Effects of Physicochemical Forms of Phenazepam and Panavir on Their Action at Ultra-Low Doses

Стовбун, С. В.; Kiselev, Aleksei V.; Zanin, A. M.; Калинина, Татьяна Сергеевна; Воронина, Т. А.; Михайлов, А. И.; Берлин, А. А.

doi:10.1007/s10517-012-1739-z

Cited by 14 publications

(20 citation statements)

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“…Sizes typically range from a fraction of one nanometer (nm) in diameter on at least one side up to 100 nanometers (European Commission on the Environment, 2011; International Organization for Standardization, 2005). Although submicron particles between 100-1000 nanometers in size have some advantages toward improving drug delivery (Oyewumi et al, 2010;Stovbun et al, 2012;Wong, 2011), much of the focus of research interest in NPs has been on particles whose size falls below 100 nm. Their small size leads to a large surface area to volume ratio, resulting in variations of properties that differ markedly from those of bulk forms of the "same" material (Buzea et al, 2007;Cao and Wang, 2011;Roduner, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nonlinear Effects of Nanoparticles: Biological Variability from Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

2013

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Researchers are increasingly focused on the nanoscale level of organization where biological processes take place in living systems. Nanoparticles (NPs, e.g., 1-100 nm diameter) are small forms of natural or manufactured source material whose properties differ markedly from those of the respective bulk forms of the "same" material. Certain NPs have diagnostic and therapeutic uses; some NPs exhibit low-dose toxicity; other NPs show ability to stimulate low-dose adaptive responses (hormesis). Beyond dose, size, shape, and surface charge variations of NPs evoke nonlinear responses in complex adaptive systems. NPs acquire unique size-dependent biological, chemical, thermal, optical, electromagnetic, and atom-like quantum properties. Nanoparticles exhibit high surface adsorptive capacity for other substances, enhanced bioavailability, and ability to cross otherwise impermeable cell membranes including the blood-brain barrier. With super-potent effects, nano-forms can evoke cellular stress responses or therapeutic effects not only at lower doses than their bulk forms, but also for longer periods of time. Interactions of initial effects and compensatory systemic responses can alter the impact of NPs over time. Taken together, the data suggest the need to downshift the dose-response curve of NPs from that for bulk forms in order to identify the necessarily decreased no-observed-adverse-effect-level and hormetic dose range for nanoparticles.

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Section: Introductionmentioning

confidence: 99%

Nonlinear Effects of Nanoparticles: Biological Variability from Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

2013

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“…Basic science studies on homeopathic remedies in non-cancer models suggest that this may be the case 210 , 211 . Consecutive potencies appear not to exhibit linear dose-response relationships but rather oscillatory or sinusoidal bidirectional types of nonlinear curves 211 , 212 …”

Section: Pulsed Dosing Biological Signaling Mechanisms and Low Dosesmentioning

confidence: 99%

Integrative Nanomedicine: treating Cancer with Nanoscale Natural Products

Bell

Sarter

Koithan

et al. 2014

Glob Adv Health Med

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Finding safer and more effective treatments for specific cancers remains a significant challenge for integrative clinicians and researchers worldwide. One emerging strategy is the use of nanostructured forms of drugs, vaccines, traditional animal venoms, herbs, and nutraceutical agents in cancer treatment. The recent discovery of nanoparticles in traditional homeopathic medicines adds another point of convergence between modern nanomedicine and alternative interventional strategies. A way in which homeopathic remedies could initiate anticancer effects includes cell-to-cell signaling actions of both exogenous and endogenous (exosome) nanoparticles. The result can be a cascade of modulatory biological events with antiproliferative and pro-apoptotic effects. The Banerji Protocols reflect a multigenerational clinical system developed by homeopathic physicians in India who have treated thousands of patients with cancer. A number of homeopathic remedy sources from the Banerji Protocols (eg, Calcarea phosphorica; Carcinosin—tumor-derived breast cancer tissue prepared homeopathically) overlap those already under study in nonhomeopathic nanoparticle and nanovesicle tumor exosome cancer vaccine research. Past research on antineoplastic effects of nano forms of botanical extracts such as Phytolacca, Gelsemium, Hydrastis, Thuja, and Ruta as well as on homeopathic remedy potencies made from the same types of source materials suggests other important overlaps. The replicated finding of silica, silicon, and nano-silica release from agitation of liquids in glassware adds a proven nonspecific activator and amplifier of immunological effects. Taken together, the nanoparticulate research data and the Banerji Protocols for homeopathic remedies in cancer suggest a way forward for generating advances in cancer treatment with natural product–derived nanomedicines.

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“…In the homeopathic NP dose range, the low dose hormetic effects can take on the sinusoidal oscillatory dose-response patterns reported in various preclinical and clinical studies [5,73,126]. To avoid toxicity but still elicit the adaptive response of hormesis with nanoforms of some agents such as poisonous plants, that are otherwise toxic at higher doses, extremely low doses, i.e., picogram/milliliter to low nanogram levels, may be necessary [21].…”

Section: Organism-dependent Response Amplification Phenomenamentioning

confidence: 99%

“…Convergent basic science studies reveal the presence of mechanically-generated source material [3][4][5] and silica/silicon nanoparticles (NPs) in homeopathically-prepared medicines [4,[6][7][8][9]. Nanobubbles made during the manufacturing process may also contribute to the final product [8,10,11], which retains physicochemical properties of the original source material [12].…”

Section: Introductionmentioning

confidence: 99%

“…Other studies have demonstrated that low doses of homeopathically-prepared metals, including cadmium and arsenic, can produce beneficial hormetic reversal of effects of higher, toxic doses of the same or crosssensitized agent on heat shock protein activation patterns [124]. Heat shock proteins are among the biological modulators of the stress response networks involved in adaptation to various environmental stressors [94,125].In the homeopathic NP dose range, the low dose hormetic effects can take on the sinusoidal oscillatory dose-response patterns reported in various preclinical and clinical studies [5,73,126]. To avoid toxicity but still elicit the adaptive response of hormesis with nanoforms of some agents such as poisonous plants, that are otherwise toxic at higher doses, extremely low doses, i.e., picogram/milliliter to low nanogram levels, may be necessary [21].…”

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confidence: 99%

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

Bell

Sarter

Koithan

et al. 2013

J Nanomed Nanotechol

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

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Effects of Physicochemical Forms of Phenazepam and Panavir on Their Action at Ultra-Low Doses

Cited by 14 publications

References 1 publication

Nonlinear Effects of Nanoparticles: Biological Variability from Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

Nonlinear Effects of Nanoparticles: Biological Variability from Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

Integrative Nanomedicine: treating Cancer with Nanoscale Natural Products

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

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