Antipsicóticos para la esquizofrenia: paradigma de los medicamentos psiquiátricos / Antipsychotics for schizophrenia: the paradigm of psychiatric drugs

Los antipsicóticos no parecen revertir las causas de la esquizofrenia y, aunque son fármacos que pueden aliviar los síntomas a corto y mediano plazo, a largo plazo pueden no ser beneficiosos e incluso ser contraproducentes. Su empleo debería limitarse a situaciones agudas con agitación y tensión incapacitante. Presentan considerables efectos adversos y, ante la negativa de una persona a seguir tomándolos, adoptar una estrategia de reducción de daños apoyando y supervisando la retirada puede ser preferible a la coerción. Existen alternativas a los neurolépticos. Los prescriptores deberían estar más atentos y considerar las valoraciones que los usuarios hacen de sus efectos. El apego a las guías de tratamiento es escaso, seguramente por basarse en ensayos clinicos de calidad deficente, que deben mejorar y prolongarse en el tiempo. La raíz del problema probablemente se encuentra en la tautología sobre la etiología y naturaleza biológica de lo que llaman esquizofrenia, que realmente no parece ser más que un constructo ideológico-comercial.

Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and although they can relieve symptoms in the short to medium term, in the long term they may not be beneficial and could even be counterproductive. Their use should be limited to acute situations in which agitation and tension is disabling. The drugs have significant adverse effects, and given the refusal of a person to continue taking them, a harm reduction strategy to support and monitor the withdrawal may be preferable to coercion. There are alternatives to neuroleptics. Prescribers should be more vigilant and consider the assessments of users regarding the drugs' effects. Adherence to treatment guidelines is low, probably because the guidelines are based on clinical trials of deficient quality which consequently should be improved and extended over a greater period of time. The root of the problem is likely the tautology on the etiology and biological nature of what is known as schizophrenia, which in fact does not seem to be more than a commercial and ideological construct.

Cell phone radiation exposure on brain and associated biological systems.

Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.

Pulmonary surfactants and their role in pathophysiology of lung disorders.

Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.

Structural insight to mutated Y116S transthyretin by molecular dynamics simulation.

Familial amyloidotic polyneuropathy (FAP) is strictly associated with point mutations of transthyretin (TTR) protein. The Tyr116->Ser (Y116S) mutant TTR is an important amyloidogenic variant responsible for FAP. Structural dynamics of monomeric TTR and its mutant (Y116S) may give some clue relating to amyloid formation. In this study, molecular dynamic simulation at 310 K has been performed on wild-type and mutant (Y116S) TTR monomer, which can provide the molecular insight of structural transition in the inner and outer strand of the protein. Results show that mutation in the H-strand (Tyr116->Ser) leads to disruption of secondary structure and H-bonding pattern of some important parts of the inner DAGH-sheet of the protein. Especially, the residues T106, A108, L110 of G-strand, S117 and T119 of H-strand are affected, which are involved in the binding of thyroxin hormone. This unfolding of mutant structure during dynamics may cause instability in the protein and thus induce amyloidgenesis.

Desenvolvimento de formulações cosméticas hidratantes e avaliação da eficácia por métodos biofísicos / Development of cosmetic moisturizer formulations and evaluation of hydrating eficcacy by biophysical methods

Introdução: A comprovação da eficiência de formulações hidratantes deve ser criteriosa e analisada por com métodos adequados. Objetivo: O objetivo principal do trabalho foi avaliar in vivo a eficácia hidratante de formulações contendo diferentes componentes ativos por capacitância elétrica e perda de água transepidérmica. Compararam-se os desempenhos entre Corneometer® e Moisturemeter® e entre o Vapometer® e Tewlmeter®. Verificou-se o comportamento in vitro das alterações causadas pelas substâncias hidratantes, em modelo de estrato córneo alternativo. Material e Métodos: Os compostos ativos selecionados (4% p/p) para incorporação nos géis a base de carbômero foram: uréia, extrato vegetal de Imperata cylindrica; complexo contendo fatores de hidratação natural; e os derivados do açúcar, sacarídeo isomerato e a mistura de xilitilglicosídeo e anidroxilitilglicosídeo. A avaliação in vivo da eficácia hidratante, teve o delineamento experimental baseado no projeto fatorial ANOVA three way. Os tempos estudados foram: após a aplicação e 30,60, 120; 240 e 360 minutos. O estudo de estabilidade acelerada das formulações envolveu condições drásticas de armazenamento (temperatura, umidade e luminosidade) durante 90 dias. Na avaliação in vitro do comportamento das substâncias hidratantes utilizou-se a espectroscopia Raman com transformada de Fourier (FT-Raman) e Calorimetria exploratória diferencial (DSC)...

