Early detection of hepatocellular carcinoma on top of liver cirrhosis: the fas receptor and ligand system

Hepatocyte aberrations, accumulation of chromosomal damage and possibly initiation of hepatic carcinogenesis is thought to be caused by the continued viral replication and the persistent attempt by a less than optimal immune response to eliminate hepatitis C virus [HCV] infected cells. The identification of the "death factors" including Fas and its Ligand [Fas-L] as a major regulator of both apoptosis and immune function has provided insight into an attractive mechanism of tumor escape from immune clearance. To assess the hepatic expression of Fas/Fas-L, the Fas receptor [Fas-R] expression on lymphocyte, and serum soluble Fas [sFas] in an attempt to analyze the role of Fas receptor/ligand system in the multistep process of fibrosis/carcinogenesis and the possible use of the serum marker as possible candidate biomarkers for an early detection of hepatocellular carcinoma [HCC]. The current study included 100 samples from cases at Theodor Bilharz Research Institute and Kasr Al Aini Hospital in Egypt. There were 90 cases of chronic hepatitis C [CHC] infection [and negative hepatitis B virus infection]. There were 30 cases without liver cirrhosis, 30 cases with liver cirrhosis and 30 cases with HCC. 10 liver biopsies were taken from healthy livers as normal controls. Histopathologic study and immunohistochemistry for detection of hepatic Fas and Fas-L expression were determined for all cases. Electron microscopy [EM] and immunoelectron microscopy [IEM] examination for detection of Fas-R expression on lymphocytes were also done. sFas, liver function tests, serologic markers for viral hepatitis, and serum alpha-fetoprotein level [alpha-FP] were done. The sFas in both HCC and CHC with cirrhosis patients were significantly higher than those of normal controls and CHC without cirrhosis [P<0.01], but there was no significant difference between the cirrhosis and HCC patients. Positive hepatic expression of both Fas and Fas-L were significantly increased in the diseased groups [p<0. 01] compared to the control specimens. A progressive Fas and FasL increase from CHC without cirrhosis to CHC with cirrhosis followed by a decline from the latter to HCC. Apoptotic Fas and Fas-L proteins expression was significantly increased with the necroinflammatory activity and the advancement of fibrosis. There was a non-significant negative correlation between sFas and hepatic Fas. In addition a significant over expression of Fas-R on separated lymphocytes was associated with a higher frequency of apoptotic cell death as detected by EM examination. Conclusion: The Fas receptor/ligand system was significantly involved in the process of liver cirrhosis converting into HCC. Down-regulation of Fas expression, up-regulation of Fas-L expression in hepatocytes and elevation of serum sFas level were important in tumor evasion from immune surveillance and in hepatic carcinogenesis

Laryngeal papillomatosis: molecular, ultrastructural and clinical evaluation

Our study was designed to correlate the prevalence of human papilloma viruses [HPV] types 6 and 11 in laryngeal papillomatosis specimens using PCR to the clinical and pathological characteristics of these patients as a trial to evaluate the usefulness of HPV typing in identifying which patients are at a higher risk for more frequently recurring aggressive disease or future malignant. This study was conducted on 36 adult patients who were identified clinically and histopathologically as laryngeal papilloma. An index of the number of procedures [laryngoscopy and carbon dioxide laser ablation] needed per year for each patient was calculated to assess the frequency of recurrence and disease aggressiveness. They were subjected to the detection of HPV6 and 11 DNA by PCR and electon microscopic examination of biopsies that were taken from laryngeal papillomas and non diseased sites as controls. We found that all papillomas [100%] were positive for HPV, among them the positive rate of either HPV6 or HPV11 was 25% [9/36] and 41.7% [15/36] respectively, the positive rate of mixed types of HPV6 + 11 was 33.3% [12/36]. Percentage of Patients needed >3 Pr/y were significantly increased [p>0.05 and 0.01] in cases with mixed infection of both HPV6+11 in comparison to those infected with HPV11 orHPV6 respectively and in HPV 11 infected cases in comparison to those infected with HPV 6 [p<0.05]. Percentage of cases revealed dysplastic features [cellular atypia, invasion, keratinization and necrosis] were significantly increased [p<0.05 and 0.01] in mixed infection of both HPV6+11 in comparison to those infected with HPV11 or HPV6 respectively and in HPV11 infected cases in comparison to those infected with HPV6 [p<0.05]. Correlation study revealed direct correlation between percentage of patients needed >3 Pr/y and the appearance of dysplastic features. Our findings suggest that viral typing is one marker that may be useful to identify patients at a higher risk for aggressive disease and, possibly, to malignant potential but more studies with a larger number of cases are needed to assess their agnostic and prognostic value

role of probiotics in controlling giardia intestinalis in experimental animals

Efficacy of Lactobacillus acidophilus [Lactospore] for the control Research Institute Warak of Giardia intestianlis infection was evaluated in hamsters. Each El-Hadar Imbaba hamster was infected orally by 10.000 Giardia lamblia cysts. Animal were divided into five groups: Group A: control infected, untreate group. Group B: infected receiving Metronidazole. Group C: infected and receiving Lactospore. Group D: infected and receiving combination of Metronidazole and Lactospore. Group E: receiving Lactospore 7 days before infection acting as a prophylactic group. Groups B, C and D were given the appmpriate drug, three weeks post infection. Two weeks later stool analysis was performed and cysts/gm stool were counted, after which scarification of all groups took place. There was a highly significant difference between control and all treated groups. The highest percentage of reduction [cure rate] was in group D [98.6%]. followed by group B which gave a reduction rate of [93.8 1%]. The effect of the drugs on the vegetative [trophozoite] forms in the small intestine of sacrificed hamsters was studied. Combination of both drugs [group D] revealed a high significant cure rate [99.32%]. On the other hand when metronidazole and lactospore were given alone a reduction rate of 92.22% and 63.4% respectively was observed. The prophylaxis effect of Lactospore was highly noticed with 93.65% parasite reduction. Assessment of cure was also performed by electron microscopic and histopathological examination of the small intestine, peyer's patches and the spleen. Ultrastructural examination of the small intestine revealed remarkable destruction of the intestinal cell projection by Gardia cyst. Partial healing of the destructeci intestinal cell projection by Metronidazole was obvious, while complete healing could be detected in both groups D and E, Combined treatment with metronidazole and lactospore revealed remarkable activation of lymphocytes and macrophages. This easy flow through the endothelial cells lining the sinus in its way to the lumen to enhance their opportunity to overcome the infection could be detected. Histopathological examination revealed complete healing of the intestinal mucosa after the combined treatment while partial healing of the lining epithelium of the intestine was noticed after metronidazole treatment. The present study proves the efficacy of lactospore as a prophylactic agent for Giardiasis when given 7 days pre infection. This might be of considerable interest in eases of travelers diarrhea. In addition, it can strengthen the effect of metronidazole when both drugs are given together