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Objective: To investigate the postoperative effect of double-lid blepharoplasty based on the histological difference in the upper eyelid of Asian patients. Material and Methods: A total of 76 patients with poor bilateral upper eyelid morphology or a single eyelid were included in this study. Different techniques of double-eyelid blepharoplasty were performed based on the thickness of the palpebral tissue. The improved PARK method (group A: 15 participants) was employed for patients with orbicularis oculi muscle being thinner, and the fat bulge of orbital septum was less. The improved traditional method (group B: 52 participants) was employed for patients with hypertrophy of the eyelid skin, orbicularis oculi muscle, and fat bulge in the orbital septum. Results: All 76 patients achieved satisfactory outcomes in a single surgical procedure. Postoperative follow-up ranged from 3 to 6 months. In group A, there was no obvious swelling of flap near the palpebral margin and the double blepharon line becomes shallow. Although some patients in group B experienced varying degrees of bruising in the early postoperative period, all patients returned to a more natural shape 1–3 months after surgery. Furthermore, after 3–6 months postoperatively, there were no obvious scar adhesion and ladder sensation in the both sides of the incision. Conclusion: Preoperative analysis of the thickness of the upper eyelid tissue is essential to determine the appropriate surgical technique for double-eyelid blepharoplasty. The improved traditional method is recommended for patients with hypertrophy of the upper eyelid tissue (group A), as it minimizes scar adhesion and reduces the stair-step sensation in the lower eyelid tissue during long-term follow-up. For patients with thin upper eyelid tissue, the improved PARK method should be employed to avoid issues such as tissue accumulation, double eyelid crease became shallower, or disappearance. In order to obtain natural and long-term surgical results, different surgical methods should be provided according to the patient's eye tissue condition. Level of Evidence II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Aluminum and silicon are contaminants found in formulations used to prepare parenteral nutrition. Both elements are leached from glass containers, mainly during the heating cycle for sterilization. Insoluble and biologically inactive species of hydroxyaluminosilicates have been shown to form in solutions containing Al and Si. Therefore, this interaction may play an important role in protecting the body against Al toxicity. In this study, the bioavailability of Al in the presence of Si, calcium gluconate (Gluc.), and potassium phosphate (Phosf.) was investigated in rats. The rats were divided into 10 groups of 5 animals each: control, Al, Si, Al + Si, Gluc, Gluc + Al, Gluc + Al + Si, Phosf, Phosf + Al, and Phosf + Al + Si. The doses, consisting of 0.5 mg/kg/day Al and 2 mg/kg/day Si in the presence or absence of Gluc. or Phosf., were intraperitoneally administered for 3 months. Tissues were analyzed for Al and Si content. Al accumulated in the liver, kidneys, and bones, and the simultaneous administration of Si decreased Al accumulation in these tissues. The presence of Si reduced the amount of Al present by 72% in the liver, by 45% in the kidneys, and by 16% in bone. This effect was lees pronounced in the presence of parenteral nutrition compounds though. Si tissue accumulation was also observed, mainly when administered together with phosphate. These results suggest that Si may act as a protector against Al toxicity, by either reducing Al absorption or increasing its excretion, probably through hydroxyaluminosilicates formation. The presence of calcium gluconate and potassium phosphate decreases or inhibits this effect. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate heavy metal deposits in the feathers, livers, and kidneys of 37 wild bird species in Thailand. Interspecies differences in metal residues were noticed in the livers and kidneys but not in the feathers. The species-specific circumstances of the granivorous birds, especially the feeding behavior, and/or the ingestion of metal-contaminated seeds may result in a higher accumulation of Cd in their livers and kidneys compared to those in water birds. The Pb concentration in the livers (>15 ppm) and feathers (>4 ppm) exceeded the thresholds, causing potential lead poisoning and affecting the reproductive success in all the groups of birds. The Cd level in the kidneys was above 2–8 ppm, indicating increased environmental exposure to Cd in these wild birds. The correlations showed the suitability of the liver or kidney as an alternative sample for each other in studying the accumulation of Cd, Pb, Ni, Zn, and Fe, while Pb in the liver could be estimated using feathers. Birds are useful as bioindicators of metal pollution, but the variety of species and tissue distribution may influence the study of heavy metal burdens in birds. The objective of this study was to determine the levels of heavy metals in wild birds' carcasses to acquire information on species differences and the tissue distribution of metals in wild birds in Thailand. Species differences in metal buildup were observed in the livers and kidneys, but not in the feathers. A significantly higher accumulation of Cd was found in the livers and kidneys of the granivorous birds compared to those in the water birds. In all the groups of birds, the Pb level in the livers (>15 ppm) and feathers (>4 ppm) exceeded the threshold limits, causing potential lead poisoning and disturbing the reproductive success. The Cd accumulation in the kidneys was above 2–8 ppm, indicating increased environmental exposure to Cd in these birds. The Cd, Pb, Ni, Zn, and Fe concentrations in the livers could be estimated using the kidneys, while the Pb level in the liver may be predicted using feathers. Furthermore, water birds' feathers may be potentially appropriate bioindicators for long-term exposure. Research on the origin of metal contamination is needed to reduce the threat of heavy metals to the health of both birds and other wildlife species. [ABSTRACT FROM AUTHOR]

Alcohol consumption alters gut microflora and damages intestinal tight junction barriers, which may affect arsenic (As) oral bioavailability. In this study, mice were exposed to arsenate in the diet (6 μg/g) over a 3-week period and gavaged daily with Chinese liquor (0.05 or 0.10 mL per mouse per day). Following ingestion, 78.0% and 72.9% of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL, significantly greater than when As was supplied alone (44.7%). Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or tissue. Significantly lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice, contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular pathway. However, As concentration in the liver, kidney, and intestinal tissue of liquor-treated mice was decreased by 24.4%–42.6%, 27.5%–38.1%, and 28.1%–48.9% compared to control mice. This was likely due to greater renal glomerular filtration rate induced by alcohol, as suggested by significantly lower expression of genes encoding for renal tight junctions. In addition, in mice gavaged daily with 0.05 mL liquor, the serum antidiuretic hormone level was significantly lower than control mice (2.83 ± 0.59 vs. 5.40 ± 1.10 pg/mL), suggesting the diuretic function of alcohol consumption, which may facilitate As elimination via urine. These results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As.

