Peripheral nerve conduction deficits and changes in skeletal muscle contractile and histochemical properties caused by 2-4 months of experimental diabetes were examined in mature rats. The effect of aldose reductase inhibitor treatment was assessed in preventative and reversal studies. The efficacy of 1% dietary myoinositol supplementation was examined in a two month preventative group. Moderate insulin therapy, which reduced but did not normalise blood glucose levels was also employed. Data from diabetic animals was compared with that obtained from rats fed a 40% galactose diet for up to four months, as well as a combined galactose/ARI treated group. The pattern of neuropathy was very similar in diabetic and galactosaemic animals. Fast conducting motor and sensory branches were the most severely affected and at two months conduction velocities were slowed by approximately 25% compared to onset levels. Ponalrestat treatment successfully prevented this effect in both models. In reversal treated diabetic animals there was a differential response to ponalrestat treatment, ranging from complete restoration of conduction in the sensory saphenous to a modest improvement (10%) in the soleus motor branches. Insulin produced a small increase in conduction velocity on its own and conduction was normal when combined with ponalrestat treatment. Myo-inositol treatment had no beneficial effect. There was a marked rise in sciatic nerve polyol levels, in both diabetic and galactosaemic animals, accompanied by a fall in nerve free myoinositol levels. Ponalrestat treatment markedly reduced sciatic nerve polyol accumulation. Nerve myo-inositol content, in both diabetic and galactosaemic animals, was significantly increased by short term ponalrestat treatment. However, in the four month preventative and reversal groups it was notv significantly different from diabetic controls. Diabetes had differential effects on slow and fast twitch muscles. For the soleus, there was a slowing of twitch and tetanic contraction and relaxation times and a reduction of maximum tetanic relaxation rate. Ponalrestat treatment largely prevented the slowing of soleus relaxation, but had little effect on contraction. For the EDL muscle there was little change in twitch contraction times but, maximum tetanic relaxation rate was reduced. In contrast to soleus, which maintained its strength performance, EDL tetanic tension was reduced. This was partly attributed to the profound wasting of the EDL with diabetes, and in particular the marked atrophy of fast glycolytic (FG) fibres. While these effects were partially prevented by ponalrestat treatment, established deficits were harder to restore in the reversal study. A similar pattern of ARI preventable dysfunction was found in both the soleus and EDL muscles of galactose fed animals. Partial insulin therapy prevented the slowing of diabetic soleus twitch contraction time but had no effect on relaxation. For EDL, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate which were antagonised by ponalrestat treatment. A 1% dietary myo-inositol supplementation had no effect on contractile function in slow or fast muscles. Diabetes produced a marked increase in soleus fatiguability. This was associated with a reduction in oxidative enzyme histochemical staining and a decrease in the capillary/fibre ratio. Preventative or reversal ponalrestat treatment produced near normal resistance to fatigue, had beneficial effects on oxidative enzyme staining and capillary/fibre ratio. Galactosaemia produced comparable deficits in soleus fatigue resistance which were prevented by ponalrestat. However, there was little disruption in oxidative enzyme staining. Sorbitol and fructose levels were increased in diabetic muscle. Levels tended to be lower in ARI treated groups. Muscle MI content was also elevated with diabetes and ARI treatment had little effect. There was a large accumulation of galactitol in galactosaemic muscles, which was markedly reduced by ARI treatment. It was concluded that polyol pathway activity is an important factor in the development of peripheral nerve and skeletal muscle dysfunction with diabetes. The data indicate that the underlying mechanisms may not depend on the restoration of myoinositol levels, and suggest that a vascular hypothesis could provide a unified explanation for diabetic effects as well as a basis for aldose reductase inhibitor treatment.

