The AC conductivity of human sweat ducts as the dominant factor in the sub-THz reflection coefficient of skin

The helical nature of human sweat ducts, combined with the morphological and dielectric properties of skin, suggests electromagnetic activity in the sub-THz frequency band. A detailed electromagnetic simulation model of the skin, with embedded sweat ducts, was created. The model includes realistic dielectric properties based on the measured water content of each layer of skin, derived from Raman Spectroscopy. The model was verified by comparing it to measurements of the reflection coefficient of the palms of 13 volunteers in the frequency band 350–410 GHz. They were subjected to a measurement protocol intended to induce mental stress, thereby also activating the sweat glands. The Galvanic Skin Response was concurrently measured. Using the simulation model the optimal ac-conductivity for each measurement was found. The range of variation for all subjects was found to be from 100 S/m to a maximum value of 6000 S/m with averages of 1000 S/m. These are one order of magnitude increase from the accepted values for water at these frequencies (~100 s/m at 100 GHz). Considering the known biochemical mechanism for inducing perspiration, we conclude that these ac-conductivity levels are probably valid, even though the real time measurements of sweat ac-conductivity levels inside the duct are inaccessible.     

Regulation of mental states and biofeedback techniques: Effects on breathing pattern

The purpose of the present study was to examine whether breathing pattern may be used as a reliable index for the effectiveness of techniques applied for the regulation of mental states. Heart rate (HR), breathing pattern, galvanic skin response (GSR), and electromyogram (EMG) of the frontalis muscle were measured in 39 male and female subjects aged 18–25 years during 10-minute treatment with relaxation technique (autogenic training and/or music) followed by 10 minutes of imagery training. In the first 7 sessions biofeedback (BFB) was not included, while during the last 6 sessions BFB was introduced and utilized by the subjects. Relaxation (music or autogenic training) led to a decrease in breathing frequency, attributed to lengthening of expiration time, as well as reduced HR, GSR, and frontalis EMG response. In most instances imagery training was related to an increase in these indices. Specifically, significant tachypnea was observed during imagery of sprint running. In most cases BFB substantially augmented the physiological responses. In conclusion, our data suggest that, compared with HR, GSR, and EMG responses, the breathing pattern is at least as sensitive to the mental techniques employed, and may be useful as a psychophysiological index for diagnosis and testing, especially in sport practice.     

A study of absorption of energy of the extremely high frequency electromagnetic radiation in the rat skin by various dosimetric methods and approaches

Using experimental and theoretical methods of dosimetry, the energy absorption of extremely high-frequency electromagnetic radiation (EHF EMR) in the skin of laboratory rats was analyzed. Specific absorption rate (SAR) in the skin was determined on the basis of both microthermometric measurements of initial rates of temperature rise in rat skin induced by the exposure and microcalorimetric measurements of specific heat of the skin. Theoretical calculations of SAR in the skin were performed with consideration for dielectric parameters of rat skin obtained from the measurements of the standing wave ratio upon reflection of electromagnetic waves from the skin surface and for the effective area of stationary overheating measured by infrared thermography. A numerical method was developed to determine electromagnetic wave energy reflected, absorbed, and transmitted in the model of flat layers. The algorithm of the method was realized in a computer program and used to calculate SAR in the skin on the basis of the complex dielectric constant of rat skin. The SAR values obtained from experimental measurements, theoretical calculations and numerical analysis are in good mutual correspondence and make about 220-280 W/kg at a frequency of 42.25 GHz and a power of 20 mW at the radiator output. The results obtained can be used for dosimetric supply of biomedical experiments on studying the physicochemical mechanisms of the biological effects of EHF EMR.     

The "Moi-peau"

