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Discusses the results of specific heat, electrical resistance and magnetic susceptibility measurements on the heavy fermion system CePtSi and compares it to CeRuSi. Preparation of polycrystalline samples; Electrical resistance measured by the alternating current four-lead method; Possible occurrence of antiferromagnetism.

Background: On 1 (st) June 2005 a contract for an integrated health-care programme (IHP) for infants, children and juveniles with bronchial asthma (2 to 18-year-olds) was concluded. Care providers are specialised paediatricians (PaedNetz Bayern) and two rehabilitation clinics; cost payers are two Bavarian health insurances (DAK, TK)., Methods: With a questionnaire (Q5) the following 5 items were collected every 12 months: absent days, hospital admissions, days at hospital, emergency visits and use of relievers. To estimate the adherence to the German asthma guidelines, every 6 months the symptoms, therapy and consecutive procedures were recorded., Results: At the end of 2008, 1280 patients had participated; the follow-up showed a significant reduction of the Q5 items 2 years later. The comparison of patients who had already participated for at least 12 months in the IHP with patients who have just started to participate showed significant reductions (p < 0.05) of all Q5 items between 54 % and 85 %. According to the guidelines - 6 months after starting the IHP - in 25 % a more intense therapy would be helpful. This percentage declines to 17 % at 24 months (p < 0.05)., Conclusion: Children and juveniles with bronchial asthma who are treated by specialised paediatricians and rehabilitation clinics by means of an integrated health-care program show a significant reduction of absent days, emergency visits, hospitalisations, days in hospital and use of relievers., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

Recent U.S. Phase III trials of the aerosolized delivery of tobramycin to cystic fibrosis (CF) patients demonstrated a significant improvement in pulmonary function and in sputum bacterial density. These trials used the Pari LC Plus nebulizer and DeVilbiss Pulmo-Aide compressor. This compressor is not generally available in Europe, and its power requirements do not match the European power supply. Thus alternate compressors were evaluated, using the LC Plus nebulizer, in preparation for European clinical trials. Aerosol particle size distribution, nebulization time (min), and the respirable dose of tobramycin (mg within 1-5 mu) were obtained for seven compressor models. The respirable quantity delivered by each of the European compressors (240 Volts, 50 Hz) was compared to the LC Plus and PulmoAide compressor (120 Volts, at 60 Hz). The U.S. system delivered 71.4 mg of the 300 mg instilled dose within the respirable range; using the European compressors, between 63.0 and 74.8 mg was delivered. With a 97% confidence that the delivered tobramycin was within 20% of the standard, we conclude that the SystAm 23ST, MedicAid CR50 and CR60, Pari Master and the Pari Boy compressors are equivalent to the U.S. standard; the Hercules and the SystAm 26ST compressors were not statistically equivalent to the standard. Using the LC Plus nebulizer, five European compressors delivered doses of TOBI that are similar to the doses delivered by the DeVilbiss PulmoAide compressors, and thus may be expected to produce clinical results similar to those of the U.S. trials.

Iron-dependent free radical reactions and renal ischemia are believed to be critical mediators of myohemoglobinuric acute renal failure. Thus, this study assessed whether catalytic iron exacerbates O2 deprivation-induced proximal tubular injury, thereby providing an insight into this form of renal failure. Isolated rat proximal tubular segments (PTS) were subjected to either hypoxia/reoxygenation (H/R: 27:15 min), "chemical anoxia" (antimycin A; 7.5 microM x 45 min), or continuous oxygenated incubation +/- ferrous (Fe2+) or ferric (Fe3+) iron addition. Cell injury (% lactic dehydrogenase [LDH] release), lipid peroxidation (malondialdehyde, [MDA]), and ATP depletion were assessed. Under oxygenated conditions, Fe2+ and Fe3+ each raised MDA (approximately 7-10x) and decreased ATP (approximately 25%). Fe2+, but not Fe3+, caused LDH release (31 +/- 2%). During hypoxia, Fe2+ and Fe3+ worsened ATP depletion; however, each decreased LDH release (approximately 31 to approximately 22%; P < 0.01). Fe(2+)-mediated protection was negated during reoxygenation because Fe2+ exerted its intrinsic cytotoxic effect (LDH release: Fe2+ alone, 31 +/- 2%; H/R 36 +/- 2%; H/R + Fe2+, 41 +/- 2%). However, Fe(3+)-mediated protection persisted throughout reoxygenation because it induced no direct cytotoxicity (H/R, 39 +/- 2%; H/R + Fe3+, 25 +/- 2%; P < 0.002). Fe3+ also decreased antimycin toxicity (41 +/- 4 vs. 25 +/- 3%; P < 0.001) despite inducing marked lipid peroxidation and without affecting ATP. These results indicate that catalytic iron can mitigate, rather than exacerbate, O2 deprivation/reoxygenation PTS injury.

