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Biomedical subjects

Sergio Bonini

Publications and source records attributed to Sergio Bonini.

16 recordsLinked to original sources
PubMed2006

Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing.

In response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-beta1 (TGF-beta1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkA(NGFR) and p75(NTR) are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkA(NGFR) and p75(NTR) were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-beta1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing.

Cell Differentiation↗
PubMed2006

Allergic conjunctivitis: the forgotten disease.

The eye is largely exposed to foreign substances, and ocular tissues have a complete array of immune cells to interact with offending antigens. In particular, the external eye represents an ideal site for immediate hypersensitivity reactions because of the high number of mast cells in the eyelids and bulbar conjunctiva, as well as for the potential local synthesis of IgE. In fact, the involvement of the eye was part of the original description of hay fever by Charles Blackley in 1873. In a large epidemiological survey of allergic patients we reported since 1987, 40% had symptoms possibly related to allergic conjunctival disease. However, the participation of the conjunctiva to the multiorgan picture of allergy is largely underestimated. Allergic eye diseases have long been referred to the classical Type I hypersensitivity mechanism according to Coombs and Gell. Recently, however, the tremendous progress in understanding allergic mechanisms and inflammation has brought new insights into the pathophysiology of several allergic diseases, including those of the eye. Accordingly, several systematic descriptions of allergic eye diseases should be revisited. In particular, the classification of the various forms of a 'red eye' of allergic origin appears inadequate to answer the progress achieved in their multifactorial pathogenesis.

Allergens↗
PubMed2005

Clinical and cytological findings in limbal stem cell deficiency.

PURPOSE: To evaluate and relate the clinical (including corneal sensitivity and tear function) and cytological (presence of goblet cells and cytokeratin 3- and 19-positive cells) features of limbal stem cell deficiency (LSCD). METHODS: Twenty-nine patients (44 eyes) with a clinical diagnosis of LSCD participated in this study. Corneal signs (epithelial alterations, superficial neovascularisation and stromal scarring) and cytological findings (presence of goblet cells and cytokeratins 3 and 19) were evaluated and scored (from 0 to 3) from each of the five corneal sectors. Corneal sensitivity (Cochet-Bonnet aesthesiometer) and tear function (Schirmer test and BUT) were also assessed. Cytological scores were correlated statistically with both corneal signs and sensitivity values. RESULTS: Cytokeratin 19-positive cells were found in 82% of corneal impression cytology samples, while goblet cells were identified in only 59% of these same samples. Cytokeratin 3-positive cells were present in 61% of LSCD eyes and in all unaffected eyes. Corneal sensitivity was significantly decreased in affected eyes compared with contralateral, healthy eyes (1.6+/-1.7 cm versus 5.7+/-0.3 cm). Tear function tests did not show significant changes. In LSCD eyes, goblet cells and cytokeratin 19-positive cells on the corneal surface were significantly correlated to corneal epithelial alterations and to corneal superficial neovascularisation (p<0.001). Corneal cytokeratin 3-positive cells were inversely related to epithelial alterations (p=0.003). Corneal sensitivity was decreased in corneal sectors with epithelial alterations (p<0.001), neovascularisation (p<0.001) and stromal abnormalities (p=0.049), and was indirectly related to the presence of goblet cells (p=0.005) and cytokeratin 19-positive cells (p<0.001). CONCLUSION: This study confirmed the importance of cytological tests in the diagnosis of LSCD. Furthermore, the absence of goblet cells may not exclude corneal conjunctivalisation as demonstrated by cytokeratin 19 immunostaining. Lastly, corneal conjunctivalisation was associated with zone-specific impairment in corneal sensitivity.

Adolescent↗
PubMed2005

Expression of Toll-like receptors in healthy and allergic conjunctiva.

PURPOSE: To investigate the expression of toll-like receptors (TLRs) in healthy and active vernal keratoconjunctivitis (VKC) conjunctiva. DESIGN: Comparative nonrandomized interventional study. PARTICIPANTS: Nine patients with vernal keratoconjunctivitis and 10 healthy subjects. METHODS: Normal and VKC conjunctiva were evaluated for TLR-2, TLR-4, and TLR-9 mRNA and proteins by relative real-time polymerase chain reaction and immunohistochemistry. Colocalization of TLRs was further evaluated by confocal microscopy and double-labeled immunofluorescence in T cells (CD4), mast cells (AA1), and eosinophils (EG2). MAIN OUTCOME MEASURES: Identification of TLRs at molecular and biochemical levels and identification of inflammatory cells that coexpress these receptors. RESULTS: Toll-like receptor 2, TLR-4, and TLR-9 were expressed in normal and VKC conjunctival epithelium and stroma, both with a more intense immunoreactivity in the stroma. In VKC tissues, TLR-4 was upregulated, TLR-9 was downregulated, and TLR-2 was slightly decreased relative to normal tissues. Toll-like receptor 4 was localized on CD4+ lymphocytes, eosinophils, and mast cells, whereas lymphocytes and eosinophils, but not mast cells, expressed TLR-9. CONCLUSIONS: Toll-like receptors are expressed in healthy and allergic conjunctiva. The upregulation or downregulation of these receptors and their presence on inflammatory cells suggest a role of TLRs in VKC.

