DNA strand break yields after post-high LET irradiation incubation with endonuclease-III and evidence for hydroxyl radical clustering

PURPOSE: To determine the increase in single- (SSB) and double-strand break (DSB) yields after post-high LET irradiation incubation of plasmid DNA with the endonuclease-III (endo-III) of Escherichia coli. MATERIALS AND METHODS: Plasmid DNA in aerobic aqueous solution was irradiated with one of five radiation types: 137Cs gamma-rays (LET approximately 0.3keV microm(-1)), 244Cm alpha-particles (140-190 keV microm(-1)), 4He ions (97 keV microm(-1)), 56Fe ions (143 keV microm(-1)) or 197Au ions (1,440 keV microm(-1)). The irradiated samples were then incubated with endo-III. SSB and DSB yields were quantified by agarose gel electrophoresis. RESULTS: Endo-III incubation produced an increase in the SSB and DSB yields. The increases were in general lower after the high LET irradiation than after gamma-irradiation. This may reflect inhibition of the activity of endo-III by the nearby DNA damage expected from high LET radiation. It can be shown that even if the activity of endo remains unchanged, significantly lower increases in SSB and DSB yields would still be expected. CONCLUSION: The results provide evidence for clustered DNA damage after high LET irradiation.     

Glutathione S-transferase T1 genetic mismatch is a risk factor for de novo immune hepatitis in liver transplantation

Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme abundantly expressed in liver and kidney cells; it is encoded by a single gene that is absent in 20% of the Caucasian population. Our group found that some liver transplantation patients developed de novo immune hepatitis (IH) and that all of them had anti-GSTT1 antibodies. The main objective of this study was to analyze the influence of a GSTT1 mismatch between donor and recipient in the immune response and the outcome of the graft. We confirmed that only under one of the four possible genetic combinations (null recipient/positive donor) is an alloimmune response triggered with production of anti-GSTT1 antibodies. Therefore, we conclude that this genetic mismatch can be considered a risk factor for de novo IH.     

Men with hip fractures have poorer nutritional status and survival than women: a prospective study of 165 patients

Background Many hip fracture patients have a poor nutritional status which may be one explanation for their increased mortality.

Patients and methods We studied nutritional status and other mortality-related factors prospectively in 165 patients with hip fractures (85 women). We concentrated on differences between death rates and survival rates at 3 months and at 1 year, and between those patients who died within 3 months and those who died later.

Results In general, men had a poorer nutritional status and a larger number of comorbidities. Also, there were more smokers and alcohol abusers amongst the men. Of the patients who died during the first 3 months, most were men, and their initial nutritional status was poorer than that of women. Multivariate logistic regression analysis revealed a correlation between mortality and total serum protein, retinol binding protein and the number of comorbidities. Among patients who died after 3 months, mortality was associated with the number of comorbidities and smoking.

Interpretation The higher mortality rate in men than in women after hip fracture may in part be explained by the poor nutritional status in men.     

Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

BACKGROUND: Endotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney. METHODS: Plasma VP and urine osmolality, and binding of [3H]VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250 microg/100 g, intraperitoneally. RESULTS: LPS injection caused prolonged decreases in urine osmolality (up to 24 hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by 3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1beta reduced VP binding. CONCLUSION: The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine.