High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease

Summary Chronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 m and the inplane resolution was 40×40 m. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.Supported by the Belgian Foundation of Medical Scientific Research (FGWO, grant 3.0096.86 and grant 3.0019.86), by the Institute for the promotion of Scientific Research in Industry and Agriculture (IWONL) and by the Scientic Research Planning Office of the Belgian Government (DPWB), contract no. 87/92-120     

Development of spinocerebellar afferents in the clawed toad, Xenopus laevis

The development of spinocerebellar projections in the clawed toad, Xenopus laevis, was studied with horseradish peroxidase as an anterograde and retrograde tracer. Early in development cells of origin of spinocerebellar projections were found, contralaterally, in or close to the medial motor column. In older tadpoles ipsilaterally projecting spinal neurons were also labeled from the cerebellum. These are virtually indistinguishable from the large primary motoneurons that occupy a very similar position in the spinal cord. Most of the labeled spinal cells were found in the thoracic spinal cord; they lie halfway between the brachial and lumbar secondary motor columns. Surprisingly, no primary spinocerebellar projection arising from dorsal root spinal ganglion cells could be demonstrated in X. laevis tadpoles and adult toads. Therefore, fibers in the cerebellum that were labeled anterogradely from the spinal cord can be expected to originate exclusively from the secondary spinocerebellar tract cells. These fibers appear to cross the cerebellum in or at the border of the granular layer. The present data suggest that in X. laevis early in the development of the cerebellum a distinct secondary spinocerebellar projection is already present, originating in neurons that can be compared with the "spinal border cells" in mammals. The relative sparseness of this secondary spinocerebellar projection and the apparent absence of primary spinocerebellar afferents probably indicate that spinocerebellar pathways are only of minor importance in X. laevis. The possibility remains, however, that the expansion of the secondary spinocerebellar pathway only starts when metamorphosis has been completed.     

A Double-Blind Comparison of Sinusoidal Wave and Brief-Pulse Electroconvulsive Therapy in Endogenous Depression

In a double-blind prospective study, 29 endogenously depressed patients (RDC) were randomized into sinusoidal wave (SW) and brief-pulse (BP) electroconvulsive therapy (ECT) groups. Bilateral modified treatments were administered on alternate days, three per week, and the treatment variables of current dosage and seizure duration were monitored for each treatment. Significantly more patients responded to SW than to BP ECT, but a comparable number of treatments was required to produce this response in the two groups. There was no difference in clinical or treatment variables between the SW and the BP groups, nor between ECT responders and nonresponders, with the exception that the SW-treated patients received larger doses of current per treatment than did the BP patients. For endogenous depression treated with ECT, we conclude that cumulative seizure duration may not be a parameter of significance, that overall rate of recovery in ECT responders is independent of stimulus waveform, and that some depressives may respond to SW but not to BP ECT. We suggest that the antidepressant effect of the ECT seizure may be characterized by a therapeutic window in current requirements; alternatively, a putative response threshold (again in terms of current requirement) may exist, which is higher in some patients than in others.     

Mania as a Side Effect of Electroconvulsive Therapy

Thirty-two endogenous depressed patients (RDC) were treated with electroconvulsive therapy. Four patients (12.5%) developed a transient manic reaction; in two cases, this reaction occurred in mid-depression. Mania is not a generally recognized side effect of ECT; we detail the clinical characteristics, but fail to define clinical predictors of vulnerability.     

Disk hypodensity and disk herniation

The authors report the case of a patient with a herniated lumbar disk and bacterial meningitis. CT scan showed central disk hypodensity at the hernia level, whilst full cytological and bacteriological study of the disk following surgery revealed no evidence of spondylodiscitis. The problem was thus that of consequences of "degenerative" events related to the herniation. Central or peripheral disk hypodensity must in no case be considered as specific of discitis when there is a concomitant disk herniation.     

Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.     

