Background: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.
Methods: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo.
Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with a polymicrobial biofilm (subgingival plaque) accreted to the tooth which results in destruction of the tooth's supporting tissues. A characteristic feature of the disease-associated plaque is the emergence of proteolytic species. One of these species, Porphyromonas gingivalis has recently been described as a keystone pathogen as it dysregulates the host immune response to favour the polymicrobial biofilm disrupting homeostasis to cause dysbiosis and disease.
View Article and Find Full Text PDFStreptococcus pneumoniae is an important human pathogen associated with pneumonia, septicaemia, meningitis and otitis media. It is estimated to result in over 3 million child deaths worldwide every year and an even greater number of deaths among the elderly. Prior to the complete sequencing of the genomes of S.
View Article and Find Full Text PDFPneumococcal surface protein C (PspC) is a virulence factor of Streptococcus pneumoniae previously shown to play a role in bacterial adherence, invasion, and evasion of complement. We investigated the role of this protein in our murine models of pneumococcal pneumonia with different pneumococcal strains. The deletion of pspC in strains of serotypes 2, 3, and 19F did not significantly alter host survival times in the pneumonia model.
View Article and Find Full Text PDFThe important human pathogen Streptococcus pneumoniae is known to be a genetically diverse species. We have used comparative genome hybridization (CGH) microarray analysis to investigate this diversity in a collection of clinical isolates including several capsule serotype 14 pneumococci, a dominant serotype among disease isolates. We have identified three new regions of diversity among pneumococcal isolates and, importantly, clearly demonstrate genetic differences between strains of the same multilocus sequence type (ST) and capsule serotype.
View Article and Find Full Text PDFThe CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae. The system is known to regulate many genes, including that for high-temperature requirement A (HtrA). This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats.
View Article and Find Full Text PDFHtrA is a major virulence factor of Streptococcus pneumoniae (the pneumococcus). Deletion of the gene for HtrA from strain D39 of the pneumococcus completely abolished its virulence in mouse models of pneumonia and bacteremia, while the virulence of a second strain (TIGR4) was dramatically reduced. HtrA-negative mutants induced much less inflammation in the lungs during pneumonia than the wild type.
View Article and Find Full Text PDFLawsonia intracellularis has been identified recently as the etiological agent of proliferative enteropathies, which are characterized by intestinal epithelial hyperplasia and associated moderate immune responses. This disease complex has been reported in a broad range of animals, prevalently in pigs, and L. intracellularis has been linked with ulcerative colitis in humans.
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