Impact of an Intravenous Magnesium Shortage on Potassium Doses in Adult Surgical Patients Receiving Parenteral Nutrition

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141001/1/jpen0688.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141001/2/jpen0688-sup-0001.pd

A Pilot Study Assessing Pharmacokinetics and Tolerability of Oral and Intravenous Baclofen in Healthy Adult Volunteers

Abstract Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P ¼ .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three-and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures

AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness.

Across bacterial species, metal binding proteins can serve functions in pathogenesis in addition to regulating metal homeostasis. We have compared and contrasted the activities of zinc (Zn2+)-binding lipoproteins AdcA and AdcAII in the Streptococcus pneumoniae TIGR4 background. Exposure to Zn2+-limiting conditions resulted in delayed growth in a strain lacking AdcAII (ΔAdcAII) when compared to wild type bacteria or a mutant lacking AdcA (ΔAdcA). AdcAII failed to interact with the extracellular matrix protein laminin despite homology to laminin-binding proteins of related streptococci. Deletion of AdcA or AdcAII led to significantly increased invasion of A549 human lung epithelial cells and a trend toward increased invasion in vivo. Loss of AdcAII, but not AdcA, was shown to negatively impact early colonization of the nasopharynx. Our findings suggest that expression of AdcAII affects invasiveness of S. pneumoniae in response to available Zn2+ concentrations

Dot blot demonstrating lack of laminin binding by AdcAII.

<p>A) Laminin (2 μg, 5 μg, and 10 μg spots) or anti-AdcAII antibody (1:100, 1:1000, 1:5000 spots) as control were probed with biotinylated recombinant AdcAII protein. B) To demonstrate laminin could interact with ligands using this method laminin protein (2 μg, 5 μg, and 10 μg spots) or anti-laminin receptor antibody (1:100, 1:1000, 1:5000 spots) as a control probed with recombinant laminin receptor and developed with anti-LR antibody.</p

Effect of AdcA and AdcAII on adhesion and invasion in A549 cell line.

<p>A) Adhesion relative to T4R (100% representing approximately 0.9% of inoculum adhered). Bacteria were incubated with A549 cells for 30 mins in 24-well plates and adherent bacteria were quantitated. ** = P<0.0005. B) Invasion relative to T4R (100% representing approximately 0.03% of inoculum invaded). Bacteria were incubated for 2 hrs with A549 cells, followed by 1 hr in the presence of antibiotics to kill extracellular bacteria; cells were lysed, and intracellular bacteria were quantitated. * = P<0.005 and ** = P<0.0005. C) Fluorescent images of A549 cells incubated with T4R, ΔAdcA ΔAdcAII, ΔAdcAII+ as in B. Cells were washed, permeabilized, and bacteria were stained with anti-TEPC-15 antibody (in red). Cell nuclei are stained with DAPI (blue). D) Invasion relative to T4R (%). Bacteria were incubated for 2 hrs with A549 cells with 200μM ZnSO₄, followed by 1 hr in the presence of antibiotics to kill extracellular bacteria; cells were lysed, and intracellular bacteria were quantitated. All experiments were conducted at least three times. Each experiment consisted of triplicate sample wells.</p

Western blot assessing pilus SP0463 expression.

<p>Lysates from T4R, ΔAdcA, and ΔAdcAII strains were blotted and probed with anti-SP0463 antibody and developed. Black arrow indicates SP0463 pilus monomer.</p