Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

Abstract Purpose: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). Methods: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. Results: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). Conclusion: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

Alterações dos parâmetros da marcha e déficit sensório-motor associado à neuropatia diabética periférica / Changes in gait parameters and sensory-motor deficit associated with peripheral diabetic neuropathy

Quando há dano no sistema nervoso periférico, com prejuízos sensoriais e motores, como observado em neuropatas diabéticos, podem ocorrer graves repercussões sobre o equilíbrio e a locomoção nesta população. Objetivo: Avaliar o desempenho da marcha e alterações sensório-motoras, decorrentes da neuropatia diabética periférica. Método: Participaram 24 indivíduos neuropatas diabéticos e 28 indivíduos saudáveis sem alterações glicêmicas indicativas de diabete. Osparticipantes foram submetidos inicialmente a avaliações clínicas para confirmação de diagnóstico de neuropatia diabética por meio de teste de sensibilidade tátil da sola dos pés com monofilamentos. Posteriormente, foram submetidos à avaliação da variação angular do tornozelo, em condição estática e durante a marcha, por meio de cinemetria. A força muscular do tornozelo foi investigada por meio de dinamometria digital. Resultados: Foi demonstrado maior duração nos períodos deduplo apoio e apoio total da marcha em indivíduos com neuropatia diabética quando comparados com o grupo controle, confirmando uma maior dificuldade no equilíbrio dinâmico destes indivíduos. Para o grupo experimental de indivíduos neuropatas foi evidenciado redução da força muscular, tanto para os músculos dorsiflexores, quanto para os plantiflexores de tornozelo. Conclusão: As perdas sensório-motoras decorrentes da NDP podem implicar em prejuízo no desempenho da marcha, com consequente perda de equilíbrio.

Peripheral nervous system impairment, with sensory and motor loss, as observed in diabetic neuropathy, can induce serious effects on balance control and gait in this population. Objective: To evaluate the performance of the gait and the sensory-motor changes, stemming from peripheral diabetic neuropathy (PDN). Method: Twenty-four individuals with PDN participated along with twenty-eight healthy individuals with no glycemic alterations indicative of diabetes. Participants were first subjected to clinical evaluations to confirm the clinical diagnosis of diabetic neuropathy by testing the tactile sensitivity of the soles of the feet with a monofilament test. Subsequently, ankle angle variations in static posture and during the gait were investigated through kinematics. The ankle muscle strength was investigated using a digital dynamometer. Results: The diabetic neuropathy group showed longer duration in double support and full support periods of gait than the control group, confirming greater difficulty in dynamic balance for these individuals. The group with neuropathy demonstrated reduced muscle strength, as much in the dorsiflexors as in the plantar flexors of the ankle. Conclusion: The sensory-motor losses stemming from PDN may cause impairment in gait performance, with consequent loss of balance.

Avaliação da qualidade de vida em pacientes com diabetes mellitus e pé ulcerado / Assessment of the quality of life of patients with diabetes mellitus and foot ulcers

INTRODUÇÃO: O pé diabético é uma das mais devastadoras complicações crônicas do diabetes mellitus, em função do grande número de casos que evoluem para amputação. O objetivo deste estudo é avaliar a qualidade de vida de pessoas diabéticas com pé ulcerado comparativamente às pessoas diabéticas sem úlceras. MÉTODO: Realizado estudo analítico, transversal, controlado e comparativo, com pacientes atendidos em 2 centros de tratamento de feridas de São Paulo. Foram selecionadas 50 pessoas para compor o grupo controle, com diabetes mellitus sem pé ulcerado, e 50 para o grupo estudo, composto de pacientes diabéticos com pé ulcerado. O instrumento usado para avaliar a qualidade de vida foi o questionário Short Form-36 Health Survey (SF-36). A inclusão dos pacientes no estudo obedeceu à ordem de chegada. RESULTADOS: Na avaliação dos pacientes do grupo controle, o escore médio do SF-36 foi 69,38 ± 21,90 e do grupo estudo, 30,34 ± 14,45 (P < 0,001). A média dos escores em todos os domínios do SF-36 do grupo estudo foi mais baixa em relação ao grupo controle (P < 0,001). CONCLUSÕES: Os pacientes diabéticos com pé ulcerado apresentam alterações na qualidade de vida, repercutindo nos domínios físico, social e psicoemocional.

