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Comment: a biological guide for electromagnetic safety: the stress response.

Questions of safety of electromagnetic (EM) fields should be based on relevant biological properties, i.e., specific cellular reactions to potentially harmful stimuli. The stress response is a well documented protective reaction of plant and animal cells to a variety of environmental threats, and it is stimulated by both extremely low frequency (ELF) and radio frequency (RF) EM fields. It involves activation of DNA to initiate synthesis of stress proteins. Thermal and non-thermal stimuli affect different segments of DNA and utilize different biochemical pathways. However, both ELF and RF stimulate the same non-thermal pathway. Since the same biochemical reactions are stimulated in different frequency ranges with very different specific absorption rates (SARs), SAR level is not a valid basis for safety standards. Studies of EM field interactions with DNA and with model systems provide insight into a plausible mechanism that can be effective in ELF and RF ranges.

Electromagnetic Fields↗

Apartment electrical wiring: a cause of extremely low frequency magnetic field exposure in residential areas.

Extremely low frequency (ELF) magnetic fields (MFs) were measured at 696 points in a room of a Japanese apartment building. The building had 124 rooms with layouts and wiring identical to those of the studied room. ELF-MFs exceeded 0.4 microT in 24% of the living space, and the maximum value, 1.8 microT, was detected at floor level. Analysis of the MF distribution revealed that 60 Hz 100 V electrical wiring for room lights within the floor and ceiling had been laid out in large rectangles, equivalent to 1 turn coils. Further plotting of the vertical components every 0.01 m on the floor indicated that the depth of the cable was 0.23 m. Further studies should be conducted in order to confirm that the building investigated in this pilot study is typical of Japanese apartment buildings in terms of ELF-MFs.

Body Burden↗

Childhood leukemia and EMF: review of the epidemiologic evidence.

All populations are exposed to varying degrees of electromagnetic fields (EMF); in this study we consider only extremely low frequency (ELF) and radio frequency (RF) fields. After the first study of ELF and childhood leukemia in 1979, intensive epidemiologic investigation has sought to shed light on the potential relation between EMF and childhood leukemia. Consistent associations from epidemiologic studies and two pooled analyses have been the basis for the classification of ELF as a possible carcinogen by the International Agency for Research on Cancer (IARC). The study of RF is still in its infancy and little is known about residential RF exposure or its potential effects on childhood leukemia. The purpose of this study, presented at the WHO Workshop on Sensitivity of Children to EMF in Istanbul, Turkey in June 2004, is to review and critically assess the epidemiologic evidence on EMF and childhood leukemia.

Bias↗

Non-cancer EMF effects related to children.

Potential adverse effects of electromagnetic field exposure on the developing child have been discussed during the last decades. Effects during fetal development could have major consequences and possibly lead to various adverse pregnancy outcomes. This study summarizes the evidence on adverse pregnancy outcomes in relation to extremely low frequency (ELF) and radiofrequency (RF) exposures and briefly discusses other potential health effects, excluding cancer, following childhood exposures to these fields. Most studies of ELF exposures have not demonstrated any consistent risk increases for adverse pregnancy outcomes, but limitations in the exposure assessment methods and very limited power to study high exposure levels prevents any conclusions. Findings of an increased risk of spontaneous abortion in relation to maximum magnetic field exposures in two studies need to be confirmed. Studies of RF exposure have mostly been limited to physiotherapists and although some positive findings have been reported, no specific type of malformation or other adverse outcome has been consistently reported. Different types of symptoms and effects on cognitive function in relation to both ELF and RF fields have been reported in adults, but scientific studies have not confirmed that these symptoms are caused by the electromagnetic fields. No information is available for children.

Abortion, Spontaneous↗

Effects of 50 Hz sinusoidal magnetic fields on Hsp27, Hsp70, Hsp90 expression in porcine aortic endothelial cells (PAEC).

The aim of the present study was to investigate the influence of 50 Hz sinusoidal magnetic field on Hsp27, Hsp70, and Hsp90 expression in a model of primary culture of porcine aortic endothelial cells (PAEC). We took into consideration the Hsp profile in terms of mRNA expression, protein expression and protein localization inside the cells. The choice of the cell system was motivated by the involvement of the endothelial cells in the onset of many diseases; moreover, only few reports describe the effects of extremely low frequency magnetic fields (ELF-MFs) on such cells. ELF-MF exposure induced an increase in the mRNA levels of the three proteins, which was statistically significant for Hsp70. On the contrary, we did not observe any influence on Hsp27, Hsp70, and Hsp90 protein levels. Analysis in situ by immunofluorescence revealed that ELF-MF exposure affected the cellular distribution of Hsp27; in particular a partial relocalization in the nucleus was observed.

