Tunable Emissive Ir(III) Benzimidazole-quinoline Hybrids as Promising Theranostic Lead Compounds.

Bioactive and luminescent cyclometallated Ir(III) complexes [Ir(ppy) L1]Cl (1) and [Ir(ppy) L2]Cl (2) containing a benzimidazole derivative (L1/L2) as auxiliary mimic of a nucleotide have been synthesised. The emissive properties of both complexes are conditioned by the nature of L1 and L2, rendering an orange and a green emitter respectively. Both are highly emissive with quantum yield increasing in absence of oxygen up to 0.

Fibroblast-Negative CD34-Negative Cells from Human Adipose Tissue Contain Mesodermal Precursors for Endothelial and Mesenchymal Cells.

There is considerable evidence that stem/progenitor cells reside in the vasculature during the prenatal and postnatal stages. The stromal vascular fraction (SVF) of human adipose tissue is markedly rich in blood vessels, and it is a source of mesenchymal/stromal cells (MSCs). Therefore, we hypothesized that, in addition to MSCs, the SVF may contain other mesodermal precursors.

Human adipose tissue-resident monocytes exhibit an endothelial-like phenotype and display angiogenic properties.

Introduction: Adipose tissue has the unique property of expanding throughout adult life, and angiogenesis is required for its growth. However, endothelial progenitor cells contribute minimally to neovascularization. Because myeloid cells have proven to be angiogenic, and monocytes accumulate in expanding adipose tissue, they might contribute to vascularization.

Human adipose tissue contains erythroid progenitors expressing fetal hemoglobin.

Aim: To investigate the origin of hematopoietic progenitors contained in the stromal vascular fraction (SVF) of human adipose tissue.

Methods: Tissue samples obtained from lipectomies were subjected to enzymatic digestion with collagenase to obtain a single-cell suspension. The centrifuged cell pellet, termed SVF, was separated immunomagnetically into CD45(+) and CD45(-) cells and cultured in serum-free medium containing hematopoietic cytokines.

Mesenchymal stem cells provide better results than hematopoietic precursors for the treatment of myocardial infarction.

Objectives: The purpose of this study was to compare the ability of human CD34(+) hematopoietic stem cells and bone marrow mesenchymal stem cells (MSC) to treat myocardial infarction (MI) in a model of permanent left descendent coronary artery (LDA) ligation in nude rats.

Background: Transplantation of human CD34(+) cells and MSC has been proved to be effective in treating MI, but no comparative studies have been performed to elucidate which treatment prevents left ventricular (LV) remodelling more efficiently.

Methods: Human bone marrow MSC or freshly isolated CD34(+) cells from umbilical cord blood were injected intramyocardially in infarcted nude rats.

IFATS collection: Identification of hemangioblasts in the adult human adipose tissue.

The stromal-vascular fraction (SVF) of human adipose tissue contains, among other cell types, mesenchymal stem cells and precursors of adipocyte and endothelial cells. Here we show that, in addition, the nonhematopoietic fraction of the SVF has hematopoietic activity, since all types of hematopoietic colony-forming units (CFUs) developed when cultured in methylcellulose-based medium. This hematopoietic activity was restricted to the CD45(-)CD105(+) cell subset, well correlated with KDR(+) cell content, and increased after culture with a combination of early-acting hematopoietic cytokines.

Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction.

Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC) that show self-renewal and multilineage differentiation and also secrete multiple proangiogenic and antiapoptotic factors. To examine whether these cells could have therapeutic potential in the repair of myocardial infarction (MI), DPSC were infected with a retrovirus encoding the green fluorescent protein (GFP) and expanded ex vivo. Seven days after induction of myocardial infarction by coronary artery ligation, 1.

Human platelet lysate enhances the proliferative activity of cultured human fibroblast-like cells from different tissues.

Several studies have shown the presence of fibroblast-like cells in the stromal fraction of different tissues with a high proliferative and differentiation potential. Platelet alpha granules contain growth factors released into the environment during activation. The effects of different supplements for culture medium (human serum, bovine serum and platelet lysate) on cultured human fibroblast-like cells from bone marrow, adipose tissue, trabecular bone and dental pulp have been compared.

The functional immaturity of dendritic cells can be relevant to increased tolerance associated with cord blood transplantation.

Background: Cord blood (CB) transplants have a significantly lower incidence of graft-versus-host disease (GVHD) compared to marrow or peripheral blood transplants. Because antigen-presenting cells and regulatory T cells (Treg) are involved in transplant tolerance, this study was aimed at analyzing the distribution of dendritic cells (DCs) and CD14+ monocyte-specific subsets in CB and adult peripheral blood (APB) and comparing the ability of DCs from these two blood sources to induce CD4+ Treg.

Study Design And Methods: Myeloid DCs (mDCs), plasmacytoid DCs, the CD14+ cell subsets CD14+CD16+ and CD14+CD209+, and CD4+ T cells were analyzed by fluorescence-activated cell sorting (FACS) in whole blood.

Selective generation of different dendritic cell precursors from CD34+ cells by interleukin-6 and interleukin-3.

There is a growing interest in generating dendritic cells (DCs) for using as vaccines. Several cytokines, especially stem cell factor (SCF) and FLT3-ligand (FL), have been identified as essential to produce large numbers of myeloid precursors and even to increase DC yield obtained by the action of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). However, there are few studies on the effect of the early-acting cytokines, commonly used to expand CD34+ progenitor cells, on DC generation.

IL-6 precludes the differentiation induced by IL-3 on expansion of CD34+ cells from cord blood.

Background And Objectives: Ex vivo expansion of hematopoietic progenitor cells (HPC) from umbilical cord blood (UCB) is an interesting strategy to obtain a sufficient number of transplantable cells for adults. To define the optimal culture conditions allowing the generation of HPC that retain their proliferative capacity without loss of long-term culture-initiating cells (LTC-IC), the effect of different cytokine combinations on the expansion of CD34+ cells from UCB was assessed.

