多培沙明,非诺多泮和丙卡特罗对心肌缺血时电生理变化影响的比较

新型多巴胺受体激动剂多培沙明(DPX)能显著减轻缺氧和缺血豚鼠心室乳头肌静息电位,动作电位幅度和O相除极速度的降低程度及动作电位时程的缩短程度,其减轻作用明显大于非诺多泮(FODA)和丙卡特罗(PCTR)。DPX能使缺氧时缩短的有效不应期(ERP)延长,而使缺血时延长的ERP缩短,其程度明显大于FODA与PCTR。提示DPX抗缺血性心律失常的作用优于其他类型的多巴胺激动剂。     

First mutation in the voltage-gated NaV1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy

Almost all mutations in the SCN1A gene, encoding the α₁ subunit of neuronal voltage-gated Na_V1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.     

Characterization of four N-3-thymidine adducts formed in vitro by the reaction of thymidine and butadiene monoxide

Four products were characterized from the reaction of thymidine with butadiene monoxide (BM), a known human mutagen and possible human carcinogen. These products were purified by HPLC and characterized as diastereomeric pairs of N-3-(1-hydroxy-3-buten-2-yl)thymidine and N-3- (2-hydroxy-3-buten-1-yl)thymidine based upon their UV spectra, 1H NMR and fast atom bombardment mass spectra. Incubation of thymidine with an excess of BM at pH 7.4 and 37 degrees C allowed calculation of the pseudo-first-order kinetic rate constants for the adduct formation, but when these rate constants were compared with the rates we previously determined with guanosine, adenosine and deoxycytidine, the results suggested a lower reactivity with thymidine in comparison with the other nucleosides. When incubations were carried out at lower BM concentrations, the formation of adducts appeared to be linearly dependent on BM concentration. The four thymidine adducts were completely stable for 1 week when incubated at 37 degrees C in pH 7.4 phosphate buffer. These results suggest that the interactions of BM with thymidine may play a role in the molecular mechanisms of mutagenesis and carcinogenesis of BM.      

Plasmacytoid myoepithelioma of minor salivary glands: report of case with emphasis in the immunohistochemical findings

Extracorporeal formation of mineralized bone-like tissue is still an unsolved challenge in tissue engineering. Embryonic stem cells may open up new therapeutic options for the future and should be an interesting model for the analysis of fetal organogenesis. Here we describe a technique for culturing embryonic stem cells (ESCs) in the absence of artificial scaffolds which generated mineralized miromasses. Embryonic stem cells were harvested and osteogenic differentiation was stimulated by the addition of dexamethasone, ascorbic acid, and ß-glycerolphosphate (DAG). After three days of cultivation microspheres were formed. These spherical three-dimensional cell units showed a peripheral zone consisting of densely packed cell layers surrounded by minerals that were embedded in the extracellular matrix. Alizarine red staining confirmed evidence of mineralization after 10 days of DAG stimulation in the stimulated but not in the control group. Transmission electron microscopy demonstrated scorching crystallites and collagenous fibrils as early indication of bone formation. These extracellular structures resembled hydroxyl apatite-like crystals as demonstrated by distinct diffraction patterns using electron diffraction analysis. The micromass culture technique is an appropriate model to form three-dimensional bone-like micro-units without the need for an underlying scaffold. Further studies will have to show whether the technique is applicable also to pluripotent stem cells of different origin.     

Localization of surface vWF on resting and stimulated platelets

We used immunoelectron microscopic localization techniques to investigate whether platelets stimulated by ADP or ristocetin in the plasma milieu bind von Willebrand factor (vWF) to their surfaces. We found by both peroxidase- and ferritin-based methods that unstimulated platelets lack vWF on their surfaces, whereas platelets that are stimulated with ADP or ristocetin have vWF associated with their surfaces. The specificity of the findings was confirmed by absorption studies using severe von Willebrand disease (vWD) and hemophilic plasmas. The anti-vWF antibodies were blocked by incubation with hemophilic plasma but not by incubation with severe vWD plasma. Thus, in the plasma environment, in the presence of fibrinogen, vWF becomes associated with the platelet surface subsequent to stimulation with ADP or ristocetin.     

Surface coil MR imaging of abdominal viscera. Part III. The pancreas

Eight healthy volunteers and 11 patients with pancreatic abnormalities were studied using a conventional body coil and a prototype magnetic resonance (MR) surface coil. Final pathologic diagnoses included carcinoma of the head (six), body (one), and tail of the pancreas (two) and chronic pancreatitis (two). In surface coil images of the volunteers, the body and tail of the pancreas was visualized in all cases but one, and the pancreatic duct was seen in five of eight cases. In-plane spatial resolution of 0.9 X 0.9 mm and 5-mm section thickness was obtained. At the same time, pancreatic surface coil images had a twofold improvement in the signal-to-noise ratio (SNR) compared with body coil images. T1-weighted spin-echo images gave greater SNR, reduced motion artifacts, provided superior anatomic detail, and offered more diagnostic information than comparable T2-weighted images. Significant abnormalities detected only by surface coil imaging included a small tumor surrounded by reactive edema and periglandular tumor invasion. This study demonstrates that surface coil imaging of the pancreas not only is feasible but provides an improved method for examining the pancreas by MR.