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Biomedical subjects

Francesco Chiappelli

Publications and source records attributed to Francesco Chiappelli.

30 records · Page 2Linked to original sources

The molecular immunology of mucositis: implications for evidence-based research in alternative and complementary palliative treatments.

The terms 'mucositis' and 'stomatitis' are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR) data has shown that applications of granulocyte-macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis.

Journal Article↗

Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients.

The defective clearance of amyloid-beta (Abeta) in the brain of Alzheimer's disease (AD) patients is unexplained. The immunohistochemical studies of the frontal lobe and hippocampus show perivascular and intraplaque infiltration by blood-borne macrophages containing intracellular Abeta but only inefficient clearance of beta deposits. Neurons and neuronal nuclei, respectively, express interleukin-1beta and the chemokine RANTES, which could induce the inflammatory cell infiltration. To clarify the pathophysiology ofbeta clearance, we examined Abeta phagocytosis by monocytes and macrophages isolated from the blood of age-matched patients and controls. Control monocytes display excellent differentiation into macrophages and intracellular phagocytosis of Abeta followed by beta degradation or export. AD monocytes show poor differentiation and only surface uptake of Abeta and suffer apoptosis. HLA DR and cyclooxygenase-2 are abnormally expressed on neutrophils and monocytes of AD patients. AD patients have higher levels of intracellular cytokines compared to controls. Thus Abeta clearance is not restricted to brain microglia and involves systemic innate immune responses. In AD, however, macrophage phagocytosis is defective, which may elicit compensatory response by the adaptive immune system.

Aged↗

Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells.

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration (one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) (one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.

Aged↗

Psychobiologic views on stress-related oral ulcers.

Recurrent aphthous stomatitis (RAS) and oral lichen planus (OLP), two of the most common stress-related ulcerations of the oral mucosa, have distinct etiologies, courses, and histopathologic features. In light of increased understanding of the psychobiology of stress, the authors propose that RAS and OLP fundamentally differ from the perspective of the psychobiologic response to stress. This article presents possible clinical implications.

Cold Temperature↗

Substance P induces interleukin-8 secretion from human dental pulp cells.

OBJECTIVE: The role of neuropeptides in recruiting leukocytes in dental pulps is not known; therefore, we investigated whether interleukin-8 (IL-8) secretion from human pulp cells is increased after stimulation with substance P (SP) or calcitonin gene-related peptide (CGRP). METHODS: Primary pulp cells exhibiting a fibroblast-like phenotype and an endothelial cell line were stimulated with various doses of SP or CGRP, and IL-8 secretion was measured by enzyme-linked immunosorbent assays. RESULTS: IL-8 secretion from pulp cells increased significantly at 10(-8) to 10(-4) mol/L of SP stimulation (5- to 13.8-fold; P <.05); however, no significant IL-8 increase with CGRP (up to 10(-4) mol/L) stimulation was observed, nor was there synergistic induction of IL-8 with SP plus CGRP. The IL-8 increase reached its maximum at 8 hours after SP stimulation of the pulp cells. SP at a concentration of 10(-4) mol/L created minimal IL-8 induction in the endothelial cells and no synergistic induction by SP and CGRP. CONCLUSIONS: Pulp cells may up-regulate IL-8 secretion by SP stimulation, which suggests that SP released in dental pulp may play a role in the influx of leukocytes, attracted by IL-8, into the pulp tissue.

Adolescent↗

Function of beta-adrenergic receptors on mononuclear cells in female patients with fibromyalgia.

OBJECTIVE: To investigate the beta-adrenergic receptors (beta AR) in patients with chronic fibromyalgia syndrome (FM). These receptors are present on circulating mononuclear cells, and activation of G-protein coupled receptors like beta AR leads to an increase in the intracellular level of cyclic aminosine monophosphate (cAMP). Therefore, cAMP levels can be used to indirectly assess the functional status of the receptor. METHODS: Eight female patients with FM and 9 matched healthy female controls participated in this study. Blood samples were drawn from subjects' anterocubital vein in the morning. Mononuclear cells were isolated from the whole blood according to Boyüm's method. Basal and stimulated intracellular cAMP levels were determined by enzyme immunoassay. Aliquots of 10(6) cells were incubated with or without stimulation of beta-agonist isoproterenol for 5 min. Two different concentrations of isoproterenol (10(-3) M and 10(-5) M) were utilized. RESULTS: The basal cAMP levels in patients with FM (3.02 +/- 0.44 pmol/10(6) cells) were slightly more elevated (but not statistically different; p = 0.124, Mann-Whitney U test) than that of the control group (2.26 +/- 0.39 pmol/10(6) cells). Proterenol 10(-3) M stimulation significantly increased intracellular cAMP from the basal levels in both groups (FM group, p = 0.008; control group, p = 0.011). However, isoproterenol 10(-5) M did not increase mean intracellular cAMP levels in the FM group (p = 0.74), while a significant increase was observed in the control group (p = 0.012). CONCLUSION: These preliminary results suggest that diminished beta AR function is associated with the chronic FM state.

Adult↗

Mental deterioration correlates with response of natural killer (NK) cell activity to physiological modifiers in patients with short history of Alzheimer's disease.

