(18)F]p-MPPF: aA radiolabeled antagonist for the study of 5-HT(1A) receptors with PET

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A) antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism.     

Influence of corticosteroids on human polymorphonuclear leukocyte function in vitro

In an experimental system in which phagocytosis or adherence of cells to surfaces were excluded as variables, we have investigated the possibility that corticosteroids may inhibit release of lysosomal constituents from viable human polymorphonuclear leukocytes into the extracellular environment. Release of-glucuronidase and lysozyme from cytochalasin B-treated cells exposed to serum-treated zymosan, heat-aggregated human IgG, and the complement component C5a was significantly reduced by pretreatment with hydrocortisone sodium succinate and methylprednisolone sodium succinate (5×10^–4 M). Both steroids also reduced superoxide production by these cells. These in vitro studies provide evidence that corticosteroids influence membrane-dependent responses of intact, viable polymorphonuclear leukocytes to immune reactants. Inhibition of these responses (lysosomal enzyme release, superoxide production) may explain, in part, both the antiinflammatory actions of steroids and their deleterious effects on host defenses.This research was supported by grants from the National Institutes of Health (AM-18531, AM-11949, and HL-15140) and by the Whitehall Foundation.Career Scientist of the Irma T. Hirschl Trust.     

Precepting humanism: strategies for fostering the human dimensions of care in ambulatory settings.

Humanistic medical care is an important element of quality health care, and teaching humanism is increasingly recognized as an integral component of medical education. The goal of this article is to illustrate a series of tools that are effective in fostering both the provision and teaching of humanistic medical care in the ambulatory setting. Through a series of discussions, workshops, literature review, and practice, the authors have identified critical elements that promote the teaching of humanistic care. These elements include establishing a humanistic learning climate, creating clear individualized learning goals within a framework of humanism, developing an educational diagnosis of the learner, integrating psychosocial issues into the teaching intervention, reflecting on the learning experience with the learner, providing feedback throughout the teaching encounter, and planning follow-up with the learner. Strategies for implementation of these critical elements are presented with an emphasis on efficient educational interactions as required by busy ambulatory settings. Through the effective use of these teaching strategies, one can promote the teaching of the human dimensions of care in the outpatient setting.     

Adenosine deaminase is not required for the generation of superoxide anion

Neutrophils and macrophages generate superoxide anion during the respiratory burst in response to various stimuli, including microorganisms. It has recently been proposed that an important source of superoxide anion during the respiratory burst that stimulates murine macrophages is the sequential metabolism of adenosine via adenosine deaminase and xanthine oxidase to uric acid. Thus, the immunodeficiency state associated with adenosine deaminase deficiency may be caused at least in part by a defect in superoxide anion generation. The ability to generate superoxide anion of stimulated neutrophils isolated from three children with adenosine deaminase deficiency and associated severe combined immunodeficiency was tested. Neutrophils from all three patients were able to generate superoxide anion. One of these generated 19.1 nmol cytochrome c reduced/10(6) cells (normals = 5.3-33.0, mean 18.4 +/- 7.1) while the other two generated low normal levels. Neutrophils from all three children also generated more superoxide anion after addition of exogenous adenosine deaminase. Thus, no evidence to support a role for cellular adenosine deaminase in the release of superoxide anion by stimulated neutrophils was found. Although neutrophils from patients deficient in adenosine deaminase appear to have no inherent defect in the generation of superoxide anion, the abnormally high concentrations of adenosine found in the plasma of these patients could, in vivo, secondarily, inhibit superoxide anion release.     

Colloidal lanthanum as a marker for impaired plasma membrane permeability in ischemic dog myocardium.

