1,720,968 research outputs found
Caratterizzazione di nuovi meccanismi di inibizione dell'attività biologica delle chemochine infiammatorie : antagonisti recettoriali e recettori decoy
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Molecular aspects of adipokine-bone interactions
No full textAdipose tissue is an endocrine organ able to produce a wide series of pleiotropic molecules, defined "adipokines". In addition to the regulation of food intake and energy metabolism, adipokines are also implicated in the complex control of bone biology and specifically of bone remodeling. Leptin, the most studied adipokine, promotes satiety and energy expenditure and its circulating levels are proportional to fat mass. Some paradoxical findings originally suggested the involvement of leptin in controlling bone mass. For example, obese postmenopausal women, with elevated circulating leptin and leptin resistance, appear protected against the development of osteoporosis. Moreover, genetically leptin-deficient mice, which are hypogonadal and obese, display a decreased trabecular volume in long bones, but an increased vertebral bone mass, which is reduced by leptin administration. The complex mechanisms of leptin regulation of bone mass appear to involve selected hypothalamic neuronal populations and the sympathetic outflow, with an important role of osteoblastic β2-adrenergic receptors. Adiponectin is another adipokine, which promotes insulin sensitivity and is reduced in obese and diabetic subjects. Adiponectin appears to exert a negative effect on bone mass and seems to be an independent predictor of lower bone mass. Although the adipokines resistin and visfatin do not seem to significantly affect bone metabolism, the potential impact of them and other adipokines is still to be determined. Moreover, the molecular adipokine-bone interactions should also be considered in the context of the adipokine changes observed in diseases such as obesity and the metabolic syndrome
Leptin, ciliary neurotrophic factor, leukemia inhibitory factor and interleukin-6 : class-I cytokines involved in the neuroendocrine regulation of the reproductive function
No full textClass-I cytokines represent a large group of molecules involved in different physiological processes including host defence, immune regulation, food intake, energy metabolism and, relevant for this review, reproduction. In this latter respect, here, we focus the attention on four of these molecules, specifically leptin, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). These cytokines present similar three-dimensional fold structure, interact with related class-I receptors, which are expressed in the same regions (i.e., hypothalamus), and activate similar intracellular pathways. Leptin and CNTF share functional similarities, by acting at hypothalamic and pituitary levels, and their receptors are colocalized in the arcuate and paraventricular nuclei of the hypothalamus. For both these molecules, no effect on GnRH migration has been described. LIF has also been shown to affect gonadotropin secretion and here we present the novel observation that it is also able to stimulate GnRH secretion in vitro. Moreover, in the mouse, LIF is prenatally expressed in nasal regions where GnRH neurons originate and start their migration, and in vitro it stimulates intrinsic cell motility and directional migration. The role of the prototypical cytokine, IL-6, on the GnRH-LH axis is not fully clear and additional information seem necessary to better clarify this aspect. In conclusion, the data here discussed suggest that this family of cytokines appears to participate to the complex control of the reproductive function by affecting the development and function of the hypothalamus-pituitary system at different ontogenic times and anatomical site
Effect of immersion in CO2-enriched water on free radical release and total antioxidant status in peripheral arterial occlusive disease
No full textAim. The aim of this paper was to investigate the release of oxygen free radicals in patients with peripheral occlusive arterial disease and the effects of immersion of the legs and feet in carbon dioxide (CO2)-enriched water. Methods. Twenty-five patients with peripheral occlusive arterial disease (Fontaine stage II) and 15 healthy controls were treated by immersing the lower legs in either CO2-enriched or normal spa water. Blood samples were collected in heparinized tubes and total antioxidant status (TAS) and reactive oxygen metabolites (ROMs) were measured after five treatments a week for two weeks. Results. d-ROM plasma levels decreased in patients with peripheral occlusive disease after immersion in CO2.enriched water (P<0.001), and in healthy controls (P<0.01), in line with a significant increase in TAS (P<0.001). Conclusion. CO2-enriched water immersion had a positive effect, reducing free radical plasma levels and raising the levels of antioxidants, suggesting an improvement in the microcirculation
Human bone disorders: pathological role and diagnostic potential of matrix metalloproteinases
