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Intestinal Muscle Effects of Clostridium Difficile Toxins
Published in William J. Snape, Stephen M. Collins, Effects of Immune Cells and Inflammation on Smooth Muscle and Enteric Nerves, 2020
The most commonly observed cellular response to Clostridium difficile toxin B exposure is the alteration of cell shape characteristically described as cell rounding. This response has been observed in several different cell types in culture, including fibroblasts and smooth muscle cells.5,6,17,18 In cultured fibroblasts exposed to toxin B, the earliest biochemical change corresponding with cytotoxity is an increase in the ratio of globular to filamentous actin, and actin disaggregation.5 The finding that toxin B had no effects on cellular actin in cell extracts led to the hypothesis that the cytotoxic effects of the toxin were based on a form of receptor-dependent transduction rather than internalization of intact toxin B, as has been previously suggested6. This does not exclude the possibility that an active subunit of toxin B may also be internalized and partially mediate morphologic and physiologic changes in the affected cells. The specific cellular target of toxin B is presently unknown. Although changes of guanosine 3,5-cyclic monophosphate have been implicated in one study as mediating the toxin B response,19 this has not been confirmed in subsequent studies.6 Whether changes of cyclic nucleotides and cytosolic calcium in combination with protein phosphorylation affect particular cytoskeletal proteins has not been determined.
Probiotics and their Effect on Maternal and Neonatal Health
Published in Martin Colin R, Derek Larkin, Probiotics in Mental Health, 2018
Caroline J Hollins Martin, Colin R Martin
Probiotics are believed to boost immune function, inhibit growth of harmful bacteria and increase resistance to some infections and disease-causing bacteria. Some evidence supports that human immune function may be facilitated by growing the number of IgA populating plasma cells, T lymphocytes, natural killer cells and improving phagocytosis in the individual (Reid et al., 2003; Ouwehand, 2002). As such, it may be advantageous to take probiotics in conjunction with antibiotics, since probiotic friendly bacteria facilitate the immune system to defend the body from pathogenic invaders. A study conducted in Pennsylvania School of Medicine (2010) found that Antibiotic Associated diarrhea (AAD) and Clostridium Difficile Infection (CDI) are common side-effects from taking broad-spectrum antibiotic therapy. In a prospective study, AAD was observed in 4.9% of patients who took long standing antibiotic medication, with 50% of participants proving positive for Clostridium Difficile toxin B (Wistrom, 2001). Since incidence of CDI is on the increase (McDonald, 2006), this emphasizes a requirement for preventative strategies to reduce rates of infection. Probiotics have been shown to reduce AAD and CDI through facilitating regeneration of intestinal microbiota, when antibiotic treatment is administered simultaneously (Hickson et al., 2007; McFarland, 2006, 2009). Evidence promotes that introducing healthy bacteria into the GI tract helps maintain immune system activity, which in sequence assists the human body to respond more rapidly to new infections. Consequently, promoting probiotic intake may be more effective than prescribing antibiotics that decrease effectiveness of the immune system by eradicating communal friendly GI tract bacteria.
Management and characteristics of patients suffering from Clostridiodes difficile infection in primary care
Published in European Journal of General Practice, 2021
Maria Klezovich-Bénard, Frédérique Bouchand, Elisabeth Rouveix, Pierre L. Goossens, Benjamin Davido
Participation rate was 8.6% (n = 43/500) with two incomplete questionnaires. Data from 41 patients with a confirmed diagnosis of CDI were used in the analyses. The large majority of CDIs (90%) were diagnosed by searching for Clostridium difficile toxin B or A by enzyme-linked immunosorbent assays (ELISA). A subsequent PCR was performed once for a patient who required hospitalisation.
How can monoclonal antibodies be harnessed against neglected tropical diseases and other infectious diseases?
Published in Expert Opinion on Drug Discovery, 2019
Before the introduction of antibiotics in the 1930s, bacterial infections were treated with animal-derived antisera comprising polyclonal antibodies [44]. These medicines presented a number of drawbacks, including a propensity to elicit adverse reactions due to the immunogenic disposition of the animal antibodies and other proteins present in the antisera, as well as difficulties in standardizing their manufacture and distribution [7]. The treatment of bacterial infections underwent a medical paradigm shift with the advent of antibiotics, such as penicillin, saving millions of lives for both humankind and livestock [2,45]. However, with the surge in antibiotic usage in the last many decades, the emergence of antimicrobial resistance now represents one of the major threats to human health [1,2]. Many of the bacterial pathogens, for which antimicrobial resistance has developed, are not strictly classified as neglected tropical diseases. However, a large number of these disease-inflicting bacteria thrive in the tropics and share many commonalities with more classical neglected tropical diseases, including poor treatment options for patients. The pathogenicity exerted by bacteria responsible for infectious diseases is often facilitated by the colonization of bacteria and production of toxic compounds that disturb the homeostasis of the host. Therefore, antibody-based therapies that target key virulence factors (toxins and adhesion/colonization factors) have successfully been developed and approved to combat bacterial infections, such as the human monoclonal antibodies Bezlotoxumab against Clostridium difficile toxin B [44,46], Raxibacumab and Obiltoxaximab against Bacillus anthracis protective antigen (co-administered with antibiotics) [47,48], and Atidortoxumab against Staphylococcus aureus alpha-toxin [49]. Common for these therapies is that they all involve intravenous administration of monoclonal immunoglobulin G (IgG) type antibodies. In the future, other antibody formats and other routes of administration, as well as the use of DNA vaccines, may find their way to the market, both for human and veterinary indications [50–55].