BACKGROUND: Diabetic foot is considered as one of the most devastating chronic complications of diabetes mellitus due to the large number of cases that eventually require amputation. In the present study, we aimed to assess the quality of life of patients with diabetes and foot ulcers compared to that of patients with diabetes but without foot ulcers. METHODS: An analytical, cross-sectional, controlled, and comparative study of patients who visited 2 wound clinics in São Paulo was performed. Fifty patients with diabetes mellitus but without foot ulcers were selected as the control group and 50 patients with diabetes and foot ulcers were selected as the study group. The Short Form-36 Health Survey (SF-36) questionnaire was used to assess the quality of life. Patients were included consecutively in the same order that they visited the clinic. RESULTS: The mean SF-36 score was 69.38 ± 21.90 in the control group and 30.34 ± 14.45 in the study group (P < 0.001). Mean scores across all SF-36 domains were lower in the study group than in the control group (P < 0.001). CONCLUSIONS: Patients with diabetes and foot ulcers experience changes in the quality of life in the physical, social, and psychoemotional domains.

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats / Efeitos da suplementação com L-glutamina sobre os neurônios mioentéricos do duodeno e jejuno de ratos diabéticos

CONTEXT: Peripheral neuropathy is one of the chronic complications of diabetes mellitus and is directly related to gastrointestinal consequences of the disease. Myenteric neurons are affected in some pathological conditions such as diabetic neuropathy. The imbalance between cellular antioxidants and free radicals, leading to an increase in oxidative stress, is considered one of the main factors responsible for neuronal damages in diabetes. Drugs that reduce the oxidative stress may play a significant role in the treatment of neurological complications of diabetes mellitus. OBJECTIVE: To evaluate the effect of L-glutamine supplementation on the myenteric neurons from the cecum and duodenum of Wistar rats with streptozotocin-induced diabetes mellitus. METHODS: The animals were divided in four groups (n = 5): non-treated normoglycemics, normoglycemics treated with L-glutamine, non-treated diabetics and diabetics treated with L-glutamine from the 4th day of diabetes induction on. The amino acid L-glutamine was added to their diet at 1 percent. Giemsa's technique was employed to stain the myenteric neurons. We determined the cell body area of 500 neurons in each group studied. The quantitative analysis was performed by sampling in an area of 16.6 mm² in the cecum and 3.6 mm² in the duodenum of each animal. RESULTS: After the supplementation with L-glutamine in the duodenum, we observed a preservation of neuronal density in groups normoglycemic and diabetic (P<0.05). We also observed a preservation of the cell bodies area in diabetic animals (group treated with L-glutamine) (P<0.05). In the cecum, that preservation was not evident. CONCLUSION: Supplementation with L-glutamine (1 percent) promoted a neuroprotective effect on the myenteric neurons from the duodenum of rats, both in terms of natural aging and of diabetes mellitus.

CONTEXTO: Os neurônios entéricos são afetados em condições patológicas, como a neuropatia diabética. A neuropatia periférica é uma das complicações crônicas do diabetes mellitus e está diretamente relacionada com as manifestações gastrointestinais da doença. O desequilíbrio entre antioxidantes celulares e radicais livres, com o consequente aumento do estresse oxidativo, é considerado um dos principais responsáveis pelas alterações neuronais provocadas pelo diabetes. Drogas que reduzem o estresse oxidativo podem ter papel relevante no tratamento das complicações neurológicas do diabetes mellitus. OBJETIVO: Avaliar os efeitos da suplementação com L-glutamina sobre os neurônios mioentéricos do ceco e duodeno de ratos Wistar com diabetes mellitus induzido pela estreptozootocina. MÉTODOS: Os animais foram divididos em quatro grupos (n = 5): normoglicêmicos, normoglicêmicos suplementados com L-glutamina, diabéticos, diabéticos suplementados com L-glutamina a partir do 4º dia da indução do diabetes. O aminoácido L-glutamina foi adicionado à ração na quantidade de 1 por cento. A técnica de Giemsa foi utilizada para evidenciar os neurônios mioentéricos. Foram avaliadas as áreas de corpos celulares de 500 neurônios em cada grupo estudado. A análise quantitativa foi realizada em uma área de 16,6 mm² no ceco e 3,6 mm² no duodeno de cada animal. RESULTADOS: Após suplementação com L-glutamina verificou-se no duodeno a preservação da densidade neuronal tanto nos animais normoglicêmicos quanto nos animais diabéticos (P<0,05), e também o restabelecimento da área do corpo celular nos animais diabéticos (P<0,05). No ceco esta preservação e restabelecimento não foram evidenciados. CONCLUSÃO: A suplementação com L-glutamina (1 por cento) teve efeito neuroprotetor sobre os neurônios mioentéricos do duodeno tanto em condições de envelhecimento natural como no diabetes mellitus.

