Germline mutations of the adenomatous polyposis coli (APC) gene in Algerian familial adenomatous polyposis cohort: first report.

BACKGROUND: Familial adenomatous polyposis (known also as classical or severe FAP) is a rare autosomal dominant colorectal cancer predisposition syndrome, characterized by the presence of hundreds to thousands of adenomatous polyps in the colon and rectum from an early age. In the absence of prophylactic surgery, colorectal cancer (CRC) is the inevitable consequence of FAP. The vast majority of FAP is caused by germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene (5q21). To date, most of the germline mutations in classical FAP result in truncation of the APC protein and 60% are mainly located within exon 15. MATERIAL AND METHODS: In this first nationwide study, we investigated the clinical and genetic features of 52 unrelated Algerian FAP families. We screened by PCR-direct sequencing the entire exon 15 of APC gene in 50 families and two families have been analyzed by NGS using a cancer panel of 30 hereditary cancer genes. RESULTS: Among 52 FAP index cases, 36 had 100 or more than 100 polyps, 37 had strong family history of FAP, 5 developed desmoids tumors, 15 had extra colonic manifestations and 21 had colorectal cancer. We detected 13 distinct germline mutations in 17 FAP families. Interestingly, 4 novel APC germline pathogenic variants never described before have been identified in our study. CONCLUSIONS: The accumulating knowledge about the prevalence and nature of APC variants in Algerian population will contribute in the near future to the implementation of genetic testing and counseling for FAP patients.

Beneficial role of Pistacia lentiscus aqueous extract in experimental colitis: anti-inflammatory and potential therapeutic effects.

BACKGROUND: Pistacia lentiscus L. (PL) is a flowering plant traditionally used in the treatment of gastrointestinal disorders. The extracts of this plant are endowed with strong pharmacological activities. The aim of our current study was to investigate the anti-inflammatory and potential therapeutic effects of PL leaves aqueous extract (PLAE) against Dextran Sulfate Sodium (DSS)-induced acute colitis. MATERIALS AND METHODS: The therapeutic effect of PLAE was evaluated after orally administration of 3% DSS alone or concomitantly with PLAE (50, 100 or 200 mg/Kg). Mucosal lesions were assessed by macroscopic and histopathological examination. In this context, hemorrhage, diarrhea, weight loss, and disease activity index (DAI) were determined daily throughout the experiment. In the same way, hematoxylin-eosin and Alcian blue staining of colonic mucosal were used to evaluate, respectively, mucosal damages and mucus production. Furthermore, the levels of nitric oxide (NO), and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were measured in plasma, as well as in colonic explants and peritoneal macrophages cultures supernatants. RESULTS: Administration of DSS + PLAE indicated a significant reduction in clinical score of acute colitis DAI compared to DSS alone administration. Interestingly, histological analysis of the mucosa showed that DSS + PLAE-treated groups exhibited almost normal histology evidenced by an intact epithelium structure and less inflammatory cell infiltration in the mucosa. Alcian bleu staining revealed that DSS + PLAE-treated groups displayed almost normal mucus production. Importantly, a significant decrease in pro-inflammatory mediators (NO, IL-6 and TNF-α) levels in dose-dependent manner was reported in plasma, and culture supernatants of colonic explants and peritoneal macrophages from DSS + PLAE-treated mice compared to the DSS group. CONCLUSION: Our results showed that the systemic and local anti-inflammatory activities of aqueous leaves extract of PL improve the clinical signs of acute colitis. Our data suggest that PLAE has beneficial effects and could constitute a promising approach against acute ulcerative colitis by targeting the deregulated immune response.

Gastro-protective, therapeutic and anti-inflammatory activities of Pistacia lentiscus L. fatty oil against ethanol-induced gastric ulcers in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia lentiscus L. (Anacardiaceae) (PL) is a flowering plant that grows in the Mediterranean area. It is traditionally used in the treatment of various skin, respiratory and gastrointestinal disorders AIM OF THE STUDY: In the present study, we investigated the anti-ulcerogenic activity of Pistacia lentiscus fatty oil (PLFO) on ethanol-induced gastric ulcers in Wistar rats MATERIAL AND METHODS: PLFO was orally administered to two experimental groups of rats before or after ethanol induction of gastric ulcer. The lesions of the gastric mucosa were evaluated by macroscopic and histopathological examination. In addition, the amount of nitric oxide (NO) and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the supernatant from cultures of gastric mucosa explants were assessed. Finally, the mucus production and iNOS (inducible NO synthase) expression were determined by histochemical and immunohistochemical analysis, respectively RESULT: Our results indicated that the PLFO pretreatment or PLFO treatment significantly reduced ulcerated and hemorrhagic areas. Additionally, pretreatment or treatment with PLFO after ethanol-induced ulceration significantly reduced the plasma concentration of NO. Furthermore, a significant decrease of NO, IL-6 and TNF-α levels was observed in explant culture supernatants. iNOS expression was also reduced in the gastric mucosa. In contrast, mucus production by goblet cells was enhanced. Interestingly, histological analysis of the gastric mucosa has indicated that PLFO- pretreated and treated groups displayed normal histology CONCLUSION: Our results demonstrate that PLFO display significant prophylactic and therapeutic effects against gastric ulcers. Importantly, the mechanism underlying PLFO activities might implicate inhibition of inflammatory responses during gastric ulcer.

High-Level Primary Clarithromycin Resistance of Helicobacter pylori in Algiers, Algeria: A Prospective Multicenter Molecular Study.

Knowledge of local antibiotic resistance is crucial to adaptation for the choice of the optimal first-line treatment for Helicobacter pylori infection. Clarithromycin is a key component of the standard triple therapy largely used worldwide and, more particularly, in Algeria. Clarithromycin resistance is the main risk factor for treatment failure. The aim of this study was to evaluate, for the first time in Algeria, the prevalence of the primary resistance of H. pylori to clarithromycin. We conducted a prospective study (2008-2014) that included 195 Algerian patients referred for gastroduodenal endoscopy to two University Hospitals, one General Hospital, and several private gastroenterologists in Algiers (Algeria). One gastric biopsy was collected for the molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin with a quadruplex real-time PCR using Scorpion primers. The Scorpion PCR detected H. pylori DNA in 91 biopsies (47%). A mutation conferring resistance to clarithromycin was detected in 32 of the 91 positive patients (35%) and in 29 of the 88 positive patients never previously treated for an H. pylori infection (33%). The prevalence of primary resistance of H. pylori to clarithromycin was 33% in the Algerian population being studied. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Algerian population that we report leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Algeria.