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Biomedical subjects

S Bonini

Publications and source records attributed to S Bonini.

At least 19 recordsLinked to original sources
PubMed2001

Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency.

BACKGROUND: Ocular burns cause depletion of limbal stem cells, which leads to corneal opacification and visual loss. Autologous cultured epithelial cells can restore damaged corneas, but this technology is still developing. We sought to establish a culture system that allows preservation of limbal stem cells and preparation of manageable epithelial sheets and to investigate whether such cultures can permanently restore total limbal stem cell deficiency. METHODS: We selected a homogeneous group of patients whose limbal cell deficiency was evaluated by scoring the gravity of the clinical picture and the keratin expression pattern. Stem cells, obtained from the limbus of the contralateral eye, were cultivated onto a fibrin substrate and their preservation was evaluated by clonal analysis. Fibrin cultures were grafted onto damaged corneas. RESULTS: Fibrin-cultured limbal stem cells were successful in 14 of 18 patients. Re-epithelialization occurred within the first week. Inflammation and vascularization regressed within the first 3-4 weeks. By the first month, the corneal surface was covered by a transparent, normal-looking epithelium. At 12-27 months follow-up, corneal surfaces were clinically and cytologically stable. Three patients had a penetrating keratoplasty approximately 1 year after restoration of their corneal surface. Their visual acuity improved from light perception or counting fingers to 0.8-1.0. CONCLUSIONS: Preservation of limbal stem cells in culture gives new perspectives on the treatment of ocular disorders characterized by complete limbal stem cell deficiency. The multicenter nature of this study and the handiness and ease of long-distance transportation of the fibrin-cultured epithelial sheets suggest that this technology can now be widely applied.

3T3 Cells↗
PubMed2001

Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair.

Nerve growth factor (NGF) is a polypeptide which, in addition to its effect on nerve cells, is believed to play a role in inflammatory responses and in tissue repair. Because fibroblasts represent the main target and effector cells in these processes, to investigate whether NGF is involved in lung and skin tissue repair, we studied the effect of NGF on fibroblast migration, proliferation, collagen metabolism, modulation into myofibroblasts, and contraction of collagen gel. Both skin and lung fibroblasts were found to produce NGF and to express tyrosine kinase receptor (trkA) under basal conditions, whereas the low-affinity p75 receptor was expressed only after prolonged NGF exposure. NGF significantly induced skin and lung fibroblast migration in an in vitro model of wounded fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not influence either skin or lung fibroblast proliferation, collagen production, or metalloproteinase production or activation. In contrast, culture of both lung and skin fibroblasts with NGF modulated their phenotype into myofibroblasts. Moreover, addition of NGF to both fibroblast types embedded in collagen gel increased their contraction. Fibrotic human lung or skin tissues displayed immunoreactivity for NGF, trkA, and p75. These data show a direct pro-fibrogenic effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF in tissue repair and fibrosis.

Actins↗
PubMed2001

The heterogeneity of allergic phenotypes: genetic and environmental interactions.

OBJECTIVE: This article reinforces the reader's knowledge of the multifactorial nature of allergic diseases and of the heterogeneity of allergic phenotypes. DATA SOURCES: Personal studies and an evidence-based approach is used to support the assumption that three major abnormalities concur in the pathophysiology of allergic diseases: 1) enhanced allergen recognition and specific immune response; 2) a T helper 2 cytokine profile that results in polyclonal immunoglobulin E activation and mast cell-eosinophilic inflammation; and 3) organ hyperreactivity. STUDY SELECTION: Examples of genetic and environmental factors that preferentially influence each of these distinct pathophysiologic abnormalities are provided. RESULTS: Data presented indicate that allergic diseases distribute along a wide spectrum depending on the preferential pathophysiologic abnormalities operating in the individual patient. CONCLUSIONS: Categorization of allergic patients into distinct clinical phenotypes might result in a more patient-oriented (rather than disease-oriented) approach, and hence, better management.

Allergens↗
PubMed2001

Epidemiology of allergic occupational diseases induced by Tetranychus urticae in greenhouse and open-field farmers living in a temperate climate area.