Diabetic peripheral neuropathies: a morphometric overview / Neuropatías diabéticas periféricas: una visión general morfométrica

Diabetes is now considered one of the main threats to human health in the 21st century and many researchers are dedicated to investigate the physiopathology of the disease, with further insights on the managements of its major complications. Since understanding the pathophysiology of the major complications of diabetes and their underlying processes is mandatory, experimental models of the disease may be useful as they allow the recognition of the early mechanisms involved in the long-term complications of diabetes. Peripheral nerve involvement is highly frequent in diabetes mellitus and it has been documented that one third of diabetic patients have peripheral neuropathy. The true prevalence is not known and reports vary from 10 percent to 90 percent in diabetic patients, depending on the criteria and methods used to define neuropathy. In this review, the most common experimental models of diabetes are presented and the pathological findings on major peripheral nerves are discussed. Also, the insights brought by morphometry to the diabetic neuropathy research are highlighted.

La diabetes es considerada hoy una de las principales amenazas para la salud humana en el siglo 21 y muchos investigadores se dedican a investigar la fisiopatología de la enfermedad, con otras visiones sobre el manejo de sus principales complicaciones. Dado que la comprensión de la fisiopatología de las principales complicaciones de la diabetes y sus procesos subyacentes es obligatorio, modelos experimentales de la enfermedad pueden ser útiles ya que permiten el reconocimiento de los primeros mecanismos implicados en las complicaciones a largo plazo de la diabetes. El compromiso de los nervios periféricos es muy frecuente en la diabetes mellitus y se ha documentado que un tercio de los pacientes diabéticos tiene neuropatía periférica. La prevalencia es desconocida y los informes varían de 10 por ciento a 90 por ciento en los pacientes diabéticos, en función de los criterios y métodos utilizados para definir la neuropatía. En esta revisión, se presentan los modelos experimentales más comunes de diabetes y se discuten los hallazgos patológicos en los principales nervios periféricos. Además, se destacan las visiones presentadas por la morfometría de la investigación la neuropatía diabética.

Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2 / Clinical heterogeneity and coexistence of diabetic neuropathies: difference and similarities between types 1 and 2 diabetes mellitus

OBJETIVO: Estudar a heterogeneidade e a coexistência das neuropatias no diabetes melito tipos 1 (DMT1) e 2 (DMT2). MÉTODOS: Foram avaliados 74 DMT2 e 20 DMT1 em relação à idade (anos), tempo de diagnóstico do DM (TDDM, em anos), índice de massa corpórea (IMC, kg/m²), HbA1c e tipo de neuropatia (critérios da American Diabetes Association). RESULTADOS: DMT1 era mais jovem (32,7 ± 11 versus 56,9 ± 10,3; p = 0,0001), com maior TDDM (17,1 ± 9,7 versus 10,4 ± 6,8; p = 0,003) e menor IMC (23,6 ± 3,8 versus 28,4 ± 5,3; p = 0,0005). A neuropatia autonômica cardiovascular (NAC) (60 por cento versus 32,4 por cento; p = 0,02) e a coexistência desta com polineuropatia (PND) (62,5 por cento versus 33,3 por cento; p = 0,03) foram mais prevalentes no DMT1; a PND dolorosa crônica (PNDDC) (60,8 por cento versus 30,0 por cento; p = 0,009) o foi no DMT2. A HbA1c (p = 0,04) foi preditiva de PND em ambos os grupos. O TDDM (p = 0,03) e a PNDDC (p = 0,003) foram preditivos de NAC no DMT1. A idade (p = 0,0004) teve valor preditivo para PNDDC no DMT2. CONCLUSÕES: As neuropatias apresentam distribuição heterogênea no DMT1 e no DMT2. Com exceção do controle glicêmico, os fatores relacionados a essa complicação diferem de acordo com o tipo de diabetes.