Abstract PO2 DEPENDENCE OF OXYGEN CONSUMPTION IN SKELETAL MUSCLE OF DIABETIC AND NON-DIABETIC RATS By: Alexander C. Liles A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Medical College of Virginia Campus, Virginia Commonwealth University Virginia Commonwealth University, 2017 Advisor: Roland N. Pittman, Ph.D. Department of Physiology and Biophysics Type 2 diabetes mellitus (T2DM) is a major medical problem around the world, affecting nearly 6% of the world’s population. This study was an attempt to better understand physiological changes the disease may cause to the microcirculation and more specifically, to assess the dependence of oxygen consumption in skeletal muscle of a diabetic animal model. The spinotrapezius muscles of Goto-Kakizaki (G-K) and Wistar control rats were used to measure interstitial using phosphorescence quenching microscopy. The G-K rats spontaneously develop T2DM and serve as an appropriate model for the disease in humans. By rapidly arresting blood flow in the tissue and observing the resulting changes, an oxygen disappearance curve (ODC) was created. The ODC was used to calculate oxygen consumption rate (VO2) over the physiological range of PO2 values. The resulting VO2 vs PO2 curves were analyzed using Hill’s equation to fit the data and obtain values of several key parameters to quantitatively describe the PO2 dependence of oxygen consumption. When compared to healthy control rats, the G-K rats exhibited a significantly higher Vmax, or maximum rate of oxygen consumption, compared to the Wistar rats. The two rat sub-strains had similar values for P50, which indicates the PO2 at half maximal consumption. The overall higher maximal rate of consumption by the diseased animals could be explained by some disconnect in the consumption of oxygen by the mitochondria and the normal corresponding production of ATP. In conclusion, it was demonstrated that in situ muscle tissue from both diabetic and non-diabetic rats had a PO2 dependence of oxygen consumption over a wide range of PO2 values and the muscles of diabetic animals consumed oxygen at a higher maximal rate.

No description available.

Approximately 7 – 9 % of the population is living with some form of diabetes. When poorly controlled (which is often the case), this disease is associated with cerebrovascular pathology such as microbleeds and impairments in cognitive function. The presence and burden of microbleeds in the brain has been strongly linked with cognitive decline and increased risk of dementia. Microglia, the resident immune cells of the central nervous system, dynamically respond to vascular insults by extending their processes to the site of injury. The rapid actions of microglia are thought to play a beneficial role in vascular repair since inhibiting these responses can exacerbate injury. Here, we hypothesized that diabetes, especially if not well controlled with insulin, will disrupt microglia responses to damaged microvessels in the brain which will lead to increased plasma leakage from damaged microvessels. Using two-photon in vivo imaging, we show that chronic hyperglycemia in the streptozotocin model of type one diabetes leads to decreased microglial process accumulation around the site of microvascular injury and increased permeability of fluorescent dyes from the damaged vessel 30 minutes after induction of the bleed. Importantly, this impaired microglial and vascular response could be partially mitigated with tight control of blood glucose levels with insulin. These results indicate that chronic hyperglycemia disrupts microglial based repair of damaged microvessels, which may help explain why poorly controlled diabetes is associated with greater a risk of cerebrovascular dysfunction and cognitive decline. / Graduate / 2018-01-12

Mucormycosis and aspergillosis are the most frequent fungal infections caused by filamentous fungi; coinfection in the same host is rare. We present a case of a 78-year-old male patient with the debut of type 2 diabetes mellitus and ketoacidosis, with swelling of the right side of the face, right facial paralysis, ptosis and a necrotic ulcer in the right palate. Facial Computed tomography showed an abscess of the right maxillary sinus. Cultured secretions revealed Aspergillus fumigatus. The pathology result of biopsies of the palate, maxillary sinus and ethmoid bone was consistent with mucormycosis. The patient was treated with voriconazole, amphotericin B deoxycholate, and surgical debridement of the maxillary sinus. The patient died despite the treatment. The coinfection of Rhinocerebral mucormycosis and aspergillosis should be suspected in immunosuppressed patients in order to establish early management that can permit an improved prognosis of the disease. / La mucormicosis y la aspergilosis son las causas más frecuentes de infecciones micóticas causadas por hongos filamentosos, la coinfección en un mismo huésped es poco frecuente. Se presenta el caso de un paciente varón de 78 años con debut de diabetes mellitus tipo 2 y cetoacidosis, que presenta tumefacción de hemicara derecha, parálisis facial derecha, ptosis palpebral y úlcera necrótica en paladar derecho. La tomografía computarizada de macizo facial evidenció un absceso del seno maxilar derecho, de cuya secreción se cultivó Aspergillus fumigatus. El resultado de anatomía patológica de biopsia de paladar, seno maxilar y hueso etmoidal fue compatible con mucormicosis. El paciente recibió tratamiento con voriconazol, anfotericina B desoxicolato y debridamiento quirúrgico del seno maxilar. Sin embargo, pese al manejo, falleció. La coinfección rinocerebral por mucormicosis y aspergilosis debería ser sospechada en pacientes inmunosuprimidos con el fin de establecer un manejo temprano que permita mejorar el pronóstico de la enfermedad.