BACKGROUND: The role of Tetranychus urticae (TU) as an occupational allergen has thus far been investigated only in selected farmer samples. METHODS: The prevalence of TU-induced sensitization and occupational diseases in a randomized sample of farmers living in a temperate climate area was investigated. Occupational/nonoccupational symptoms, skin prick test (SPT) results with common allergens and TU, specific occupational test results, and greenhouse or open-field sources of TU exposure were assessed. The study design was cross-sectional. RESULTS: The prevalence of positive SPT to TU was 6%. TU-induced allergic/nonallergic complaints accounted for 65% of farmers with challenge-confirmed occupational disease. In all farmers, sensitization to common allergens was a risk factor for both current occupational and nonoccupational complaints, while TU sensitization was a prominent risk factor for occupational complaints. Furthermore, in SPT-positive farmers, only the presence of seasonal occupational complaints was significantly associated with TU sensitization. Common allergen sensitization was a risk factor for development of TU sensitization, which was more frequent in greenhouse than in open-field workers. CONCLUSIONS: TU was a common nontraumatic, allergic occupational hazard for farmers. Since occupational seasonal symptoms could be directly related to the presence of TU sensitization, allergy to this mite should be routinely investigated in farmers.

Adolescent↗
PubMed2000

Mimicking microbial 'education' of the immune system: a strategy to revert the epidemic trend of atopy and allergic asthma?

Deficient microbial stimulation of the immune system, caused by hygiene, may underly the atopy and allergic asthma epidemic we are currently experiencing. Consistent with this 'hygiene hypothesis', research on immunotherapy of allergic diseases also centres on bacteria-derived molecules (eg DNA immunostimulatory sequences) as adjuvants for allergen-specific type 1 immune responses. If we understood how certain microbes physiologically 'educate' our immune system to interact safely with environmental nonmicrobial antigens, we might be able to learn to mimic their beneficial actions. Programmed 'immunoeducation' would consist of safe administration, by the correct route, dose and timing, of those microbial stimuli that are necessary to 'train' the developing mucosal immune system and to maintain an appropriate homeostatic equilibrium between its components. Overall, this would result in a prevention of atopy that is not limited to certain specific allergens. Although such a strategy is far beyond our present potential, it may in principle revert the epidemic trend of atopy and allergic asthma without jeopardizing the fight against infectious diseases.

Asthma↗
PubMed2000

Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study.

OBJECTIVE: To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. DESIGN: Retrospective case-control study. PARTICIPANTS: 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. SETTING: Air force school in Caserta, Italy. MAIN OUTCOME MEASURES: Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. RESULTS: Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18% v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0. 70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). CONCLUSION: Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.

Adolescent↗
PubMed2000

Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup.

OBJECTIVE: This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred and ninety-five patients with VKC. METHODS: Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. MAIN OUTCOME MEASURES: (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. RESULTS: VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. CONCLUSIONS: VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex-related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Adolescent↗
PubMed2000

Topical treatment with nerve growth factor for neurotrophic keratitis.

OBJECTIVE: To evaluate the efficacy of nerve growth factor (NGF) in patients with neurotrophic keratitis. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Forty-five eyes of 43 consecutive patients with moderate (stage 2, n = 17) to severe (stage 3, n = 28) neurotrophic keratitis unresponsive to other nonsurgical therapies. METHODS: After a 10-day washout with preservative-free artificial tears, 45 eyes with neurotrophic keratitis received murine NGF (200 microg/ml) every 2 hours for 2 days followed by one drop six times daily until the ulcer healed. A maintenance dose of one drop NGF (100 microg/ml) was administered four times daily for the 2 weeks subsequent to ulcer healing. MAIN OUTCOME MEASURES: Size and depth of the ulcer or the epithelial defect, corneal sensitivity, best corrected visual acuity, side effects, and relapse of the disease in the follow-up period. RESULTS: All patients had a complete resolution of the persistent epithelial defect (with or without an ulcer) after 12 days to 6 weeks of treatment with NGF. Patients affected by both stages of the disease demonstrated both improved corneal sensitivity and visual acuity (P<0.001). No significant differences were observed in the time to complete corneal healing between stage 2 and stage 3 patients. Hyperemia and ocular and periocular pain were side effects reported during the first days of treatment. No relapse of the disease was observed during the follow-up period, with the exception of three patients with trigeminal nerve resection, who required a single retreatment. CONCLUSIONS: Nerve growth factor eye drops improved corneal sensitivity and promoted corneal epithelial healing in both moderate and severe neurotrophic keratitis. Although performed in an uncontrolled and nonrandomized series of patients, this therapy shows promise for the restoration of ocular surface integrity and visual function in neurotrophic corneal disease.

Administration, Topical↗
PubMed2000

Do sex and hormonal status influence choroidal circulation?