OBJECTIVE: To evaluate the heterogeneity and the coexistence of diabetic neuropathy (DNP) in type 1 (T1DM) and 2 (T2DM) diabetes mellitus. METHODS: 74 T2DM and 20 T1DM patients were evaluated according to age (years), time from diagnosis of diabetes (TDD, years), body mass index (BMI, kg/m²), HbA1c and DNP type (American Diabetes Association criteria). RESULTS: T1DM was younger (32.7 ± 11.0 versus 56.9 ± 10.3; p = 0.0001), leaner (BMI: 23.6 ± 3.85 versus 28.4 ± 5.3; p = 0.0005) and they had longer TDD (17.1 ± 9.7 versus 10.4 ± 6.8; p = 0.003). Cardiovascular autonomic neuropathy (CAN) (60 percent versus 32.4 percent; p = 0.02) and its coexistence with polyneuropathy (PN) (62.5 percent versus 33.3 percent; p = 0.03) were more common in T1DM. Chronic painful polyneuropathy (CPP) was more prevalent in T2DM (60.8 percent versus 30.0 percent; p = 0.009). Logistic regression showed HbA1c as an independent variable related to PN (p = 0.04) in both groups. TDD (p = 0.03) and CPP (p = 0.003) were related to CAN in T1DM. Age (p = 0.0004) was related to CPP in T2DM. CONCLUSIONS: The DNP have shown a heterogeneity distribution in type 1 and type 2 diabetes mellitus. The related factors to different phenotypes of this complication, apart from hyperglycemia, may be variable between these two types of diabetes mellitus.

Atualização em neuropatias periféricas relacionadas às alterações neurais e vasculares ocorrentes na diabetes mellitus em modelos animais / Update on peripheral neuropathies related to neural and vascular changes that occur in diabetes mellitus in animal models

O trabalho de revisão sistemática aponta os principais aspectos patogênicos relacionados às lesões neurais e vasculares da neuropatia diabética, estudados em modelos animais. Tem como escopo comparar as diversas espécies animais utilizadas nos estudos, salientando os aspectos semelhantes encontrados nos animais e os ocorrentes na doença humana. Foram revistos os trabalhos publicados a partir de 2000, inserindo-se alguns anteriores que serviram de referência para trabalhos atuais.

The systematic review shows the main aspects related to pathological neural and vascular lesions of diabetic neuropathy, studied in animal models. It has the scope to compare the various species of animals used in studies, highlighting the similar aspects found in animals and the issues occurring in human disease. We reviewed the papers published since 2000, as well as some earlier ones that served as a reference for the present studies.

Hacia una prevención primaria y secundaria del pie diabético. Semiología del pie / Toward a primary and secondary prevention for amputations of the feet in diabetic patientss

Chronic complications of diabetes are the most important cause of morbidity of the disease, which constitutes a major public health problem. Patientes with diabetes are more prone to develop premature atherosclerotic disease in the lower extremities, which leads to frequent hospitalizations for common lower extremity amputations... This report offers guidelines for the management of a foot, which is threatened, with loss of the blood supply due to impairment of the circulation of the lower limbs, in diabetic patients.

Fisiopatología y clínica del pie diabético / Pathophysiology and clinical features that involve the foot in diabetic patients

Emergencies that involve the foot in diabetic patients are a very common cause of morbidity. Ischemia is of prime importance but, in addition, neuropathy (with hypoesthesia) and sepsis are factors. Infections may follow minor trauma, or may be secondary, either to a long-standing ulcer or to an area of gangrene. The major importance of chronic ulcers of the feet, is that they are a portal of entry for infection. All these considerations are described in the article, with special considerations to the shoes employed and the stay.

