A deuterium tracer experiment for simulating accumulation and elimination of organically bound tritium in an edible flatfish, olive flounder.

Tritium (3H, T) is discharged by nuclear facilities into coastal oceans as tritiated water (HTO). When the concentration of HTO in seawater increases, the accumulation of organically bound tritium (OBT) in edible fish becomes a concern because of its longer residence time than HTO. To evaluate the accumulation potential of OBT in olive flounder (Paralichthys olivaceus), a commercially important edible fish in northeast Asia, we experimentally exposed the fish to seawater enriched with deuterium (2H, D) as a substitute for tritium. Progressive increases and decreases in the concentration of organically bound deuterium (OBD) were observed in the edible part (i.e., muscle) of the fish during the period of exposure to 2H (161 days) and the subsequent period of elimination of OBD (196 days). The measured concentration of OBD was analyzed using a newly developed single-compartment model to describe the metabolism of OBD in muscle via the following three transfer pathways: formation of OBD from 2H in water, elimination of OBD by catabolism, and ingestion of feed with natural abundance of OBD. The model estimates were in good agreement with the measured muscle OBD concentrations. The formation and elimination rate constants for OBD in the muscle were estimated by fitting our model to the measured data. The biological half-life of OBT in the muscle, estimated from the elimination rate constant, was 133 days, which was far longer than that of HTO in the free water of the muscle. Our model facilitates the estimation of OBT accumulation potential in olive flounder inhabiting coastal areas near nuclear facilities, and thus, will help to assess the radiation dose that humans are exposed to from ingesting seafood.

An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report.

BACKGROUND Alcohol abuse inhibits the ability of the liver to release glucose into the bloodstream, primarily by inhibiting gluconeogenesis, so chronic alcohol abusers exhibit hypoglycemia after drinking alcohol without eating; this is called alcohol-induced hypoglycemia. Central adrenal insufficiency (AI) is characterized by cortisol deficiency due to a lack of adrenocorticotropic hormone. It is challenging to diagnose central AI, as it usually presents with nonspecific symptoms, such as asthenia, anorexia, and a tendency toward hypoglycemia. Here, we report a rare case of central AI that presented with AI symptoms shortly after an alcohol-induced hypoglycemic coma. CASE REPORT An 81-year-old Japanese man who had been a moderate drinker for >40 years developed a hypoglycemic coma after consuming a large amount of sake (alcohol, 80 g) without eating. After the hypoglycemia was treated with a glucose infusion, he rapidly recovered consciousness. After stopping alcohol consumption and following a balanced diet, he had normal plasma glucose levels. However, 1 week later, he developed asthenia and anorexia. The endocrinological investigation results indicated central AI. He was started on oral hydrocortisone (15 mg/day), which relieved his AI symptoms. CONCLUSIONS Cases of central AI associated with alcohol-induced hypoglycemic attacks have been reported. Our patient developed AI symptoms following an alcohol-induced hypoglycemic attack. His alcohol-induced hypoglycemic attack likely occurred in combination with a developing cortisol deficiency. This case highlights the importance of considering central AI in chronic alcohol abusers presenting with nonspecific symptoms, including asthenia and anorexia, especially when patients have previously experienced alcohol-induced hypoglycemic attacks.

Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.

Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Hypoglycemic Hemiplegia Associated with Reversible Narrowing of the Contralateral Middle Cerebral Artery in a Patient with Adrenal Insufficiency.

A 56-year-old man with a 2.5-month history of anorexia developed sweating, weakness, and left hemiplegia and hemispatial neglect. Brain magnetic resonance imaging detected no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery (MCA). The focal neurological signs and narrowing of the MCA resolved after detection and correction of hypoglycemia. Endocrinological examinations indicated adrenal insufficiency. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, although the mechanisms involved remain unknown. Combined hypoglycemia and decreased MCA blood flow associated with vasospasm probably induced regionally severe neuroglycopenia with ischemia, which presented as focal neurological symptoms.

RETENTION OF ORGANICALLY BOUND DEUTERIUM IN GRASS PLANTS EXPOSED TO HEAVY WATER VAPOUR AT DIFFERENT GROWTH STAGES.

