102,669 research outputs found
T Regulatory Lymphocytes Function Increased, by Induction Of Ho-1, Improves Type-1 Cardio-Renal Syndrome
No full textRationale: Type-1 cardio-renal syndrome (CRS) is characterized by an acute kidney dysfunction due to renal arteriolar vasoconstriction following an acute worsening of cardiac function. It is well know that HO-1 upregulation has a cardio protective and renoprotective function mediated by anti-oxidative, anti-inflammatory, anti-apoptotic and vasodilating effects. An alteration of T-lymphocyte-related immune response seems to be one of the potential mechanisms involved in type-1 CRS.
Objective: The aim of this study was to assess 1) if HO-1 upregulation could be a therapeutic target for type 1 CRS and 2) the role of T-lymphocytes in HO-1 induced effects on renal function in type 1 CRS.
Methods: Post-ischemic heart failure was induced by left anterior coronary artery ligation in C57Bl6 and SCID (T lymphocytes deficient) mice. Animals were divided into 4 groups: sham, myocardial infarction (MI), MI treated with HO-1 inducer cobalt protoporphyrin (CoPP) with and without the HO activity inhibitor stannous mesoporphyrin (SnMP). All mice underwent echocardiography (fractional area shortening, FAS) and renal Doppler sonography (intrarenal pulsatility index, PI) 30 days after surgery.
Results: Heart function was significantly reduced in MI groups (C57: FAS: sham 0.36±0.06, MI 0.26±0.04, p<0.05; SCID: FAS: sham 0.34±0.04, MI: 0.24±0.04, p<0.01) and PI was significantly increased in MI groups compared to sham groups (C57: PI: sham 0.98±0.05, MI: 1.12±0.11, p<0.05; SCID: PI: sham 0.72±0.08, MI 1.37±0.37, p<0.05). HO-1 induction improved heart function in both C57 and SCID mice but only in SCID mice was a significant improvement of renal vasoconstriction observed (SCID; PI: MI+CoPP 0.9±0.19 p<0.05). In SCID mice SnMP treatment reversed the effect of CoPP on heart function and renal vasoconstriction.
Conclusion: Our novel study showed that T lymphocyte mediated immunity is involved in type 1 CRS and upregulation of HO-1, in this setting, could be a therapeutic target for improving type 1 CRS.
Author Disclosures: P. Pesce: None. D. Sacerdoti: None. M. Boldrin: None. R. Rezzani: None. N.G. Abraham: None.
Key Words: Renal circulation • Heart failure • Immunologic factors • Oxidative stres
Fertility and Social Security
No full textThe data show that an increase in government provided old-age pensions is strongly correlated with a reduction in fertility. What type of model is consistent with this finding? We explore this question using two models of fertility: one by Barro and Becker (1989), and one inspired by Caldwell (1978, 1982) and developed by Boldrin and Jones (2002). In Barro and Becker's model parents have children because they perceive their children's lives as a continuation of their own. In Boldrin and Jones' framework parents procreate because children care about their parents' utility, and thus provide them with old-age transfers. The effect of increases in government provided pensions on fertility in the Barro and Becker model is very small, whereas the effect on fertility in the Boldrin and Jones model is sizeable and accounts for between 55 and 65% of the observed Europe-U.S. fertility differences both across countries and across time.Social security ; Financial markets
Essential Role of Immunosuppressive T-Regulatory Cells in Improving Heart Function in Post-Ischemic Myocardium via Up-Regulation of Heme-Oxygenase 1
No full textRationale: Post ischemic heart failure is the consequence of pathological remodeling after myocardial ischemic damage. T lymphocyte mediated immune response is known to play an important role in post-ischemic cardiac remodeling. T regulatory lymphocytes (Treg) are a subpopulation of T helper lymphocytes with a regulatory and immunosuppressive role. Heme oxygenase (HO)-1 induction improves heart function after ischemic damage by its anti-inflammatory, anti-oxidative and anti-apoptotic effect.