Natural killer (NK) cell activity of peripheral blood mononuclear (PBM) cells was measured in 16 subjects with mild to moderate senile dementia of Alzheimer's type (sDAT) chosen for short history of disease and no medication, and in 17 age- and sex-matched controls. Levels of cytotoxicity at baseline and after PBM cell exposure to modifiers either negative (cortisol 10(-6) M) or positive (rIL-2 650 IU/ml and rIFN-gamma 100 UI/ml, respectively) were related to indices of hypothalamic-pituitary-adrenal (HPA) function and Gottfries Bråne Rating Scale (GBS) score for mental deterioration. Spontaneous NK cell activity was not significantly different in sDAT subjects vs controls. In vitro inhibition by cortisol was lower in sDAT (P<0.05); cytokine-induced changes were greater (rIL-2, P<0.02; rIFN-gamma, P<0.05). Percent negative or positive variations from baseline significantly correlated with GBS scores (P<0.05 or less). Serum cortisol and cortisol/DHEAS molar ratio at 0800 h were significantly higher in sDAT (P<0.05 and P<0.02, respectively). Cortisol/DHEA ratio positively correlated with GBS scores (P<0.02). Moreover, the ratios of incremental area of response ACTH/cortisol and beta-endorphin/cortisol after 1 microg/kg ovine-corticotrophin-releasing hormone (o-CRH) positively correlated with percent increase of NK cell activity after rIL-2 (P<0.01). Data indicate that patients with mild cognitive impairment and short history of sDAT show abnormal responsiveness of NK cell activity to physiological modifiers while maintaining normal spontaneous activity. Furthermore, data are compatible with partial glucocorticoid resistance at the immune level. Progressing sDAT longitudinal studies are needed to address: i) the clinical applicability of these abnormalities as prognostic factors; ii) the role played by pro-opiomelanocortin (POMC)-derived peptides and adrenal androgens in the control of NK cell activity.

Aged↗

Psychoneuroimmunology: new avenues of research for the twenty-first century.

Psychoneuroimmunology (PNI) investigates the relations between the psychophysiological and immunophysiological dimensions of living beings. PNI brings together researchers in a number of scientific and medical disciplines, including psychology, the neurosciences, immunology, physiology, pharmacology, psychiatry, behavioral medicine, infectious diseases, and rheumatology. All are scientists with profound interest in interactions between the nervous and immune systems, and the relation between behavior and health. Despite the variety in domains and approaches to research, the outcome common to all research endeavors is the discovery of new information, of uncovered facts, of novel evidence, which contributes to the continuing generation of knowledge. In this paper we discuss psychoneuroimmune aspects of some conditions that are not routinely immediately associated with immunity, such as the condition of being the caregiver of somebody suffering from dementia; the effect on the brain-body modulations of aluminum, a metal that is not a component of the human body; and insomnia, a fairly common but disturbing disease, that even today lacks an effectual treatment.

Aluminum↗

Psychoneuroimmunology in oral biology and medicine: the model of oral lichen planus.

Rheumatoid arthritis involves psychoneuroendocrine-immunopathological comorbidities. In the stoma, patients with rheumatoid arthritis frequently show signs of periondontal disease consequent to elevated levels of crevicular proinflammatory cytokines. It is not clear whether rheumatoid arthritis may manifest in association with immunopathological manifestations of the oral soft mucosa. Oral lichen planus (OLP), first described by E. Wilson in 1859, is a T-cell-mediated inflammatory disease whose lesions characteristically lack B cells, plasma cells, immunoglobulin. or complement. It is increasingly well characterized and recognized as a model for psychoneuroimmunology research in oral biology and medicine. To date, we have shown an association between changes in hypothalamic-pituitary-adrenal (HPA) regulation, systemic markers of cellular immunity and mood states, with clinical stages of OLP (i.e., atrophic vs. erosive vs. bullous lesions). We report significant associations (p < 0.05) between the stage of OLP, HPA deregulation, and altered distribution and functional responses of naïve CD4(+) cells. We emphasize the need to study in greater details the psychoneuroendocrine-immune inter-relationships in OLP, and we propose a novel neuroimmune hypothesis for OLP.

Apoptosis↗

Evidence-based dentistry for the 21st century.

Evidence-based clinical dental practice relies upon the best available research evidence to formulate novel or improved modes of intervention specific to the needs of each patient. Evidence-based dentistry is a complex field. It is essential that its elements are clearly defined and understood for it to serve adequately and appropriately in clinical decision making. This paper discusses salient issues in evidence-based dentistry and examines the modality by which evidence-based dentistry will become the instrument for the integration of certain cutting-edge areas of science in dentistry in the new millennium.

Decision Making↗

Dental needs of the elderly in the 21st century.

The average age of the world's population is increasing rapidly. The "graying of America" presents new opportunities and new challenges for improving the oral health of the elderly, particularly those afflicted with neurocognitive impairments. The dental problems associated with these conditions include but are not limited to a decrease in oral hygiene; difficulty in controlling and retaining dentures; xerostomia, which often is drug-associated, and consequential root caries, recurrent decay, and purposeless chewing. Parkinson's disease and Alzheimer's disease are the most prevalent type of progressive neurocognitive impairing illnesses, affecting millions of elderly Americans. As the adult population increases, a greater number of patients with these diagnoses will require dental care. Dental providers need to be aware of the special problems associated with the treatment of the older healthy subject and the neurocognitively impaired patient.

Adult↗