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Summary A “walker” tool was developed to assist successful placement of Diaphorina citri Kuwayama (Hemiptera: Liviidae) adults at predetermined sites on citrus (Sapindales: Rutaceae) trees in behavioral bioassays. Use of the walker resulted in a significantly higher proportion of successful placements and a significantly lower number of jumps away from the predetermined site compared with the use of a brush, although on average it required an additional 108 s more than the 41 s required with the brush to complete a successful placement. Females and males performed similarly with both devices. Potentially, the walker is a useful placement tool under conditions where it is time and labor intensive to provide large numbers of insects with specific physiological characteristics for testing, e.g., when it is difficult to supply large numbers of D. citri adults of known sex, mating status, and age. Because phototaxis is commonly observed in psyllids, the walker may be of use also for bioassays with other econom...

The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as well as the peptide's absorption, distribution, and excretion. Analysis of these data support a model wherein ShK-186 is absorbed slowly from the injection site, resulting in blood concentrations above the Kv1.3 channel-blocking IC50 value for up to 7 days in monkeys. Pharmacodynamic studies on human peripheral blood mononuclear cells showed that brief exposure to ShK-186 resulted in sustained suppression of cytokine responses and may contribute to prolonged drug effects. In delayed-type hypersensitivity, chronic relapsing-remitting experimental autoimmune encephalomyelitis, and pristane-induced arthritis rat models, a single dose of ShK-186 every 2 to 5 days was as effective as daily administration. ShK-186's slow distribution from the injection site and its long residence time on the Kv1.3 channel contribute to the prolonged therapeutic effect of ShK-186 in animal models of autoimmune disease.

The Potassium Kv1.3 channel on effector memory T cells is a target to treat autoimmune diseases. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the development of methods to establish a pharmacokinetic (PK) - pharmacodynamic (PD) relationship for ShK-186, and test the hypothesis that the drug has a sustained PD effect in autoimmune disease models. The PK of ShK-186 was evaluated in rats and cynomolgus monkeys using HPLC-MS/MS and ELISA methods to measure the free fraction in plasma. These results were compared with SPECT/CT data collected with an 111In-DOTA-conjugate of ShK to assess whole blood PK parameters as well as the drug’s absorption, distribution and excretion. Our data suggest ShK-186 is absorbed slowly from the injection site resulting in blood concentrations above the Kv1.3 channel-blocking Kd for up to 7 days in monkey. PD studies on human peripheral blood mononuclear cells show that transient ShK-186 treatment results in a sustained suppression of cytokine responses and may contribute to prolonged drug effects. Moreover, in rat delayed-type hypersensitivity and chronic relapsing experimental autoimmune encephalomyelitis, a single dose of drug every 3 - 5 days is as effective as daily administration. These data suggest the PD effects of ShK-186 are governed primarily by slow distribution from peripheral tissues and long residence time on the Kv1.3 channel.