Neuropatia autonômica: uma complicação de alto risco no diabetes melito tipo 1: [revisão] / Autonomic neuropathy: a high risk complication for type 1 diabetes mellitus: [review]

O acometimento patológico do sistema nervoso no diabetes melito é muito amplo e, freqüentemente, bastante grave. A prevalência de neuropatia diabética atinge níveis elevados com a evolução temporal do diabetes, chegando, geralmente, a freqüências acima de 50 por cento de lesão neurológica em diferentes grupos de pacientes analisados em nosso meio e no exterior. A lesão neurológica nesta situação patológica é extensa no organismo humano diabético, envolvendo amplamente todo o sistema nervoso periférico nos seus componentes sensitivo-motor e autonômico: com clínica característica e concordante com as hipóteses patogênicas de natureza metabólica e/ou microvascular. O sistema nervoso autonômico é o elemento fundamental na regulação da função da maior parte dos sistemas ou órgãos no organismo, portanto, a sua lesão pode trazer importantes alterações para as funções cardiovascular, respiratória, digestiva, urinária e genital, podendo influir na função vital de alguns desses órgãos ou sistemas. Este artigo aborda as alterações decorrentes da lesão do sistema nervoso autonômico, especialmente nos pacientes diabéticos tipo 1, procurando dimensionar o risco de morbimortalidade.

The pathological alteration of the nervous system in diabetic patients is extensive and frequently severe. The prevalence of the diabetic neuropathy reach high levels with the evolution of the diabetes, often showing frequencies higher than 50 percent in several groups of patients. The neurological lesion in this pathological situation is extensive in the diabetic patient, including widely the peripheral nervous system with its components sensory, motor and autonomic: with typical symptoms and in accordance with the pathogenesis of metabolic origin and/or microvascular disease. The autonomic nervous system is a main regulator of many systems in the human body. Then its lesion can promote significant alterations in the function of the cardiovascular, respiratory, gastrointestinal, urogenital system, that can be related to increased motality. This review anlyses the abnormalities related to lesion of the autonomic nervous system, particularly in type 1 diabetic patients, trying to characterize the risk of morbidity and mortality.

Focal and multifocal diabetic neuropathies

Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The vast majority of the patients with clinical diabetic neuropathy have a distal symmetrical form that progress following a fiber-length dependent pattern, with predominant sensory and autonomic manifestations. This pattern of neuropathy is associated with a progressive distal axonopathy. Patients are exposed to trophic changes in the feet, pains and autonomic disturbances. Less often, diabetic patients may develop focal and multifocal neuropathy that includes cranial nerve involvement, limb and truncal neuropathies. This neuropathic pattern tends to occur after 50 years of age, mostly in patients with longstanding diabetes mellitus. The LDDP does not show any trend to improvement and either relentlessly progresses or remain relatively stable over years. Conversely the focal diabetic neuropathies, which are often associated with inflammatory vasculopathy on nerve biopsies, remain self limited, sometimes after a relapsing course.

A neuropatia diabética é a mais predominante das neuropatias nos países industrializados apresentando uma gama variável de manifestações clinicas. A maioria dos pacientes com neuropatia diabética apresenta uma forma simétrica distal que progride para um padrão fibra comprimento dependente com manifestações sensitivas e autonomicas. Este tipo de neuropatia é associado com uma axonopatia distal progressiva. Os pacientes apresentam modificações tróficas nos pés, dores e distúrbios autonômicos. Menos freqüentemente os pacientes diabéticos podem desenvolver neuropatia focal e multifocal que incluem envolvimento de nervos cranianos, tronco e membros inferiores. Este padrão de neuropatia é mais freqüente em pacientes com mais de 50 anos e com longa historia de diabetes. Este tipo de neuropatia fibra-comprimento dependente não apresenta melhora, progride lentamente ou permanece estável por vários anos. As neuropatias focais que são associadas freqüentemente com vasculopatias inflamatórias nas biópsias de nervo, permanecem auto limitadas por vezes com surtos de remissão.