Adolescent↗
PubMed2005

The hygiene hypothesis: does it function worldwide?

PURPOSE OF REVIEW: This article intends to be a systematic review of papers published during 2003-2004 quoted in a Medline search for 'hygiene hypothesis'. The worldwide perspective of the article does not refer just to a geographical concept, but tries also to address the question of whether the consensus on the hypothesis is global or whether it applies to all types of allergic or immunologic disease, to any age sample or infectious agent. Furthermore, the article outlines those clinical and experimental studies which, in the authors' opinion, may represent significant contributions to a better understanding of the hygiene hypothesis and may guide further investigations on the subject. RECENT FINDINGS: The association between a reduced exposure to infectious agents (as a part of a changed lifestyle) and a higher prevalence of atopy seems now to be confirmed by consistent evidence. Mechanisms underlying this association, however, are not yet completely clear (immune deviation or immune regulation). SUMMARY: Further experimental and clinical studies are needed, with special reference to the time, duration and intensity of exposure to any specific infectious agent which is related to well-defined allergy outcomes. The background information for using microbial products in allergy prevention and treatment is still limited.

Environmental Exposure↗
PubMed2004

Nerve growth factor and the immune system: old and new concepts in the cross-talk between immune and resident cells during pathophysiological conditions.

PURPOSE OF REVIEW: This review provides an overview of nerve growth factor and its involvement in the immune system. Furthermore, recent data are provided revealing new important insights into the mechanisms of action of nerve growth factor in allergic reaction. RECENT FINDINGS: Recent studies on the effects of nerve growth factor on the immune cells involved allergic reaction, and on the potential role of nerve growth factor in tissue remodelling are presented. SUMMARY: Nerve growth factor has an extended function from the nervous system to a wide range of activities in the immune system. Several papers have highlighted the role of the factor in allergic inflammation. This review describes old and new concepts of nerve growth factor in the immune system: the relation between nerve growth factor and the main cells taking part in allergic inflammatory disorders, structural cells, mediators and cytokines/chemokines, as well as the mechanisms leading to nerve growth factor increase. Understanding these complex mechanisms will introduce new therapeutic approaches for nerve growth factor in the immune system, in addition to those already established in the nervous system.

Cell Communication↗
PubMed2003

Montelukast, a leukotriene receptor antagonist, in vernal keratoconjunctivitis associated with asthma.

OBJECTIVE: To evaluate the effects on signs and symptoms of a coexisting vernal keratoconjunctivitis in patients treated with oral montelukast sodium for asthma. METHODS: Twelve patients with vernal keratoconjunctivitis and asthma were enrolled in this pilot study. Topical eyedrops or any systemic treatment was discontinued for at least 7 days before montelukast treatment. Patients were asked to grade their ocular discomfort daily. The following signs and symptoms were also recorded and graded through medical examination at baseline,after 15 days of treatment, and 15 days after treatment discontinuation: physician-evaluated tarsal and bulbar papillae, hyperemia, secretion, and chemosis; and patient-evaluated itching, burning, tearing, photophobia, foreign body sensation, secretion, and redness. Peak expiratory flow rate at 8 AM was also recorded. Samples were collected at the same time points for enzyme-linked immunosorbent assay measurement of leukotriene B4 in tears and leukotriene E4 in urine. RESULTS: Eight of the 10 patients evaluated reported a reduction in symptoms at the end of treatment. Montelukast treatment significantly decreased physician-rated hyperemia, secretion, and chemosis as well as patient-rated burning, tearing, photophobia, secretion, and redness. Effects persisted 15 days after discontinuation of treatment. Clinical changes were associated with a significant increase in leukotriene B4 in tears and a significant decrease in leukotriene E4 in urine after 15 days of treatment. CONCLUSION: The significant and persistent reduction of ocular signs and symptoms in asthmatic patients with vernal keratoconjunctivitis treated for 15 days with montelukast strongly suggests the need for double-masked placebo-controlled trials to confirm the potential of this new treatment in vernal keratoconjunctivitis.

