[Frontiers in Bioscience S5, 685-708, January 1, 2013]

Adaptive network nanomedicine: an integrated model for homeopathic medicine

Iris R. Bell1-4, Gary E. Schwartz2,4

1Department of Family and Community Medicine, College of Medicine, The University of Arizona, 1450 North Cherry, Tucson, AZ 85719 USA, 2Department of Medicine (Center for Integrative Medicine), College of Medicine, The University of Arizona, Tucson, AZ 85724 USA, 3College of Nursing, The University of Arizona, Tucson, AZ 85721 USA, 4Department of Psychology, The University of Arizona, Tucson, AZ

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Homeopathic medicines as "top-down" nanoparticles
3.1. Overlaps between homeopathic remedy manufacturing and nanoparticle manufacturing methods
3.2. Basic science findings on homeopathic remedies
3.3. Clinical characteristics of nanoparticles
4. Hormesis and adaptation: homeopathic remedies as exogenous low intensity stressors
5. Homeopathy as adaptive network nanomedicine
6. Summary and conclusions
7. Acknowledgements
8. References

1. ABSTRACT

This paper presents an evidence-based model for the nature and mode of action of homeopathic remedies. Recent studies reveal that homeopathic remedies contain nanoparticles (NPs) of source materials formed by "top-down" mechanical grinding in lactose and/or succussion (forceful agitation) in ethanolic solutions. Silica nanostructures formed during succussions in glass and/or biosynthesized by specific plant extract tinctures also may acquire and convey epitaxial information from remedy source materials into higher potencies. NPs have enhanced bioavailability, adsorptive capabilities, adjuvant reactivity, electromagnetic and quantum properties compared with their bulk forms. NPs induce adaptive changes in the organism at nontoxic doses (hormesis), serving as salient, low level danger signals to the biological stress response network. Activation of stress response effectors, including heat shock proteins, inflammasomes, cytokines and neuroendocrine pathways, initiate beneficial compensatory reactions across the interconnected networks of the organism as a complex adaptive system. Homeopathic remedies act by stimulating hormetic adaptive rather than conventional pharmacological effects. Updating terminology from "homeopathy" to "adaptive network nanomedicine" reflects the integration of this historical but controversial medical system with modern scientific findings.

2. INTRODUCTION: FROM HOMEOPATHIC MEDICINE TO ADAPTIVE NETWORK NANOMEDICINE

Homeopathy is a more than 200-year-old whole system of complementary and alternative medicine (CAM) (1). Despite historical skepticism of the field from mainstream medicine, homeopathic medicines (remedies) are used by approximately 500 million people worldwide (2) as a low-risk treatment approach for acute and chronic conditions, though utilization rates vary markedly from country to country (3, 4). In recent decades, homeopathy has developed a growing basic science, clinical, and health services research literature showing unique physico-chemical properties, biological activity in vitro and in vivo, good real-world effectiveness, exceptional safety, and, in many studies, cost-effectiveness (5-10).

However, skepticism and uncertainty about the nature of the remedies and their mode of action has slowed more widespread acceptance and utilization of homeopathy in integrative medicine. Skeptics keep returning to their belief that homeopathic remedies per se cannot exert any effects other than placebo effects. That is, homeopathy is claimed to be "implausible" on "scientific" grounds (11), which revolve around a focus on the serial dilution component of remedy manufacturing. Typically skeptics selectively ignore the basic science and preclinical data, discount any positive clinical studies (12, 13) and point to the more mixed placebo-controlled, double-blind randomized clinical trial literature and one flawed meta-analysis dependent on 8 homeopathy trials (12, 14) as definitive "proof" that this entire field is invalid (13). Patient-provider factors are an emerging focus of clinical study in homeopathy (15-17).

On the other hand, CAM investigators emphasize significant problems of poor external and model validity in applying conventional clinical trial designs to study homeopathic treatment (18-20). For instance, one large study of homeopathically-prepared, but not homeopathically-prescribed, dust mite 30C medicine in asthmatics revealed the seemingly paradoxical finding that verum and placebo groups were not clinically different after a 16-week trial (21), but the pattern of changes in the verum group over time was oscillatory and distinct from the flatter response pattern in the placebo group (22). Observational studies on thousands of homeopathic patients suggest improvement rates that can range between 60-90%, with earlier improvements in acute illnesses compared with standard of care, reduction in concomitant symptomatic medications, and associated cost-savings in many studies (5, 6, 23-26). Objective sleep and waking electroencephalographic studies indicate that homeopathic remedies exert measurable nonlinear effects different from placebos in human subjects and animals (27-36). Multiple in vitro studies demonstrate that remedies can evoke complex patterns of changes in immune, inflammatory, oxidative stress, and biological signaling pathways (8, 9, 37-58).

A clearer understanding of homeopathic remedies and their mode of action would assist scientists in putting the total research literature into better context and in designing more appropriate future studies. Homeopathic clinicians would be able to practice clinically-relevant evidence-based care. Taken together, the available scientific evidence now points to a testable comprehensive model for the nature of homeopathic remedies and their interactions with living systems (59). The empirical data indicate that "something" is indeed happening when a cell or organism encounters a homeopathic remedy. Despite the seemingly confusing body of observations, three broad research literatures coalesce to provide a scientific explanatory model, i.e., (a) the properties of nanoparticles (NPs); (b) the biology of the stress response; and (c) the complex adaptive network nature of the organism as a whole. The purpose of the present paper is to summarize this evidence-based understanding of the nature of homeopathic medicines and how they act.

The core elements and implications of the Nanoparticle-Cross-Adaptation-Sensitization model are summarized in Table 1. Evidence indicates that homeopathic remedies prepared in serial dilutions with initial trituration (mechanical grinding) and/succussion (intense agitation of ethanolic solutions) contain nanoparticles of their source materials (60, 61). Other lines of evidence suggest that plant (62) and other source materials can adsorb onto the surface of silica, polymer, or other nanoparticles previously shown to result from the succussion process (63, 64). NPs trigger local biological signaling events in the stress response pathways that defend against exogenous dangers and mobilize the global living system to adapt as an interconnected complex adaptive network (65-68). In small quantities, NPs stimulate adaptive changes across the organism without exerting damage, i.e., hormesis (69, 70). The remainder of the paper discusses each element in greater detail below to provide the scientific foundation for reconceptualizing homeopathic medicine as adaptive network nanomedicine.

3. HOMEOPATHIC MEDICINES AS "TOP-DOWN" NANOPARTICLES

3.1. Overlaps between homeopathic remedy manufacturing and nanoparticle manufacturing methods

Homeopathic medicines or remedies contain crude nanoparticles, nanoaggregates, and/or nanocrystals of their original source substance (60, 61). The starting point of the model is that homeopathic remedies are nanoparticle (NP) forms of their source material because of the ways in which they are manufactured from bulk form substances (61, 63). Remedy manufacturing begins with mechanical milling and grinding (trituration) in lactose and/or vigorous agitation in ethanol-water solution by manual pounding of the container on a hard elastic surface (succussion), vortexing, or sonication (44, 63, 71). Classical remedy preparation uses glass containers, though some contemporary manufacturers may employ polymer containers of polypropylene or polyethylene (63). Table 2 lists studies involving homeopathic remedies and nanoparticles.

Mechanical milling (72), sonication (73), microfluidization and flash nanoprecipitation (74), and using botanical extracts (75), including homeopathic plant tinctures (62, 76, 77), for biochemical catalysis and NP generation are among a variety of ways in which modern nanotechnologists make nanoparticle forms of source materials. The intense bidirectional fluid turbulence during succussion would cause particle collisions and shear off smaller and smaller particles from the bulk starting material, as well as generate nanobubbles (78). In turn, nanobubbles create tiny areas of localized high temperatures and pressures to shear off additional smaller nanoparticles from larger source particles and perhaps silicates in solution (64, 79-82), leading to their uneven distribution in colloidal solutions (82). In parallel with homeopathic trituration and succussion, combining wet grinding with sonication in nanotechnology is more effective than grinding alone or sonication alone in limiting nanoparticle aggregation that otherwise occurs in solutions (73).

Nanoparticles (NPs) are small particles of source material with at least one dimension measuring less than 100 nanometers (83, 84). Ethanol as a solvent tends to foster generation of relatively smaller-sized nano-structures during ultrasound treatment of solutions (82). This point has clinical implications, as some smaller NPs tend to be more toxic than larger NPs, including nanosilica and nanopolystyrene (85-87). In addition, NPs are generally much more bioavailable than their respective bulk forms (76, 77, 83, 88-91). Thus, to use the extensive variety of source NPs that homeopaths utilize safely in therapeutic applications (6), very low doses are indicated. In fact, many studies of nano-forms of herbs, nutriceuticals, vaccines, and drugs suggest that doses can be 10 to 1000 times lower than typical bulk form doses to produce the same direct biological effects (77, 89, 90, 92, 93). To minimize direct adverse effects (70, 94) but still mobilize beneficial endogenous adaptive responses (69, 95, 96), nanomedicine doses need to be very low (70, 97-100).

Modern nanotechnologists make nanoparticles and nanocrystals in one of two ways - by "top-down" mechanical milling or grinding methods (72, 101, 102) or by "bottom-up" molecular self-assembly (103). The top-down process for making nanoparticles from bulk form materials was first developed in modern nanotechnology in 1966 (72). One company, Elan Drug Technologies, even patented a top-down drug milling method named "NanoCrystal®." The purpose of this approach for nanomedicine is to improve bioavailability of otherwise poorly soluble drugs (101, 102, 104, 105) reportedly by as much as 600% (http://ir.elan.com/phoenix.zhtml?c=88326&p=irol-newsArticle&ID=1365330&highlight=, accessed 8/03/12).

Notably, mechanical milling of lactose will itself generate complex nanocrystalline and other nanostructures of the source sugar (106). Succussion in glass generates small but measurable amounts of biologically active silica from the walls of the container (64). The heightened capacity of nanoparticles for adsorbing other materials onto their surfaces has been shown for animal serum albumin with both lactose (107) and silica (108). Thus, lactose (106) and/or silica (109) nanoparticles may be "nanocontaminants" in most homeopathic remedies, depending on potency, potentially serving as nanoadjuvants to stimulate heightened reactions to remedy source particles (cf., (89)) and drug delivery vehicles to reduce dose levels (77, 110, 111). If the remedy is succussed in a polyethylene rather than glass tube, other data suggest that the container releases nanoparticles of the polymer into the colloidal solution (63).

During the 1800's, Samuel Hahnemann, MD, the physician-chemist who founded homeopathy, originally described a manual method of drug grinding and turbulent fluid agitation with ethanol-water solutions in small glass containers (71). Hahnemann pointedly emphasized the essential role of trituration requiring prolonged intense mechanical grinding of source material in lactose with mortar and pestle, per step and succussions (many repetitions of violent manual pounding of the liquid solution in a glass container against a hard elastic surface), for generating active homeopathic remedies. In his book, the Organon of Medicine 6th edition, completed in 1842, he observed (71): "...This remarkable alteration in the properties of natural bodies is achieved through mechanical action on their smallest particles by trituration and succussion while these particles are separated from one another by means of an intervening, indifferent substance that is either dry (e.g., lactose) or liquid (e.g., ethanol-water solution)...Likewise, rubbing a medicinal substance and succussing its solution (dynamization, potentization) develops the medicinal powers lying hidden in the medicinal substance and discloses these powers more and more..."

Skeptics of homeopathy mistakenly focus on the serial dilution steps that are also performed in making homeopathic remedy potencies, e.g., with dilution factors of 1 part source in 10 parts diluent (X potencies) or 1 part source in 100 parts diluent (C potencies). They claim that such dilutions render a solution no different from plain water. Even Hahnemann agreed with this point with regard to bulk form materials (71). Dilution without trituration and/or succussion, i.e., to make small medicinal particles, does not make a homeopathic remedy. Clearly, modern NP manufacturing methods are more sophisticated than those used in classical homeopathic manufacturing, but they are nonetheless all procedures that can generate nanoforms from bulk form materials.

3.2. Basic science findings on homeopathic remedies

In contrast with the misleading assumptions of skeptics about dilution, the nanostructured nature of triturated and/or succussed homeopathic remedies has empirical support (9, 60, 61, 63, 76, 106) (Table 2). For example, using transmission electron microscopy, Chikramane et al (61) demonstrated that source nanoparticles persist in six different commercial homeopathic metal remedies from two different manufacturers, at liquid potencies of 6C, 30C, and 200C (where C potencies mean a dilution factor of 1 part source to 100 parts diluents per step, with initial trituration and 10 or more succussions after each dilution step). The metal remedy preparation involved both initial trituration in lactose and subsequent dilutions and succussions in ethanol-water solutions within glass containers. With ordinary dilution of bulk materials, conventional pharmacological principles suggest that no active source material should remain in homeopathic remedies higher than 24X or 12C, i.e., past Avogadro's number of molecules (6 x 1023). Nonetheless, biological activity does persist (9, 112).

Trituration alone, even without succussion, using traditional methods for sampling part of each "dilution" in order to make the next successive dilution, also generates biologically active homeopathic remedy at potencies up to 200C (44). Conversely, succussion alone using ethanolic plant mother tinctures without initial trituration, produces remedy source NPs. Upadhyay and Nayak (60) reported finding source nanoparticles and crystalline aggregates as well as silicon in three different plant remedies made from mother tinctures into homeopathic potencies from 1C to 15C. The latter researchers pointed out the possibility that the silicon/silica in the nanostructures succussed off the walls of the glass containers could carry specific remedy source-modified structural information into higher potencies.

Remedy source materials could adsorb onto and modify lactose or silica nanoparticles even upon their initial formation in the 1C or 1X preparation step (Figure 1). Using four different homeopathic plant mother tinctures, i.e., concentrates, to synthesize silver nanoparticles, Das et al observed subtle but detectable differences in the sizes, physical characteristics and biological properties of the resultant silver NPs (113). If specific remedy source materials in homeopathically-prepared medicines similarly modify silica NPs and crystallites from the glass container at lower potencies, the resultant nanostructures could acquire, seed, and convey a persistent silica-based structural "memory" of source information at higher potencies (60, 64). Silica can not only carry other nanomaterials per se, but also self-assemble "bottom-up" nanostructures using DNA, proteins, crystals or living cells as epitaxial templates (114) (Table 3). Plant extracts can biocatalyze formation of oligomers and/or aggregrated silica nanostructures from very small silica nanoparticles in aqueous solutions at room temperature (115).

Furthermore, data from Raman and UV-vis spectroscopy as well as fluorescence spectroscopy, tools used to characterize nanomaterials, also show that specific homeopathic remedies differ from one another and from plain solvent controls (63, 78, ). Like other types of nanoparticles (84, 116-118), homeopathic remedies also differ from controls in their thermal, electrical, and optical properties (119-122). Like NPs (84, 118, 123), homeopathic remedies may also exhibit quantum macroentanglement-like characteristics under certain experimental conditions (124). Consistent with the nonlinear dependency of NP properties on particle sizes, shapes, and quantities (70, 84-87, 90, 94, 108, 125, 126), homeopathic remedies exhibit more variability in their effects than conventional bulk form drugs (5). The enhanced bioavailability (76, 88, 91) and biological reactivity (83, 89, 90) of NPs, like homeopathic remedies (38, 45, 47, 55, 57, 58, 77, 127-129), enable the use of much lower doses, by orders of magnitude (see also Section 3.3. below).

