Arginine vasopressin receptor 2 activation promotes microvascular permeability in sepsis.

Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is a severe condition associated with vascular leakage and poor prognosis. The hemodynamic management of sepsis targets hypotension, but there is no specific treatment available for vascular leakage. Arginine vasopressin (AVP) has been used in sepsis to promote vasoconstriction by activating AVP receptor 1 (V1R). However, recent evidence suggests that increased fluid retention may be associated with the AVP receptor 2 (V2R) activation worsening the outcome of sepsis. Hence, we hypothesized that the inhibition of V2R activation ameliorates the severity of microvascular hyperpermeability during sepsis. The hypothesis was tested using a well-characterized and clinically relevant ovine model of MRSA pneumonia/sepsis and in vitro assays of human lung microvascular endothelial cells (HMVECs). in vivo experiments demonstrated that the treatment of septic sheep with tolvaptan (TLVP), an FDA-approved V2R antagonist, significantly attenuated the sepsis-induced fluid retention and markedly reduced the lung water content. These pathological changes were not affected by the treatment with V2R agonist, desmopressin (DDAVP). Additionally, the incubation of cultured HMVECs with DDAVP, and DDAVP along with MRSA significantly increased the paracellular permeability. Finally, both the DDAVP and MRSA-induced hyperpermeability was significantly attenuated by TLVP. Subsequent protein and gene expression assays determined that the V2R-induced increase in permeability is mediated by phospholipase C beta (PLCß) and the potent permeability factor angiopoietin-2. In conclusion, our results indicate that the activation of the AVP-V2R axis is critical in the pathophysiology of severe microvascular hyperpermeability during Gram-positive sepsis. The use of the antagonist TLVP should be considered as adjuvant treatment for septic patients. The results from this clinically relevant animal study are highly translational to clinical practice.

Improvement of the salvage-rate of flap after venous thrombosis with intraparenchymatous venous pressure monitoring.

PURPOSE: Intraparenchymatous venous pressure (IVP) monitoring in flap can measure venous pressure with catheter placement. Among patients with IVP monitoring, this study reviewed postoperative microvascular complications for investigating the transplanted-tissue salvage-rate. PATIENTS AND METHODS: Two hundred and seventy-one patients (male, 132; female, 139; mean age, 52.3 years; age range, 9-82 years) underwent free flap transfer and postoperative continuous IVP monitoring, which performed as follows; a venous catheter was connected to a transducer, and venous pressure in the flap was recorded for three consecutive days postoperatively. The threshold of alarm for elevated venous pressure was set at 50 mm Hg. When abnormal measurements or fluctuation were observed, the vascular anastomotic site was exposed immediately. The flap salvage-rate of non-IVP monitoring group (n = 393; male, 305; female, 81; mean age, 61.3 years; age range, 23-83 years), which were confirmed by a portable ultrasonographic device, was compared with that of IVP-monitoring group. RESULTS: Twenty-one patients developed postoperative microvascular complications at the vascular anastomosis sites. Sensitivity rate of IVP monitoring was 86%; specificity rate, 96%; positive predictive value rates, 64%; negative predictive value rate, 99%; false positive rate, 4%. The flap salvage-rate was 83% in venous thrombosis cases and only 33% in arterial thrombosis cases. In non-IVP monitoring group, flap salvage-rate was 20% with arterial thrombosis and 36% with venous thrombosis, resulting in an increasing the salvage-rate (P = .021). CONCLUSIONS: IVP monitoring could visualize and quantify venous pressure waves in flap and detect early microvascular complications, resulting in a marked improvement in the graft-tissue salvage-rate.

Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine With Burn and Smoke Inhalation Injury.

OBJECTIVES: To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (ß2-adrenergic receptor agonism) and attenuation of airway hyperemia (α1-adrenergic receptor agonism) with minimal systemic effects. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal ICU. SUBJECTS: Twelve chronically instrumented sheep. INTERVENTIONS: The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6. MEASUREMENTS AND MAIN RESULTS: Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment. CONCLUSIONS: Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.

