Antimicrobial activity of isoquinoline alkaloids and their N-oxide derivatives.
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Biomedical subjects
Publications and source records attributed to S T Lu.
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Confounding factors influencing the sensitivity of biological indicators of microwave exposure--lethality, colonic temperature (Tco), decreased body mass (dW), corticosterone (CS), thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), and prolactin (PRL) concentration--were studied in Long-Evans (LE), Wistar-Kyoto (WKY), and spontaneous hypertensive (SHR) rats. The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Test power density ranged from 1 to 50 mW/cm2 for 2 h. In contrast to the LE and WKY rats, the SHR rats were characterized by intolerance (death) between 40 and 50 mW/cm2 (9.2 to 11.5 W/kg). The lowest lethal Tco was 41.1 degrees C. Survivors including all the LE and WKY rats were capable of maintaining Tco lower than 41.0 degrees C. In general, strain of rat seemed to influence other bioindicators and to interact with power density on these bioindicators. Except for Tco and PRL, baseline for the various bioindicators varied among the different strains of rats. Responses of T4 and FT4 were limited in magnitude and inconsistent among strains of rats. In general, the magnitude of Tco increase was more pronounced in SHR than in WKY. Differences between SHR and LE, however, could be noted only at 1, 10, and 50 mW/cm2. Increased Tco, increased magnitude of Dw, increased CS, decreased TSH, and increased PRL (stress reactions) could be noted in rats exposed to 30 mW/cm2 (approximately 6 W/kg) or higher, irrespective of strain. At least two of three strains of rats (WKY and SHR) exposed to 20 mW/cm2 (approximately 4 W/kg) showed changes in Tco, CS, TSH, and PRL. At 10 mW/cm2 (2 W/kg), increased Tco could be found in all three strains of rats accompanied by changes in dW and TSH in LE, TSH in WKY, and dW and CS in SHR. At 1 mW/cm2 (0.2 W/kg), increased Tco could be noted in two of three strains (LE and SHR) and increased PRL in LE only. The smallest Tco increases for a consistent response (increased magnitude of response with power density) were 1.59 degrees C for dW, 0.70 degrees C for CS, 0.24 degrees C for TSH, and 0.97 degrees C for PRL. Tentatively, the threshold intensity for response to microwave exposure for rats could be considered as 2 W/kg or a 0.24 degrees C increase at 24 degrees C ambient temperature.
Data are available regarding interactions of radiofrequency radiation (RFR) with normal human mononuclear leukocytes. However, no data have emerged regarding effects of RFR on human leukocytes already challenged by a commonly encountered alternate agent, such as a virus. Therefore, in these studies, uninfected (control) and in vitro influenza virus-infected human mononuclear leukocytes were exposed to 2450 MHz RFR as continuous waves or pulse-modulated at 60 or 16 Hz, at a specific absorption rate of 4 mW/ml. Such exposures produced no significant effects on leukocyte viability or on mitogen-stimulated DNA synthesis by either uninfected or influenza virus-infected leukocytes when compared to sham-RFR-exposed of cells.
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Exposure of the general public and in particular certain occupational groups to radiofrequency radiation (RFR) is ubiquitous and of growing concern. No clear and widely accepted understanding of the biological effects and health implications of such RFR exposure has emerged. This paper reviews the data available, including reports of RFR effects on single cells or cell components, on genetic composition or development, on developed organs, tissues, or cell systems, and on integrative and regulatory biological systems. Reports of RFR effects on the immunological system, with consideration of the influence of neuroendocrine responses, are critically reviewed in greater detail to illustrate important points regarding data acquisition and assessment, and understanding and application of the RFR bioeffects literature in general. Factors affecting RFR bioeffects research are reviewed, and recommendations for future studies are provided.