Aplicação de métodos de biofísica no estudo da eficácia de produtos dermocosméticos / Application of biophysical methods to study the efficacy of skin care products

O trabalho aborda a aplicação dos métodos de biofísica no estudo de eficácia de produtos dermocosméticos. A qualidade de um produto cosmético engloba a segurança de seu uso, a estabilidade da formulação, o aspecto, o sensorial e a sua eficácia. As técnicas de biofísica têm sido amplamente empregadas na avaliação do efeito de formulações dermocosméticas, principalmente devido ao fato de possibilitarem a avaliação de produtos em suas reais condições de uso, ou seja, na pele humana. A comprovação dos efeitos de produtos cosméticos e a elucidação de seu mecanismo de ação por meio de protocolos experimentais devidamente elaborados, que utilizem as técnicas de biofísica da pele, dentre outras, tornam-se de fundamental importância e, assim, a serem amplamente exploradas e ainda bastante desenvolvidas, visando à melhoria da qualidade de vida dos usuários de tais produtos.

The authors consider the application of biophysical techniques in the study of cosmetics effectiveness. The quality of a cosmetic product includes the safety of its use, the formulation stability , the visual and other sensorial aspects, and its effectiveness. The biophysical techniques have been widely used in the evaluation of the effect of formulations of topical use, mainly due to the fact of facilitating the evaluation of products in its real use conditions, that is to say, directly in the human skin. The confirmation of the effects of cosmetic products and its action mechanism, by means of experimental protocols properly elaborated using the skin biophysics is of fundamental importance. It should be thoroughly explored and quite developed seeking the improvement of the life quality of users of such products.

Quantum nature of photon signal emitted by Xanthoria parietina and its implications to biology.

The properties of living systems are usually described in the semi-classical framework that makes phenomenological division of properties into four classes--matter, psyche, soft consciousness and hard consciousness. Quantum framework provides a scientific basis of this classification of properties. The scientific basis requires the existence of macroscopic quantum entity entangled with quantum photon field of a living system. Every living system emits a photon signal with features indicating its quantum nature. Quantum nature of the signal emitted by a sample of X. parietina is confirmed by analysing photo count distributions obtained in 20000 measurements of photon number in contiguous bins of sizes of 50, 100, 200, 300 and 500 ms. The measurements use a broadband detector sensitive in 300-800 nm range (Photo count distributions of background noise and observed signal are measured similarly. These measurements background noise corrected squeezed state parameters of the signal. The parameters are signal strength expressed in counts per bin, r = 0.06, theta = 2.76 and phi = 0.64. The parameters correctly reproduce photo count distribution of any bin size in 50 ms-6 s range. The reproduction of photo count distributions is a credible evidence of spontaneous emission of photon signal in a quantum squeezed state for macroscopic time by the sample. The evidence is extrapolated to other living systems emitting similar photon signals. It is suggested that every living system is associated with a photon field in squeezed state. The suggestion has far reaching implications to biology and provides two ways of observing and manipulating a living system--either through matter or field or a combination of the two. Some implications and possible scenarios are elaborated.

Physical basis of adverse and therapeutic effects of low intensity microwave radiation.

