Background and Purpose Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia.Methods We evaluated the effects of depletion of circulating neutrophils by administration of an antineutroph.il monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion.Results In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P<.05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P<.01; caudate putamen, P<.05),

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Distal nephron segments are heterogenous with respect to adenylate cyclase responses to stimulation with parathyroid hormone (PTH) or calcitonin (CT). We examined effects of these hormones and of 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPTcAMP) on net Ca absorption (Jnet Ca2+, pmol.min-1.mm-1) in rabbit distal nephron segments by in vitro microperfusion technique. We studied three segments, including distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). PTH (1 nM) in bath significantly increased Jnet Ca2+ from 2.28 +/- 0.35 to 9.44 +/- 1.13 in CNT, but did not affect Jnet Ca2+ in DCT or CCD. CT (1 nM) in bath significantly increased Jnet Ca2+ from 1.58 +/- 0.29 to 4.45 +/- 1.01 in DCT, whereas it did not affect Jnet Ca2+ either in CNT or in CCD. CPTcAMP (30 microM) in bath significantly increased Jnet Ca2+ from 2.29 +/- 0.42 to 3.97 +/- 0.43 in DCT and from 2.43 +/- 0.18 to 5.83 +/- 0.37 in CNT, but it did not affect Jnet Ca2+ in CCD. When Na+ was removed from bathing fluid or when 0.1 mM ouabain was added to bath, Jnet Ca2+ in both DCT and CNT significantly decreased. Furthermore, stimulatory effects of PTH and CT on Ca2+ absorption in the respective segments were abolished under these conditions. These results suggest that PTH and CT increase Ca2+ absorption in CNT and DCT, respectively, through cAMP-mediated mechanisms. Presence of a basolateral Na(+)-Ca2+ exchange process seems to be a prerequisite for effects of these hormones. However, exact intracellular mechanisms remain uncertain.

Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation. Kidney tissue accumulation of cisplatin administered at 3.75 mg/kg was similar to that of nedaplatin administered at 24 mg/kg. At these doses, the plasma creatinine level and urinary excretion of glucose and N-acetyl-b b-D-glucosaminidase (NAG) similarly increased. There was a correlation between kidney accumulation of cisplatin and nedaplatin and the increases in plasma creatinine level and urinary excretion of NAG. Therefore, our results suggest that nedaplatin less frequently causes renal toxicity in comparison to cisplatin due to lower kidney accumulation.

To determine the exact site and mechanism of action of thiazide diuretics, effects of 104 M trichlormethiazide (TCM) on NaCJ transport were examined in the distal convoluted tubule (DCT), the connecting tubule (CNT) and the cortical collecting duct (CCD) of rabbit kidney by the in vitro microperfusion technique. TCM added to the lumen decreased lumen-to-bath 'Cl flux (JC(LB)) only in the CNT without changing the transmural voltage (VT). In the DCT, 10-4 M furosemide did not change JCI(LB) even if it was added to the lumen with 10-4 M TCM, whereas 10-5 M amiloride in the lumen decreased the lumen-to-bath 22Na flux (JNa(LB)) and VT. In the CNT, TCM added to the lumen did not affect the bath-to-lumen OC1 flux. Addition of TCM to the bath slightly decreased JC(LB). Luminal addition of 10-4 M TCM also decreased JNa(LB). Amiloride at 10-5 M in the lumen decreased both JNa(LB) and VT.Addition of TCM with 10-5 M amiloride further decreased JNa(LB) without affecting VT, indicating that TCM affects the electroneutral Na+ transport, which is distinct from the amiloride-sensitive conductive Na' pathway. When Na+ was removed from the lumen, JCI(LB) was markedly decreased, but addition of TCM did not cause further decrease in JCI(LB). Furosemide did not affect JC(LB), but addition of both 10-4 M TCM and furosemide decreased JCI(LB), indicating that Na+-K+-2CI-cotransport is not involved in the action of TCM.Removal of HCO3 slightly decreased JCI(LB), and TCM caused further decrease in JCI(LB). Amiloride at 10-3 M, a concentration supposed to inhibit the Na+/H+ antiport, slightly decreased JCI(LB), and addition of TCM caused a further marked decrease in JJI(LB). The similar results were also obtained when the combined effects of 10-3 M 4,4'-diisothiocyano-stilben-2,2'-disulfonate(DIDS) and 10'-M TCM were examined.These findings suggest that the parallel antiport of Na+/H+ and Cl-/HCO-is not involved in the action of TCM. By excluding other possible mechanisms involving neutral Na+-dependent Cl-transport, we conclude that TCM inhibits Na+-ClI cotransport in the luminal membrane of the rabbit CNT. IntroduptionAlthough thiazide diuretics have been widely used in the treatment of edema and hypertension for many years, the exact Address reprint requests to Dr. Imai,