Multigenerational effects of whole body exposure to 2.14 GHz W-CDMA cellular phone signals on brain function in rats.

The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.24 W/kg), low (<0.08 W/kg), and 0 (sham exposure). Pregnant mothers (4 rats/group) were exposed from gestational day (GD) 7 to weaning and then their offspring (F1 generation, 4 males and 4 females/dam, respectively) were continuously exposed until 6 weeks of age. The F1 females were mated with F1 males at 11 weeks old, and then starting from GD 7, they were exposed continuously to the electromagnetic field (EMF; one half of the F1 offspring was used for mating, that is, two of each sex per dam and 8 males and 8 females/group, except for all offspring for the functional development tests). This protocol was repeated in the same manner on pregnant F2 females and F3 pups; the latter were killed at 10 weeks of age. No abnormalities were observed in the mother rats (F0 , F1 , and F2 ) and in the offspring (F1 , F2 , and F3 ) in any biological parameters, including neurobehavioral function. Thus, it was concluded that under the experimental conditions applied, multigenerational whole body exposure to 2.14 GHz W-CDMA signals for 20 h/day did not cause any adverse effects on the F1 , F2 , and F3 offspring.

Geochemical distribution of heavy metal elements and potential ecological risk assessment of Matsushima Bay sediments during 2012-2016.

Heavy metal pollution of marine sediments has attracted a great deal of attention because of its persistence, bioaccumulation, and toxicity. To evaluate the effects of mega-tsunami, anthropogenic activities, and redox conditions on heavy metal accumulation in coastal areas, sediments from Matsushima Bay, Miyagi Prefecture, Japan, were sampled to test variations in heavy metal spatial distribution on the bay floor during 4 years following the 2011 Tohoku Earthquake tsunami. Cluster analysis and principal component analysis were performed to assess the influencing factors and potential sources of heavy metal enrichment in the sediments of the bay. Additionally, the sediment enrichment levels of heavy metals were assessed on the basis of the enrichment factor (EF). The results of multivariate statistical analyses showed that the Ti, Fe, V, Pb, and Zn contents in Matsushima Bay sediments, which were transported mainly from Sendai Bay, depended on the mud content. The value of EF < 2 for Fe, V, Pb, and Zn indicated that these elements were not enriched. The value of EF > 7 for Cu suggested that the contamination levels in western Matsushima Bay were moderate to severe in every sampling year from 2012 to 2016 by anthropogenic activities. From the values of EF > 5 for U and Mo during 2012 and 2014, the severe enrichment of both elements in these periods may be explained by contamination with 2011 tsunami deposits; the improvement in 2015-2016 suggests that there was recovery of the tsunami-affected sediment composition to its original state. The values of EF > 3 for Mn and As indicated moderate to severe contamination with these heavy metals in the bay mouth area during 2015. This was likely explained by more oxic bottom conditions in the mouth of Matsushima Bay during that year.

Adipose-derived stem cells improve grafted burn wound healing by promoting wound bed blood flow.

BACKGROUND: Researchers have explored the use of adipose-derived stem cells (ASCs) as a cell-based therapy to cover wounds in burn patients; however, underlying mechanistic aspects are not completely understood. We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways. METHODS: To test the hypothesis, we used an ovine burn model. A 5 cm2 full thickness burn wound was induced on each side of the dorsum. After 24 hours, the burned skin was excised and a 2 cm2 patch of autologous donor skin was grafted. The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment (phosphate-buffered saline [PBS]). Effects of ASCs culture media was also compared to those of PBS. Wound healing was assessed at one and two weeks following the application of ASCs. Allogeneic ASCs were isolated, cultured and characterized from non-injured healthy sheep. The identity of the ASCs was confirmed by flow cytometry analysis, differentiation into multiple lineages and gene expression via real-time polymerase chain reaction. Wound blood flow, epithelialization, graft size and take and the expression of vascular endothelial growth factor (VEGF) were determined via enzyme-linked immunosorbent assay and Western blot. RESULTS: Treatment with ASCs accelerated the patch graft growth compared to the control (p < 0.05). Topical application of ASCs significantly increased wound blood flow (p < 0.05). Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control (p < 0.05). CONCLUSIONS: ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.