Pie diabético en el servicio de clínica médica del Hospital Central del Instituto de Previsión Social / Diabetic foot in the service of medical clinic of Hospital Central del Instituto de Previsión Social

El pie diabético es la complicación crónica de la diabetes millitus con mayores implicaciones económicas y sobre la calidad de vida de los pacientes. Objetivos: determinar y evaluar la incidencia, características clínicas y evolución de los pacientes con pie diabético durante su internación. Diseño metodológico: estudio descriptivo, retrospectivo, tranversal, que incluye todos los pacientes con diagnóstico de pie diabético, internados en el Servicio de Clínica Médica del HCIPS desde el 1 de enero al 31 de diciembre del 2005; mediante la revisión de epicrisis de dichos pacientes. Resultados: en el periodo citado ingresaron 4041 pacientes, de los cuales 1200 (30%) eran diabéticos; 116 (10%) presentaban pie diabético, que cosntituye el 3% del total de pacientes internados; de los 116 pacientes; 58 (50%) eran femeninos y 58 (50%) masculinos, promedio de edad 66,3 años; 105/116 (90,5%) eran hipertensos; 91/116 (78%) recibía tratamiento farmacológico; 68/91 en forma regular; 40/68 (59%) insulina NPH; 17/116 tenían amputación previa; a 65/16 (56%) se le practicó amputación del miembro afecto; 23/65 (35%) dedo; 10/65 (15%) infracondilea; 32/65 (50%) supracondilea; 102/116 recibieron el alta médica; 6/116 traslado a UTI; 4/116 fallecieron; 3/116 traslado a cirugía general; 1/116 alta voluntaria; promedio de internación 14,99 días. Discusión: la incidencia del pie diabético en el Servicio es el doble a lo que describe la literatura, así como la amputación como tratamiento definitivo. Conclusión: el pie diabético presente una alta incidencia en el Servicio, afectando fundamentalmente a personas de la tercera edad y que en la mayoría de los casos requiere de amputación del miembro como tratamiento definitivo, con elevado valor de días de internación.

Neuropatía diabética periférica: correlación de la escala clínica de toronto y la bioestesiometría / Periphereal diabetic neuropathy: correlation between toronto's clinical

La Neuropatía Periférica (NPD) es la complicación crónica más frecuente en los pacientes con diabetes mellitus (DM), e importante factor de riesgo para el desarrollo del pie diabético, pero no hay un consenso clínico preciso para su diagnóstico. La Escala clínica de Toronto (ECT) es una propuesta reciente que clasifica la NDP. La bioestesiometría cuantifica de manera no invasiva el umbral de sensibilidad vibratoria (USV) con el objetivo de relacionar estos métodos diagnósticos. Estudio comparativo del tipo caso control, transvrsal, al azar, en 170 pacientes con DM que acudieron a la Unidad de Diabetes del Hospital Vargas durante el período Junio-Septiembre del 2003, y 100 sujetos sanos, sin sesgo interobservador. A los primeros se les realizó anamnesis, evaluación clínica subjetiva, de los aspectos contenidos de la ETC, e instrumental a través de la bioestesiometría y la prueba del clavo en manos y pies; a los sujetos sanos se les aplicó evaluación instrumental. La ETC detectó 68 por ciento de casos de NDP en los pacientes con DM y se correlacionó con la bioestesiometría en los pies, con sensibilidad y especificidad de 100 y 79 por ciento respectivamente. Se documentó la utilidad del test de clavo en los pies para el diagnóstico de NDP. La ETC es correlacionable con los niveles de USV por biotensiometría, y este método cuantitativo logró detectar anormalidades neurológicas dístales no evidenciadas por la ETC

Repercussões das alterações da inervação autonômica no diabetes melito / Impact of autonomic dysfunction in diabetes mellitus

Com o objetivo de esclarecer aspectos da patogênese e do diagnóstico das polineuropatias do diabetes e complicações a ele relacionadas, temos desenvolvido alguns estudos. Assim como outros autores, observamos, nos pacientes diabéticos com desnervação simpática, hipertensão arterial sistêmica relacionada a posição supina e normo ou hipotensão relacionada a ortostatismo, o que torna o manejo dessa condição bem peculiar. Recentemente, foi demonstrado que as alterações do sistema simpático cardíaco no diabetes correspondiam tanto a áreas de desnervação (distais) como de hiperinervação (proximais) do ventrículo esquerdo. Pacientes com desnervação simpática e parassimpática grave apresentam, além de sintomas relacionadas ao comprometimento do sistema nervoso somático, tais como paresias e parestesias, manifestações clínicas que decorrem da desnervação de outros órgãos, tais como tonturas, disfagia, vômitos, diarréia, incontinência fecal, retenção urinária e sudorese gustatória. Evidências de disfunção autonômica simpática predizem mortalidade de 60 por cento em 5 anos. Essa alta mortalidade está relacionada à ocorrência de insuficiência renal, cardiopatia isquêmica e arritmias. Na presente revisão, descrevem-se os métodos utilizados para diagnosticar essa condição.

