Human Atherosclerotic Plaque Progression Is Dependent on Apoptosis According to Bomb-Pulse 14C Dating.

Individuals with rapidly progressing atherosclerotic plaques are at higher risk of experiencing acute complications. Currently, we lack knowledge regarding factors in human plaque that cause rapid progression. Using the 14C bomb-pulse dating method, we assessed the physical age of atherosclerotic plaques and which biological processes were associated with rapidly progressing plaques. Interestingly, increased apoptosis was the main component associated with a young physical plaque age, reflecting rapid plaque progression. Our findings in combination with recent advances in imaging techniques could guide future diagnostic imaging strategies to identify rapidly progressing plaques or therapeutic targets, halting plaque progression.

Direct association between diet and the stability of human atherosclerotic plaque.

Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ(13)C) and nitrogen (δ(15)N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ(13)C and δ(15)N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ(13)C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ(15)N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability.

Bomb-pulse 14C analysis combined with 13C and 15N measurements in blood serum from residents of Malmö, Sweden.

The (14)C content of 60 human blood serum samples from residents of Malmö (Sweden) in 1978, obtained from a biobank, has been measured to estimate the accuracy of (14)C bomb-pulse dating. The difference between the date estimated using the Calibomb software and sampling date varied between -3 ± 0.4 and +0.2 ± 0.5 years. The average age deviation of all samples was -1.5 ± 0.7 years, with the delay between production and consumption of foodstuffs being probably the dominating cause. The potential influence of food habits on the (14)C date has been evaluated using stable isotope δ(13)C and δ(15)N analysis and information about the dietary habits of the investigated individuals. Although the group consisting of lacto-ovo vegetarians and vegans (pooled group) was not completely separated from the omnivores in a stable isotopic trophic level diagram, this analysis proved to add valuable information on probable dietary habits. The age deviation of the sampling date from the respective Calibomb date was found strongly correlated with the δ(13)C values, probably due to influence from marine diet components. For the omnivore individuals, there were indications of seasonal effects on δ(13)C and the age deviation. No significant correlation was found between the age deviation and the δ(15)N values of any dietary group. No influence of sex or year of birth was found on neither the (14)C nor the δ(13)C and δ(15)N values of the serum samples. The data were also divided into two groups (omnivores and pooled group), based on the level of δ(15)N in the samples. The consumption of high δ(15)N-valued fish and birds can be responsible for this clustering.

Short communication: Dating components of human atherosclerotic plaques.

RATIONALE: Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. OBJECTIVE: In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. METHODS AND RESULTS: Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. CONCLUSIONS: These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

14CO2 dispersion around two PWR nuclear power plants in Brazil.

Atmospheric air samples were taken within 3 km from power plants encompassing five different distances and wind directions. Samples were taken between 2002 and 2005 aiming to evaluate the environmental (14)C enrichment due to the operation of Brazilian nuclear power plants. The sampling system consisted of a pump connected to a trapping column filled with a 3M NaOH solution. The trapped CO(2) was analyzed for (14)C by using a single stage accelerator mass spectrometry (SSAMS). All sampling sites revealed measurable (14)C excess values. The maximum excesses were of 15 and 14 mBq/m(3) for sampling sites placed at NE of the power plants, which is the main wind direction in the area. The mean excesses values were 12 mBq/m(3) to the NE direction, 8 mBq/m(3) to the E, 10 mBq/m(3) to the N, 8 mBq/m(3) to the WNW and 7 mBq/m(3) to the W direction (increasing distances from NE to W). Compared to other Light Water Reactors (LWR) data, these means' values are significantly higher than the average worldwide reported value of 3 mBq/m(3). Available data indicate that the observed values are not related to (14)C emission by the power plants vent stack. Other factors, such as topography, seem to have an important role because it affects wind dispersion thus favoring (14)C accumulation in the sampled area. Moreover, the high elevations around the power plants enhance the chances to measure high values of (14)C since the plume can be intercepted before it is drawn to the ground. Modeling of the plume has shown that its dispersion does not follow a Gaussian model and that agreement between atmospheric CO(2) and vegetation (14)C activities occurs only for sampling sites placed at NE of the power plants.

(14)C, delta(13)C and total C content in soils around a Brazilian PWR nuclear power plant.

Nuclear power plants release (14)C during routine operation mainly as airborne gaseous effluents. Because of the long half-life (5730 years) and biological importance of this radionuclide (it is incorporated in plant tissue by photosynthesis), several countries have monitoring programs in order to quantify and control these emissions. This paper compares the activity of (14)C in soils taken within 1km from a Brazilian nuclear power plant with soils taken within a reference area located 50km away from the reactor site. Analyses of total carbon, delta(13)C and (137)Cs were also performed in order to understand the local soil dynamics. Except for one of the profiles, the isotopic composition of soil organic carbon reflected the actual forest vegetation present in both areas. The (137)Cs data show that the soils from the base of hills are probably allocthonous. The (14)C measurements showed that there is no accumulation due to the operation of the nuclear facility, although excess (14)C was found in the litter taken in the area close to power plant. This indicates that the anthropogenic signal observed in the litter fall has not been transferred yet to the soil. This study is part of an extensive research programme in which other samples including air, vegetation and gaseous effluents (taken in the vent stack of the Brazilian nuclear power reactors Angra I and II) were also analyzed. The present paper aimed to evaluate how (14)C emissions from the nuclear power plant are transferred and stored by soils present in the surroundings of the reactor site. This is the first study concerning anthropogenic (14)C in soils in Brazil.

