Effect of neuropeptide Y on inflammatory paw edema in the rat: involvement of peripheral NPY Y1 and Y5 receptors and interaction with dipeptidyl-peptidase IV (CD26)

Several lines of evidence suggest that neuropeptide Y (NPY) may exert regulatory effects in local inflammatory responses. Here, we show that intraplantarly (i.pl.) applied NPY, peptide YY (PYY), and an NPY Y5 receptor-selective agonist dose-dependently potentiate concanavalin A (Con A)-induced paw edema in the rat. The NPY Y1 receptor antagonist BIBO 3304 abolishes the pro-inflammatory action of both NPY and PYY while the dipeptidyl-peptidase IV (CD26) inhibitor Ile-thiazolidide exerted synergistic and potentiating effects in vivo. Taken together, the present data reveal an NPY Y1/Y5 receptor interplay and an involvement of CD26 in the NPY-induced potentiation of paw edema in the rat.     

Acquired leukoderma in congenital pigmented nevus associated with vitiligo-like depigmentation

We report a 6-year-old boy who developed depigmentation within a congenital melanocytic nevus at the age of 3 years. During the following months a halo phenomenon and vitiligo-like lesions distant from the nevus appeared. A thorough search for malignant melanoma was negative. A second patient, a 45-year-old woman, had a large congenital nevus on the trunk with marked satellitosis. At the age of 20 years, partial regression of the large nevus occurred and, in addition, halos developed around almost all smaller nevi. Repeated searches for associated malignant melanoma were negative. We review the rare cases of halo congenital nevi and emphasize that depigmentation is not necessarily associated with malignant degeneration.     

Refractory status epilepticus: frequency, risk factors, and impact on outcome

BACKGROUND: Refractory status epilepticus (RSE) is a life-threatening condition in which seizures do not respond to first- and second-line anticonvulsant drug therapy. How often RSE occurs, risk factors that predispose to this condition, and the effect of failure to control seizures on clinical outcome are poorly defined. OBJECTIVE: To determine the frequency, risk factors, and impact on outcome of RSE. DESIGN: Retrospective cohort study. SETTING: Large academic teaching hospital. PATIENTS: Consecutive sample of 83 episodes of status epilepticus in 74 patients (mean age, 63 years). MAIN OUTCOME MEASURES: Refractory status epilepticus was defined as seizures lasting longer than 60 minutes despite treatment with a benzodiazepine and an adequate loading dose of a standard intravenous anticonvulsant drug. Factors associated with RSE were identified using univariate and backward stepwiselogistic regression analyses. RESULTS: In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE (P=.03) and focal motor seizures at onset (P=.04) were identified as independent risk factors for RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line agent (usually phenobarbital). Although mortality was not increased (17% overall), RSE was associated with prolonged hospital length of stay (P<.001) and more frequent functional deterioration at discharge (P=.02). CONCLUSIONS: Refractory status epilepticus occurs in approximately 30% of patients with SE and is associated with increased hospital length of stay and functional disability. Nonconvulsive SE and focal motor seizures at onset are risk factors for RSE. Randomized controlled trials are needed to define the optimal treatment of RSE.     

A Shaker homologue encodes an A-type current in Xenopus laevis

In Xenopus laevis, several distinct K(+)-channels (xKv1.1, xKv1.2, xKv2,1, xKv2.2, xKv3.1) have been cloned, sequenced, and electrophysiologically characterized. K(+)-channels significantly shape neuronal excitability by setting the membrane potential, and latency and duration of action potentials. We identified a further Shaker homologue, xKv1.4, in X. laevis. The open reading frame encodes a K(+)-channel that shares 72% of its 698 amino acids with the human Shaker homologue, hKv1.4. Northern blot analysis revealed xKv1.4 in the brain, muscle, and spleen but not in the ovary, intestine, heart, liver, kidney, lung, and skin. Whole-cell patch clamp recording from rat basophilic leukaemia (RBL) cells transfected with xKv1.4 revealed a voltage-gated, outward rectifying, transient A-type, K(+) selective current. xKv1.4 was strongly dependent on extracellular K(+). Exposure of cells to K(+) free bath solution almost completely abolished the current, whereas in the presence of high K(+), inactivation in response to a maintained depolarizing step and the frequency-dependent cumulative inactivation decreased. Ion channels encoded by xKv1.4 are sensitive to 4-aminopyridine and quinidine but insensitive to tetraethylammonium and the peptide toxins, charybdotoxin, margatoxin, and dendrotoxin. In conclusion, our results indicate that the biophysical and pharmacological signature of xKv1.4 closely resemble those of the A-current described in Xenopus embryonic neurons and is similar to the human Shaker homologue, hKv1.4.     

