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Biomedical subjects

Fionnuala T Lundy

Publications and source records attributed to Fionnuala T Lundy.

8 recordsLinked to original sources

Vasoactive intestinal polypeptide (VIP) and VPAC1 receptor in adult human dental pulp in relation to caries.

OBJECTIVE: To quantitatively measure VIP levels and to qualitatively study the distribution of VIP fibres and demonstrate the presence of the VPAC1 receptor in human dental pulp from carious and non-carious adult human teeth. DESIGN: Dental pulp samples were collected from non-carious, moderately carious and grossly carious adult human teeth. VIP levels were determined using radioimmunoassay. The distribution of VIP fibres was studied using immunohistochemistry. The VPAC1 receptor protein expression was determined by Western blotting. RESULTS: VIP levels were found to be significantly elevated in the dental pulp of moderately carious compared with non-carious (p=0.0032) or grossly carious teeth (p=0.0029). The distribution of VIP fibres was similar in non-carious and carious teeth, except that nerve bundles appeared thicker in the pulp samples from carious compared with non-carious teeth. Western blotting indicated that the VPAC1 receptor proteins were detected in similar levels in pooled dental pulp samples from both carious and non-carious teeth. CONCLUSION: It is concluded that quantitative changes in the levels of VIP in human dental pulp during the caries process and the expression of VPAC1 receptor proteins in membrane extracts from carious and non-carious teeth suggests a role for VIP in modulating pulpal health and disease.

Adult↗

The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro.

Alpha-defensin or human neutrophil peptide-1 (HNP1) is a neutrophil-derived antimicrobial peptide with cytotoxic effects towards cancer cells. Lactoferrin is also stored in human neutrophils and is a glycoprotein involved in mediating cytotoxicity towards tumour cells. This study investigated the sensitivity of normal oral keratinocyte and oral squamous cell carcinoma (OSCC) cells to HNP1 and lactoferrin in various combinations. A concentration of 100 microg/ml HNP1 induced the most significant cytotoxic effect on both normal and OSCC cells. Lactoferrin (12.5, 25 and 250 microg/ml) also significantly induced cell death in OSCC cells after 72 h. Of note, a combination of 10 microg/ml HNP1 and 50 microg/ml lactoferrin induced a differential effect, not observed with either concentration alone, which stimulated proliferation in normal cells, but induced cell death in OSCC cells throughout the study. These results indicate a potentially important co-operative role for HNP1 and lactoferrin in facilitating a selective cytotoxic effect on tumour cells.

Carcinoma, Squamous Cell↗

Caries-induced changes in the expression of pulpal neuropeptide Y.

Recent evidence suggests that the sympathetic nervous system may have a role in modulating neurogenic inflammation and bone remodelling. Neuropeptide Y (NPY) is a well-characterized neuropeptide transmitter in the peripheral sympathetic nervous system. NPY is known to be present in human dental pulp; however, quantitative data on NPY levels in pulpal health and disease in an adult population remain to be determined. The aims of the current study were to assess, quantitatively, NPY levels by radioimmunoassay and confirm the distribution of NPY fibres by immunocytochemistry in carious and non-carious adult human pulp tissue. Our results suggest changes in the levels and distribution of NPY in human dental pulp during the caries process, with significantly higher levels of NPY in carious compared with non-carious adult human teeth. Within the carious samples studied, our finding, that NPY levels were significantly elevated in mild/moderate caries, concurs with the hypothesis that NPY could have a modulatory role in pulpal inflammation and in reparative dentine formation.

Adult↗

Radioimmunoassay quantification of adrenomedullin in human gingival crevicular fluid.

OBJECTIVE: To investigate whether adrenomedullin (ADM), a multifunctional peptide with key roles in host antimicrobial defence and inflammation, was present and quantifiable in human gingival crevicular fluid (GCF) and to study its relationship with periodontal health and disease. DESIGN: GCF samples (30s) were collected using perio-paper strips from one diseased site in 21 subjects with periodontal disease and one healthy site from 19 control subjects with no evidence of periodontal disease. Samples were analysed by radioimmunoassay using a specific anti-human ADM antibody. RESULTS: Measurable adrenomedullin-like immunoreactivity (ADM-LI) was present in all the GCF samples collected. ADM-LI was significantly higher in periodontitis sites (mean 493.6 pg) than in control healthy sites (mean 248.5 pg), p = 0.0016. CONCLUSION: It is concluded that ADM is present in GCF at levels at which it could have an antibacterial role in the gingival crevice and modulate the pathophysiology of periodontal inflammation.

