الفهرس 
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Abstract
Hepatitis C virus (HCV) is the main cause of chronic hepatitis and liver lethal diseases. An average of 170 million people had been infected worldwide. The HCV has the ability to cause a chronic infection in about 70% of the cases that lead to the development of many serious liver diseases. chronic HCV has a high rank in worldwide morbidity and global suffering. The Egyptian Ministry of Health and Population proposed a national strategy to control the HCV epidemic, and promoted Sofosbuvir (Sovaldi™ by Gilead Sciences) as its primary treatment. Sovaldi™ has pan genotypic antiviral activity and a high genetic barrier to resistance, thus it resulted in high clinical efficacy and tolerability in patients with chronic hepatitis C. However, clinical evaluation reports illustrated that in any treatment combination including Sovaldi has ranging different side effects on other tissues of the body.
Aim:
The primary aim of this study was to assess the effect of Sofosbuvir on buccal mucosa in Albino rats; while the secondary aim of this study was to compare between two different treatment durations of Sofosbuvir.
Methodology:
Twenty-eight adult male wistar Albino rats, weight ranging from 200-250 gm were used in this study. Rats were randomly divided evenly into two main groups fourteen rats each, as follows:
group I (control): 14 albino rats given only distilled water daily by gastric tube.
group II (experimental): 14 albino rats given SOF dissolved in distilled water by gastric tube. (40mg/kg/day).
Each group were furtherly subdivided into two subgroups according to the time of sacrifice:
Subgroup A: rats were sacrificed on day 45.
Subgroup B: rats were sacrificed on day 60.
The animals were euthanized by overdose of anesthesia and immediately dissected to obtain the buccal mucosa. The buccal mucosa specimens were processed and examined by the light microscope and immunohistochemical Ki-67 staining. Statistical analysis was carried out for area percentage of (+ve) immunohistochemical stained cells to detect differences between groups.
Results:
H&E results:
In Subgroups IA & IB there was normal histological features of the buccal mucosa with apparent normal epithelial thickness. The epithelium and the lamina propria were separated by well-defined basement membrane. The epithelial rete pegs appeared short, broad and numerous. The epithelium is underlined with normal fibrous dense connective tissue lamina propria continuous with submucosa and the underlying muscle fibers. The lamina propria consisted of dense vascular connective tissue with fibroblasts and collagen fiber bundles. Submucosa showed collagen fibers and muscle cells.
In subgroup IIA basilar hyperplasia with loss of polarity was seen and the parabasal cell layer appeared with paler cytoplasm, pale stained nuclei and diffuse cytoplasmic vacuolization. Cells of the spinous cell layer appeared swollen and with faintly stained cytoplasm and pale stained nuclei. The keratin layer appeared thickened with some areas of separation and some flat horny scales, some areas show separation of the epithelium. The connective tissue appeared irregularly arranged with dilated blood vessels. The submucosa had areas of separations especially surrounding the muscle layer.
In subgroup IIB the basal cell layer was composed of a single row of non-columnar cells, some cells of the basal and parabasal layer showed signs of degeneration appeared as wide perinuclear haloing and vacuolization. Cells of the spinous cell layer appeared to have obvious pale stained nuclei. The connective tissue appeared to have disorganized connective tissue fiber bundles and the submucosa appeared disorganized with some areas of matrix degeneration with dilated blood vessels. The thickness of the granular cell layer was markedly diminished and consequently, the amount of keratohyaline granules was fewer than in subgroup IIA. The keratin layer appeared thinner than subgroup IIA. Some cells showed almost complete degeneration of nuclei in prickle and granular cell layers while some regions showed swelling in prickle cells with binucleation and mitotic figures.
Immunohistochemical results:
Ki-67 expression in subgroup IIA showed apparently lower immunoreactivity than that detected in group I. Ki-67 expression in subgroup IIB presented apparently decreased reactivity to Ki-67 when compared to group I.
Statistical analysis:
The mean of area percentage of immune positive cells, was significantly higher in subgroup IA than subgroup IIA, and the mean of area percentage of immune positive cells, was significantly higher in in subgroup IB than subgroup IIB and the mean of area percentage of immune positive cells, was significantly higher in subgroup IIA than subgroup IIB. Value measured at day 45 was significantly higher than that measured at day 60. Which proves that the longer the administration of SOF the lower the proliferation rate in the tissues.