The marked adsorptive properties of remedy source and silica NPs (130-132) and nanobubbles formed during succussion in ethanolic solutions (78) contribute to NP formation and persistence from low to high homeopathic remedy potencies. That is, skeptics may be correct that the bulk form materials are serially diluted out of solution past Avogadro's number; however, empirical evidence indicates that nanoforms of the source material and/or specific structural information remain (60, 61, 63, 113). The source NPs per se may be more reliably present in the lower potencies (61), i.e., less diluted potency forms. However, data show that some persistent source NPs and the remedy-modified silica nanostructures (or polymer NPs if made in non-glass vials (63)) are present across all potencies to convey and amplify remedy source-specific information (60,61).

At the same time, the data suggest the potential for greater variability of NP quantities and perhaps sizes and shapes at higher homeopathic potencies as currently manufactured. Data from a group studying the remedy Gelsemium's properties suggest that NPs from plant remedies may be variable in surface qualities and biological properties as a function of manufacturing methods (63). On the other hand, homeopathic remedies are made from mineral, animal, and plant source materials. A different study observed some surface irregularities but not major size differences on electron microscopic imaging of different potencies of metal-derived remedies (61). Although certain specimen preparation methods in the latter study may have affected the totality of findings, this study nonetheless demonstrated remedy source-specific nanoparticles up to 200C.

For NPs, it is not only quantity, but also sizes, shapes, and other features of small particles that significantly change their biological effects (70, 83, 84, 133). Increasing numbers of total succussions after serial dilution steps at higher homeopathic potencies would be equivalent to increased sonication time durations in modern nanotechnology (116, 134). If so, then the properties of the resultant homeopathic source NPs should potentially differ nonlinearly at higher versus lower potencies of the "same" remedy, given likely smaller NP sizes and reduced aggregation after succussion. One study in animals did find more prolonged duration of effects at 200C versus 30C potencies of four different homeopathic remedies (135). Moreover, consistent with available data on size- and shape-dependency of NP effects (84), consecutively or successively higher potencies exert nonlinear and even sinusoidal oscillatory effects on bacterial cells, plants, and animals (9, 136-138). Catalytic effects of NPs can fluctuate up and down sinusoidally as a function of progressively increasing nanocrystal aggregate size (84). Recency of succussions may play a role by dispersing particles into smaller sizes (82, 133, 139) and thus altering the nature of physico-chemical and biological findings in homeopathic studies (121). Adding more trituration grinding steps in lactose for dry potencies or adding succussion steps after each dilution step in liquid potencies would serve to disperse any larger, aggregated nanostructures and thus potentially change their properties (73, 116).

Testable hypotheses for why the remedy source NPs persist at high potencies with bulk source molecules removed by dilution include NP adsorption onto inner surfaces of containers and other glassware (silica or polyethylene or other polymer tubes) used in preparation (60) and vial-to-vial transfer (61), as well as to silica crystals or polyethylene nanocontaminants shown to be present in solutions made in glass or synthetic polymers (60, 63, 64). Like other types of NPs (84), silica nanoparticles are highly reactive and adsorptive (140), with the capacity for augmenting immune responses to antigens and triggering systemic biological signaling by themselves (65-68, 87, 141-144). Some homeopathic clinicians, including Hahnemann in his later writings (71), prefer that patients self-administer remedies in water after additional succussions of their treatment bottle, rather than simply dissolving dry pellets (previously sprayed with remedy and dried) under the tongue.

The hypothesis related to this clinical observation is that the additional succussions will release more nanosilica with its non-specific immune-stimulating adjuvant effects and disperse remedy source material nanoparticles into smaller sizes that may have aggregated from Ostwald ripening during shelf storage or light exposure (133, 139, 145-149). Ostwald ripening is a spontaneous thermodynamic process in sol solutions, whereby nanoparticles redeposit onto larger particles in solution, thereby changing the physico-chemical properties of the material. The silica NPs would serve as an additional but not always essential vehicle, as well as a potential non-specific amplifier of remedy source NPs biological effects and their informational properties in liquid potencies prepared in glass (60, 64, 113). Table 3 indicates proposed nano-forms and their hypothesized roles in the effects of homeopathic remedies interacting with the living organism.

3.3. Clinical characteristics of nanoparticles

The significance of finding nanoparticles in homeopathic remedies is that NPs have very different properties from those of their respective bulk form materials, as a function of their small size (83, 84). NPs are not merely small versions of their respective bulk forms. Such unique properties can help account for various findings on homeopathic remedies (59, 112, 121). Nanosizing by mechanical milling of drugs leads to (a) greater bioavailability with improved absorption from oral, gastrointestinal, nasal, or dermal administration; (b) higher adsorptive capacity to attach other nanomaterials onto their surfaces and serve as drug, vaccine, or gene delivery vehicles for self-assembled agents; and (c) enhanced catalytic ability for chemical and biochemical reactions (83, 91, 111, 150-152).

Nanovaccines can elicit immunological responses in a single adjuvant dose for antigen quantities 1,000-fold lower, e.g., 2.5 nanograms, compared with amounts in ordinary vaccines of the same antigen (89). "Dose-sparing," i.e., ability to use lower doses, is a general feature of nanomedicines (90, 91, 153), as well as reduced side effect risks and better intracellular access (91). Silica NPs are particularly effective in an immune-boosting adjuvant role (142, 143).

The NP vaccine delivery vehicle adjuvants boost the danger signal quality of the intervention for the organism (90, 142-144, 154-156). As a result, the organism mounts an even more vigorous immune response than usual to minute amounts of antigen or other foreign material (68, 89). The body then sees the tiny quantity of antigen as an exaggerated external threat requiring a vigorous compensatory immune response. On the other hand, if a nanoparticle is toxic, the quantities that can still exert adverse environmental effects on living systems are also extremely low, e.g., 1 nanomolar concentration of nanoceria NPs (nano-Ce-O(2)) (94).

NPs cross membranes, including blood-brain barrier (157, 158), without difficulty, and travel, mainly via lymph but also blood, throughout the organism (83). Nanoforms of drugs, herbs, nutriceuticals, and vaccines can all dramatically reduce by orders of magnitude the dose of the agent needed to produce a given biological effect (76, 77, 88, 96, 159-161). Moreover, because of their large surface area to volume ratio, NPs are more atom-like in behavior, acquiring the different electrical, magnetic, thermal, optical, chemical, biological, and quantum effects compared with their bulk forms (84, 162). Electrons are located closer to the surface of NPs (84). Bacterial DNA nanoparticulates prepared with dilution and succussion show ability to transmit measurable electromagnetic signals (163). Gold, which is non-magnetic in bulk form, becomes magnetic in nanoparticle form (84, 162). Some NPs, like certain forms of silica, exhibit quantum macro-entanglement effects (118).

The properties of NPs are nonlinear in nature (98, 164). For instance, increasing amounts of sonication time (a modern method for creating intense turbulence in a solution, cf., succussion (63)), produce nonlinear changes in thermal conductivity properties of a carbon nanostructure (116). Low doses of a carbon nanocrystalline material can protect healthy cells while inducing anticancer effects via autophagy in human and rat glioma cells (98); the biomechanisms for high doses of the same nanomaterial differ. A study of the homeopathic plant derived remedy Ruta graveolens 6C with Calcium Phosphate 3X potencies reported similar findings in human glioma cells (45). Notably, modern nanotechnologists use calcium phosphate nanoparticles as effective drug and gene delivery vehicles (151, 165).

Nanoparticles also induce systemic immune responses, based at least in part on their ability to mobilize components of the reticuloendothelial network (68). Moreover, not only bacteria and viruses (166-169), but also silica nanoparticles and other non-viral NPs can also activate intracellular inflammasomes (142, 170). Inflammasomes are a protein complex considered to serve as danger sensors for environmental threats to the cell's survival (171-173).

Once activated, inflammasomes release pro-inflammatory cytokines such as interleukin-1 beta (174). In turn, cytokines modulate immune and inflammatory responses (156) as well as brain function and behavior (175, 176). Overall, NPs, infectious agents (e.g., viruses, which are also often nanosized) (83), and many other types of exogenous stressors (biological, chemical, physical, or psychological) can set into motion the multiple defense pathways in the cellular stress response network (68, 142, 170, 177-180). Similarly, homeopathic remedies can modulate cytokine release and immune function in vitro (47, 58), in addition to activating different patterns of heat shock proteins (52-54), one of the key sets of endogenous proteins in the stress response network of the body (179-183).

If homeopathic remedies are nanoparticles and nanocrystals of source material, how would they exert therapeutic effects? Are NPs not often toxic for cells and organisms? Even if homeopathic NPs are benign, how could such small quantities in the low doses used in homeopathic remedies initiate such large, organism-wide changes? The remedy source also has no relationship to the original causes of the patient's disease. How could an unrelated homeopathic agent trigger reversal of the adverse effects of an accumulation of prior stressors? The answers lie not in conventional pharmacology, but rather, in the body of empirical research on the biological stress response (52, 53, 69, 184, 185), physiological adaptation (186-193), cross-adaptation (194, 195) and cross-sensitization (196-201), as well as in complex adaptive systems science (10, 22, 35, 59, 189, 202, 203).

4. HORMESIS AND ADAPTATION: HOMEOPATHIC REMEDIES AS EXOGENOUS LOW INTENSITY STRESSORS

Both nanoparticles (69) and homeopathic remedies (52-54) can initiate hormesis. Hormesis is a term from pharmacology-toxicology and physiology that refers to universal biological adaptive processes of living organisms in response to low levels of an environmental stressor or toxin (69, 186, 193, 204, 205). In hormesis, the dose-response curve is nonlinear, typically biphasic, with low doses serving as stimulatory and higher doses serving as inhibitory for function. The beneficial adaptive responses of hormesis have been demonstrated in more than 8,000 scientific studies for agents ranging from low level radiation to chemotherapy drugs to environmental toxins to physical or psychological stressors per se (193, 206). The hormetic dose-response range in which such phenomena are observed falls into the nontoxic range, below the cut-off for the no-observed-adverse-effect-level (NOAEL) (193, 204). Hormesis mobilizes cellular defenses of the stress response system (54, 187, 188). Various investigators have concluded that the low doses stimulate the organism to recover from past effects of or to prepare itself for a future assault by the same or a cross-adapted, higher intensity stressor that would threaten survival (69, 187, 188, 190, 191, 207-211). Several have suggested that episodic low level hormetic stressors over a lifetime could promote longevity via enhanced systemic resilience (187, 190, 191).

If nanoparticles are highly bioavailable, active, and reactive and require much lower doses to produce pharmacological or toxic effects than their bulk forms (70, 77, 89), then the doses of NPs that fall into the beneficial hormetic dose range, i.e., below the NOAEL, would of necessity have to be extremely low (69, 70). Figure 2 illustrates the lowering of the NOAEL dose cut-off for hormesis with nanoparticle forms versus bulk forms of a given material. This point translates into the scientific plausibility of exceedingly small amounts of homeopathic remedy nanoparticles being able to exert biological effects in a cell or organism (9). Homeopathic NPs, which are typically delivered in a pulsed or intermittent dosing regimen, would act not by direct pharmacological effects on receptors, but rather, as by inducing self-propagating adaptive responses in the organism to the remedy dose as an exogenous stressor or danger signal (68, 185). Khuda-Bukhsh et al have demonstrated the ability of homeopathic remedies to modulate biological signaling (40).

The organism then amplifies and self-organizes its responses with the passage of time (32, 35, 59, 184, 197, 203, 212-218). For example, Chikramane et al found a range of very low quantities of the homeopathic source material nanoparticles at the higher 30C and 200C potencies, e.g., approximately 10 to 4,000 picograms/milliliter (where 1 picogram per milliliter = 0.001 nanograms per milliliter)(61). The 6C potencies contained concentrations ranging from roughly 75 picograms/ml to 1300 picograms/ml. Consistent with the primary role of homeopathic nanoparticles as very low dose adaptive danger signals to the organism, even repeated olfactory administration of single homeopathic remedies at both lower and higher potencies in placebo-controlled studies on human subjects initiates progressive amplification and/or oscillation of quantitative electroencephalographic responses over time (27, 28, 30-32).

Variability in the comparatively crude manual grinding methods for traditional manufacturing of homeopathic top-down nanoparticles could certainly contribute to the variability from study to study and patient to patient in the effects of a given dose of remedy (5, 56, 74). Differences in the sizes and shapes, as well as the quantities, of source nanoparticles modify the nature and direction of their effects (84, 113, 116). It is also uncertain if or how the known quantum effects of nanoparticles (70, 84, 118, 123) might come into play in affecting biological function. Evidence with quantum dot types of nanoparticles indicates that very low dose nanomolar to picomolar concentrations exert long-lasting effects in living systems (70). However, these points do not support complete rejection of homeopathy as an implausible whole system of CAM.

Rather, understanding that homeopathic remedies are made in ways that can generate variable amounts of different sized and shaped source nanoparticles should steer scientists to explore modern nanotechnology methods for improving their production and nanomedicine uses (45, 72, 74, 101, 102, 113). Thoughtful examination of current procedures could lead to new developments for homeopathy on how to enhance remedy manufacturing standards and testing procedures (132, 219-220). Nonetheless, even with potential limitations of its traditional manufacturing methods, the therapeutic potential and safety of homeopathy remain well documented in the literature (5, 6, 221, 222).

In the case of NPs, the quantities needed to activate the endogenous processes of beneficial adaptation of hormesis are extremely low (9, 69). Within homeopathy, Hahnemann focused on the adaptive reaction of the organism to the remedy as the origin of the therapeutic effects. He actually used low doses to minimize or avoid the initial direct actions of medicines on the organism, i.e., the toxic effects of conventional drug doses. Instead, he pointed out the importance of using low doses of medicines to evoke the adaptive reactions that throw off the pre-existing disease processes in the organism from within (71): "...This back-action belongs to our sustentive power of life and is an automatic function of it, called the after-action or counter-action."

5. HOMEOPATHY AS ADAPTIVE NETWORK NANOMEDICINE

Hormetic adaptations engage the biological plasticity and metaplasticity of the organism as a complex living system. In modern scientific terminology, the counter-actions that Hahnemann described are considered adaptive responses of the organism as a complex adaptive system or network (69, 184, 218, 223-227). Any medicine constitutes a perturbation of the biological steady state internal milieu of the organism, though high doses produce such strong direct actions that the adaptive reactions are masked until the drug is withdrawn. In contrast, for homeopathy, the low doses of the individually-salient nanomedicine, given intermittently, primarily reveal the organism's robust counter-action after only a minor or undetectable direct action. Conventional pharmacology relies on direct drug actions; homeopathic treatment relies on indirect organism reactions or adaptations (71).

The current research literature recognizes that the biology of the stress response in adaptation involves a multi-factorial set of interactive and self-regulatory pathways in the immune, endocrine, central nervous, autonomic nervous, and metabolic systems of the body (8, 40, 177, 181, 184, 215, 216, 218). Mobilizing one element of these stress response pathways typically cascades into activation of others throughout the rest of the interconnected network (68, 96, 179, 180, 184, 216-218, 228, 229). In an intact organism, the brain plays a hub role in coordinating and regulating the bidirectional information flow to and from the other components of the stress response network (216, 230). The stress response network is the organism's interface with or first responder to environmental change, threat, or danger (8, 68, 89, 171, 197). Furthermore, this adaptive network is an amplifier of endogenous reactivity to the same or a subsequent cross-sensitized threat (194, 195, 197, 198, 231, 232).