This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice. AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications. The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed. Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury. The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure. [ABSTRACT FROM AUTHOR]

Birds are useful as bioindicators of metal pollution, but the variety of species and tissue distribution may influence the study of heavy metal burdens in birds. The objective of this study was to determine the levels of heavy metals in wild birds’ carcasses to acquire information on species differences and the tissue distribution of metals in wild birds in Thailand. Species differences in metal buildup were observed in the livers and kidneys, but not in the feathers. A significantly higher accumulation of Cd was found in the livers and kidneys of the granivorous birds compared to those in the water birds. In all the groups of birds, the Pb level in the livers (>15 ppm) and feathers (>4 ppm) exceeded the threshold limits, causing potential lead poisoning and disturbing the reproductive success. The Cd accumulation in the kidneys was above 2–8 ppm, indicating increased environmental exposure to Cd in these birds. The Cd, Pb, Ni, Zn, and Fe concentrations in the livers could be estimated using the kidneys, while the Pb level in the liver may be predicted using feathers. Furthermore, water birds’ feathers may be potentially appropriate bioindicators for long-term exposure. Research on the origin of metal contamination is needed to reduce the threat of heavy metals to the health of both birds and other wildlife species.

8‐Prenylnaringenin (8‐PN), a hop flavonoid, is a promising food substance with health benefits. Compared with nonprenylated naringenin, 8‐PN exhibits stronger estrogenic activity and prevents muscle atrophy. Moreover, 8‐PN prevents hot flushes and bone loss. Considering that prenylation reportedly improves the bioavailability of flavonoids, we compared the parameters related to the bioavailability [pharmacokinetics and tissue distribution in C57/BL6 mice, binding affinity to human serum albumin (HSA), and cellular uptake in HEK293 cells] of 8‐PN and its mother (non‐prenylated) compound naringenin. C57/BL6 mice were fed an 8‐PN or naringenin mixed diet for 22 days. The amount of 8‐PN (nmol/g tissue) in the kidneys (16.8 ± 9.20), liver (14.8 ± 2.58), muscles (3.33 ± 0.60), lungs (2.07 ± 0.68), pancreas (1.80 ± 0.38), heart (1.71 ± 0.27), spleen (1.36 ± 0.29), and brain (0.31 ± 0.09) was higher than that of naringenin. A pharmacokinetic study in mice demonstrated that the Cmax of 8‐PN (50 mg/kg body weight) was lower than that of naringenin; however, the plasma concentration of 8‐PN 8 h after ingestion was higher than that of naringenin. The binding affinity of 8‐PN to HSA and cellular uptake in HEK293 cells were higher than those of naringenin. 8‐PN bioavailability features assessed in mouse or human model experiments were obviously different from those of naringenin. [ABSTRACT FROM AUTHOR]

It has been over a decade since oxidative enzymes were first used to degrade carbon‐based nanomaterials (CBNs). Although enormous progress has been achieved in this field, many questions and problems remain unresolved that need to be answered to usher these materials toward their true destiny. Nanobioscience researchers now know that ignoring the biomolecular corona (BMC) in nanobiomedical studies, either inadvertently or intentionally, is by no means justified. However, a major drawback to progress is that BMC effects on CBN biodegradation have been omitted from a large number of studies. What's more, many studies in the field have eliminated the BMC source in the relevant experiments. Thus, the most critical question that one needs to probe is whether the BMC and its characteristics affect the biodegradability of CBNs? In this conceptual perspective paper, recent progress and significant research in CBNs biodegradation are summarized. Then, the importance of the BMC and its possible impacts on the biodegradation of CBNs are thoroughly explored as a conceptual guide. Finally, remaining challenges and the direction of future research are provided, and barriers that need to be overcome to advance the field are discussed including recommendations regarding BMC considerations and study design and reporting guidelines. [ABSTRACT FROM AUTHOR]

The pronounced lethality of N -(1,3-dimethylbutyl)- N '-phenyl- p -phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O -sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Cadmium (Cd) has been recognized as one of the most toxic heavy metals, which is continuously discharged into environments through anthropogenic (industrial activities, fertilizer production, and waste disposal) and natural sources with anthropogenic sources contributing greater than the natural sources. Therefore, Cd concentration sometimes increases in feeds, fodders, water bodies, and tissues of livestock including poultry in the vicinity of the industrial areas, which causes metabolic, structural, and functional changes of different organs of all animals. In poultry, bioaccumulation of Cd occurs in several organs mainly in the liver, kidney, lung, and reproductive organs due to its continuous exposure. Intake of Cd reduces growth and egg laying performance and feed conversion efficiency in poultry. Chronic exposure of Cd at low doses can also alter the microscopic structures of tissues, particularly in the liver, kidney, brain, pancreas, intestine, and reproductive organs due to increased content of Cd in these tissues. Continuous Cd exposure causes increased oxidative stress at cellular levels due to over-production of reactive oxygen species, exhausting antioxidant defense mechanisms. This leads to disruption of biologically relevant molecules, particularly nucleic acid, protein and lipid, and subsequently apoptosis, cell damage, and necrotic cell death. The histopatholocal changes in the liver, kidneys, and other organs are adversely reflected in hemogram and serum biochemical and enzyme activities. The present review discusses about Cd bioaccumulation and histopathological alterations in different tissues, pathogenesis of Cd toxicity, blood-biochemical changes, and its different ameliorative measures in poultry. [ABSTRACT FROM AUTHOR]