Animals↗

Measurement of small mechanical vibrations of brain tissue exposed to extremely-low-frequency electric fields.

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposure cell is a section of X-band waveguide that was modified by the addition of a center conductor to form a small TEM cell within the waveguide structure. The ELF signal is applied to the center conductor of the TEM cell. The applied ELF electric field generates an electrostrictive force on the surface of the brain tissue. This force causes the tissue to vibrate at a frequency equal to twice the frequency of the applied sinusoidal signal. An X-band signal is fed through the waveguide, scattered by the vibrating sample, and detected by a phase-sensitive receiver. Using a time-averaging spectrum analyzer, a vibration sensitivity of approximately 0.2 nmp-p can be achieved. The amplitude of the brain tissue vibrational response is constant for vibrational frequencies below 50 Hz; between 50 and 200 Hz resonant phenomena were observed; and above 200 Hz the amplitude fall-off is rapid.

Animals↗

Effects of 60 Hz electric and magnetic fields on maturation of the rat neopallium.

This study was undertaken to determine the effects of extremely low frequency (ELF; 60 Hz) electromagnetic (EM) fields on somatic growth and cortical development, as well as biochemical and morphological maturation, of the rat neopallium. On the fifth day of pregnancy, female rats were put in pairs into plastic cages that were housed in a specially constructed apparatus for irradiation under three separate sets of combination and intensity: 1) 1 kV/m and 10 gauss; 2) 100 kV/m and 1 gauss; and 3) 100 kV/m and 10 gauss. The dams were exposed for 23 h daily, from days 5 through 19 postconception, after which they were returned to cages outside the exposure apparatus until they littered. The neonates were culled to eight pups per litter. At 0 (birth), 5, 12, and 19 days postnatally, they were killed for biochemical and morphological studies. Another group of pregnant rats was sham-exposed in an identical apparatus, which was not energized, and the pups were used as controls. The irradiated rats exhibited no physical abnormalities, nor did they show brain deformities such as swelling or herniation following exposure to ELF-EM fields. There was no difference in somatic growth between control and exposed rats, but a small reduction in cortical weight was observed in rats exposed at 1 kV/m and 10 gauss, and 100 kV/m and 1 gauss, respectively. Biochemical measurements of DNA, RNA, protein, and cerebroside concentrations indicated that among the three separate exposures, only the neopallium of rats exposed at 1 kV/m and 10 gauss showed a small reduction in DNA level, as well as small reductions in RNA and protein levels. No changes were noticed in cerebroside levels in any exposed animals, and there were no differences in protein/DNA and cerebroside/DNA ratios between control and exposed rats. Morphological observations did not reveal any detectable alterations in the irradiated rats. These results indicate that exposure to ELF-EM fields caused minimal or no changes in somatic growth and cerebral development of the rat.

Animals↗

Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation.

There is presently an intense discussion if electromagnetic field (EMF) exposure has consequences for human health. This include exposure to structures and appliances that emit in the extremely low frequency (ELF) range of the electromagnetic spectrum, as well as emission coming from communication devices using the radiofrequency part of the spectrum. Biological effects of such exposures have been noted frequently, although the implication for specific health effects is not that clear. The basic interaction mechanism(s) between such fields and living matter is unknown. Numerous hypotheses have been suggested, although none is convincingly supported by experimental data. Various cellular components, processes, and systems can be affected by EMF exposure. Since it is unlikely that EMF can induce DNA damage directly, most studies have examined EMF effects on the cell membrane level, general and specific gene expression, and signal transduction pathways. In addition, a large number of studies have been performed regarding cell proliferation, cell cycle regulation, cell differentiation, metabolism, and various physiological characteristics of cells. Although 50/60 Hz EMF do not directly lead to genotoxic effects, it is possible that certain cellular processes altered by exposure to EMF indirectly affect the structure of DNA causing strand breaks and other chromosomal aberrations. The aim of this article is to present a hypothesis of a possible initial cellular event affected by exposure to ELF EMF, an event which is compatible with the multitude of effects observed after exposure. Based on an extensive literature review, we suggest that ELF EMF exposure is able to perform such activation by means of increasing levels of free radicals. Such a general activation is compatible with the diverse nature of observed effects. Free radicals are intermediates in natural processes like mitochondrial metabolism and are also a key feature of phagocytosis. Free radical release is inducible by ionizing radiation or phorbol ester treatment, both leading to genomic instability. EMF might be a stimulus to induce an "activated state" of the cell such as phagocytosis, which then enhances the release of free radicals, in turn leading to genotoxic events. We envisage that EMF exposure can cause both acute and chronic effects that are mediated by increased free radical levels: (1) Direct activation of, for example macrophages (or other cells) by short-term exposure to EMF leads to phagocytosis (or other cell specific responses) and consequently, free radical production. This pathway may be utilized to positively influence certain aspects of the immune response, and could be useful for specific therapeutic applications. (2) EMF-induced macrophage (cell) activation includes direct stimulation of free radical production. (3) An increase in the lifetime of free radicals by EMF leads to persistently elevated free radical concentrations. In general, reactions in which radicals are involved become more frequent, increasing the possibility of DNA damage. (4) Long-term EMF exposure leads to a chronically increased level of free radicals, subsequently causing an inhibition of the effects of the pineal gland hormone melatonin. Taken together, these EMF induced reactions could lead to a higher incidence of DNA damage and therefore, to an increased risk of tumour development. While the effects on melatonin and the extension of the lifetime of radicals can explain the link between EMF exposure and the incidence of for example leukaemia, the two additional mechanisms described here specifically for mouse macrophages, can explain the possible correlation between immune cell system stimulation and EMF exposure.