Six-hundred-and-one male Long-Evans rats were used to study the effect of microwaves on adrenocortical secretion. Power density ranged from 0.1 to 55 mW/cm2 (SAR 0.02 to 11 W/kg). The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Serum corticosterone (CS) concentration was used as an index of adrenocortical function. Ten different exposure protocols were used to identify confounding factors influencing the sensitivity of adrenal cortex to microwave exposure. Increases in CS concentration were proportional to power density or colonic temperature and inversely proportional to the baseline CS. Increased CS concentration was never observed without increased colonic temperature and was not persistent 24 h after exposure. Acclimation (reduction in magnitude of response) could be noted after the tenth exposure. Facilitated heat loss attenuated the magnitude of CS increases by limiting the degree of hyperthermia. Ethanol enhanced the hyperthermic response and desensitized the adrenal response to microwave hyperthermia by increased baseline CS. Ether stimulated adrenal secretion irrespective of previous microwave exposure or adrenal stimulation induced by microwaves. Minor inhibition was also noted occasionally as decreased CS concentration at lower intensity (less than 20 mW/cm2) and decreased postexposure urinary CS excretion at 40 mW/cm2. Adrenal stimulation required minimally a 20 mW/cm2 (4 W/kg) or 0.7 degrees C increase in colonic temperature. An SAR lower than 4 W/kg may stimulate adrenal secretion by potentiating the hyperthermic effect if the ambient temperature is well above 24 degrees C.
Hyperthermia is being used clinically in the treatment of neoplasms, and mononuclear leukocytes are commonly present in a heated tumor or in surrounding tissues. Therefore, we examined the effects of exposure of human mononuclear leukocytes to less than 41 degrees or greater than 42.5 degrees hyperthermia for 2 h. The ability of the cells to exclude dyes, used as a measurement of leukocyte viability, was not altered by such exposures. Exposure of the cells to less than 41 degrees hyperthermia generally did not alter unstimulated or mitogen-stimulated DNA, RNA, or total protein synthesis. In contrast, exposure to greater than 42.5 degrees hyperthermia resulted in decreased unstimulated RNA and total protein synthesis, as well as delayed synthesis of DNA, RNA, and total protein in response to stimulation with the optimal concentration of mitogen and decreased synthesis in response to suboptimal concentrations of mitogen.
The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)
Although decreased serum thyrotropin (TSH) concentration has been found to be part of the endocrine response pattern in rats exposed to microwaves and other stimuli, the response of individual endocrine organs was not activated simultaneously by a given irradiance. Therefore, analytical evaluation of the function of endocrine organs individually as well as collectively is required to characterize the extent of biological involvement in microwave exposure. We have studied the changes in TSH concentration in unanesthetized rats exposed to 2.45 GHz amplitude modulated (120 Hz) microwaves in the far field for 2 and 4 h, between 0 and 55 mW/cm2, and from 1 to 10 times to demonstrate any possible cumulation, acclimation, or sensitization process. Ether inhalation was administered to test the responsiveness of TSH in groups of rats that failed to respond to microwave exposure by lowering TSH concentration. In addition, groups of rats were sampled 24 h after microwave exposure to test the persistency of the microwave effect on serum TSH concentration. Results showed that TSH concentration decreased in rats after microwave exposure. Influence of microwave exposure on serum TSH concentration was independent of the number of exposures indicating absence of cumulation, acclimation, or sensitization. The microwave effect on serum TSH could be dependent on duration of exposure. Decreased TSH concentration was usually accompanied by increased colonic temperature. For 4-h exposure, the lowest irradiance was 20 mW/cm2 or a 0.3 degree C increase in colonic temperature independent of the number of exposures. For 2-h exposure, the lowest irradiance was 30 mW/cm2 or a 1.1 degree C increase in colonic temperature regardless of the number of exposures. All the rats exposed at 10 mW/cm2 for 2 h had a lower TSH concentration than those of sham-exposed rats. Occasionally, significant reduction in TSH concentration could not be found in rats exposed to 20 or 25 mW/cm2 for 2 h. None of the rats exposed at an irradiance lower than 10 mW/cm2 had any change in TSH concentration. Failure of change in TSH concentration in response to microwave exposure was not a reflection of a deficiency since these rats responded to ether inhalation by lowering their TSH concentration. The effect of microwave exposure on TSH concentration was not persistent after exposure. The relation between TSH concentration and colonic temperature was curvilinear (exponential). From these results, two mechanisms and their implications for man were discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