• Behavioral effects of neonicotinoid pesticide clothianidin were compared in adult and aging mice. • A sub-NOAEL level of clothianidin decreased the locomotor activity in some behavioral tests in the aging mice, but not in the adult mice. • The concentrations of most CLO and its metabolites were higher in the blood and brain in the aging group than the adult group. • These results suggested age-related differences in the adverse effects of neonicotinoids in mammals. Neonicotinoids, which act as agonists of the nicotinic acetylcholine receptors of insects, are widely used pesticides worldwide. Although epidemiological studies revealed that the detection amounts of neonicotinoids in urine are higher in the elderly population than other age-groups, there is no available information regarding the risks of neonicotinoids to older mammals. This study was aimed to investigate aging-related differences in the behavioral effects of the neonicotinoid pesticide clothianidin (CLO). We acutely administered a sub-NOAEL level (5 mg/kg) of CLO to adult (12-week-old) and aging (90-week-old) mice and conducted four behavioral tests focusing on the emotional behavior. In addition, we measured the concentrations of CLO and its metabolites in blood, brain and urine. There were age-related changes in most parameters in all behavioral tests, and CLO significantly decreased the locomotor activity in the open field test and elevated plus-maze test in the aging group, but not in the adult group. The concentrations of most CLO and its metabolites were significantly higher in the blood and brain and were slightly lower in the urine in the aging group compared to the adult group. These findings should contribute to our understanding of age-related differences in the adverse effects of neonicotinoids in mammals. [ABSTRACT FROM AUTHOR]

Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by Candida albicans. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC0–24/MIC ratio of 53.51 ± 11.12, whereas VFEND® resulted in a 2.5-fold lower AUC0–24/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.

This study investigates the effects of different inorganic arsenic (As III) concentrations (0, 125, 500 and 1000 μg As/L) following two exposure times (7 and 14 days) on gills, digestive gland and muscle of scallop Aequipecten tehuelchus from Patagonia, Argentina. A biochemical approach was used to investigate oxidative stress-related parameters after different As concentrations and exposure times. Although the accumulation of As was of the same order of magnitude in all tissues, the results showed distinct tissue-specific oxidative responses to this metalloid. Furthermore, the variation in exposure time had no significant effect on As accumulation in any of the three tissues. In gills, despite no reactive oxygen and nitrogen species (RONS) were detected, there was an increase in catalase (CAT) activity and metallothionein (MT) levels. Conversely, digestive gland showed RONS production without a rise in CAT and glutathione S -transferases (GST) activities, but with an increase in MT levels. In muscle, RONS production and CAT activity kept constant or decreased, while MT levels remained unchanged. In addition, exposure time demonstrated its critical role in gills by influencing the response of CAT, GST and MT, particularly at high As concentrations, while exposure time did not affect the biochemical stress parameters in the digestive gland and muscle. Interestingly, neither concentration of As produced lipid damage, showing the effectiveness of the antioxidant mechanisms to avoid it. These results emphasize that A. tehuelchus exhibited no time-dependent effects in response to As exposure, while showing tissue-specific responses characterized by significant concentration-dependent effects of As. This study provides a comprehensive insight by considering the combined effects of time and concentration of a contaminant and distinguishing its effects on specific tissues, a dimension often overlooked in the existing literature. Subsequent studies should prioritize the analysis of additional contaminants in species with increased sensitivity. [Display omitted] • Arsenic accumulation was slightly higher in digestive gland than in gills and muscle. • Oxidative stress parameters were As concentration-dependent but not time-dependent. • Higher As exposure led to increased RONS only in the digestive gland. • MT increased in gills and digestive gland for all concentrations and exposure times. • Nor As concentration nor exposure time had significant effect on lipoperoxidation. [ABSTRACT FROM AUTHOR]

Abstract Selenium (Se) plays an important role in the immune system and is essential for growth. An 8-week growth trial was conducted to determine the dietary Se requirement of juvenile black sea bream, Acanthopagrus schlegelii. A basal diet was supplemented with Se polysaccharide at levels of 0.34, 0.52, 0.68, 0.91, 1.08 and 3.06 mg Se/kg. Triplicates of black sea bream (13.00 ± 0.20 g) were each hand fed one of the diets. Abnormal fish behavior was not observed, and mortality was not influenced by dietary treatment. Increased levels of Se significantly increased the weight gain in fish fed ≤0.91 mg Se/kg diets, while higher inclusion levels showed a slightly decreasing trend for growth performance. The activities of superoxide dismutase, glutathione peroxidase, catalase and glutathione reductase in the serum and liver significantly increased and levelled off in the fish fed ≥1.08 mg Se/kg diets, while the liver and serum malonaldehyde contents significantly decreased with increasing Se levels. The liver and muscle Se contents linearly increased with increasing dietary Se levels. On the basis of the obtained results, it can be concluded that the dietary Se requirement for juvenile black sea bream appears to be 0.86 mg/kg based on weight gain. Highlights • 0.34–0.91 mg Se/kg improved the growth performance of juvenile black sea bream. • Increased Se level improved the activity of GSH-Px and also enhanced antioxidative status. • Se accumulation in liver and muscle linear increased with dietary Se levels. [ABSTRACT FROM AUTHOR]

