The effects of BPA-BNCT on normal bone: determination of the CBE value in mice‡.

Boron neutron capture therapy (BNCT) with p-boronophenylalanine (BPA) is expected to have less effect on the decrease in normal bone strength than X-ray therapy. However, the compound biological effectiveness (CBE) value necessary to convert the boron neutron capture reaction (BNCR) dose into a bioequivalent X-ray dose has not been determined yet. The purpose of this study was to evaluate the influence of BNCT on normal bone in mice and to elucidate the CBE factor. We first searched the distribution of BPA in the normal bone of C3H/He mice and then measured the changes in bone strength after irradiation. The CBE value was determined when the decrease in bone strength was set as an index of the BNCT effect. The 10B concentrations in the tibia after subcutaneous injection of 125, 250 and 500 mg/kg BPA were measured by prompt gamma-ray spectroscopy and inductively coupled plasma (ICP)-atomic emission spectrometry. The 10B mapping in the tibia was examined by alpha-track autoradiography and laser ablation-ICP-mass spectrometry. The 10B concentration increased dose-dependently; moreover, the concentrations were maintained until 120 min after BPA administration. The administered 10B in the tibia was abundantly accumulated in the growth cartilage, trabecular bone and bone marrow. The bone strength was analyzed by a three-point bending test 12 weeks after irradiation. The bending strength of the tibia decreased dose-dependently after the irradiation of X-ray, neutron and BNCR. The CBE factor was obtained as 2.27 by comparing these dose-effect curves; the value determined in this study will enable an accurate dosimetry of normal bone.

Lipoprotein lipase concentration in umbilical cord blood reflects neonatal birth weight.

BACKGROUND: Insulin resistance (IR) is exacerbated during pregnancy via increases in insulin counterregulatory hormones. Maternal lipids are strong determinants of neonatal growth, although triglyceride-rich lipoproteins (TGRLs) cannot be transferred directly to the fetus through the placenta. The catabolism of TGRLs under physiological IR and the reduced synthesis of lipoprotein lipase (LPL) are poorly understood. We examined the association of maternal and umbilical cord blood (UCB)-LPL concentrations with maternal metabolic parameters and fetal development. METHODS: Changes in anthropometric measures and lipid-, glucose-, and insulin-related parameters, including maternal and UCB-LPL concentrations, were examined in 69 women during pregnancy. The relationship between those parameters and neonatal birth weight was assessed. RESULTS: Parameters reflecting glucose metabolism did not change during pregnancy, whereas those associated with lipid metabolism and IR changed markedly, particularly in the second and third trimesters. In the third trimester, the maternal LPL concentration gradually decreased, by 54%, whereas the UCB-LPL concentration was âˆ¼2-fold higher than the maternal LPL concentration. Univariate and multivariate analyses showed that the UCB-LPL concentration was a significant determinant of neonatal birth weight, together with placental birth weight. CONCLUSION: The LPL concentration in UCB reflects neonatal development under a decreased LPL concentration in maternal serum.

Comparison of lithium levels between suicide and non-suicide fatalities: Cross-sectional study.

Ecological studies have suggested the protective effect of micro-dose lithium in drinking water against suicide, however, the association between body lithium level and suicide is unknown. We aimed to compare body lithium levels between suicide and non-suicide fatalities. This cross-sectional study included 12 suicides and 16 non-suicides who were examined or dissected at the Tokyo Medical Examiner's Office from March 2018 to June 2021. The aqueous humor lithium concentration was measured twice using inductively coupled plasma mass spectrometry. Analysis of covariance (ANCOVA) was used to compare the lithium concentration between suicides and non-suicides. Mixed-effects model was conducted to account for all lithium concentration data. The aqueous humor lithium concentration did not change after death (t(7) = -0.70, [Formula: see text], SE = 0.03, 95% CI = [-0.09, 0.05], P = 0.51, Cohen's d = 0.01). The aqueous humor lithium concentration was lower in suicides (mean 0.50 µg/L (variance s2 0.04)) than in non-suicides (mean 0.92 µg/L (s2 0.07)) (t(26) = 4.47, [Formula: see text], SE = 0.09, 95% CI = [0.22 to 0.61], P < 0.001, Cohen's d = 1.71). The ANCOVA showed that death by suicide was significantly associated with lower lithium concentration (F(1, 24) = 8.57, P = 0.007), and the effect size was large (ηp2 = 0.26). The random intercept model showed a significant effect of suicide on aqueous humor lithium concentration (b = -0.261, SE = 0.102, 95% CI = [-0.471 to -0.051], t(24) = -2.568, P = 0.017). The results of this study demonstrate that even micro-dose lithium is associated with suicide death. Clinical studies are warranted to examine the effects of micro-dose lithium on suicide prevention.

