ABSTRACT
PURPOSE: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. METHODS: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. RESULTS: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. CONCLUSION: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level.
Subject(s)
Diabetic Cardiomyopathies/drug therapy , Inflammation Mediators/metabolism , Interleukin-8/metabolism , Phosphodiesterase 5 Inhibitors/pharmacology , Sildenafil Citrate/pharmacology , Case-Control Studies , Cell Proliferation , Cells, Cultured , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Female , Follow-Up Studies , Humans , In Vitro Techniques , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , PrognosisABSTRACT
Increasing evidence provides support that mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, biology and their role in liver cell turnover and regeneration remain to be further clarified. In this study, we report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potentiality distinct from other previously described liver precursor/stem cells. RLSCs, derived from fetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alpha-fetoprotein+ and albumin-. This molecular phenotype suggests a non-hematopoietic origin. RLSC transcriptional profile, defined by microArray technology, highlighted the expression of a broad spectrum of 'plasticity-related genes' and 'developmental genes' suggesting a multi-differentiative potentiality. Indeed, RLSCs spontaneously differentiate into hepatocytes and cholangiocytes and, when cultured in appropriate conditions, into mesenchymal and neuro-ectodermal cell lineages such as osteoblasts/osteocytes, chondrocytes, astrocytes and neural cells. RLSC capability to spontaneously differentiate into hepatocytes, the lack of albumin expression and the broad differentiative potentiality locate them in a pre-hepatoblast/liver precursor cells hierarchical position. In conclusion, RLSCs may provide a useful tool to improve liver stem cell knowledge and to assess new therapeutic approaches for liver diseases.
Subject(s)
Hepatocytes/cytology , Liver/cytology , Multipotent Stem Cells/cytology , Animals , Animals, Newborn , Cell Differentiation , Cell Lineage , Cell Separation , Cells, Cultured , Chondrocytes/cytology , Gene Expression Profiling , Hepatocytes/metabolism , Immunophenotyping , Liver/embryology , Mice , Multipotent Stem Cells/metabolism , Neurons/cytology , Oligonucleotide Array Sequence Analysis , Osteoblasts/cytology , PhenotypeABSTRACT
1. Nurses who care for AIDS patients are challenged to effectively manage two common problems: AIDS dementia complex (ADC) and depression. 2. Nurses can briefly assess certain neuropsychological functions related to ADC and differentiate dementia from depression. 3. Nursing interventions to manage the behaviors associated with ADC and depression can ensure patients' safety and promote the quality of their lives.