Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

Basal and metoclopramide-stimulated prolactin (PRL) serum levels in users and non-users of a copper intrauterine device (TCu-380 IUD).

The study was undertaken to analyze the basal and metoclopramide-stimulated serum PRL levels in healthy parous women users (group 1, n = 12) and non-users (group 2, n = 12) of a TCu-380 IUD. All women had regular menses and were studied between days 18 to 22 of their cycle; none had lactated nor regularly ingested any type of medication during the last six months. After a 10-12 hour overnight fast, peripheral venous blood samples were obtained through an indwelling catheter at -30, -15 and 0 minutes and at 60, 90 and 120 minutes after oral metoclopramide (10 mg). There were no significant differences in serum PRL between both groups, in basal levels nor throughout the test, whether analyzing the mean values at each sampling time, the sum of PRL levels from 60-120 minutes, or the peak levels. No correlation was observed between PRL levels and any of the clinical or obstetric characteristics of the women in both groups. Serum progesterone was greater than or equal to 4.0 ng/ml in all women. Thus, the use of alpha TCu-380 IUD did not induce any significant changes in basal nor in stimulated serum PRL levels.     

Differentiation of Motor Activity of Normally Active and Hyperactive Boys in Schools: Some Preliminary Results

All non-task-related body movements during school hours were listed in 11 normally active and 12 hyperactive boys. The mean number of movements was 48 +/- 7 per 45 minutes in the normal actives and 79 +/- 16 per 45 minutes in the hyperactives. The rather monotonous increment and decrement of motor activity during the 4-hr registration period was noticed only in hyperactive boys. These results could be a consequence of a circadian rhythm, as there was independence of type of school hours and of teacher personality. The cyclical level of activity in hyperactive boys was sometimes in the range of the normal actives.     

Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization.

The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been established to control skeletal tissue formation and biomineralization via the regulation of gene expression. This action involves the well-characterized nuclear 1,25(OH)2D3 receptor. However, it has been recognized that several cellular responses to 1,25(OH)2D3 may not to be related to the exclusive nuclear receptor. Indeed, this secosteroid is able to generate rapid responses that have been proposed to be mediated by interactions of the ligand, which is a putative cell membrane-associated rapid-response steroid (MARRS) binding protein for 1,25(OH)2D3 [1,25D3-MARRS]. The nongenomic pathway of 1,25(OH)2D3 was studied here in detail by immunolocalization of the 1,25D3-MARRS during the specific context of human prenatal development. Western blotting with proteins extracted from 4 week- to 27-week-old embryos was performed, evidencing a 65-kDa molecular species recognized by antibody Ab 099 generated against synthetic peptides corresponding to the N terminus of the 1,25D3-MARRS from chick intestinal basolateral membranes. Based on this biochemical conservation of protein in the human species, the temporospatial expression patterns were established in the craniofacial skeleton at the same ages. Comparative analysis was performed in teeth and bones from early morphogenesis to terminal cell differentiation and extracellular biomineralization. The data show the potential implication of 1,25D3-MARRS in the heterogeneous cell population including ameloblasts, odontoblasts, osteoblasts, and osteoclasts. The epithelial-mesenchymal cascade related to odontogenesis was coincident with a sequence of up- and down-regulation of immunoreactive 1,25D3-MARRS. Biomineralization was associated with a striking up-regulation in the adjoining secretory cells in all tissues. Finally, osteoclasts appeared also to express the 1,25D3-MARRS during these early phases of bone modeling. Previously obtained data of the nuclear vitamin D receptor (VDR) expression and this study on 1,25D3-MARRS suggest the existence of cross-talk between the genomic and nongenomic pathways during human development.     

Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks

The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non-competitive Enzyme Linked-Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti-LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunophenotypes) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co-dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c-,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g-) genotype). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body-mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus.     

Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes

We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine.