Nonlinear Response Amplification Mechanisms for Low Doses of Natural Product Nanomedicines: Dynamical Interactions with the Recipient Complex Adaptive System

Abstract

The purpose of the present paper is (a) to outline the self-organized, complex adaptive network nature of the organism as recipient of nanomedicines; (b) to propose several nonlinear endogenous amplification processes by which pulsed low doses of traditional, homeopathically-manufactured natural product nanomedicines may stimulate a return toward healthier function; and (c) to discuss their potential relevance to novel, but safer than conventional dosing strategies for contemporary nanomedicines. Homeopathy is an over 200-year-old system of complementary and alternative medicine (CAM) that uses low doses of natural plant-, mineral-, and animal-sourced nanomedicines. Homeopathic manufacturing is "green", with mechanical grinding in lactose and agitation in ethanol-water as primary reagents. Agitation within glass containers at room temperature may also contribute nanosilica and nanosilicon as drug delivery vehicles and biological amplifiers. The medicine selection is matched to the recipient organism's systemic patterns of dysfunction and pulsed in the timing of the discrete doses. Endogenous amplification processes within the recipient organism may involve hormesis, time-dependent sensitization, and/or stochastic resonance. Effects are adaptive and systemically diffuse, i.e., causally indirect, rather than pharmacological and local, i.e., direct. All of these nonlinear response processes require interaction of the nanoparticle (NP) dose with the organism as a complex adaptive system. The pulsed NP dose serves as a low intensity salient danger signal for the organism to make network-wide adaptive changes that can lead to healing. The historically safe therapeutic approach of homeopathic nanomedicine dosing avoids risks of high, continuous doses and cumulative toxicity that contemporary nanomedicine researchers are now trying to solve while using NPs as if they were conventional bulk drugs. Integrating the insights, technical procedures, and clinical dosing approaches from modern and homeopathic nanomedicine could lead to major advances in the field for more effective and safer translational applications.NPs in homeopathic medicines [3]. NP concentrations are low, but measurable [3]. Like modern manufactured NPs [13], homeopathicallymanufactured medicines in solution also can exhibit aging effects [9,14]. These nanomedicines are delivered either in ethanolic liquids or sprayed and dried onto lactose or lactose/sucrose pellets for oral administration.Homeopathic manufacturing materials and methods are inherently "green" [15,16]. Previous papers have addressed the striking similarities between modern top-down mechanical attrition procedures for making nanoparticles (NPs) [17] and historical homeopathic medicine manufacturing methods and materials [15,[18][19][20][21]. These similarities include mechanically grinding source materials in lactose for hours and repeatedly agitating ethanol-water solutions containing the source Citation: Bell IR, Sarter B, Koithan M, Standish LJ, Banerji P, et al. (2013) Nonlinea...

Transcriptome analysis of Catarina scallop (Argopecten ventricosus) juveniles treated with highly-diluted immunomodulatory compounds reveals activation of non-self-recognition system

“…Low decimal dilution (D) effects are attributed to diluted molecules and nanoparticles while high centesimal dilution (C) effects are attributed to nanoparticles and electromagnetic fields [14], which are sensed by traditional molecular receptors or photoelectrochemical sensing system activated by ultra-weak photo emission signals [15]. These highly-diluted molecules work as low intensity danger signals that generate endogenous amplification by hormesis effect, time-dependent sensitisation and stochastic resonance process [16,17].…”

Extending the Adaptive Network Nanomedicine Model for Homeopathic Medicines: Nanostructures as Salient Cell Danger Signals for Adaptation

“…Overall, these networks involve modulation of gene expression patterns, cytokine release, cell signaling mediator release, cell and mitochondrial stress responses [77,81]. The effects can cascade into nonlinear amplified responses [23].…”

“…Copyright: © 2015 Bell et al [23] have elsewhere discussed multiple endogenous nonlinear amplification mechanisms by which complex adaptive systems such as human beings or animals can respond to a small, pulsed but salient signal [197], especially from a nanomaterial. Such processes include not only hormesis, but also stochastic resonance and time-dependent sensitization/cross-sensitization [23].…”

“…In recent years, the empirical data on HMs support a testable, hypothesis-driven model based on the generation of source and silica and/or other container-and reagent-derived nanoparticles (NPs) in HMs during the manufacturing process [1,2,23,24]. In nanotechnology, grinding or ball milling of materials (comparable to the initial homeopathic manufacturing steps of trituration in dry lactose for very low potencies) as well as sonication and/or water jet treatment (comparable to homeopathic manufacturing steps of repeated succussions in water or water-ethanol diluents at room temperature for higher potencies), generate micro-and nano-sized particles of the original source material [20,[25][26][27][28][29] (Table 3).…”

“…Endogenous response amplification to NPs is nonlinear and potentially multi-factorial [23], including but not limited to immune/inflammatory/metabolic mediator modulation [81], nervous system cross-sensitization [2], and adaptive changes of hormesis [82]. Nanomaterials are often inherently more potent than their bulk form counterparts [63,83], lowering doses needed for direct effects by orders of magnitude [84], and even lower for adaptive phenomena like vaccine immune responses [53,54,56,85] and hormesis [1,7,8,82].…”