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Query: UMLS:C0004153 (atherosclerosis)
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Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.
Atherosclerosis 2000 Feb
PMID:Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland. 1065 61

Universally, the general population is exposed to a variety of "toxic" substances. Some of these are from manufactured goods and some from air and water pollution. Toxins are also normally found in many foods; however, unless the exposure is overwhelming, we are many times (even unknowingly) protected by the foods we eat. A judicious choice of food will counteract noxious agents. Therefore, the diet can be a major factor in determining who does and who does not show toxic symptoms following exposure. This review will cover three aspects. The first will be on protectors against metal toxicity. For example, whereas humans can consume fish that have absorbed mercury from contaminated bay water, selenium can act as a natural antagonist for mercury poisoning. (Naturally, too much selenium itself can be detrimental!) Some vegetables can accumulate cadmium from contaminated soil, and zinc from a variety of nuts is an antagonist of cadmium toxicity. Nitrites in preserved meats can be converted into nitroamines by saliva or mild stomach acid. Vitamin C found in oranges and bell peppers can inhibit that conversion. In addition, calcium antagonizes both lead and aluminum toxicity. The second aspect is on oxidants and antioxidants. Oxidative stress can lead to some cancers, atherosclerosis, and adverse effects of aging. Antioxidants are the best protectors of the damage caused by reactive oxygen species (ROS). The most effective antioxidants are found in highly colored fruits and vegetables such as carrots, tomatoes, and berries, called carotenoids. Flavonoids (polyphenols), another class of effective antioxidants that negate ROS, may or may not be colored. The third aspect is on gaps in current knowledge. Many foods naturally contain chemicals that are, in larger concentrations, quite toxic or carcinogenic. Biotransformations (detoxification mechanisms) involving type I and type II enzymes are known. Some foods do modify these enzymes either positively or negatively. Grapefruit contains a substance that inhibits an isoform of P450, making some cardiac drugs, as substrates, more toxic. There is inadequate information on what specific components are in a variety of foods that are associated with cancer prevention. The experimental carcinogenic compound (and suspected as a human carcinogen) found in overcooked, burnt, and fried meats and fish, namely IQ (2-amino-3-methyl-3H-imidazo[4,5f]quinoline, will be used as a prototype for what needs to be known about foods that will affect toxins.
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PMID:Can nutrition affect chemical toxicity? 1239 88

Endothelial cells are covered by a surface layer of membrane-associated proteoglycans, glycosaminoglycans, glycoproteins, glycolipids, and associated plasma proteins. This layer may limit transendothelial solute transport. We determined dimension and transport properties of this endothelial surface layer (ESL) in isolated arteries. Rat mesenteric small arteries (diameter approximately 150 microm) were isolated and cannulated with a double-barreled -pipette on the inlet side and a regular pipette on the outlet side. Dynamics and localization of intra-arterial fluorescence by FITC-labeled dextrans (FITC-Deltas) and the endothelial membrane dye DiI were determined with confocal microscopy. Large FITC-Delta (148 kDa) filled a core volume inside the arteries within 1 min but was excluded from a 2.6 +/- 0.5-microm-wide region on the luminal side of the endothelium during 30 min of dye perfusion. Medium FITC-Delta (50.7 kDa) slowly penetrated this ESL within 30 min but did not permeate into the arterial wall. Small FITC-Delta (4.4 kDa) quickly passed the ESL and accumulated in the arterial wall. Prolonged luminal fluorochrome illumination with a bright mercury lamp destroyed the approximately 3-microm exclusion zone for FITC-Delta 148 within a few minutes. This study demonstrates the presence of a thick ESL that contributes to the permeability barrier to solutes. The layer is sensitive to phototoxic stress, and its damage could form an early event in atherosclerosis.
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PMID:Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy. 1290 18