McEwen (215), Csermely (181), and others have postulated that many chronic diseases of developed societies reflect a cumulative overload on the adaptive capacity of the individual. As a result, genetic vulnerabilities interact with epigenetic influences, i.e., environmental stressors of all types at higher intensity, to induce dysfunctional shifts in physiological setpoints for protecting the cells and organism from adverse effects of stress. Thus, chronic diseases reflect cumulative maladaptation to what McEwen terms "allostatic overload" at the organism level (215) or Csermely calls "chaperone (protein) overload" at the cellular level (181) of network organizational scale.

In one-cell model systems, mobilizing heat shock proteins in the stress response network causes a self-reorganization of functional links between molecular effectors (179, 180). The adaptive changes in network linkages prepare the system biologically for better resisting or recovering from the environmental threat that the stressor represents (179, 180). Recovering from the effects of the stressor translates into restoration of the unstressed network configuration and interactional patterns (233, 234). Figure 3 illustrates the different types of functional network self re-organization that cells undertake in response to different levels of stress. Such processes also appear to have parallels in the nature of integrative healing from acute or chronic disease at the organism level of scale (202, 203, 212, 235). Complex network systems exhibit recurrent, interactive themes or motifs between global and local levels of scale (236). Given the essential contribution of the complex system to remedy effects, the model suggests that homeopathic NPs will only reveal their fullest capacity to trigger adaptive changes when evaluated in an intact organism rather than just a cell. In fact, Baumgartner, in reviewing the basic science research literature on homeopathic remedies, concluded that the most robust effects of homeopathic remedies appear to occur in whole organisms rather than isolated cell systems (112).

Thus, homeopathic nanoparticles are potent, salient environmental stressors for cells and the global organism as complex adaptive systems or networks. The endogenous adaptive response of the organism is strong enough in many cases to boost systemic recovery processes and overcome the established acute or chronic disease by reversing the complex set of adaptations originally made in response to past cumulative stressors of all types. Data show that endogenous adaptive responses can and do grow in magnitude with the passage of time (197, 237). The pulsed timing or intermittent dosing regimen of homeopathic remedies allows the organism sufficient time to react to a given discrete dose and to evolve its most complete self-amplified response.

The intensity of the reaction to a salient remedy stems from the enhanced adjuvant and stressor qualities of the nanoparticles in the remedy (69). The ability of the remedy to address the net adaptive dysfunctions of the whole system derives from cross-adaptation (194, 195, 232). That is, the adaptive responses that the remedy's source material can elicit are specifically cross-adapted (238) to the individual's unique pattern of previously established adaptations made in response to past higher intensity stressors (59, 215, 239, 240).

The scientific precedent for this type of cross-adaptation is found in an extensive research literature in physiology and neuroscience (194, 195, 197, 232). Stressors from different categories can cross-adapt or cross-sensitize with one another, e.g., hypoxia and cold temperature (195, 232), stress and amphetamine or cocaine (196, 241), formaldehyde and cocaine (199), sucrose and amphetamine or cocaine or ethanol (200, 242-245). Early life stress leads to persistent pro-inflammatory changes in modulation of immune function and increases susceptibility to multiple different diseases in adulthood (215, 239, 240, 246). Even adaptations to a single environmental toxin exposure with a fungicide in previous generations can carry over transgenerationally by inherited epigenetic changes (cf., "miasms" in homeopathic terminology (247)). The resultant adverse epigenetic adaptations lead to alterations in the brain chemistry, function, and behavior in subsequent generations' responses to stress (248).

A remaining question is why would a homeopathic remedy trigger the organism to reverse course and recover from a disease? Here the answer is that directionality of responses in a complex adaptive system is flexible, dependent partly on the intensity of the stressor (9, 214) and partly on the state of organism (197, 202, 249-251). A system at its physiological limits is potentially susceptible to undergoing massive changes, with nonlinear dynamical shifts upon the arrival of a small salient stressor such as a low dose of homeopathic medicine NPs (202, 237). The impact would be an abrupt self-organized phase transition into a new and different dynamical pattern (202, 251).

Low intensity stressors initiate adaptations in the opposite direction to those of higher intensity stressors (214). Adaptive plasticity is itself modulated by the phenomenon of metaplasticity in the organism, e.g., the plasticity of synaptic plasticity in the central nervous system (252). That is, the last stressor or stimulus potentially preconditions or primes the system to respond back in the opposite direction on the subsequent encounter with the same or cross-adapted/cross-sensitized stressor or stimulus (252). Thus, if prior higher intensity life stressors, infections, traumas, and adverse biological events have accumulated a stressor overload on the adaptive capacity of the organism (215), then the small intensity stressor of salient nanoparticles in a homeopathic remedy could trigger a sudden reversal in direction back towards health (202).

Metaplasticity reflects the effort of the organism to maintain function within a physiologically viable range around a set point as compatible as possible with good function and survival (218, 252). When adaptations to previous stressors have pushed function too far from the healthy set point in one direction, the arrival of the next relevant stimulus can trigger adaptive changes that push function back in the opposite direction. The homeopathic remedy, with its salience to the emergent global themes or motifs of the organism (236, 253) in adapting to the established acute infection, injury, or chronic disease state (e.g., homeopathic modalities of worse at altitude or in cold temperatures, better at a certain time of day or after eating) would activate the organism's existing metaplastic priming to reverse direction and shift the set point and physiological range back toward a healthy normal.

As a precedent, prior treatment with a given stressor or drug in animals or people can elicit a change in the opposite direction for responses to the same or cross-adapted/cross-sensitized agent when the system is close to its physiological limits (213, 214, 237). A properly timed discrete pulse can also interrupt a cardiac arrhythmia or seizure in the brain, causing the system to revert to normal dynamical function (254-256).

Biphasic or oscillatory dynamics are a well-known phenomenon to researchers in nonlinear dynamical systems and complex systems science, especially at phase transitions from one steady state into another (202, 249, 250, 257). Empirically, homeopathic remedies can induce biphasic oscillatory responses in human subjects and animals in central nervous system and other psychophysiological outcomes that placebos do not cause, even when the remedy is not acting therapeutically (22, 27, 35, 48).

On the other hand, if clinical recovery occurs, homeopathic practice theory postulates that symptoms will reorganize over time to affect different bodily subsystems in a hierarchical manner. The correct remedy serves as an inducer of a qualitative phase transition in the overall organism (202, 212, 250). That is, during successful homeopathic treatment, changes shift spatially over time after the remedy dose, down the body, from inner organs outward toward the skin, and in reverse order of original appearance in time (235). The self-organizing properties of complex adaptive systems (180, 254, 258) would account for the latter observations under clinically effective homeopathic treatment.

6. SUMMARY AND CONCLUSIONS

The Nanoparticle-Cross-Adaptation-Sensitization model for homeopathic remedies (59) provides an evidence-based foundation for a comprehensive research program and new clinical approaches to integrative medical treatment. The perspectives of this paper and the data that will emerge from such a research program can help practitioners better understand when and how to utilize homeopathic remedies for their patients. For instance, the strong real-world track record of homeopathy in treating a range of infectious diseases (8, 222, 259-262) may be explained by the ability of salient remedy along with silica nanoparticles, to act as super-adjuvants, stimulate a vigorous increased immune response, and overcome the infectious agent (68, 89, 90).

The model also helps account for the importance of administering remedies only in a pulsed, intermittent manner until symptoms begin to change (263). At that point, it is the organism, not the remedy, that is carrying the response forward. Consequently, it is essential to stop giving additional remedy doses unless and until symptoms begin to plateau or relapse (263). The risk of excessive dose frequency in homeopathy would be inducing worsened symptoms, as is found in homeopathic remedy pathogenetic testing on initially healthy human subjects or animals (48, 264, 265).

Homeopathic remedies, because of the way they are made by intensive manual grinding in lactose (72, 101, 102, 106) and/or vigorous shaking to create turbulence in ethanol-water solutions (74), are small quantities of nanoparticles of their source material (60, 61, 63). Remedies stored in glass and delivered after additional succussions in water could also contribute nanosilica NPs as immune adjuvants and conveyors of remedy source-specific structural information. Succussions could also disperse source nanostructure aggregrates into smaller sizes at the moment of administration. Consistent with remedy NP aggregation, Elia et al (121) previously showed that shelf storage of liquid remedies in small volumes leads to measurable changes in thermal and electrical conductivity properties. Such findings could relate to changes in NP morphology from Ostwald ripening during storage. Nanoparticles are highly adsorptive, active and reactive agents with properties that differ markedly from those of their bulk forms (83, 84). Used homeopathically in very low, intermittent doses within the hormetic dose-response range, remedies trigger adaptive, self-amplified reactions in the local cells (52-54) and global organism (28, 30, 59).

Because of the interconnected network nature of complex living systems (202, 224, 225), the changes that a small dose of remedy nanoparticles can initiate in one component of the stress response network, lead to a large, systemic cascade of adaptive changes. The homeopathically-induced adaptations constitute a nonlinear phase transition of system setpoints and dynamics of the organism into a qualitatively different, healthier state. The remedy source's salience to the pre-existing adaptations that the organism with disease currently experiences is the basis for large magnitude salutary changes throughout the organism as an integrative whole system (cusp catastrophe (202) or self-organized criticality (251) events in complexity science terminology). Global and local levels of organization within the organism share interactive themes or motifs to which the salient remedy effects are well-matched (247, 253, 263, 266-268). Once initiated, changes at global and local levels of the system shape each other's dynamics back towards recovery and better health (18, 59, 212).

Based on the evidence, trying to invoke direct linear, local interactions of ordinary drug ligands with specific receptors that characterize conventional pharmacological effects is insufficient to explain the data on homeopathic remedies. Unlike conventional biomedical drugs, homeopathic remedies are chosen to be specific to the emergent themes of dysfunction in the entire organism, not necessarily to the mechanism of only one specific local symptom (263, 269). Placebo effects are also inadequate to explain the totality of the data (5, 6). A large number of placebo controlled plant, animal, and cellular studies, as well as preclinical and clinical studies on human subjects, indicate that remedies exert effects distinct from placebo (5, 8, 270-273).

Homeopathy is not a conventional pharmaceutical practice; remedies are not conventional drugs. Rather, as nanoparticles, homeopathic remedies are low intensity environmental stressors that the organism detects as threats to its survival. The biology of the stress response networks mobilizes to address the remedy-specific challenge. The nanoparticles in the remedy, augmented by silica nanostructures, also act as adjuvants and/or non-immunological stressors to provoke a disproportionately strong systemic reaction. Immune, inflammatory, metabolic, endocrine, and nervous system pathways (8, 68, 170, 180, 184, 193, 216, 218, 230, 233, 274) are likely involved in carrying out the adaptive changes in response to an individually salient remedy. Quantum properties of nanoparticles (84, 118, 123) may also contribute to some findings with homeopathic remedies (124).

The political biases against homeopathy remain intense. Biases fuel skepticism even when scientific evidence shows the skeptics' assumptions and beliefs to be incorrect in their total rejection of the plausibility of homeopathy. If anything, this CAM/IM field was centuries ahead of its time, and modern science is finally providing measurement tools such as atomic force and transmission electron microscopy (60, 61, 84), specialized forms of spectroscopy (63, 78) and nanoparticle sizing techniques (219), multivariate biological stress response profiling (177), systems biology (275, 276) and nonlinear dynamical analytic methods for physiology and behavior (18, 35, 202, 203, 257, 277) to test and refine the model. However, in view of the unrelenting skepticism that homeopathy has faced since its inception, we propose that future research on "homeopathic remedies" and the practice theory of "homeopathy" instead begin using new terminology.

Taken together, the evidence indicates that a modern, scientifically more relevant, but neutral integrative term for homeopathy should be "adaptive network nanomedicine."

7. ACKNOWLEDGEMENTS

This study was supported in part by National Center for Complementary and Alternative Medicine grant T32 AT01287 (PI: IRB). Dr. Bell serves as a consultant to Standard Homeopathic Co./Hyland's Inc., a homeopathic manufacturer whose products were not used in the cited studies. Standard Homeopathic Co./Hyland's Inc. did not provide any funding for cited studies, the current paper or publication costs.

8. REFERENCES

1. P. Fisher: What is homeopathy? An introduction. Front Biosci (Elite Ed) 4, 1669-82 (2012)

2. P. N. Kaul: Alternative therapeutic modalities. Alternative medicine. Progress in Drug Research 47, 251-277 (1996)
PMid:8961769

3. M. Frass, R. P.Strassl, H. Friehs, M. Mullner, M. Kundi and A.D. Kaye: Use and acceptance of complementary and alternative medicine among the general population and medical personnel: a systematic review. Ochsner J 12(1), 45-56 (2012)
PMid:22438782    PMCid:3307506

4. R. L. Nahin, P. M. Barnes, B. J. Stussman and B. Bloom: Costs of Complementary and Alternative Medicine (CAM) and Frequency of Visits to CAM Practitioners: United States, 2007. In: National Health Statistics Reports. National Center for Health Statistics, Hyattsville, MD (2009)

5. C. Witt and H. Albrecht: New Directions in Homeopathy Research. KVC Verlag, Essen, Germany (2009)

6. G. Bornhoft and P. F. Matthiessen: Homeopathy in Healthcare -- Effectiveness, Appropriateness, Safety, Costs. Springer (2011)
http://dx.doi.org/10.1007/978-3-642-20638-2

7. M. Rossignol, B. Begaud, P. Engel, B. Avouac, F. Lert, F. Rouillon, J. Benichou, J. Massol, G. Duru, A. M. Magnier, D. Guillemot, L. Grimaldi-Bensouda, L. Abenhaim and for the EPI3-LA-SER group: Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort. Pharmacoepidemiol Drug Saf (2012)
http://dx.doi.org/10.1002/pds.3316
PMid:22782803

8. P. Bellavite, M. Marzotto, S. Chirumbolo and A. Conforti: Advances in homeopathy and immunology: a review of clinical research. Front Biosci (Schol Ed) 3, 1363-89 (2011)
http://dx.doi.org/10.2741/230

9. E. Malarczyk, M. Pazdzioch-Czochra, M. Graz, J. Kochmanska-Rdest and A. Jarosz-Wilkolazka: Nonlinear changes in the activity of the oxygen-dependent demethylase system in Rhodococcus erythropolis cells in the presence of low and very low doses of formaldehyde. Nonlinear Biomed Phys 5(1), 9 (2011)
http://dx.doi.org/10.1186/1753-4631-5-9
PMid:22104369    PMCid:3229444

10. P. Bellavite, Signorini, A.: The Emerging Science of Homeopathy. Complexity, Biodynamics, and Nanopharmacology. North Atlantic Books, Berkeley (2002)

11. Lancet: The end of homeopathy. Lancet 366, 690 (2005)
http://dx.doi.org/10.1016/S0140-6736(05)67149-8

12. R. Ludtke and A. L. Rutten: The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol 61(12), 1197-204 (2008)
http://dx.doi.org/10.1016/j.jclinepi.2008.06.015
PMid:18834714

13. A. Shang, K. Huwiler-Muntener, L. Nartey, P. Juni, S. Dorig, J. A. Sterne, D. Pewsner and M. Egger: Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathyLancet 366(9487), 726-32 (2005)

14. M. Aickin: The end of biomedical journals: there is madness in their methods. Journal of Alternative & Complementary Medicine 11(5), 755-757 (2005)
http://dx.doi.org/10.1089/acm.2005.11.755
PMid:16296895

15. J. Jacobs, A. L. Williams, C. Girard, N. V.Y. and D. Katz: Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized controlled trial. Journal of Alternative & Complementary Medicine 11(5), 799-806 (2005)
http://dx.doi.org/10.1089/acm.2005.11.799
PMid:16296913

16. S. Brien, L. Lachance, P. Prescott, C. McDermott and G. Lewith: Homeopathy has clinical benefits in rheumatoid arthritis patients that are attributable to the consultation process but not the homeopathic remedy: a randomized controlled clinical trial. Rheumatology (Oxford) 50(6), 1070-82 (2011)
http://dx.doi.org/10.1093/rheumatology/keq234
PMid:21076131    PMCid:3093927

17. A. P. Bikker, S. W. Mercer and D. Reilly: A pilot prospective study on the consultation and relational empathy, patient enablement, and health changes over 12 months in patients going to the Glasgow Homoeopathic Hospital. J Altern Complement Med 11(4), 591-600 (2005)
http://dx.doi.org/10.1089/acm.2005.11.591
PMid:16131282

18. I. R. Bell, M. Koithan and D. Pincus: Research methodological implications of nonlinear dynamical systems models for whole systems of complementary and alternative medicine. Forschende Komplementarmedizin und Klassische Naturheilkunde 19(Supplement 1), 15-21 (2012)
http://dx.doi.org/10.1159/000335183
PMid:22327547

19. R. T. Mathie, H. Roniger, M. Van Wassenhoven, J. Frye, J. Jacobs, M. Oberbaum, M. F. Bordet, C. Nayak, G. Chaufferin, J. A. Ives, F. Dantas and P. Fisher: Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study. BMC Med Res Methodol 12(1), 49 (2012)
http://dx.doi.org/10.1186/1471-2288-12-49
PMid:22510227    PMCid:3394086

20. H. Frei, R. Everts, K. von Ammon, F. Kaufmann, D. Walther, S. F. Schmitz, M. Collenberg, M. Steinlin, C. Lim and A. Thurneysen: Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial. Homeopathy 96(1), 35-41 (2007)
http://dx.doi.org/10.1016/j.homp.2006.11.004
PMid:17227746

21. G. T. Lewith, A. D. Watkins, M. E. Hyland, S. Shaw, J. A. Broomfield, G. Dolan and S. T. Holgate: Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial. BMJ 324(7336), 520-523 (2002)
http://dx.doi.org/10.1136/bmj.324.7336.520
PMid:11872551    PMCid:67767

22. M. E. Hyland and G. T. Lewith: Oscillatory effects in a homeopathic clinical trial: an explanation using complexity theory, and implications for clinical practice. Homeopathy 91(3), 145-149 (2002)
http://dx.doi.org/10.1054/homp.2002.0025
PMid:12322867

23. M. van Wassenhoven and G. Ives: An observational study of patients receiving homeopathic treatment. Homeopathy 93(1), 3-11 (2004)
http://dx.doi.org/10.1016/j.homp.2003.11.010
PMid:14960096

24. R. Pomposelli, V. Piasere, C. Andreoni, G. Costini, E. Tonini, A. Spalluzzi, D. Rossi, C. Quarenghi, M. E. Zanolin and P. Bellavite: Observational study of homeopathic and conventional therapies in patients with diabetic polyneuropathy. Homeopathy 98(1), 17-25 (2009)
http://dx.doi.org/10.1016/j.homp.2008.11.006
PMid:19135955

25. E. Rossi, C. Endrizzi, M. A. Panozzo, A. Bianchi and M. Da Fre: Homeopathy in the public health system: a seven-year observational study at Lucca Hospital (Italy). Homeopathy 98(3), 142-8 (2009)
http://dx.doi.org/10.1016/j.homp.2009.04.001
PMid:19647207

26. M. Trichard, Chaufferin, G., Nicoloyannis, N.: Pharmacoeconomic comparison between homeopathic and antibiotic treatment strategies in recurrent acute rhinopharyngitis in children. Homeopathy. Journal of the Faculty of Homeopathy 94(1), 3-9 (2005)
http://dx.doi.org/10.1016/j.homp.2004.11.021
PMid:15751328

27. I. R. Bell, Howerter, A., Jackson, N., Brooks, A.J., Schwartz, G.E.: Multi-week resting EEG cordance change patterns from repeated olfactory activation with two constitutionally-salient homeopathic remedies in healthy young adults. J Alternative and Complementary Medicine 18(5), 445-53 (2012)
http://dx.doi.org/10.1089/acm.2011.0931
PMid:22594648

28. I. R. Bell, D. A. Lewis, 2nd, G. E. Schwartz, S. E. Lewis, O. Caspi, A. Scott, A. J. Brooks and C. M. Baldwin: Electroencephalographic cordance patterns distinguish exceptional clinical responders with fibromyalgia to individualized homeopathic medicines. Journal of Alternative & Complementary Medicine 10(2), 285-99 (2004)
http://dx.doi.org/10.1089/107555304323062275
PMid:15165409

29. I. R. Bell, A. Howerter, N. Jackson, M. Aickin, C. M. Baldwin and R. R. Bootzin: Effects of homeopathic medicines on polysomnographic sleep of young adults with histories of coffee-related insomnia. Sleep Med 12(5), 505-11 (2011)
http://dx.doi.org/10.1016/j.sleep.2010.03.013
PMid:20673648    PMCid:2972403

30. I. R. Bell, D. A. Lewis, 2nd, S. E. Lewis, G. E. Schwartz, A. J. Brooks, A. Scott and C. M. Baldwin: EEG alpha sensitization in individualized homeopathic treatment of fibromyalgia. International Journal of Neuroscience 114(9), 1195-220 (2004)
http://dx.doi.org/10.1080/00207450490475724
PMid:15370183

31. I. R. Bell, Brooks, A.J., Howerter, A., Jackson, N., Schwartz, G.E.: Short term effects of repeated olfactory administration of homeopathic Sulphur or Pulsatilla on electroencephalographic alpha power in healthy young adults. Homeopathy 100(4), 203-11 (2011)
http://dx.doi.org/10.1016/j.homp.2011.06.005
PMid:21962194

32. I. R. Bell, A. J. Brooks, A. Howerter, N. Jackson and G. E. Schwartz: Acute electroencephalographic effects from repeated olfactory administration of homeopathic remedies in individuals with self-reported chemical sensitivity. Alternative Therapies in Health and Medicine in press (2012)
PMCid:3376904

33. G. Ruiz-Vega, Perez-Ordaz, L., Cortes-Galvan L., Juarez-G, F.M.: A kinetic approach to caffeine-Coffea cruda interaction. Homeopathy: the Journal of the Faculty of Homeopathy., 92(1), 19-29 (2003)

34. G. Ruiz-Vega, Poitevin, B., Pérez-Ordaz, L.: Histamine at high dilution reduces spectral density in delta band in sleeping rats. Homeopathy94(2), 86-91 (2005)
http://dx.doi.org/10.1016/j.homp.2004.10.002
PMid:15892488

35. I. R. Bell, A. Howerter, N. Jackson, M. Aickin and R. R. Bootzin: Nonlinear dynamical systems effects of homeopathic remedies on multiscale entropy and correlation dimension of slow wave sleep EEG in young adults with histories of coffee-induced insomnia. Homeopathy 101(3), 182-92 (2012)
http://dx.doi.org/10.1016/j.homp.2012.05.007
PMid:22818237

36. G. Ruiz, Torres, J.L.: Homeopathic effect on the sleep pattern of rats. British Homoeopathic Journal 86, 201-206 (1997)
http://dx.doi.org/10.1016/S0007-0785(97)80045-2

37. M. A. Myagkova, T. V. Abramenko, O. N. Panchenko and O. I. Epstein: Antibodies to delta sleep-inducing peptide in ultralow doses: study of the effect by enzyme immunoassay. Bull Exp Biol Med 135 Suppl 7, 102-4 (2003)
http://dx.doi.org/10.1023/A:1024759503580
PMid:12949667

38. D. Das, A. De, S. Dutta, R. Biswas, N. Boujedaini and A. R. Khuda-Bukhsh: Potentized homeopathic drug Arsenicum Album 30C positively modulates protein biomarkers and gene expressions in Saccharomyces cerevisae exposed to arsenate. Zhong Xi Yi Jie He Xue Bao 9(7), 752-60 (2011)
http://dx.doi.org/10.3736/jcim20110709
PMid:21749826

39. A. R. Khuda-Bukhsh: Towards understanding molecular mechanisms of action of homeopathic drugs: an overview. Mol Cell Biochem 253(1-2), 339-45 (2003)
http://dx.doi.org/10.1023/A:1026048907739
PMid:14619985

40. A. R. Khuda-Bukhsh, S. S. Bhattacharyya, S. Paul, S. Dutta, N. Boujedaini and P. Belon: Modulation of Signal Proteins: A Plausible Mechanism to Explain How a Potentized Drug Secale Cor 30C Diluted beyond Avogadro's Limit Combats Skin Papilloma in Mice. Evid Based Complement Alternat Med 2011, 286320 (2011)
PMid:19617203    PMCid:3136355

41. A. R. Khuda-Bukhsh, A. De, D. Das, S. Dutta and N. Boujedaini: Analysis of the capability of ultra-highly diluted glucose to increase glucose uptake in arsenite-stressed bacteria Escherichia coli. Zhong Xi Yi Jie He Xue Bao 9(8), 901-12 (2011)
http://dx.doi.org/10.3736/jcim20110813
PMid:21849152

42. P. Mallick, J. C. Mallick, B. Guha and A. R. Khuda-Bukhsh: Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice. BMC Complement Altern Med 3, 7 (2003)
http://dx.doi.org/10.1186/1472-6882-3-7
PMid:14570596    PMCid:521186

43. P. Gal, T. Vasilenko, I. Kovac, M. Kostelnikova, J. Jakubco, P. Szabo, B. Dvorankova, F. Sabol, H. J. Gabius and K. Smetana, Jr.: Atropa belladonna L. water extract: modulator of extracellular matrix formation in vitro and in vivo. Physiol Res (2012)

44. E. C. Ive, I. M. Couchman and L. Reddy: Therapeutic effect of Arsenicum album on leukocytes. Int J Mol Sci 13(3), 3979-87 (2012)
http://dx.doi.org/10.3390/ijms13033979
PMid:22489193    PMCid:3317753

45. S. Pathak, A. S. Multani, P. Banerji and P. Banerji: Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer. Int J Oncol23(4), 975-82 (2003)
PMid:12963976

46. S. Porozov, L. Cahalon, M. Weiser, D. Branski, O. Lider and M. Oberbaum: Inhibition of IL-1beta and TNF-alpha secretion from resting and activated human immunocytes by the homeopathic medication Traumeel S. Clinical & Developmental Immunology 11(2), 143-9 (2004)
http://dx.doi.org/10.1080/10446670410001722203
PMid:15330450    PMCid:2270708

47. C. Ramachandran, P. K. Nair, R. T. Clement and S. J. Melnick: Investigation of cytokine expression in human leukocyte cultures with two immune-modulatory homeopathic preparations. J Altern Complement Med 13(4), 403-7 (2007)
http://dx.doi.org/10.1089/acm.2007.6292
PMid:17532732

48. S. Bertani, S. Lussignoli, G. Andrioli, P. Bellavite and A. Conforti: Dual effects of a homeopathic mineral complex on carrageenan-induced oedema in rats. British Homoeopathic Journal, 88(3), 101-5 (1999)
http://dx.doi.org/10.1054/homp.1999.0310
PMid:10449049

49. S. Das, S. K. Saha, A. De, D. Das and A. R. Khuda-Bukhsh: Potential of the homeopathic remedy, Arnica Montana 30C, to reduce DNA damage in Escherichia coli exposed to ultraviolet irradiation through up-regulation of nucleotide excision repair genes. Zhong Xi Yi Jie He Xue Bao 10(3), 337-46 (2012)
http://dx.doi.org/10.3736/jcim20120314
PMid:22409925

50. A. De, D. Das, S. Dutta, D. Chakraborty, N. Boujedaini and A. R. Khuda-Bukhsh: Potentized homeopathic drug Arsenicum Album 30C inhibits intracellular reactive oxygen species generation and up-regulates expression of arsenic resistance gene in arsenine-exposed bacteria Escherichia coli. J Chinese Integrative Med 10(2), 210-27 (2012)
http://dx.doi.org/10.3736/jcim20120212
PMid:22313889

51. S. Lussignoli, S. Bertani, H. Metelmann, P. Bellavite and A. Conforti: Effect of Traumeel S, a homeopathic formulation, on blood-induced inflammation in rats. Complementary Therapies in Medicine 7(4), 225-30 (1999)
http://dx.doi.org/10.1016/S0965-2299(99)80006-5

52. R. Van Wijk and F. A. Wiegant: Postconditioning hormesis and the homeopathic Similia principle: molecular aspects. Hum Exp Toxicol 29(7), 561-5 (2010)
http://dx.doi.org/10.1177/0960327110369860

53. R. Van Wijk and F. A. Wiegant: Postconditioning hormesis and the similia principle. Front Biosci (Elite Ed, 3, 1128-38 (2011)

54. F. A. Wiegant, H. A. Prins and R. Van Wijk: Postconditioning hormesis put in perspective: an overview of experimental and clinical studies. Dose Response 9(2), 209-24 (2011)
http://dx.doi.org/10.2203/dose-response.10-004.Wiegant
PMid:21731537    PMCid:3118768

55. C. C. de Oliveira, S. M. de Oliveira, V. M. Goes, C. M. Probst, M. A. Krieger and F. Buchi Dde: Gene expression profiling of macrophages following mice treatment with an immunomodulator medication. J Cell Biochem 104(4), 1364-77 (2008)
http://dx.doi.org/10.1002/jcb.21713
PMid:18286468

56. P. Belon, Cumps J, Ennis M, Mannaioni PF, Roberfroid M, Sainte-Laudy J, Wiegant FA.: Histamine dilutions modulate basophil activation. Inflamm Res 53(5), 181-8 (2004)
http://dx.doi.org/10.1007/s00011-003-1242-0
PMid:15105967

57. C. O. Coelho Moreira, J. de Fatima Ferreira Borges da Costa, M. F. Leal, E. Ferreira de Andrade, A. P. Rezende, A. A. Imbeloni, J. A. Pereira Carneiro Muniz, M. de Arruda Cardoso Smith, R. R. Burbano and P. P. de Assumpcao: Lymphocyte proliferation stimulated by activated Cebus apella macrophages treated with a complex homeopathic immune response modifiers. Homeopathy 101(1), 74-9 (2012
http://dx.doi.org/10.1016/j.homp.2011.09.001
PMid:22226318

58. W. K. Pereira, M. V. Lonardoni, R. Grespan, S. M. Caparroz-Assef, R. K. Cuman and C. A. Bersani-Amado: Immunomodulatory effect of Canova medication on experimental Leishmania amazonensis infection. J Infect 51(2), 157-64 (2005)
http://dx.doi.org/10.1016/j.jinf.2004.09.009
PMid:16038768

