Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study

Background: The main forms of mercury (Hg) exposure in the general population are methylmercury (MeHg) from seafood, inorganic mercury (I-Hg) from food, and mercury vapor (Hg0) from dental amalgam restorations. While the distribution of MeHg in the body is described by a one compartment model, the distribution of I-Hg after exposure to elemental mercury is more complex, and there is no biomarker for I-Hg in the brain. The aim of this study was to elucidate the relationships between on the one hand MeHg and I-Hg in human brain and other tissues, including blood, and on the other Hg exposure via dental amalgam in a fish-eating population. In addition, the use of blood and toenails as biological indicator media for inorganic and organic mercury (MeHg) in the tissues was evaluated. Methods: Samples of blood, brain (occipital lobe cortex), pituitary, thyroid, abdominal muscle and toenails were collected at autopsy of 30 deceased individuals, age from 47 to 91 years of age. Concentrations of total-Hg and I-Hg in blood and brain cortex were determined by cold vapor atomic fluorescence spectrometry and total-Hg in other tissues by sector field inductively coupled plasma-mass spectrometry (ICP-SFMS). Results: The median concentrations of MeHg (total-Hg minus I-Hg) and I-Hg in blood were 2.2 and 1.0 μg/L, and in occipital lobe cortex 4 and 5 μg/kg, respectively. There was a significant correlation between MeHg in blood and occipital cortex. Also, total-Hg in toenails correlated with MeHg in both blood and occipital lobe. I-Hg in both blood and occipital cortex, as well as total-Hg in pituitary and thyroid were strongly associated with the number of dental amalgam surfaces at the time of death. Conclusion: In a fish-eating population, intake of MeHg via the diet has a marked impact on the MeHg concentration in the brain, while exposure to dental amalgam restorations increases the I-Hg concentrations in the brain. Discrimination between mercury species is necessary to evaluate the impact on Hg in the brain of various sources of exposure, in particular, dental amalgam exposure

Boosters of a therapeutic HIV-1 vaccine induce divergent T cell responses related to regulatory mechanisms

AbstractTherapeutic human immunodeficiency virus (HIV) vaccines aim to reduce disease progression by inducing HIV-specific T cells. Vacc-4x are peptides derived from conserved domains within HIV-1 p24 Gag. Previously, Vacc-4x induced T cell responses in 90% of patients which were associated with reduced viral loads. Here we evaluate the effects of Vacc-4x boosters on T cell immunity and immune regulation seven years after primary immunization. Twenty-five patients on effective antiretroviral therapy received two Vacc-4x doses four weeks apart and were followed for 16 weeks. Vacc-4x T cell responses were measured by proliferation (CFSE), INF-γ, CD107a, Granzyme B, Delayed-Type Hypersensitivity test (DTH) and cytokines and chemokines (Luminex). Functional regulation of Vacc-4x-specific T cell proliferation was estimated in vitro using anti-IL-10 and anti-TGF-ß monoclonal antibodies.Vacc-4x-specific CD8+ T cell proliferation increased in 80% after either the first (64%) or second (16%) booster. Only 40% remained responders after two boosters with permanently increased Vacc-4x-specific proliferative responses (p=0.005) and improved CD8+ T cell degranulation, IFN-γ production and DTH. At baseline, responders had higher CD8+ T cell degranulation (p=0.05) and CD4+ INF-γ production (p=0.01), whereas non-responders had higher production of proinflammatory TNF-α, IL-1α and IL-1ß (p<0.045) and regulatory IL-10 (p=0.07).Notably, IL-10 and TGF-ß mediated downregulation of Vacc-4x-specific CD8+ T cell proliferation increased only in non-responders (p<0.001). Downregulation during the study correlated to higher PD-1 expression on Vacc-4x-specific CD8+ T cells (r=0.44, p=0.037), but was inversely correlated to changes in Vacc4x-specific CD8+ T cell proliferation (r=−0.52, p=0.012).These findings show that Vacc-4x boosters can improve T cell responses in selected patients, but also induce vaccine-specific downregulation of T cell responses in others. Broad surveillance of T cell functions during immunization may help to individualize boosting, where assessment of vaccine-related immune regulation should be further explored as a potential new parameter

Inter-individual variations of human mercury exposure biomarkers: a cross-sectional assessment