Effect of cilostazol on the neuropathies of streptozotocin-induced diabetic rats

OBJECTIVES: This study examined the effect of cilostazol, a potent phosphodiesterase inhibitor, on the progression of neuropathies associated with streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. METHODS: Eight weeks after streptozotocin treatment, a pelleted diet containing 0.03% cilostazol (15 mg/kg body weight) was given for four weeks. Body weight, blood glucose level, motor nerve conduction velocity (MNCV), myelinated fiber density and size distribution of sciatic nerves were compared between age-matched normal rats (Group 1), control diabetic rats (Group 2) and cilostazol-treated diabetic rats (Group 3). RESULTS: Body weight was significantly reduced and blood glucose level was significantly increased in diabetic rats (Group 2 and 3) compared to normal rats. MNCV and cAMP content of sciatic nerves were significantly reduced in diabetic rats 12 weeks after streptozotocin treatment. Myelinated fiber size and density were also significantly reduced, and thickening of the capillary walls and duplication of the basement membranes of the endoneural vessels were observed in the diabetic rats. Whereas both body weight and blood glucose level of Group 3 did not differ significantly from those of Group 2, cilostazol treatment significantly increased MNCV and cAMP content of sciatic nerves in Group 3 but not to the levels observed in Group 1. MNCV positively correlated with cAMP content of sciatic nerves (r = 0.86; p < 0.001). Cilostazol treatment not only restored myelinated fiber density and size distribution but reversed some of the vascular abnormalities. CONCLUSION: These findings suggest that a reduced cAMP content in motor nerves may be involved in the development of diabetic neuropathy, and that cilostazol may prevent the progression of diabetic neuropathy by restoring functional impairment and morphological changes of peripheral nerves.

Ultrastructure of neuromuscular junction in vacor-induced diabetic rats

OBJECTIVES: Rodenticide Vacor causes a severe peripheral neuropathy in humans. Electrophysiologic studies on a peripheral motor nerve-skeletal system of Vacor-treated rat showed decreased amplitude of muscle action potential without conduction velocity abnormalities. The ultrastructural studies of the neuromuscular junction were performed to clarify the anatomic site of the Vacor-induced peripheral neuropathy in male Wistar rats. METHODS: After oral administration of a single dose of Vacor, 80 mg/kg of body weight, to the experimental animals, neuromuscular junctions within the interosseous muscles of the hind foot were observed in time. RESULTS: No axon terminal change was noted until 24 hours after the administration of Vacor. Remarkable loss of presynaptic vesicles and swollen endoplasmic reticulum in the axon terminal were developed at 3 days after Vacor treatment. Progressive degenerative changes consisting of marked loss of presynaptic vesicles, focal disruption of membrane in the axon terminal with disappearance of the number of the damaged axon terminal appeared, and flattening of postsynaptic folds was also seen. CONCLUSIONS: These results suggest that degenerative changes in axon terminal at neuromuscular junction may contribute to the peripheral neuropathy developed in the early phase of Vacor poisoning.

Limits of variation of fiber distribution in the sural nerve of man

Although the sural nerve is the most extensively studied nerve in man, there is a dearth of data regarding the normal variations in the size-frequency distribution of axons in normal subjects; criteria for assessing the normality of a given individual are not available. Therefore, in everyday practice, the surgical pathologist may meet with difficulty in interpretit the biopsy of one particular individual, in whom the distribution is slightly different from the curves published. The object of this work is to detect the normal limits of variation in the distribution of diameters of muelinated and unmyelinated fibers in normal subjects and to establish the criteria that permit the calculated curves to be used in veryday clinical practice. Normal sural nerves of 19 patients were analyzed. Ages ranged between 18 months and 55 years. Morphometric analysis was performed with the Histoscan X automatic image processing analyzer, and , for statistical analysis, mixtures of lognormal distributions were fitted and tested with Pearson's statistics. Nerves of three diabetic patients were used for testing the method. They were clearly classified as abnormal. The curves, therefore, have been proven useful for everyday surgical pathology practice