To construct a coherent identity, humans must distinguish what belongs to the external, perceived world from what belongs to their own inner world and the inner world of other individuals. Based on the theory developed by S. Freud and on work by ethologists, a number of psychoanalysts (J. Bowlby, R.A. Spitz, D.W. Winnicott, etc.) have underlined the importance of early tactile exchanges with the mother if a child is to become an autonomous individual who feels secure within what he or she perceives to be sound and reliable mental and physical boundaries. More recently, other psychoanalysts (E. Bick, W.R. Bion, etc.) have studied the fantasized mental structures that form the limits between an individual's inner mental space and the external world (including other individuals). As part of this theoretical psychoanalytical movement, Didier Anzieu, a French psychoanalyst, started to develop the concept of the "Moi-peau" in 1974. The "Moi-peau" designates a fantasized reality that a child uses during its early development to represent itself as "me", based on its experience of the body surface. The child, enveloped in its mother's care, fantasizes of a skin shared with its mother: on one side the mother (the outer layer of the "Moi-peau"), and on the other side the child (the inner layer of the "Moi-peau"). These two layers must separate gradually if the child is to acquire its own me-skin. D. Anzieu's work allowed dermatologists and other specialists, such as pediatricians, to focus on the quality of early tactile exchanges between a mother and her child, including the child with a chronic skin disorder. It also helped dermatologists to recognize patients with "borderline" states, which are particularly frequent in dermatology (ereutophobia, dysmorphophobia, tattooing, self-mutilation, artefacta dermatitis). These borderline patients are adults who, as a result of their mental conflicts, adopt defense mechanisms derived from both neurotic and psychotic functioning. Their complaints reflect difficulties with the solidity of their mental and physical limits: their real skin is metaphorically linked to the fantasized mental structure that delimits the individual mental space. Among other clinical characteristics, they have a "pathology of action" and frequently attack their own skin, paradoxically, in order to test the solidity and reliability of their own limits. Finally, D. Anzieu's work encouraged dermatologists to use psychotherapeutic approaches in parallel to classical dermatologic approaches, when necessary, and helped them better understand how psychoanalysts work with patients who have not yet acquired their own "Moi-peau". As a result, D. Anzieu was among the first to reconcile dermatologists and psychoanalysts.     

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women

Mental stress is thought to underlie cardiovascular events, but there is information on oxidative stress induced by mental stress in association with cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2-nonenal (HNE), as a marker for oxidative stress, we addressed the relation between pressor responses and oxidative stress induced by mental or physical stress in premenopausal and postmenopausal women. Healthy subjects (7 postmenopausal and 8 premenopausal women, in early and late follicular phases) were subjected to mental and physical stress evoked by a Color Word Test (CWT) and isometric handgrip, respectively. The CWT induced a rapid elevation of diastolic blood pressure (DBP), at a higher level in the postmenopausal than in the premenopausal women (p<0.01), and this higher DBP was sustained during the CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma noradrenaline in premenopausal women in the early follicular phase and in postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in postmenopausal than in the premenopausal women in the late follicular phase (p<0.05), but did not change during exposure to the two types of stress in either group. Plasma HNE was increased during recovery from the CWT, but not the handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant difference in the time course of the CWT-induced HNE response between the postmenopausal and premenopausal women (p<0.05). These findings suggest that mental, but not physical, stress causes sustained diastolic blood pressure elevation in postmenopausal women, accompanied by heightened oxidative stress.     

Human skin permittivity determined by millimeter wave reflection measurements

Millimeter wave reflection from the human skin was studied in the frequency range of 37-74 GHz in steps of 1 GHz. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. To fit the reflection data, a homogeneous unilayer and three multilayer skin models were tested. Skin permittivity in the mm-wave frequency range resulted from the permittivity of cutaneous free water which was described by the Debye equation. The permittivity increment found from fitting to the experimental data was used for determination of the complex permittivity and water content of skin layers. Our approach, first tested in pure water and gelatin gels with different water contents, gave good agreement with literature data. The homogeneous skin model fitted the forearm data well. Permittivity of the forearm skin obtained with this model was close to the skin permittivity reported by others. To fit reflection from the palmar skin with a thick SC, a skin model containing at least two layers was required. Multilayer models provided better fitting to both the forearm and palmar skin reflection data. The fitting parameters obtained with different models were consistent with each other.     

Shining light on the alphaproteobacterial general stress response

The general stress response (GSR) allows many bacterial species to react to myriad different stressors. In Alphaproteobacteria, this signaling pathway proceeds through the partner‐switching PhyR‐EcfG sigma‐factor mechanism and is involved in multiple life processes, including virulence in Brucella abortus. To date, details of the alphaproteobacterial GSR signaling pathway have been determined using genetic and biochemical work on a diverse set of species distributed throughout the clade. Fiebig and co‐workers establish Erythrobacter litoralis DSM 8509 as a genetically tractable lab strain and use it to both directly and indirectly delineate photoresponsive GSR pathways mediated by multiple HWE/HisKA_2 histidine kinases. The existence of a new phototrophic lab strain allows researchers to compare the GSR across different Alphaproteobacteria, as well as study the interplay between the GSR and phototrophy. Additionally, the discovery of new HWE/HisKA_2 kinases regulating the GSR poses new questions about how different stimuli feed into this widespread stress pathway.     