Spatial localization of cadmium and metallothionein in the kidneys of mice at the early phase of cadmium accumulation.

Chronic exposure to cadmium (Cd) leads to an accumulation of Cd in the kidneys. Metallothionein (MT) is a low-molecular-weight protein having a high affinity for Cd. Cd bound to MT in serum is filtered through the glomeruli of kidney nephrons and reabsorbed by endocytosis into the proximal tubules from the luminal side. Accumulation of Cd in renal cells induces MT synthesis, leading to long-term deposition of Cd and the suppression of Cd toxicity. Recently, many studies have investigated the tissue distribution of metals using laser ablation ICP-MS (LA-ICP-MS). However, little information has been available regarding renal Cd distribution. Hence, we dually investigated the renal distribution of Cd by LA-ICP-MS and that of MT by immunohistochemistry to clarify the dose- and time-dependent changes in the distributions of Cd and MT in mice exposed to Cd from drinking water for 1, 2, and 4 months. Both Cd and MT exhibited characteristic heterogeneous distribution patterns in the renal cortex. The accumulation of Cd and MT near the surface of the cortex suggests a preferential accumulation of Cd in the surface nephrons. MT distribution was more pronounced in the proximal tubules than in the distal tubules, and there were clear differences in MT immunostaining even among the proximal tubules. The heterogeneous localization of MT may reflect the nephron-specific accumulation of Cd. Combining elemental imaging of Cd with immunostaining of MT proved a successful strategy to reveal the characteristic renal Cd distribution, especially in the early stages of Cd accumulation.

Blood cobalt ion level in patients with different sizes of cobalt/chrome femoral head with the Accolade TMZF stem.

BACKGROUND: Corrosion of stem-cobalt/chromium (Co/Cr) head interface and subsequent systemic Co ion complication have been a clinical concern after total hip arthroplasty (THA). The aim of this study is to investigate correlation between type of femoral head and blood Co ion level. METHODS: One hundred four patients with THA using accolade TMZF and Co/Cr femoral head (32-mm; 55 cases, 36-mm; 20 cases, dual mobility system (DM) with 22.2 or 28-mm inner head; 29 cases) participated in this study, and blood Co ion concentration test was performed in patients a minimum of four years after THA. RESULTS: DM group was significantly older than 32-mm and 36-mm group (DM: 73.9 ± 4.6, 32-mm: 63.3 ± 8.5, 36-mm: 66.8 ± 10.5). The median (interquartile range) blood Co concentration of each group was 32-mm group 0.26 µg/L (0.69), 36-mm group; 0.21 µg/L (0.30); and DM group 0.21 µg/L (0.13). There was a significant difference of Co concentration between DM and 32-mm group (p = 0.023). Abnormal values of the blood Co concentration (> 1 µg/L) were observed in the 32-mm group; 12 cases (21.8%), 36-mm group; 2 cases (10.0%); and DM group; 0 case (0%) (p = 0.018). CONCLUSIONS: Co blood concentration differed among the different sizes of Co/Cr femoral head. THA using DM is a safe option with low risk of complication from cobalt ion if it is used for elderly patients.

Improvement of spatial resolution of elemental imaging using laser ablation-ICP-mass spectrometry.