BACKGROUND: Biomarkers for mercury (Hg) exposure have frequently been used to assess exposure and risk in various groups of the general population. We have evaluated the most frequently used biomarkers and the physiology on which they are based, to explore the inter-individual variations and their suitability for exposure assessment. METHODS: Concentrations of total Hg (THg), inorganic Hg (IHg) and organic Hg (OHg, assumed to be methylmercury; MeHg) were determined in whole blood, red blood cells, plasma, hair and urine from Swedish men and women. An automated multiple injection cold vapour atomic fluorescence spectrophotometry analytical system for Hg analysis was developed, which provided high sensitivity, accuracy, and precision. The distribution of the various mercury forms in the different biological media was explored. RESULTS: About 90% of the mercury found in the red blood cells was in the form of MeHg with small inter-individual variations, and part of the IHg found in the red blood cells could be attributed to demethylated MeHg. THg in plasma was associated with both IHg and MeHg, with large inter-individual variations in the distribution between red blood cells and plasma. THg in hair reflects MeHg exposure at all exposure levels, and not IHg exposure. The small fraction of IHg in hair is most probably emanating from demethylated MeHg. The inter-individual variation in the blood to hair ratio was very large. The variability seemed to decrease with increasing OHg in blood, most probably due to more frequent fish consumption and thereby blood concentrations approaching steady state. THg in urine reflected IHg exposure, also at very low IHg exposure levels. CONCLUSION: The use of THg concentration in whole blood as a proxy for MeHg exposure will give rise to an overestimation of the MeHg exposure depending on the degree of IHg exposure, why speciation of mercury forms is needed. THg in RBC and hair are suitable proxies for MeHg exposure. Using THg concentration in plasma as a measure of IHg exposure can lead to significant exposure misclassification. THg in urine is a suitable proxy for IHg exposure

Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial

Background Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant. Methods Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-ß. Results Vacc-4x proliferative T cell responses increased only among the vaccinated (p=0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p<0.001) and high regulation (r = 0.61, p = 0.010) at baseline. Conclusion Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation

Effect of grain particle size and milling method on broiler performance and apparent metabolisable energy

An experiment was conducted to determine the effect of sorghum particle size and milling type on broiler performance and feed apparent metabolisable energy (AME). Results show that AME was improved by feeding a pelleted diet containing whole sorghum, but the best performance (lowest FCR) was elicited by feeding a rolled sorghum diet at a common commercial grind size. Feed particle size may influence the rate of excretion of different fractions of the digesta and AME of a feed. AME may not be an accurate indicator of the nutritive value of grain as the same feed can have a different AME values based on physical structure

Metaller i miljön - riskfaktorer under graviditet och amning

Sammanfattning Vid studier av metallkoncentrationer i blod hos gravida är det viktigt att beakta den fysiologiska utspädning av blodkropparna som sker och är som mest uttalad i början av tredje trimestern. Belastningen av kadmium förefaller öka efter genomgången graviditet, vilket till stor del kan förklaras av en ökad absorption av kadmium i tarmen på grund av samtidigt ökad järnabsorption. Hos kvinnor som sammantaget fött flera barn var ökning av urinkadmium med stigande ålder mer uttalad än för de kvinnor som fött inget eller ett barn. Metylkvicksilver utgjorde 75% av den gravida kvinnans totalkvicksilver i blod och var dessutom nästan dubbelt så hög i navelsträngsblod som i moderns före förlossning. Halten av metylkvicksilver i navelsträngsblod var relaterat till moderns fiskintag medan halten av oorgansikt kvicksilver hos barnet var relaterat till antalet amalgamfyllningar hos modern. Halten oorganiskt kvicksilver i blod sjönk under och efter amningsperioden vilket kan förklaras av en utsöndring till modersmjölken. Koncentrationen av bly i navelsträngsblod var lika hög som hos modern fyra veckor före förlossning. Blodblyhalten hos modern efter genomgången graviditet föreföll öka vilket kanske kan förklaras av en högre benomsättning under amningsperioden än under graviditeten, och därmed en frisättning av bly från benvävnad. Detta kommer senare att utvärderas i förhållande till markörer för benomsättning.Abstract When investigating metal concentrations during pregnancy, it is important to consider the physiological hemodilution of the maternal blood that occurs, and which is most prominent in the beginning of the third trimester. The cadmium load seemed to increase after a terminated pregnancy. This can, to a large extent, be explained by an increased absorption of cadmium in the intestine due to a concomitant increased absorption of iron. In women with two or more children the increase in urinary cadmium with increasing age was more pronounced than in women with none or one previous child. Methyl mercury constituted about 75% of the total amount of mercury in the maternal blood. Moreover, it was almost twice as high in the cord blood compared to the maternal blood in late gestation. The concentration of methyl mercury in cord blood was related to the maternal intake of fresh water fish, while the level of inorganic mercury was related to the maternal number of amalgam fillings. The level of inorganic mercury decreased during and after lactation which can be explained by an elimination to the milk. The levels of lead in cord blood was similar to that of the mother four weeks before delivery. The concentration of maternal blood lead seemed to increase after the terminated pregnancy. This may partly be explained by a higher bone turn over during lactation than during pregnancy, and thereby an increased release of lead from bone tissue. This will be further evaluated in relation to markers of bone metabolism