In vitro study of the stress response of human skin cells to GSM-1800 mobile phone signals compared to UVB radiation and heat shock

The evolution of mobile phone technology is toward an increase of the carrier frequency up to 2.45 GHz. Absorption of radiofrequency (RF) radiation becomes more superficial as the frequency increases. This increasingly superficial absorption of RF radiation by the skin, which is the first organ exposed to RF radiation, may lead to stress responses in skin cells. We thus investigated the expression of three heat-shock proteins (HSP70, HSC70, HSP27) using immunohistochemistry and induction of apoptosis by flow cytometry on human primary keratinocytes and fibroblasts. A well-characterized exposure system, SXC 1800, built by the IT'IS foundation was used at 1800 MHz, with a 217 Hz modulation. We tested a 48-h exposure at an SAR of 2 W/kg (ICNIRP local exposure limit). Skin cells were also irradiated with a 600 mJ/cm2 single dose of UVB radiation and subjected to heat shock (45 degrees C, 20 min) as positive controls for apoptosis and HSP expression, respectively. The results showed no effect of a 48-h GSM-1800 exposure at 2 W/kg on either keratinocytes or fibroblasts, in contrast to UVB-radiation or heat-shock treatments, which injured cells. We thus conclude that the GSM-1800 signal does not act as a stress factor on human primary skin cells in vitro.     

Evaluation of the Potential In Vitro Antiproliferative Effects of Millimeter Waves at Some Therapeutic Frequencies on RPMI 7932 Human Skin Malignant Melanoma Cells

The potential antiproliferative effects of low power millimeter waves (MMWs) at 42.20 and 53.57 GHz on RPMI 7932 human skin melanoma cells were evaluated in vitro in order to ascertain if these two frequencies, comprised in the range of frequency used in millimeter wave therapy, would have a similar effect when applied in vivo to malignant melanoma tumours. Cells were exposed for 1 h exposure/day and to repeated exposure up to a total of four treatments. Plane wave incident power densities <1 mW/cm² were used in the MMWs-exposure experiments so that the radiations did not cause significant thermal effects. Numerical simulations of Petri dish reflectivity were made using the equations for the reflection coefficient of a multilayered system. Such analysis showed that the power densities transmitted into the aqueous samples were ≤0.3 mW/cm². Two very important and general biological endpoints were evaluated in order to study the response of melanoma cells to these radiations, i.e. cell proliferation and cell cycle. Herein, we show that neither cell doubling time nor the cell cycle of RPMI 7932 cells was affected by the frequency of the GHz radiation and duration of the exposure, in the conditions above reported.     

Millimeter wave dosimetry of human skin

To identify the mechanisms of biological effects of mm waves it is important to develop accurate methods for evaluating absorption and penetration depth of mm waves in the epidermis and dermis. The main characteristics of mm wave skin dosimetry were calculated using a homogeneous unilayer model and two multilayer models of skin. These characteristics included reflection, power density (PD), penetration depth (delta), and specific absorption rate (SAR). The parameters of the models were found from fitting the models to the experimental data obtained from measurements of mm wave reflection from human skin. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. The thin SC produced little influence on the interaction of mm waves with skin. On the contrary, the thick SC in the palm played the role of a matching layer and significantly reduced reflection. In addition, the palmar skin manifested a broad peak in reflection within the 83-277 GHz range. The viable epidermis plus dermis, containing a large amount of free water, greatly attenuated mm wave energy. Therefore, the deeper fat layer had little effect on the PD and SAR profiles. We observed the appearance of a moderate SAR peak in the therapeutic frequency range (42-62 GHz) within the skin at a depth of 0.3-0.4 mm. Millimeter waves penetrate into the human skin deep enough (delta = 0.65 mm at 42 GHz) to affect most skin structures located in the epidermis and dermis.     