59. I. R. Bell: Homeopathy as systemic adaptational nanomedicine: the nanoparticle-cross-adaptation-sensitization model. American Journal of Homeopathic Medicine in press (2012)

60 R.P. Upadhyay, C. Nayak: Homeopathy emerging as nanomedicine. Int J High Dilution Res 10(37), 299-310 (2011)

61. P. S. Chikramane, A. K. Suresh, J. R. Bellare and S. G. Kane: Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Homeopathy 99(4), 231-42 (2010)
http://dx.doi.org/10.1016/j.homp.2010.05.006
PMid:20970092

62. S. S. Bhattacharyya, J. Das, S. Das, A. Samadder, D. Das, A. De, S. Paul and A. R. Khuda-Bukhsh: Rapid green synthesis of silver nanoparticles from silver nitrate by a homeopathic mother tincture Phytolacca Decandra. Zhong Xi Yi Jie He Xue Bao 10(5), 546-54 (2012)
http://dx.doi.org/10.3736/jcim20120510
PMid:22587977

63. S. S. Bhattacharyya, S. K. Mandal, R. Biswas, S. Paul, S. Pathak, N. Boujedaini, P. Belon and A. R. Khuda-Bukhsh: In vitro studies demonstrate anticancer activity of an alkaloid of the plant Gelsemium sempervirens. Exp Biol Med (Maywood) 233(12), 1591-601 (2008)
http://dx.doi.org/10.3181/0805-RM-181
PMid:18997108

64. J. A. Ives, J. R. Moffett, P. Arun, D. Lam, T. I. Todorov, A. B. Brothers, D. J. Anick, J. Centeno, M. A. Namboodiri and W. B. Jonas: Enzyme stabilization by glass-derived silicates in glass-exposed aqueous solutions. Homeopathy 99(1), 15-24 (2010)
http://dx.doi.org/10.1016/j.homp.2009.11.006
PMid:20129173

65. B. M. Mohamed, N. K. Verma, A. Prina-Mello, Y. Williams, A. M. Davies, G. Bakos, L. Tormey, C. Edwards, J. Hanrahan, A. Salvati, I. Lynch, K. Dawson, D. Kelleher and Y. Volkov: Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity. J Nanobiotechnology 9, 29 (2011)
http://dx.doi.org/10.1186/1477-3155-9-29
PMid:21801388    PMCid:3164618

66. X. Yang, J. Liu, H. He, L. Zhou, C. Gong, X. Wang, L. Yang, J. Yuan, H. Huang, L. He, B. Zhang and Z. Zhuang: SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells. Part Fibre Toxicol 7, 1 (2010)
http://dx.doi.org/10.1186/1743-8977-7-1
PMid:20180970    PMCid:2830991

67. M. Zhu, Y. Li, J. Shi, W. Feng, G. Nie and Y. Zhao: Exosomes as extrapulmonary signaling conveyors for nanoparticle-induced systemic immune activation. Small 8(3), 404-12 (2012)

68. M. Zhu, X. Tian, X. Song, Y. Li, Y. Tian, Y. Zhao and G. Nie: Nanoparticle-Induced Exosomes Target Antigen-Presenting Cells to Initiate Th1-Type Immune Activation. Small (2012)

69. I. Iavicoli, E. J. Calabrese and M. A. Nascarella: Exposure to nanoparticles and hormesis. Dose Response 8(4), 501-17 (2010)
http://dx.doi.org/10.2203/dose-response.10-016.Iavicoli
PMid:21191487    PMCid:2990066

70. F. M. Winnik and D. Maysinger: Quantum Dot Cytotoxicity and Ways To Reduce It. Acc Chem Res (2012)
http://dx.doi.org/10.1021/ar3000585
PMid:22775328

71. S. Hahnemann: Organon of the Medical Art. 6th ed. Birdcage Books, Redmond, WA (1843)

72. C. L. DeCastro and B. S. Mitchell: Nanoparticles from mechanical attrition. In: Synthesis, Functionalization, and Surface Treatment of Nanoparticles. Ed M. I. Baraton. American Scientific Publisher, Valencia, CA (2002)

73. C. Tang, T. Zhou, J. Yang, Q. Zhang, F. Chen, Q. Fu and L. Yang: Wet-grinding assisted ultrasonic dispersion of pristine multi-walled carbon nanotubes (MWCNTs) in chitosan solution. Colloids Surf B Biointerfaces 86(1), 189-97 (2011)
http://dx.doi.org/10.1016/j.colsurfb.2011.03.041
PMid:21530188

74. Z. Zhu, K. Margulis-Goshen, S. Magdassi, Y. Talmon and C. W. Macosko: Polyelectrolyte stabilized drug nanoparticles via flash nanoprecipitation: a model study with beta-carotene. J Pharm Sci 99(10), 4295-306 (2010)
http://dx.doi.org/10.1002/jps.22090
PMid:20143406

75. D. Philip: Green synthesis of gold and silver nanoparticles using Hibiscus rosa sinensis. Physica E: Low Dimens Sys Nanostruct 42, 1417-24 (2010)
http://dx.doi.org/10.1016/j.physe.2009.11.081

76. S. S. Bhattacharyya, S. Paul and A. R. Khuda-Bukhsh: Encapsulated plant extract (Gelsemium sempervirens) poly (lactide-co-glycolide) nanoparticles enhance cellular uptake and increase bioactivity in vitro. Exp Biol Med (Maywood) 235(6), 678-88 (2010)
http://dx.doi.org/10.1258/ebm.2010.009338
PMid:20511672

77. D. J. Prakash, S. Arulkumar and M. Sabesan: Effect of nanohypericum (Hypericum perforatum gold nanoparticles) treatment on restraint stress induced behavioral and biochemical alteration in male albino mice. Pharmacognosy Res 2(6), 330-4 (2010)
http://dx.doi.org/10.4103/0974-8490.75450
PMid:21713134    PMCid:3111690

78. M. L. Rao, R. Roy, I. R. Bell and R. Hoover: The defining role of structure (including epitaxy) in the plausibility of homeopathy. Homeopathy 96(3), 175-82 (2007)
http://dx.doi.org/10.1016/j.homp.2007.03.009
PMid:17678814

79. M. A. Hampton and A. V. Nguyen: Nanobubbles and the nanobubble bridging capillary force. Adv Colloid Interface Sci 154(1-2), 30-55 (2010)
http://dx.doi.org/10.1016/j.cis.2010.01.006
PMid:20152956

80. E. Y. Lukianova-Hleb, X. Ren, P. E. Constantinou, B. P. Danysh, D. L. Shenefelt, D. D. Carson, M. C. Farach-Carson, V. A. Kulchitsky, X. Wu, D. S. Wagner and D. O. Lapotko: Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems. PLoS ONE 7(4), e34537 (2012)
http://dx.doi.org/10.1371/journal.pone.0034537
PMid:22509318    PMCid:3317980

81. D. Wen: Intracellular hyperthermia: Nanobubbles and their biomedical applications. Int J Hyperthermia 25(7), 533-41 (2009)
http://dx.doi.org/10.3109/02656730903061617
PMid:19848616

82. A. R. Abbasi and A. Morsali: Influence of solvents on the morphological properties of AgBr nano-structures prepared using ultrasound irradiation. Ultrason Sonochem 19(3), 540-5 (2012)
http://dx.doi.org/10.1016/j.ultsonch.2011.08.002
PMid:21963874

83. C. Buzea, I. I. Pacheco and K. Robbie: Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2(4), MR17-71 (2007)
http://dx.doi.org/10.1116/1.2815690
PMid:20419892

84. E. Roduner: Size matters: why nanomaterials are different. Chemical Society Reviews 35(7), 583-92 (2006)
http://dx.doi.org/10.1039/b502142c
PMid:16791330

85. M. Song, S. Yuan, J. Yin, X. Wang, Z. Meng, H. Wang and G. Jiang: Size-dependent toxicity of nano-C60 aggregates: more sensitive indication by apoptosis-related Bax translocation in cultured human cells. Environ Sci Technol 46(6), 3457-64 (2012)
PMid:22352688

86. D. Napierska, L. C. Thomassen, V. Rabolli, D. Lison, L. Gonzalez, M. Kirsch-Volders, J. A. Martens and P. H. Hoet: Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small, 5(7) 846-53 (2009)
http://dx.doi.org/10.1002/smll.200800461
PMid:19288475

87. R. Yanagisawa, H. Takano, K. I. Inoue, E. Koike, K. Sadakane and T. Ichinose: Size effects of polystyrene nanoparticles on atopic dermatitislike skin lesions in NC/NGA mice. Int J Immunopathol Pharmacol 23(1), 131-41 (2010)
PMid:20378001

88. H. B. Nair, B. Sung, V. R. Yadav, R. Kannappan, M. M. Chaturvedi and B. B. Aggarwal: Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem Pharmacol 80(12), 1833-43 (2010)
http://dx.doi.org/10.1016/j.bcp.2010.07.021
PMid:20654584    PMCid:2974020

89. A. Bershteyn, M. C. Hanson, M. P. Crespo, J. J. Moon, A. V. Li, H. Suh and D. J. Irvine: Robust IgG responses to nanograms of antigen using a biomimetic lipid-coated particle vaccine. J Control Release 157(3), 354-65 (2012)
http://dx.doi.org/10.1016/j.jconrel.2011.07.029
PMid:21820024

90. M. Diwan, P. Elamanchili, M. Cao and J. Samuel: Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery. Curr Drug Deliv 1(4), 405-12 (2004)
http://dx.doi.org/10.2174/1567201043334597
PMid:16305402

91. A. L. Armstead and B. Li: Nanomedicine as an emerging approach against intracellular pathogens. Int J Nanomedicine 6, 3281-93 (2011)
PMid:22228996    PMCid:3252676

92. L. Zhongfa, M. Chiu, J. Wang, W. Chen, W. Yen, P. Fan-Havard, L. D. Yee and K. K. Chan: Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice. Cancer Chemother Pharmacol 69(3), 679-89 (2012)
http://dx.doi.org/10.1007/s00280-011-1749-y
PMid:21968952

93. M. O. Oyewumi, A. Kumar and Z. Cui: Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines 9(9), 1095-107 (2010)
http://dx.doi.org/10.1586/erv.10.89
PMid:20822351    PMCid:2963573

94. H. Zhang, X. He, Z. Zhang, P. Zhang, Y. Li, Y. Ma, Y. Kuang, Y. Zhao and Z. Chai: Nano-CeO2 exhibits adverse effects at environmental relevant concentrations. Environ Sci Technol 45(8), 3725-30 (2011)
http://dx.doi.org/10.1021/es103309n

95. I. Iavicoli, V. Leso, L. Fontana and A. Bergamaschi: Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci 15(5), 481-508 (2011)
PMid:21744743

96. P. Kovacic and R. Somanathan: Biomechanisms of nanoparticles (toxicants, antioxidants and therapeutics): electron transfer and reactive oxygen species. J Nanosci Nanotechnol 10(12), 7919-30 (2010)
http://dx.doi.org/10.1166/jnn.2010.3028
PMid:21121279

97. K. Wittmaack: Novel dose metric for apparent cytotoxicity effects generated by in vitro cell exposure to silica nanoparticles. Chem Res Toxicol 24(2), 150-8 (2011)
http://dx.doi.org/10.1021/tx100331w
PMid:21171596

98. L. Harhaji, A. Isakovic, N. Raicevic, Z. Markovic, B. Todorovic-Markovic, N. Nikolic, S. Vranjes-Djuric, I. Markovic and V. Trajkovic: Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. Eur J Pharmacol 568(1-3), 89-98 (2007)
http://dx.doi.org/10.1016/j.ejphar.2007.04.041
PMid:17560995

99. A. R. Khuda-Bukhsh, S. S. Bhattacharyya, S. Paul and N. Boujedaini: Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375. Zhong Xi Yi Jie He Xue Bao 8(9), 853-62 (2010)
http://dx.doi.org/10.3736/jcim20100909
PMid:20836976

100. B. Yang, Q. Wang, R. Lei, C. Wu, C. Shi, Y. Yuan, Y. Wang, Y. Luo, Z. Hu, H. Ma and M. Liao: Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics. J Nanosci Nanotechnol 10(12), 8527-37 (2010)
http://dx.doi.org/10.1166/jnn.2010.2481
PMid:21121362

101. E. Merisko-Liversidge and G. G. Liversidge: Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev 63(6), 427-40 (2011)
http://dx.doi.org/10.1016/j.addr.2010.12.007
PMid:21223990

102. E. Merisko-Liversidge, G. G. Liversidge and E. R. Cooper: Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci 18(2), 113-20 (2003)
http://dx.doi.org/10.1016/S0928-0987(02)00251-8

103. M. Elsabahy and K. L. Wooley: Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 41(7), 2545-61 (2012)
http://dx.doi.org/10.1039/c2cs15327k
PMid:22334259

104. S. K. Singh, K. K. Srinivasan, K. Gowthamarajan, D. S. Singare, D. Prakash and N. B. Gaikwad: Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide. Eur J Pharm Biopharm 78(3), 441-6 (2011)
http://dx.doi.org/10.1016/j.ejpb.2011.03.014
PMid:21439378

105. M. Wang, G. C. Rutledge, A. S. Myerson and B. L. Trout: Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing. J Pharm Sci 101(3), 1178-88 (2012)
http://dx.doi.org/10.1002/jps.23024
PMid:22189503

106. V. Caron, J. F. Willart, R. Lefort, P. Derollez, F. Danede and M. Descamps: Solid state amorphization kinetic of alpha lactose upon mechanical milling. Carbohydr Res 346(16), 2622-8 (2011)
http://dx.doi.org/10.1016/j.carres.2011.09.004
PMid:21983262

107. M. A. Tavares Cardoso, M. Talebi, P. A. Soares, C. U. Yurteri and J. R. van Ommen: Functionalization of lactose as a biological carrier for bovine serum albumin by electrospraying. Int J Pharmaceutics 414(1-2), 1-5 (2011)
http://dx.doi.org/10.1016/j.ijpharm.2011.04.045
PMid:21536114

108. L. Song, K. Yang, W. Jiang, P. Du and B. Xing: Adsorption of bovine serum albumin on nano and bulk oxide particles in deionized water. Colloids Surf B Biointerfaces 94, 341-6 (2012)
http://dx.doi.org/10.1016/j.colsurfb.2012.02.011
PMid:22405471

109. D. J. Anick and J. A. Ives: The silica hypothesis for homeopathy: physical chemistry. Homeopathy., 96(3), 189-95 (2007)
http://dx.doi.org/10.1016/j.homp.2007.03.005
PMid:17678816

110. Y. Liu, C. Lou, H. Yang, M. Shi and H. Miyoshi: Silica nanoparticles as promising drug/gene delivery carriers and fluorescent nano-probes: recent advances. Curr Cancer Drug Targets, 11(2), 156-63 (2011)
http://dx.doi.org/10.2174/156800911794328411
PMid:21158720

111. G. Bhakta, A. Shrivastava and A. Maitra: Magnesium phosphate nanoparticles can be efficiently used in vitro and in vivo as non-viral vectors for targeted gene delivery. J Biomed Nanotechnol, 5(1), 106-14 (2009)
http://dx.doi.org/10.1166/jbn.2009.029
PMid:20055113

112. S. Baumgartner: The State of Basic Research on Homeopathy. In: New Directions in Homeopathy Research. Ed C. Witt&H. Albrecht. KVC Verlag, Essen, Germany (2009)