Club Cell Protein, CC10, Attenuates Acute Respiratory Distress Syndrome Induced by Smoke Inhalation.

OBJECTIVES: To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII); specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal intensive care unit. SUBJECTS: Thirty-six adult female sheep were surgically prepared and allocated into five groups (Sham (no SII), n = 6; 1 mg/kg/d CC10, n = 8; 3 mg/kg/d CC10, n = 7; 10 mg/kg/d CC10, n = 8; Control SII, n = 7). INTERVENTIONS: All groups except the sham group were subjected to SII with cooled cotton smoke. Then, the animals were placed on a ventilator, treated with 1, 3, and 10 mg/kg/d of intravenous rhCC10 or vehicle, divided evenly into two administrations per day every 12 h, fluid resuscitated, and monitored for 48 h in a conscious state. MEASUREMENTS AND MAIN RESULTS: The group treated with 10 mg/kg/d rhCC10 attenuated changes in the following variables: PaO2/FiO2 ratio, oxygenation index, and peak inspiratory pressure; neutrophil content in the airway and myeloperoxidase levels; obstruction of the large and small airways; systemic leakage of fluid and proteins, and pulmonary edema. CONCLUSIONS: In this study, high-dose rhCC10 significantly attenuated ARDS progression and lung dysfunction and significantly reduced systemic extravasation of fluid and proteins, normalizing fluid balance. Based on these results, rhCC10 may be considered a novel therapeutic option for the treatment of SII-induced ARDS.

Effects of 915 MHz electromagnetic-field radiation in TEM cell on the blood-brain barrier and neurons in the rat brain.

The aim of this study was to determine whether albumin leakage and dark neurons were present in rat brains 14 and 50 days after a single 2-h exposure to a 915 MHz electromagnetic field, as reported by Salford et al. (Environ. Health Perspect. 111, 881-883, 203). Sixty-four male F344 rats (12 weeks old) were exposed to a 915 MHz electromagnetic field at whole-body average specific absorption rates of 0, 0.02, 0.2 and 2.0 W/kg in TEM cells for 2 h, following the protocol reported by Salford et al. The brains were examined histologically and immunohistochemically. No albumin immunoreactivity was observed in the exposed groups. In addition, dark neurons, assessed using hematoxylin and eosin staining, were rarely present, with no statistically significant difference between exposed and sham-exposed animals. This study thus failed to confirm the results of Salford et al.

Modeling time variation of blood temperature in a bioheat equation and its application to temperature analysis due to RF exposure.

The present study discusses a scheme to take into account core temperature variation in a well-known bioheat equation. First, the limitation in conventional modeling of the bioheat equation was investigated for a problem in which the whole-body phantom should be taken into account. Then, schemes for varying body-core temperature in the bioheat equation were discussed for radio-frequency exposures. The computational uncertainty in the core temperature elevation was found to be reasonable when a proper scheme for computing the net rate of heat acquisition by blood from body tissue was introduced.

Influence of electromagnetic polarization on the whole-body averaged SAR in children for plane-wave exposures.

The present study investigated the whole-body averaged specific absorption rate (WBSAR) in an infant model with the finite-difference time-domain method. The focus of the present study is the effect of polarization of incident electromagnetic waves on the WBSAR. This is because most previous studies investigated the WBSAR for plane-wave exposure with a vertically aligned electric field. Our computational results revealed that the WBSAR for plane-wave exposure with a vertically aligned electric field is smaller than that with a horizontally aligned electric field for frequencies above 2 GHz. The main reason for this difference is attributed to be the component of the surface area perpendicular to the electric field of the incident wave.

Effects of gestational exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats.