Animals↗

Alteration in cellular functions in mouse macrophages after exposure to 50 Hz magnetic fields.

The aim of the present study is to investigate whether extremely low frequency electromagnetic fields (ELF-EMF) affect certain cellular functions and immunologic parameters of mouse macrophages. In this study, the influence of 50 Hz magnetic fields (MF) at 1.0 mT was investigated on the phagocytic activity and on the interleukin-1beta (IL-1beta) production in differentiated macrophages. MF-exposure led to an increased phagocytic activity after 45 min, shown as a 1.6-fold increased uptake of latex beads in MF-exposed cells compared to controls. We also demonstrate an increased IL-1beta release in macrophages after 24 h exposure (1.0 mT MF). Time-dependent IL-1beta formation was significantly increased already after 4 h and reached a maximum of 12.3-fold increase after 24 h compared to controls. Another aspect of this study was to examine the genotoxic capacity of 1.0 mT MF by analyzing the micronucleus (MN) formation in long-term (12, 24, and 48 h) exposed macrophages. Our data show no significant differences in MN formation or irregular mitotic activities in exposed cells. Furthermore, the effects of different flux densities (ranging from 0.05 up to 1.0 mT for 45 min) of 50 Hz MF was tested on free radical formation as an endpoint of cell activation in mouse macrophage precursor cells. All tested flux densities significantly stimulated the formation of free radicals. Here, we demonstrate the capacity of ELF-EMF to stimulate physiological cell functions in mouse macrophages shown by the significantly elevated phagocytic activity, free radical release, and IL-1beta production suggesting the cell activation capacity of ELF-EMF in the absence of any genotoxic effects.

Animals↗

Blood transfusion and pulmonary lipid peroxidation in ventilated premature babies.

Urinary malondialdehyde (MDA; a biochemical marker of lipid peroxidation) is increased following the receipt of blood transfusions in premature babies. This indicates an increased level of oxidative damage somewhere in the body. The aim of this study was to determine whether the lung may be a site of increased oxidative damage following blood transfusions. This was achieved by examining the relationship between blood transfusion and levels of MDA in bronchoalveolar lavage (BAL) fluid from ventilated premature babies. The study was a retrospective analysis of data obtained from a group of 42 ventilated premature babies of less than 32 weeks' gestation. Twenty-seven babies received blood transfusions, and 9 received at least one transfusion during the first week of life when daily BAL samples were being taken. Pulmonary epithelial lining fluid (ELF) was sampled by BAL daily during the first week of life and weekly thereafter. MDA was measured by an established high performance liquid chromatography (HPLC) technique. There was a significant positive correlation between volume of blood transfusions received and peak and mean ELF MDA levels (r=0.810, peak; r=0.740, mean; n=21). During the first week of life, when daily samples were being taken, the mean ELF MDA level after blood transfusion (1.829 microM; SE, 0.529) was significantly greater than before transfusion (0.928 microM; SE, 0.297) (n=9). In babies who received 2 transfusions within the first week (n=5), the MDA level was elevated further following the second transfusion (2.825 microM; SE, 0.346). The results of this study indicate that pulmonary oxidative damage increases after the receipt of blood transfusions. Babies receiving blood transfusions show a greater incidence of pulmonary oxidative stress and poor clinical outcome. This may simply reflect that the sickest babies are those most in need of blood transfusion, and that there is no causal relationship. However, the possibility of a causal relationship between blood transfusions and oxidative damage exists and should be investigated.