113. S. Das, J. Das, A. Samadder, S. Bhattacharyya, D. Das, A. R. Khuda-Bukhsh: Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra, Gelsemium sempervirens, Hydastis canadensis and Thuja occidentalis induce differential cytotoxicity through G2/M arrest in A375 cells. Colloids Surf B: Biointerfaces 101, 325-336 (2013)
http://dx.doi.org/10.1016/j.colsurfb.2012.07.008

114. H. K. Baca, E. C. Carnes, C. E. Ashley, D. M. Lopez, C. Douthit, S. Karlin, C. J. Brinker: Cell-directed-assembly: directing the formation of nano/bio interfaces and architectures with living cells. Biochim Biophys Acta 1810(3), 259-67 (2011)
http://dx.doi.org/10.1016/j.bbagen.2010.09.005
PMid:20933574    PMCid:3090153

115. C. C. Perry and T. Keeling-Tucker: Model studies of colloidal silica precipitation using biosilica extracts from Equisetum telmateia. Colloid Polym Sci 281, 652-664 (2003)
http://dx.doi.org/10.1007/s00396-002-0816-7

116. B. Ruan and M. Jacobi: Ultrasonication effects on thermal and rheological properties of carbon nanotube suspensions. Nanoscale Research Letters 7(1), 127 (2012)
http://dx.doi.org/10.1186/1556-276X-7-127
PMid:22333487    PMCid:3359157

117. H. Konakanchi, R. Vajjha, D. Misra and D. Das: Electrical conductivity measurements of nanofluids and development of new correlations. J Nanosci Nanotechnol 11(8), 6788-95 (2011)
http://dx.doi.org/10.1166/jnn.2011.4217
PMid:22103081

118. P. Yao and S. Hughes: Macroscopic entanglement and violation of Bell's inequalities between two spatially separated quantum dots in a planar photonic crystal system. Opt Express 17(14), 11505-14 (2009)
http://dx.doi.org/10.1364/OE.17.011505
PMid:19582066

119. V. Elia and M. Niccoli: New physico-chemical properties of extremely diluted aqueous solutions. Journal of Thermal Analysis and Calorimetry 75, 815-836 (2004)
http://dx.doi.org/10.1023/B:JTAN.0000027178.11665.8f

120. V. Elia and M. Niccoli: Thermodynamics of extremely diluted aqueous solutions. Annals of the New York Academy of Sciences 879, 241-248 (1999)
http://dx.doi.org/10.1111/j.1749-6632.1999.tb10426.x
PMid:10415834

121. V. Elia, E. Napoli and R. Germano: The 'Memory of Water': an almost deciphered enigma. Dissipative structures in extremely dilute aqueous solutions. Homeopathy 96(3), 163-9 (2007)
http://dx.doi.org/10.1016/j.homp.2007.05.007
PMid:17678812

122. L. Rey: Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride. Physica A: Statistical mechanics and its applications 323, 67-74 (2003)

123. V. N. Pustovit and T. V. Shahbazyan: Fluorescence quenching near small metal nanoparticles. J Chem Phys 136(20), 204701 (2012)
http://dx.doi.org/10.1063/1.4721388
PMid:22667575

124. H. Walach: Entanglement model of homeopathy as an example of generalised entanglement predicted by weak quantum theory. Forschende Komplementarmedizin/Research in Complementary Medicine 10(4), 192-200 (2003)

125. O. A. Williams, J. Hees, C. Dieker, W. Jager, L. Kirste and C. E. Nebel: Size-dependent reactivity of diamond nanoparticles. ACS Nano 4(8), 4824-30 (2010)
http://dx.doi.org/10.1021/nn100748k
PMid:20731457

126. S. S. Mano, K. Kanehira, S. Sonezaki and A. Taniguchi: Effect of Polyethylene Glycol Modification of TiO2 Nanoparticles on Cytotoxicity and Gene Expressions in Human Cell Lines. Int J Mol Sci 13(3), 3703-17 (2012)
http://dx.doi.org/10.3390/ijms13033703
PMid:22489177    PMCid:3317737

127. J. Zilinskas, J. Zekonis, G. Zekonis, R. Sadzeviciene, M. Sapragoniene, J. Navickaite and I. Barzdziukaite: Inhibition of peripheral blood neutrophil oxidative burst in periodontitis patients with a homeopathic medication Traumeel S. Med Sci Monit 17(5), CR284-91 (2011)
PMid:21525811

128. C. R. Patil, A. D. Rambhade, R. B. Jadhav, K. R. Patil, V. K. Dubey, B. M. Sonara and S. S. Toshniwal: Modulation of arthritis in rats by Toxicodendron pubescens and its homeopathic dilutions. Homeopathy 100(3), 131-7 (2011)
http://dx.doi.org/10.1016/j.homp.2011.01.001
PMid:21784329

129. D. R. Patel, I. A. Ansari, Y. N. Kachchhi, R. B. Patel, K. R. Patil, R. B. Jadhav and C. R. Patil: Toxicodendron pubescens retains its anti-arthritic efficacy at 1M, 10M and CM homeopathic dilutions. Homeopathy 101(3), 165-70 (2012)
http://dx.doi.org/10.1016/j.homp.2012.02.007
PMid:22818234

130. G. E. Batley, J. K. Kirby and M. J. McLaughlin: Fate and Risks of Nanomaterials in Aquatic and Terrestrial Environments. Acc Chem Res (2012)
http://dx.doi.org/10.1021/ar2003368
PMid:22759090

131. J. Feng, J. M. Slocik, M. Sarikaya, R. R. Naik, B. L. Farmer and H. Heinz: Influence of the Shape of Nanostructured Metal Surfaces on Adsorption of Single Peptide Molecules in Aqueous Solution. Small (2012
http://dx.doi.org/10.1002/smll.201102066
PMid:22323430

132. S. Guha, X. Ma, M. J. Tarlov and M. R. Zachariah: Quantifying Ligand Adsorption to Nanoparticles Using Tandem Differential Mobility Mass Analysis. Anal Chem (2012)
http://dx.doi.org/10.1021/ac301149k
PMid:22769867

133. Y. Liu, K. Kathan, W. Saad and R. K. Prudhomme: Ostwald ripening of B-carotene nanoparticles. Physical Review Letters98(035102), 1-4 (2007)

134. C. Sengel, C. Hascicek and N. Gonul: Design of vitamin E d-alpha-Tocopheryl Polyethylene Glycol 1000 Succinate-Emulsified Poly (D,L-Lactide-co-Glycolide) Nanoparticles: Influence of Duration of Ultrasonication Energy. J Young Pharm 3(3), 171-5 (2011)
http://dx.doi.org/10.4103/0975-1483.83754
PMid:21897654    PMCid:3159268

135. N. C. Sukul, Bala, S.K., Bhattacharyya, B.: Prolonged cataleptogenic effects of potentized homoeopathic drugs. Psychopharmacology 89, 338-339 (1986)
http://dx.doi.org/10.1007/BF00174371
PMid:3088660

136. W. Pongratz, Nograsek, A., Endler, C.: Highly diluted agitated silver nitrate and wheat seedling development. Effect kinetics of a process of successive agitation phases. In: Fundamental Research in Ultra High Dilution and Homeopathy. Ed J. Schulte, Endler, P.C. Kluwer Academic Publishers, Dordrecht, The Netherlands (1998)
http://dx.doi.org/10.1007/978-94-011-5878-7_10

137. W. Pongratz and P. C. Endler: Reappraisal of a classical botanical experiment in ultra high dilution research. Energetic coupling in a wheat model. In: Ultra High Dilution. Ed P. C. Endler and J. Schulte. Kluwer Academic Publishers, Dordrecht, Netherlands (1994)

138. P. Magnani, A. Conforti, E. Zanolin, M. Marzotto and P. Bellavite: Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology (Berl) 210(4), 533-45 (2010)
http://dx.doi.org/10.1007/s00213-010-1855-2
PMid:20401745    PMCid:2877813

139. H. L. Xin and H. Zheng: In situ Observation of Oscillatory Growth of Bismuth Nanoparticles. Nano Lett (2012)
http://dx.doi.org/10.1021/nl2041854
PMid:22313455

140. X. Zhang, M. R. Servos and J. Liu: Ultrahigh Nanoparticle Stability against Salt, pH, and Solvent with Retained Surface Accessibility via Depletion Stabilization. J Am Chem Soc 134(24), 9910-3 (2012)
http://dx.doi.org/10.1021/ja303787e
PMid:22646098

141. T. R. Downs, M. E. Crosby, T. Hu, S. Kumar, A. Sullivan, K. Sarlo, B. Reeder, M. Lynch, M. Wagner, T. Mills and S. Pfuhler: Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. Mutat Res 745(1-2), 38-50 (2012)
http://dx.doi.org/10.1016/j.mrgentox.2012.03.012
PMid:22504169

142. S. L. Demento, S. C. Eisenbarth, H. G. Foellmer, C. Platt, M. J. Caplan, W. Mark Saltzman, I. Mellman, M. Ledizet, E. Fikrig, R. A. Flavell and T. M. Fahmy: Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27(23), 3013-21 (2009)
http://dx.doi.org/10.1016/j.vaccine.2009.03.034
PMid:19428913    PMCid:2695996

143. WJ Sandberg, M Lag, JA Holme, B Friede, M Gualtieri, M Kruszewski, PE Schwarze, T Skuland, M Refsnes: Comparison of non-crystalline silica nanoparticles in IL-1beta release from macrophages. Part Fibre Toxicol 9(1), 32 (2012)
http://dx.doi.org/10.1186/1743-8977-9-32
PMid:22882971

144. T. Wang, H. Jiang, Q. Zhao, S. Wang, M. Zou and G. Cheng: Enhanced mucosal and systemic immune responses obtained by porous silica nanoparticles used as an oral vaccine adjuvant: Effect of silica architecture on immunological properties. Int J Pharm (2012)
http://dx.doi.org/10.1016/j.ijpharm.2012.06.028
PMid:22721849

145. I. Blute, R. J. Pugh, J. van de Pas and I. Callaghan: Silica nanoparticle sols. Part 3: Monitoring the state of agglomeration at the air/water interface using the Langmuir-Blodgett technique. J Colloid Interface Sci 336(2), 584-91 (2009)
http://dx.doi.org/10.1016/j.jcis.2009.04.039
PMid:19520375

146. L. Y. Chang, E. Osawa and A. S. Barnard: Confirmation of the electrostatic self-assembly of nanodiamonds. Nanoscale 3(3), 958-62 (2011)
http://dx.doi.org/10.1039/c0nr00883d
PMid:21258697

147. V. K. Sharma: Aggregation and toxicity of titanium dioxide nanoparticles in aquatic environment--a review. J Environ Sci Health A Tox Hazard Subst Environ Eng 44(14), 1485-95 (2009)

148. S. Mahesh, A. Gopal, R. Thirumalai and A. Ajayaghosh: Light-induced Ostwald ripening of organic nanodots to rods. J Am Chem Soc 134(17), 7227-30 (2012)

149. S. Verma, R. Gokhale and D. J. Burgess: A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm 380(1-2), 216-22 (2009)
PMid:19596059

150. K. Khosravi-Darani, M. R. Mozafari, L. Rashidi and M. Mohammadi: Calcium based non-viral gene delivery: an overview of methodology and applications. Acta Med Iran 48(3), 133-41 (2010)
PMid:21137647

151. A. Kovtun, R. Heumann and M. Epple: Calcium phosphate nanoparticles for the transfection of cells. Biomed Mater Eng 19(2-3), 241-7 (2009)
PMid:19581719

152. L. Sun, L. C. Chow, S. A. Frukhtbeyn and J. E. Bonevich: Preparation and Properties of Nanoparticles of Calcium Phosphates With Various Ca/P Ratios. J Res Natl Inst Stand Technol 115(4), 243-255 (2010)
http://dx.doi.org/10.6028/jres.115.018
PMid:21037948    PMCid:2965602

153. C. Ruggiero, L. Pastorino and O. L. Herrera: Nanotechnology based targeted drug delivery. Conf Proc IEEE Eng Med Biol Soc 2010, 3731-2 (2010)
PMid:21096863

154. B. D. Ulery, D. Kumar, A. E. Ramer-Tait, D. W. Metzger, M. J. Wannemuehler and B. Narasimhan: Design of a protective single-dose intranasal nanoparticle-based vaccine platform for respiratory infectious diseases. PLoS ONE 6(3), e17642 (2011)
http://dx.doi.org/10.1371/journal.pone.0017642
PMid:21408610    PMCid:3048296

155. S. D. Xiang, C. Selomulya, J. Ho, V. Apostolopoulos and M. Plebanski: Delivery of DNA vaccines: an overview on the use of biodegradable polymeric and magnetic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(3), 205-18 (2010)
http://dx.doi.org/10.1002/wnan.88
PMid:20391461

156. S Gariboldi, M Palazzo, L Zanobbio, GF Dusio, V Mauro, U Solimene, D Cardani, M Mantovani, C Rumio: Low dose oral administration of cytokines for treatment of allergic asthma. Pulm Pharmacol Ther 22(6), 497-510 (2009)
http://dx.doi.org/10.1016/j.pupt.2009.05.002

157. J. Ali, M. Ali, S. Baboota, J. K. Sahani, C. Ramassamy, L. Dao and Bhavna: Potential of nanoparticulate drug delivery systems by intranasal administration. Curr Pharm Des 16(14), 1644-53 (2010)
http://dx.doi.org/10.2174/138161210791164108
PMid:20210751

158. G. A. Silva: Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS. BMC Neurosci 9 Suppl 3, S4 (2008)
http://dx.doi.org/10.1186/1471-2202-9-S3-S4
PMid:19091001    PMCid:2604882

159. S. S. Bansal, M. Goel, F. Aqil, M. V. Vadhanam and R. C. Gupta: Advanced drug delivery systems of curcumin for cancer chemoprevention. Cancer Prev Res (Phila) 4(8), 1158-71 (2011)
http://dx.doi.org/10.1158/1940-6207.CAPR-10-0006
PMid:21546540    PMCid:3151314

160. D. Ghosh, S. T. Choudhury, S. Ghosh, A. K. Mandal, S. Sarkar, A. Ghosh, K. D. Saha and N. Das: Nanocapsulated curcumin: oral chemopreventive formulation against diethylnitrosamine induced hepatocellular carcinoma in rat. Chem Biol Interact 195(3), 206-14 (2012)
http://dx.doi.org/10.1016/j.cbi.2011.12.004
PMid:22197969

161. S. Chakraborty, S. Stalin, N. Das, S. T. Choudhury, S. Ghosh and S. Swarnakar: The use of nano-quercetin to arrest mitochondrial damage and MMP-9 upregulation during prevention of gastric inflammation induced by ethanol in rat. Biomaterials 33(10), 2991-3001 (2012)
http://dx.doi.org/10.1016/j.biomaterials.2011.12.037
PMid:22257724

162. M. C. Daniel and D. Astruc: Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104(1), 293-346 (2004)
http://dx.doi.org/10.1021/cr030698+
PMid:14719978

163. L. Montagnier, J. Aissa, S. Ferris, J.-L. Montagnier and C. Lavallee: Electromagnetic signals are produced by aqueous nanostructures derived from bacterial DNA sequences. Interdisciplinary Sci Comput Life Sci 1, 81-90 (2009)
http://dx.doi.org/10.1007/s12539-009-0036-7
PMid:20640822