Potted timothy grass plants were exposed to heavy water (HDO) vapour at seven different periods during the third growth of harvestable shoots (the part 5-cm above the ground surface), and the concentration of non-exchangeable organically bound deuterium (NE-OBD) was measured in harvestable shoots, stubbles and roots at the third harvest. The excess concentration of NE-OBD was obtained as an increase in the concentration of NE-OBD against the background level. On average, this value was 1.8- to 2.6-fold higher in the harvestable shoots than in the stubble for plants exposed to HDO vapour during the period when the harvestable shoots grew faster than the stubble. Our results suggest that the separation of harvestable shoots and stubble, both of which are generally combined as one part in studies on the metabolism of organically bound tritium (OBT) in grass, could contribute to a realistic evaluation of OBT transfer from timothy to livestock.

METABOLISMS OF 13C IN CATTLE SEMITENDINOSUS MUSCLE AFTER ADMINISTRATION OF 13C LABELED ORCHARD GRASS.

14C released from nuclear facilities is transferred to cattle through their consumption of 14C contaminated grasses. To estimate the concentrations of 14C in their meat, we conducted two sets of experiments. In the first experiment, 230 mg of 13C per day was administered to cattle aged 10 months for 28 days in the form of 13C-labeled grass. The 13C concentration in the semitendinosus muscle decreased exponentially after reaching its peak value. The mean half-life was 76 ± 13 days. In the second experiment, 550 mg of 13C per day was administered to 24-month-old cattle. The change in the semitendinosus muscle was smaller than that recorded in the first experiment, even though the amount of 13C administered per body weight was slightly higher than that in the first experiment. Consequently, the half-life was not determined. Therefore, further studies are required to clarify the metabolism of carbon in 2-year-old cattle.

Investigation of ratio of carbon to hydrogen (C/H ratio) in agricultural plants for further estimation of their productivity of organically bound tritium.

The carbon to hydrogen ratio (C/H ratio, w/w) in plants is a key factor in estimating the amount of hydrogen in the photosynthetic product. The amount of hydrogen calculated from photosynthetic model estimation associated with the C/H ratio is an essential parameter of the estimation model of productivity of organically bound tritium (OBT) by plants. To propose a sophisticated estimation model of OBT by agricultural plants, temporal changes in the C/H ratio of six plant species (Japanese radish, cabbage, orchard grass, paddy field rice, apple, and radish) during their cultivation were investigated for each plant part. The C/H ratio in the plants cultivated in the field and growth chamber generally exceeded 6, which is the value for the primary photosynthetic monosaccharides, such as glucose and fructose (both chemical formulae, C6H12O6). In the vegetative parts (e.g. Japanese radish leaves, cabbage leaves and roots, rice leaves and roots, and radish leaves and fine roots) the C/H ratio fluctuated irregularly or remained constant within an approximate range of 6.6-7.3 during cultivation. The C/H ratio in enlarged organs (e.g. Japanese radish root, rice ear, apple fruit, and radish main root) decreased continuously, approaching 6. These results suggest that the C/H ratio can be generally set as approximately 6.9 except for enlarged organs, in which the ratio may change over time during cultivation, within an approximate range of 6-7.

Imaging Findings in a Case of Bacteremia Caused by Non-Typhoidal Salmonella Associated with a Congenital Venous Malformation.

Non-typhoidal Salmonella infection is a typical food-poisoning disease, which rarely causes bacteremia, except in immunocompromised individuals. We report the case of a healthy adult in whom a varicose vein associated with a lower-leg venous malformation was considered the source of Salmonella bacteremia.

