Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator.

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).     

Mn Concentration in Organs of Rats After Implantation of Battery Cathode Material

The distribution of Mn, originating from MnO₂ in miniaturized batteries, was studied in rats. Forty young male Wistar rats were included in a randomized block experiment with body weight, weight gain, relative organ weight, and the concentration of Mn as dependent variables. Mn containing cathode material was implanted subcutaneously and after 1 month, animals were sacrificed and organs collected. Mn levels were determined by ICPES after destruction of the organic matter using microwave energy. Body weight, weight gain, and relative weight of heart, brain, liver, and kidneys were not significantly altered after implantation of cathode material. However, Mn levels were largely increased in the four organs under study. These high levels did not provoke any of the well-known clinical signs associated with Mn intoxication. Effects of Mn in larger farm animals can be considered as insignificant.     

View ordering for magnetization prepared steady state free precession acquisition: application in contrast-enhanced MR angiography.

Magnetization prepared segmented acquisition requires a view order that maximizes signal contrast during the acquisition of the central portion of k-space. Steady state free precession (SSFP) acquisition further requires a view order that minimizes changes in phase-encoding gradients from one repetition to the next in order to minimize eddy current artifacts. In this article, optimal view ordering schemes satisfying these two requirements are formulated and applied to inversion prepared 3D SSFP contrast-enhanced MR angiography (MRA). Experiments on phantoms and pigs demonstrated improved background suppression and reduced image artifacts.     

Cyclic AMP increases the release of parathyroid hormone-related protein from a lung-cancer cell line

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line (BEN). In supervised cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-I-methylxanthine or dibutyryl cAMP even in the presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The calcitonin-mediated stimulation was not accompanied by. concomitant changes in PTHrP mRNA. The microfilament-disrupter cytocha-lasin D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.     

The effect of racemic ketamine on the large conductance Ca-activated potassium (BK) channels in GH3 cells

Recently, inhalation anesthetics have been reported to block BK channels in adrenal chromaffin cells. To determine if BK block was characteristic only of inhalation anesthetics or was also a property of other general anesthetics we examined the effects of ketamine, an intravenous general anesthetic which is structurally different than inhalation anesthetics. Cell-attached and excised patch single channel and standard whole cell recording techniques were used to examine the effect of racemic ketamine on the BK channel activity in GH₃ cells. When solutions containing 150 mM KCl are used in both the pipette and bath, the BK channels are characterized as a voltage-dependent channel with a unit conductance of 150–300 pS. Racemic ketamine (at clinically relevant concentrations; 2–500 μM) selectively blocked BK channels in a dose-dependent, reversible manner as evidenced by decreases in NP_o (number of channels × open probability). This decrease was due to both a decrease in mean open time and an increase in the mean closed time but without a decrease in single-channel current amplitude. Ketamine shifts the P_o vs voltage curve to higher potentials without a change in the slope of the voltage dependence. Ketamine also shifts the P_o vs [Ca⁺²] relationship to higher Ca⁺² concentrations. The IC₅₀ for the single-channel block by ketamine is 20.3 ± 15.9 μM. In an effort to confirm that the effect of ketamine was predominantly due to a block of the BK channels, standard whole cell techniques were utilized. As with the single-channel experiments, ketamine (2–500 μM) produced a dose-dependent, voltage-independent and reversible decrease in outward current with an IC₅₀ of 23.7 ± 11.5 μM. Addition of 100 μM ketamine to cells pretreated with the BK channel blocker, charybdotoxin (ChTX), did not result in a further decrease in outward current. These results demonstrate a selective effect of ketamine at clinically relevant concentrations which is consistent with results reported for inhalation anesthetics.     

Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [H]5-HT, in frontal cortex and the hippocampal region of the human brain

In human cortex and hippocampus area, [³H]5-HT (5 nM) labels 5-HT_1A, 5-HT_1D and 5-HT_1E sites. After masking 5-HT_1A receptors by 0.1 μM 8-OH-DPAT, the binding displaced by 0.1 μM 5-CT presumably represented 5-HT_1D sites and the remaining binding 5-HT_1E sites. In frontal cortex, 5-HT_1A receptors represented the main binding in layers II and VI and a lower fraction on other layers. 5-HT_1D and 5-HT_1E sites, were more homogeneously distributed in layers II to VI (21–34% of specific [³H]5-HT binding). 5-HT_1E sites were of similar affinities (K_D close to 6–8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT_1A receptors represented the major fraction, 5-HT_1D sites a significant fraction and 5-HT_1E a minor fraction of the specific [³H]5-HT binding. In CA3–CA4 fields, 5-HT_1A receptors were less densely present, 5-HT_1D sites were predominant and 5-HT_1E sites represented a significant fraction (27%). The highest densities of 5-HT_1E sites have been measured in subiculum, where 5-HT_1A, 5-HT_1D, and 5-HT_1E binding sites were equally represented and in entorhinal cortex where 5-HT_1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT_1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT_1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT_1E were detected in choroid plexus, where [³H]5-HT was dramatically reduced by mesulergine (5-HT_2C receptors). No significant displacement of [³H]5-HT by mesulergine was measured in other structures.