Immunoreactive neuropeptides in the cells of human thymus

The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall's corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P lt 0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P lt 0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P lt 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis

Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids

Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and beta(2)- and alpha(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of beta(2)- and alpha(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine beta-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of alpha(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation

Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning

The packaging and organization of genomic DNA into chromatin represents an additional regulatory layer of gene expression, with specific nucleosome positions that restrict the accessibility of regulatory DNA elements. The mechanisms that position nucleosomes in vivo are thought to depend on the biophysical properties of the histones, sequence patterns, like phased di-nucleotide repeats and the architecture of the histone octamer that folds DNA in 1.65 tight turns. Comparative studies of human and P. falciparum histones reveal that the latter have a strongly reduced ability to recognize internal sequence dependent nucleosome positioning signals. In contrast, the nucleosomes are positioned by AT-repeat sequences flanking nucleosomes in vivo and in vitro. Further, the strong sequence variations in the plasmodium histones, compared to other mammalian histones, do not present adaptations to its AT-rich genome. Human and parasite histones bind with higher affinity to GC-rich DNA and with lower affinity to AT-rich DNA. However, the plasmodium nucleosomes are overall less stable, with increased temperature induced mobility, decreased salt stability of the histones H2A and H2B and considerable reduced binding affinity to GC-rich DNA, as compared with the human nucleosomes. In addition, we show that plasmodium histone octamers form the shortest known nucleosome repeat length (155bp) in vitro and in vivo. Our data suggest that the biochemical properties of the parasite histones are distinct from the typical characteristics of other eukaryotic histones and these properties reflect the increased accessibility of the P. falciparum genome

Dual chamber pacemaker in the treatment of paroxysmal atrial fibrillation

Background. Atrial fibrillation is the most frequent cardiac dysrhythmia. The aim of this study was to show the role and the efficacy of a dual chamber pacemaker with the algorithm of atrial dynamic overdrive, in the suppression of paroxysmal atrial fibrillation. Case report. A woman with a classical bradycardia-tachycardia syndrome, and frequent attacks of atrial fibrillation, underwent the implantation of a single chamber permanent pacemaker (VVI). Pacemaker successfully treated the episodes of symptomatic bradycardia, but the patient had frequent attacks of atrial fibrillation, despite the use of different antiarrhythmic drugs, which she did not tolerate well. The decision was made to reimplant a permanent dual chamber pacemaker with the algorithm of atrial dynamic overdrive. The pacemaker was programmed to the basic rate of 75/min, while rate at rest was 55/min. In addition, sotalol was administered. After three months, the patient became asymptomatic with only 4 short − term episodes of atrial fibrillation, and a high level of atrial pacing (99%). Conclusion. In selected patients with bradycardia−tachycardia syndrome, atrial-based pacing seemed to be very effective in reducing the incidence of paroxysmal atrial fibrillation

Udarna žilavost laminarnih termoplastičnih kompozitnih materijala ojačanih aramidnim vlaknima

In order to obtain a composite material with desired improved resistance to penetration of ballistic projectile, a poly(p-phenyleneterephthalamide) reinforced laminar thermoplastic composite material has been made. This paper describes the procedure of manufacturing such composite material, and its behavior during the ballistic and micromechanical testing as well. The analysis of impact resistance results obtained from ballistically tested and untested composite panel specimens has shown an improved mechanical energy absorption capability due to effect of strong aramid fibers, ductile thermoplastic matrix and interface between fiber and matrix. This interface enables load transfer between the two constituents using high load-bearing capacity of the reinforcement. Another feature of the interface is deflection of propagating cracks within the material and thus raising toughness.Sa ciljem dobijanja materijala poboljšane otpornosti na prodor balističkog projektila napravljen je laminarni kompozitni materijal sa termoplastičnom matricom ojačan poli (p-fenilentereftalamidom). U ovom radu je opisan način izrade pomenutog kompozitnog materijala kao i njegovo ponašanje prilikom balističkih i mikromehaničkih ispitivanja. Analiza rezultata dobijenih ispitivanjem udarne žilavosti balistički testirane i netestirane kompozitne ploče, pokazala je poboljšanu sposobnost apsorpcije mehaničke energije u materijalu usled uticaja jakih aramidnih vlakana, duktilne termoplastične matrice i ostvarene granične površine između njih koja sa jedne strane omogućuje prenos opterećenja između konstituenata tako da se koristi sposobnost ojačanja kao nosioca opterećenja, a sa druge strane reflektuje propagaciju prsline u materijalu i na taj način doprinosi povećanju žilavosti kompozita