The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7-17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243-271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses.

Peroxynitrite decomposition catalyst reduces vasopressin requirement in ovine MRSA sepsis.

BACKGROUND: Sepsis is one of the most frequent causes of death in the intensive care unit. Host vascular hypo-responsiveness to vasopressors during septic shock is one of the challenging problems. This study tested the hypothesis that adjunct therapy with peroxynitrite decomposition catalyst (WW-85) would reduce arginine vasopressin (AVP) requirements during sepsis resuscitation, using ovine sepsis model. METHODS: Thirteen adult female Merino sheep, previously instrumented with multiple vascular catheters, were subjected to "two-hit" (cotton smoke inhalation and intrapulmonary instillation of live methicillin-resistant Staphylococcus aureus; 3.5 × 1011 colony-forming units) injury. Post injury, animals were awakened and randomly allocated to the following groups: (1) AVP: injured, fluid resuscitated, and titrated with AVP, n = 6 or (2) WW-85 + AVP: injured, fluid resuscitated, treated with WW-85, and titrated with AVP, n = 7. One-hour post injury, a bolus intravenous injection of WW-85 (0.1 mg/kg) was followed by a 23-h continuous infusion (0.02 mg/kg/h). Titration of AVP started at a dose of 0.01 unit/min, when mean arterial pressure (MAP) decreased by 10 mmHg from baseline, despite aggressive fluid resuscitation, and the rate was further adjusted to maintain MAP. After the injury, all animals were placed on a mechanical ventilator and monitored in the conscious state for 24 h. RESULTS: The injury induced severe hypotension refractory to aggressive fluid resuscitation. High doses of AVP were required to partially attenuate the sepsis-induced hypotension. However, the cumulative AVP requirement was significantly reduced by adjunct treatment with WW-85 at 17-24 h after the injury (p < 0.05). Total AVP dose and the highest AVP rate were significantly lower in the WW-85 + AVP group compared to the AVP group (p = 0.02 and 0.04, respectively). Treatment with WW-85 had no adverse effects. In addition, the in vitro effects of AVP on isolated artery diameter changes were abolished with peroxynitrite co-incubation. CONCLUSIONS: The modulation of reactive nitrogen species, such as peroxynitrite, may be considered as a novel adjunct treatment option for septic shock associated with vascular hypo-responsiveness to vasopressors.

FDTD analysis of body-core temperature elevation in children and adults for whole-body exposure.

The temperature elevations in anatomically based human phantoms of an adult and a 3-year-old child were calculated for radio-frequency whole-body exposure. Thermoregulation in children, however, has not yet been clarified. In the present study, we developed a computational thermal model of a child that is reasonable for simulating body-core temperature elevation. Comparison of measured and simulated temperatures revealed thermoregulation in children to be similar to that of adults. Based on this finding, we calculated the body-core temperature elevation in a 3-year-old child and an adult for plane-wave exposure at the basic restriction in the international guidelines. The body-core temperature elevation in the 3-year-old child phantom was 0.03 degrees C at a whole-body-averaged specific absorption rate of 0.08 W kg(-1), which was 35% smaller than in the adult female. This difference is attributed to the child's higher body surface area-to-mass ratio.

Conservative estimation of whole-body-averaged SARs in infants with a homogeneous and simple-shaped phantom in the GHz region.

We calculated the whole-body-averaged specific absorption rates (WBSARs) in a Japanese 9-month-old infant model and its corresponding homogeneous spheroidal and ellipsoidal models with 2/3 muscle tissue for 1-6 GHz far-field exposure. As a result, we found that in comparison with the WBSAR in the infant model, the ellipsoidal model with the same frontally projected area as that of the infant model provides an underestimate, whereas the ellipsoidal model with the same surface area yields an overestimate. In addition, the WBSARs in the homogenous infant models were found to be strongly affected by the electrical constant of tissue, and to be larger in the order of 2/3 muscle, skin and muscle tissues, regardless of the model shapes or polarization of incident waves. These findings suggest that the ellipsoidal model having the same surface area as that of the infant model and electrical constants of muscle tissue provides a conservative WBSAR over wide frequency bands. To confirm this idea, based on the Kaup index for Japanese 9-month-old infants, which is often used to represent the obesity of infants, we developed linearly reduced 9-month-old infant models and the corresponding muscle ellipsoidals and re-calculated their whole-body-averaged SARs with respect to body shapes. Our results reveal that the ellipsoidal model with the same surface area as that of a 9-month-old infant model gives a conservative WBSAR for different infant models, whose variability due to the model shape reaches 15%.

