Over the past few decades, finding more efficient and selective administration routes has gained significant attention due to its crucial role in the bioavailability, absorption rate and pharmacokinetics of therapeutic substances. The pulmonary delivery of drugs has become an attractive target of scientific and biomedical interest in the health care research area, as the lung, thanks to its high permeability and large absorptive surface area and good blood supply, is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Nevertheless, the pulmonary drug delivery is relatively complex, and strategies to mitigate the effects of mechanical, chemical and immunological barriers are required. Herein, engineered erythrocytes, the Erythro–Magneto–Hemagglutinin (HA)–virosomes (EMHVs), are used as a novel strategy for efficiently delivering drugs to the lungs. EMHV bio-based carriers exploit the physical properties of magnetic nanoparticles to achieve effective targeting after their intravenous injection thanks to an external magnetic field. In addition, the presence of hemagglutinin fusion proteins on EMHVs’ membrane allows the DDS to anchor and fuse with the target tissue and locally release the therapeutic compound. Our results on the biomechanical and biophysical properties of EMHVs, such as the membrane robustness and deformability and the high magnetic susceptibility, as well as their in vivo biodistribution, highlight that this bio-inspired DDS is a promising platform for the controlled and lung-targeting delivery of drugs, and represents a valuable alternative to inhalation therapy to fulfill unmet clinical needs.

Cardiac hypertrophy, in its aspects of localized thickening of the interventricular septum and concentric increase of the left ventricle, constitutes a risk factor of heart failure. Myocardial hypertrophy, in the presence of different degree of myocardial fibrosis, is paralleled by significant molecular, cellular, and histological changes inducing alteration of cardiac extracellular matrix composition as well as sarcomeres and cytoskeleton remodeling. Previous studies indicate osteopontin (OPN) and more recently survivin (SURV) overexpression as the hallmarks of heart failure although SURV function in the heart is not completely clarified. In this study, we investigated the involvement of SURV in intracellular signaling of hypertrophic cardiomyocytes and the impact of its transcriptional silencing, laying the foundation for novel target gene therapy in cardiac hypertrophy. Oligonucleotide-based molecules, like theranostic optical nanosensors (molecular beacons) and siRNAs, targeting SURV and OPN mRNAs, were developed. Their diagnostic and therapeutic potential was evaluated in vitro in hypertrophic FGF23-induced human cardiomyocytes and in vivo in transverse aortic constriction hypertrophic mouse model. Engineered erythrocyte was used as shuttle to selectively target and transfer siRNA molecules into unhealthy cardiac cells in vivo. The results highlight how the SURV knockdown could negatively influence the expression of genes involved in myocardial fibrosis in vitro and restores structural, functional, and morphometric features in vivo. Together, these data suggested that SURV is a key factor in inducing cardiomyocytes hypertrophy, and its shutdown is crucial in slowing disease progression as well as reversing cardiac hypertrophy. In the perspective, targeted delivery of siRNAs through engineered erythrocytes can represent a promising therapeutic strategy to treat cardiac hypertrophy. Theranostic SURV molecular beacon (MB-SURV), transfected into FGF23-induced hypertrophic human cardiomyocytes, significantly dampened SURV overexpression. SURV down–regulation determines the tuning down of MMP9, TIMP1 and TIMP4 extracellular matrix remodeling factors while induces the overexpression of the cardioprotective MCAD factor, which counterbalance the absence of pro-survival and anti-apoptotic SURV activity to protect cardiomyocytes from death. In transverse aortic constriction (TAC) mouse model, the SURV silencing restores the LV mass levels to values not different from the sham group and counteracts the progressive decline of EF, maintaining its values always higher with respect to TAC group. These data demonstrate the central role of SURV in the cardiac reverse remodeling and its therapeutic potential to reverse cardiac hypertrophy.

