Mild renal ischemia activates primed neutrophils to cause acute renal failure.

The role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN.     

Aromatic ethers of 1-aryl 2-(1H-azolyl)ethanol: study of antifungal activity

Aromatic ethers related to antifungal azole miconazole were synthesized and tested against various strains of Candida. We found that activity is related to the nature of the aromatic ring and the position of substituents on this ring. Activity is more strongly dependent on the substituent in the 2 position of the ethyl chain than on the aromatic group linked through the oxygen. Triazoles were always less potent than the corresponding imidazole analogues.     

Noble gas radionuclides in RBMK-1500-type reactor.

The presence of noble gas and other short-lived radionuclides in air borne effluents from RBMK-1500-type reactor has been investigated using experimental and theoretical instrumentation for detection purposes. Activity concentrations of (85m)Kr, (87)Kr, (88)Kr, (135m)Xe, (135)Xe, (133)Xe and (41)Ar were measured in air emissions from Ignalina NPP using a special method and special equipment. Theoretical detection of reactor-borne radionuclides and investigation of their behaviour in a nuclear fuel during operation of nuclear reactor was performed using an analytical model based on reactor physics. An innovative method for the estimation of noble gas flow time from the defective nuclear fuel element through the ventilation stack of NPP to the atmosphere based on comparison of the experimentally and theoretically evaluated activity ratios of (88)Kr/(85m)Kr; (135)Xe/(133)Xe has been proposed. The estimated flow time of noble gas provides an excellent possibility to obtain modelling-based information about the qualitative and quantitative content of atmospheric releases from NPP.     

Mechanism of the antihypertensive effect of K depletion in the spontaneously hypertensive rat

K depletion reverses hypertension in the SHR (systolic blood pressure: K deplete 122 +/- 5 vs. K replete 164 +/- 4 mm Hg, P less than 0.001). To determine the role of the renin angiotensin system in the protective effect of K depletion, we performed studies of vascular reactivity in intact SHR and of angiotensin II (Ang II) binding to mesenteric artery particles and vascular smooth muscle cells (VSMC) in culture from SHR. Pressor sensitivity to Ang II (+/- converting enzyme inhibition) but not norepinephrine was reduced in K depleted SHR. Thus, the decreased vascular reactivity in K depletion was specific for Ang II rather than a generalized defect. Ang II binding and receptor number (Bmax) (156 +/- 20 vs. 81 +/- 5 fmol/mg of protein, P less than 0.01) were increased in K depleted mesenteric artery particles. Since K depletion and increases in Ang II have both been associated with increased Ang II binding, Ang II binding was measured after bilateral nephrectomy. Despite reduction of plasma renin activity, total binding and Bmax were still increased in nephrectomized K depleted SHR. To determine the specific effect of K depletion independent of Ang II on Ang II binding, studies were performed in mesenteric artery VSMC from SHR grown in culture. VSMC from K replete SHR were grown to confluency in K replete medium and then were incubated in K depleted medium for 24 hours. Binding was saturable, time and temperature-dependent in K replete and K depleted cells. Total binding and Bmax (139 +/- 13 vs. 93 +/- 7 fmol/mg protein, P less than 0.01) were increased in K depleted cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin-1 treatment increases neutrophils but not antioxidant enzyme activity or resistance to ischemia-reperfusion injury in rat kidneys

Hearts from rats treated with interleukin-1 (IL-1) intraperitoneally developed a rapid (6 h after IL-1), transient increase in neutrophils, tissue hydrogen peroxide (H₂O₂), and oxidized glutathione (GSSG) levels, and a subsequent (36 h after IL-1) increase in myocardial glucose-6-phosphate dehydrogenase (G6PD) activity and tolerance to ischemia-reperfusion. In the present investigation, we found that rats treated similarly with IL-1 had increased numbers of neutrophils in their kidneys, which were comparable to myocardial neutrophil increases, but did not develop increased renal tissue H₂O₂ or GSSG levels acutely (6 h after IL-1) or increased G6PD activity or resistance to ischemia-reperfusion injury later (36 h after IL-1). Our findings indicate that IL-1 treatment increased neutrophil accumulation in rat kidneys but did not increase oxidative stress, antioxidant enzyme activity, or resistance to ischemia-reperfusion injury. We conclude that organ-to-organ differences exist with respect to IL-1-induced tolerance.     