Design And Methods: CD34+ cells were cultured in serum-free culture medium with four cytokine combinations: stem cell factor plus thrombopoietin plus flk2/flt3 ligand (STF), STF plus interleukin-3 (IL-3), STF plus interleukin-6 (IL-6) and STF plus IL-6 plus IL-3.

CD34+CD38- is a good predictive marker of cloning ability and expansion potential of CD34+ cord blood cells.

Background: Ex vivo expansion of HPCs is an attractive approach to overcoming the current limitations of human cord blood transplantation. It is important not only to define the optimal culture conditions but also to know the number of progenitor cells that can be obtained. CD34+ cells have a great variability in their cloning capacity and in their ability to expand HPCs.

Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease.

The glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy.

Altered modulation of soluble guanylate cyclase in lymphocytes from patients with liver disease.

Studies of animal models suggest that the activation of soluble guanylate cyclase by nitric oxide is altered in liver disease. We studied 77 patients with liver disease and 17 controls, to investigate whether the activation of soluble guanylate cyclase is altered in lymphocytes from patients with liver disease. The basal content of guanosine 3',5'-cyclic monophosphate (cGMP) in lymphocytes was decreased both in patients with liver cirrhosis (by 52%) and in patients with chronic hepatitis (by 62%).

PH changes at the surface of root dentin after intracanal dressing with calcium oxide and calcium hydroxide.

This study was designed to compare pH changes at the cervical and apical surfaces of root dentin after canal obturation with calcium oxide or calcium hydroxide pastes. The effect of the exposure to CO2 on the pH at the root surface also was assessed for both materials. Thirty-six extracted human canines were selected and instrumented.

Prenatal exposure to aluminum reduces expression of neuronal nitric oxide synthase and of soluble guanylate cyclase and impairs glutamatergic neurotransmission in rat cerebellum.

Exposure to aluminum (Al) produces neurotoxic effects in humans. However, the molecular mechanism of Al neurotoxicity remains unknown. Al interferes with glutamatergic neurotransmission and impairs the neuronal glutamate-nitric oxide-cyclic GMP (cGMP) pathway, especially in rats prenatally exposed to Al.

Chronic hyperammonemia in rats impairs activation of soluble guanylate cyclase in neurons and in lymphocytes: a putative peripheral marker for neurological alterations.

Chronic hyperammonemia impairs the glutamate-nitric oxide-cGMP pathway in rat brain in vivo. The aims of this work were to assess whether hyperammonemia impairs modulation of soluble guanylate cyclase, and to look for a peripheral marker for impairment of this pathway in brain. We activated the pathway at different steps using glutamate, SNAP, or YC-1.

Chronic hyperammonemia impairs the glutamate-nitric oxide-cyclic GMP pathway in cerebellar neurons in culture and in the rat in vivo.

The aim of this work was to assess whether ammonia concentrations similar to the increase found in the brain of hyperammonemic rats (100 microM), impair N-methyl-D-aspartate (NMDA) receptor-mediated signal transduction. We first measured glutamate neurotoxicity, which in these neurons is mediated by activation of NMDA receptors, as an initial parameter reflecting activation of NMDA receptor-mediated pathways. Long-term treatment of cultured neurons with ammonia prevents glutamate-induced neuronal death.

Nicotine prevents glutamate-induced proteolysis of the microtubule-associated protein MAP-2 and glutamate neurotoxicity in primary cultures of cerebellar neurons.

The aim of this work was to assess whether nicotine prevents glutamate neurotoxicity in primary cultures of cerebellar neurons, to try to identify the receptor mediating the protective effect and to shed light on the step of the neurotoxic process which is prevented by nicotine. It is shown that nicotine prevents glutamate and NMDA neurotoxicity in primary cultures of cerebellar neurons. The protective effect of nicotine is not prevented by atropine, mecamylamine or dihydro-beta-erythroidine, but is slightly prevented by hexamethonium and completely prevented by tubocurarine and alpha-bungarotoxin, indicating that the protective effect is mediated by activation of alpha7 neuronal nicotinic receptors.

Neurotoxicity of ammonia and glutamate: molecular mechanisms and prevention.

Ammonia is a main factor in the pathogenesis of hepatic encephalopathy. We found that acute ammonia toxicity is mediated by activation of NMDA receptors. Chronic moderate hyperammonemia prevents acute ammonia toxicity in rats.

Carbachol-induced hydrolysis of phospholipids in hippocampal slices may be mediated in part by subsequent activation of metabotropic glutamate receptors.

We observed that AP-3, an antagonist of metabotropic glutamate receptors, reduced carbachol-induced hydrolysis of phospholipids in hippocampal slices. This inhibition could be explained in different ways, e.g.

Chronic exposure to aluminum impairs neuronal glutamate-nitric oxide-cyclic GMP pathway.

Humans are exposed to aluminum from environmental sources and therapeutic treatments. However, aluminum is neurotoxic and is considered a possible etiologic factor in Alzheimer's disease and other neurological disorders. The molecular mechanism of aluminum neurotoxicity is not understood.

Modulation of glutamine synthesis in cultured astrocytes by nitric oxide.

1. Previous results suggest that glutamine synthesis in brain could be modulated by nitric oxide. The aim of this work was to assess this possibility.

Determination of intracellular ATP in primary cultures of neurons.

The aim of this work was to develop and characterize a quick and simple procedure to determine the intracellular content of ATP in monolayer primary cultures of neurons. The baseline was to use the minimum amount of cells which still provides reproducible results. The first step consists of releasing intracellular ATP from the cells.