Measurement of temperature within the cerebral cortex, hypothalamus, cerebellum and medulla of rats sham-, heat- or microwave-exposed revealed the presence of a thermal gradient within the brain. In all groups, cerebral cortex and the cerebellum were cooler than the deeper hypothalamus and medulla. Exposure to 2450 MHz CW microwaves or ambient heat (42 +/- 2 degrees C) resulted in measurable elevation of regional brain temperature, but without alteration of temperature gradients normally observed within the brain. Exposure to 20 mW/cm2 (SAR approximately equal to 4 W/kg) for 30, 90 or 180 min induced a small, but significantly (U = 0, P less than 0.05) increased temperature of the colon, and in each region of the brain studied. Exposure to an incident power density of 65 mW/cm2 (SAR approximately equal to 13.0 W/kg) for 30 or 90 min or to ambient heat (42 +/- 2 degrees C) for 90 min resulted in a substantially greater thermal response as indicated by higher colonic and brain temperatures. Comparison of regional brain temperature with individual colonic temperatures is expressed as delta T = t degrees Cbrain--t degrees Ccolon. In general delta T values for ambient heat or microwave-exposed rats did not differ significantly from those of sham-exposed animals. Exposure to microwaves or ambient heat did not alter the general relationships between regional brain and colonic temperatures, i.e., cortical and cerebellar temperatures were always below and hypothalamic and medullary temperatures always above corresponding colonic temperatures. The plotted temperature data (brain vs colonic temperature) indicate a linear relationship between brain and colonic temperatures. Levels of sodium fluorescein (NAFl), horseradish peroxidase (HRP) and [14C]sucrose (described in preceding papers) within the brain show a high correlation (P less than 0.05) with brain temperature. Suppression of blood-brain barrier permeability to hydrophilic tracers was most pronounced at brain temperatures exceeding approximately 40 degrees C and is demonstrated to be temperature dependent.
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Human mononuclear leukocytes were exposed to microwaves at energies relevant to current public safety recommendations. No detectable effects on viability or function of the leukocytes resulted from exposure to microwaves at specific absorption rates up to 4 milliwatts per milliliter. The results were highly reproducible and provided no evidence that current safety standard recommendations are inappropriate insofar as leukocyte function is concerned.
A waveguide exposure system operated between 2 and 4 GHz was assembled in a laboratory incubator in order to study potential temperature-dependent and temperature-independent actions of microwaves. Two vials containing cell cultures were exposed simultaneously in a single waveguide in order to reduce the space required, and to allow concurrent study of autologous cell cultures in two different functional states (resting and stimulated) during exposure. Dosimetry was performed using three techniques with different underlying assumptions, as well as the technique of differential power measurement. Each of the four techniques yielded different results, although differences between the two vials using any single technique were negligible. A significant 'hot spot' occurred at the center of each vial. The ratio between maximum and minimum absorption rate within a single vial was 33-fold using a vial of 1.2-cm diameter and 1.6-cm height. With agitation and exposure at specific absorption rate (SAR) equal to 21 mW/ml, the thermal gradient was less than 0.1 degrees C between these two points. The averaged SAR can be determined by steady-state heating analysis. The exposure system can be calibrated readily by calculation for the measured powers, but not by differential power measurement.
Heat stable serum enzymes were studied in rats exposed to microwaves (2.45 GHz, 120 Hz amplitude modulated) 24 hr after a single 4-hr exposure or immediately after 3 and 10 exposures to 0.1 to 55 mW/cm2. In addition, stable colonic temperature at 41.5 degrees C for 30 min was maintained by microwave exposure in a group of five rats under barbiturate anesthesia. Alkaline phosphatase and lactic dehydrogenase did not increase as a result of microwave exposure. Increased serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were noted in the 41.5 degrees C group 24 hr after exposure. A threshold body temperature for acute cellular injury after microwave exposure was demonstrated. The acute cellular injury could be in the liver. These mild elevations in the serum enzyme levels (mean +/- SE, GOT = 167 +/- 40 U/liter: GPT = 74 +/- 26 U/liter) indicated that the injuries were not accompanied by any significant sequelae in the rat. From this threshold and colonic temperature (41.5 degrees C for 30 min) in barbiturate-anesthetized, microwave-exposed rats, we derived a tentative threshold for the whole-body average absorption rate at 14 W/kg (70 mW/cm2 at 2.45 GHz for adult rats) for 4 hr. This tentative threshold is subject to changes by duration of exposure and by compounding variables influencing maintenance of body temperature.
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