Abstract Carotenoids are phytochemicals with strong antioxidant activity against reactive oxygen species that are widely distributed in fruits and vegetables. The beneficial effects of carotenoids on human health have attracted considerable attention. The plasma carotenoid profile in humans is generally recognized to reflect the dietary carotenoid composition. Although carotenoid profile in plasma is believed to correlate well with that in other tissues, the data for tissue accumulation of carotenoids in humans is very limited and poorly understood. In order to test the hypothesis that blood carotenoids reflect tissue accumulation of dietary carotenoids, the cynomolgus monkey was used as a model to determine it's suitable for extrapolation of data on tissue accumulation of carotenoids to humans. Herein, plasma carotenoids were measured in cynomolgus monkeys given a dietary mixture of carotenoids. The findings indicate that cynomolgus monkeys and humans are similar with regard to preferential accumulation of β-cryptoxanthin in the blood and brain. These results suggested that cynomolgus monkeys could be used to collect data on tissue accumulation of carotenoids for extrapolation to humans. The tissue accumulation of carotenoids in other tissues of cynomolgus monkeys that have not yet been evaluated in humans were also investigated, revealing marked differences in carotenoid levels and composition among plasma and various monkey tissues. These results suggest that accumulation of carotenoids in plasma does not reflect necessarily that in tissues, so that predicting the tissue accumulation of carotenoids from plasma carotenoid levels and profiles alone could lead to errors. [ABSTRACT FROM AUTHOR]

Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by Candida albicans. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC0-24/MIC ratio of 53.51 ± 11.12, whereas VFEND® resulted in a 2.5-fold lower AUC0-24/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections. [ABSTRACT FROM AUTHOR]

Increasing anthropogenic activities in the Amazon have led to elevated metals in the aquatic environment. Since fish are the main source of animal protein for the Amazonian population, understanding metal bioaccumulation patterns and physiological impacts is of critical importance. Juvenile tambaqui, a local model species, were exposed to chronic dietary Cu (essential, 500 μg Cu/g food) and Cd (non-essential, 500 μg Cd/g food). Fish were sampled at 10–14, 18–20 and 33–36 days of exposure and the following parameters were analyzed: growth, voluntary food consumption, conversion efficiency, tissue-specific metal bioaccumulation, ammonia and urea-N excretion, O 2 consumption, P crit , hypoxia tolerance, nitrogen quotient, major blood plasma ions and metabolites, gill and gut enzyme activities, and in vitro gut fluid transport. The results indicate no ionoregulatory impacts of either of the metal-contaminated diets at gill, gut, or plasma levels, and no differences in plasma cortisol or lactate. The Cd diet appeared to have suppressed feeding, though overall tank growth was not affected. Bioaccumulation of both metals was observed. Distinct tissue-specific and time-specific patterns were seen. Metal burdens in the edible white muscle remained low. Overall, physiological impacts of the Cu diet were minimal. However dietary Cd increased hypoxia tolerance, as evidenced by decreased P crit , increased time to loss of equilibrium, a lack of plasma glucose elevation, decreased plasma ethanol, and decreased NQ during hypoxia. Blood O 2 transport characteristics (P 50 , Bohr coefficient, hemoglobin, hematocrit) were unaffected, suggesting that tissue level changes in metabolism accounted for the greater hypoxia tolerance in tambaqui fed with a Cd-contaminated diet. [ABSTRACT FROM AUTHOR]

Engineered magnetite nanoparticles (Fe 3 O 4 NPs) have been used in many fields. To prevent particle agglomeration, stabilizers or coatings are often required. While such coatings have been shown to enhance performances, the environmental impact or toxicity of stabilized or coated Fe 3 O 4 NPs remain poorly understood. In an effort to understand the impacts of such coatings on the toxicity of Fe 3 O 4 NPs, we used the transcriptome sequencing (RNA-seq) technique to characterize the gill and liver transcriptomes from adult zebrafish when exposed to bare and starch-stabilized Fe 3 O 4 NPs for 7 days, demonstrating remarkable differences in gene expression profiles, also known as differentially expressed genes (DEGs) profiles, in both tissues. Bare Fe 3 O 4 NPs exerted greater toxicity than starch-coated Fe 3 O 4 NPs in gill; in contrast, starch-Fe 3 O 4 NPs triggered more severe damage on liver, though both bare and stabilized NPs appeared to share similar regulatory mechanisms. Quantitative real-time polymerase chain reactions using six genes each for the two tissues verified the RNA-seq results. The surface coatings play an important role in determining the nanoparticle toxicity, which in turn modulate cell uptake and biological responses, consequently impacting the potential safety and efficacy of nanomaterials. [ABSTRACT FROM AUTHOR]