164. M. Tang, T. Zhang, Y. Xue, S. Wang, M. Huang, Y. Yang, M. Lu, H. Lei, L. Kong and P. Yuepu: Dose dependent in vivo metabolic characteristics of titanium dioxide nanoparticles. J Nanosci Nanotechnol 10(12), 8575-83 (2010)
http://dx.doi.org/10.1166/jnn.2010.2482
PMid:21121368

165. A. Maitra: Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy. Expert Rev Mol Diagn 5(6), 893-905 (2005)
http://dx.doi.org/10.1586/14737159.5.6.893
PMid:16255631

166. S. L. Fink, T. Bergsbaken and B. T. Cookson: Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci U S A 105(11), 4312-7 (2008)
http://dx.doi.org/10.1073/pnas.0707370105
PMid:18337499    PMCid:2393760

167. T. Ichinohe, I. K. Pang and A. Iwasaki: Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 11(5), 404-10 (2010)
http://dx.doi.org/10.1038/ni.1861
PMid:20383149    PMCid:2857582

168. H. M. Lee, J. M. Yuk, K. H. Kim, J. Jang, G. Kang, J. B. Park, J. W. Son and E. K. Jo: Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and p62/SQSTM1. Immunol Cell Biol (2011)

169. T. Strowig, J. Henao-Mejia, E. Elinav and R. Flavell: Inflammasomes in health and disease. Nature 481(7381), 278-86 (2012)
http://dx.doi.org/10.1038/nature10759
PMid:22258606

170. M. Winter, H. D. Beer, V. Hornung, U. Kramer, R. P. Schins and I. Forster: Activation of the inflammasome by amorphous silica and TiO2 nanoparticles in murine dendritic cells. Nanotoxicology 5(3), 326-40 (2011)
http://dx.doi.org/10.3109/17435390.2010.506957
PMid:20846021

171. V. Petrilli, C. Dostert, D. A. Muruve and J. Tschopp: The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol 19(6), 615-22 (2007)
http://dx.doi.org/10.1016/j.coi.2007.09.002
PMid:17977705

172. V. Petrilli and F. Martinon: The inflammasome, autoinflammatory diseases, and gout. Joint Bone Spine 74(6), 571-6 (2007)
http://dx.doi.org/10.1016/j.jbspin.2007.04.004
PMid:17714972

173. V. Petrilli, S. Papin, C. Dostert, A. Mayor, F. Martinon and J. Tschopp: Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ 14(9), 1583-9 (2007)
http://dx.doi.org/10.1038/sj.cdd.4402195
PMid:17599094

174. V. Hornung, F. Bauernfeind, A. Halle, E. O. Samstad, H. Kono, K. L. Rock, K. A. Fitzgerald and E. Latz: Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9(8), 847-56 (2008)
http://dx.doi.org/10.1038/ni.1631
PMid:18604214    PMCid:2834784

175. I. J. Elenkov, D. G. Iezzoni, A. Daly, A. G. Harris and G. P. Chrousos: Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12(5), 255-69 (2005)
http://dx.doi.org/10.1159/000087104
PMid:16166805

176. H. Wei, K. K. Chadman, D. P. McCloskey, A. M. Sheikh, M. Malik, W. T. Brown and X. Li: Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta (2012)

177. D. Demirovic and S. I. Rattan: Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis. Exp Gerontol (2012
http://dx.doi.org/10.1016/j.exger.2012.02.005
PMid:22525591

178. B. Dancso, Z. Spiro, M. A. Arslan, M. T. Nguyen, D. Papp, P. Csermely and C. Soti: The heat shock connection of metabolic stress and dietary restriction. Curr Pharm Biotechnol 11(2), 139-45 (2010)
http://dx.doi.org/10.2174/138920110790909704
PMid:20166967

179. A. Mihalik and P. Csermely: Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation. PLoS Comput Biol 7(10), e1002187 (2011)
http://dx.doi.org/10.1371/journal.pcbi.1002187
PMid:22022244    PMCid:3192799

180. M. S. Szalay, I. A. Kovacs, T. Korcsmaros, C. Bode and P. Csermely: Stress-induced rearrangements of cellular networks: Consequences for protection and drug design. FEBS Lett 581(19), 3675-80 (2007)
http://dx.doi.org/10.1016/j.febslet.2007.03.083
PMid:17433306

181. P. Csermely: Chaperone overload is a possible contributor to 'civilization diseases'. Trends Genet 17(12), 701-4 (2001)
http://dx.doi.org/10.1016/S0168-9525(01)02495-7

182. I. A. Kovacs, M. S. Szalay and P. Csermely: Water and molecular chaperones act as weak links of protein folding networks: energy landscape and punctuated equilibrium changes point towards a game theory of proteins. FEBS Lett 579(11), 2254-60 (2005)
http://dx.doi.org/10.1016/j.febslet.2005.03.056
PMid:15848154

183. G. Nardai, E. M. Vegh, Z. Prohaszka and P. Csermely: Chaperone-related immune dysfunction: an emergent property of distorted chaperone networks. Trends Immunol 27(2), 74-9 (2006)
http://dx.doi.org/10.1016/j.it.2005.11.009
PMid:16364688

184. I. N. Karatsoreos and B. S. McEwen: Psychobiological allostasis: resistance, resilience and vulnerability. Trends Cogn Sci 15(12), 576-84 (2011)
http://dx.doi.org/10.1016/j.tics.2011.10.005
PMid:22078931

185. S. I. Rattan and T. Deva: Testing the hormetic nature of homeopathic interventions through stress response pathways. Hum Exp Toxicol 29(7), 551-4 (2010)
http://dx.doi.org/10.1177/0960327110369858

186. E. J. Calabrese, K. A. Bachmann, A. J. Bailer, P. M. Bolger, J. Borak, L. Cai, N. Cedergreen, M. G. Cherian, C. C. Chiueh, T. W. Clarkson, R. R. Cook, D. M. Diamond, D. J. Doolittle, M. A. Dorato, S. O. Duke, L. Feinendegen, D. E. Gardner, R. W. Hart, K. L. Hastings, A. W. Hayes, G. R. Hoffmann, J. A. Ives, Z. Jaworowski, T. E. Johnson, W. B. Jonas, N. E. Kaminski, J. G. Keller, J. E. Klaunig, T. B. Knudsen, W. J. Kozumbo, T. Lettieri, S. Z. Liu, A. Maisseu, K. I. Maynard, E. J. Masoro, R. O. McClellan, H. M. Mehendale, C. Mothersill, D. B. Newlin, H. N. Nigg, F. W. Oehme, R. F. Phalen, M. A. Philbert, S. I. Rattan, J. E. Riviere, J. Rodricks, R. M. Sapolsky, B. R. Scott, C. Seymour, D. A. Sinclair, J. Smith-Sonneborn, E. T. Snow, L. Spear, D. E. Stevenson, Y. Thomas, M. Tubiana, G. M. Williams and M. P. Mattson: Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol 222(1), 122-8 (2007)
http://dx.doi.org/10.1016/j.taap.2007.02.015
PMid:17459441

187. V. Calabrese, C. Cornelius, S. Cuzzocrea, I. Iavicoli, E. Rizzarelli and E. J. Calabrese: Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol Aspects Med 32(4-6), 279-304 (2011)
http://dx.doi.org/10.1016/j.mam.2011.10.007
PMid:22020114

188. V. Calabrese, C. Cornelius, A. T. Dinkova-Kostova, I. Iavicoli, R. Di Paola, A. Koverech, S. Cuzzocrea, E. Rizzarelli and E. J. Calabrese: Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta 1822(5), 753-83 (2012)
http://dx.doi.org/10.1016/j.bbadis.2011.11.002
PMid:22108204

189. A. R. Stebbing: A mechanism for hormesis--a problem in the wrong discipline. Crit Rev Toxicol 33(3-4), 463-7 (2003)
http://dx.doi.org/10.1080/713611038
PMid:12809435

190. A. M. Vaiserman: Hormesis, adaptive epigenetic reorganization, and implications for human health and longevity. Dose Response 8(1), 16-21 (2010)
http://dx.doi.org/10.2203/dose-response.09-014.Vaiserman
PMid:20221294    PMCid:2836156

191. A. M. Vaiserman: Hormesis and epigenetics: is there a link? Ageing Res Rev 10(4), 413-21 (2011)
PMid:21292042

192. E. J. Calabrese: Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson Law are manifestations of hormesis. Ageing Res Rev 7(1), 8-20 (2008)
http://dx.doi.org/10.1016/j.arr.2007.07.001
PMid:17768095

193. E. J. Calabrese and M. P. Mattson: Hormesis provides a generalized quantitative estimate of biological plasticity. J Cell Commun Signal 5(1), 25-38 (2011)
http://dx.doi.org/10.1007/s12079-011-0119-1
PMid:21484586    PMCid:3058190

194. H. B. Hale: Cross-adaptation. Environmental Research 2, 423-34 (1969)
http://dx.doi.org/10.1016/0013-9351(69)90013-9

195. J. C. Launay, Y. Besnard, A. Guinet-Lebreton and G. Savourey: Acclimation to intermittent hypobaric hypoxia modifies responses to cold at sea level. Aviat Space Environ Med 77(12), 1230-5 (2006)
PMid:17183918

196. S. M. Antelman, A. J. Eichler, C. A. Black and D. Kocan: Interchangeability of stress and amphetamine in sensitization. Science 207(4428), 329-31 (1980)
http://dx.doi.org/10.1126/science.7188649
PMid:7188649

197. S. M. Antelman, J. Levine and S. Gershon: Time-dependent sensitization: the odyssey of a scientific heresy from the laboratory to the door of the clinic. Molecular Psychiatry 5(4), 350-6 (2000)
http://dx.doi.org/10.1038/sj.mp.4000721
PMid:10889544

198. F. A. Wiegant, N. Spieker and R. van Wijk: Stressor-specific enhancement of hsp induction by low doses of stressors in conditions of self- and cross-sensitization. Toxicology 127(1-3), 107-19 (1998)
http://dx.doi.org/10.1016/S0300-483X(98)00035-3

199. B. A. Sorg, M. L. Tschirgi, S. Swindell, L. Chen and J. Fang: Repeated formaldehyde effects in an animal model for multiple chemical sensitivity. Annals of the New York Academy of Sciences 933, 57-67 (2001)
http://dx.doi.org/10.1111/j.1749-6632.2001.tb05814.x

200. B. A. Gosnell: Sucrose intake enhances behavioral sensitization produced by cocaine. Brain Res 1031(2), 194-201 (2005)
http://dx.doi.org/10.1016/j.brainres.2004.10.037
PMid:15649444

201. B. A. Sorg, J. R. Willis, R. E. See, B. Hopkins and H. H. Westberg: Repeated low-level formaldehyde exposure produces cross-sensitization to cocaine: possible relevance to chemical sensitivity in humans. Neuropsychopharmacology 18(5), 385-94 (1998)
http://dx.doi.org/10.1016/S0893-133X(97)00179-6

202. D. Pincus and A. Metten: Nonlinear dynamics in biopsychosocial resilience. Nonlinear Dynamics Psychol Life Sci 14(4), 353-80 (2010)

203. M. Koithan, I. R. Bell, K. Niemeyer and D. Pincus: A complex systems science perspective for whole systems of CAM research. Forschende Komplementarmedizin und Klassische Naturheilkunde 19(Supplement 1), 7-14 (2012)

204. E. J. Calabrese: Hormesis and medicine. Br J Clin Pharmacol 66(5), 594-617 (2008)
PMid:18662293    PMCid:2661975

205. M. P. Mattson: Hormesis defined. Aging Research Rev7(1), 1-7 (2008)

206. E. J. Calabrese: Stress biology and hormesis: the Yerkes-Dodson law in psychology--a special case of the hormesis dose response. Crit Rev Toxicol 38(5), 453-62 (2008)
http://dx.doi.org/10.1080/10408440802004007
PMid:18568865

207. G. Li and H. He: Hormesis, allostatic buffering capacity and physiological mechanism of physical activity: a new theoretic framework. Med Hypotheses 72(5), 527-32 (2009)
http://dx.doi.org/10.1016/j.mehy.2008.12.037
PMid:19211194

208. S. I. Rattan: Hormetic modulation of aging and longevity by mild heat stress. Dose Response 3(4), 533-46 (2005)
http://dx.doi.org/10.2203/dose-response.003.04.008
PMid:18648625    PMCid:2477195

209. A. Salminen and K. Kaarniranta: ER stress and hormetic regulation of the aging process. Ageing Res Rev 9(3), 211-7 (2010)
http://dx.doi.org/10.1016/j.arr.2010.04.003
PMid:20416402

210. I. Martins, L. Galluzzi and G. Kroemer: Hormesis, cell death and aging. Aging (Albany NY) 3(9), 821-8 (2011)

211. F. P. Perez, X. Zhou, J. Morisaki and D. Jurivich: Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response. Exp Gerontol 43(4), 307-16 (2008)
http://dx.doi.org/10.1016/j.exger.2008.01.004
PMid:18325704

212. I. R. Bell and M. Koithan: Models for the study of whole systems. Integrative Cancer Therapies 5(4), 293-307 (2006)
http://dx.doi.org/10.1177/1534735406295293
PMid:17101758

213. S. M. Antelman, A. R. Caggiula, S. Gershon, D. J. Edwards, M. C. Austin, S. Kiss and D. Kocan: Stressor-induced oscillation. A possible model of the bidirectional symptoms in PTSD. Annals of the New York Academy of Sciences 821, 296-304 (1997)
http://dx.doi.org/10.1111/j.1749-6632.1997.tb48288.x
PMid:9238213

214. S. M. Antelman, A. R. Caggiula, D. Kocan, S. Knopf, D. Meyer, D. J. Edwards and H. Barry, 3rd: One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability. Brain Research 566(1-2), 276-83 (1991)
http://dx.doi.org/10.1016/0006-8993(91)91709-A

215. A. Danese and B. S. McEwen: Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav 106(1), 29-39 (2012) 216. B. S. McEwen: The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886(1-2), 172-189 (2000)
PMid:11119695

217. B. S. McEwen: Allostasis, allostatic load, and the aging nervous system: role of excitatory amino acids and excitotoxicity. Neurochem Res 25(9-10), 1219-31 (2000)
http://dx.doi.org/10.1023/A:1007687911139
PMid:11059796

218. B. S. McEwen: Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci 8(4), 367-81 (2006)
PMid:17290796    PMCid:3181832

219 NC Bell, C Minelli, J Tompkins, MM Stevens, AG Shard: Emerging techniques for submicrometer particle sizing applied to stober silica. Langmuir 28(29), 10860-10872 (2012)
http://dx.doi.org/10.1021/la301351k
PMid:22724385

220. L. Richter, V. Charwat, C. Jungreuthmayer, F. Bellutti, H. Brueckl and P. Ertl: Monitoring cellular stress responses to nanoparticles using a lab-on-a-chip. Lab Chip 11(15), 2551-60 (2011)
http://dx.doi.org/10.1039/c1lc20256a
PMid:21687846

221. C. M. Witt, Luedtke R, Baur R, Willich SN.: Homeopathic Medical Practice: Long-term results of a Cohort Study with 3981 Patients. BMC Public Health 5(1), 115 epub (2005)

