[Overestimation of the degree of stenosis in the intracranial internal carotid artery determined by magnetic resonance angiography compared to conventional arteriography]. / Sobreestimación del grado de estenosis de la arteria carótida interna intracraneal por la angiorresonancia respecto a la arteriografía convencional.

INTRODUCTION: In the evaluation of stenoses of the extracranial internal carotid artery (ICA), there are studies that suggest that magnetic resonance angiography (MRA) can be a substitute for conventional arteriography (CA), although it seems it has a tendency to overestimate the degree of stenosis. No similar comparison of the two techniques has been conducted in intracranial ICA. We report the case of a patient suffering from an acute ischemic stroke and symptomatic intracranial stenosis that was overestimated when MRA was used, compared to the results obtained using CA. CASE REPORT: We report the case of a 64-year-old male with a history of arterial hypertension, hypercholesterolemia and intermittent claudication who visited the emergency department because of the sudden onset of paresthesias in the left hemiface and hand. The cranial tomography scan performed in the emergency unit ruled out any acute bleeding or early signs of a stroke. Magnetic resonance (MR) diffusion imaging showed an acute ischemic stroke in the right parietal cortex. Extracranial MRA was normal and in the intracranial area a 73% stenosis was detected in the cavernous segment of the right ICA, whereas the use of CA showed the stenosis to be only 55%. On repeating the MRA to rule out a possible rechanneling of the ICA, the image obtained was exactly the same as the earlier one. CONCLUSIONS: Our observations suggest that, as occurs with the extracranial part, MRA tends to magnify the degree of stenosis in the intracranial vessels, and this technique would therefore appear to be less efficient than CA in the evaluation of intracranial stenoses.

Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes.

Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in vitro. We investigated whether oxidative stress mediates hypertrophy and apoptosis in cyclically stretched ventricular myocytes. Neonatal rat ventricular myocytes cultured on laminin-coated silastic membranes were stretched cyclically (1 Hz) at low (nominal 5%) and high (nominal 25%) amplitudes for 24 hours. Stretch caused a graded increase in superoxide anion production as assessed by superoxide dismutase (SOD)-inhibitable cytochrome c reduction or electron paramagnetic resonance spectroscopy. The role of reactive oxygen species (ROS) was assessed using the cell-permeable SOD/catalase mimetics Mn(II/III)tetrakis(1-methyl-4-peridyl) (MnTMPyP) and EUK-8. Stretch-induced increases in protein synthesis ((3)H-leucine incorporation) and cellular protein content were completely inhibited by MnTMPyP (0.05 mmol/L) at both low and high amplitudes of stretch. In contrast, while MnTMPyP inhibited basal atrial natriuretic factor (ANF) mRNA expression, the stretch-induced increase in ANF mRNA expression was not inhibited by MnTMPyP. In contrast to hypertrophy, only high-amplitude stretch increased myocyte apoptosis, as reflected by increased DNA fragmentation on gel electrophoresis and an approximately 3-fold increase in the number of TUNEL-positive myocytes. Similarly, only high-amplitude stretch increased the expression of bax mRNA. Myocyte apoptosis and bax expression stimulated by high-amplitude stretch were inhibited by MnTMPyP. Both low- and high-amplitude stretch caused rapid phosphorylation of ERK1/2, while high-, but not low-, amplitude stretch caused phosphorylation of JNKs. Activation of both ERK1/2 and JNKs was ROS-dependent. Thus, cyclic strain causes an amplitude-related increase in ROS, associated with differential activation of kinases and induction of hypertrophic and apoptotic phenotypes.

The in vivo metabolism of cholecystokinin (CCK-8) is essentially ensured by aminopeptidase A.