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Objetivo: Establecer la prevalencia y factores de riesgo para disfunción eréctil (DE) en diabéticos del Hospital Alberto Sabogal 2003. Metodología: Se diseño un estudio descriptivo-explicativo, y transversal. Se incluyeron 100 diabéticos tipo 2 con actividad sexual en últimos 6 meses, excluyéndose otras causas de DE. Todos los pacientes fueron sometidos a una encuesta sobre diabetes mellitus, comorbilidad, medicación y el Índice Internacional de Disfunción Eréctil score abreviado (IIDE-5); se revisaron las historias clínicas. Se utilizo el programa Epi-info 2000. Resultados: La edad promedio era 62.63±9.65 años. El tiempo de diabetes fue 9.63±10.43 años, los niveles de hemoglobina glicosilada 6.19±2.61%, el 69% se trataba con hipoglicemiantes orales, 13% con insulina, 14% solo dieta y 4% terapia combinada. El promedio de relaciones sexuales fue 3.84±3.74 al mes. La prevalencia de DE fue del 70%. La prevalencia se incremento con la edad, en el grupo de 31-50 años fue 46.7%, llegando al 85.7% en aquellos de 71-80 años de edad (p =0.0239). La severidad DE. aumento con la edad (p =0.022). DE fue asociado a: tiempo de diabetes mayor de 20 años (p =0.000026), indicadores indirectos severidad de la diabetes como uso hipoglicemiantes (p =0.011) , insulina (p =0.0043). No se encontrarón relación .con otras variables. Conclusión: Existe una alta prevalencia DE en la población diabética. La edad y el tiempo de diabetes fueron los principales factores asociados. / --- Objective: To determine the prevalence and risk factors of erectile dysfunction (ED) in diabetics type 2 from Alberto Sabogal Hospital 2003. Methods: I designed a cross over and descriptive and explicative study. A total of 100 diabetics type 2 with sexual activity in last 6 months were evaluated; others causes of ED were excluded. All patients were interviewed and asked to about diabetes mellitus, morbility, drugs, and abbreviate form of International Index of Erectile Dysfunction (IIED), To revised clinical archives. It analysed Epi-info 2000 program. Results: The average age was 62.63±9.65 years. The diabetes time was 9.63±10.43 years, the level of glycosylated haemoglobin was 6.19±2.61%, the diabetes treatments were hypoglycaemic drugs 69%, insulin 13%, only diet 14% and mixed treatment 4%. The average rate of sexual activity was 3.84±3.74 coitus monthly. The prevalence of ED was 70%. The ED prevalence increase with age, It was 46.7% in the 31-50 years group, rather It was 85.7% in 71-80 years group (p =0.0239). On other hand the ED severity was directly associated with age (p =0.022). ED was associate with diabetes time major of 20 years (p =0.000026), hipoglicemiantes treatment (p =0.011) , insulin treatment (p =0.0043). I did not find association with other variables. Conclusions: Diabetic population have a high prevalence of DE. The age, and diabetes time were strong associated to ED.

