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Recognizing the urgent need for an up-to-date review of new and
innovative research on growth hormone (GH) secretagogues, this
exclusive work furnishes the state of the art on the mechanisms of
action, design, synthesis, evaluation, and clinical applications of
GH secretagogues, including orally active and xenobiotic
GH-releasing compounds. Beginning with a thorough historical
perspective on the discovery and evolution of GH-releasing peptides
(GHRPs) as therapeutic agents, Growth Hormone Secretagogues in
Clinical Practice analyzes structural requirements for GH
secretagogue efficacy demonstrates the use of mathematical models
to predict differential values of individual stimuli for GH
secretion from the pituitary reports on the development of a simple
screening system based on polyclonal antibodies discusses
laboratory synthesis of agonistic analogs intended for human and
veterinary use proposes applications in managing conditions such as
Turner's syndrome, acromegaly, diabetic retinopathy,
glomerulosclerosis, tumors, and cancer provides physiological
evidence for the effects of GHRP on behavior with a series of
trials involving voluntary and forced exercise describes a new
diagnostic test for evaluating pituitary function in slowly growing
children and aging adults explores the interactions of GH
secretagogues with other hormones and endogenous substances from
sex steroids to interferons and much more!
Recognizing the urgent need for an up-to-date review of new and
innovative research on growth hormone (GH) secretagogues, this
exclusive work furnishes the state of the art on the mechanisms of
action, design, synthesis, evaluation, and clinical applications of
GH secretagogues, including orally active and xenobiotic
GH-releasing compounds. Beginning with a thorough historical
perspective on the discovery and evolution of GH-releasing peptides
(GHRPs) as therapeutic agents, Growth Hormone Secretagogues in
Clinical Practice -analyzes structural requirements for GH
secretagogue efficacy -demonstrates the use of mathematical models
to predict differential values of individual stimuli for GH
secretion from the pituitary -reports on the development of a
simple screening system based on polyclonal antibodies -discusses
laboratory synthesis of agonistic analogs intended for human and
veterinary use -proposes applications in managing conditions such
as Turner's syndrome, acromegaly, diabetic retinopathy,
glomerulosclerosis, tumors, and cancer -provides physiological
evidence for the effects of GHRP on behavior with a series of
trials involving voluntary and forced exercise -describes a new
diagnostic test for evaluating pituitary function in slowly growing
children and aging adults -explores the interactions of GH
secretagogues with other hormones and endogenous substances from
sex steroids to interferons -and much more!
This book is a compendium of proceedings from the Symposium on
Growth Hormone II: Basic and Clinical Aspects. The intent of the
sym posium was to review current aspects of the rapidly expanding
science of growth hormone (GH) neuroendocrinology, especially those
develop ments that occurred since our last meeting in 1985. The
meeting was timely since there have been many new and exciting
developments in basic research on the GH axis, and several new
clinical applications for GH other than growth have been
identified. For example, significant strides have been made into
use of the bioengineered hormone as an anabolic in debilitated
states and as an immunorestorative agent. Both these areas have
received most attention as they relate to geriatric popu lations.
Furthermore, recent focus on a novel family of GH secretagogues
that complement the action of GHRH has shown that in animal models,
these compounds have the potential to restore GH secretion in
deficient or insufficient states, including growth retardation,
obesity, and aging. Accordingly, these xenobiotics may have
significant potential as drug products to stimulate physiological
GH secretion and, thus, resist or reverse some of the maladaptive
changes in form and function resulting from GH insufficiency. The
importance of these agents as drug candidates is underscored by the
diversity of molecules that have been studied by various
pharmaceutical companies and the recent discovery that non peptide
analogs with high oral bioavailability can be synthesized."
The traditional concept of a neuroendocrine mechanism for
regulation of growth hormone (GH) secretion is based in large part
on the work of Roger Guillemin. The work of Dr. Guillemin, who was
awarded the 1977 Nobel Prize in Physiology and Medicine, supported
the view that quantita tive change in GH secretion was the net
result of pituitary stimulation and inhibition by the hypothalamic
neurohormones, GH releasing hormone (GHRH), and somatostatin
(somatotropin release inhibiting factor; SRIF), respectively.
During the 1970s, another endocrine research pioneer, Dr. Cyril
Bowers, discovered that structural modification of enkephalin re
sulted in a family of peptides with GH releasing properties. These
com pounds, simply called GH releasing peptide (GHRP), were
originally thought to mimic GHRH. However, upon subsequent
investigation they were found to supplement the activity of the
natural hormone through a different mechanism. Nearly two decades
after their discovery, the differ ences between GHRP and GHRH have
been described by many different laboratories throughout the world.
The complementary GH secretagogues have different binding sites,
second messengers, and effects on gene expres sion. Based on these
differences, it has been suggested that expansion of the original
two hormone mechanisms for GH regulation to include a third
molecule may be appropriate, even though the naturally occurring
ana logue of GHRP has not yet been identified. Despite our lack of
knowledge concerning the natural product mimicked by GHRP, clinical
development of the new family of GH secretagogues for diagnostic
and therapeutic purposes has begun in earnest."
Since the fall of the Soviet Union and the end of the Cold War, the
United States has found itself involved in an increasing number of
small scale interventions in support of national objectives,
humanitarian efforts, and United Nation resolutions. Interventions
have been manpower intensive and have increased the burden on our
military forces. The dilemma the US finds itself in today is
similar to the problem faced by Great Britain as she tried to
maintain control of her empire after World War I. The solution
developed by the British was the concept of "Air Control," intended
to minimize both the number of ground troops required to maintain
order in the colonies, and their associated expense. Airpower would
not replace the ground units, but it would significantly reduce the
required forces by increasing the mobility and firepower support
available to ground garrisons. As the United States takes on
increasing numbers of operations around the world, it too has
increasingly shifted toward a policy of using airpower to maintain
control while minimizing the footprint and cost of the operation.
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