Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity

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.

A rare coexistence of primary hyperparathyroidism and hyperthyroidism due to toxic nodular goiter--a case report

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.     

Amiodarone induced pneumonitis and hyperthyroidism: case report

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.     

Association of coronary atherosclerosis with insulin resistance in patients with impaired glucose tolerance

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.     

The Influence of Curing Systems on the Cure Characteristics and Physical Properties of Styrene–Butadiene Elastomer

The goal of this work is to study the influence of different curing systems on the cure characteristics and performance of styrene–butadiene elastomer (SBR) filled with carbon black or nanosized silica. A multifunctional additive for rubber compounds, namely Activ8, was applied as an additional activator and accelerator to increase the efficiency of sulfur vulcanization and to reduce the content of zinc oxide elastomers cured in the presence of 2-mercaptobenzothizole or 1,3-diphenylguanidine as a primary accelerator. The influence of the curing system composition on the crosslink density and physical properties of SBR vulcanizates, such as mechanical properties, thermal stability, and resistance to thermo-oxidative aging, is also reported. Activ8 effectively supports the vulcanization of SBR compounds, especially filled with nanosized silica. It reduces the optimal vulcanization time of SBR compounds and increases the crosslink density of the vulcanizates. Moreover, vulcanizates with Activ8 exhibit higher tensile strength and better damping properties than elastomer with zinc oxide. Activ8 allows the amount of ZnO to be reduced by 40% without detrimental effects on the crosslink density and mechanical performance compared to the vulcanizates conventionally crosslinked with ZnO. This is an important ecological goal since ZnO is classified as being toxic to aquatic species.     

Antitumor Effects of Recombinant Antivascular Protein ABRaA-VEGF121 Combined with IL-12 Gene Therapy

Development and neoplastic progression strongly rely on tumor microenvironment cells. Various kinds of cells that form such tumor milieu play substantial roles in angiogenesis and immunosuppression. Attempts to inhibit tumor vascularization alter tumor milieu and enhance immune response against the tumor. Anticancer therapeutic strategy bringing together antiangiogenic and immunostimulating agents has emerged as a promising approach. We here investigated whether therapy directed against preexisting vessels, combined with an immunomodulatory factor would be equally effective in arresting tumor growth. To this goal, we investigated the effectiveness of ABRaA-vascular endothelial growth factor isoform 121 (VEGF₁₂₁), an antivascular drug constructed by us. It is a fusion protein composed of VEGF₁₂₁, and abrin A chain (translation-inhibiting toxin). We used it in combination with interleukin (IL-12) gene therapy and tried to inhibit B16-F10 melanoma tumor growth. ABRaA-VEGF₁₂₁ is a chimeric recombinant protein capable of destroying tumor vasculature and triggering necrosis in the vicinity of damaged vessels. IL-12 cytokine, in turn, activates both specific and non-specific immune responses. Our results demonstrate that combination of ABRaA-VEGF₁₂₁ antivascular agent with immunostimulatory cytokine IL-12 indeed inhibits tumor growth more effectively than either agent alone, leading to complete cure of ca. 20 % mice. Post-therapeutic analysis of tumors excised from mice treated with combination therapy showed decreased numbers of blood microvessels in the tumor microenvironment, lowered numbers of regulatory T lymphocytes, as well as showed higher levels of CD4⁺ and CD8⁺ as compared to control mice. It seems that bringing together antivascular strategy and the action of immunostimulating agents indeed inhibits growth of tumors.