Complementary and Alternative Medicine Research for Military Operations and
Healthcare [MIL-CAM]
Program Description: The Complementary and Alternative Medicine Research for
Military
Operations and Healthcare (MIL-CAM) systematically identifies and
investigates selected areas of Complementary and Alternative Medicine for
enhancing and maintaining military personnel readiness, effectiveness and
well-being, and for the mitigation of damage from battlefield and terrorist
attack. The program is run under contract for the Department of Defense.
Background and Rationale: Complementary and alternative or integrative medicine
[CAM] is a new area for scientific investigation, especially for the military.
The 1999 National Health Interview Survey of more than 30,000 U.S. adults found
that 29% had used some form of CAM within the past year. Nearly 50% of military
veterans were recently shown to use CAM therapies. The Department of Defense has
been mandated by Congress to provide chiropractic benefits to both enlisted
personnel and veterans, and acupuncture services are available at some clinical
sites.
CAM is regularly used by the American public and the military, including its
incorporation into military hospitals, clinics, field units and self-care
practices. In addition, a substantial number of soldiers and their families go
outside military health care facilities to obtain CAM services and products. It
has been estimated that up to a third of the military may be using a CAM product
or practice in any given year. Very few of these products or practices have
been evaluated for their safety, efficacy and impact on readiness, performance
and disease. Rapid, flexible and efficient investigation of these practices is
needed.
This need for a full range of research methods and services and flexibility in
their application has been written about extensively by the director of the SIIB
and others. The range of research methods that need to be applied in a
coordinated manner include theory development, basic and laboratory research,
outcomes research, pilot studies, observational studies and medium and large
randomized controlled trials.
Focus: Nine research projects were funded in the first year of the program (FY
2003). The foci of these investigations included a particular emphasis placed on
the study of CAM therapies with the potential for direct impact on U.S. military
operations such as easily administered, portable treatments for acute and
chronic pain, wound healing, the protection from chemical and biological warfare
and the treatment of key diseases impacting readiness and deployment. In the
second year of the program, the range has been expanded to include
acupuncture-based technologies, bioelectromagnetic devices , low-dose protection
methods, and manipulative medicine that soldiers can use in field environments.
Management: The project is a coordinated effort between the Uniformed Services
University of the Health Sciences (USUHS), and the Samueli Institute for
Information Biology (SIIB). Scientific review and management is conducted for
USUHS by SIIB, and research is conducted at locations determined after
peer-review of research proposals. Funding is utilized for personnel salaries,
research equipment and supplies, travel, publications and patient care as
related to the research.
Research Opportunities: The funding for this current
second year of the program became available
during the Spring of 2004. Two RFAs were published in January 2004, and
potential investigators submitted over 17 applications for review by the
Scientific Review Committee convened in April 2004. Money from this
past year’s grant
has been set aside for potential renewal applications from some of the original
nine applications funded in the first year.
Currently Funded Research Programs Include the Following:
Analyzing the Chemical Aspects of Samples Derived from CAM and MIL CAM Research Projects.
Principle Investigator: Jose A Centeno PhD
Affiliation: American Registry of Pathology, Armed Forces Institute of Pathology
Hypotheses or Aims:
1: To establish a facility for the chemical characterization and analysis of samples derived from CAM and MIL-CAM research projects.
2: To provide quality control/assurance for the analysis of low and ultra-low dose homeopathic preparations using existing validated and standardized methodology.
Methods and Materials:
Existing equipment in the laboratories will be utilized to perform analysis of trace and ultra-trace elemental levels, to characterize CAM and MIL-CAM preparations and to provide tissue archival and repository capabilities.
Practice Outcomes Evaluation Management System for Complementary, Alternative and Traditional Medicine
Principle Investigator: Christine H Goertz DC, PhD
Affiliation: Epidemiological Documentation Service [EDS], National Foundation for Alternative Medicine [NFAM] and the Samueli Institute
1: Hypotheses or Aims;
Design, test and implement the SIIB EDS Coordination Center, a prospective outcomes evaluation infrastructure [do you want to use prospective outcomes documentation systems?] that can be used to systematically evaluate clinical outcomes of complementary and alternative medicine practices from around the world, within practice-based settings.
2: Utilize a Field Investigation Center (FIC) to identify, screen and prioritize CAM clinical practices that use promising therapies, are of particular military relevance and are capable of participating in the PODS [EDS] protocols.
3: Develop EDS protocols for the study of CAM clinical practices using appropriate research methodologies based on the current state of the science, the type of CAM practice to be evaluated, and the targeted disease.