Biomarkers↗

The interaction of rabbit reticulocyte guanine nucleotide exchange factor eIF-2B with chain initiation factor 2: studies with N-ethylmaleimide and trypsin.

Treatment of eIF-2B and eIF-2 with NEM abolishes nucleotide exchange and GTP-binding activities of the proteins. Incubation of eIF-2B with [14C]NEM results in strong labeling of the 82- and 55-kDa subunits and with less labeling of the other subunits. Preincubation of eIF-2B with eIF-2 interferes with [14C]NEM labeling of the 82- and 55-kDa subunits. All three (alpha, beta, and gamma) subunits of eIF-2 are labeled strongly by [14C]NEM. Limited digestion of eIF-2B with trypsin inhibits nucleotide exchange activity but does not interfere with GTP binding. Under these conditions, the 65-kDa subunit is degraded completely while the other subunits remain intact. Treatment of eIF-2 with trypsin results in the generation of eIF-2 lacking the beta-subunit (eIF-2 alpha gamma). eIF-2(alpha gamma) binds [3H]GDP equally well as intact elf-2. In the presence of elf-2B, the exchange of [3H]GDP for GTP from elf-2. [3H]GDP prepared with eIF-2(alpha gamma) is diminished considerably. [3H]GTP binding to eIF-2(alpha gamma) is also four- to five-fold less than to intact eIF-2. In addition, the association of eIF-2B with intact eIF-2, but not with eIF-2(alpha gamma), reduces by two-fold the rate and extent of removal of 32P by alkaline phosphatase from CK-2-phosphorylated 82-kDa subunit.

Amino Acid Sequence↗

Host responses and persistence of vector genome following intrabronchial administration of an E1(-)E3(-) adenovirus gene transfer vector to normal individuals.

Adenovirus (Ad)-mediated gene transfer to the respiratory epithelium of experimental animals and to nasal and airway epithelium of individuals with cystic fibrosis is followed by transient gene expression. Extensive studies in experimental animals are consistent with the concept that local cellular host anti-vector immune responses account for this short-term expression, and systemic and local [lung epithelial lining fluid (ELF)] anti-Ad neutralizing antibodies are generated following Ad vector administration to the respiratory epithelial surface. To determine if this paradigm holds in normal humans, a first-generation Ad vector (Ad(GV)CD.10, an E1(-)E3(-) Ad serotype 5-based vector coding for the Escherichia coli cytosine deaminase gene) was sprayed locally in escalating doses (8 x 10(8)-8 x 10(10) particle units (pu), n = 2/group) into the lung airway epithelium of six normal individuals. Serum, ELF, and endobronchial biopsies were obtained at baseline and at various time points following vector administration. In contrast to the observations in experimental animals in which lung administration of first-generation Ad vectors is followed by strong systemic and local host response, bronchial spray administration of the Ad vector to normal humans showed: (1) minimal inflammation in bronchial biopsies, bronchial brushing, and bronchoalveolar lavage fluid; (2) no blood lymphocyte proliferation in five of six individuals in response to in vitro stimulation with Ad antigens; and (3) no significant increase from baseline in blood or lung ELF anti-Ad neutralizing antibodies. Despite this minimal normal human anti-Ad host response, dose-dependent levels of vector DNA in the airway epithelium were transient. Vector DNA in the targeted airway epithelial cells peaked in a dose-dependent fashion at 0.007 to 1.1 copies/cell at day 7 and declined thereafter, reducing to <10% of peak levels by 2 weeks. These observations demonstrate both the strengths and the limits of using experimental animals to predict human responses to gene transfer vectors. While the transient nature of Ad vector persistence in the airway epithelium is predicted by most experimental animal studies, respiratory epithelial administration of first-generation Ad vectors at doses up to 10(10) pu to airway epithelium of healthy individuals elicits minimal to no detectable systemic and mucosal humoral and cellular immune responses, an observation diametrically opposed to the host responses measured in experimental animals. These findings suggest that, while adaptive anti-Ad immune responses likely play some role in the disappearance of the vector DNA following vector administration to the human lung, other mechanisms may also be involved in the response of humans to Ad gene transfer vectors.

