Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure

Ischemic acute renal failure is characterized by damages to the proximal straight tubule in the outer medulla. Lesions include loss of polarity, shedding into the tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It was recently shown that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction. Therefore, whether PPARbeta/delta could contribute also to the control of tubular epithelium death after renal ischemia/reperfusion was tested. It was found that PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney dysfunction and injury than wild-type counterparts after a 30-min renal ischemia followed by a 36-h reperfusion. Conversely, wild-type mice that were given the specific PPARbeta/delta ligand L-165041 before renal ischemia were completely protected against renal dysfunction, as indicated by the lack of rise in serum creatinine and fractional excretion of Na+. This protective effect was accompanied by a significant reduction in medullary necrosis, apoptosis, and inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to exert their role by activating the antiapoptotic Akt signaling pathway and, unexpectedly, by increasing the spreading of tubular epithelial cells, thus limiting potentially their shedding and anoikis. These results point to PPARbeta/delta as a remarkable new target for preconditioning strategies.     

Early event-related potential changes during working memory activation predict rapid decline in mild cognitive impairment

BACKGROUND: The conversion of mild cognitive impairment (MCI) to Alzheimer's disease is associated with substantial compromise of neocortical circuits subserving rapid cognitive functions such as working memory. Event-related potential (ERP) analysis is a powerful tool to identify early impairment of these circuits, yet research for an electrophysiological marker of cognitive deterioration in MCI is scarce. Using a "2-back" activation paradigm, we recently described an electrophysiological correlate of working memory activation (positive-negative working memory [PN(wm)] component) over parietal electrodes. METHODS: Ours was a longitudinal study of 24 MCI patients with ERP analysis at inclusion and neuropsychological follow-up after 1 year. We used ERP waveform subtraction analysis between the n-back and control tasks. Analysis of variance (ANOVA) was used to compare electroencephalograph latencies between progressive MCI (PMCI) and stable MCI (SMCI), and univariate regression was used to assess the relationship between neuropsychological measures at baseline and clinical outcome. RESULTS: Thirteen (54%) MCI patients showed PMCI, and 11 (46%) remained stable (SMCI). In SMCI, a PN(wm) component with significantly larger density compared to baseline was identified when subtracting the detection task for both the 1- and 2-back tasks. In contrast, in PMCI, the PN(wm) component was absent in both 1-back and 2-back conditions. Neuropsychological variables and n-back test performance at inclusion did not predict cognitive deterioration 1 year later. CONCLUSIONS: In conjunction with recent functional imaging data, the present results support the notion of an early dysfunction of neural generators within the parietal cortex in MCI. They also reveal that the absence of the PN(wm) component may provide an easily applicable qualitative predictive marker of rapid cognitive deterioration in MCI.     

Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation

OBJECTIVE: Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance. METHODS: The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery. CONCLUSION: The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term.     

In situ hybridization of dihydroxyacetone phosphate acyltransferase, the regulating enzyme involved in plasmalogen biosynthesis

In situ hybridization can be carried out using different methods. The experimenter has to choose various parameters: the type of tissue fixation, the time of incubation, and the duration of the exposure time. All these parameters are determinant for the sensitivity and the resolution of this technique. This publication of technical aspects described different experiments performed for in situ hybridization on liver tissue. We may conclude on the parameters to optimize each step of the hybridization procedure. Moreover, this technique could be transposed to the brain and applied to little structures with a light expression of DHAP-AT.     

Generalized eczema craquele as a presenting feature of systemic lymphoma: report of seven cases

Eczema craquele, or asteatotic eczema, has been associated with malignant lymphoma although this is rare. Since 1986, we have observed seven patients, six men and one woman, mean age 71.5 years (range 43-86 years), with systemic lymphoma and concurrent eczema craquele. Five patients had T-cell lymphoma, one had a B-cell lymphoma and one had Hodgkin's disease. All patients shared several characteristics: (1) a synchronous onset of eczema craquele and lymphoma, (2) generalized eczema, (3) absence of alternative disease or conditions that could favour the onset of eczema craquele, and (4) eczema refractory to topical corticosteroids and emollients, but which resolved upon lymphoma remission and invariably recurred with the lymphoma relapse. All the patients except one died within 1 year, most with active lymphoma. The finding of recalcitrant generalized eczema craquele should prompt a search for lymphoma, particularly in older men. Lymphoma-associated eczema craquele has most characteristics of paraneoplastic syndromes and may be a hallmark of aggressive lymphoma.     