Computational model for calculating body-core temperature elevation in rabbits due to whole-body exposure at 2.45 GHz.

In the current international guidelines and standards with regard to human exposure to electromagnetic waves, the basic restriction is defined in terms of the whole-body average-specific absorption rate. The rationale for the guidelines is that the characteristic pattern of thermoregulatory response is observed for the whole-body average SAR above a certain level. However, the relationship between energy absorption and temperature elevation was not well quantified. In this study, we improved our thermal computation model for rabbits, which was developed for localized exposure on eye, in order to investigate the body-core temperature elevation due to whole-body exposure at 2.45 GHz. The effect of anesthesia on the body-core temperature elevation was also discussed in comparison with measured results. For the whole-body average SAR of 3.0 W kg(-1), the body-core temperature in rabbits elevates with time, without becoming saturated. The administration of anesthesia suppressed body-core temperature elevation, which is attributed to the reduced basal metabolic rate.

Computation of temperature elevation in rabbit eye irradiated by 2.45-GHz microwaves with different field configurations.

This study calculated the temperature elevation in the rabbit eye caused by 2.45-GHz near-field exposure systems. First, we calculated specific absorption rate distributions in the eye for different antennas and then compared them with those observed in previous studies. Next, we re-examined the temperature elevation in the rabbit eye due to a horizontally-polarized dipole antenna with a C-shaped director, which was used in a previous study. For our computational results, we found that decisive factors of the SAR distribution in the rabbit eye were the polarization of the electromagnetic wave and antenna aperture. Next, we quantified the eye average specific absorption rate as 67 W kg(-1) for the dipole antenna with an input power density at the eye surface of 150 mW cm(-2), which was specified in the previous work as the minimum cataractogenic power density. The effect of administrating anesthesia on the temperature elevation was 30% or so in the above case. Additionally, the position where maximum temperature in the lens appears is discussed due to different 2.45-GHz microwave systems. That position was found to appear around the posterior of the lens regardless of the exposure condition, which indicates that the original temperature distribution in the eye was the dominant factor.

Intercomparison of methods for measurement of dielectric properties of biological tissues with a coaxial sensor at millimeter-wave frequencies.

Coaxial sensors are effective for measurement of dielectric properties of biological tissues. Several measurement methods used to derive dielectric properties have been investigated for the measurement with a coaxial sensor at microwave frequencies. While the measurement accuracy depends on the method used, there has been insufficient intercomparison of these methods and their model approximation errors. On the other hand, we have developed a coaxial sensor for the measurement of complex permittivity at millimeter-wave (MMW) frequencies of up to 100 GHz. However, the scarcity of reference data at MMW frequencies makes the validation of the measurement system difficult. Thus, it is essential to clarify the model approximation error of the method used in the measurement system, particularly at MMW frequencies. This study aims to clarify the model approximation errors of methods for dielectric property measurement using a coaxial sensor at MMW frequencies. The model approximation errors were assessed by comparing results obtained by the methods with those based on the theoretical formula of the full-wave modal expression of Maxwell's equations. The measurement uncertainty for the theoretical formula was estimated for a standard liquid sample to clarify the contribution of the model approximation errors to the uncertainty. Furthermore, the methods were applied to the measurement of porcine tissues at body temperature, and the measurement accuracy and usability for measurement at MMW frequencies are discussed.

Dosimetry in Japanese male and female models for a low-frequency electric field.

