Beknopte handleiding ‘Zorg voor dwarslaesiepatiënten’ Bij dwarslaesiepatiënten kunnen zich specifieke problemen voordoen, zoals stoornissen in vasomotoriek, sensibiliteit, blaas-/darmfunctie en seksualiteit. Speciaal voor de huisarts daarom een beknopt overzicht van aandachtspunten in de zorg voor dwarslaesiepatiënten in de chronische fase. Urineweginfecties (UWI) De symptomen v
- A |
J |K |
U |V |
Microsoft word - fact sheet - rbche_nov 2011.docRECOMBINANT HUMAN BUTYRYLCHOLINESTERASE (rBChE) FOR THE
PREVENTION AND TREATMENT OF NERVE AGENT TOXICITY
Butyrylcholinesterase (BChE) is a naturally occurring protein found in minute quantities
in human blood (2 mg/liter). BChE functions as a natural bioscavenger, like a sponge, to
absorb and degrade organophosphate poisons (e.g. nerve agents) before they cause
PharmAthene has developed a recombinant form of human butyrylcholinesterase which
is being developed as a pre- and post-exposure therapy for casualties on the battlefield or
civilian victims of nerve agent attacks.
Nerve agents belong to a class of compounds known as organophosphate (OP) agents.
OP nerve agents, such as sarin gas, soman, tabun or VX, enter the blood stream via
inhalation or absorption through the skin. The nerve agents travel in the circulatory
system to the brain and muscles causing the nerves to become over-stimulated which lead
to massive convulsions and death in severe cases.
Pyridostigmine bromide (PB) is the only FDA approved product for use as a "pre-
treatment adjunct" only for poisoning by the nerve agent, soman. It confers no protection
on its own but enhances the protection conferred by post-exposure treatment. The current
standard of care for post-exposure treatment involves repeated doses of a cocktail of
drugs including atropine, oxime reactivators (2PAM) and anti-convulsants. Available
pre-and post-treatment options are inadequate and there is a clear need for more
The Nerve Agent Threat
The potency of OP agents was recognized during World War II, when they were
developed as nerve agents for use in chemical weapons. In recent history, terrorists have
deployed nerve agents as weapons of mass destruction. The sarin nerve gas attack in the
Tokyo subway system in 1995 exposed the vulnerability of North American and
European cities to chemical weapons. Following 9/11, the U.S. government embarked
upon an intensive anti-terrorism campaign and has allocated unprecedented financial
resources through Project BioShield to develop new technologies and products to address
rBChE Mechanism of Action
The mechanism of action of rBChE is reversal of the acute toxicity associated with OP
agents used in chemical warfare (cholinergic crisis). Rescue therapy removes nerve
agents directly from the bloodstream by breaking them down into inactive components,
rather than just treating the neurotoxic symptoms, as is the case with existing therapies.
Multiple efficacy studies using a broad spectrum of live nerve agents have demonstrated
that rBChE is a potent bioscavenger of nerve agents and can act as both a prophylactic as
well as a post-exposure therapeutic.
Both the U.S. Department of Defense (DoD) and the civilian Health and Human services
(HHS) have requirements for a broad spectrum pre and post exposure prophylaxis for
nerve agent exposure. The current DoD requirement is for full force protection so the
stockpile would need to be sufficient to protect all of the branches of the military as well
as civilian first-responders.
A Phase I human safety trial using a transgenic-derived rBChE product candidate called
Protexia® was completed in 2009. The Phase I clinical study was a randomized, placebo-
controlled, third-party double-blind, dose-escalating study conducted to assess the safety
and tolerability of Protexia administered intramuscularly at one or two time points in
healthy human volunteers.
A second generation Advanced Expression System (AES) rBChE using a human cell line
is now being actively developed with support and funding from the U.S. DoD. This
program will allow for the production of a significant number of doses of human-like
rBChE at a fraction of the cost of a human plasma derived product. It is believed that this
program will move into pre-clinical and clinical development rapidly as a result of the
experience gained with the Protexia program.
What Is Cholesterol-Lowering Medicine? If your doctor has decided that you need to take medicine to reduce high cholesterol, it’s because you’re at high risk for heart disease or stroke. Usual y the treatment combines diet and medicine. Most heart disease and many strokes are caused by a buildup of fat, cholesterol and other substances cal ed plaque in the inner wal s of your arteries. Th