Thrombogenicity of various endovascular stent types: an in vitro evaluation

PURPOSE: The aim of this study was to evaluate the thrombogenicity of different peripheral stent types in a standardized in vitro model with fresh human whole blood. MATERIALS AND METHODS: Different stents (N = 77; n = 7 of each of 11 types) were implanted in polyvinyl chloride tubing loops and filled with donor blood samples. After 120 minutes of blood circulation, the thrombin-antithrombin III complex (TAT) levels, beta-thromboglobulin (beta-TG) levels, and platelet counts were assessed. RESULTS: After 2 hours, significant differences were seen. TAT values (+/- SD) with the investigated stents were 31 micro g/mL +/- 20 (control, no stent), 328 micro g/mL +/- 206 (Saxx stent, peripheral medium CrNi31 L), 651 micro g/mL +/- 760 (Palmaz Corinthian Stent, 316 L stainless steel, electropolished), 1,609 micro g/mL +/- 1,264 (Palmaz Corinthian Stent, 316 L stainless steel, not electropolished), 810 micro g/mL +/- 578 (Palmaz Schatz long medium stent), 569 micro g/mL +/- 347 (Smart Nitinol stent), 1,037 micro g/mL +/- 577 (Megalink peripheral stent), 543 micro g/mL +/- 487 (peripheral stent, electropolished), 1,674 micro g/mL +/- 2,057 (peripheral stent, not electropolished), 3,128 micro g/mL +/- 1,812 (SelfX Nitinol stent, polished), 5,897 micro g/mL +/- 2,380 (SelfX Nitinol stent, unpolished), and 1,458 micro g/mL +/- 887 (bridge stent). The platelet count (x1,000/ micro L +/- SD) was 218 +/- 35 (control, no stent), 188 +/- 22 (Saxx stent), 187 +/- 20 (Palmaz Corinthian stent, electropolished), 135 +/- 37 (Palmaz Corinthian stent, not electropolished), 170 +/- 24 (Palmaz Schatz stent), 180 +/- 36 (Smart Nitinol stent), 159 +/- 26 (Megalink peripheral stent), 173 +/- 17 (peripheral stent, electropolished), 133 +/- 51 (peripheral stent, not electropolished), 123 +/- 37 (SelfX Nitinol stent, polished), 52 +/- 27 (SelfX Nitinol stent, unpolished), and 130 +/- 31 (bridge stent). CONCLUSION: This standardized study showed a wide range of platelet activation after stent implantation. Electropolishing clearly reduced the thrombogenicity of the stents.     

Noninvasive visualization of coronary arteries using contrast-enhanced multidetector CT: influence of heart rate on image quality and stenosis detection

OBJECTIVE: Although multidetector CT (MDCT) with retrospectively ECG-gated image reconstruction has been shown to permit noninvasive visualization of the coronary arteries, the 125-250 msec required for image acquisition frequently causes motion artifacts. We investigated the influence of a patient's heart rate on the presence of motion artifacts and on accuracy of stenosis detection on contrast-enhanced MDCT. MATERIALS AND METHODS: In 100 patients, MDCT was performed, and ECG-gated cross-sectional images were retrospectively reconstructed. From the 10 data sets obtained for each patient (reconstructed at 0-90% of the cardiac cycle in increments of 10%), we chose the best data set for every coronary artery. The images of the arteries were evaluated for occurrence of artifacts and the presence of high-grade stenosis (diameter reduction exceeding 70%) or occlusions. MDCT results were compared with coronary angiographic findings. RESULTS: Of the 400 coronary arteries, 115 (29%) could not be evaluated because of motion artifacts (n = 84) or other reasons (n = 31). Overall, 51 (49%) of 104 stenoses were revealed on MDCT. For detecting stenosis in those arteries that we could evaluate, MDCT had a sensitivity of 91% (51 of 56 stenoses detected) and a specificity of 89%. As the heart rate increased, the number of arteries that could be evaluated decreased, and overall sensitivity for stenosis detection decreased from 62% (heart rate < or = 70 beats per minute) to 33% (heart rate > 70 beats per minute). CONCLUSION: MDCT can reveal coronary stenoses, but the usefulness of MDCT as an aid in accurately evaluating stenoses decreases as a patient's heart rate increases.     

Evaluation of retrospective multisector and half scan ECG-gated multidetector cardiac CT protocols with moving phantoms

PURPOSE: We evaluated independently retrospective half scan and multisector mode manufacturer's protocols and compared them with modified acquisition protocols to determine optimal imaging parameters for cardiac scanning. MATERIALS AND METHODS: Data were acquired using two fabricated gated moving phantoms. In half scan mode, the manufacturer's recommended pitch values were compared with adjacent values at different motion rates. In multisector mode, the manufacturer's protocols were compared with ones with different gantry speeds and pitch values at the same motion rates. Weighted CT dose indexes (CTDI) were obtained for all protocols. Gated and reformatted reconstructed images of the moving phantoms were evaluated. RESULTS: In half scan mode, slightly better image quality was observed by lowering the pitch value, but with an increase of 6.3% of the weighted CTDI. Better results were obtained in multisector mode by lowering the pitch value up to 0.2, but with an increase of 14.3% of the weighted CTDI. Optimal images were obtained with the lowest temporal resolution. CONCLUSIONS: Gated moving phantom studies offer the advantage of testing acquisition protocols of complex motions and of helping to establish appropriate protocols.