TRAIL-Based High Throughput Screening Reveals a Link between TRAIL-Mediated Apoptosis and Glutathione Reductase,a Key Component of Oxidative Stress Response

A high throughput screen for compounds that induce TRAIL-mediated apoptosis identified ML100 as an active chemical probe, which potentiated TRAIL activity in prostate carcinoma PPC-1 and melanoma MDA-MB-435 cells. Follow-up in silico modeling and profiling in cell-based assays allowed us to identify NSC130362, pharmacophore analog of ML100 that induced 65-95% cytotoxicity in cancer cells and did not affect the viability of human primary hepatocytes. In agreement with the activation of the apoptotic pathway, both ML100 and NSC130362 synergistically with TRAIL induced caspase-3/7 activity in MDA-MB-435 cells. Subsequent affinity chromatography and inhibition studies convincingly demonstrated that glutathione reductase (GSR), a key component of the oxidative stress response, is a target of NSC130362. In accordance with the role of GSR in the TRAIL pathway, GSR gene silencing potentiated TRAIL activity in MDA-MB-435 cells but not in human hepatocytes. Inhibition of GSR activity resulted in the induction of oxidative stress, as was evidenced by an increase in intracellular reactive oxygen species (ROS) and peroxidation of mitochondrial membrane after NSC130362 treatment in MDA-MB-435 cells but not in human hepatocytes. The antioxidant reduced glutathione (GSH) fully protected MDA-MB-435 cells from cell lysis induced by NSC130362 and TRAIL, thereby further confirming the interplay between GSR and TRAIL. As a consequence of activation of oxidative stress, combined treatment of different oxidative stress inducers and NSC130362 promoted cell death in a variety of cancer cells but not in hepatocytes in cell-based assays and in in vivo, in a mouse tumor xenograft model.     

Physical stress primes the immune response of Galleria mellonella larvae to infection by Candida albicans

Larvae of the greater wax moth (Galleria mellonella) that had been subjected to physical stress by shaking in cupped hands for 2 min showed reduced susceptibility to infection by Candida albicans when infected 24 h after the stress event. Physically stressed larvae demonstrated an increase in haemocyte density and elevated mRNA levels of galiomicin and an inducible metalloproteinase inhibitor (IMPI) but not transferrin or gallerimycin. In contrast, previous work has demonstrated that microbial priming of larvae resulted in the induction of all four genes. Examination of the expression of proteins in the insect haemolymph using 2D electrophoresis and MALDI TOF analysis revealed an increase in the intensity of a number of peptides showing some similarities with proteins associated with the insect immune response to infection. This study demonstrates that non-lethal physical stress primes the immune response of G. mellonella and this is mediated by elevated haemocyte numbers, increased mRNA levels of genes coding for two antimicrobial peptides and the appearance of novel peptides in the haemolymph. This work demonstrates that physical priming increases the insect immune response but the mechanism of this priming is different to that induced by low level exposure to microbial pathogens.     

The Galvanic Skin Response as a Reflection of the Decision-making Process under Conditions of Time Deficit

It is now difficult to find any studies in psychophysiology in which the galvanic skin response (GSR) is not recorded, but there is still no consensus concerning the functional significance of this reaction. The GSR reflects the degree of emotional tension [5], and is also one of the autonomic components of an orienting response [2].     

Antigraft responses to the H-28c antigen by B6 and B6D2F1 mice

The survival of minor H antigen-bearing skin grafts from donors congenic with C57BL/6 (B6) was compared in B6, B6D2, and AB6 hybrid recipients. In a case singled out for further study, B6 mice were found to reject HW 110 skin (H-28^c antigen) rapidly, whereas B6D2 mice rejected HW110 skin much more slowly and variably. Both major histocompatibility complex (MHC)-linked and non-MHC genes appeared to affect the survival of HW110 strain skin grafts on B6 and B6D2 recipients. Results of several experiments appear to rule out the sharing of H-28° epitopes between donors and recipients as an explanation for the relatively poor response of B6D2 mice to HW 110 skin grafts. Experiments involving bone marrow chimeras produced by the reciprocal exchange of bone marrow between irradiated B6 and B6D2 mice suggest that bone marrow-derived donor cells and non-bone-marrow-derived host cells each contribute to the immune response phenotype with respect to the H-28° antigen. An attempt was made to determine whether B6D2 mice that failed to reject HW110 strain skin grafts possessed suppressor cells specific for the H-28^c antigen. Spleen cells from poorly responsive B6D2 mice failed to suppress the rejection of HW 110 skin grafts when assayed in immunodeficient mice that were provided with cells from immune 136132 donors that were highly responsive to HW110 skin grafts.     