A physical basis of adverse and therapeutic effects of low intensity microwave radiation is presented based on the concept of oscillatory similitude between the frequency of an external microwave field (together with any lower frequency modulations thereof) and those of certain endogenous dipolar coherent excitations allied to aliveness, which play the role of 'tuned circuits' via which a living organism is electromagnetically sensitised in a non-linear way to external fields too weak to be able to cause heating. From this perspective, an external electromagnetic field affects a living system not as a toxin but rather by perturbing its endogenous electromagnetic activity. The possibility of adverse perturbation is illustrated by reference to the microwave fields used in mobile telecommunications whose signals interfere in a non-thermal way with biofunctionality--in particular, undermining the efficacy of processes that would otherwise afford natural protection against the development of pathology. Therapeutic modalities of microwave exposure, on the other hand, are illustrated using the example of microwave resonance therapy--which can be considered as an electromagnetic version of acupuncture, and as an example of 'quantum medicine'--whose normalising effect on a wide range of pathologies is striking, and which affords a novel alternative to conventional pharmacological interventions.

Principles of complementary medicine in terms of a suggested scientific basis.

In order to create a scientific basis of complementary medicine it is certainly necessary to add a more non-local approach to the molecular substance of orthodox "life-sciences". It should be able to explain strange phenomena like healing by homeopathy or acupuncture. A possible frame concerns oscillatory electromagnetic interactions as regulatory and - in case of disease--deregulatory impulses of the organisms. These couplings are found, for instance, in biological rhythms, external rhythmical influences (sun exposure, atmospheric disturbances), and vibrations of the body over a huge range of frequencies. One basic example is biophotons and "delayed luminescence".

Imaging of biophoton emission from electrostimulated skin acupuncture point jg4: effect of light enhancers.

Using an ultrasensitive CCD camera, an extremely low light intensity from the acupuncture-sensitive point JG4 at the left hand was recorded. As the intensity of the light was very weak and the time of electrostimulation exceeded the recommended period, the quality of biophoton images was poor. Chemiluminescent and fluorescent hydrophilic, hydrophobic and amphyphilic molecular probes were used to: (i) ensure penetration of probes into skin, (ii) enhance the intensity of BP emission, (iii) shorten time and (iv) obtain information about mechanisms of biophotons generation in EAP-sensitive points and channels. The results obtained partially fulfilled expectations and indicate on the necessity to elaborate special techniques of probes deposition on the skin.

Biophysical aspects of cancer--electromagnetic mechanism.

Hypothesis of coherent vibration states in biological systems based on nonlinear interaction between longitudinal elastic and electric polarization fields with metabolic energy supply was formulated by Frohlich. Conditions for excitation of coherent states and generation of electromagnetic fields are satisfied in microtubules which form electrical polar structures. Numerical models are used for analysis of Frohlich's vibration states in cells. Reduction of activity and of energy production in mitochondria, and disintegration of cytoskeleton structures by phosphorylation on the pathway of cancer trasformation can diminish excitation of the Frohlich's vibration states and of the generated electromagnetic field, which results in disturbances of the interaction forces between cells. Interaction forces between cancer cells may be smaller than interaction forces between healthy cells and cancer cells as follows from numerical models. Mechanism of malignity, i.e. local invasion, detachment of cancer cells, and metastasis, is assumed to depend on the electromagnetic field.

Laser-ultraviolet-A induced ultra weak photon emission in human skin cells: A biophotonic comparison between keratinocytes and fibroblasts.

Photons participate in many atomic and molecular interactions and processes. Recent biophysical research has discovered an ultraweak radiation in biological tissues. It is now recognized that plants, animal and human cells emit this very weak biophotonic emission which can be readily measured with a sensitive photomultiplier system. UVA laser induced biophotonic emission of cultured cells was used in this report with the intention to detect biophysical changes between young and adult fibroblasts as well as between fibroblasts and keratinocytes. With suspension densities ranging from 1-8 x 106 cells/ml, it was evident that an increase of the UVA-laser-light induced photon emission intensity could be observed in young as well as adult fibroblastic cells. By the use of this method to determine ultraweak light emission, photons in cell suspensions in low volumes (100 microl) could be detected, in contrast to previous procedures using quantities up to 10 ml. Moreover, the analysis has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of more than 100 milliseconds. These significant changes lead to an improvement factor up to 106 in comparison to classical detection procedures. In addition, different skin cells as fibroblasts and keratinocytes stemming from the same donor were measured using this new highly sensitive method in order to find new biophysical insight of light pathways. This is important in view to develop new strategies in biophotonics especially for use in alternative therapies.