Enzymatic synthesis of penicillins

Different penicillins (phenylacetyl, 2-hydroxyphenylacetyl, 4-hydroxyphenylacetyl, phenoxyacetyl and 2-thiopheneacetylpenicillin) have been synthesized "in vitro" by direct N-acylation of 6-aminopenicillanic acid (6-APA) with the acyl group of several acyl-CoA derivatives. The enzyme that catalyzes these reactions, acyl-CoA: 6-APA acyltransferase of Penicillium chrysogenum, was purified to homogeneity (374-fold) and its amino acid composition is given. This protein accepts as substrates several aliphatic acids and different aromatic acids with the only requirement that an acetyl-CoA moiety must be present in the substrate molecule. Shortening or lengthening of the acyl moiety prevents the 6-APA-N-acylation reaction. The presence of an amino group in the alpha-position of the acetyl group does not allow this molecule to be used as substrate. However, different substitutions in the phenyl group (hydroxylation of the carbons 2 and 4) or its replacement by another aromatic ring (thiophene) were accepted with varying reactions rates in the acylation reaction when a 176-fold purified acyltransferase was employed. The homogeneity pure enzyme accepts as substrate thiophene acetyl-CoA but it did not 2-hydroxyphenyl and 4-hydroxyphenylacetyl-CoA. The presence of an oxygen atom between the aromatic and the acetyl moieties did not affect the catalysis.     

The effect of isoluminant and isochromatic stimuli on latency and amplitude of saccades

When two stimuli are presented in different positions successively at short time intervals saccadic eye movements are usually directed at intermediate positions. This phenomenon of "averaging" of saccadic eye movements has been studied in responses to double-step target displacements in different stimulus conditions. In these conditions isoluminant and isochromatic stimuli were used with variable contrast and at different background luminances. Although the critical duration of temporal summation differed considerably in these stimulus conditions the duration of the phenomenon of "averaging" remained the same in all conditions. This indicates that temporal properties of the sensory system are not the prime cause of "averaging". Moreover, the onset time of "averaging" relative to the second target displacement turned out to be highly correlated with the mean latency of saccades in the different conditions. The implications of the results for models of oculomotor control are discussed.     

Chemical derivatization as a strategy to enhance detectability of agents used in cancer management

The bioanalysis of drugs used in the management of cancer is often complicated by the lack of selectivity and sensitivity. Chemical derivatization of these drugs prior to their chromatographic analysis represents a viable strategy to improve chromatographic resolution and to enhance detectability. This review provides examples of how this approach can meet these objectives. Derivatization of racemic cyclophosphamide with a chiral acylating agent, following hydroxyalkylation to introduce a reactive centre into the molecule, provides the basis for its stereospecific analysis. The analysis of dianhydrogalactitol is described, in which diethyldithiocarbamate is used as a nucleophilic derivatizing agent that improves chromatographic behaviour and analytical sensitivity. The final example that is described is the design and preparation of improved fluorogenic reagents (o-phthalaldehyde analogues) for the derivatization of peptides and application of these reagents to the trace analysis of leu-enkephalin in plasma.     

Heterogeneity of human basophils and mast cells in response to muscle relaxants

We investigated thein vitro effects of increasing concentrations (10^–5–10^–3 M) of four muscle relaxants (succinylcholine, d-tubocurarine, vecuronium and atracurium) on histamine release (HR) from human peripheral blood basophils and mast cells isolated from lung parenchyma (HLMC) and skin tissues (HSMC). Basophils released less than 5% of their histamine content when incubated with any one of the muscle relaxants. In contrast, mast cells showed a marked heterogeneity in their response. Succinylcholine did not induce HR from any type of mast cell, and only high concentrations of d-tubocurarine (10^–3 M) caused HR from HSMC and HLMC. Vecuronium concentration-dependently induced HR from HLMC and HSMC. Atracurium concentration-dependently caused marked HR from HLMC and HSMC up to a maximum of 46.2±15.1% and 30.6±6.0%, respectively. From both HLMC and HSMC HR caused by atracurium and vecuronium was extremely rapid (t_1/2<1 min).=" the=" releasing=" activity=" of=" atracurium=" and=" vecuronium=" on=" hlmc=" and=" hsmc=" was=" reduced,=" but=" not=" abolished,=" by=" lowering=" the=" temperature=" of=" the=" incubation=" buffer=" to=" 22°c=" and=" 4°c.=" these=" results=" confirm=" that=" there=" are=" functional=" differences=" between=" human=" basophils=" and=" mast=" cells=" and=" among=" mast=" cells=" isolated=" from=" different=" anatomical=" sites=" in=" response=" to=" the=" muscle=" relaxants=">