AIMS: To investigate the relation between pulse amplitude (PA), pulsatile ocular blood flow (POBF), and sex and hormonal status. METHODS: Measurements of POBF and PA were obtained by ocular blood flow tonography in 76 healthy subjects: 32 males and 44 females (age range 17-77 years). Females were divided into two age groups: group 1 (premenopausal) 17-42 years, and group 2 (post-menopausal) 55 years old and over. Two groups of age matched males served as controls. RESULTS: Premenopausal females demonstrated a significantly higher rate of POBF and PA than age matched males and post-menopausal females. CONCLUSION: Sex and hormonal status were shown to influence choroidal circulation.

Adolescent↗
PubMed2000

Conjunctival fibroblasts enhance the survival and functional activity of peripheral blood eosinophils in vitro.

PURPOSE: To examine the effect of human conjunctival fibroblasts on the survival and functional activity of human peripheral blood eosinophils. METHODS: Eosinophils were purified by negative immunoselection [magnetic activated cell sorter (MACS), purity > 97%] from volunteers with mild atopia. Fibroblasts were cultured from conjunctival specimens of healthy donors. Eosinophils were cultured on confluent monolayers of conjunctival fibroblasts or in culture medium alone. Eosinophil survival was evaluated by the trypan blue exclusion test. Eosinophil adherence was assessed by counting the attached cells after washing the cultures. Eosinophil viability and adherence in coculture were also assessed in the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-interleukin (IL)-3, and anti-IL-5 neutralizing antibodies. Cocultured eosinophils were activated by lipopolysaccharide (LPS) after 4 days in culture, and eosinophil peroxidase (EPO) release was determined as a marker of their activation. RESULTS: Eosinophils cocultured with conjunctival fibroblasts had a significantly increased viability of 35.9% (P = 0.004) and 12.8% (P = 0.003) on days 4 and 8, respectively. Fibroblast-conditioned medium did not enhance the survival of eosinophils. The increase in eosinophil survival in coculture was partially inhibited by anti-GM-CSF (P = 0.019), anti-IL-3 (P = 0.033), or anti-IL-5 (P = 0.011), whereas eosinophil adherence was reduced by anti-GM-CSF alone (P = 0.034). LPS activation of eosinophils cultured for 4 days with conjunctival fibroblasts induced higher EPO release than in freshly isolated eosinophils (P = 0.01). CONCLUSIONS: Human conjunctival fibroblasts induced prolonged survival and increased secretory function of human peripheral blood eosinophils. Increased survival is partially mediated by IL-3, IL-5, and GM-CSF. The coculture of conjunctival fibroblasts with eosinophils can serve as an in vitro system for the study of eosinophil behavior in the ocular surface and of cellular interactions in allergic eye diseases.

Adolescent↗
PubMed2000

Nerve growth factor promotes corneal healing: structural, biochemical, and molecular analyses of rat and human corneas.

PURPOSE: A recent clinical report demonstrated that topical nerve growth factor (NGF) treatment in patients affected by corneal neurotrophic ulcers induced epithelial and stromal healing restoring corneal integrity. Mechanisms(s) undergoing these clinical NGF actions are still unclear. The aim of this study was to investigate the role of NGF in human and rat cornea physiopathology. METHODS: Expression of high-affinity NGF receptors, NGF-mRNA, and NGF protein was evaluated in human and rat normal corneas, in human and rat corneal epithelial cell cultures, in human corneal organ culture, and in the rat cornea after an experimental model of epithelial injury, by means of immunohistochemistry, in situ hybridization reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: The resultant data demonstrated that NGF is a constitutive molecule present and produced in normal human and rat corneas. In vitro human and rat corneal epithelial cells produce, store, and release NGF and also express high-affinity NGF receptors (TrkA). In human organ culture, epithelium, keratocytes, and endothelium have been shown to bind exogenous radiolabeled NGF, and the epithelial cells' binding was increased after epithelium injury. In vivo, after rat corneal epithelial injury, a transient increase of corneal NGF levels was observed. Inhibition of endogenous NGF activity by neutralizing anti-NGF antibodies delayed the corneal epithelial healing rate, whereas exogenous administration of NGF accelerated healing. CONCLUSIONS: Taken together, the above findings show that NGF plays an important role in corneal physiopathology and suggest that this neurotrophin may exert therapeutic action in wide-spectrum corneal diseases.

Aged↗