Ultrasmall superparamagnetic iron oxide nanoparticles with a size <5 nm are emerging nanomaterials for their excellent biocompatibility, chemical stability, and tunable surface modifications. The applications explored include dual-modal or multi-modal imaging, drug delivery, theranostics and, more recently, magnetic resonance angiography. Good biocompatibility and biosafety are regarded as the preliminary requirements for their biomedical applications and further exploration in this field is still required. We previously synthesized and characterized ultrafine (average core size of 3 nm) silica-coated superparamagnetic iron oxide fluorescent nanoparticles, named sub-5 SIO-Fl, uniform in size, shape, chemical properties and composition. The cellular uptake and in vitro biocompatibility of the as-synthesized nanoparticles were demonstrated in a human colon cancer cellular model. Here, we investigated the biocompatibility of sub-5 SIO-Fl nanoparticles in human Amniotic Mesenchymal Stromal/Stem Cells (hAMSCs). Kinetic analysis of cellular uptake showed a quick nanoparticle internalization in the first hour, increasing over time and after long exposure (48 h), the uptake rate gradually slowed down. We demonstrated that after internalization, sub-5 SIO-Fl nanoparticles neither affect hAMSC growth, viability, morphology, cytoskeletal organization, cell cycle progression, immunophenotype, and the expression of pro-angiogenic and immunoregulatory paracrine factors nor the osteogenic and myogenic differentiation markers. Furthermore, sub-5 SIO-Fl nanoparticles were intravenously injected into mice to investigate the in vivo biodistribution and toxicity profile for a time period of 7 weeks. Our findings showed an immediate transient accumulation of nanoparticles in the kidney, followed by the liver and lungs, where iron contents increased over a 7-week period. Histopathology, hematology, serum pro-inflammatory response, body weight and mortality studies demonstrated a short- and long-term biocompatibility and biosafety profile with no apparent acute and chronic toxicity caused by these nanoparticles in mice. Overall, these results suggest the feasibility of using sub-5 SIO-Fl nanoparticles as a promising agent for stem cell magnetic targeting as well as for diagnostic and therapeutic applications in oncology.

Magnetic iron oxide nanoparticles (IONPs), for their intriguing properties, have attracted a great interest as they can be employed in many different biomedical applications. In this multidisciplinary study, we synthetized and characterized ultrafine 3 nm superparamagnetic water-dispersible nanoparticles. By a facile and inexpensive one-pot approach, nanoparticles were coated with a shell of silica and contemporarily functionalized with fluorescein isothiocyanate (FITC) dye. The obtained sub-5 nm silica-coated magnetic iron oxide fluorescent (sub-5 SIO-Fl) nanoparticles were assayed for cellular uptake, biocompatibility and cytotoxicity in a human colon cancer cellular model. By confocal microscopy analysis we demonstrated that nanoparticles as-synthesized are internalized and do not interfere with the CaCo-2 cell cytoskeletal organization nor with their cellular adhesion. We assessed that they do not exhibit cytotoxicity, providing evidence that they do not affect shape, proliferation, cellular viability, cell cycle distribution and progression. We further demonstrated at molecular level that these nanoparticles do not interfere with the expression of key differentiation markers and do not affect pro-inflammatory cytokines response in Caco-2 cells. Overall, these results showed the in vitro biocompatibility of the sub-5 SIO-Fl nanoparticles promising their safe employ for diagnostic and therapeutic biomedical applications.

Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/ systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/ her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.

Heretofore only observed in living systems, we report that weak-field ion cyclotron resonance (ICR) also occurs in inanimate matter. Weak magnetic field (50 nT) hydronium ICR at the field combination (7.84 Hz, 7.5 mu T) markedly changes water structure, as evidenced by finding an altered index of refraction exactly at this combined field. This observation utilizes a novel technique which measures the scattering of a He-Ne laser beam as the sample is exposed to a ramped magnetic field frequency. In addition to the hydronium resonance, we find evidence of ICR coupling to a more massive structure, possibly a tetrahedral combination of three waters and a single hydronium ion. To check our observations, we extended this technique to D2O, successfully predicting the specific ICR charge-to-mass ratio for D3O+ that alters the index of refraction.

Several years ago just before Christmas, in a small meeting room at the Institute of Pharmacology at the University of Rome, we had the opportunity to attend a meeting on "The role of QED in medicine" by Emilio Del Giudice and Giuliano Preparata. Before that meeting, we were more oriented towards a mechanistic view of Biochemistry and Medicine, believing that chemical reactions could only take place when a random collision between molecules with a gain in energy takes place. We envisioned water as just a solvent in which was possible to dissolve a solute. After we listened to Giuliano's and Emilio's speech on the "New physics of water", and on "The possible origin of coherence in cell, tissues and the interaction of very weak and low frequency magnetic fields with the ions, systems of the cell", we realized that living organisms are complex electrochemical systems which evolved in a relatively narrow range of well-defined environmental parameters. Environmental natural electro-magnetic fields are an ubiquitous factor in nature. If nature gave certain organisms the ability to receive information about the environment via invisible electromagnetic signals, then there must also the capability to discriminate between significant and meaningless ones. Bearing in mind that electromagnetic fields can be perceived by living organisms by means a resonance effect, we should not be amazed if they can be able to induce different biological effects. The work that we will present in memory of Emilio is based on the hypotheses that an aqueous system a chemical differentiation agent such as retinoic acid (RA) were electronically captured and transferred to the culture medium of Neuroblastoma Cell Line (LAN-5) and the proliferation rate was assessed to assess cell responses to the electromagnetic information transfer through the aqueous system. Like those enfolded in living organisms could play a synergic role in modulating biological functions, generating dissipative structures under appropriate patterns of electromagnetic signals providing basis for storing and retrieving biological activities. An external electro-magnetic stimulus from a source molecule can be stored, translated, and transferred by the aqueous systems to the biological target, selectively driving their endogenous activity and mimicking the effect of a source molecule.