Mode coupling in living systems: implications for biology and medicine.

Complex systems, and in particular biological ones, are characterized by large numbers of oscillations of widely differing frequencies. Various prejudices tend to lead to the assumption that such oscillators should generically be very weakly interacting. This paper reviews the basic ideas of linearity and nonlinearity as seen by a physicist, but with a view to biological systems. In particular, it is argued that large couplings between different oscillators of disparate frequencies are common, being present even in rather simple systems which are well-known in physics, although this issue is often glossed over. This suggests new experiments and investigations, as well as new approaches to therapies and human-environment interactions which, without the concepts described here, may otherwise seem unlikely to be interesting. The style of the paper is conversational with a minimum of mathematics, and no attempt at a complete list of references.

Nonlinear mechanism for weak photon emission from biosystems.

The nonlinear mechanism for the origin of the weak biophoton emission from biological systems is suggested. The mechanism is based on the properties of solitons that provide energy transfer and charge transport in metabolic processes. Such soliton states are formed in alpha-helical proteins. Account of the electron-phonon interaction in macromolecules results in the self-trapping of electrons in a localized soliton-like state, known as Davydov's solitons. The important role of the helical symmetry of macromolecules is elucidated for the formation, stability and dynamical properties of solitons. It is shown that the soliton with the lowest energy has an inner structure with the many-hump envelope. The total probability of the excitation in the helix is characterized by interspine oscillations with the frequency of oscillations, proportional to the soliton velocity. The radiative life-time of a soliton is calculated and shown to exceed the life-time of an excitation on an isolated peptide group by several orders of magnitude.

Physical properties of biophotons and their biological functions.

Biophotons (BPHs) are weak photons within or emitted from living organisms. The intensities of BPHs range from a few to several hundred photons s(-1) x cm(-2). BPH emission originates from a de-localized coherent electromagnetic field within the living organisms and is regulated by the field. In this paper based on the experimental results of Poisson and sub-Poisson distributions of photocount statistics, the coherent properties of BPHs and their functions in cell communication are described. Discussions are made on functions which BPHs may play in DNA and proteins functioning including the process of DNA replication, protein synthesis and cell signalling and in oxidative phosporylation and photosynthesis.

In vivo visualization of bonghan ducts inside blood vessels of mice by using an Alcian blue staining method.

An in vivo method using Alcian blue (AB) was developed for visualizing floating threadlike tissues inside blood vessels of mice. These novel structures called intravascular Bonghan ducts (IBHDs) are considered as extension of acupuncture meridians. For in vivo imaging of IBHDs, AB solution (pH 7.4) that stains mucopolysaccharides like hyaluronic acid was used. After injecting AB solution into the femoral vein of a mouse, the threadlike structures, stained deep blue, inside the inferior vena cava. The histological results, such as hematoxylin, eosin, and AB staining, show the compositions of the cells and the extracellular matrix in the IBHD. Further studies are needed to investigate their physiological functions, especially in relation with those of other circulatory systems.

Quantum squeezed state analysis of spontaneous ultra weak light photon emission of practitioners of meditation and control subjects.

Research on human ultra-weak photon emission (UPE) has suggested a typical human emission anatomic percentage distribution pattern. It was demonstrated that emission intensities are lower in long-term practitioners of meditation as compared to control subjects. The percent contribution of emission from different anatomic locations was not significantly different for meditation practitioners and control subjects. Recently, a procedure was developed to analyze the fluctuations in the signals by measuring probabilities of detecting different numbers of photons in a bin and correct these for background noise. The procedure was tested utilizing the signal from three different body locations of a single subject, demonstrating that probabilities have non-classical features and are well described by the signal in a coherent state from the three body sites. The values indicate that the quantum state of photon emitted by the subject could be a coherent state in the subject being investigated. The objective in the present study was to systematically quantify, in subjects with long-term meditation experience and subjects without this experience, the photon count distribution of 12 different locations. Data show a variation in quantum state parameters within each individual subject as well as variation in quantum state parameters between the groups.

