A review of in vivo experimental methods to determine the composition of the human body

This review of experimental methods employed in the measurement of the composition of the human body covers the developments that have occurred over the past 30 years. Early methods such as hydrodensitometry and skinfold anthropometry have been superseded by dual-energy x-ray absorptiometry and bioelectrical impedance spectroscopy. The measurement of the whole-body abundance of certain elements by isotopic dilution, neutron activation analysis and x-ray fluorescence can give important information of clinical significance, but neutron activation facilities remain available in only a few centres worldwide. The relatively simple, rapid and risk-free electrical methods such as multifrequency bioelectrical impedance analysis, which can be employed at the bedside, have been found to be more complicated in their interpretation. Electromagnetic methods may only measure the composition of the human body at its surface. X-ray computed tomography and magnetic resonance imaging have not yet been employed much in body composition measurements. Some models for the composition of the human body are reviewed.     

Myositis ossificans of the chest wall

We report the unusual case of a young man with progressive pain in the thoracic wall. The radionuclide bone scan revealed an increased uptake, and the bone roentgenogram, a calcified soft-tissue mass. Based on computed tomography findings, biopsy was avoided, and evolution was favourable for myositis ossificans. Although rare, myositis ossificans is one of the potential causes of thoracic pain, not to be mistaken for a malignant or infectious lesion.     

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs. The preparation of multiply substituted 2-methoxynaphthalene-1,4-diones was effected via Diels-Alder methodology utilizing substituted butadienes with 2-methoxybenzoquinones followed by aromatization. Structural modifications, such as elimination of the aromatic ring, removal of the 3-hydroxyl group, and transfer of the hydroxyl group from C-3 to C-4, were also studied. An initial evaluation of NMDA antagonism was performed using a [3H]MK801 binding assay. HBADs demonstrating NMDA antagonist activity as indicated by inhibition of [3H]MK801 binding were further evaluated employing a [3H]-5,7-dichlorokynurenic acid (DCKA) glycine site binding assay. Selected HBADs were characterized for functional antagonism of NMDA and AMPA receptors using electrophysiological assays in Xenopus oocytes and cultured rat cortical neurons. Antagonist potency of HBADs showed good correlation between the different assay systems. HBADs substituted at the 8-position possessed the highest potency with the 8-methyl (5), 8-chloro (6), and 8-bromo (7) analogs being the most active. For HBAD 6, the IC50 in [3H]-DCKA binding assays was 0.013 microM and the Kb values for antagonism of NMDA receptors in oocytes (NR1a/2C) and cortical neurons were 0.026 and 0.048 microM, respectively. HBADs also antagonized AMPA-preferring non-NMDA receptors expressed in oocytes but at a lower potency than corresponding inhibition of NMDA receptors. HBADs demonstrating a high potency for NMDA glycine sites showed the highest steady-state selectivity index relative to AMPA receptors. Substitution at the 6-, 7-, and 9-positions generally reduced or eliminated glycine site affinity. Moving the hydroxyl group from C-3 to C-4 reduced receptor affinity, and potency was eliminated by the removal of the aromatic ring or the hydroxyl group. These data indicate that the HBAD series has specific structural requirements for high receptor affinity. With the exception of substitution at C-8, modified HBADs generally have a lower affinity at NMDA receptor glycine sites than the parent compound 3. Mouse maximum electroshock-induced seizure studies show that the three HBADs selected for testing have in vivo potency with the 6,8-dimethyl analog (52) being the most potent (ED50 = 3.9 mg/kg, iv).     

Understanding signal transduction during bacterial infection

Many known or suspected bacterial virulence factors require environmentally responsive control factors for expression. In Bordetella species, the BvgAS system represses and activates sets of genes, and mediates a biphasic phenotypic transition. Studies using mutants with altered signaling pathways and reversed regulatory connections have provided insights into the role of BvgAS and this phenotypic transition during the Bordetella-host interaction.     

