Sneddon's syndrome: generalized livedo reticularis and cerebrovascular disease. Importance of hemostatic screening.

We report two cases of Sneddon's syndrome. Both cases had widespread livedo reticularis with repeated cerebrovascular accidents without persistent neurological deficit. In one case, hemostatic examination revealed an imbalance of plasminogen activator-inhibitor values, possibly related to the thrombogenic propensity of the syndrome. Treatment with acetylsalicylic acid led to normalization of hemostatic parameters and resulted in a symptom-free period of more than 10 months. The importance of hemostatic screening in patients with Sneddon's syndrome is discussed.     

Uptake and toxicity of copper oxide nanoparticles in cultured primary brain astrocytes

To test for consequences of an exposure of brain cells to copper oxide nanoparticles (CuO-NPs), we synthesised and characterised dimercaptosuccinate-coated CuO-NPs. These particles had a diameter of around 5 nm as determined by transmission electron microscopy, while their average hydrodynamic diameter in aqueous dispersion was 136 ± 4 nm. Dispersion in cell-culture medium containing 10% fetal calf serum increased the hydrodynamic diameter to 178 ± 12 nm and shifted the zeta potential of the particles from –49 ± 7 mV (in water) to –10 ± 3 mV. Exposure of cultured primary brain astrocytes to CuO-NPs increased the cellular copper levels and compromised the cell viability in a time-, concentration- and temperature-dependent manner. Application of CuO-NPs in concentrations above 100 µM copper (6.4 µg/ml) severely compromised the viability of the cells, as demonstrated by a lowered 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction capacity, a lowered cellular lactate dehydrogenase activity and an increased membrane permeability for the fluorescent dye propidium iodide. Copper internalisation as well as cell toxicity of astrocytes exposed to CuO-NPs were similar to that observed for cells that had been incubated with copper salts. The CuO-NP-induced toxicity was accompanied by an increase in the generation of reactive oxygen species (ROS) in the cells. Both, ROS formation and cell toxicity in CuO-NP-treated astrocytes, were lowered in the presence of the cell-permeable copper chelator tetrathiomolybdate. These data demonstrate that CuO-NPs are taken up by cultured astrocytes and suggest that excess of internalised CuO-NPs cause cell toxicity by accelerating the formation of ROS.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.      

Soil Dissipation of Diuron, Chlorotoluron, Simazine, Propyzamide, and Diflufenican Herbicides After Repeated Applications in Fruit Tree Orchards

In a pear tree orchard planted on loam soil, each plot was treated in April 1998 with either one of the ureas diuron or chlorotoluron, or triazine simazine herbicides applied at 3, 4, and 2 kg AI ha⁻¹, respectively. Some plots had not been previously treated with one of these herbicides. Other plots had been treated annually during the past 12 years with the same herbicide. One herbicide, and always the same, was thus applied to each plot. In the plots treated for the first time with either diuron, chlorotoluron, or simazine, the soil half-lives of these herbicides in the 0–10 cm surface soil layer were 81, 64, and 59 days, respectively. In the plots treated with the same herbicide for 12 years, the corresponding soil half-lives were 37, 11, and 46 days. Diuron thus produced a moderately enhanced biodegradation, chlorotoluron a high one, and simazine a low but significant one. In another pear tree orchard planted on sandy loam soil, each plot was treated in April 1998 with one of the amide propyzamide (1.25 or 1.0 AI kg ha⁻¹) or diflufenican (250 g AI ha⁻¹) herbicides. In the plots not previously treated with propyzamide, the propyzamide soil half-life was the same for both doses, i.e., about 30 days. In the plots treated annually for 3 or 14 years with propyzamide, the soil half-life was 12 and 10 days, respectively. In the plots treated for the first time with diflufenican and in those treated annually with diflufenican for 3 years, the diflufenican soil half-life was the same, i.e., 65 days. Propyzamide thus already showed a highly accelerated biodegradation after 3 years of repeated annual applications. Diflufenican, however, did not show enhanced biodegradation after 3 years of repeated annual applications. Received: 9 July 1999/Accepted: 17 December 1999     

Partial isolation and function of the prostacyclin regulating plasma factor

Rat aortic rings stop producing prostacyclin upon prolonged washing in buffer. This 'exhaustion' is caused by inhibition of cyclo-oxygenase, since these rings still convert cyclic endoperoxides but not arachidonic acid into prostacyclin, and most probably is due to high concentrations of peroxides: it can be accelerated by H2O2 or by interrupting the glutathione cycle, while it is delayed by reduced glutathione. Incubation of exhausted rings in human plasma or in a plasma filtrate restores to some extent prostacyclin formation. This filtrate, in particular from uraemic subjects, also inhibits the H2O2 initiated oxidation of guaiacol by ram seminal vesicle microsomes or horseradish peroxidase. The prostacyclin regulating plasma factor has been partially purified and identified as a stable and very polar molecule of mol. wt. 300-400, able to reactivate prostacyclin generation by exhausted rings. We suggest that one or more low mol. wt. plasma components prolong vascular prostacyclin formation by acting as reducing cofactor for cyclo-oxygenase peroxidase. The main physiological role of this plasma activity is probably to protect the vascular prostacyclin forming system from exhaustion during persistent irritation.     

The pelvic digit ��eleventh finger��

Described as asymptomatic and an incidental finding on a plain x-ray film, the “pelvic digit” is a rare congenital anomaly. A 35-year-old man is of a rare symptomatic pelvic digit that warranted surgical excision. Its importance lies in its differentiation from acquired abnormalities due to trauma such as myositis ossificans and avulsion injuries of pelvis. If this entity is kept in mind, unnecessary investigations or interventions can be avoided.