Ultra-low luminescence of humid air and its possible role in negative air ion therapy.

One of the unresolved questions related to the mechanism of action of light negative air ions (reactive oxygen species) produced by air ionizers upon humans and animals is transmission of these short-living chemical species upon long distances from the place of their origin. We discovered the phenomenon which may probably resolve this problem. When a thin layer of water hydrating a hygroscopic surface absorbs rare UV-photons capable to split water molecules a flash of photon emission in UV- and visible regions of spectrum is observed. This flash (or oxygen-dependent oxidative processes underlying it) initiate reactions accompanied with generation of electronic excitation in the air contacting water film. Excitation propagates through the air at macroscopic distances, and the level of propagating excitation increases with elevation of air humidity. When air humidity exceeds 50% air excitation gains oscillatory-wave character. This phenomenon may endow into the mechanism of action of air ions generated artificially, and also into some natural processes where ordered water films may form and the latter may serve targets for energy impulses initiating oxygen-dependent oxidative processes in these films.

Free radicals and low-level photon emission in human pathogenesis: state of the art.

Convincing evidence supports a role for oxidative stress in the pathogenesis of many chronic diseases. The model includes the formation of radical oxygen species (ROS) and the misassembly and aggregation of proteins when three tiers of cellular defence are insufficient: (a) direct antioxidative systems, (b) molecular damage repairing systems, and (c) compensatory chaperone synthesis. The aim of the present overview is to introduce (a) the basics of free radical and antioxidant metabolism, (b) the role of the protein quality control system in protecting cells from free radical damage and its relation to chronic diseases, (c) the basics of the ultraweak luminescence as marker of the oxidant status of biological systems, and (d) the research in human photon emission as a non-invasive marker of oxidant status in relation to chronic diseases. In considering the role of free radicals in disease, both their generation and their control by the antioxidant system are part of the story. Excessive free radical production leads to the production of heat shock proteins and chaperone proteins as a second line of protection against damage. Chaperones at the molecular level facilitate stress regulation vis-à-vis protein quali y control mechanisms. The manifestation of misfolded proteins and aggregates is a hallmark of a range of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amylotrophic lateral sclerosis, polyglutamine (polyQ) diseases, diabetes and many others. Each of these disorders exhibits aging-dependent onset and a progressive, usually fatal clinical course. The second part reviews the current status of human photon emission techniques and protocols for recording the human oxidative status. Sensitive photomultiplier tubes may provide a tool for non-invasive and continuous monitoring of oxidative metabolism. In that respect, recording ultraweak luminescence has been favored compared to other indirect assays. Several biological models have been used to illustrate the technique in cell cultures and organs in vivo. This initiated practical applications addressing specific human pathological issues. Systematic studies on human emission have presented information on: (a) procedures for reliable measurements, and spectral analysis, (b) anatomic intensity of emission and left-right symmetries, (c) biological rhythms in emission, (d) physical and psychological influences on emission, (e) novel physical characteristics of emission, and (f) the identification of ultraweak photon emission with the staging of ROS-related damage and disease. It is concluded that both patterns and physical properties of ultraweak photon emission hold considerable promise as measure for the oxidative status.

Corresponding measurements of delayed luminescence and impedance spectroscopy on acupuncture points.

Measurements of impedance spectroscopy and delayed luminescence have been performed on the acupuncture points PC4 and PC8 and other two control points of ten volunteers. The results show that there is a highly significant difference between the imaginary parts of the impedance of the acupunctural points and that of the control points. The same difference has not be observed in the values of the total number of counts of delayed luminescence. However a relationship has been detected between the imaginary part of the impedance of PC8 point and the total number of delayed luminescence counts, similar to that one found before for collagen, and it has been seen that the temporal dynamics of the two phenomena measured on one control points are similar. In particular, these final results confirm the close connection between the delayed luminescence and the dielectric properties of biological tissues.