The study explored (I) the concentration of heavy metals in water samples (II) their bioaccumulation in common carp Cyprinus carpio (III) and the subsequent genotoxicity in the selected organs of carp; from river Kabul, Khyber Pakhtunkhwa Pakistan. Except for Mercury (Hg) the water samples had all the heavy metals within permissible limits of recommended dietary allowance (RDA). Nonetheless a number of heavy metals (Zn, Ni, Cr, Cd, Pb and Hg) showed bioaccumulation at levels higher than permissible. Zinc (Zn) was the most while Cadmium (Cd) was the least accumulated metal in all tissue samples analyzed. The metal burden in different organs of C. carpio was in sequence of intestine > skin > liver > gills > muscle. The Comet assay established DNA damage in selected organs to be in accordance with metal burden; the most to least damage being in sequence of blood > intestine > skin > liver > gills > muscle. In conclusion assessment of DNA damage in the organs of C. carpio appears to be a useful bio-marker to evaluate genotoxic effects of heavy metal pollution. [ABSTRACT FROM AUTHOR]

This feeding trial was carried out to evaluate the effects of different dietary cadmium levels on growth and tissue cadmium content in juvenile parrotfish, Oplegnathus fasciatus, using cadmium chloride (CdCl2) as the cadmium source. Fifteen fish averaging 5.5±0.06 g (mean±SD) were randomly distributed into each of twenty one rectangular fiber tanks of 30 L capacity. Each tank was then randomly assigned to one of three replicates of seven diets containing 0.30 (C0), 21.0 (C21), 40.7 (C41), 83.5 (C83), 162 (C162), 1,387 (C1,387) and 2,743 (C2,743) mg cadmium/kg diet. At the end of sixteen weeks of feeding trial, weight gain (WG), specific growth rate (SGR) and feed efficiency (FE) of fish fed C21 were significantly higher than those of fish fed C83, C162, C1,387 and C2,743 (p

A 12-week growth trial was conducted in a flow-through system to determine dietary selenium (Se) requirement for on-growing gibel carp (initial body weight: 76.2 ± 0.05 g, mean ± SEM). Selenomethionine was supplemented to the basal diet to formulate seven semi-purified diets containing 0.26, 0.58, 0.72, 1.14, 1.34, 1.73 and 2.09 mg Se kg−1 diet. The results showed that plasma superoxide dismutase (SOD) activity significantly increased when fish were fed with 0.58 mg Se kg−1 diet ( P < 0.05) and then decreased at 2.09 mg Se kg−1 diet ( P < 0.05). Plasma T-AOC activity was higher in fish fed with 0.72 mg Se kg−1 diet ( P < 0.05) and plasma malondialdehyde (MDA) was higher in fish fed with 0.26 mg Se kg−1 diet ( P < 0.05). When fish were fed 1.14 mg Se kg−1 diet, hepatic GSH-Px, T-AOC, GSH and CAT activities were significantly higher than those fed with 0.26 mg Se kg−1 diet ( P < 0.05). Hepatic superoxide dismutase (SOD) activity was higher at 1.34 mg Se kg−1 diet ( P < 0.05). Fish liver Se concentrations were significantly higher when fed with 0.72 mg Se kg−1 diet ( P < 0.05) and then kept constant when Se ≥ 0.72 mg kg−1 ( P > 0.05). Whole-body and muscle Se concentrations were higher when fed with 1.34 mg Se kg−1 diet ( P < 0.05) and kept a plateau when Se ≥ 1.34 mg kg−1 ( P > 0.05). In conclusion, based on broken-line regression of hepatic Se concentrations, hepatic SOD activity and hepatic T-AOC activity, dietary Se requirements for on-growing gibel carp was 0.73 mg kg−1, 1.12 mg kg−1 and 1.19 mg kg−1 diet respectively. [ABSTRACT FROM AUTHOR]

Alcohol consumption alters gut microflora and damages intestinal tight junction barriers, which may affect arsenic (As) oral bioavailability. In this study, mice were exposed to arsenate in the diet (6 μg/g) over a 3-week period and gavaged daily with Chinese liquor (0.05 or 0.10 mL per mouse per day). Following ingestion, 78.0% and 72.9% of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL, significantly greater than when As was supplied alone (44.7%). Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or tissue. Significantly lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice, contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular pathway. However, As concentration in the liver, kidney, and intestinal tissue of liquor-treated mice was decreased by 24.4%-42.6%, 27.5%-38.1%, and 28.1%-48.9% compared to control mice. This was likely due to greater renal glomerular filtration rate induced by alcohol, as suggested by significantly lower expression of genes encoding for renal tight junctions. In addition, in mice gavaged daily with 0.05 mL liquor, the serum antidiuretic hormone level was significantly lower than control mice (2.83 ± 0.59 vs. 5.40 ± 1.10 pg/mL), suggesting the diuretic function of alcohol consumption, which may facilitate As elimination via urine. These results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hongbo Li reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China and Jiangsu Agricultural Independent Innovation Program., (© 2023 The Author(s).)

Twelve male 8-month-old lambs were used in a 6-month feeding experiment to determine the effects of dietary Mo, Mo + S and Zn supplements on the body retention and tissue accumulation of dietary Cu, Zn and Fe. The lambs were divided into four groups of three lambs each and each group was fed ad libitum one of four diets. A control diet was based on palm kernel cake (PKC) and grass hay. Three additional diets were the control supplemented with either Mo or Mo + S or Zn. At 3 months of the experiment, feces and urine were collected and sampled for 6 days. At the end of the experiment (6 months), blood was sampled and then the sheep were slaughtered. The liver and kidney were removed and sampled for chemical analysis. In comparison with the control, each dietary supplement decreased (P < 0.05) the Cu concentration in the liver, but only the Mo + S supplement decreased it to a safe range of below 350 μg/g dry matter. This was accompanied by the body retention of dietary Cu of 24.6%, 6.7%, 2.5% and 6.5% for the control, Mo, Mo + S and Zn treatments, respectively. The blood plasma concentration of Cu was decreased (P < 0.05) by the Zn supplement, but was not affected by other supplements (P > 0.05). It was concluded that from the supplements tested, only Mo + S appeared to be effective in reducing the retention and liver accumulation of the dietary Cu to prevent chronic Cu toxicity in sheep fed PKC-based diets.

