Antioxidant, anti-inflammatory, and microbial-modulating activities of essential oils: Implications in colonic pathophysiology

Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. However, there are still few clinical studies aimed to understand their role in the modulation of the intestinal pathophysiology. Many EOs and some of their molecules have demonstrated their efficacy in inhibiting bacterial, fungi and virus replication and in modulating the inflammatory and oxidative processes that take place in experimental colitis. In addition to this, their antitumor activity against colorectal cancer models makes them extremely interesting compounds for the modulation of the pathophysiology of the large bowel. The characterization of these EOs is made difficult by their complexity and by the different compositions present in the same oil having different geographical origins. This review tries to shift the focus from the EOs to their individual compounds, to expand their possible applications in modulating colon pathophysiology

Infliximab in the treatment of Crohn's disease

The recent introduction of infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha, has greatly modified the treatment of Crohn's disease (CD). Data from the literature show encouraging results after intravenous infusion both for closure of intestinal or perianal fistulas and for induction and maintenance of remission in patients with moderate to severe intestinal disease unresponsive to other treatments. However, some contraindications such as fibrostenosing CD and sepsis have been identified. In addition, the data on long-term outcomes and safety is still limited. Our initial experience showed that in selected cases local injection of infliximab is effective in the treatment of complex perianal disease offering the possibility of using such treatment even in small bowel obstructing disease with minimal systemic effects. This paper analyzes the state of the use of both intravenous and local injection of infliximab in patients with CD

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study.

AIM: To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis. METHODS: In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function

Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis

AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls. RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study.

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study

Lactobacillus GG in inducing and maintaining remission of Crohn's disease

BACKGROUND: Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. METHODS: Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 × 10(9 )CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. RESULTS: 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group (p = 0.5). CONCLUSION: In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD

Rhinosinusitis derived Staphylococcal enterotoxin B possibly associates with pathogenesis of ulcerative colitis

BACKGROUND: During clinical practice, we noticed that some patients with both ulcerative colitis (UC) and chronic rhinosinusitis (CRS) showed amelioration of UC after treatment of CRS. This study was designed to identify a possible association between CRS and UC. METHODS: Thirty-two patients with both CRS and UC received treatment with functional endoscopic sinus surgery (FESS) for CRS. Clinical symptom scores for CRS and UC, as well as serum levels of anti-Staphylococcal enterotoxin B (SEB) were evaluated at week 0 and week 12. Sinus wash fluid SEB content was measured with enzyme-linked immunosorbent assay (ELISA). The surgically removed tissues were cultured to identify growth of Staphylococcus. aureus (S. aureus). Immunohistochemistry was employed to identify anti-SEB positive cells in the colonic mucosa. Colonic biopsies were obtained and incubated with SEB. Mast cell activation in the colonic mucosa in response to incubation with SEB was observed with electron microscopy and immunoassay. RESULTS: The clinical symptom scores of CRS and UC severe scores (UCSS) were significantly reduced in the UC-CRS patients after FESS. The number of cultured S. aureus colonies from the surgically removed sinus mucosa significantly correlated with the decrease in UCSS. High levels of SEB were detected in the sinus wash fluids of the patients with UC-CRS. Histamine and tryptase release was significantly higher in the culture supernate in the patients with UC-CRS than the patients with UC-only and normal controls. Anti-SEB positive cells were located in the colonic mucosa. CONCLUSION: The pathogenesis of UC in some patients may be associated with their pre-existing CRS by a mechanism of swallowing sinusitis-derived SEB. We speculate that SEB initiates inappropriate immune reactions and inflammation in the colonic mucosa that further progresses to UC

Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells

Colorectal cancer (CRC) has an elevated incidence worldwide and represents one of the most aggressive human tumours. Many experimental data provide the evidence of a strong association between cyclooxygenase-2 (COX-2) enzyme overexpression and colon tumorigenesis. Furthermore, it has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs, a class of COX-2 inhibitors), partially protects patients from CRC development and progression. Unfortunately, NSAIDs have been shown to induce severe side effects in chronically treated patients and, therefore, new strategies for selective COX-2 blockade are needed. In this paper we present an innovative COX-2 silencing approach mediated by RNA Interference (RNAi) which is a mechanism we have already described as a powerful tool to knockdown COX-2 protein in CRC cells. In particular, we developed an improved method to gain a highly selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short hairpin RNA (shCOX-2). Moreover, we efficiently delivered shCOX-2 expressing vectors in CRC cells, in vitro and ex vivo, by using engineered Escherichia coli strains, capable of infecting and invading human tumour cells (InvColi). Combining the highly selective shCOX-2 expression and the delivery of COX-2 silencers mediated by InvColi strains, we obtained a strong reduction of both proliferative and invasive behaviour of tumour cells and we also confirmed the pivotal role of COX-2 overexpression for the survival of CRC cells. Finally, ex vivo data showed a global anti-inflammatory and anti-tumour effect elicited by COX-2 silencing