The vascular endothelium is involved in the release of various vasodilators, including nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in the regulation of vascular tone, the inhibition of platelet aggregation, and the suppression of smooth muscle cell proliferation. Several diseases are associated with changes in endothelial function mediated through reduced NO bioavailability. In addition, endothelial dysfunction is an early feature of atherosclerosis and vascular diseases in humans. Therefore, it is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Recently, we have evaluated the effects of intra-arterial infusion of infusion of NO agonists, such as acetylcholine, methacholine, and bradykinin, and NO antagonists on forearm blood flow using mercury-filled Silastic strain-gauge plethysmography. The response to the intra-arterial infusion of vasoactive agents should be considered the gold standard in assessing endothelial function, because the use of agonists to stimulate NO release allow us to draw more specific conclusions concerning the role of basal and stimulated NO release. However, the invasive method is time-consuming and is a burden for patients. A noninvasive method of measuring forearm blood flow response to reactive hyperemia also is useful in assessing endothelial function. In this review we would like to explain in detail the methods of assessing endothelial function in humans using strain-gauge plethysmography.
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PMID:New methods to evaluate endothelial function: method for assessing endothelial function in humans using a strain-gauge plethysmography: nitric oxide-dependent and -independent vasodilation. 1473 8

In order to explore the observed association among mercury, atherosclerosis, and coronary heart disease, the effects of mercury, copper, and iron on the peroxidation of low-density lipoprotein (LDL) and on the enzymatic activities of glutathione peroxidase and myeloperoxidase were investigated in vitro. On the basis of our nuclear magnetic resonance (NMR) experiments, we conclude that mercury does not promote the direct nonenzymatic peroxidation of LDL, like copper and iron. In our enzyme measurements, mercury inhibited slightly myeloperoxidase, although not significantly in presence of LDL. Instead, inorganic mercury, but not methylmercury chloride, inhibited glutathione peroxidase effectively and copper even at 10 micromol/L, below physiological concentrations, doubled the inhibition rate. Copper and iron had no direct effect on glutathione peroxidase, but they both seem to activate production of HOCl by myeloperoxidase. We conclude here that, first, mercury and methylmercury do not promote direct lipid peroxidation, but that, second, a simultaneous exposure to high inorganic mercury, copper, and iron and low selenium concentrations can lead to a condition in which mercury promotes lipid peroxidations. This mechanism provides a plausible molecular-level explanation for the observed association between high body mercury content and atherosclerosis.
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PMID:Does mercury promote lipid peroxidation? An in vitro study concerning mercury, copper, and iron in peroxidation of low-density lipoprotein. 1555 76

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.
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PMID:The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. 1740 90

Results obtained by the modern automatic blood pressure (BP) monitors using oscillometric method [5] are highly dependent on conditions of cardiovascular system of the monitored person. Especially, with people who suffer from cardiovascular diseases (e.g. atherosclerosis) the resulting values differ significantly from those measured by the traditional auscultation method. A reasonable solution for improvement of quality of oscillometric method could be a sophisticated intelligent BP measuring system which applies for evaluation of BP more complex approach taking into account the monitored person's condition of patient cardiovascular system (CS) i.e. the hemodynamic parameters of CS (e.g. heart rate, stroke volume, total peripheral resistance, systemic arterial compliance, pulse wave velocity, augmentation index etc.). Such a system has to be based on appropriate models of the considered diseases which are validated on real life data. For that purpose, we have started to build a database of real-life oscillometric pulsations waveforms (OPW) complemented by the values of "auscultation" blood pressure measurements and additional relevant information about the considered patients (age, sex, etc.) as well as their diagnosis. This data collection requires a special HW device for measurement of the OPW--we have developed such a device and it has been validated in Czech Certified Metrological Centre. Our OPW monitor is connected through the T-pieces and tubes to the cuff, mercury sphygmomanometer and automatic "oscillometric" blood pressure monitor.
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PMID:Comparative study of non-invasive blood pressure measurement methods in elderly people. 1800 30