Waterborne zinc (Zn) is known to cause toxicity to freshwater animals primarily by disrupting calcium (Ca) homeostasis during acute exposure, but its effects in marine and estuarine animals are not well characterized. The present study investigated the effects of salinity on short-term Zn accumulation and sub-lethal toxicity in the euryhaline green shore crab, Carcinus maenas . The kinetic and pharmacological properties of short-term branchial Zn uptake were also examined. Green crabs (n = 10) were exposed to control (no added Zn) and 50 μM (3.25 mg L −1 ) of waterborne Zn (∼25% of 96 h LC 50 in 100 seawater) for 96 h at 3 different salinity regimes (100%, 60% and 20% seawater). Exposure to waterborne Zn increased tissue-specific Zn accumulation across different salinities. However, the maximum accumulation occurred in 20% seawater and no difference was recorded between 60% and 100% seawater. Gills appeared to be the primary site of Zn accumulation, since the accumulation was significantly higher in the gills relative to the hepatopancreas, haemolymph and muscle. Waterborne Zn exposure induced a slight increase in haemolymph osmolality and chloride levels irrespective of salinity. In contrast, Zn exposure elicited marked increases in both haemolymph and gill Ca levels, and these changes were more pronounced in 20% seawater relative to that in 60% or 100% seawater. An in vitro gill perfusion technique was used to examine the characteristics of short-term (1–4 h) branchial Zn uptake over an exposure concentration range of 3–12 μM (200–800 μg L −1 ). The rate of short-term branchial Zn uptake did not change significantly after 2 h, and no difference was recorded in the rate of uptake between the anterior (respiratory) and posterior (ion transporting) gills. The in vitro branchial Zn uptake occurred in a concentration-dependent manner across different salinities. However, the rate of uptake was consistently higher in 20% seawater relative to 60% or 100% seawater – similar to the trend observed with tissue Zn accumulation during in vivo exposure. The short-term branchial Zn uptake was found to be inhibited by lanthanum (a blocker of voltage-independent Ca channels), suggesting that branchial Zn uptake occurs via the Ca transporting pathways, at least in part. Overall, our findings indicate that acute exposure to waterborne Zn leads to the disruption of Zn and Ca homeostasis in green crab, and these effects are exacerbated at the lower salinity. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) were analyzed in 12 tissues of prey (mud carp) and predator (northern snakehead) fish from an e-waste area, South China. The TBBPA concentrations in different tissues ranged from 0.03 to 2.85 ng/g wet weight (ww) in mud carp and 0.04 to 1.30 ng/g ww in northern snakehead. The concentrations of HBCDs ranged from 0.07 to 96.9 ng/g ww in mud carp and 0.18 to 240 ng/g ww in northern snakehead. HBCD levels in tissues were correlated with lipid content for both fish species, while this correlation was only found in mud carp for TBBPA. Meanwhile, northern snakehead exhibited higher HBCD levels but lower TBBPA levels than mud carps. These observations are attributed to the more polar and reactive properties of TBBPA than HBCDs. α-HBCD was the predominant diastereoisomer of HBCDs in all tissues of mud carp and northern snakehead, except for chyme of mud carp. All the analyzed tissues in mud carp showed an enrichment of (+)-α-HBCD enantiomer with EF (enantiomeric fraction) values of 0.53-0.62, but that in northern snakehead showed an enrichment of (−)-α-HBCD enantiomer with EF values of 0.35-0.5. Considering the fact that the mud carp is one of the diet items of northern snakehead, the different enantiomer accumulation characteristics of α-HBCD between the two fish species in the present study indicated that prey and predator fish could prefer to biotransform different enantiomers of α-HBCD. [ABSTRACT FROM AUTHOR]

Ca2+-Mg2+-ATPase is a membrane-bound enzyme and is responsible for regulating cytosolic free calcium.In vitroandin vivoeffects of cadmium were studied on Ca2+-Mg2+-ATPase activity in plasma membrane/mitochondrial fraction ofPenaeus monodonpost larvae.In vitrostudies revealed a concentration-dependent decrease in enzyme activity with an IC50value of 11.02 µM.In vivoexperiments were conducted by exposing the post larvae to 1/10th (0.12 ppm) and 1/5th (0.24 ppm) of LC50values of cadmium for 30 days. Both ATPase activity and metal accumulation were estimated in post larvae exposed to 0.12 and 0.24 ppm of cadmium at different intervals of 24 h, 48 h, 96 h, 10 days and 30 days. ATPase activity showed a gradual decrease in post larvae on exposure to both the sub-lethal concentrations with respect to their controls and the decrease was significant (p < .05) from 96 h onwards in post larvae exposed to 0.24 ppm and 10 days onwards on exposure to 0.12 ppm of cadmium. However, the effect of cadmium was higher in 1/5th than 1/10th sub-lethal concentration and also time-dependent. These enzyme studies were found to correlate with metal accumulation in post larvae at both the exposure concentrations. Disruption of calcium homeostasis might be one of the possible mechanisms of cadmium toxicity in these organisms. [ABSTRACT FROM PUBLISHER]