Accelerator mass spectrometry.

In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples.

14C content in vegetation in the vicinities of Brazilian nuclear power reactors.

(14)C specific activities were measured in grass samples collected around Brazilian nuclear power reactors. The specific activity values varied between 227 and 299 Bq/kg C. Except for two samples which showed (14)C specific activities 22% above background values, half of the samples showed background specific activities, and the other half had a (14)C excess of 1-18%. The highest specific activities were found close to the nuclear power plants and along the main wind directions (NE and NNE). The activity values were found to decrease with increasing distance from the reactors. The unexpectedly high (14)C excess values found in two samples were related to the local topography, which favors (14)C accumulation and limits the dispersion of the plume. The results indicate a clear (14)C anthropogenic signal within 5 km around the nuclear power plants which is most prominent along northeastwards, the prevailing wind direction.

Long-term biokinetics and radiation exposure of patients undergoing 14C-glycocholic acid and 14C-xylose breath tests.

The (14)C-glycocholic acid and (14)C-xylose breath tests are clinically used for the diagnosis of intestinal diseases, such as bacterial overgrowth in the small intestine. The two tests have in earlier studies been thoroughly evaluated regarding their clinical value, but due to the long physical half-life of (14)C and the limited biokinetic and dosimetric data, which are available for humans, several hospitals have been restrictive in their use. The aim of this study was to investigate the long-term biokinetics and dosimetry of the two (14)C compounds in patients and volunteers, using the highly sensitive accelerator mass spectrometry (AMS) technique. Eighteen (18) subjects were included, 9 for each compound. The (14)C content in samples from exhaled air, urine, and, for some subjects, also feces were analyzed with both liquid scintillation counting (LSC) and AMS. The results from the glycocholic acid study showed that, up to 1 year after the administration, 67%+/-6% (mean+/-standard deviation) of the administered activity was recovered in exhaled air, 2.4%+/-0.4% was found in urine, and 7.6% (1 subject) in feces. In the xylose study, the major part was found in the urine (66%+/-2%). A significant part was exhaled (28%+/-5%), and the result from an initial 72-hour stool collection from 2 of the subjects showed that the excretion by feces was insignificant. The absorbed dose to various organs and tissues and the effective dose were calculated by using biokinetic models, based on a combination of experimental data from the present study and from earlier reports. In the glycocholic acid study, the highest absorbed dose was received by the colon (1.2 mGy/MBq). In the xylose study, the adipose tissue received 0.8 mGy/MBq. The effective dose was estimated to 0.5 (glycocholic acid) and 0.07 mSv/MBq (xylose). Thus, from a radiation protection point of view, we see no need for restrictions in using the two (14)C-labeled radiopharmaceuticals on adults with the activities normally administered (0.07-0.4 MBq).

Assessment of the environmental contamination with long-lived radionuclides around an operating RBMK reactor station.

The presence of man-made gamma emitting radionuclides in the region within 32km radius of the Ignalina NPP/Lithuania has been investigated during the period 2001-2004, prior to the closure of the first of the two operating RBMK 1500-type reactors. Gamma spectrometric measurements of various terrestrial and aquatic plants as well as of soil samples showed moderate environmental contamination with the fission product (137)Cs and with the neutron activation products (60)Co and (54)Mn. Traces of the activation products (65)Zn and (110m)Ag were found in the nearest vicinity of the NPP. Activity concentrations were inhomogeneously distributed in the area of interest. Moss and algae samples showed the highest uptake of radionuclides. In addition to the gamma spectrometric measurements, the levels of (14)C were determined in the same bio-indicator samples using accelerator mass spectrometry.

Biokinetics and radiation dosimetry for patients undergoing a glycerol tri[1-14C]oleate fat malabsorption breath test.

The glycerol tri[1-14C]olein test for fat malabsorption was carried out in two male volunteers and measurements of the loss of 14C in expired air, urine and faeces and the retention of 14C in biopsy samples of abdominal fat were made using accelerator mass spectrometry. Exhalation accounted for 73% and 55% of the administered activity and could be described by three-component exponential functions with halftimes of about 1h, 2 days and 150 days, respectively. Urinary excretion accounted for 24% of the administered activity, almost all during the first 24h after administration; about 2% was excreted in the faeces in 48h. The halftime of retention of 14C in fat ranged from 137 to 620 days. Absorbed dose calculations indicate that for a normal adult the largest dose, 1.5-7.0mGy/MBq is received by the adipose tissue, and that the effective dose is 0.3-0.5mSv/MBq. It is concluded that no restrictions need to be placed on radiation safety grounds on the administration of 0.05-0.1MBq 14C-triolein for the triolein breath test.