From oxygen sensing to heart failure: role of thioredoxin

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.     

Types of nuclear endonuclease activity capable of inducing internucleosomal DNA fragmentation are completely different between human CD34+ cells and their granulocytic descendants

A hallmark of apoptosis is internucleosomal DNA fragmentation resulting from the activation of endonucleases. We characterized the endonuclease activity of human myeloid cell nuclei that cleaved their own nuclear chromatin to oligonucleosomal length fragments. Polymorphonuclear leukocytes (PMNs) of normal peripheral blood contained both Ca2+/Mg(2+)- dependent and DNase II-like acidic endonuclease activities in their nuclei. Immature myeloid cells of normal bone marrow at various stages of granulocytic maturation had similar nuclease activities. In contrast, a clear difference was shown in the circulating CD34+ cells, in that only Mg(2+)-dependent, Ca(2+)-independent endonuclease activity was detected. Consistent with these findings is the emergence of the Ca2+/Mg(2+)-dependent and acidic endonuclease concomitantly with the disappearance of the Mg(2+)-dependent endonuclease when CD34+ cells were induced to differentiate in vitro toward granulocytes. Leukemic cell lines of all lineages also had Mg(2+)-dependent nuclease activity. Our results suggest an association of the Mg(2+)-dependent endonuclease with hematopoietic progenitor cells and that the relative activities of the nuclear nuclease in human myeloid cells change substantially during granulocytic differentiation.     

A case of ulcerative colitis with hematuria and renal dysfunction after leukocytapheresis]

A 53-year-old man had steroid-dependent ulcerative colitis. Leukocytapheresis (LCAP) was carried out to induce remission, but soon hematuria and renal dysfunction appeared. Since he had no autoimmune hemolytic anemia, and there was no possibility of his having had hemolytic uremic syndrome, it was considered that this hemolysis could have been caused by mechanical stimulation on the LCAP column, and then the hemolysate flowed into his body. We should be aware that hematuria might occur as a side effect of LCAP.     

Mild hyperglycemia and insulin treatment in experimental cerebral ischemia in rats

We investigated the effects of mild hyperglycemia and insulin treatment on the metabolism of the ischemic brain in spontaneously hypertensive rats with acute hyperglycemia (n = 9), acute hyperglycemia treated with insulin during ischemia (n = 10), and normoglycemia (n = 10). Cerebral blood flow was measured by the H₂ clearance method. Cerebral ischemia induced occlusion of the bilateral carotid arteries. Cerebral glycolytic metabolites were measured enzymatically. Blood glucose levels were significantly higher in hyperglycemic animals (11.8 to 13.7 mM/I) than in normoglycemic animals (6.0 mM/I). At 60 min of ischemia, the blood flow to the parietal cortex was decreased to 3% of the resting value in all groups. Blood glucose levels at 60 min of ischemia in the hyperglycemic rats were 1.9–3 times higher than the treated hyperglycemic rats and normoglycemic rats. Glucose concentrations were significantly and positively correlated with the ATP level (p < .0001) but not with the lactate levels in the ischemic brain. Our results suggest that mild hyperglycemia may preserve glucose metabolism in the presence of ischemic insult.     

Plasma cortisol levels in paediatric anaesthesia

We measured plasma cortisol levels during surgery in seven neonates within ten days after birth and in 14 infants ranging in age from three months to 11 months. The 14 infants were divided into two groups; Group I included eight infants in whom general anaesthesia was maintained with oxygen, nitrous oxide and a muscle relaxant, Group II, six infants in whom general anaesthesia was maintained with oxygen, nitrous oxide, halothane and a muscle relaxant. In the neonates, the changes in mean plasma cortisol levels during anaesthesia were not statistically significant. In both Group I and Group II infants, the mean cortisol levels gradually rose during anaesthesia, but the initial rise in plasma cortisol levels was suppressed in the patients who received halothane.