The cause of CD remains unknown. Recent advances in the pathogenesis of CD involve interactions of three elements: genetic factors, enteric microflora and immune-mediated tissue injury. Furthermore cigarette smoking has been described as the main risk factor for relapse and poor evolution of the disease [1]. Genetic Factors

CD appears to have a genetic tendency, with multiple susceptibility genes. The first susceptibility locus for CD, which was found in replica-tive studies worldwide [2, 3], is on the pericen-tromeric region of chromosome 16 (IBD1 locus). Mutations of the NOD2 gene in this region have been conclusively associated with CD. Homo-zygosity and compound heterozogosity increase the relative risk of developing CD by 20- to 40-fold compared to non-NOD2-mutated subjects. Nods proteins are thought to be cytosolic receptors for pathogenic bacterial signals. Nod2 recognizes muramyl dipeptide (MDP) [4], a conserved structure in bacterial peptidoglycan. Nod2 is expressed in monocytes and activates nuclear factor kappa B (NF-kB), which is a key transcriptional factor involved in the initiation of the inflammatory response [5]. Since NOD2 variants seem to account for less than 20% of CD, other candidate susceptibility genes need to be investigated. Enteric Microflora

The absence of evidence for transmission of either CD or ulcerative colitis argues against a transmissible infectious etiology. However, there are several pieces of indirect evidence that commensal microflora contribute to the patho-genesis of CD, such as:

1. The failure of induction of colitis in germ-free animals [6]

2. The occurrence of inflammatory bowel disease (IBD) lesions in areas of greatest bacterial exposure

3. The induction of relapse in ileal CD by the fecal stream [7]

4. The difference of fecal and mucosal flora composition between patients with CD and healthy subjects [8]

5. The loss of tolerance to the components of endogenous flora in patients with CD [9]

6. The influence of antibiotics and probiot-ics in experimental animals and in some clinical situations (postoperative relapse of CD) [10]. Immune-Mediated Tissue Injury

Host-microbial interactions involve commensal species that reside permanently within the gastrointestinal tract and this adaptation actively contributes to immunological tolerance and homoeostasis within the healthy gut. Molecular mechanisms of this prokaryote/eukaryote crosstalk involve different bacterial signals and pattern recognition receptors (PPRs) such as tolllike receptors (TLRs) and NODs [11]. The bacterial stimuli represent a cluster of various signals called pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), peptidoglycans and bacterial nucleic acids (CpG DNA). TLR are key regulators of the innate immune response, and different changes in selective epithelial expression of TLRs have been reported to occur in CD [12]. In CD tissue damage arises from excessive TH1 cytokine responses or a failure to turn off such responses after pathogenic infection in genetically susceptible individuals. Additionally, cytokines act on local microvasculature, upregulate adhesion molecules and facilitate the recruitment of neutrophils and phagocytes, which contribute to the amplification of the inflammatory response and further tissue damage. In healthy individuals, activated mucosal T cells are controlled through regulatory T cells and apoptosis pathways, both of which seem to be defective in patients with CD [13].

A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

Get My Free Ebook

Post a comment