Laser ablation-ICP-mass spectrometer (LA-ICPMS) now becomes one of the most principal analytical technique for mapping analysis for major to trace elements in rocks, minerals, functional materials, or biological tissue samples. In this study, imaging analysis was conducted with coupling of small volume cell and off-set laser ablation protocol to improve the spatial resolution. Combination of newly designed small volume cell and in-torch gas mixing protocols provides faster washout time of the signals (about 0.8 s for reducing 238U being one part in a hundred, 1% level). This is very important to improve the spatial resolution in a direction of laser scanning. Moreover, combination of small distances between the laser-line scan (laser pitch distance) and preferential and total ablation of only biological tissue samples placed on glass substrate results in laser ablation of smaller areas than the size of laser ablation pit (shaving ablation). With the shaving ablation, laser-line scanning with narrower-band width (e.g., 2 µm) can be achieved even by the laser beam of 8 µm diameter. To demonstrate the practical usage of the present technique, imaging analysis of Gd-ethylenediamine tetra-methylene phosphonic acid-doped mouse bone was conducted. Preferential distribution of Gd at the edge of the apatite cell was more clearly identified by the present technique. Combination of the shorter washout system setup and the shaving ablation protocol enables us to improve the spatial resolution of the elemental imaging obtained with the LA-ICPMS technique.

Naturally absorbed lithium may prevent suicide attempts and deliberate self-harm while eicosapentaenoic acid may prevent deliberate self-harm and arachidonic acid may be a risk factor for deliberate self-harm: The updated different findings in new analyses.

Background: Since our previous investigation on the effects of trace lithium, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) on deliberate self-harm and suicide attempts in 2018, to our knowledge, no replication study has been conducted on this topic. Subjects and methods: We increased 37 new patients and totally 234 patients were re-analyzed to further investigate the association of suicide-related behaviors with levels of trace lithium, EPA, DHA, and AA in a different way to avoid multicollinearity. Results: Higher lithium levels were significantly associated with fewer suicide attempts and deliberate self-harm, higher EPA levels were significantly associated with fewer deliberate self-harm, and higher AA levels were significantly associated with more deliberate self-harm. Discussion: Although the sample size was only slightly larger than the previous study, the present results were clearly different from the previous ones due to the use of different statistical analyses to avoid multicollinearity. Conclusion: The present findings suggest that naturally absorbed lithium may protect against suicide and deliberate self-harm, while naturally absorbed EPA may protect against deliberate self-harm. However, naturally absorbed AA may be a risk factor for deliberate self-harm.

Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.

Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.

An Investigation of the Wild Rat Crown Incisor as an Indicator of Lead (Pb) Exposure Using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and Laser Ablation ICP-MS.

Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats (Rattus rattus) sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of R. rattus rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated (r = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and R. rattus rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.

Horror of three synergistic factors in THA: high mechanical stress, dissimilar metals, low elasticity stem: a case report.

BACKGROUND: A large-diameter femoral head is effective in preventing dislocation after total hip arthroplasty. However, although rare, catastrophic stem tribocorrosion may occur at the head-stem junction. CASE PRESENTATION: A 70-year-old woman underwent revision surgery 7.5 years after total hip arthroplasty because of catastrophic stem corrosion with dissociation of the metal head (cobalt/chromium) and stem (TiMo12Zr6Fe2). Abnormal levels of cobalt were found in the intra-articular fluid, capsule, hip muscle, and blood. Revision surgery was performed via the direct anterior approach. The well-fixed femoral stem was explanted, and a cemented stainless stem with stainless head was implanted. Three months after the revision surgery, the cobalt concentration in the blood had decreased to normal. CONCLUSIONS: Stem dissociation in the present case might have been caused by synergistic combination of a 36-mm-diameter femoral head and long neck length offset with high frictional torque, a cobalt-chromium head with a high risk of galvanic corrosion, and a TMZF (TiMo12Zr6Fe2) alloy stem with a low Young's modulus of elasticity. The combination of these factors must be avoided.