Parkinson's disease and parkinsonism: Clinicopathological discrepancies on diagnosis in three patients.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The cardinal neuropathological features of PD include selective and progressive loss of pigmented neurons in the substantia nigra, deficiencies in dopaminergic signaling in the striatum, and occurrence of phosphorylated α-synuclein-identified Lewy bodies in the nervous system. Parkinsonism, the clinical presentation of movement disorders seen in PD, is a feature shared commonly by other pathologically distinct neurodegenerative diseases, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Consequently, it is sometimes difficult to distinguish PD from such parkinsonism-related neurological disorders. In addition, parkinsonism is not always a feature of certain neurodegenerative diseases, and it can sometimes develop as a result of various forms of drug intoxication or cerebrovascular disease. Here, we describe the clinicopathological features of three patients (cases 1, 2, and 3) diagnosed as having PSP, MSA, and PD, respectively, in each of whom the postmortem histopathological diagnosis differed from the final clinical diagnosis. Neuropathologically, they had suffered from coexistent disorders: PD, MSA, and argyrophilic grain disease (case 1); PD (case 2); and vascular parkinsonism (case 3). The variety of patients showing features of parkinsonism underlines the importance of careful long-term follow up followed by postmortem neuropathological evaluation.

Ten-year radiocesium fluvial discharge patterns from watersheds contaminated by the Fukushima nuclear power plant accident.

After the Fukushima Dai-ichi nuclear power plant accident in March 2011, the fluvial discharge of 137Cs from watersheds to rivers was analyzed between 2011 and 2021. The concentrations of dissolved and particulate 137Cs were measured in river water samples collected from two rivers (the Hiso and Wariki rivers, mainly draining farmlands and forests, respectively) draining approximately 4-7 km2 watersheds in a montane area (the areal deposition of 134+137Cs; 1-3 MBq·m-2 in March 2011) of Iitate Village, Fukushima. Over the 10 yr analysis, the particulate 137Cs concentrations in the Hiso and Wariki rivers decreased by 70 and 50 times, respectively, and that of the dissolved form decreased by 150 and 130 times, respectively. Moreover, the apparent Kd (distribution coefficient) of 137Cs for water samples from both rivers have increased gradually over these periods. In 2011, the 137Cs discharge rates through the Hiso and Wariki rivers were 0.63% and 0.46% per year of the total amount of 137Cs deposited in their catchments, respectively; however, by 2021, these rates had decreased to 0.09% and 0.03% per year. The cumulative 137Cs discharge rates over 10 yr in the farmland- and forest-dominated rivers were 1.95% and 1.33%, respectively. These rates of the farmland-dominated river were ∼1.4-fold greater than those of the forest-dominated river. Moreover, ∼90% of the of the discharge occurred in particulate form while the remaining ∼10% was in the dissolved form. Thus, 137Cs deposited within these watersheds due to the accident was gradually discharged by the rivers over the 10-yr period; however, the majority remains stored in soils and litters etc. of the catchment area. These results indicate that 137Cs outflow from land-to-ocean will be limited in the future, as the river export of 137Cs is expected to continue decreasing.

In situ experimental exposure of fruit-bearing shoots of apple trees to 13CO2 and construction of a dynamic transfer model of carbon.

Evaluating the transfer and metabolism of carbon (C) in apple fruit is key to estimating the potential accumulation of atmospheric 14C in fruit near and around nuclear facilities. We developed a dynamic compartment model for apple fruit-bearing shoots, assuming that the shoots are a simple unit of source and sink for photoassimilates. Fruit-bearing shoots of Malus domestica "Fuji" at different fruit growth stages were exposed to 13CO2in situ, followed by sampling at 72 h after exposure or at harvest. The 13C/(13C+12C) mole ratio in fruits, leaves, and current branch were measured to construct a five-compartment model of 13C (fruit, each fast and slow component of leaves, and current branch). The C inventories in the compartments were presented in accordance with the measured growth curves of C in the organs. The model simulated the 13C dynamics in plant tissues well. Simulation results of photoassimilate distribution using the model indicated that the retention of photoassimilated C at the harvest depended on the growth rate of C in the organs at the exposure.

A Case of Acute Kidney Injury Associated with Leriche Syndrome.

Leriche syndrome is an aortoiliac occlusive disease with three chief symptoms: claudication, impotence, and weak femoral pulse. It can also cause occlusion of the aorta up to the level of the renal arteries. We report a case in which aortoiliac bypass and renal artery thrombectomy were effective in ameliorating acute kidney injury caused by bilateral renal artery thrombosis.

Short-term metabolism of biologically incorporated 125I ingested by olive flounder (Paralichthys olivaceus).