Stable gene silencing in human monocytic cell lines using lentiviral-delivered small interference RNA. Silencing of the p110alpha isoform of phosphoinositide 3-kinase reveals differential regulation of adherence induced by 1alpha,25-dihydroxycholecalciferol and bacterial lipopolysaccharide

Studying mononuclear phagocyte cell biology through genetic manipulation by non-viral transfection methods has been challenging due to the dual problems of low transfection efficiency and the difficulty in obtaining stable transfection. To overcome this problem, we developed a system for mediating RNA interference in monocytic cells. The p110alpha isoform of phosphoinositide 3-kinases (PI3Ks) was silenced using a lentiviral vector expressing short hairpin RNA (shRNA). This resulted in the generation of stable THP-1 and U-937 monocytic cell lines deficient in p110alpha. Notably, p110alpha was silenced without affecting levels of either the other class I(A) PI3K catalytic subunits p110beta and p110delta, or the p85alpha regulatory subunit. The role of p110alpha in mediating cell adherence was examined. Monocyte adherence induced in response to either lipopolysaccharide (LPS) or 1alpha,25-dihydroxycholecalciferol (D(3)) was blocked by the PI3K inhibitor LY294002. However, although adherence induced in response to D(3) was sensitive to silencing of p110alpha, LPS-induced adherence was not. Expression of the monocyte differentiation marker CD11b was also induced by D(3) in a PI3K-dependent manner and gene silencing using shRNA showed that p110alpha was also required for this effect. Taken together, these findings demonstrate that LPS and D(3) use distinct isoforms of class I(A) PI3K to induce functional responses and that lentiviral-mediated delivery of shRNA is a powerful approach to study monocyte biology.     

Effect of cold air inhalation on core temperature in exercising subjects under heat stress

Whether increasing respiratory heat loss (RHL) during exercise under heat stress can contain elevation of rectal temperature (Tre) was examined. Eight men cycled twice at 45-50% their maximum work rate until exhaustion at ambient temperature and relative humidity of 38 degrees C and 90-95%, respectively. They inspired either cold (3.6 degrees C) or ambient air in random sequence. When subjects breathed cold air during 23 min of exercise, a ninefold increase in RHL was observed vs. similar work during hot air inhalation (32.81 vs. 3.46 W). Respiratory frequency (f) and rate of rise in Tre decreased significantly (P less than or equal to 0.004 and P less than or equal to 0.002, respectively). The rise in skin temperature in each inhalant gas condition was accompanied by a parallel almost equal increase in core temperature above basal (delta Tre) for equivalent gains in skin temperature. The increase in tidal volume and decreased f in the cold condition allowed more effective physical conditioning of cold inspirate gas in the upper airways and aided RHL. Cold air inhalation also produced a significant (P less than or equal to 0.05) decrease in heart rate vs. hot air inhalation in the final stages of exercise. Insignificant changes in O2 consumption and total body fluid loss were found. These data show that cold air inhalation during exercise diminishes elevation of Tre and suggest that both the intensity and duration of work can thus be extended. The importance of the physical exchange of heat energy and any physiological mechanisms induced by the cold inspirate in producing the changes is undetermined.     

Electromagnetic and thermal evaluation of an applicator specialized to permit high‐resolution non‐perturbing optical evaluation of cells being irradiated in the W‐band

To permit epi‐illuminated, high‐resolution optical microscopy of cells in monolayer culture during unperturbed W‐band (75–110 GHz) irradiation, a new class of applicator has been developed based upon WR10 rectangular waveguide components: the cells are normally plated onto the underside of a coverslip which is then placed against the under side of a waveguide flange and receives a roughly circular exposure pattern, with the ±1 dB central spot roughly 1 mm in diameter. Constructed and tested with 94 GHz millimeter waves, water‐immersion optics, and free‐convection cooling, the applicator works robustly and permits SARs at the cell layer as high as 4500 W/kg before the steady‐state temperature rise at the cell layer exceeds 0.5 K. Bioelectromagnetics 31:140–149, 2010. © 2009 Wiley‐Liss, Inc.