222. M. Haidvogl, Riley DS, Heger M, Brien S, Jong M, Fischer M, Lewith GT, Jansen G, Thurneysen AE.: Homeopathic and conventional treatment for acute respiratory and ear complaints: a comparative study on outcome in the primary care setting. BMC Complement Altern Med 2(7), 7 (2007)
http://dx.doi.org/10.1186/1472-6882-7-7
PMid:17335565    PMCid:1831487

223. A. L. Barabasi: Linked. How everything is connected to everything else and what it means for business, science, and everyday life. Plume, Cambridge, MA (2003)

224. A. L. Barabasi, N. Gulbahce and J. Loscalzo: Network medicine: a network-based approach to human disease. Nat Rev Genet 12(1), 56-68 (2011)
http://dx.doi.org/10.1038/nrg2918
PMid:21164525    PMCid:3140052

225. J. Loscalzo and A. L. Barabasi: Systems biology and the future of medicine. Wiley Interdiscip Rev Syst Biol Med 3(6), 619-27 (2011)
http://dx.doi.org/10.1002/wsbm.144
PMid:21928407

226. M. Vidal, M. E. Cusick and A. L. Barabasi: Interactome networks and human disease. Cell 144, 986-98 (2011)
http://dx.doi.org/10.1016/j.cell.2011.02.016
PMid:21414488    PMCid:3102045

227. A. R. Stebbing: Interpreting 'dose-response' curves using homeodynamic data: with an improved explanation for hormesis. Dose Response 7(3), 221-33 (2009)
http://dx.doi.org/10.2203/dose-response.08-020.Stebbing
PMid:19809541    PMCid:2754536

228. R. P. Juster, G. Bizik, M. Picard, G. Arsenault-Lapierre, S. Sindi, L. Trepanier, M. F. Marin, N. Wan, Z. Sekerovic, C. Lord, A. J. Fiocco, P. Plusquellec, B. S. McEwen and S. J. Lupien: A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development. Dev Psychopathol23(3), 725-76 (2011)
http://dx.doi.org/10.1017/S0954579411000289
PMid:21756430

229. R. P. Juster, B. S. McEwen and S. J. Lupien: Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev 35(1), 2-16 (2010)
http://dx.doi.org/10.1016/j.neubiorev.2009.10.002

230. B. S. McEwen: Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87(3), 873-904 (2007)
http://dx.doi.org/10.1152/physrev.00041.2006
PMid:17615391

231. F. J. Kelling, F. Ialenti and C. J. Den Otter: Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies. Medical & Veterinary Entomology 16(2), 161-9 (2002)
http://dx.doi.org/10.1046/j.1365-2915.2002.00359.x
PMid:12109710

232. H. C. Lunt, M. J. Barwood, J. Corbett and M. J. Tipton: 'Cross-adaptation': habituation to short repeated cold-water immersions affects the response to acute hypoxia in humans. J Physiol 588(Pt 18), 3605-13 (2010)
http://dx.doi.org/10.1113/jphysiol.2010.193458
PMid:20643773    PMCid:2988521

233. P. Csermely, V. Agoston and S. Pongor: The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol Sci 26(4), 178-82 (2005)
http://dx.doi.org/10.1016/j.tips.2005.02.007
PMid:15808341

234. P. Csermely, T. Korcsmaros, I. A. Kovacs, M. S. Szalay and C. Soti: Systems biology of molecular chaperone networks. Novartis Found Symp 291, 45-54; discussion 54-8, 137-40 (2008)

235. S. B. Brien, H. Harrison, J. Daniels and G. Lewith: Monitoring improvement in health during homeopathic intervention. Development of an assessment tool based on Hering's Law of Cure: the Hering's Law Assessment Tool (HELAT). Homeopathy101(1), 28-37 (2012)
http://dx.doi.org/10.1016/j.homp.2011.10.002
PMid:22226312

236. A. Vasquez, R. Dobrin, D. Sergi, J. P. Eckmann, Z. N. Oltvai and A. L. Barabasi: The topological relationship between the large-scale attributes and local interaction patterns of complex networks. Proceedings of the National Academy of Sciences of the United States of America 101(52), 17940-17945 (2004)
http://dx.doi.org/10.1073/pnas.0406024101
PMid:15598746    PMCid:539752

237. S. M. Antelman and A. R. Caggiula: Oscillation follows drug sensitization: implications. Critical Reviews in Neurobiology 10(1), 101-17 (1996)
http://dx.doi.org/10.1615/CritRevNeurobiol.v10.i1.50
PMid:8853956

238. T. Randolph: Specific adaptation. Annals of Allergy 40, 333-345 (1978)
PMid:347991

239. E. Chen, M. D. Hanson, L. Q. Paterson, M. J. Griffin, H. A. Walker and G. E. Miller: Socioeconomic status and inflammatory processes in childhood asthma: the role of psychological stress. J Allergy Clin Immunol 117(5), 1014-20 (2006)
http://dx.doi.org/10.1016/j.jaci.2006.01.036
PMid:16675327

240. G. Miller and E. Chen: Unfavorable socioeconomic conditions in early life presage expression of proinflammatory phenotype in adolescence. Psychosom Med 69(5), 402-9 (2007)
http://dx.doi.org/10.1097/PSY.0b013e318068fcf9
PMid:17556642

241. H. E. Covington, 3rd and K. A. Miczek: Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration "binges". Psychopharmacology 158(4), 388-98 (2001)
http://dx.doi.org/10.1007/s002130100858
PMid:11797060

242. N. M. Avena, C. A. Carrillo, L. Needham, S. F. Leibowitz and B. G. Hoebel: Sugar-dependent rats show enhanced intake of unsweetened ethanol. Alcohol 34(2-3), 203-9 (2004)
http://dx.doi.org/10.1016/j.alcohol.2004.09.006
PMid:15902914

243. N. M. Avena and B. G. Hoebel: A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine. Neuroscience 122(1), 17-20 (2003)
http://dx.doi.org/10.1016/S0306-4522(03)00502-5

244. N. M. Avena and B. G. Hoebel: Amphetamine-sensitized rats show sugar-induced hyperactivity (cross-sensitization) and sugar hyperphagia. Pharmacol Biochem Behav 74(3), 635-9 (2003)
http://dx.doi.org/10.1016/S0091-3057(02)01050-X

245. P. Rada, N. M. Avena and B. G. Hoebel: Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 134(3), 737-44 (2005)
http://dx.doi.org/10.1016/j.neuroscience.2005.04.043
PMid:15987666

246. S. R. Dube, V. J. Felitti, M. Dong, W. H. Giles and R. F. Anda: The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Prev Med 37(3), 268-77 (2003)
http://dx.doi.org/10.1016/S0091-7435(03)00123-3

247. L. Klein: Miasms and Nosodes. Narayana Publishers, Toronto, ON Canada (2009)

248. D. Crews, R. Gillette, S. V. Scarpino, M. Manikkam, M. I. Savenkova and M. K. Skinner: Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci U S A (2012)
http://dx.doi.org/10.1073/pnas.1118514109
PMid:22615374    PMCid:3384163

249. A. M. Hayes, Laurenceau JP, Feldman G, Strauss JL, Cardaciotto L.: Change is not always linear: the study of nonlinear and discontinuous patterns of change in psychotherapy. Clin Psychol Rev 27(6), 715-23 (2007)
http://dx.doi.org/10.1016/j.cpr.2007.01.008
PMid:17316941    PMCid:3163164

250. T. Hollenstein: State space grids: analyzing dynamics across development. International Journal of Behavioral Development 31(4), 384-96 (2007)
http://dx.doi.org/10.1177/0165025407077765

251. P. Bak: How Nature Works: the Science of Self-Organized Criticality. Copernicus Press, New York, NY (1996)

252. W. C. Abraham: Metaplasticity: tuning synapses and networks for plasticity. Nat Rev Neurosci 9(5), 387 (2008)
http://dx.doi.org/10.1038/nrn2356
PMid:18401345

253. R. Sankaran: The Synergy in Homoeopathy. Homoeopathic Medical Publishers, Mumbai, India (2012)

254. D. S. Coffey: Self-organization, complexity, and chaos: the new biology for medicine. Nature Medicine 4(8), 882-885 (1998)
http://dx.doi.org/10.1038/nm0898-882
PMid:9701230

255. A. Garfinkel, M.L. Spano, W. L. Ditto, J. N. Weiss: Controlling cardiac chaos. Science 257(5074), 1230-5 (1992)
http://dx.doi.org/10.1126/science.1519060
PMid:1519060

256. S. J. Schiff, K. Jerger, D. H. Duong, T. Chang, M. L. Spano and W. L. Ditto: Controlling chaos in the brain. Nature 370, 615-20 (1994)
http://dx.doi.org/10.1038/370615a0
PMid:8065447

257. S. J. Guastello, Koopmans, M, Pincus, D. : Chaos and Complexity in Psychology: The Theory of Nonlinear Dynamical Systems. Cambridge University Press, New York, NY (2009)

258. S. Kauffman: At Home in the Universe. The Search for the Laws of Self-Organization and Complexity. Oxford University Press, NY (1995)

259. R. Papp, et al.: Oscillococcinum in patients with influenza-like syndromes: a placebo-controlled double blind evaluation. British Homeopathy Journal 87, 69-76 (1998)
http://dx.doi.org/10.1054/homp.1999.0208

260. J. P. Ferley, D. Zmirou, D. D'Adhemar and F. Balducci: A controlled evaluation of a homoeopathic preparation in the treatment of influenza-like syndromes. British Journal of Clinical Pharmacology 27(3), 329-35 (1989)
http://dx.doi.org/10.1111/j.1365-2125.1989.tb05373.x
PMid:2655683    PMCid:1379831

261. A. Berchieri, Jr., W. C. Turco, J. B. Paiva, G. H. Oliveira and E. V. Sterzo: Evaluation of isopathic treatment of Salmonella enteritidis in poultry. Homeopathy 95(2), 94-7 (2006)
http://dx.doi.org/10.1016/j.homp.2006.01.007
PMid:16569625

262. P. Colin: An epidemiological study of a homeopathic practice. British Homoeopathic Journal 89(3), 116-21 (2000)
http://dx.doi.org/10.1054/homp.1999.0415
PMid:10939766

263. G. Vithoulkas: The Science of Homeopathy. Grove Weidenfeld, N.Y. (1980)

264. H. Möllinger, Schneider, R., Walach, H.: Homeopathic pathogenetic trials produce specific symptoms different from placebo. Forsch Komplementmed 16(2), 105-10 (2009)
http://dx.doi.org/10.1159/000209386

265. H. Walach, Möllinger H, Sherr J, Schneider R.: Homeopathic pathogenetic trials produce more specific than non-specific symptoms: results from two double-blind placebo controlled trials. J Psychopharmacol 22(5), 543-52 (2008)
http://dx.doi.org/10.1177/0269881108091259
PMid:18701641

266. J. Sherr: Dynamic Materia Medica. Syphilis: A Study of Syphilitic Miasm through Remedies. Dynamis Books, Great Malvern Worcestershire, England (2002)

267. P. Vijayakar: Genetic Materia Medica: Tri-miasmatic Materia Medica. Preeti Vijayakar Mumbai, India (2008)

268. J. Scholten: Homeopathy and the Elements. Stichting Alonnissos, Utrecht, the Netherlands (1996)

269. M. Oberbaum, Singer SR, Vithoulkas G.: The colour of the homeopathic improvement: the multidimensional nature of the response to homeopathic therapy. Homeopathy 94(3), 196-9 (2005)
http://dx.doi.org/10.1016/j.homp.2005.05.004
PMid:16060205

270. A. Banerjee, S. Pathak, S. J. Biswas, S. Roy-Karmakar, N. Boujedaini, P. Belon and A. R. Khuda-Bukhsh: Chelidonium majus 30C and 200C in induced hepato-toxicity in rats. Homeopathy 99(3), 167-76 (2010)
http://dx.doi.org/10.1016/j.homp.2010.05.008
PMid:20674840

271. P. Endler, K. Thieves, C. Reich, P. Matthiessen, L. Bonamin, C. Scherr and S. Baumgartner: Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10(-23): a bibliometric study. Homeopathy 99(1), 25-36 (2010)
http://dx.doi.org/10.1016/j.homp.2009.11.008
PMid:20129174

272. P. C. Endler, Schulte, J.: Ultra High Dilution. Physiology and Physics. In: Kluwer Academic Publishers, Dordrecht, The Netherlands (1994)

273. M. Frass, C. Dielacher, M. Linkesch, C. Endler, I. Muchitsch, E. Schuster and A. Kaye: Influence of potassium dichromate on tracheal secretions in critically ill patients. Chest 127(3), 936-41 (2005)
http://dx.doi.org/10.1378/chest.127.3.936
PMid:15764779

274. P. Bellavite, A. Conforti, M. Marzotto, P. Magnani, M. Cristofoletti, D. Olioso and M. E. Zanolin: Testing homeopathy in mouse emotional response models: pooled data analysis of two series of studies. Evid Based Complement Alternat Med 2012, 954374 (2012)
http://dx.doi.org/10.1155/2012/954374
PMid:22548123    PMCid:3324905

275. M. Abu-Asab, H. Amri, M. Koithan and J. Shaver: A systems biology approach: parsimony phylogenetics. Forsch Komplementarmed 19(Supplement 1), 42-48 (2012)
http://dx.doi.org/10.1159/000335190
PMid:22327551    PMCid:3292783

276. E. Antman, S. Weiss and J. Loscalzo: Systems pharmacology, pharmacogenetics, and clinical trial design in network medicine. Wiley Interdisciplinary Reviews-Systems Biology and Medicine 4(4), 367-383 (2012)
http://dx.doi.org/10.1002/wsbm.1173
PMid:22581565

277. C. A. Hidalgo, N. Blumm, A. L. Barabasi and N. A. Christakis: A dynamic network approach for the study of human phenotypes. PLoS Comput Biol 5(4), e1000353 (2009)
http://dx.doi.org/10.1371/journal.pcbi.1000353
PMid:19360091    PMCid:2661364

278. M. V. Yigit, A. Moore and Z. Medarova: Magnetic nanoparticles for cancer diagnosis and therapy. Pharm Res, 29(5), 1180-8 (2012)
http://dx.doi.org/10.1007/s11095-012-0679-7
PMid:22274558

279. M. Koithan, M. Verhoef, I. R. Bell, C. Ritenbaugh, M. White and A. Mulkins: The process of whole person healing: "unstuckness" and beyond. J Altern Complement Med 13(6), 659-68 (2007)
http://dx.doi.org/10.1089/acm.2007.7090
PMid:17718649

280. B. L. Fredrickson and M. F. Losada: Positive affect and the complex dynamics of human flourishing. American Psychologist 60(7), 678-86 (2005)
http://dx.doi.org/10.1037/0003-066X.60.7.678
PMid:16221001    PMCid:3126111

Key Words: Nanomedicine, Nanoparticles, Homeopathy, Adaptation, Cross-Adaptation, Network Medicine, Time-Dependent Sensitization, Hormesis, Stress Response Network, Complex Adaptive Systems, Review

Send correspondence to: Iris R. Bell, Department of Family and Community Medicine, The University of Arizona College of Medicine, 1450 North Cherry, MS 245052, Tucson, AZ 85719 USA, Tel: 5206264188, Fax: 5206262030, E-mail: ibell@email.arizona.edu