4: Conduct a minimum of 6 site visits/practice descriptions, 3 filed investigations and 3 new practice-based EDS studies per year.
Methods and Materials:
The EDS will be organized into two synergistic components that include: 1) field investigation and site visits implemented by the NFAM Field Investigations Center (FIC) which will provide screening, site visits, practice descriptions, field investigations and best case series, and 2) a Prospective Outcomes Documentation Service (PODS) conducted by SIIB through a EDS Review Committee, a EDS coordinating center and standardized EDS protocol development and implementation with defined outcome measures. An EDS Advisory Committee (EAC) will provide guidance to the EDS PI and feedback to the SIIB Director and Deputy Director on the overall implementation of the EDS. The operations of the FIC and PODS will be closely coordinated by and EDS Executive Committee.
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Homeopathic Nosodes for the Treatment of VEE Infection
Principle Investigator: Radha K Maheshwari PhD
Affiliation: Uniformed Services University of the Health Sciences, Department of Pathology
Hypotheses:
1: To determine whether homeopathic nosodes render any protection to astrocytes/microglial cell death following Venezuelan equine encephalitis [VEE] infection in vitro.
2: To determine and test homeopathic nosodes induced differential gene and protein expression patterns that best predicts its protective effect in VEE virus infected brain tissue and atrocytes/microglial cells.
Methods and Materials:
The steps involved in this research include preparation of VEE homeopathic nosodes, isolation and characterization of astrocytes and microglial cell cultures, the effected of homeopathic nosode of VEE growth kinetics, immunoperoxidase staining of VEE-infected astrocytes, cell viability and cell death, analysis of pathway specific DNA microarrays, ribonuclease protection assays and RNA isolation and RT-PCR for differentially expressed genes
Mechanisms of Receptor Signaling Following Low and Ultra-low Treatment of Macrophages with Lipopolysaccharide and Interleukin-6
Principle Investigator: Florence M Rollwagen PhD
Affiliation: Uniformed Services University of the Health Sciences, Department of Pathology
Hypotheses:
1: Treatment of macrophages with low or ultra-low dilutions of LPS will modulate cytokine secretion following restimulation with LPS. This can be seen as a form of endotoxin tolerance at low levels.
2: Treatment of macrophages with low or ultra-low dilutions of IL-6 will selectively modulate subsequent IL-6 secretion upon restimulation with LPS, without changing secreted levels of other inflammatory cytokines (IL-6, TNF-ٱ)
3: The mechanisms of low vs ultra-low modulation are different.
Methods and Materials:
The modulatory effects of low and ultra-low dose LPS and IL-6 pretreatment of macrophages before administration of a stimulatory dose of LPS will be determined via analysis of downstream LPS signals such as TRAF-6, and IRAK-1 phosphorylation and translocation of NFٱB to the nucleus of treated cells as well as cytokine secretion. Examination of STAT-3 phosphorylation following IL-6 stimulation also will be studied. Using new RNA interference technology (RNAi), the TLR-4R and the IL-6R will be knocked out to verify that ultra-low modulation involoves stimulation of cells via novel mechanisms. The experiments will use a RAW 264.7 cells, a commercially available humanmacrophage cell line. Cells will be grown in Dulbecco's Modified Eagle's Medium (high glucose) with added fetal calf serum and antibiotics. Cells will be plated at 5X105 cells/well in COSTAR 24-well culture dishes and subsequently exposed to the desired stimulation. Cells will be treated with low and ultra-low doses of LPS or IL-6 according to the schedule outlined below. Supernatants will be harvested at intervals, and frozen at -20o until tested in cytokine ELISA tests (BioSource CytoSets). Interventions will include stimulation with various low and ultra-low concentrations of LPS ranging from 1D to 200C prepared under sterile conditions in LPS-free water. Controls include sucussed water, media alone, and natural water. To control for osmotic concentration, cells will be given 10-fold concentrated Dulbecco's MEM every time the low and ultra-low LPS or IL-6 stimulations are given. Following supernatant collection, cells will be harvested, lysed with appropriate buffers for DNA, RNA and protein collection. Samples will be frozen at -20o until analyzed in NFٱB ELISA, or phosphorylation specific Western blots. Additional cells will be analyzed by flow cytometry to determine cell surface expression of TLR-4 and IL-6R. Low and ultra-low concentrations of LPS or IL-6 will range, for example, from 10-5, 10-6, 10-7 for the low doses, to 10-12, 10-30, 10-200 for the ultra-low doses.
Effects of SCENAR Therapy on Pain Modulation, Swelling, Reflex Muscle Inhibition, Ankle Functional Status, and Recovery Time Following Acute Ankle Sprain.
