Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vasculardependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.

I/R induces oxidative stress and consequently damages the proximal convolute renal tubules. Rats supplemented with DHEA and subjected to I/R had reduced pro-oxidant state, oxidative damage, and improved renal functionality, indicating an attenuation of oxidative injury and dysfunctions mediated by I/R.

No abstract

Diabetics have at least twice the risk of stroke and may show performance deficit in a wide range of cognitive domains. The mechanisms underlying this gradually developing end-organ damage may involve both vascular changes and direct damage to neuronal cells as a result of overproduction of superoxide by the respiratory chain and consequent oxidative stress. The study aimed to assess the role of oxidative stress on the aldose reductase-polyol pathway, on advanced glycated end-product (AGE)/AGE-receptor interaction, and on downstream signaling in the hippocampus of streptozotocin-treated rats. Data show that, in diabetic rats, levels of prooxidant compounds increase, whereas levels of antioxidant compounds fall. Receptor for AGE and galectin-3 content and polyol flux increase, whereas glyceraldehyde-3-phosphate dehydrogenase activity is impaired. Moreover, nuclear factor kappaB (p65) transcription factor levels and S-100 protein are increased in the hippocampus cytosol, suggesting that oxidative stress triggers the cascade of events that finally leads to neuronal damage. Dehydroepiandrosterone, the most abundant hormonal steroid in the blood, has been reported to possess antioxidant properties. When dehydroepiandrosterone was administered to diabetic rats, the improved oxidative imbalance and the marked reduction of AGE receptors paralleled the reduced activation of nuclear factor kappaB and the reduction of S-100 levels, reinforcing the suggestion that oxidative stress plays a role in diabetes-related neuronal damage.

non-small cell lung carcinoma (NSCLC) may be challenging. 8,9 The latter shows striking pleomorphism in contrast to the monotonous appearance of SMARCA4-DTS, is frequently positive for Hepar-1 and cytokeratin-7, and usually shows some degree of glandular differentiation which is always absent in SMARCA4-DTS. 8 Nevertheless, SMARCA4-DTS and SMARCA4-deficient NSCLC show considerable overlap in their clinicopathological profiles: male preponderance, association with smoking, pattern of metastases, poor clinical outcomes, histomorphology, immunoprofile, and molecular alterations such as concurrent TP53 and KRAS alterations. 5,8 Whether these two tumours represent spectral ends of the same entity needs further clarification.We document, for the first time, an innocuous presentation of SMARCA4-DTS wherein a small tumour (w4 cm grossly) was incidentally detected in the soft tissue of chest wall around an ICD insertion site in a patient suffering from chronic empyema thoracis of uncertain aetiology for over 10 months. We believe it is unlikely that the SMARCA4-DTS was masquerading as chronic empyema as the initial computed tomography images do not show any mass lesion. The lung parenchyma was completely clear except for smoking related parenchymal changes. Although an autopsy was refused in this patient, the rapidly fatal outcome after development of tumour highlights its aggressiveness. A link with chronic infection/inflammation as an inciting/contributing factor for SMARCA4-DTS has not been noted previously and should be explored.