The role of aminopeptidase A (APA) in inactivating cholecystokinin (CCK-8) was investigated in in vitro and in vivo experiments. EC 33 (3-amino-4-thio-butyl sulfonate), a selective APA inhibitor, decreased the formation of CCK7 after incubation of CCK-8 with rat brain synaptic membranes. The Km of purified APA for CCK-8, determined by quantifying CCK-7 production, was 144 microM and the Kcat 1400 s-1 . EC 33 protected endogenous CCK-like immunoreactivity (CCK-LI) released from brain slices by evoked depolarizations. The serine/thiol protease inhibitor Ala-Ala-Pro-Val-COCH2Cl (AAPV), alone or in combination with EC 33, did not modify significantly the level of CCK-LI released from the hippocampus, whereas it weakly protected the CCK-LI released from the cortex. Intracerebroventricular coadministration of CCK-8 and EC 33 in mouse brain led to a significant increase in the apparent affinity of CCK-8 as determined by the inhibition of the selective CCKB receptor agonist binding [3H]pBC 264 (ID50 = 88 pmol vs. 8250 pmol for CCK-8 alone); AAPV was less potent (ID50 = 445 pmol). In the same experiment the ID50 of pCCK-8, protected from aminopeptidases by a propionyl group was 86 pmol. These results strongly suggest that APA plays a major role in the inactivating pathway of CCK-8.

Characterization of a cholecystokinin 8-generating endoprotease purified from rat brain synaptosomes.

An endoproteolytic activity that specifically cleaves CCK 33, producing CCK 8, has been purified from a rat brain synaptosome preparation. The purification, which included anion exchange, chromatofocusing, hydroxyapatite, and gel filtration chromatography, resulted in a greater than 3000-fold increase in specific activity. This neutral endoprotease (pH optimum 8) exists as a 90-kDa species, which can be dissociated into active 40-kDa species. The enzyme is a non-trypsin serine protease, which is inhibited by diisopropyl-fluorophosphate and p-aminobenzamidine but not by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride, aprotinin, or a number of thiol or metalloprotease inhibitors. It is highly substrate-specific and cleaves neither trypsin, enteropeptidase, kallikrein substrates, nor analogues of mono- or dibasic cleavage sites of prohormones other than pro-CCK. The endoprotease will not cleave CCK 12 desulfate or CCK (20-29), although these peptides contain common sequences with CCK-33. The protease does cleave [Glu27]CCK (20-29), a peptide in which the glutamate mimics the negative charge normally present on tyrosine sulfate. This suggests that the negative charge at position 27 is important in substrate recognition. The enzyme will also cleave CCK 33 and CCK (1-21) on the carboxyl-terminal side of a single lysine residue in position 11. The subcellular location and specificity of this endoprotease make it a good candidate for a CCK-processing protease.

Inhibition of potassium-evoked release of cholecystokinin from rat caudate-putamen, cerebral cortex and hippocampus incubated in vitro by phencyclidine and related compounds.

Potassium-evoked release of cholecystokinin (CCK) from slices of caudate-putamen, hippocampus, and cerebral cortex was inhibited in a dose-related fashion by phencyclidine (PCP). In order to further examine this effect, PCP-like ligands (dexoxadrol, levoxadrol, PCMP and MK-801) as well as compounds known to interact with the sigma receptor ((+)-SKF, DTG, (+)-3-PPP, and pentazocine) were tested. While some of these compounds inhibited CCK release, their rank order potency (Dex = Lev greater than PCP = PCMP greater than DTG = MK-801 = (+)-3-PPP) differs from that of known PCP-N-methyl-D-aspartate linked effects or sigma interactions. These results suggest that the mechanism by which PCP acts to inhibit CCK release may involve a novel type of PCP interaction.

[Transcutaneous PO2 measurement in postoperative monitoring following thoracic surgery]. / Die transcutane PO2-Messung in der postoperativen Uberwachung nach thoraxchirurgischen Eingriffen.

Continuous transcutaneous PO2 measurement controlling the arterial PO2 was performed in 40 patients undergoing thoracotomy. The close correlation between the PO2 levels measured transcutaneously and those found in the capillary blood prove that the method is very suitable for monitoring the postoperative course after thoracotomy. Postoperative PO2 values with and without the administration of increasing amounts of oxygen showed great variations in the patients' response to oxygen, thus emphasizing the need for continuous monitoring of the arterial PO2 values. This continuous PO2 measurement gives an indication of the possible need for the application of oxygen, and controls the effectiveness of oxygen therapy.