Glycation starts from nonenzymatic amino-carbonyl reaction that binds carbonyl group of reducing sugars to the amino group of amino acids. Glycation leads to further complex reactions to form advanced glycation end products (AGE). Because AGE are implicated in the gradual development of diabetic complications, tissue accumulation of AGE has been widely examined in various tissues of rats. Avian species are known to have high body temperature and blood glucose concentration compared with mammals. Although these characteristics enabled chickens to be used as experimental models for diabetes mellitus, the information of AGE accumulation in various tissues of chickens has not been limited so far. In the present study, therefore, the radioactive AGE prepared by reacting 14C-glucose and amino acids were intravenously administrated, and comparison of tissue accumulation of 14C-labeled AGE was made between chickens and rats. At 30 min after administration, tissues (18–20) were collected, and the radioactivity incorporated into tissues was determined. High levels of radioactivity per gram of tissue in the liver and kidney were observed in both rats and chickens. In chickens but not rats, a large amount of 14C-labeled AGE incorporated into 1 g of spleen was observed, and the specific accumulation of AGE in the avian spleen might have a particular role in immune response in avian species. [ABSTRACT FROM AUTHOR]

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an important role in maintaining the physiological functions of tissues, and the beneficial effects of DHA/EPA in phospholipid forms have been widely reported. Although lysophosphatidylcholine (LPC) is considered to be the preferred form of DHA supplementation for the brain, the kinetics of DHA and EPA recovery and corresponding changes of n-6 docosapentaenoic acid (DPA) and arachidonic acid (AA) levels in different phospholipid molecules and different tissues after administration of EPA in phosphatidylcholine (PC) and LPC forms and DHA in the LPC form are not clear. Here, we measured the total fatty acids in tissues and fatty acid composition of different phospholipid molecules after gavage administration of equal molar amounts of EPA/DHA in mice with n-3 polyunsaturated fatty acid (PUFA) deficiency induced by maternal dietary deprivation of n-3 PUFA during pregnancy and lactation. The results showed that dietary supplementation with EPA-PC, EPA-LPC, and DHA-LPC exhibited different priorities for EPA or DHA accretion and supplementation efficiency curves in different tissues during the developing period. EPA-PC exhibited a more optimal efficacy in DHA and EPA repletion in serum and hepatic total fatty acids. In terms of DHA recovery in the brain, EPA-LPC and DHA-LPC showed great effects. Meanwhile, the DHA level in total fatty acids and major fractions of phospholipids (PC, PE, and PI + PS) in the heart and bone marrow with the supplementation of DHA-LPC displayed a relatively considerable increase compared with that of EPA supplementation groups. The study provides a reference for the time course of DHA or EPA recovery in phospholipid molecular species in different tissues after the supplementation of EPA-PC, EPA-LPC, and DHA-LPC.

Highlights: [•] There is wide tissue and plasma lycopene variability in response to dietary consumption. [•] Dietary factors include fat amount and type, food matrix, and geometric isomeric configuration. [•] Genetic factors may be lipid transporters, lipoproteins, and carotenoid cleavage enzymes. [•] Most intact lycopene is found in the adipose, liver, and serum. [•] Lycopene products include epoxides, alcohols, aldehydes, carboxylic acids, and carbon dioxide. [ABSTRACT FROM AUTHOR]

Abstract: Brassica juncea and Brassica chinensis were subjected to varying doses of V for 40days to investigate the effects on uptake, tissue accumulation and subcellular distribution of V in two cultivars by differential centrifugation. Subcellular distribution level of V in plant organs was in sequence as follows: root>leaf>stem. There was a significant difference of V accumulation and distribution in roots and shoots between the two vegetables: V content in B. juncea was more than that in B. chinensis. Plant fractionation indicated that 73.4%–78.6% of V in roots, 74.9%–79.8% in stems, and 86.6%–93.2% in leaves were accumulated in cell walls and soluble fractions. V accumulation in roots and leaves increased in cell wall but decreased in soluble fractions with V level increasing. V accumulation in stems increased in soluble fractions but decreased in cell nucleus, mitochondria and chloroplasts. At all doses of V stress, B. juncea had higher tolerance to V than B. chinensis did. It suggests that there is a joint contribution of cell walls and vacuoles in V accumulation and detoxification of B. juncea and B. chinensis. [Copyright &y& Elsevier]

