Nitric oxide induces murine thymocyte apoptosis by oxidative injury and a p53-dependent mechanism.

Previously, we showed that NO induces thymocyte apoptosis via a caspase-1-dependent mechanism [(1) ]. In the present study, we investigated the role of heme oxygenase, catalase, bax, and p53 in this process. The NO donor, S-nitroso-N-acetyl penicillamine (SNAP), induced DNA fragmentation in thymocytes in a time- and concentration-dependent way. SNAP (100 microM) induced 50--60% apoptosis; higher doses did not increase the rate of apoptosis significantly. SNAP decreased catalase and heme iron (Fe) levels without affecting superoxide dismutase, glutathione, or total Fe stores in thymocytes. SNAP significantly increased the expression of heme oxygenase 1 (HSP-32), p53, and bax but not bcl-2. Treatment with the heme oxygenase inhibitor, tin protoporphyrin IX inhibited SNAP-induced thymocyte apoptosis. Furthermore, thymocytes from p53 null mice were resistant to NO-induced apoptosis. Our data suggest that NO may induce its cytotoxic effects on thymocytes by modulating heme oxygenase and catalase activity as well as up-regulating pro-apoptotic proteins p53 and bax.

Indicators of genitourinary tract injury or anomaly in cases of pediatric blunt trauma.

PURPOSE: Microscopic hematuria (> or = 20) RBCs per high-power field [HPF] has been used frequently as an indicator for genitourinary (GU) tract injury in pediatric cases of blunt trauma. The aim of this study was (1) to determine whether a certain threshold of microscopic hematuria was associated with GU tract injury in our patient population, and (2) to identify additional factors warranting evaluation of the GU tract. METHODS: The records of 100 patients under 18 years of age whose discharge diagnosis in the trauma registry included hematuria or GU tract injury were reviewed retrospectively (1989 through 1993). The following data were collected: age, sex, mechanism of injury, physical findings, associated injuries, urinalysis results, radiographic study results, disposition, and outcome. Data were analyzed using the SPSS program. RESULTS: The majority of children were victims of motor vehicle accidents. All but one study patient had an intravenous pyelogram and/or computed tomography scan. Twenty-seven patients had GU tract injuries or previously unrecognized congenital anomalies (9 contusions, 5 lacerations, 1 vascular pedicle injury, 4 bladder injuries, 3 urethral/vaginal tears, 5 anomalies). Twenty-seven percent (3 of 11) of children with minor injuries and 25% (2 of 8) of those with major injuries had microscopic hematuria of less than 20 RBCs/HPF. Mechanism of injury and hypotenison were not associated with GU tract injury. One third of the patients with isolated chest or abdominal injuries, and 50% of those with combined chest/abdominal injuries had GU tract injuries or anomalies identified. Pelvic fracture was associated with GU tract injury or anomaly in 50% of cases (P < 0.02). CONCLUSION: The authors found that (1) a threshold of > or = 20 RBCs/HPF as an indication for radiograph evaluation would have missed 28% of cases with GU tract injuries or occult anomalies, and (2) pelvic fractures and abdominal/chest injuries help to identify patients who require evaluation of the GU tract. The need for GU tract evaluation in pediatric trauma patients is based as much on clinical judgment as on the presence of hematuria.