Angiogenesis and arteriogenesis are increased in fibrin gel chambers implanted in prehypertensive spontaneously hypertensive rats

OBJECTIVE: Microvascular rarefaction by an unbalanced angiogenesis could promote the onset of hypertension in spontaneously hypertensive rats and in hypertensive patients. We studied the angiogenic potency in the fibrin gel chamber model in prehypertensive spontaneously hypertensive rats and their controls, Wistar-Kyoto rats. METHODS: Four-week-old prehypertensive spontaneously hypertensive rats (n = 9) and Wistar-Kyoto rats (n = 9) were implanted with four fibrin gel chambers located in the dorsal subcutaneous space. After 14 days, vasculoconjunctive buds had invaded the fibrin gel through the 10 hole-perforated bottom slip of the chamber. The intact vascular buds were studied using optical microscopy, alpha-actin and von Willebrand factor stainings. Capillaries and arterialized vessels were counted in three peripheral and one central field in each bud. The immunodetection of vascular endothelial growth factor and fibroblast growth factor 2 was performed on the neovascular buds. RESULTS: In fibrin chambers implanted in spontaneously hypertensive rats, the number of peripheral vessels was significantly higher than in Wistar-Kyoto rats. There were significantly more arterialized vessels in spontaneously hypertensive rats compared with Wistar-Kyoto rats. The number of immunostained cells for fibroblast growth factor 2 was significantly greater in spontaneously hypertensive rats compared with Wistar-Kyoto rats. There was no significant difference in vascular endothelial growth factor staining between the two strains of rats. CONCLUSION: Angiogenesis and arteriogenesis are increased in fibrin chambers implanted in prehypertensive spontaneously hypertensive rats compared with Wistar-Kyoto rats. These results argue against microvascular rarefaction as a cause of hypertension using this model of angiogenesis.     

Coronary artery stenosis: direct comparison of four-section multi-detector row CT and 3D navigator MR imaging for detection--initial results

PURPOSE: To prospectively compare the diagnostic accuracy of multi-detector row computed tomography (CT) and of three-dimensional (3D) navigator magnetic resonance (MR) imaging in patients referred for conventional coronary angiography for detection of coronary artery stenosis. MATERIALS AND METHODS: All patients gave written informed consent for the study, which was approved by the local ethics committee. Twenty-seven patients underwent multi-detector row CT and 3D navigator free-breathing MR imaging a mean of 5 days before undergoing invasive coronary angiography. The acquired multi-detector row CT and MR images were graded for the presence of greater than 50% stenosis in vessels larger than 1.5 mm in diameter. The diagnostic accuracies of the two examinations were compared with that of quantitative coronary angiography (QCA) by using the McNemar test. RESULTS: Owing to claustrophobia, MR images were not acquired in one patient; thus, 26 patients were included for analysis. According to QCA findings, 21 of the 26 patients had significant coronary artery disease and 58 (20%) of a total of 294 coronary artery segments larger than 1.5 mm in diameter had significant (>50%) stenosis. Multi-detector row CT had significantly higher sensitivity (46 [79%] of 58 segments) than MR imaging (36 [62%] segments, P < .05) for detection of segments with significant stenosis. Conversely, MR imaging had significantly higher specificity (198 [84%] of 236 segments) than did CT (168 [71%] segments, P < .001) for exclusion of segmental coronary artery stenosis. Both examinations had high negative predictive value for exclusion of segmental stenosis: 93% (168 of 180 segments) for CT and 90% (198 of 220 segments) for MR imaging. The overall diagnostic accuracy of MR imaging (80% [234 of 294 segments]) was significantly higher than that of CT (73% [214 segments], P < .05). CONCLUSION: MR imaging had significantly higher diagnostic accuracy than multi-detector row CT in the evaluation of coronary artery stenosis. Both techniques have high negative predictive value, making them particularly useful for ruling out coronary artery disease in symptomatic patients.     

131I in blood samples: a danger for professionals? A problem for immunoassays?

OBJECTIVE: Our objective was to investigate the safety of radioactive blood samples from patients receiving 131I and whether the radioactivity affects the validity of assays. METHODS: First, the activity of samples from patients given 131I was measured by 3 methods and compared with the upper threshold. Then, pilot sera were spiked with 131I, and possible interference was investigated using 2 immunoradiometric assays. RESULTS: The activity of 13 of the 15 samples was below the European limit; the other 2 samples were from patients with reduced renal clearance rates. No differences in thyroglobulin level or thyroid-stimulating hormone level were found between sera that were spiked with 131I and sera that were not. CONCLUSION: These blood samples are safe because they contain negligible activity, and the use of radioimmunoassays or immunoradiometric assays on them produces reliable results.