Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury.

Norepinephrine exacerbates renal medullary hypoxia in experimental septic acute kidney injury. Here we examined whether dexmedetomidine, an α2-adrenergic agonist, can restore vasopressor responsiveness, decrease the requirement for norepinephrine and attenuate medullary hypoxia in ovine gram-negative sepsis. Sheep were instrumented with pulmonary and renal artery flow probes, and laser Doppler and oxygen-sensing probes in the renal cortex and medulla. Conscious sheep received an infusion of live Escherichia coli for 30 hours. Eight sheep in each group were randomized to receive norepinephrine, norepinephrine with dexmedetomidine, dexmedetomidine alone or saline vehicle, from 24-30 hours of sepsis. Sepsis significantly reduced the average mean arterial pressure (84 to 67 mmHg), average renal medullary perfusion (1250 to 730 perfusion units), average medullary tissue pO2 (40 to 21 mmHg) and creatinine clearance (2.50 to 0.78 mL/Kg/min). Norepinephrine restored baseline mean arterial pressure (to 83 mmHg) but worsened medullary hypoperfusion (to 330 perfusion units) and medullary hypoxia (to 9 mmHg). Dexmedetomidine (0.5 µg/kg/h) co-administration significantly reduced the norepinephrine dose (0.8 to 0.4 µg/kg/min) required to restore baseline mean arterial pressure, attenuated medullary hypoperfusion (to 606 perfusion units), decreased medullary tissue hypoxia (to 29 mmHg), and progressively increased creatinine clearance (to 1.8 mL/Kg/min). Compared with vehicle time-control, dexmedetomidine given alone significantly prevented the temporal reduction in mean arterial pressure, but had no significant effects on medullary perfusion and oxygenation or creatinine clearance. Thus, in experimental septic acute kidney injury, dexmedetomidine reduced norepinephrine requirements, attenuated its adverse effects on the renal medulla, and maintained renal function.

Antimicrobial resistance in swine production.

Large amounts of antimicrobial agents are still being used in modern swine production in many countries around the world. This facilitates the emergence and development of antimicrobial resistance. Bacteria causing infections in swine have in several cases acquired resistance to a number of the agents most commonly used for treatment, making it difficult to predict the efficacy of different antimicrobial agents without prior susceptibility testing. This review gives an overview of recent susceptibility data from different parts of the world and discusses the importance of the development of resistance not only in the treatment of infections in swine but also taking into account the human health implications of antimicrobial resistance.

Encoded chemical synthesis coupled to screening: "Pot Assay".

A variety of screening methodologies is available to identify lead compounds. Screening methods that would permit the direct use of libraries made via the Radiofrequency Encoded Combinatorial chemistry paradigm (each individual small molecule in the library is presented separately on an individual encoded support) have the potential to diminish burdensome steps in this process. Here we report on our studies leading to such a direct method, which we have termed a Pot Assay. Pot Assay is a multiplex assay, which simultaneously measures specific binding of a number of ligands to at least one target. Pot Assay uses specific radiofrequency signals to decode compounds that are high affinity binders. We validated this approach by evaluating the interaction of biotin and its analogs with labeled streptavidin. This report introduces Pot Assay as a rapid, simple, sensitive and accurate format for identifying active members of libraries synthesized on solid supports. The success of this study demonstrates the power of coupling Radiofrequency Encoded Combinatorial chemistry and screening. This assay format may be applied to a wide range of screens that are based on binding events: ligand/receptor, inhibitor/enzyme, antigen/antibody, protein/protein, DNA/protein, and RNA/DNA.

Tumor size: effect on monoclonal antibody uptake in tumor models.

Studies were performed to determine the effect of tumor size on the incorporation of radiolabeled monoclonal antitumor antibodies (MoAbs) into human tumors growing in nude mice. The colon tumors ranged in size from 0.03-1.6 g, the melanoma from 0.1 to 6.7 g, and the lymphoma from 0.06 to 10.2 g. Indium-111 was primarily used as the radiolabel, however, both 125I and 111In were used as tracers for the MoAb in one experiment. The per g radiopharmaceutical uptake by tumors was inversely proportional to tumor size when tumor specific MoAb was administered. This finding was independent of the radiolabel and was demonstrable when the mice bore two tumors of differing size. When the MoAb was not specific for the tumor, the data were less well defined and a statistically significant correlation with size did not occur. These data are strong evidence for a decrease in per g uptake of labeled tumor specific antibodies as tumors increase in size.