Antioxidant administration inhibits exercise-induced thymocyte apoptosis in rats

PURPOSE: The purpose of this study was to investigate the effect of antioxidant on exercise-induced apoptosis in rat thymocytes. METHODS: After exercise at 13.8 m x min(-1) for 60-90 min x d(-1) on a motor-driven drum exerciser for 2 consecutive days, rat thymocyte apoptosis was monitored by the feature of DNA fragmentation. To study the effect of antioxidant, rats were administered with butylated hydroxyanisole (BHA) for 7 d before exercise. RESULTS: Exercise could induce thymocyte DNA fragmentation as detected on electrophoretic gel and by cell death detection ELISA kit. Further studies indicated that pretreatment with antioxidant BHA to rats resulted in a blockage of exercise-induced DNA fragmentation. The concentrations of glutathione (GSH) were not significantly changed in rat thymocytes after exercise with or without BHA treatment. CONCLUSION: These results suggest that reactive oxygen species may play a role in thymocyte apoptosis induced by exercise. However, changes in GSH levels were not observed in this exercise model.     

Mechanism of adrenal insufficiency following trauma and severe hemorrhage: role of hepatic 11beta-hydroxysteroid dehydrogenase

BACKGROUND: Although adrenal insufficiency may not occur with moderate hypotension, it does occur with severe hemorrhage. Since hepatocellular function is depressed following severe hemorrhage, it remains unknown whether the liver plays any role in regulating adrenal function after trauma and hemorrhagic shock. HYPOTHESIS: Hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD), a microsomal enzyme responsible for the degradation of bioactive corticosterone, plays a major role in the development of adrenal insufficiency following trauma and severe hemorrhage. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male rats underwent laparotomy to induce trauma before hemorrhage. They were then bled to and maintained at a blood pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer lactate. The rats were then resuscitated with 4 times the volume of maximal bleed-out with Ringer lactate during a 60-minute period. Plasma levels of corticosterone and corticotropin were measured at various intervals. In additional groups, corticotropin-induced corticosterone release, adrenal contents of corticosterone and cyclic adenosine monophosphate (cAMP), hepatic 11beta-HSD activity, and plasma levels of corticosterone-binding globulin were determined at 1.5 hours after resuscitation. Moreover, a model of moderate hypotension (blood pressure, 80 mm Hg) was used to determine whether adrenal function is depressed under such conditions. RESULTS: At the time of maximal bleed-out, plasma corticosterone and corticotropin levels increased by 245% (P<.001) and 293% (P<.001), respectively. Despite corticotropin levels being similar to those of the animals undergoing sham operation after resuscitation, corticosterone levels in hemorrhaged animals remained elevated up to 4 hours after resuscitation (by 158%-207%; P<.001). In addition, corticotropin-induced corticosterone release decreased by 78% at 1.5 hours after resuscitation (P = .009). In contrast, moderate hypotension did not reduce corticotropin-induced corticosterone release. Adrenal corticosterone content and cAMP levels (i.e., the second messenger of corticotropin action) decreased by 55% (P<.001) and 25% (P = .03), respectively. Hepatic 11beta-HSD activity decreased significantly at 1.5 hours after resuscitation (P<.001). CONCLUSIONS: Sustained increase in plasma corticosterone levels following hemorrhage and resuscitation may be, in part, due to the decreased hepatic 11beta-HSD activity. The high level of corticosterone negatively regulates corticotropin release, further reducing adrenal responsiveness to corticotropin stimulation. Thus, the liver appears to play an important role in regulating adrenal function following trauma and severe hemorrhage.     

Intimate combination of low- and high-resolution image data: I. Real-space PET and (1)H(2)O MRI, PETAMRI.

Two different types of (co-registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel-by-pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial (18)FDG PET and (1)H(2)O MR images of the human brain are used as the low- and high-resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low-resolution image type is coded as hue, while that of the high-resolution type is coded as value, a reasonably independent parameter. Furthermore, the high-resolution image must have high contrast and be quantitative in the same sense as the low-resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative (1)H(2)O spin-density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of (18)FDG PET images with gray-matter (GM) relaxographic (1)H(2)O images produces visually "GM-edited" (18)FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of (1)H(2)O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345-360, 1999. Published 1999 Wiley-Liss, Inc.     