Adrenomedullin↗

Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue.

To date, little attention has been paid to the possible role of alpha-defensins (human neutrophil peptides 1-3), HNP-1, HNP-2 and HNP-3 in innate host defence against tumour invasion. In the current study, using a single-dimensional high pressure liquid chromatography (HPLC) method for peptide separation, followed by mass spectrometry and amino acid sequencing for identification and quantitation, we report the overexpression of HNP-1, HNP-2 and HNP-3 in squamous cell carcinomas of the human tongue compared with autogenous non-tumour tissue. Using a specific antibody we show that the defensins are abundant in neutrophils infiltrating human oral squamous cell carcinoma tissue. In the context of their previously reported oncolytic activity, our results may imply a role for alpha-defensins in host defence against oral squamous cell carcinoma.

Adult↗

Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in gingival crevicular fluid associated with painful human teeth.

The aim of this study was to investigate the presence of substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) in the gingival crevicular fluid of teeth diagnosed with pain of pulpal origin compared with clinically healthy teeth, and to detect any changes in the levels of these neuropeptides in gingival crevicular fluid after removal of the pulp from the painful teeth. Gingival crevicular fluid was collected at baseline from one interproximal site at a painful and a non-painful contralateral tooth from 54 adult patients. Sampling was repeated after 1 wk in a subset of 21 subjects. Samples were analysed for SP, NKA, and CGRP using radioimmunoassay. The mean levels of SP and NKA were significantly higher in gingival crevicular fluid from painful teeth compared with non-painful teeth. The level of SP in the GCF of painful teeth fell significantly 1 wk after pulpectomy. In contralateral teeth, there were no significant differences in the levels of SP and NKA after 1 wk. It is concluded that SP and NKA are present in significantly greater amounts in the GCF of painful teeth compared with healthy teeth.

Adolescent↗

Changes in vasoactive intestinal peptide in gingival crevicular fluid in response to periodontal treatment.

AIMS: To evaluate the role of the anti-inflammatory neuropeptide vasoactive intestinal peptide (VIP) in periodontal health and disease and to determine the effects of periodontal treatment, resulting in a return to periodontal health, on the levels of VIP in gingival crevicular fluid (GCF). METHODS: At baseline, 10 subjects with periodontitis (nine females, one male, mean age 43.0, SD 7.3) started a course of non-surgical periodontal treatment. Clinical indices were measured at one periodontitis and one clinically healthy site at an initial visit and at 8 weeks after the completion of treatment in each subject. A 30-s sample of GCF was collected from each test site using perio paper strips. The volume of GCF was measured and each sample subsequently analysed for VIP by radioimmunoassay. One healthy site was sampled from each member of a control group (10 females, mean age 29.9, SD 8.2 years) with clinically healthy gingiva and no periodontitis. RESULTS: The clinical condition of all periodontitis sites improved as a result of periodontal treatment. The levels of VIP (pg/30 s sample) in periodontitis-affected sites fell significantly from 302.0 (SD 181.2) at the initial visit to 78.0 (54.4) after treatment, p = 0.007. The reduction in the concentration of VIP (pg/ micro L) in GCF from 524.3 (322.3) to 280.8 (280.2) was not statistically significant. The levels of VIP in clinically healthy sites fell from 115.5.5 (74.3) to 77.8 (32.3), n.s. and the concentration changed little from 883.8 (652.1) to 628.7 (323.3), n.s. There were substantially smaller amounts of VIP (25.8, SD 12.8) pg in healthy sites sampled from control subjects. CONCLUSIONS: VIP is present in GCF in greater quantities in periodontitis-affected than clinically healthy sites. In addition, the reduction in inflammation resulting from effective periodontal treatment is associated with a reduction in the levels of VIP in gingival crevicular fluid.

Adult↗

Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression.

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha-SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor -beta1 and -beta3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7-day period. alpha-SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme-linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor-beta1 and -beta3, over the concentration range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel contraction and alpha-SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.

Actins↗