Cynicism, hostility, and suicidal ideation in depressed outpatients

Differences between depressed patients with and without suicidal ideation were examined, focusing on anger, aggression, and hostility. The Adult Suicide Ideation Questionnaire was used to compare 42 outpatients with major depression in relationship to measures of anger, aggression, hostility, cynicism, life events, and depression. There were no differences on measures of anger, aggression, hostility, and on most measures of severity of depression, but the suicidal group demonstrated more evidence of cynicism. Suicidal ideation is associated with cynicism but is unrelated to measures of hostility, anger, or aggression or to severity of depression in outpatients.     

Effects of diabetes and uremia on mesenteric vascular reactivity

BACKGROUND: Diabetes and uremia are comorbid conditions that have significant effects on cardiovascular physiology. These studies were designed to examine the effects of diabetes and uremia on vascular reactivity. METHODS: Sprague-Dawley rats were divided into control (C), diabetic (D), uremic (U), and diabetic/uremic (D + U) groups. Diabetes (D, D + U groups) was induced with an injection of streptozotocin. Uremic (U, D + U groups) was produced by seven-eighths nephrectomy. Serum glucose, blood urea nitrogen, creatinine, creatinine clearance, and protein excretion were measured at baseline and before microvascular studies at 4 or 8 weeks after injection. Vascular reactivity was studied in isolated, pressurized, and superfused segments of mesenteric arterioles (300 microns). Changes in internal vessel diameter were measured in response to phenylephrine (10(-8) to 10(-4) mol/L), acetylcholine (10(-9) to 10(-5) mol/L), and nitroprusside (10(-9) to 10(-2) mol/L). RESULTS: Results at 4 and 8 weeks were similar in all groups. Vasoconstrictor responses to phenylephrine and endothelium-independent vasodilator responses to nitroprusside were not altered in any experimental group. Endothelium-dependent vasodilator responses to acetylcholine were significantly depressed in both diabetic groups (D and D + U, p < 0.01 versus control), and there were no differences between the two diabetic groups. CONCLUSIONS: Streptozotocin-induced diabetes results in impairment of endothelial-dependent (nitric oxide mediated) vasodilator responses in mesenteric resistance vessels, which are unaffected by coexisting uremia. Uremia has little effect on mesenteric vascular reactivity in this model.     

Interaction between alpha- and beta-adrenergic receptor agonists modulating the slow Ca(2+)-activated K+ current IAHP in hippocampal neurons

Noradrenaline inhibits the Ca(2+)-activated K+ current IAHP, which underlies the slow afterhyperpolarization and spike frequency adaptation in hippocampal and neocortical neurons. The resulting increase in excitability probably contributes to the state control of the forebrain during arousal and attention. The modulation of IAHP by noradrenaline has previously been shown to be mediated by beta 1 receptors, cyclic AMP and protein kinase A, but not by alpha receptors. We have now tested the possibility that alpha receptors also contribute to IAHP modulation through interaction with beta receptors, by the use of whole-cell recordings in CA1 pyramidal cells of rat hippocampal slices. The alpha-receptor agonist 6-fluoro-noradrenaline strongly potentiated the effect of isoproterenol on IAHP. The synergistic effect of 6-fluoro-noradrenaline and isoproterenol was blocked by the beta-receptor antagonist timolol, but the receptor type mediating the effect of 6-fluoro-noradrenaline could not be unequivocally identified by using alpha-receptor antagonists. The effect of high concentrations of noradrenaline on IAHP was only partly blocked by the beta-receptor antagonist timolol, and was further reduced by blocking alpha receptors, again suggesting a contribution from alpha receptors. In contrast, the effect of low concentrations of noradrenaline seemed to be potentiated by the alpha-receptor antagonist phentolamine in 57% of the cells, suggesting concentration-dependent antagonistic interaction between alpha and beta receptors. Further tests indicated that the cross-talk between 6-fluoro-noradrenaline and isoproterenol occurs upstream from cyclic AMP production, and that protein kinase A serves as a final common path for the modulation of IAHP by noradrenaline, and by the combination of 6-fluoro-noradrenaline and isoproterenol.