Amphotericin B (AB) may induce acute renal failure by vasoconstrictive and tubulo-toxic effects. Although mannitol, Ca2+ channel blockers, and lipid-based AB preparations have been suggested to mitigate in vivo AB nephrotoxicity, whether they confer direct tubular cytoprotection has not been defined. Therefore, this study assessed the impact of mannitol, verapamil/extracellular Ca2+, and cholesteryl sulfate (CS) AB binding on AB cytotoxicity, employing an isolated rat proximal tubular segment (PTS) preparation. After 30 to 60 minutes of incubation, 0.2 mg/ml of AB (Fungizone) caused marked toxicity, as assessed by LDH release (29 to 44%) and ATP depletion (greater than 90%). Approximately 40% of the LDH release could be attributed to deoxycholate, the standard AB (Fungizone) solubilizing agent. Both 100 mM mannitol and 100 mM glucose decreased AB-mediated LDH release, despite having a quantitatively trivial impact on ATP concentrations (increments of less than or equal to 1% at normal values). Dimethylthiourea (25 mM; equipotent to 100 mM mannitol/glucose as a hydroxyl radical scavenger) did not decrease LDH release. Neither verapamil addition (100 microM) nor Ca2+ removal from the PTS buffer had a protective effect. CS binding completely eliminated AB's toxicity (no LDH or ATP losses). The effect of AB and CS-AB on concomitant O2 deprivation/reoxygenation (30 min/15 min) PTS injury was also assessed. AB and hypoxia/reoxygenation caused additive, not synergistic, LDH release whereas CS-AB had no adverse effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to assess whether proximal renal tubules generate excess hydroxyl radical (.OH) during hypoxia/reoxygenation or ischemia/reperfusion injury, thereby supporting the hypothesis that reactive oxygen species contribute to the pathogenesis of postischemic acute renal failure. In the first phase of the study, rat isolated proximal tubular segments (PTS) were subjected to hypoxia (95% N2- 5% CO2) for 15, 30, or 45 min, followed by 15 to 30 min of reoxygenation in the presence of sodium salicylate, a stable .OH trap. Cellular injury after hypoxia and reoxygenation was assessed by lactate dehydrogenase release; .OH production was gauged by hydroxylated salicylate by-product generation (2,3-, 2,5-dihydroxybenzoic acids (DHBA); quantified by HPLC/electrochemical detection). Continuously oxygenated PTS served as controls. Despite substantial lactate dehydrogenase release during hypoxia (8 to 46%) and reoxygenation (8 to 11%), DHBA production did not exceed that of the coincubated, continuously oxygenated control PTS. In the second phase of the study, salicylate-treated rats were subjected to 25 or 40 min of renal arterial occlusion +/- 15 min of reperfusion. No increase in renal DHBA concentrations occurred during ischemia or reperfusion, compared with that in sham-operated controls. To validate the salicylate trap method, PTS were incubated with a known .OH-generating system (Fe2+/Fe3+); in addition, rats were treated with antioxidant interventions (oxypurinol plus dimethylthiourea). Fe caused marked DHBA production, and the antioxidants halved in vivo DHBA generation. In conclusion, these results suggest that exaggerated .OH production is not a consequence of O2 deprivation/reoxygenation tubular injury.