No full textBone undergoes continuous remodeling under physiological and pathological conditions. Failure of the regulation of this process leads to several disorders involving bone erosion. This series of events is mainly based on the action of proteinases, particularly matrix metalloproteinases (MMPs). MMPs have been recently suggested as potential bone resorption markers which could be added to the commonly used ones, in order to predict outcome of disease processes and healing, and to monitor disease response to treatment. As for classical biochemical bone markers, MMPs are far from being applied in primary clinical diagnosis, but they could be promising in some cases for disease prognosis. MMPs as bone remodeling biomarkers could provide information that boosts our understanding of the prognosis, disease activity and pathogenesis of bone disorders. Clarifying the MMPs'' role in bone remodeling and healing could potentially help predict disease progression and the effects of direct specific therapy
Okadaic acid induces apoptosis in Down syndrome fibroblasts
No full textDown's syndrome (DS) is characterized by several pathological aspects leading to an increased susceptibility to cardiovascular diseases, infections, leukemia, endocrine alterations. DS patients display some of the physiopathological characteristics of aging, observed also in Alzheimer disease (AD), such as abnormalities in lipids metabolism, diabetes, high cholesterol fraction, senile plaques and neurofibrillary tangles. For this reason DS is considered a precocious and accelerated model of senescence, in which increased apoptosis is the main cornerstone. In order to better understand the apoptotic process in pathological cellular aspects of DS, the aim of this study was to investigate the apoptotic response of DS fibroblasts to OA, a toxin that induces malformations and inhibits growth in different cell lines. We focused specifically on the mitochondrial response by investigating changes in mitochondrial membrane potential (evaluate by flow cytometry and fluorescence microscopy using JC-1 probe) and alterations of mitochondrial outer membrane (evaluated by flow cytometry using annexin V/propidium iodide). Results indicates that DS Fibroblasts have a baseline of apoptosis higher than normal fibroblasts and are more susceptible to the pro-apoptotic effect of OA. Understanding the mechanism of apoptosis in DS fibroblasts could provide new insight in the pathogenic mechanism of this pathology and suggest potential therapeutical targets to the clinical treatment at complex diseases associated to this pathology
Chemokines and chemokine receptors : an overview
No full textChemokines are chemotactic cytokines orchestrating leukocyte recruitment in physiological and pathological conditions. This complex system includes 42 molecules and 19 receptors and is subjected to different levels of regulation, including ligand production, post-translational modifications and degradation, as well as receptor expression and signaling activity. Here we analyze the chemokine system, with particular attention to available information on clinical situations in which chemokines or their receptors might assume diagnostic valu
Matrix metalloproteases MMP-2 and MMP-9: are they early biomarkers of bone remodelling and healing after arthroscopic acromioplasty?
No full textArthroscopic acromioplasty, one of the most frequent procedures in shoulder surgery, can promote tissue healing process by the release of growth/angiogenic factors from the acromion. Matrix metalloproteinases MMP-2 and MMP-9 are involved in such process. The purpose of this study was to measure MMP-2 and MMP-9 levels in the articular fluid and in the peripheral blood of patients undergoing arthroscopic acromioplasty in order to better understand the local involvement of such factors in the healing process after surgical procedures. Concentrations of MMP-2 and MMP-9 in the subacromial space and peripheral blood collected shortly after surgery were determined by ELISA. MMP-2 and MMP-9 concentrations were measured in the subacromial fluid of 23 patients. In subacromial fluid, the levels between MMP-2 and MMP-9 did not reach statistical significance (127.15±45.56 vs 149.41±53.61 pg/ml, respectively, p>0.05). Peripheral blood levels of MMP-2 (130.75±47.48 pg/ml) were comparable to the subacromial fluid ones (127.15±45.56 pg/ml) whereas MMP-9 level was higher in the subacromial space (149.41±53.61 pg/ml) than in the peripheral blood (67.61±12.62 pg/ml, p<0.001). This work suggests that the measurement of bone specific MMPs (MMP-2 and MMP-9) can be an useful tool to be monitored in parallel with growth factor levels and other bone turnover markers in order to evaluate the bone remodelling and tissue healing processes. This study suggests that the measurement of bone specific MMPs levels, in particular MMP-9, may evaluate the bone remodelling and healing after arthroscopic shoulder acromioplasty
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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