Aim: Aim of this study was to assess the role of HO-1 mediated increased levels of T-reg lymphocytes in post-ischemic cardiac remodeling.
Methods: We compared the effect of HO-1 induction on post-ischemic heart failure induced by left anterior coronary artery ligation in T-lymphocytes immunodeficient mice (SCID) and in immunocompetent mice (C57). Mice were divided into 4 groups: sham, myocardial infarction (MI), MI treated with the HO-1 inducer cobalt protoporphyrin (CoPP) with and without the HO activity inhibitor stannous mesoporphyrin (SnMP). 30 days after surgery all mice underwent echocardiography and an assessment of T-lymphocyte subpopulations via fluorescence activated cell sorting (FACS).
Results: Mice with MI had increased levels of inflammatory cytokines (p<0.05), significant myocardial fibrosis (SCID: 3.9±0.9% vs 0.7±0.1%; p<0.02) and lower capillary density (SCID: 1.2±0.7% vs 4.3±0.9%; p<0.01) compared to controls. Echocardiography showed that the left ventricle end diastolic area (EDA) was significantly reduced in CoPP treated compared to MI groups (EDA: MI: 0.22±0.02 cm; MI+CoPP: 0.17±0.03 cm; -13%, p<0.01) and the beneficial effect of HO-1 induction was more evident in SCID mice (EDA: MI: 0.19±0.02 cm; MI+CoPP: 0.10±0.01 cm, -25%, p<0.01). In CoPP treated C57 mice the T-reg subpopulation was significantly increased (20±3% vs 5±3%; p<0.01). All these beneficial effects were reversed by SnMP.
Conclusion: HO-1, via its effect on T-cell mediated immunity, reverses dysfunctional remodeling and enhances peri-infarct survival in the post-ischemic myocardium. Targeted enhancement of T-reg cells via HO- induction could thus provide adjuvant avenues for reducing morbidity and mortality in patients with post-MI heart failure.
Author Disclosures: P. Pesce: None. S.J. Peterson: None. R. Rezzani: None. M. Boldrin: None. D. Sacerdoti: None. N.G. Abraham: None.
Key Words: Heart failure • Remodeling • Oxidative stress • Immunologic factor
Epistemological understanding in different judgment domains: Relationships with gender, grade level, and curriculum
No full textThis article reports a theoretically based study on the model of development of epistemological understanding proposed by Kuhn (2000) [Kuhn, D. (2000). Theory of mind, metacognition, and
reasoning: A life-span perspective. In P. Mitchell & K. J. Riggs (Eds.), Children’s reasoning and the mind (pp. 301–326). Hove, UK: Psychology Press], which includes three levels of thinking about knowledge and knowing: absolutist, multiplist, and evaluativist. The study involved 881 Italian elementary (5th
grade), middle (8th grade) and high school students (11th and 13th grades). The latter attended two different branches of high school, one following a scientific, and the other a technical–commercial curriculum. Their epistemological understanding was assessed in the five judgement domains included in
the instrument developed by Kuhn, Cheney, and Weinstock (2000) [Kuhn, D., Cheney, R., & Weinstock,
M. (2000). The development of epistemological understanding. Cognitive Development, 15, 309–328).
Data show that more than 70% of identified patterns were consistent and interpretable within the underlying theoretical framework. Absolutist positions were more frequent in judgments about values even when the shift to non-absolutism was attained in all other domains. Gender, grade level, and curriculum significantly differentiated participants for the first developmental transition, from absolutism to multiplism. Overall, boys showed more absolutist positions than girls, 8th graders more than 13th
graders, and participants in the scientific branch more than those in the technical–commercial one
CELLULAR DETERMINANTS OF ECTOPIC BONE FORMATION IN ALBRIGHT HEREDITARY OSTEODYSTROPHY, PSEUDOHYPOPARATHYROIDISM AND GNAS-RELATED DISEASES
No full textPseudohypoparathyroidism is a term used to identify a heterogeneous group of rare diseases associated with genetic and/or epigenetic defects at the imprinted GNAS locus, that encodes also for the α subunit of the stimulatory G protein (Gsα).
