Method and an apparatus for stimulating/ modulating...

Surgery – Magnetic field applied to body for therapy – Electromagnetic coil

Reexamination Certificate

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Reexamination Certificate

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06561968

ABSTRACT:

FIELD OF THE INVENTION
The present invention provides a method and an apparatus for stimulating and/or modulating growth and differentiation in biological or plant tissue, seeds, plants, and microorganisms. An apparatus of this type includes a pulse generator and a plurality of coils, in which pulsed currents cause fluctuating magnetic fields in a predetermined region holding the material to be stimulated. The fluctuating magnetic fields will induce an electric field in the material.
BACKGROUND OF THE INVENTION
Pulsed electromagnetic fields (PEMF) have been used widely to treat delayed non-heating fractures, pseudoarthrosis, osteoarthritis, bone fractures and related problems (Bassett, C. A., Mitchell, S. N. & Gaston, S. R. (1981); (Trock et al., 1994). “Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields”,
Journal of Bone and Joint Surgery [American],
63-A, 511-523 and Bassett, C. A. L., Pilla, A. A. & Pawluk, R. J. (1977) “A non-operative salvage of surgically-resistant pseudarthroses and non-unions by pulsing electromagnetic fields: a preliminary report”,
Clinical Orthopaedics,
128-143) and have also been suggested for the treatment of nerve growth and wound healing (Sisken, B. F., Kanje, M., Lundborg, G., Herbst, E. & Kurtz, W. (1989), “Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields”,
Brain Research,
485, 309-316 and Patino, O., Grana, D., Bolgiani, A., Prezzavento, G., Mino, J., Merlo, A. & Benaim, F. (1996), and “Pulsed electromagnetic fields in experimental cutaneous wound healing in rats”
Joural of Burn Care and Rehabilitation,
17, 528-531). It has been suggested that some of the important effects relating to an enhanced bone growth is the PEMF-induced promotion of angiogenesis, but this issue is not yet resolved (The National Institute of Environmental Health Services (NIEHS): “Assessment of Health Effects from Exposure to Power-Line Frequency Electric and Magnetic Fields”. (http://www.niehs.nih.gov/emfrapid/home.htm)).
A temporarily varying magnetic flux through an area induces an electric field, E, along the perimeter of the area according to the basic laws of electromagnetism. If the varying magnetic field, B(t), is applied to a material containing free (or mobile) charge carriers, these will be accelerated by the electric field thereby generating eddy currents in the material. The induced electric field or the generated current depends upon the rate of change, dB/dt, of the magnetic field, the electric field or current increasing with increasing rate of change.
The main point in treating biological tissue i.e. bone healing, wound healing, nerve growth, and angiogenesis is the introduction of tissue currents with an intensity and duration that can activate cellular signalling processes and extracellular signals, thus initiating cell proliferation and differentiation and other biological processes.
WO 85/00293 and WO 99/10041 describe the use of conducting coils to stimulate growth and healing in living tissue. The coils are positioned so as to generate a strong field at the region to be treated and a pulsating current signal is supplied for conduction in the coils.
PEMF has been used for activating muscle and neural cells as an alternative method to electrodes see e.g. EP 788 813 or U.S. Pat. No. 5,738,625. PEMF induced by conducting coils has the advantage that no electrodes in direct contact with the skin have to be used. The PEMF used for activating cells must be fast and/or large enough to induce electric potentials large enough to elicit the action potentials of excitable cells. In order to achieve such large electrical potentials, very large currents are used in the coil and the fields from several coils are added. In EP 788 813, the PEMF is used to activate muscle cells to flex a group of pelvic floor muscles in order to treat urinary incontinence. In U.S. Pat. No. 5,738,625, the PEMF is used to activate neural cells in order to investigate or diagnose the nervous system.
The effects of fluctuating magnetic fields in the tissue can be anticipated to be due to the effect of the induced electric field upon charged particles and entities (ions, molecules and macromolecules such as proteins, and inositol phosphates and other signalling compounds, cells and their extracellular signalling compounds such as hormones and other neurotransmitters etc.). Hence, the effects of fluctuating magnetic fields can be anticipated to be due to the extracellular as well as intracellular events caused by the electric fields and currents.
Regarding extracellular effects it can be expected that the on and off rate constants for the associations between neurotransmitters, hormones and their receptors will be affected, to the extent that net positive or negative charges are associated with the process, as well as inducing piezo-electric currents in bone tissue, thus mimicking physiological processes. The intracellular effects that might be the most affected are biochemical reactions that are involved in promoting cell division and differentiation. Amongst cellular signalling processes that have been suggested to be essential for the initiation of cell proliferation is the activation of protein kinase A. This enzyme is activated by cAMP (cyclic adenosine 5′ monophophate) that is synthesised from ATP by a receptor activated adenylyl cyclase. cAMP binds to protein kinase A and forms catalytic subunits, and this signal can be carried to the nucleus. Here it leads to activation of cAMP-inducible genes. Activation of the synthesis of cGMP, by iron containing enzymes such as nitrogen oxide synthetase that in turn activates classes of protein kinase G, are also important candidates. Several studies have implicated that the activation of ornithine decarboxylase, causing synthesis of prutescine and other related compounds, that promotes DNA transcription, also appear to be essential. The mechanism by which signalling processes are initiated appear to be due to a combined effect of proteins with a net charge, that will move in the cell interior (G-proteins, protein kinases, mRNA binding proteins etc.). Those can associate with target proteins and exert a biological effect and changes in the association constants for these processes will affect cellular function. Other ions, such as Ca
2+
, are highly affected by electrical fields, and will also exert a biological effect by associating with intracellular proteins and ion channels. The essential point is that signalling molecules with net charges or areas with net charges will be affected by the changing magnetic fields and all charged particles will rotate in magnetic fields depending on movements relative to the magnetic field.
One important aspect of promoting growth of osteoblasts, chondroblasts, chondrocytes and their derivatives (bone and cartilage), nerve cells, and other tissues is the induction of growth of small vessels (capillaries) that supply the blood cells, hormones and nutrients for sustaining cell proliferation and differentiation. The small vessels consist of endothelial cells, smooth muscle cells, and other cell types that together will protrude into new areas following the activation of nitric oxide (NO) and growth factors. These cells are also connected to each other both through signalling by chemical substances but also electrically through gap junctions. Both NO, vascular endothelial growth factor (VEGF) and other factors, appear to play an essential role in activating growth and differentiation amongst other things through activation of MAP kinase signalling pathways. However, the intracellular signalling processes play an equally important role in the cellular activation and when considering the effects of PEMF on angiogenesis both extracellular as well intracellular events should be considered.
The induced electric field from a circular coil can be calculated in a plane parallel to the coil, at a given distance from the coil. Due to the cylindrical symmetry, the induced electric field will have a circular symmetry in the pl

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