c Clostridium difficile is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for C. difficile infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for Clostridium difficile pathogenesis. Given the toxin-centric mechanism by which C. difficile pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat C. difficile-associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB in vitro. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic-or chemotherapy-induced C. difficile infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB.C lostridium difficile is a leading cause of antibiotic-associated diarrhea (AAD) and is the etiologic agent responsible for C. difficile-associated infection (CDI). CDI typically starts as a mild diarrhea but rapidly degenerates into a variety of potentially lifethreatening conditions, including sepsis syndrome and pseudomembranous colitis (1). In the United States, approximately 330,000 cases of CDI are estimated to occur each year (2); however, the incidence of C. difficile infection continues to increase (2, 3). The increasing CDI rates highlight the fact that the current infection control procedures and treatment options are insufficient.In the health care setting, C. difficile endospores are transmitted to patients via the fecal-oral route (4). Following exposure, the host's gastrointestinal microbiota typically either quells a nascent C. difficile infection or suppresses it to subclinical levels (5). As a result of the latter, approximately 20% of hospitalized adults become asymptomatic C. difficile carriers, and the carriage rates approach 50% for patients in long-term care (6-9). The likelihood of development of CDI increases in patients with dysbiotic gastrointestinal microbiota, since C. difficile can thrive in the dysbiotic niche (5, 10). This dysbiosis is often the result of nonspecific chemotherapies that are used to treat conditions unrelated to C. difficile infection (e.g., antibacterial agents or antineoplastic drugs).The antibiotics metronidazole and vancomycin are currently used to treat CDI (11). Unfortunately, given the conflicting roles of antibiotics in the establishment and resolution of CDI, C. difficile AAD recurs in up to 1 in 5 patients (12)...
). Hardcover and softcover, 326 pages.Most, if not perhaps all, models of language and literacy in mainstream scholarship are constructed exclusively within human parameters, whether this is done through claims to representation, or through interpretation, construction, or deconstruction. The road one walks with David Abram, however, takes a different pathto the very grounding of language in a sensuous world that exists as "more than human." Abram takes us directly into the realms of sensuous perception within reciprocal relations with one's surroundings, relations that give rise to utterances, to language, to literacy.Reading Abram's award-winning book, the reader is in for a treat of superb quality. (Abram is an ecologist and philosopher, who received a doctorate in philosophy from SUNY-Stony Brook.
INTRQDUCTION: Opiates are hypothesized to cause a vasodepressor effect by acting on the rostral vantrolateral medulla (RVLM) wherein lie neurons which control sympathetic tone. Using voltammetry which measures catecholamine oxidation currents (CA.OC) generated by adrenergic activity in these neurons, our objective was to demonstrate the in vivo effect of morphine on the RVLM. METHODS: Halothane anaesthetized rats were implanted stereotaxically with carbon-fibre electrodes to monitor CA-OC by differential normal pulse voltammetry. Mean arterial pressure (MAP) was monitored by a femoral arterial line. After stabilization, rats received either intracerebroventricular (icy) morphine 10/zg (n =5) followed 45 minutes later by intravenous (iv) naloxone 1 mg-kg" or icy saline 5/Jl (n=5) followed by iv saline 0.45 ml. Changes in MAP and CA. OC were compared to baseline. RESULTS: The CA-OC was maximally depressed by 39 percent 45 minutes following morphine (Fig 1). Naloxone reversed the effects of morphine and produced a significant 21 percent rebound increase in the CA.OC. MAP was maximally depressed by 21 percent 45 minutes following morphine (Fig 1). This decrease in MAP was reversed by naloxone. Saline treatment had no significant effect on the CA.OC (ANOVA, p=0.321) or MAP (ANOVA, p=.531). Fig 1 40 30 Change 20 from lO Baseline o (percent)-lO-20-3O-40 n CA'OC naloxone 9 MAP r (mean + SEM) 9 , , , Y '* ,p < 0.05; Dunnstt's 0 15 30 45 60 75 90 Time (rain) DISCUSSION: An increase in the CA.OC in the RVLM accompanies induced hypotension possibly by way of a baroreceptor reflex. However, our results suggest that morphine depresses adrenergic neurons in the RVLM to produce a vasodepressor effect. The rebound effect following the antagonism of morphine with iv naloxone is analogous to the observation of excessive sympathetic activity in post-operative patients receiving naloxone. This acute opiate withdrawal phenomenon is possibly mediated through the RVLM and if so, it may be prevented by attenuation of activity in this area. REFERENCES= i.
Exploratory measurements of the 4.43-Mev gamma rays from the reaction C^o^OC 12 * and of the total cross section for the reaction C u (a,n)0 16 for incident energies between 15 and 19 Mev are reported. The two excitation curves appear somewhat anticorrelated, the maxima of the O 15 yield occurring at 15.5, 16.6, 17.3, and 18.5 Mev, those of the gamma-ray yield at 15.9 and 18.0 Mev. There is no evident correlation between these curves and the differential (a,p) cross section reported by Priest, Tendam, and Bleuler.
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