Porphyromonas gingivalis is one of the principal organisms associated with adult periodontitis. Bacterial surface proteins such as fimbriae and gingipain hemagglutinin domains have been implicated as adhesins that actuate colonization of epithelium lining the gingival sulcus. We investigated the genetics of P. gingivalis adhesion to monolayers of epithelial cells using wild-type and gingipain mutant strains. These experiments suggested that arginine-specific gingipain (Rgp) catalytic activity modulated adhesion. From the data obtained with rgp mutants, we constructed a working hypothesis predicting that attachment and detachment of P. gingivalis to epithelial cells were mediated by gingipain adhesin and Rgp catalytic domains, respectively. A membrane-based epithelial cell binding assay, used to locate adhesins in extracellular fractions of wild-type and mutant strains, recognized gingipain peptides as adhesins rather than fimbriae. We developed a capture assay that demonstrated the binding of gingipain adhesin peptides to oral epithelial cells. The adherence of fimbrillin to epithelial cells was detected after heat denaturation of cell fractions. The prediction that Rgp catalytic activities mediated detachment was substantiated when the high level of attachment of an rgp mutant was reduced in the presence of wild-type cell fractions that contained gingipain catalytic activities.Porphyromonas gingivalis, a gram-negative anaerobe present in subgingival plaque, is one of the bacteria strongly associated with adult periodontitis. The molecular mechanisms leading to colonization of the epithelium that lines the gingival sulcus are poorly understood. Fimbria-deficient mutants of P. gingivalis showed reduced attachment to and invasion of oral epithelial cells (24,36,40). In addition, cysteine proteinase (gingipain) hemagglutinin domains have been implicated in tissue colonization either directly through adhesion to extracellular matrix proteins (17, 31) or indirectly by processing the fimbrillin subunit of fimbriae (23). Gingipains are secreted proteins found on the bacterial cell surface, associated with extracellular vesicles, and in culture supernatants. Gingipain genes rgpA and rgpB encode Arg-gingipains (Rgp) A and B, respectively. These enzymes possess arginine-specific amidolytic activity, while a third gene, kgp, encodes an enzyme with lysine-specific amidolytic activity (Lys-gingipain [Kgp]). The Rgp isozymes contain propeptide and catalytic domains, but only RgpA contains a carboxy-terminal extension known as the adhesin domain (Fig. 1). Kgp also contains propeptide, catalytic, and adhesin domains, and the latter shares over 97% homology with the adhesin domain of RgpA (4). Within this family is an additional gene encoding a surface protein, hemagglutinin A. hagA contains three or four copies of a 1.35-kb direct repeat (15) encoding protein sequences that also contain homology to the adhesin domains of RgpA and Kgp. Autoprocessing of the adhesin domains yields a series of peptides (Fig. 1), and it has been de...
In patients with scar-related VT undergoing catheter ablation, pLVAD support was able to safely maintain end-organ perfusion despite extended periods of hemodynamically unstable VT. Randomized studies are necessary to determine whether this enhanced ability to perform entrainment and activation mapping will translate into a higher rate of clinical success.
Background: Transcatheter Aortic Valve Replacement (TAVR) is a new minimally-invasive surgical procedure in which a bioprosthetic aortic valve is placed via a small skin incision in the groin, over either the left or right iliac artery. TAVR was recently approved by the FDA as a treatment option for aortic stenosis in patients who may be too frail to undergo open heart surgery. Anesthetic management of TAVR is complicated by the fact that rapid left ventricular pacing (to at least 180 beats per minute) is required at multiple points throughout the procedure. Aim: This rapid pacing creates a profound pathophysiologic stress on the heart, sometimes leading to severe left ventricular dysfunction and resultant complete hemodynamic collapse. We report that the use of prophylactic infusion of epinephrine and/or norepinephrine in patients undergoing TAVR results in improved recovery from rapid pacing as reflected by intraoperative trends in systolic systemic blood pressure and systolic pulmonary arterial pressure. Cases: Here we report three cases. During the first of these, we reacted to intraoperative hemodynamic changes by administering boluses of vasoactive medications as needed. During the other two cases, we preemptively infused vasopressors to facilitate a more rapid recovery from some of the hemodynamic disturbance associated with either TAVR or rapid pacing. Conclusion: The two patients in this series who were managed with a preemptive strategy had higher ratios of systemic systolic blood pressure to pulmonary arterial systolic blood pressure at the end of the case than did the patient who was managed reactively. This suggests that the preemptive strategy may lead to decreased left ventricular impairment and improved overall cardiac function after TAVR. W. Bethune et al.
In order to optimize anesthetic management and avoid adverse maternal and fetal outcomes, a clear understanding of the changes in cardiovascular physiology that occur during pregnancy is paramount. The effects of normal gestation on the cardiovascular system are particularly significant in a parturient with cardiac valvular pathology. We present a case of a 27-year-old G2P0 at 37 weeks with a past medical history of diabetes, macrosomia, congenital bicuspid aortic valve with severe stenosis (valve area 0.7 cm2) who was scheduled for elective C-section. A multidisciplinary discussion involving cardiologists, cardiac surgeons, obstetric surgeons, neonatal intensivists, perfusion staff, anesthesiologists, and nursing staff was held to formulate a plan for the perioperative management of this parturient. Also, contingency plans were formulated and discussed with the care providers, in the event of acute decompensation of the mother and baby and possible need for emergency aortic valvuloplasty and/or aortic valve replacement.
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