The paleopathological study of 31 Italian Renaissance mummies from the Basilica of S. Domenico Maggiore in Naples has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 3 metabolic (obesity, atherosclerosis, gallstones), I articular (DISH) and 2 neoplastic (colon adenocarcinoma and skin carcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (14C: 1569 +/- 60), presented a diffuse vesiculopustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM revealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria d'Aragona, Marquise of Vasto (1503-1568), revealed on the left arm an oval, cutaneous ulcer (15 x l0 mm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. Electron microscopy evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. Further examination of the mummy showed a large peduncolate arborescent neoformation (2 x 7 mm) of the right inguinal region, which was rehydrated and submitted to histology by hematoxylineosin, Van Gieson and Masson's trichromic staining. Light microscopy evidenced an exophytic, papillary skin lesion, with typical connective axis and pronounced parakeratosis. These macroscopic and histological aspects seemed peculiar of condyloma acuminatum, a papillomavirus-induced squamous lesion also called "venereal wart". Molecular study revealed the presence of HPV 18, a virus with high oncogenic potential. Automated sequencing of several clones revealed 100% similarity sequences of both HPV 18 and JC9813 DNA, a putative novel HPV with low oncogenic potential. This study represents the first molecular diagnosis of HPV in mummies and could pave the way for further research about the secular evolution of these viruses, very important in human oncology. The buccal surfaces of the teeth of Isabella d'Aragona, duchess of Milan ((1470-1524), covered by a black patina with high mercury levels, have been intensively and intentionally abraded. The black patina can be attributed to chronic mercury intoxication, used therapeutically in the treatment of syphilis. The mummy of Ferrante I d'Aragona, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12: the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a case of cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of this wealthy classes of the Italian Renaissance.
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PMID:[The Aragonese mummies of the Basilica of Saint Domenico Maggiore in Naples]. 1817 25

Few studies have been performed on trace elements in tissues and serum in cardiovascular disease and none in aortic aneurysm. In this study the concentrations of 10 trace elements were determined in serum and aneurysmatic aortic tissue from 23 patients undergoing thoracic surgery. Macroscopically, normal thoracic aortic tissue specimens from 10 forensic autopsies and serum from 23 healthy blood donors served as controls. DNA from the intracellular respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), which may be involved in the pathogenesis of atherosclerosis, was found in 26% (6/23) of the patients but in none of the controls. The serum copper/zinc ratio, a well-known marker of ongoing infection and/or inflammation, was higher (26%, p<0.001) in aneurysm patients. C. pneumoniae requires iron for its growth. In our aneurysm patients iron was higher in serum (by 54%, p<0.001) and aneurysmal tissue (by 60%, p<0.001). Although calcium was lower in patient sera (by 8%, p<0.001), it tended to be higher (by 20%, ns) in aneurysmatic tissue. In addition, mercury concentrations in serum and aneurysmatic tissue were positively correlated (r=0.51, p<0.05). Moreover, C. pneumoniae-positive aneurysmatic tissues had lower concentrations of manganese (46%, p<0.05) and zinc (26%, ns) but a higher concentration of mercury (50%, p<0.05) than C. pneumoniae-negative aneurysmatic tissues. In conclusion, aneurysm patients showed a shift in trace element levels in serum and in the diseased part of the aorta, the pattern being partly different in C. pneumoniae-positive compared with C. pneumoniae-negative patients. The results are compatible with active infection and/or inflammation, possibly initiated by C. pneumoniae.
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PMID:Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed a shift in trace element levels in serum and diseased aortic tissue. 1939 57

In hemodialysis (HD) patients, routine dialysis center blood pressure (BP) measurements may be a poor indicator of BP control. Ambulatory blood pressure monitoring (ABPM) improves the predictability of BP as a risk factor for target organ damage. Carotid intima-media thickness (IMT) is an important indicator of asymptomatic atherosclerosis and a predictor of cardiovascular events. The purpose of our study was to evaluate the possible association between different BP measurements and carotid IMT in HD patients. Eighty-five HD patients were included in our study. BP was measured with a standard mercury sphygmomanometer before and after each HD session. The average one-monthly values of routine BP measurements were also analyzed. 24- and 48-h ABPM was performed after the end of each HD session using non-invasive ABPM. The average values of systolic and diastolic BP were analyzed separately for the first (HD) and second (interdialytic) days ABPM, and for both days together. Using B-mode ultrasonography, carotid IMT was measured and plaque occurrence investigated. We found a statistically significant correlation between carotid IMT and the average one-monthly pre-HD diastolic BP (P < 0.05), diastolic BP on the HD-day ABPM, the interdialytic-day ABPM, and during 48-h ABPM (P < 0.05). By multiple regression analysis, we found a statistically significant correlation only between carotid IMT and diastolic BP on the HD-day ABPM, the interdialytic-day ABPM, and during 48-h ABPM (P < 0.05). Only longer BP measurements (24- and 48-h ABPM) were associated with carotid IMT in HD patients.
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PMID:Blood pressure measurements and carotid intima media thickness in hemodialysis patients. 1969 61


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