There is an ongoing question regarding the structure forming capabilities of water at ambient temperatures. To probe for different structures, we studied effects in pure water following magnetic field exposures corresponding to the ion cyclotron resonance of H3O+. Included were measurements of conductivity and pH. We find that under ion cyclotron resonance (ICR) stimulation, water undergoes a transition to a form that is hydroxonium-like, with the subsequent emission of a transient 48.5Hz magnetic signal, in the absence of any other measurable field. Our results indicate that hydronium resonance stimulation alters the structure of water, enhancing the concentration of EZ-water. These results are not only consistent with Del Giudice's model of electromagnetically coherent domains, but they can also be interpreted to show that these domains exist in quantized spin states.

We have performed a series of experiments applying high voltage between two electrodes, immersed in two beakers containing bidistilled water in a way similar to experiments conducted by Fuchs and collaborators, which showed that a water bridge can be formed between the two containers. We also observed the formation of water bridge. Moreover, choosing different pairs of electrodes depending on the material they are made up of, we observed that copper ions flow can pass along the bridge if the negative electrode is made up of copper. We show that the direction of the flux not only depends on the applied electrostatic field but on the relative electronegativity of the electrodes too. These results open new perspectives in understanding the properties of water. We suggest a possible explanation of the obtained results.

In vivo control of osteoblast differentiation is an important process needed to maintain the continuous supply of mature osteoblast cells for growth, repair, and remodeling of bones. The regulation of this process has also an important and significant impact on the clinical strategies and future applications of cell therapy. In this article, we studied the effect of nonpulsed sinusoidal electromagnetic field radiation tuned at calcium-ion cyclotron frequency of 50 Hz exposure treatment for bone differentiation of human mesenchymal stem cells (hMSCs) alone or in synergy with dexamethasone, their canonical chemical differentiation agent. Five days of continuous exposure to calcium-ion cyclotron resonance affect hMSC proliferation, morphology, and cytoskeletal actin reorganization. By quantitative real-time polymerase chain reaction, we also observed an increase of osteoblast differentiation marker expression such as Runx2, alkaline phosphatase (ALP), osteocalcin (OC), and osteopontin (OPN) together with the osteoprotegerin mRNA modulation. Moreover, in these cells, the increase of the protein expression of OPN and ALP was also demonstrated. These results demonstrate bone commitment of hMSCs through a noninvasive and biocompatible differentiating physical agent treatment and highlight possible applications in new regenerative medicine protocols.

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Some experimental evidences of the procedure defined as electro-magnetic information delivery, mediated through aqueous system, have accumulated in the last two decades. The present work is based on the hypotheses that an aqueous system like those enfolded in livings, could play an additional synergic role in modulating biological functions. Aqueous system could generate dissipative structures under appropriate patterns of electromagnetic signals providing basis for storing and retrieving biologic activities. External electro-magnetic stimuli in resonant conditions with some of the coherent domains of water can induce dipole moments re-patterning in a way that these structure start to oscillate coherently each other generating a new phase correlation. This procedure allows to an external electro-magnetic stimulus to be stored, translated and transferred by the aqueous systems to the biological target, driving selectively their endogenous activity mimicking the effect of a specific source molecule. Signals from a chemical differentiation agent such as Retinoic Acid (RA) was captured and transferred to the target culture medium of Neuroblastoma Cell Line (LAN-5) and the proliferation rate was assessed, in order to investigate cell responses to electromagnetic information system.

Only recently has the critical importance of electromagnetic (EM) field interactions in biology and medicine been recognized. We review the phenomenon of resonance signaling, discussing how specific frequencies modulate cellular function to restore or maintain health. The application of EM-tuned signals represents more than merely a new tool in information medicine. It can also be viewed in the larger context of EM medicine, the all-encompassing view that elevates the EM over the biochemical. The discovery by Zhadin that ultrasmall magnetic intensities are biologically significant suggests that EM signaling is endogenous to cell regulation, and consequently that the remarkable effectiveness of EM resonance treatments reflects a fundamental aspect of biological systems. The concept that organisms contain mechanisms for generating biologically useful electric signals is not new, dating back to the nineteenth century discovery of currents of injury by Matteucci. The corresponding modern-day version is that ion cyclotron resonance magnetic field combinations help regulate biological information. The next advance in medicine will be to discern and apply those EM signaling parameters acting to promote wellness, with decreasing reliance on marginal biochemical remediation and pharmaceuticals.

