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Ashley L. Waldron Patricia A. Schroder Kelly L. Bourgon Jessie K. Bolduc James L. Miller Adriana D. Pellegrini Amanda L. Dubois Magdalena Blaszkiewicz Kristy L. Townsend Sandra Rieger 《Journal of diabetes and its complications》2018,32(3):249-257
Background
A complication of diabetes is neuropathy, a condition of sensory axon degeneration that originates in the epidermis. The mechanisms remain unknown but reactive oxygen species (ROS) have been implicated in this condition. In this study, we assessed the role of ROS and a candidate downstream target, MMP-13 in glucose-induced sensory axon degeneration in zebrafish and mice.Methods
The effects of glucose on metabolism and sensory axon degeneration were assessed using qPCR and live imaging. ROS were analyzed using pentafluorobenzene-sulfonyl fluorescein and activation of the NF-κB stress response was determined using Tg(NF-κB:GFP) zebrafish. The role of MMP-13 and ROS in glucose-dependent axon degeneration was determined in zebrafish following treatment with the antioxidant, N-acetylcysteine and the MMP-13 inhibitor, DB04760. Neuropathic mice fed on a high-fat/high-sugar diet were treated with the MMP-13 inhibitor, CL-82198 to assess sensory recovery.Results
Glucose treatment of zebrafish induced metabolic changes that resemble diabetes. Sensory axon degeneration was mediated by ROS-induced MMP-13 and prevented upon antioxidant treatment or MMP-13 inhibition. MMP-13 inhibition also reversed neuropathy in diabetic mice.Conclusion
We demonstrate that zebrafish are suitable to study glucose-induced neurotoxicity. Given the effects in zebrafish and mice, MMP-13 inhibition may be beneficial in the treatment of human diabetic neuropathy. 相似文献85.
Bolko P Jaskuła M Waśko R Bednarek J Sowiński J 《Polskie Archiwum Medycyny Wewn?trznej》2003,109(2):165-169
The frequent association of thyroid and parathyroid disorders has been reported. Most commonly, hyperthyroidism may coexist with hypercalcemia, but the latter is successfully treated when euthyroidism is achieved. However, the concomitant hyperthyroidism with primary hyperparathyroidism is of a rare occurrence. Moreover, it may frequently go unrecognized. In this paper we report a case of a patient with hypercalcemia due to PTH--secreting parathyroid adenoma associated with hyperthyroidism due to toxic nodular goiter. This case demonstrates the dramatic outcome of those two coexisting disorders. We point out that in patients with primary hyperparathyroidism thyroid function test should always be carried out. A proper, first-line treatment of hyperthyroidism will prevent the deterioration of primary hyperparathyroidism course, and thus surgical parathyroid treatment may safely be introduced. 相似文献
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Castedo E Cabo RA Núñez I Monguió E Montero CG Burgos R Serrano-Fiz S Téllez G González M Cavero MA Ugarte J 《Revista espa?ola de cardiología》2004,57(8):751-756
INTRODUCTION AND OBJECTIVES: Five percent of the patients with hypertrophic obstructive cardiomyopathy (HOCM) have symptoms unresponsive to medical treatment and are candidates for invasive therapy. The objective of this study was to analyze our results with surgical treatment of HOCM during the last 10 years. PATIENTS AND METHOD: Between July 1993 and January 2004 26 patients with HOCM refractory to drug therapy were operated on. An extended septal myectomy was performed, in combination with anterior mitral leaflet plication in 19 cases (73%) and with mitral valve replacement in 5 (19%). Evolution of the grade of dyspnea, left ventricle outflow tract gradient (LVOTG), mitral regurgitation, and systolic anterior motion after surgery was analyzed. RESULTS: Mean follow-up was 63 (37) months. After surgery, a significant reduction in LVOTG (from 96.5 to 19.5 mmHg; P<.001), grade of mitral regurgitation (from 2.54 to 0.69; P<.001) and systolic anterior motion (from 2.92 to 0.23; P<.001) was achieved, which led to improvement in functional class. Hospital mortality and need for pacemaker implantation due to complete heart block after surgery was 3.8% (n=1). There were no cases of iatrogenic ventricular septal defect or mitro-aortic valve injury. Actuarial survival at 5 years was 96% (4%). CONCLUSIONS: Surgery in patients with HOCM yields great clinical improvements with low morbidity and mortality. Simultaneous intervention for both myocardial and valvular components of the disease allows not only reduction in the LVOTG but also correction of mitral regurgitation and abolition of systolic anterior motion. 相似文献
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Grabczak EM Zielonka TM Wiwała J Bareła AD Opuchlik A Potulska A Ambroziak U Chazan R 《Polskie Archiwum Medycyny Wewn?trznej》2008,118(9):524-529
Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy. 相似文献
88.
Stochmal E Szurkowska M Czarnecka D Stochmal A Klecha A Kawecka-Jaszcz K Szybiński Z 《Acta cardiologica》2005,60(3):325-331
OBJECTIVES: The purpose of the study was to evaluate the role of insulin resistance (IR) in the development of coronary atherosclerosis in patients with impaired glucose tolerance. METHODS AND RESULTS: The study group consisted of 42 patients with impaired glucose tolerance. Based upon coronary angiography the patients were divided into group A--with prior myocardial infarction and critical coronary stenosis (n=20) and group B--without prior myocardial infarction and without critical coronary stenosis (n=22). In each patient glucose disposal rate (GDR) during metabolic clamp, insulinaemia in the fasting state and during the clamp, glycaemia during oral glucose tolerance test (OGTT), BMI and body mass composition were measured. The groups did not differ in age, BMI, percent fat content and distribution, and blood pressure. Fasting insulinaemia (56.7 microU/ml) was higher in group A than in group B (22.3 microU/ml). GDR in group A (2.96 mg/kg b.m./min) was lower than in group B (5.36 mg/kg b.m./min). There was a negative correlation between the number of critically narrowed coronary vessels and GDR in group A. GDR below 3.97 mg/kg b.m./min was found, based on regression analysis, to be a powerful risk factor for myocardial infarction. CONCLUSIONS: The relationship between IR and severity of coronary atherosclerosis implies its unfavourable role in the development of atherosclerosis. The present findings indicate a negative role of IR in the development of myocardial infarction and suggest that it is an independent risk factor, which identifies high-risk patients requiring treatment that would increase tissue insulin sensitivity. 相似文献
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