This study was undertaken to explore the protective influence of mannitol against the glycerol model of myohemoglobinuric acute renal failure. Three hypotheses were tested: (1) mannitol confers cytoprotection by acutely blunting renal hypoperfusion, thereby improving tubular cell energetics; (2) as an hydroxyl radical (OH.) scavenger, mannitol mitigates Fe-driven lipid peroxidation and, hence, decreases tubular cell necrosis; and (3) mannitol prevents intrarenal heme pigment trapping, decreasing cast formation. Rats were injected with 50% glycerol (10 mL/kg im), followed immediately by an iv mannitol (1.25 mL/100 g over 1 h) or sham infusion. Mannitol induced a brisk diuresis (approximately 5.7 mL/2 h; approximately 35 mg of heme protein excreted), whereas glycerol controls were anuric. Mannitol did not significantly increase postglycerol RBF (2.8 mL/min), and it paradoxically worsened cellular energetics, halving cortical ATP concentrations at 1 h. However, this adverse effect on ATP was transient, correlating with active diuresis. Glycerol did not induce convincing in vivo lipid peroxidation (malondialdehyde; conjugated diene assay), and mannitol did not block Fe-driven in vitro lipid peroxidation of isolated brush border membrane vesicles. Na benzoate, an OH. scavenger, conferred no in vivo or in vitro protection. However, Na2SO4, not an OH. scavenger, reproduced the diuretic and in vivo protective effects of mannitol. Purified myoglobin infusion (35 mg) largely negated the beneficial action of mannitol. It was concluded that mannitol confers functional but not cytoprotection against the glycerol acute renal failure model, it acutely worsens renal bioenergetics, and its protective influence is probably due to a diuretic, not an antioxidant, effect.

Unlabelled: Body temperature (T) profoundly alters the severity of ischemic acute renal failure. Therefore, the present study evaluated T effects on: (a) in vitro proximal tubular cell killing during hypoxia/reoxygenation to assess when it exacerbates injury; (b) renal ATP losses and metabolic rate (O2 consumption) during hemorrhagic shock (55-60 mm Hg); and (c) membrane deacylation (assessed by free fatty acid, FFA, release) to determine if T modifies this pathway of ischemic renal damage. Hypoxic cell kill (45 minutes) was 20 +/- 1% 47 +/- 4%, and 61 +/- 2% at 32 degrees C, 37 degrees C, and 40 degrees C respectively (by lactate dehydrogenase release; p less than 0.001). During reoxygenation (15 minutes), minimal lactate dehydrogenase was released, irrespective of T. ATP decrements during shock were profoundly T dependent (% loss of ATP; 15%, 30%, 58% at 32.5 degrees C, 37 degrees C, and 39.5 degrees C, respectively; p less than 0.001), reflecting T-dependent increments in renal metabolic rate, not decreased O2 delivery (arterial O2 content; renal blood flow). ATP losses during shock correlated with the extent of S3 proximal tubular morphologic damage. O2 deprivation dramatically increased FFA levels both in vivo and in vitro but the increments were only slightly T dependent. In vitro, % lactate dehydrogenase release and FFA levels did not significantly correlate and bovine serum albumin, a FFA binder, conferred no protection., Conclusions: (a) T dramatically accentuates hypoxic, not reoxygenation, injury; (b) changes in membrane deacylation do not appear to underlie this effect; and (c) T has a profound impact on renal ATP losses during shock, thereby affecting the severity of ischemic renal damage.

Unlabelled: Renal cortex (C) has predominantly aerobic metabolism, whereas inner medulla (IM) has both aerobic and anaerobic capacities. This study was undertaken (1) to assess how well rat IM anaerobic metabolism maintains this region's ATP content during ischemia; and (2) to determine whether regional variations in adenylate pool/catabolite responses to ischemia exist, obscuring interpretation of cellular energetics in rat studies of acute renal failure (ARF). Adenine nucleotides/catabolites were measured in rat C, IM and outer medulla (OM) after 15 and 45 min of ischemia. After 15 min, all regions showed profound ATP depletion, although the IM maintained slightly higher (by 0.23 mumol/g) absolute ATP levels than C/OM tissues (normal ATP value = 8.7 mumol/g). By 45 min, significant differences in regional ATP levels did not exist. Striking regional catabolite differences were apparent at both 15 and 45 min. Most prominent were: (1) intrarenal purine base/inosine gradients, levels falling approx. 22-50% from C to IM; and (2) preferential OM AMP/IMP/adenosine accumulation. To assess whether more homogeneous results might be found in rabbit kidney, possibly making this animal preferable to rats for studies of renal ischemia, rabbit C, OM and IM adenylate pools were analyzed after 15 min of ischemia. C vs. IM ATP differences were greater (approx. 1.3 mumol/g) and large catabolite concentration differences were still apparent., Conclusions: (1) anaerobic mechanisms support IM ATP levels during ischemia but, in terms of normal concentrations, the impact is small, particularly in the rat; and (2) marked regional differences in adenylate catabolite levels exist within ischemic kidneys. These need to be recognized when analyzing adenylate pool responses in ischemic ARF.