In regenerative medicine finding a new method for cell differentiation without pharmacological treatment or gene modification and minimal cell manipulation is a challenging goal. In this work we reported a neuronal induced differentiation and consequent reduction of tumorigenicity in NT2 human pluripotent embryonal carcinoma cells exposed to an extremely low frequency electromagnetic field (ELF-EMF), matching the cyclotron frequency corresponding to the charge/mass ratio of calcium ion (Ca(2+)-ICR). These cells, capable of differentiating into post-mitotic neurons following treatment with Retinoic Acid (RA), were placed in a solenoid and exposed for 5 weeks to Ca(2+)-ICR. The solenoid was installed in a μ-metal shielded room to avoid the effect of the geomagnetic field and obtained totally controlled and reproducible conditions. Contrast microscopy analysis reveled, in the NT2 exposed cells, an important change in shape and morphology with the outgrowth of neuritic-like structures together with a lower proliferation rate and metabolic activity alike those found in the RA treated cells. A significant up-regulation of early and late neuronal differentiation markers and a significant down-regulation of the transforming growth factor-α (TGF-α) and the fibroblast growth factor-4 (FGF-4) were also observed in the exposed cells. The decreased protein expression of the transforming gene Cripto-1 and the reduced capability of the exposed NT2 cells to form colonies in soft agar supported these last results. In conclusion, our findings demonstrate that the Ca(2+)-ICR frequency is able to induce differentiation and reduction of tumorigenicity in NT2 exposed cells suggesting a new potential therapeutic use in regenerative medicine.

Since the time of Hyppocrates it is very well known that is possible to transfer biochemical information for the treatment of human diseases by using molecules as active principle.This strategy has been the most efficient one until the time of Becker and Frohlich when we become aware that it was also possible transfer effective information to biological target by the use of electromagnetic field in the ELF range. Later on Benveniste suggested that for every chemical molecule there is only and only one electromagnetic image a kind of electromagnetic signature. Benveniste and coworkers demonstrated that picking up the physical signals of a chemical compound and transferring it to an aqueous system by mean of an electronic device this procedure was mimicking the same effect of the chemical source molecule. The transfer of the physical activity is probably mediated and can be amplified by water biophysical re-patterning. Electromagnetic Information Transfer of Specific Molecular Signals according to previous report and ours was performed in order to understand the possible role of water in mediating the electro-magnetic information transfer of biological active molecules such as retinoic acid (RA). The electromagnetic information signals from the retinoic acid solution (RA-EMIT) was captured and transferred to the target by a commercially available oscillator (Vega Select 719). The retinoic acid signals was transferred to a cell culture medium (RPMI). Neuroblastoma Cell Line (LAN-5) was seeded and grown up for four days in presence of Retinoic Acid signal and/or chemical molecule. The experimental findings demonstrated that the RA signal shows the tendency to behave as a differentiating agent such as the original molecule.

Aiming to explore the mechanisms modulating cell-carbon nanotube interactions, we investigated whether Ca2+ ion balancing between intra-and extracellular environments could be affected by multiwalled carbon nanotubes (MWCNTs). We analyzed the effects induced by two different kinds of MWCNTs (as prepared and annealed at 2400 degrees C) on the intracellular Ca2+ ion levels in rat electrically sensitive cells and on the intercellular junction integrity of rat adenocarcinoma colon cells and platelet aggregation ability, which depend on the Ca2+ concentration in the medium. MWCNTs, purified by annealing and more electroconductive as compared to nonannealed MWCNTs, affected Ca2+ ion balancing between extra-and intracellular environments and induced changes on Ca2+ ion-dependent cellular junctions and platelet aggregation, behaving as the calcium chelator ethylene glycol tetraacetic acid. This could be due to the sorption of cationic Ca2+ ions on CNTs surface because of the excess of negatively charged electrons on the aromatic units formed on MWCNTs after annealing.