Se desarrolló el presente estudio en la Unidad de Pie Diabético del Servicio de Medicina Interna Nro 3 del Hospital Nacional Guillermo Almenara Irigoyen ESSALUD de Lima en 100 pacientes que presentaron Pie Diabético con compromiso lsquémico o neuroinfeccioso hospitalizados en dicha unidad entre setiembre de 1999 a febrero del 2000. Los datos fueron consignados en una ficha pre-elaborada, se excluyeron pacientes con datos incompletos clínicos, epidemiológicos o de laboratorio y aquellos en quienes fue imposible realizar el seguimiento de la lesión. Los pacientes enrolados en el estudio fueron sometidos a un interrogatorio con la finalidad de obtener datos referentes a la diabetes, factores de riesgo y factores desencadenantes, luego se procedió al examen clínico buscando identificar lesiones en los pies clasificándolos según estadíos de Wagner y clasificación cubana de Mc-Cook. En un grupo de pacientes se efectuó estudios laboratoriales para evaluar el control metabólico de la diabetes mediante el estudio de los valores de hemoglobina glicosilada, así como también el perfil lipídico, función renal y albuminemia. Se evaluaron los niveles anatómicos de obstrucción mediante arteriografía, considerándose válido este examen si fue realizado en los seis meses anteriores al estudio. Con todos los resultados, y enfocados en cada tipo de paciente, se seleccionó la opción terapéutica más adecuada, cotejándose ésta de acuerdo al tipo inicial de lesión y otras variables incluidas en el estudio. Los resultados nos muestran que:. El mayor porcentaje de pacientes en nuestra serie correspondió al Pie Diabético lsquémico (60% de casos estudiados). Los pacientes fueron predominantemente mayores de 60 años y con un tiempo de diabetes de 17 años en promedio. EL 55% correspondió al sexo masculino. El 12% de diabéticos tuvo antecedentes de DVC isquémico, el 12% de enfermedad coronaría y el 50% antecedentes de Hipertensión Arterial. Los pacientes acudieron en estadíos avanzados de enfermedad, así el 61.6% de Pies lsquémicos en estadío IV de Wagner y el 42.5 de Pies Neuroinfecciosos en estadío III de Wagner. Respecto a las manifestaciones clínicas se halló predominancia estadísticamente significativa en cada grupo, como cambios de coloración para el Pie lsquémico, y la presencia de úlceras, eritema, secreción, tumefacción y calor para el Pie Neuroinfeccioso. En cuanto al evento desencadenante el porcentaje de pacientes que no lo recuerdan es alto (61%), y de los que lo registran, la cortadura de callos ocupa un porcentaje importante (14%). Los datos de laboratorio mostraron mal control de la diabetes en el 60% de casos, dislipídemia en más del 50%, compromiso de la función renal en casi el 50% e hipoalbumineia en el 26% de nuestra serie. El compromiso arteriográfico predominante fue el territorio tibio-peroneo (80%). El tratamiento instaurado para el Pie Diabético Neuroinfeccioso fue mayoritariamente el de Limpieza Quirúrgica con excéresis de huesos comprometidos en los casos necesarios, mas curaciones tópicas e injertos plásticos. La amputación mayor se realizó en sólo el 15% en este grupo de pacientes. En el caso del Pie Diabético lsquémico la amputación fue el tratamiento predominante (58.33%), y dentro de éste, las amputaciones supracondíleas ocuparon el 93.5% de la casuística evaluada, siendo bajos los porcentajes de revascularización y angioplastía. El Tiempo de Hospitalización fue en promedio 19 días. Se ha querido con este trabajo de investigación conocer la magnitud de la patología del Pie Diabético en la Unidad de Pie Diabético del Hospital Nacional Guillermo Almenara lrigoyen-ESSALUD; contribuir a su manejo integral, con el objeto de conservar la integridad física, funcional y emocional del paciente, y siendo éste el primer estudio realizado en la Unidad de Pie Diabético, establecer una pauta de comparación a futuros trabajos sobre esta patología, en beneficio del paciente a quien le debemos todo nuestro esfuerzo.

English abstract Diabetes mellitus (DM) is the best known endocrine disease of the pancreas where the incidence of the affected individuals is increasing rapidly worldwide. It is caused by defects in both the pancreatic islets and in the pancreas to produce enough insulin resulting in impaired glucose homeostasis leading to higher than normal glucose levels in the blood (hyperglycaemia) which is considered to be the hallmark of diabetes. Consequently the main aim of diabetes management is to monitor the glycaemic status. Diabetes mellitus can be subdivided into two classes, type 1 diabetes mellitus (T1DM) which is also known as insulin- dependent diabetes mellitus and type 2 diabetes mellitus (T2DM) which is known as non- insulin-dependent diabetes mellitus. Management of either type of DM requires a number of lifestyle modifications such as increased exercise and decreased weight with the intention of improving metabolic control and enhancing the quality of life. Unfortunately, the majority of patients will eventually require administration of antidiabetic drugs. The present study was performed with the intention of reviewing the currently available scientific literature about both types of DM and discuss the current and novel approaches of treatment, thus giving more emphasis on the novel advances. For...

Fluorescein angiography is used in the routine clinical examination of patients with suspected retinopathy. Conventional angiography involves the photography of a subject's retina after injection with a small quantity of fluorescein dye. In this study, we have developed a technique to measure the movement of this dye through the retinal circulation. Two implementations of angiography have been investigated - conventional photography and capture of the angiographic frames using the scanning laser ophthalmoscope (SLO). After pre-processing to remove any noise present, the images are registered via cross-correlation to remove the effects of patient movement. A gamma variate plus 2nd order polynomial dye-dilution model is then fitted to the temporal change in fluorescein intensity at each point in the retina. Parameters are extracted from these fitted curves and their values combined to form functional images of the retinal circulation. A total of 16 angiograms of varying quality have been analysed using this technique. A distinctive filling pattern has been detected in the parametric images of the normal angiograms analysed, indicating a preferential flow of fluorescein, and hence blood, to the macula region of the retina. A number of abnormal angiograms were also analysed and the time to maximum images of these patients showed good agreement with their various pathologies. This included identifying occluded vessels, areas of ischaemia and oedema, as well as more subtle features such as leakage and microaneurysms. The generation of functional parametric images from fluorescein angiograms enables various aspects of the retinal circulation to be quantified. The technique offers a potential aid to diagnosis enabling the onset of retinopathy to be detected and its progression closely monitored.