The Feinstein Institutes for Medical Research

The General Hospital Corporation

University of Pittsburgh

Howland Shaw Warren

Kevin J Tracey

Mitchell P Fink

Huan Yang

Michael Allen Faltys

Jared M Huston

Christine N Metz

Christopher J Czura

Carol Ann Amella

Devices, systems and methods for stimulating (e.g., noninvasively) a subject's inflammatory reflex are provided to reduce bleed time. The method may include the step of non-invasively stimulating the inflammatory reflex (e.g., the vagus nerve, the splenic nerve, the hepatic nerve, the facial nerve, and the trigeminal nerve) of a subject, such as by mechanical stimulation, in a manner which significantly reduces bleed time in the subject. Devices for non-invasively stimulating the inflammatory reflex may include a movable tip or actuator that is controlled to mechanically stimulate the ear. The devices may be hand-held or wearable, and may stimulate the cymba conchae region of the subject's ear.

Treatment of bleeding by non-invasive stimulation

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

Antibodies to high mobility group-1(HMGB1) B-box polypeptides

Described herein are methods, devices and systems for inhibition of granulocyte activation by appropriate stimulation of the vagus nerve. Methods of treating granulocyte-mediated disorders (including inflammatory disorders) by stimulating the vagus nerve to inhibit granulocyte activation (particularly neutrophil activation) are also described. Appropriate stimulation may be very low levels of stimulation, including stimulation that does not result in desensitization. The level of granulocyte activation may be detected and used to at least partially control stimulation.

Devices and methods for inhibiting granulocyte activation by neural stimulation

Use of HMGB fragments as anti-inflammatory agents

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Cambridge, MA, United States of America

Howland Shaw Warren