Principle Investigator: Ann Gill Taylor EdD, RN, FAAN
Affiliation: University of Virginia School of Nursing
Hypotheses:
SCENAR® therapy will reduce pain and swelling, reverse muscle inhibition, improve ankle functional status, and shorten the functional recovery time following acute ankle sprains.
Methods and Materials:
This controlled randomized study in athletes with acute ankle sprains will use an experimental two group design (active SCENAR® and sham SCENAR) stratified by type of ankle sprain (high vs. low sprains). Diagnostic result will be confirmed by MRI and a physician. After stratifying on type of sprain, participants will be randomly assigned in equal numbers to the active SCENAR® and the sham SCENAR groups. Study outcome measures will be assessed each day until functional recovery and prior to the first rehabilitation session.
Analyzing Genomic and Proteomic Profiles of CAM Research Samples
Principle Investigator: Richard I Somiari PhD
Affiliation: Windber Research Institute
Hypotheses or Aims:
To provide each CAM/MIL CAM investigator maximum DNA and RNA recovery with minimal or no degeneration on biological samples obtained from projects with defined goals, deliverables and definition.
Methods and Materials:
Using standard operating procedures, this facility will make available services related to molecular biology, biochemistry, immunology, cDNA microarray 2-D proteomic capabiligy, construction and analysis capability, comparative genomic hybridization, genotyping, two-dimensional gel electrophoresis-mass spectrometry, microscopy, bioimaging, laser capture, microdissection, bioinformatics and data warehousing. The availability and full integration of these core technologies in one facility will markedly enhance the efforts of the MIL CAM funded researchers.
Homeopathic Treatment of Paraoxon Intoxication in an Animal Model-A Feasibility Study
Principle Investigator: Menachem Oberbaum MD MFHom
Affiliation: The Center for Integrated Complementary Medicine, Shaare Zedek Medical Center
Hypotheses:
The poison Arsenicum album, applied as a homeopathic remedy in C30 (10-60 of the stem solution), is capable of reducing the symptoms or cure a paraoxon intoxication in small rodents.
Methods and Materials:
Mice (Sabra, ICR, C57BI), rats (Sprague Dawley, Wistar, Fisher 344) and Guinea pigs (Duncan Hartley) will be used in these experiments. Paraoxon (O,O diethyl p-nitrophenyl phosphate) will be obtained commercially, dissolved in saline and applied by intra-peritoneal injection. Arsenicum album (As2O3) will be diluted by serial centesimal dilution and vigorous shaking in 40% alcohol with the last two dilutions prepared in distilled water. The theoretical As2O3-concntration will be at the end of the procedure 10-60 of the stem substance. The control solutions will be prepared in the same manner. ChE activity in blood as well as AchE activity in brain, will be determined by a spectrophotometric method. Both study and control animals will be intoxicated by intraperitoneal application of paraoxon solution in a dosage which is equivalent to the LD75 determined previously. The treatment will start 2 minutes post injection, by applying orally either 5 drops of Arsenicum album C30 (trated group) or 5 drops of the control solution (control group). This treatment will be repeated every 15 minutes, until the death or recovery of the animals.
Induced Neuroprotection for Biochemical Warfare
Principle Investigator: Aryan Namboodiri PhD
Affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences
Hypotheses:
Low to ultra low dose exposure to biochemical warfare agents, such as cyanide and botulinum toxin, provides protection against normally toxic doses of similar biochemical warfare agents.
Methods and Materials:
The aim of developing an animal model of neuroprotection using cyanide as a model biochemical warfare agent and the aim of studying the biochemical mechanisms involved in neuroprotection will be pursued by determining the specific changes at the protein level in substantia nigra and cortex, two brain areas that are differently affected by cyanide neurotoxicity. To accomplish these goals, mice will be pre- post- and pre/post- treated with low or ultra low doses of cyanide, using conditions of high (acute) as well as low (chronic) cyanide neurotoxicity. The pre-exposure will occur 24 hours before exposing them to the toxic (subacute and chronic) doses. In the case of the post and pre/post conditions, the post exposure will be either once every four hours up to 24 hours following the acute exposure or everyday up to 12 days following the chronic exposure and treatment. Neurotoxicity will be evaluated by mortality at 24 hours in the case of the acute exposure, and by analyzing multiple biochemical parameters; specifically, increased concentrations of lactate and glutathione, and increased lipid peroxidation, in the case of the chronic exposure. Concentrations of N-acetylaspartate (NAA), a reliable marker for the functional integrity of neurons, will be determined in different areas of the brain in the case of the chronic exposure.