Endothelial cells regulate proximal tubule epithelial cell sodium transport

BACKGROUND: Proximal tubule epithelial cells are in close contact with the renal microvasculature, but the effect of endothelial cells (ECs) on proximal tubule epithelial cell (PTEC) function is not known. METHODS: To determine if ECs regulate PTECs, we coincubated ECs with PTECs in a system that permitted cross-talk between the two cell types and the vectorial transport of sodium. RESULTS: In the presence (but not absence) of ECs, adding bradykinin or acetylcholine increased cGMP and decreased sodium transport, as well as Na,K-ATPase in PTECs. Interleukin (IL)1B preconditioning of ECs also increased cGMP and decreased sodium transport and Na,K-ATPase in PTECs. Bradykinin, acetylcholine, and IL1B EC-dependent effects were reversed with the nitric oxide (NO) synthase inhibitor L-NNA. In the absence of ECs, the addition of NO donors to PTECs increased cGMP and decreased sodium transport and Na,K-ATPase. 8Br-cGMP also decreased PTEC sodium transport and Na,K-ATPase. CONCLUSION: Endothelial cells regulate PTEC function. This effect is mediated by NO synthase-dependent up-regulation of cGMP in PTECs.     

Training the Next Generation’s Nephrology Workforce

The subspecialty of nephrology faces several critical challenges, including declining interest among medical students and internal medicine residents and worrisome declines in the number of applicants for nephrology fellowships. There is an urgent need to more clearly define the subspecialty and its scope of practice, reinvigorate meaningful research training and activities among trainees, and ensure that fellows who complete training and enter the practice of nephrology are experts in the broad scope of nephrology. This need requires a critical look at fellowship training programs and training requirements. A new workforce analysis is also needed that is not focused on primarily meeting estimated future clinical needs but rather, ensuring that there is alignment of supply and demand for nephrology trainees, which will ensure that those entering nephrology fellowships are highly qualified and capable of becoming outstanding nephrologists and that there are desirable employment opportunities for them when they complete their training.     

Mayo's Older Americans Normative Studies: Age- and IQ-Adjusted Norms for the Wechsler Memory Scale--Revised

ABSTRACT

Normative data sets for standardized neuropsychometric instruments often include adjustments for subject variables. There are reasons to believe, however, that improvements in interpretive accuracy that result from such adjustments are less than optimal. In particular, “years of formal education” may be less closely related to test performances than is general intellectual functioning. In this third of four reanalyses of results from the Mayo Clinic's Older Americans Normative Studies (MOANS) databases, age-adjusted index and scaled scores for the Wechsler Memory Scale-Revised were found to be more strongly associated with Mayo age-adjusted WAIS-R Full Scale IQ scores (rs = .271 to .631) than with education (rs = .089 to .310) for healthy older examinees between 56 and 99 years of age. These associations were strongest for Attention/Concentration and General Memory Index scores and, in general, for individuals with average intelligence (cf. Dodrill, 1997 Dodrill , C. B. ( 1997 ). Myths of neuropsychology . The Clinical Neuropsychologist , 11 , 1 – 17 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar] 1999 Dodrill , C. B. ( 1999 ). Myths of neuropsychology: Further considerations . The Clinical Neuropsychologist , 13 , 562 – 572 . [PUBMED] [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Tables of age- and IQ-adjusted percentile equivalents of Mayo age-adjusted WMS-R index scores and MOANS age-adjusted WMS-R subtest scaled scores are presented for eleven age ranges and seven IQ ranges.     

Older Adult Norms for the Southern California Figure-Ground Visual Perception Test

Older adult norms for men are provided for the Southern California Figure-Ground Visual Perception Test (FG; Ayres, 1966), based on the performance of 117 patients from a geriatric medicine and rehabilitation facility ranging in age from 40 to 77 years. Reasons are presented for administering the entire test rather than using the traditional cutoff. When comparing FG performance to norms of younger adults (Bieliauskas, Newberry, Gerstenberger, 1988), results indicate that figure-ground discrimination is poorer in older individuals. The norms provided here serve to complement the previous study employing FG, and it is hoped that they will encourage its wider use.