The present study quantified induced current in anatomically based Japanese male and female models for exposure to low-frequency electric fields. A quasi-static finite-difference time-domain (FDTD) method was applied to analyze this problem. For our computational results, the difference of the induced current density averaged over an area of 1 cm(2) between Japanese male and female models was less than 30% for each nerve tissue. The difference of induced current density between the present study and earlier works was less than 50% for the same conductivities, despite the different morphology. Particularly, maximum current density in central nerve tissues appeared in the retina of Japanese models, the same as in the earlier works.

FDTD analysis of human body-core temperature elevation due to RF far-field energy prescribed in the ICNIRP guidelines.

This study investigated the relationship between the specific absorption rate and temperature elevation in an anatomically-based model named NORMAN for exposure to radio-frequency far fields in the ICNIRP guidelines (1998 Health Phys. 74 494-522). The finite-difference time-domain method is used for analyzing the electromagnetic absorption and temperature elevation in NORMAN. In order to consider the variability of human thermoregulation, parameters for sweating are derived and incorporated into a conventional sweating formula. First, we investigated the effect of blood temperature variation modeling on body-core temperature. The computational results show that the modeling of blood temperature variation was the dominant factor influencing the body-core temperature. This is because the temperature in the inner tissues is elevated via the circulation of blood whose temperature was elevated due to EM absorption. Even at different frequencies, the body-core temperature elevation at an identical whole-body average specific absorption rate (SAR) was almost the same, suggesting the effectiveness of the whole-body average SAR as a measure in the ICNIRP guidelines. Next, we discussed the effect of sweating on the temperature elevation and thermal time constant of blood. The variability of temperature elevation caused by the sweating rate was found to be 30%. The blood temperature elevation at the basic restriction in the ICNIRP guidelines of 0.4 W kg(-1) is 0.25 degrees C even for a low sweating rate. The thermal time constant of blood temperature elevation was 23 min and 52 min for a man with a lower and a higher sweating rate, respectively, which is longer than the average time of the SAR in the ICNIRP guidelines. Thus, the whole-body average SAR required for blood temperature elevation of 1 degrees C was 4.5 W kg(-1) in the model of a human with the lower sweating coefficients for 60 min exposure. From a comparison of this value with the basic restriction in the ICNIRP guidelines of 0.4 W kg(-1), the safety factor was 11.

No adverse effects detected for simultaneous whole-body exposure to multiple-frequency radiofrequency electromagnetic fields for rats in the intrauterine and pre- and post-weaning periods.

In everyday life, people are exposed to radiofrequency (RF) electromagnetic fields (EMFs) with multiple frequencies. To evaluate the possible adverse effects of multifrequency RF EMFs, we performed an experiment in which pregnant rats and their delivered offspring were simultaneously exposed to eight different communication signal EMFs (two of 800 MHz band, two of 2 GHz band, one of 2.4 GHz band, two of 2.5 GHz band and one of 5.2 GHz band). Thirty six pregnant Sprague-Dawley (SD) 10-week-old rats were divided into three groups of 12 rats: one control (sham exposure) group and two experimental (low- and high-level RF EMF exposure) groups. The whole body of the mother rats was exposed to the RF EMFs for 20 h per day from Gestational Day 7 to weaning, and F1 offspring rats (46-48 F1 pups per group) were then exposed up to 6 weeks of age also for 20 h per day. The parameters evaluated included the growth, gestational condition and organ weights of the dams; the survival rates, development, growth, physical and functional development, memory function, and reproductive ability of the F1 offspring; and the embryotoxicity and teratogenicity in the F2 rats. No abnormal findings were observed in the dams or F1 offspring exposed to the RF EMFs or to the F2 offspring for any of the parameters evaluated. Thus, under the conditions of the present experiment, simultaneous whole-body exposure to eight different communication signal EMFs at frequencies between 800 MHz and 5.2 GHz did not show any adverse effects on pregnancy or on the development of rats.