The tissue-specific accumulation and species-specific metabolism of polybrominated diphenyl ethers (PBDEs) in two predator fish species (redtail catfish and oscar fish) feeding on the same prey (tiger barb) that was exposed to technical pentabrominated diphenyl ether (DE-71) in the laboratory were investigated. The trends in the wet-weight tissue concentration of PBDEs in two predatory fish species suggested that the tissue distribution of PBDEs occurs through a series of events involving passive diffusion to the lipid compartment. A comparison of the fugacities of PBDEs in various tissues and in the serum revealed that the liver, gill, and perivisceral adipose tissue readily achieved equilibrium with the serum, but the muscle, kidney, and intestine exhibited the potential to accumulate PBDEs. The lower fugacities of PBDEs in the intestine may have significance in the transportation of PBDEs from prey to predatory fish. No tissue-specific differences in PBDE congener profiles were found, while interspecies differences in PBDE profiles were evident. The difference in profiles between two species could be attributed to species-specific debromination of PBDE. No metabolic debromination of PBDE was observed in redtail catfish, but extensive debromination of PBDEs occurred in oscar fish. Several hydroxylated PBDEs (OH-PBDEs) were detected in serum samples from the two fish species, but no methoxylated PBDEs were found. The similarities in the OH-PBDE congener profile and the ratio of OH-PBDEs to total PBDEs between the two fish species indicated that the hydroxylation of PBDEs might not be species-specific. Environ. Toxicol. Chem. 2013;32:757-763. © 2013 SETAC [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present feeding trial with iodine was to assess pigs' growth performance and carcass characteristics, the iodine accumulation in tissues, and their influences on the thyroid hormones in plasma. Methods: Eighty pigs (33-115 kg body weight) were allotted to 5 dietary treatments: a control group (150 μg I/kg), two potassium iodide [KI] groups (4,000 and 10,000 μg I/kg), and two potassium iodate [KIO] groups (4,000 and 10,000 μg I/kg). Iodine concentration was determined in thyroid gland, liver, kidney, muscle, fat, and skin by ICP-MS. Furthermore, thyroxine (T) and triiodothyronine (T) in plasma were evaluated. Results: High dietary iodine tended to have a negative effect on younger animals' growth (average daily gain, ADG). However, during the entire growth period, the growth performance and carcass characteristics were not influenced by iodine dosages or sources. Irrespective of iodine source, higher iodine doses of diets affected higher iodine stores in all tested tissues except for abdominal fat. Thus, iodine supplementation with 10,000 μg I/kg feed significantly increased iodine content in thyroid gland (+122%), liver (+260%), kidney (+522%), muscle (+131%), and skin (+321%) compared to the control group. However, there was no significance of thyroid hormones in plasma. Conclusions: As a result, pork and fat of pigs showed only low iodine accumulation even in the high-iodine groups. Thus, there should be no risk of an iodine excess in human nutrition and animal health, and the EU-upper level for iodine in pig feed can be maintained. [ABSTRACT FROM AUTHOR]

The resultant effects of lead exposure are seen in almost all the systems of the body and results in toxicity to many organs. Since toxicity depends on its degree of uptake, distribution and metabolism, the authors investigated the differential uptake, accumulation and distribution of lead in organs of males and female Wistar rats following various routes of administration. Group 1 served as control male and control female; group 2 males and females received 5 mg/kg body weight of lead intraperitoneally for 8 days while group 3 males and female rats were administered drinking water containing 100 ppm of lead acetate for 18 days. Tissues were collected for analysis of the lead content using atomic absorption spectroscopy. The relative retention of lead by the tissues was greater in rats exposed to lead by the i.p. route varying in the order of accumulation / uptake in males as lungs > spleen > stomach > kidney > blood > heart and in females as spleen > stomach > heart > kidney > blood > lungs (i.p. route) and (oral route) as for males kidney > lungs > stomach > blood > heart > spleen, and females as kidney > lungs > stomach > blood > heart > spleen. Male Wistar rats showed more accumulation with oral exposure in lungs, spleen and blood with values for kidney and stomach being significantly (p < 0.05) higher when compared with females. Female Wistar rats showed more accumulation with i.p. exposure for spleen and stomach tissues while values for the heart was significantly (p < 0.05) higher than the males. Our findings suggest that lead retention and the organ distribution varied depending upon the sex and route of lead administration. [ABSTRACT FROM PUBLISHER]

WHAT IT IS ALREADY KNOW ABOUT THIS SUBJECT • Amiodarone is a highly effective antiarrhythmic drug, but is limited in practice by its adverse effects, which are frequent on long-term administration and can be severe. • Amiodarone is very lipophilic and attains high concentrations in many tissues. • Excessive accumulation in tissues is suspected as a possible cause of some of its adverse events, but sampling affected tissues (e.g. lung, thyroid, heart) in vivo is difficult. • Subcutaneous adipose tissue is more easily obtained, and studying concentrations of amiodarone and N-desethyl-amiodarone there could help to understand how amiodarone distributes and accumulates in tissues in general. WHAT THIS STUDY ADDS • No evidence of excessive or unexpected accumulation of amiodarone in fat tissue, with respect to dose, was found in patients treated for >3 months. • Concentrations in plasma and subcutaneous fat tissue were better related to maintenance daily dose than to cumulated dose or treatment duration. • Clinically relevant adverse effects of amiodarone, for the most part hypothyroidism, were significantly associated with longer duration of treatment and larger cumulated doses. • In contrast, adverse events were not correlated with higher amiodarone or N-desethyl-amiodarone concentrations, whether in plasma or in adipose subcutaneous tissue. • The measurement of these concentrations does not seem useful in predicting the risk of adverse effects. AIMS To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects. METHODS Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas. Concentrations were measured by liquid chromatography–tandem mass spectrometry. RESULTS Plasma levels of amiodarone and N-desethyl-amiodarone were significantly correlated with daily maintenance doses ( R= 0.52, P= 0.003). Amiodarone concentrations in fat tissue were four to 226 times (mean 55) higher than in plasma, and well correlated with plasma levels ( R= 0.68, P < 0.001). Concentrations of amiodarone and N-desethyl-amiodarone in adipose tissue did not significantly increase with higher total cumulated doses or longer treatment duration. Nine of 12 patients who had received amiodarone for ≥2 years developed clinically important adverse effects, predominantly hypothyroidism ( n= 6), compared with two of 18 patients treated for less time (relative risk 6.75; 95% confidence interval 1.8, 26). The incidence of those adverse effects was not significantly associated with amiodarone concentrations, whether in plasma or in adipose tissue. CONCLUSIONS We found no evidence of excessive or unexpected accumulation of amiodarone in fat tissue on long-term administration. Late amiodarone adverse effects, particularly hypothyroidism, are associated with longer exposure times, but do not seem to be explained by higher concentrations in plasma or in fat tissue. [ABSTRACT FROM AUTHOR]

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