Adenoviridae↗

Modeling the interactions of ozone with pulmonary epithelial lining fluid antioxidants.

Water soluble antioxidant--ascorbate (AA), urate (UA), and reduced glutathione (GSH)--consumption by ozone (O3) was investigated in a range of pulmonary epithelial lining fluid (ELF) models. Antioxidants were exposed individually and as a composite mixture, with and without human albumin to a range of ambient O3 concentrations: 0-1500 ppb using a continually mixed, interfacial exposure setup. We observed the following: (1) UA constituted the most o3-reactive substrate in each of the models examined. Reactivity hierarchies in each were as follows: UA > AA >> GSH (individual antioxidant), UA > AA > GSH (composite antioxidant), and UA >> AA approximately equal to GSH (composite antioxidant + albumin). Consumption of GSH as a pure antioxidant solution was associated with a 2:1 stoichiometric conversion of GSH to GSSG. This simplistic relationship was lost in the more complex models. (3) Consumption of antioxidants by O3 occurred without alteration of sample pH. (4) Protein carbonyl formation was observed when albumin alone was exposed to O3. However, in the presence of the composite antioxidant solution no evidence of this oxidative modification was apparent. These data indicate that GSH does not represent an important substrate for O3. In contrast, UA displays high reactivity consistent with its acting as a sacrificial substrate in the ELF. As UA concentrations are highest in the ELF of the proximal airways, its localization, allied to its reactivity, suggesting that it plays important roles, both in conferring protection locally and also by "scrubbing" O3, from inhaled air, limiting its penetration to the more sensitive distal lung.

Antioxidants↗

Proteolytically active 2A proteinase of human rhinovirus 2 is toxic for Saccharomyces cerevisiae but does not cleave the homologues of eIF-4 gamma in vivo or in vitro.

During the replication of rhino- and enteroviruses, the translation initiation factor elF-4 gamma is specifically cleaved by the virally encoded 2 A proteinase. This cleavage has been proposed to lead to the inability of the host cell to translate its own capped mRNA and to stimulate internal initiation of protein synthesis from the viral mRNA. However, a direct causal relationship between these effects and 2A proteinase-mediated cleavage of elF-4 gamma has remained difficult to prove, mainly because of the toxicity of the 2A proteinase in mammalian expression systems. As an alternative approach, we placed the cDNA sequences for the human rhinovirus 2 2A proteinase and two mutants defective in proteolytic activity under the control of an inducible yeast Gal1-10 promoter and stably integrated them into the yeast genome. Induction of the wildtype enzyme led to changes in cellular morphology, an inhibition of cell division activity, and finally to cell death. As the yeast homologues of mammalian elF-4 gamma, p150 and p130, were shown to be refractory to cleavage by human rhinovirus 2A proteinase both in vivo and in vitro and the rate of protein synthesis was unaffected, the toxicity of the 2A proteinase toward budding yeast must be due to its interaction with at least one other cellular protein essential for viability.

Amino Acid Sequence↗

Tenascin is increased in epithelial lining fluid in fibrotic lung disorders.

Tenascin is an extracellular matrix glycoprotein increased immunohistochemically in tumorous and fibrotic lung tissues as demonstrated by immunohistochemistry. We hypothesized that in bronchoalveolar lavage (BAL) fluid also the tenascin concentration would be elevated in patients with various fibrotic lung disorders. The aim of our study was to investigate whether BAL fluid tenascin would be increased compared with serum tenascin in patients with usual interstitial pneumonia (UIP), sarcoidosis, and extrinsic allergic bronchioloalveolitis. For this purpose BAL fluid was collected from five patients with UIP, 12 patients with sarcoidosis, five patients with extrinsic allergic bronchioloalveolitis, and six patients in a control group. BAL fluid and serum tenascin concentrations were detected by the enzyme immunoassay method. The BAL fluid results were expressed as tenascin concentrations in the epithelial lining fluid (ELF), as estimated by the urea method. The ELF tenascin concentration was increased in the patients with fibrotic lung disorders relative to the control group (mean 0.12 microg/ml) and was highest in the UIP group (mean 5.72 microg/ml) and sarcoidosis group (mean 4.76 microg/ml). It is concluded that the tenascin concentration in the ELF is increased in patients with UIP, sarcoidosis, and extrinsic allergic bronchioloalveolitis, suggesting active synthesis of tenascin in the lower respiratory tract in such disorders.

Adult↗

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats.

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO4) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B4 (LTB4), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB4 concentration in the control ELF (ca. 5 x 10(-7) M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB4 in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO4-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of insulin and amino acids on leucine metabolism in young and middle-aged humans.