Rhenium-188-Labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h ( n =5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats ( n=5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.     

A comparison among nalbuphine, meperidine, and placebo for treating postanesthetic shivering

Postanesthetic shivering (PS) is distressing for patients and may induce a variety of complications. In this prospective, double-blinded, randomized study, we evaluated the value of nalbuphine, compared with meperidine and saline, for treating PS. Ninety adult patients were included in the study. Group 1 (n = 30) received i.v. nalbuphine 0.08 mg/kg, Group 2 (n = 30) received i.v. meperidine 0.4 mg/kg, and Group 3 (n = 30) received i.v. saline. Treatment that stopped shivering was considered to have been successful. The results demonstrated that, 5 min after treatment, both nalbuphine and meperidine provided a rapid and potent anti-shivering effect on PS, with high response rates of 80% and 83%, compared with those of saline (0%) (P < 0.01). Thirty minutes after injection, the response rates of nalbuphine and meperidine were 90% and 93%, respectively, compared with 17% in the saline group (P < 0.01). The differences between nalbuphine and meperidine were not significant. We conclude that nalbuphine may be an alternative to meperidine for treating PS. IMPLICATIONS: We evaluated nalbuphine versus meperidine and saline for treating postanesthetic shivering. Our results demonstrate that both nalbuphine and meperidine provide a similar rapid and potent anti-shivering effect. Nalbuphine may be an alternative to meperidine for treating postanesthetic shivering.     

Postoperative behavioral outcomes in children: effects of sedative premedication

BACKGROUND: Although multiple studies document the effect of sedative premedication on preoperative anxiety in children, there is a paucity of data regarding its effect on postoperative behavioral outcomes. METHODS: After screening for recent stressful life events, children undergoing anesthesia and surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using validated measures of anxiety, children were evaluated before and after administration of the intervention and during induction of anesthesia. On postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children was assessed using the Post Hospitalization Behavior Questionnaire. RESULTS: The intervention group demonstrated significantly lower anxiety levels compared with the placebo group on separation to the operating room and during induction of anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression model, the authors found that the presence or absence of postoperative behavioral changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that during postoperative days 1-7, a significantly smaller number of children in the midazolam group manifested negative behavioral changes. At week 2 postoperatively, however, there were no significant differences between the midazolam and placebo groups. CONCLUSIONS: Children who are premedicated with midazolam before surgery have fewer negative behavioral changes during the first postoperative week.     

Apoptotic cascade of neurons in the subcortical sensory relay nuclei following the neonatal infraorbital nerve transection

A terminal transferase-mediated dUTP nick end labeling (TUNEL) method was utilized for detection of neuronal death in the subcortical relay nuclei of the trigeminosensory system following the infraorbital nerve transection in newborn rats. At 18-24 h after injury, numerous TUNEL-positive profiles were found within the ventroposteromedial thalamic nucleus (VPM) contralateral to the injury, whereas the VPM on the ipsilateral side and of the age-matched normal control contained only a few profiles per section. Electron microscopy revealed that the TUNEL-positive profiles were apoptotic neurons. The ventral part of the ipsilateral brainstem sensory trigeminal nuclear complex (the nucleus principalis, and the subnuclei oralis and interpolaris) exhibited statistically significant 65-70% increase in number of apoptotic neurons compared to the contralateral side. Taken together with our previous study [T. Sugimoto, C. Xiao, H. Ichikawa, Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism, Brain Res. 807 (1998) 147-154], the present results demonstrated a cascade of apoptosis in the primary, secondary and tertiary order sensory neurons along the neuroaxis.     

Injury induces neuropsin mRNA in the central nervous system

We have shown that neuropsin is expressed in the neurons of the limbic system in the adult mouse. After the central nervous system was injured by incision or intraperitoneal kainate injection, neuropsin mRNA was induced in the peri-lesioned region. The cells in which neuropsin mRNA was induced were localized mainly in axon fiber pathways and closely associated to proteolipid protein (PLP) mRNA expressing oligodendrocytes.