This study was designed to evaluate the hypothesis that impaired brain angiotensin signal termination contributes to the sustained blood pressure elevations noted in the genetically hypertensive rat model of human essential hypertension. A technique that combined the intracerebroventricular injection of [125I]angiotensins, followed by focused microwave fixation to stop all peptidase activity and subsequent HPLC analyses, was used for determining half-lives of [125I]angiotensin II and [125I]angiotensin III in the ventricular space. The results indicate that the spontaneously hypertensive rat evidenced significantly longer half-lives for intracerebroventricularly injected [125I]angiotensin II over those measured for the Wistar-Kyoto and Sprague-Dawley normotensive rat strains: 45.0, 27.2, and 25.0 s, respectively. This was also true for intracerebroventricularly administered [125I]angiotensin III: 19.5, 11.4, and 9.0 s, respectively. These results support the notion that a dysfunction in central aminopeptidase activity in the spontaneously hypertensive rat may result in prolonged half-lives of endogenously synthesized angiotensins II and III, which are known to serve as ligands at central angiotensin receptors responsible for the control of cardiovascular function. The extended half-lives of these ligands may contribute to the sustained elevations in blood pressure observed in this animal model.

The purpose of this study was to assess the degree, time sequence, and biochemical correlates of hypothermic protection against ischemic acute renal failure. Rats subjected to 40 minutes of bilateral renal artery occlusion (RAO) were made mildly hypothermic (32 degrees-33 degrees C, by cold saline peritoneal lavage) during the following time periods: 1) RAO only, 2) reperfusion only (beginning at 0, 15, 30, or 60 minutes after RAO and maintained for 45 minutes), or 3) during and after (0-45 minutes) RAO. Continuously normothermic (37 degrees C) RAO rats served as controls. The control rats developed severe acute renal failure (blood urea nitrogen [BUN], 95 +/- 4 mg/dl; creatinine, 2.2 +/- 0.1 mg/dl; and extensive tubular necrosis at 24 hours). Hypothermia confined to RAO was highly protective (BUN, 33 +/- 5 mg/dl; creatinine, 0.62 +/- 0.07 mg/dl; and minimal necrosis). Hypothermia partially preserved ischemic renal adenylate high-energy phosphate (ATP and ADP), increased AMP and inosine monophosphate concentrations, and lessened hypoxanthine/xanthine buildup (assessed at end of RAO). Hypothermia confined to the reflow period (beginning at 0, 15, and 30 minutes) was only mildly protective (e.g., BUN, 58-63 mg/dl); the degree of protection did not differ according to the time of hypothermic onset. Lowering reflow temperature to 26 degrees C had no added benefit. Hypothermia that started at 60 minutes after RAO conferred no protection. Combining ischemic and postischemic hypothermia abolished all renal failure (assessed at 24 hours). This study offers the following conclusions: Mild hypothermia can totally prevent experimental ischemic acute renal failure. Hypothermia is highly effective during ischemia, and it is mildly protective during early reflow; these benefits are additive. During early reflow, hypothermic protection is not critically time dependent. By 60 minutes of reflow, no effect is elicited; this absence of effect possibly signals completion of the reperfusion injury process. Hypothermia's protective effects may be mediated, in part, by improvements in renal adenine nucleotide content and, possibly, by decreasing postischemic oxidant stress.