Vascular restenosis is affecting 30-40% of patients treated by percutaneous coronary angioplasty (PTCA). The advent of stenting reduced but not abolished restenosis. The introduction of drug eluting stent (DES) further reduced restenosis, but impaired endothelization exposed to intracoronary thrombosis as late adverse event. It is widely accepted that the endothelial denudation and coronary wall damages expose Vascular Smooth Muscle Cells (VSMC) to multiple growth factors and plasma circulating agents thus activating migration and proliferative pathways leading to restenosis. Among the major players of this processes, phosphorylated Elk-1, forming the Elk-1/SRF transcription complex, controls the expression of a different set of genes responsible for cell proliferation. Therefore, it is feasible that gene-specific oligonucleotide therapy targeting VSMC migration and proliferation genes can be a promising therapeutic approach. While a plethora of vehicles is suitably working in static in vitro cultures, methods for in vivo delivery of oligonucleotides are still under investigation. Recently, we have patented a novel erythrocyte-based drug delivery system with high capability to fuse with targeted cells thus improving drug bioavailability at the site of action. Here, the potential of these engineered porcine erythrocytes to deliver a synthetic DNA Elk-1 decoy inside syngenic porcine VSMC was tested. The results of this study indicate that Elk-1 decoy is actually able to inhibit cell proliferation and migration of VSMC. Our data also suggest that erythrocyte-based carriers are more efficient in delivering these oligonucleotides in comparison to conventional vehicles. As a consequence, a lower dose of Elk-1 decoy, delivered by engineered erythrocytes, was sufficient to inhibit cell growth and migration. This approach represents the translational step to reach in vivo experiments in pigs after PTCA and/or stent implantation where oligonucleotide drugs will be site-specific administered by using erythrocyte-based carriers to prevent restenosis.

Controlling cell differentiation and proliferation with minimal manipulation is one of the most important goals for cell therapy in clinical applications. In this work, we evaluated the hypothesis that the exposure of myoblast cells (C2C12) to nonionizing radiation (tuned at an extremely low-frequency electromagnetic field at calcium-ion cyclotron frequency of 13.75 Hz) may drive their differentiation toward a myogenic phenotype. C2C12 cells exposed to calcium-ion cyclotron resonance (Ca2+-ICR) showed a decrease in cellular growth and an increase in the G(0)/G(1) phase. Severe modifications in the shape and morphology and a change in the actin distribution were revealed by the phalloidin fluorescence analysis. A significant upregulation at transcriptional and translational levels of muscle differentiation markers such as myogenin (MYOG), muscle creatine kinase (MCK), and alpha skeletal muscle actin (ASMA) was observed in exposed C2C12 cells. Moreover, the pretreatment with nifedipine (an L-type voltage-gated Ca2+ channel blocker) led to a reduction of the Ca2+-ICR effect. Consequently, it induced a downregulation of the MYOG, MCK, and ASMA mRNA expression affecting adversely the differentiation process. Therefore, our data suggest that Ca2+-ICR exposure can upregulate C2C12 differentiation. Although further studies are needed, these results may have important implications in myodegenerative pathology therapies.

Background: Recently the authors reported the experimental evidence of the developing concept of Electro Magnetic Information Transfer (EMIT) of specific molecular signals directly and continuously on target cell picking up the molecular signals from the source chemical effector. This was in agreement with the pioneering work of Jaques Benveniste suggesting that the electronic transmission of the 4-phorbol-12-myristate-13-acetate (PMA) signals could be transferred to target neutrophils by an oscillator when coupled to two electromagnetic coils demonstrating the same biologic activity and so mimicking the biologic function of the original chemical active molecule. The present work is the further development of recent research designed to verify the hypotheses that water could record and replay the EMIT from biologic active chemical molecules. Methods: Retinoic acid, a well-known chemical differentiating agent, was placed at room temperature in the input coil connected to an oscillator (VEGA select 719), while culture medium for human neuroblastoma cell (LAN-5) and NT2/D1 stem teratocarcinoma human cells was placed into the output coil and exposed to signals for 1 hour. At the end the oscillator was switched off and LAN-5 neuroblastoma and NT2/D1 stem teratocarcinoma cells were seeded, respectively, into the medium conditioned as reported into an incubator under controlled conditions. After 5 days of incubations, cells were examined by different strategies such as morphological and biochemical parameters. Results: It was demonstrated that the electromagnetic signals coming from the retinoic acid molecule could be recorded and stored by the aqueous system of the cell culture medium. Cells seeded in the electronically conditioned medium received physical information generating a statistically significant decrease in metabolic activity and changes in phenotypical structure with protrusion typical of differentiated neuronal cells. Conclusions: These experimental results provide some evidence that water could be tuned in a resonant manner by the EMIT procedure appropriately carried through a carrier frequency provided by the oscillator in a manner that seems related to the chemical structure of the source molecule as, in this case, retinoic acid.