Radioprotection of cells in culture by WR-2721 and derivatives: form of the drug responsible for protection

Studies of V79-171 cells were undertaken to determine what extracellular or intracellular derivative of the drug WR-2721 is associated with radioprotection. The effect of preincubation at 23 +/- 1 degree C with WR-2721, and with derivatives of WR-2721 produced in medium containing alkaline phosphatase, upon survival of cells following subsequent gamma-irradiation was examined. It was established that WR-2721, WR-1065, WR-33278, WRSSCys, and other disulfide forms produced by reactions of WR-1065 with the medium do not provide significant protection when present only extracellularly. Protection was found to correlate with cellular levels of the thiol form of the drug (WR-1065) but not with the cellular level of the disulfide forms of WR-1065. Similar results were obtained with HeLa, Me-180, Ovary 2008, HT-29/SP-1d, and Colo 395 cell lines showing that human tumor cell lines behave in the same fashion as the V79-171 nontumorigenic hamster diploid cell line. None of the drug forms produced significant cytotoxicity under the conditions used. It was concluded that it is the cellular level of WR-1065 at the time of irradiation which determines protection. The results are consistent with protection mechanisms involving scavenging of hydroxyl radicals, hydrogen atom transfer to DNA radicals, depletion of oxygen near DNA, enhancement of rapid biochemical repair processes, or some combination of these mechanisms.     

Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-1 (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.The members of the HTLV Spanish Study Group are listed in the Appendix.     

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.