type 1 diabetes (Chapter Three). For the four diets assessed, there did not appear to be significant differences between dietary groups with respect to the time course and extent of development of hyperglycaemia, mechanical allodynia or opioid hyposensitivity in the ZDF rat model of PDN. The study described in Chapter Five investigated the effect of both diabetes and dietary composition on opioid receptor mRNA expression in tissue samples collected from the five groups of ZDF rats used in the behavioural studies described in Chapter Four and outlined above. Briefly, mRNA expression for each of the - (MOP), - (DOP), and - (KOP) receptors were quantified in mid-brain and spinal cord tissues prepared from 29-wk old diabetic ZDF rats maintained on one of four diets from 7-wks age, and compared with the respective expression levels in samples prepared from pre-diabetic ZDF rats euthanised at 7-wks of age. Overall, the findings suggest that diabetes does not alter opioid receptor mRNA expression in the mid-brain or spinal cord of diabetic ZDF rats at 29-wks of age relative to the corresponding levels of mRNA expression in the mid-brain and spinal cord of pre-diabetic ZDF rats at 7-wks of age. Hence, the marked reduction in the anti-allodynic potency of morphine and oxycodone observed in diabetic ZDF rats at 29-wks of age relative to that observed in pre-diabetic ZDF rats at 7-wks of age (Chapter Four) does not appear to be associated with a decrease in opioid receptor mRNA expression. In Chapter Six, the effect of both advanced diabetes and dietary composition on opioid-agonist stimulated [35S]GTPγS binding was examined in spinal cord tissue membranes from the ZDF rat. Specifically, [35S]GTPγS binding assays were used to assess the ability of a -opioid ligand (DAMGO) to stimulate -opioid receptor coupling to inhibitory G proteins in homogenates prepared from spinal cord samples of 29-wk old ZDF rats maintained on one of four different diets from 7-wks age (Chapter Four), relative to [35S]GTPγS binding in homogenates prepared from spinal cord samples of pre-diabetic 7-wk old ZDF rats. As specific MOP agonist-stimulated [35S]GTPγS binding was significantly decreased in spinal cord homogenates from diabetic ZDF rats at 29-wks of age relative to that for pre-diabetic ZDF rats (7-wks), this may contribute, at least in part, to the morphine hyposensitivity observed in diabetic ZDF rats at 29-wks of age relative to the pre-diabetic ZDF group. However, closer examination of these data revealed that specific MOP agonist-stimulated [35S]GTPγS binding above basal did not differ significantly between the pre-diabetic group and the longterm diabetic group of ZDF rats. Instead, there was significantly lower basal [35S]GTPγS binding in the spinal cord of ZDF rats at 29-wks c.f. 7-wks of age. Together, the findings suggest that impaired basal G-protein function rather than impaired coupling of MOP-r to its inhibitory G-protein may, at least in part, underpin -opioid agonist hyposensitivity in 29-wk ZDF rats. Finally, Chapter 7 contains a brief description of the main conclusions and discussion of the relevance of this doctoral research project, including potential future research directions.