Disturbances in dexamethasone suppression test and lower availability of L-tryptophan and tyrosine in early puerperium and in women under contraceptive therapy.

This study investigates the function of the hypothalamic-pituitary-adrenal (HPA)-axis and the availability of L-tryptophan and tyrosine to the brain in postpartum women and in women taking long-term oral contraceptives. To this end, we have measured the following parameters in 50 women (i.e. 9 normal controls, 10 women taking oral contraceptives, and 31 postpartum females): plasma cortisol, L-tryptophan, tyrosine and the amino acids (CAA) known to compete with them for transport through the blood-brain barrier. We have determined the effects of 1 mg of dexamethasone on the above-mentioned biological markers in postpartum females. Plasma cortisol and tyrosine were significantly higher and lower, respectively, in puerperium and in women under contraceptive therapy as opposed to normal controls. L-Tryptophan was significantly lower in postpartum females, whilst the L-tryptophan/CAA ratio did not differ across the three study groups. Postpartum females revealed a significant negative relationship between the availability of L-tryptophan to the brain and postpartum mood, as measured by Zung's Depression and Anxiety Scales and State Anxiety Inventory. Dexamethasone had a significant suppressive effect on L-tryptophan/CAA and tyrosine/CAA ratios, with cortisol nonsuppression appearing in 82% of the postpartum females.     

Visualization of myocardial infarction 6 h after injection of 111In-antimyosin antibodies using a blood pool subtraction technique.

111In-antimyosin antibodies are capable of visualizing myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. In this pilot study, a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection, is validated. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged a few minutes, 6 and 24 h after an injection of 111 MBq 111In-labelled antimyosin antibodies. Three planar views are obtained each time. Using software which performs the geometric registration, the grey level normalization and the subtraction of images, the blood pool image (obtained a few minutes postinjection) is subtracted from the 6 h image. The resulting image is the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and impossible MI localizations was counted. The number of correct localizations is 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. Then, with this blood pool subtraction method, it is possible to visualize MI 6 h postinjection. This has to be taken into account when discussing the role of antimyosin scintigraphy in the management of patients with MI.     

Human tonsil,blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: Differences in the requirements for factors and for adherent and bone marrow stromal cells,as well as distinctive adhesion molecule expression

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2–3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-α, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA^+/? CD44⁺ CD49d⁺ CD49e^? Leu-8^+/?, the blood cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8⁺ and the BM cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8^?. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.     

Maturational changes in retinal excitatory amino acid receptors

The appearance, kinetics and pharmacological properties of receptors for n-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate (KA), L-glutamate (Glu) and L-aspartate (Asp) was investigated using 3H-ligand binding during the development of chick embryo retina. Receptors for AMPA are maximally concentrated at embryonic day 7 (ED 7) and decline 50% in subsequent days; L-Glu receptors are low until ED 11, and the same is true for Asp and NMDA receptors which increase at ED 14 and 18 respectively. All receptors studied underwent an increase in pharmacological specificity, whereas only AMPA-receptors showed an important change in affinity during ontogeny. Results demonstrate that receptors for excitatory amino acids in the retina suffer maturational changes and suggest that while NMDA and aspartate could interact with the same receptor, AMPA and glutamate seem to bind to different sites.     

Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine: involvement of H3 receptors.

Strips of the porcine small intestine were incubated in vitro, and the release of 5-hydroxytryptamine (5-HT) was determined by high-pressure liquid chromatography with electrochemical detection. Removal of the mucosa resulted in a large reduction (95%) of tissue 5-HT, suggesting that enterochromaffin cells are the main source of 5-HT. The release of 5-HT was reduced by 70% after omission of calcium. Tetrodotoxin and hexamethonium reduced the release of 5-HT by 30%-40% in a nonadditive manner, indicating a spontaneous neuronal (nicotinic) excitatory input to the enterochromaffin cells. Histamine inhibited the release of 5-HT by about 50%. This effect was not affected by mepyramine or cimetidine but was effectively blocked by thioperamide, indicating the involvement of H3 receptors. The selective H3-receptor agonist R-alpha-methyl-histamine also inhibited 5-HT release. Because the effect of R-alpha-methyl-histamine was also observed in the presence of tetrodotoxin, an indirect, neuronally mediated action could be excluded. Therefore, the inhibitory H3 receptors may be localized directly at the enterochromaffin cells.     

Propranolol disposition in the rat: variation in hepatic extraction with unbound drug fraction.

The plasma protein binding of propranolol has been described as nonrestrictive for its hepatic extraction to explain the observation that propranolol is efficiently removed by the liver, in spite of extensive protein binding. The present study was designed to examine the relationship between propranolol protein binding, metabolism by isolated hepatocytes, and extraction by the isolated perfused rat liver. In isolated hepatocytes, the intrinsic clearance of free drug increased three- to fourfold as albumin and alpha 1-acid glycoprotein (AAG) concentrations increased, suggesting that albumin and AAG facilitate the elimination of propranolol by hepatocytes. In the isolated perfused liver, propranolol extraction was almost complete (E = 0.996) in the absence of albumin and AAG. With 40 g/L of albumin and 2 g/L of AAG in the perfusate, the free fraction of propranolol decreased to 0.031, but extraction remained high (E = 0.960). With 40 g/L of albumin and 10 g/L of AAG in the perfusate, the free fraction further decreased to 0.014 and extraction dropped sharply (E = 0.820). The observed relationship between propranolol extraction and the free fraction of propranolol was in good agreement with that predicted using estimates of intrinsic clearance measured in isolated hepatocytes suspensions. These data indicate that propranolol extraction is sensitive to changes in binding at very low free fraction values and suggest a facilitation of propranolol clearance by albumin and AAG.     

Peptides for calling? An immunohistochemical study of the avian n. intercollicularis.

We used two phylogenetically distant avian species (dark-eyed junco, hyemalis, Passeriformes; domestic pigeon, Columba livia, Columbiformes) to determine the immunocytochemical distribution of opioid (leucine-enkephalin, dynorphin B) and non-opioid (adrenocorticotropic hormone) peptides in the n. intercollicularis (ICo), a midbrain region which plays a central role in the control of vocalizations. We found that, in both species, the peptides under study are present as fibers and terminal-like structures, and are similarly distributed. The n. dorsomedialis intercollicularis division contains much less immunoreactivity than the rest of the ICo. Based on this and previous studies, we propose that opioid peptides, possibly transported from the preoptic and hypothalamic regions of the diencephalon to the ICo, regulate vocal behavior by altering respiratory function rather than syringeal mechanisms.     

Human spumaretrovirus antibody reactivity in multiple sclerosis

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.     

Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism

The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.