BACKGROUND: Aging is characterized by loss of muscle mass. In healthy subjects this process is associated with hormone and nutritional changes which take place over many decades. Aim of the study To investigate the effects of insulin and amino acids on amino acid metabolism in middle-aged humans. METHODS: We evaluated leucine kinetics by means of the intravenous infusion of [1-(14C)]leucine, in 8 young (age 24 +/- 2 yr, BMI 21+/- 2 kg/M2) and in 6 middle-aged (age 53 +/- 4 yr, BMI 26 +/- 1 kg/M2) healthy subjects. Studies were performed under fasting conditions (basal), and after 180 min of euglycemic hyperinsulinemic clamp (study I), or 180 min of euglycemic hyperinsulinemia in combination with an intravenous amino acid infusion (study II). RESULTS: In the basal state endogenous leucine flux (ELF, an index of proteolysis), normalized for IBW, averaged 1.71 +/- 0.12 and 1.66 +/- 0.14 micromol/kg x min in young and middle-aged subjects, respectively. Basal leucine oxidation (0.22 +/- 0.03 vs 0.28 +/- 0.03 micromol/ kg x min, p < 0.05) was lower in middle-aged with respect to young subjects. Non-oxidative leucine disposal (NOLD, an index of protein synthesis: 1.44 +/- 0.11 vs 1.43 +/- 0.11 micromol/kg x min) was similar in young and middle-aged subjects, respectively. In response to insulin (study I) the absolute and percent decline of ELF and LOX were similar in young and middle-aged subjects: ELF declined to 1.05 +/- 0.06 micromol/kg x min (-39 +/- 5 %) and 1.07 +/- 0.14 micromol/kg x min (-36 +/- 4%), in young and middle-aged, respectively (both p < 0.01 vs basal); LOX declined to 0.21 +/- 0.02 micromol/kg min (-35 +/- 3 %), and 0.18 +/- 0.05 micromol/kg x min (-28 +/- 3%, p < 0.05 vs basal) in young and middle-aged individuals respectively (both p < 0.01 vs basal). In contrast, insulin-mediated whole-body glucose uptake was lower in middle-aged subjects (6.6 +/- 1.4 mg/ kg x min) with respect to young individuals (8.1+/-1.7 mg/kg min, p < 0.05). During study II (insulin plus AA) a significant rise in NOLD was obtained in both young (1.72 +/- 0.10 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (1.76 +/- 0.25 micromol/kg x min, p < 0.01 vs basal). Similarly, net leucine balance rose significantly in both young (+0.62 +/- 0.13 vs -0.25 +/- 0.02 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (+0.37 +/- 0.08 vs -0.22 +/- 0.03 micromol/ kg x min, p < 0.01 vs basal) suggesting that the anabolic response to amino acids is preserved in middle-aged subjects. CONCLUSIONS: In middle-aged subjects we observed 1) a moderate decline in basal leucine oxidation; 2) a normal antiproteolytic response to insulin and a reduction in glucose uptake; and 3) a normal anabolic response to AA plus insulin. In conclusion, the data provide evidence for a normal regulation of protein anabolism and an early dissociation between the metabolic effects of insulin on glucose uptake and proteolysis in middle-aged subjects.

Adult↗

Differences in surfactant lipids collected from pleural and pulmonary lining fluids.

PURPOSE: The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS: Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately followed by a pleural lavage (PL). Lipid was extracted from lavage fluid and then analyzed for saturated, primarily dipalmitoylphosphatidylcholine (DPPC), and unsaturated phosphatidylcholine (PC) species using high-performance liquid chromatography (HPLC) with combined fluorescence and ultraviolet detection. Dilution of ELF in lavage fluids was corrected for using the urea method. RESULTS: DPPC (494.7 +/- 213.9 microg/mL) was the predominant PC present in ELF collected from the alveolar surface. In contrast, significantly higher (p = 0.028) proportions of unsaturated PC species were measured in PL fluid (approximately 105 microg/mL), particularly stearoyl-linoleoyl-phosphatidylcholine (SLPC), which could not be measured in fluid collected from the alveoli, compared to DPPC (2.6 +/- 2.0 microg/mL). CONCLUSIONS: This study indicates that unsaturated PC species seem to be more important than saturated species, particularly DPPC, in the pleural cavity, which has implications for surfactant replenishment following pleural disease or thoracic surgery.

1,2-Dipalmitoylphosphatidylcholine↗