Acetates↗
PubMed2003

CD34-positive cells in human umbilical cord blood express nerve growth factor and its specific receptor TrkA.

In this study, we investigated whether hematopoietic stem cells (HSC) and progenitors present in human cord blood can express nerve growth factor (NGF)-specific receptors, TrkA and p75. Our results showed a marked expression of TrkA and NGF in cord blood CD34(+) cells. A gradient of TrkA and NGF expression exists and is highest in cord blood CD34(+) cells, reduced in cord blood mononuclear cells (MNC) and minimal in mononuclear cells isolated from adult peripheral blood. Our findings suggest that NGF may play a role in the differentiation of hematopoietic progenitors and indicate a different requirement for NGF by immune cells, depending on their state of maturity.

Adult↗
PubMed2003

Allergic chronic inflammation of the ocular surface in vernal keratoconjunctivitis.

PURPOSE OF REVIEW: The purpose of this review is to describe the new immunopathologic features of vernal keratoconjunctivitis: the involvement of cytokines, growth factors, cells, mediators and neurotransmitters, as well as the mechanism leading to tissue remodelling. RECENT FINDINGS: Vernal keratoconjunctivitis is an allergic eye disease affecting young boys living in a warm climate. It is characterized by conjunctival giant papillae, hyperemia and frequent involvement of the cornea. Approximately 50% of the patients with vernal keratoconjunctivitis do not have a family or medical history of atopic diseases, and do not show IgE sensitization, suggesting that this disease is not solely IgE mediated. Vernal keratoconjunctivitis is a Th2 lymphocyte driven disease with a Th2 cytokine derived pattern, increased levels of mRNA for IL-3, IL-4, IL-5 and IL-13. Th2 lymphocytes induce IgE hyperproduction, activation of mast cells, eosinophils, neutrophils and their toxic products. An overexpression of adhesion molecules, RANTES, eotaxin and metalloproteinases contribute to chronic inflammation. A role for substance P and nerve growth factor has been postulated, as well as for other growth factors (epidermal growth factor, fibroblast growth factor and transforming growth factor beta 1) that induce fibroblast growth and new collagen production. Recent studies have also pointed out the role of resident conjunctival cells, such as epithelial cells and fibroblasts, in the inflammatory and remodelling process of vernal keratoconjunctivitis. The pathogenesis of the condition is probably multifactorial, with the interaction of the immune, nervous and endocrine systems. SUMMARY: Vernal keratoconjunctivitis is a chronic inflammatory and potentially blinding disease. Understanding of the complex interactions and cross talk between cells, cytokines and other mediators is relevant for new therapeutic approaches.

Adolescent↗
PubMed2002

Hay fever and asthma in relation to markers of infection in the United States.

BACKGROUND: The hygiene hypothesis proposes that declining exposure to infections is implicated in the rising trend of allergy and asthma. OBJECTIVE: We sought to test this hypothesis by examining the relationship of hay fever, asthma, and atopic sensitization with markers of infection in a large general population sample of the United States. METHODS: We analyzed the data of 33,994 US residents recorded in a public database of a nationally representative cross-sectional survey (Third National Health and Nutrition Examination Survey, 1988-1994). The variables examined were sociodemographic information, lifetime diagnosis and age at first diagnosis of hay fever or asthma, current skin sensitization to 9 airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes simplex viruses type 1 and 2, and hepatitis A, B, and C viruses. RESULTS: Hay fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P <.001) and asthma (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P <.001) were less frequent in subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex virus 1 versus seronegative subjects after adjusting for age, sex, race, urban residence, census region, family size, income, and education. Skin sensitization to peanut and to all the airborne allergens examined, except for cockroach, was less frequent among HAV-seropositive versus HAV-seronegative subjects younger than 40 years of age. The prevalence of hay fever and asthma diagnosed at or before 18 years of age in HAV-seronegative subjects increased progressively from 2.7% (95% CI, 0.7%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%), respectively, in cohorts born in the 1960s, whereas they remained constant at around 2% in all cohorts of HAV-seropositive subjects. CONCLUSION: In the United States serologic evidence of acquisition of certain infections, mainly food-borne and orofecal infection, is associated with a lower probability of having hay fever and asthma. Third National Health and Nutrition Examination Survey data support the hypothesis that hygiene is a major factor contributing to the increase in hay fever, asthma, and atopic sensitization in westernized countries.

Adolescent↗