Most GNAS-based disorders share the common feature of episodic de novo formation of heterotopic ossifications (HO), a pathological formation of bone in extra-skeletal tissues. The mosaic tissue distribution of HOs suggested that their pathogenesis involved the abnormal differentiation of precursor cells located in subcutaneous tissues, mesenchymal stem cells, and that GNAS defects provided a sensitized background promoting osteoblastogenesis.
This study attempted to clarify the molecular mechanisms underlying HO formation in GNASrelated diseases, as, although the growing knowledge, they are not completely understood. To this aim, we developed an in vitro human model of adipose-derived mesenchymal stem cells (ADMSCs) from surgically removed samples of subcutaneous fat of healthy donors. Firstly, we confirmed the ability of our ADMSCs to differentiate into osteoblasts and adipocytes by specific biochemical assays, stainings and lineage-specific markers expression. We determined that in vitro manipulation did not affect the maintenance of GNAS imprinting status. Finally, In order to investigate the effect of GNAS haploinsufficiency, we transfected ADMSCs with siRNAs designed to specifically silence different GNAS transcripts, obtaining an efficiency of about 75% at day 4, which decreased at about 50% at day 21. Then, we analyzed the expression of different osteogenic markers in GNAS-silenced ADMSCs and we observed that Gs alpha haploinsufficiency promoted their commitment towards the osteoblastic differentiation.
In conclusion, our study showed that ADMSCs are a good model to study the osteogenic differentiation and the formation of HOs in GNAS-related diseases. In particular, we observed that GNAS silencing promotes ADMSCs commitment towards the osteoblast lineage, even in the absence of additional osteogenic-inducing stimuli. Moreover, no significant differences due to use of different GNAS siRNAs were observed, further supporting the hypothesis that the formation of ectopic bone in GNAS-related diseases is predominantly Gsα-mediated
Swimmers in trappole per il sedimento nel Nord Adriatico.
No full textAbstract – Swimmers collected by two sediment traps moored at 15 and 25 m depth in a Northern Adriatic off-shore site were analysed. The most abundant taxa were copepods and larvae and juveniles of bivalves, mainly in the warm season. The organisms collected at the two depth significantly differed in some cases. Regressions with organic carbon fluxes were significant only at 25 m, probably due to resuspension events
The Complex GNAS Imprinted Locus and Mesenchymal Stem Cells Differentiation
No full textAll tissues and organs derive from stem cells, which are undifferentiated cells able to differentiate into specialized cells and self-renewal. In mammals, there are embryonic stem cells that generate germ layers, and adult stem cells, which act as a repair system for the body and maintain the normal turnover of regenerative organs. Mesenchymal stem cells (MSCs) are nonhematopoietic adult multipotent cells, which reside in virtually all postnatal organs and tissues, and, under appropriate in vitro conditions, are capable to differentiate into osteogenic, adipogenic, chondrogenic, myogenic, and neurogenic lineages. Their commitment and differentiation depend on several interacting signaling pathways and transcription factors. Most GNAS-based disorders have the common feature of episodic de novo formation of islands of extraskeletal, qualitatively normal, bone in skin and subcutaneous fat. The tissue distribution of these lesions suggests that pathogenesis involves abnormal differentiation of MSCs and/or more committed precursor cells that are present in subcutaneous tissues. Data coming from transgenic mice support the concept that GNAS is a key factor in the regulation of lineage switching between osteoblast and adipocyte fates, and that its role may be to prevent bone formation in tissues where bone should not form. Despite the growing knowledge about the process of heterotopic ossification in rare genetic disorders, the pathophysiological mechanisms by which alterations of cAMP signaling lead to ectopic bone formation in the context of mesenchymal tissues is not fully understood
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