Hair Metal Levels and Childhood Weight Gain.

BACKGROUND: Exposure to toxic metals remains a public health problem with lifelong impacts on childhood growth and development. We aimed to investigate metals effects on preschool children's anthropometric variables. METHODS: The study was conducted in Tehran, Iran, from Jul 2013 to Mar 2016. We measured scalp hair metal concentrations (lead, cadmium, arsenic, zinc, manganese, and cobalt), using inductively coupled plasma mass spectrometry, in 207 preschool children's (36 to 72 months old). RESULTS: A significant negative correlation between children's hair lead levels and children's weight was found (r= -0.178, P<0.05). Linear regression analysis confirmed the relationship when adjusted for the confounders, including children's age, sex, height, family income, and maternal education (ß= -0.191; t= -3.426, P< 0.01). The ANOVA analysis showed a significant (P<0.01) difference between hair lead level and children's weight-for-age percentiles. Totally and separately, in almost all weight percentiles, hair lead levels were higher in girls than boys. CONCLUSION: The present study on Iranian children showed the current levels of lead exposure might negatively influence on children growth, with higher risk for girls than boys.

Single-dose toxicity study by intra-arterial injection of 10BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma.

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as 10B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of 10BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of 10B compound as multidisciplinary treatments for HCC.

Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry.

Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells.

Cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine treated by percutaneous cardiopulmonary bypass: a case report.

BACKGROUND: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass. CASE PRESENTATION: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state. CONCLUSIONS: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.

Risk factors for occupational accidents in agricultural enterprises in Japan.

In Japan, the agricultural working environment has undergone significant changes from self-employment to enterprises and employees. As the structure of the agricultural industry changes, there has been a growing interest in occupational health and safety because agriculture is a hazardous industry. However, the public is not aware of the actual situation regarding occupational accidents in agricultural enterprises because most Japanese farmers are not necessarily required to report occupational accidents. The aim of this study is to explore the risk factors regarding occupational accidents for Japanese agricultural employees. We conducted a cross-sectional study among 1,606 employees at 101 agricultural enterprises in Japan. Information on occupational accidents, personal characteristics, and working conditions was collected by questionnaires. A total of 337 valid responses were obtained. Of these respondents, 104 (30.9%) experienced occupational accidents. Multiple logistic regression analysis revealed that permanent employment (OR 3.67, 95% CI, 1.84-7.33), pesticide use (OR 2.61, 95% CI, 1.52-4.47), and long working hours (OR 1.76, 95% CI, 1.15-2.68) were associated with the risk of occupational accidents. This study revealed the risk factors for occupational accidents for Japanese agricultural employees. It is suggested that work-hour restrictions for permanent employees might contribute to reducing occupational accidents.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

Characterization and imaging of lead distribution in bones of lead-exposed birds by ICP-MS and LA-ICP-MS.

Lead (Pb) poisoning in raptors and water birds is a serious problem in many countries. However, only a small fraction of Pb poisoning has been detected in birds. Bone specimens may be useful indices of Pb exposure because bones contain ∼90% of the total Pb body burden. The original purpose of this study was to comprehensively analyze Pb accumulation in various bone types using inductively coupled plasma-mass spectrometry (ICP-MS). Since our results showed that Pb accumulation differed greatly depending on bone type, a secondary objective was defined, aiming to investigate the fine Pb distribution and its relation to bone structure and bone marrow by using laser ablation (LA)-ICP-MS. Our findings suggested that bone samples (1) consisting of trabecular tissue and (2) those that contain bone marrow could accumulate high levels of Pb following acute exposure. The shorter turnover time of trabecular bone can cause a rapid accumulation of Pb, and bone marrow may have an important role for internal exposure of Pb to bone tissue. Pb is accumulated in bones via blood flow, and bone marrow receives blood from outside the bones. In conclusion, bone samples provide valuable information on Pb exposure and could be useful to investigate and understand mortalities related to suspected Pb poisoning.

Changes in thallium distribution in the scalp hair after an intoxication incident.

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.