Colloidal lanthanum salts have an average particle size of 40 degrees A; consequently, this electron-opaque marker remains extracellular and does not cross the intact plasma membrane. The affinity of lanthanum for calcium-binding sites on mitochondrial membranes makes it possible to demonstrate loss of plasma membrane integrity at the cellular level in ischemic myocardium. Biopsies were obtained from infarcted, marginal and normal areas 3 1/2 hours after ischemia was produced in 9 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. The tissue was immediately fixed in 4% glutaraldehyde and 0.1 M cacodylate buffer containing 1.3% La(NO3)3, pH 7.4, for 2 hours. In normal control tissue prepared this way the lanthanum tracer, as expected, was confirmed to the extracellular spaces, including, basement membranes, gap junctions and portions of the intercalated discs. Specimens taken near the center of frank infarctions all contained intracellular as well as extracellular lanthanum. Intracellular lanthanum could be seen evenly distributed around lipid droplets and in focal deposits around mitochondria. Only when mitochondria were disrupted did lanthanum gain access to internal sites on mitochondrial membranes. Areas marginal to the infarct contained cells in varying stages of degeneration including many that appeared normal by morphologic criteria alone. Intracellular lanthanum was present in many but not all of the marginal cells in which degenerative changes could be seen. Similarly a few of the cells that appeared morphologically normal contained intracellular lanthanum. The entry of lanthanum into some of these marginal cells and its exclusion from adjacent cells demonstrated that ischemic injury affects the permeability properties of the plasma membrane and independently of other intracellular morphologic changes and that lanthanum can be a sensitive indicator of such alteration in membrane permeability.     

Zardaverine and aerosolised iloprost in a model of acute respiratory failure.

In this study, the impact of aerosolised prostacyclin (PGI2) and iloprost in the absence or presence of subthreshold intravascular doses of the dual-selective phosphodiesterase-3/4 inhibitor zardaverine was investigated in an experimental model of acute respiratory failure. In perfused rabbit lungs, continuous infusion of the thromboxane-A2-mimetic U46619 provoked pulmonary hypertension, accompanied by progressive lung oedema formation and severe ventilation-perfusion mismatch with predominance of shunt flow (increasing from approximately 2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI2 (in total 1.05 microg x kg(-1) for 15 min caused a decrease in pulmonary artery pressure (Ppa) and a limitation of maximum shunt flow to approximately 37%. When nebulised PGI2 was combined with subthreshold intravascular zardaverine, which did not affect pulmonary haemodynamics per se, the duration of the PGI2 effect was increased. Aerosolisation of 3 microg x kg(-1) PGI2 resulted in a transient decrease in Ppa and a reduction in shunt flow. In the presence of subthreshold zardaverine, the effects of this PGI2 dose were only marginally increased. Aerosolisation of iloprost (in total 0.7 microg x kg(-1)) for 15 min caused a more sustained decrease in Ppa, some enhanced reduction of oedema formation as compared with PGI2 and a decrease in shunt flow to approximately 32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to <15% and shunt flow to approximately 8%. In conclusion, combined use of aerosolised iloprost and subthreshold systemic phosphodiesterase-3/4 inhibitor may result in selective intrapulmonary vasodilation, a reduction in oedema formation and an improvement in ventilation-perfusion matching in acute respiratory failure.     

Estimate of oxygen consumption and intracellular zinc concentration of human spermatozoa in relation to motility

Aim: To investigate the human sperm oxygen/energy consumption and zinc content in relation to motility. Methods: In washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility. Results: The oxygen consumption averaged 0.24μmol/106 sperm×24 h, 0.28μmol/106 live sperm×24 h and 0.85μmol/106 live & motile sperm×24 h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/106 motile spermatozoa×24 h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/106 spermatozoa×24 h. The correlation of the oxygen/ energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, res     

Distribution of alpha-1 and alpha-2 binding sites in the rat locus coeruleus.

Precise anatomical distribution of alpha-1 and alpha-2 adrenergic binding sites has been investigated in the rat locus coeruleus (LC) using quantitative radioautography of brain sections incubated with 3H-prazosin or 3H-idazoxan. Distribution patterns of 3H-prazosin (alpha-1 sites) and 3H-idazoxan (alpha-2 sites) were heterogeneous and different along a postero-anterior axis in the LC. Comparison between distribution of alpha-2 binding sites and noradrenergic (NA) cellular density suggests that at least a fraction of these sites might be localized on NA perikarya or dendrites in this structure. Quantitative estimations of the binding parameters along this postero-anterior axis in the LC have revealed that the heterogeneous distributions of alpha-1 and alpha-2 binding sites are due not only to variations in the maximal densities of sites but also to variations in the affinities of these sites for their respective ligand.