الفهرس 
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Abstract
Ulcers are very common diseases of the oral mucosa with high prevalence all over the world. They are characterized by interruption in the epithelium, connective tissue or both and are painful in general. The focus on oral ulcer research helped to establish a better way for early prevention and effective treatment.
Several anti-inflammatory treatments such as topical steroids and antibiotics were used to promote tissue repair and prevent further infection. They are prescribed to relieve the pain or reduce both the duration and frequency of ulcer onset time. However, long term application of topical antibiotics or steroids may cause atrophy, irritation, discoloration, fungal infection and bacterial resistance.
Topical application of Aoe Vera (AV) and Silver nanoparticles (AgNPs) showed regenerative, anti-inflammatory and anti-microbial capabilities enabling them for being a good treatments option for ulcer healing.
• Aim of the study
The aim of this study was to compare between the possible healing effect of application of AV and AgNPs on acid induced lower labial mucosal ulcer in Albino rats histologically and immunohistochemically by using anti-proliferating cell nuclear antigen (anti-PCNA).
• Materials and methods
Forty-two adult male Albino rats (200-250 gm) were used in this study. Chemical ulcer was induced by rounded filter paper 3 mm in diameter. The filter paper soaked in 15ml of 50% acetic acid and was pressed onto the lower labial mucosa for 30 sec. Rats were randomly divided into three equal main groups (14 rats each) as follows:
1) group I (untreated ulcerated group): where rats did not receive treatment.
2) group II (AV group): where rats received daily topical application of AV gel (0.25ml/kg) on ulcer site from the day following ulcer induction till the day of sacrification.
3) group III (AgNPs group): where rats received daily topical application of AgNPs gel (2mg/kg) on ulcer site from the day following ulcer induction till the day of sacrification.
Each group was subdivided equally into two subgroups (seven rats each) according to time of sacrification:
Subgroup A: Rats were sacrificed after three days from ulcer induction.
Subgroup B: Rats were sacrificed after nine days from ulcer induction.
At the end of the experimental period for each group, rats were injected intraperitoneally by an overdose of ketamine anesthesia. The lower labial mucosa was excised in each subgroup. Then samples were processed for Hematoxylin and Eosin staining, immunohistochemical stain and statistical analysis.
• Results
I) Histological (H&E) results
Untreated ulcerated group (I)
1-Subgroup IA (three days after ulcer induction)
The ulcerated area showed loss of epithelium. Heavy inflammatory cells infiltration and dilated BVs were seen in the lamina propria (LP) with areas of degeneration.
2-Subgroup IB (nine days after ulcer induction)
The ulcerated area showed discontinuity of epithelium. Some inflammatory cells, normal blood vessels (BVs) and large areas of degeneration were seen in the LP.
Aloe Vera group (II)
1- Subgroup IIA (three days after ulcer induction)
The ulcerated area showed discontinuity of epithelium. Apparent few inflammatory cells compared to subgroup IA and areas of degeneration were seen in the LP.
2-Subgroup IIB (nine days after ulcer induction)
A continuous epithelial layer covered the area of the ulcer. Some areas of degeneration were observed in the LP as well as few inflammatory cells compared to subgroup IB and fibroblasts.
Silver Nanoparticles group (III)
1-Subgroup IIIA (three days after ulcer induction)
The healed ulcer area showed continuity of epithelium. The LP showed few inflammatory cells, BVs engorged with RBCs and minimal areas of degeneration.
2-Subgroup IIIB (nine days after ulceration)
This subgroup almost revealed a histological picture of the covering keratinized stratified squamous epithelium in the healed area. The LP showed many fibroblasts and minimal areas of degeneration.
II) Immunohistochemical results (anti-PCNA immuno-staining)
Untreated ulcerated group (I)
1-Subgroup IA (three days after ulcer induction)
Proliferating cell nuclear antigen (PCNA) immuno-positivity was observed in nuclei of the basal and prickle epithelial cell layers lateral to the ulcer. The LP showed few cells with immuno-positive nuclei.
2-Subgroup IB (nine days after ulcer induction)
Proliferating cell nuclear antigen immuno-positivity was detected in nuclei of the basal and prickle epithelial cell layers lateral to the ulcer. The LP showed some cells with immuno-positive nuclei.
Aloe Vera group (II)
1- Subgroup IIA (three days after ulcer induction)
The immuno-positivity of PCNA in this group was observed in nuclei of the basal and prickle epithelial cell layers lateral to the ulcerated area. The LP showed few cells with immuno-positive nuclei.
2-Subgroup IIB (nine days after ulcer induction)
The PCNA immuno-positivity was detected mainly in nuclei of the basal and prickle epithelial cell layers of the healed area. The LP showed some cells with immuno-positive nuclei.
Silver Nanoparticles group (III)
1-Subgroup IIIA (three days after ulcer induction)
Marked PCNA immuno-positivity was noted in nuclei of the basal and prickle epithelial cell layers of the healed area. The LP showed some cells with immuno-positive nuclei.
2-Subgroup IIIB (nine days after ulceration)
This subgroup revealed many cells with immuno-positive nuclei in the basal and prickle epithelial cell layer of the healed area. The LP showed marked cells with immuno-positive nuclei.
III) Statistical results
1-Epithelial thickness
At three days, a significant increase in the epithelial thickness of AgNPs subgroup (IIIA) was found compared to untreated ulcerated subgroup (IA). There was no significant increase between ulcerated untreated subgroup (IA) and AV subgroup (IIA), nor between AV subgroup (IIA) and AgNPs subgroup (IIIA).
At nine days, a significant increase in the epithelial thickness of AgNPs subgroup (IIIB) was found compared to untreated ulcerated subgroup (IB) and AV subgroups (IIB).
Comparing between three and nine days, a statistical significant increase of epithelial thickness was detected in AgNPs subgroup (IIIB) at nine days when compared to the same subgroup (IIIA) at three days. Untreated ulcerated (IA&IB) and AV (IIA&IIB) subgroups showed non significant increase between three and nine days.
2- Area fraction % of PCNA immuno-positivity
At three days, AgNPs subgroup (IIIA) showed significant increase in area fraction % of PCNA immuno-positivity compared to untreated ulcerated subgroup (IA). However, no significant increase was found between untreated ulcerated (IA) and AV subgroups (IIA) nor between AV (IIA) and AgNPs subgroups (IIIA).
At nine days, significant increase in area fraction % of PCNA immuno-positivity in AgNPs subgroup (IIIB) was detected compared with untreated ulcerated (IB) and AV (IIB) subgroups. No significant increase was detected between ulcerated (IB) and AV (IIB) subgroups.
Comparing between three and nine days, AV subgroup (IIB) and AgNPs subgroup (IIIB) showed significant increase in area fraction % of PCNA immuno-positivity at nine days when compared with the same subgroups at three days. Untreated ulcerated subgroups (IA&IB) didn’t show significant increase between three and nine days.