Iodine-129 with a long half-time of 1.6 × 107 y was discharged into the Pacific Ocean during the final safety tests of the first commercial nuclear fuel reprocessing plant in Japan, at Rokkasho, Aomori Prefecture. Olive flounder (Paralichthys olivaceus) is an important fishery along this coast. It is necessary to determine whether 129I accumulates in this species to assess the possible public acceptance. We developed a short-term metabolism model of 125I in the flounder using retention data for 1-6 days after the olive flounder had ingested a freshwater fish species, medaka (Oryzias latipes), that had been labeled with 125I by keeping them in water containing 125I for 7 days. A single compartment model constructed from whole-body retention data for 125I in the olive flounder, excluding the gastrointestinal tract and its contents, revealed a biological half-time of 2.9 days for 125I. When the gill and other tissues were separated to individual compartments, the biological half-time in the gill was three times longer than that in the other tissue, though the half-time in the gill is not statistically significant. The distribution of 125I among various tissues in the flounder 6 days after the ingestion of labeled medaka once a day for 6 days differed from that of stable I, suggesting that the biological half-time is longer in certain tissues. Further study is necessary to elucidate the metabolism of radioiodine in the flounder.

Inhibition of tissue-nonspecific alkaline phosphatase protects against medial arterial calcification and improves survival probability in the CKD-MBD mouse model.

Medial arterial calcification (MAC) is a major complication of chronic kidney disease (CKD) and an indicator of poor prognosis. Aortic overexpression of tissue-nonspecific alkaline phosphatase (TNAP) accelerates MAC formation. The present study aimed to assess whether a TNAP inhibitor, SBI-425, protects against MAC and improves survival probability in a CKD-mineral and bone disorder (MBD) mouse model. CKD-MBD mice were divided in three groups: vehicle, SBI-10, and SBI-30. They were fed a 0.2% adenine and 0.8% phosphorus diet from 14 to 20 weeks of age to induce CKD, followed by a high-phosphorus (0.2% adenine and 1.8% phosphorus) diet for another 6 weeks. At 14-20 weeks of age, mice in the SBI-10 and SBI-30 groups were given 10 and 30 mg/kg SBI-425 by gavage once a day, respectively, while vehicle-group mice were given distilled water as vehicle. Control mice were fed a standard chow (0.8% phosphorus) between the ages of 8 and 20 weeks. Computed tomography imaging, histology, and aortic tissue calcium content revealed that, compared to vehicle animals, SBI-425 nearly halted the formation of MAC. Mice in the control, SBI-10 and SBI-30 groups exhibited 100% survival, which was significantly better than vehicle-treated mice (57.1%). Aortic mRNA expression of Alpl, encoding TNAP, as well as plasma and aortic tissue TNAP activity, were suppressed by SBI-425 administration, whereas plasma pyrophosphate increased. We conclude that a TNAP inhibitor successfully protected the vasculature from MAC and improved survival rate in a mouse CKD-MBD model, without causing any adverse effects on normal skeletal formation and residual renal function. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Isolated Adrenocorticotropic Hormone Deficiency Presenting with Severe Hyponatremia and Rhabdomyolysis: A Case Report and Literature Review.

BACKGROUND Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder characterized by central adrenal insufficiency (AI) but normal secretion of pituitary hormones other than adrenocorticotropic hormone. IAD usually presents with unspecific symptoms of AI, such as anorexia and fatigue, but some patients present with a variety of atypical manifestations. Rhabdomyolysis is a potentially life-threatening clinical syndrome caused by skeletal muscle injury with the release of muscle cell contents into the circulation. A wide variety of disorders can cause rhabdomyolysis. Herein, we report an unusual case of IAD presenting with hyponatremia and rhabdomyolysis. CASE REPORT A 67-year-old Japanese woman with a 2-month history of anorexia and fatigue was diagnosed with severe hyponatremia (serum sodium, 118 mEq/L) and rhabdomyolysis (serum creatine phosphokinase, 6968 IU/L), after 2 days of vomiting and muscle weakness. Physical and laboratory findings did not show dehydration or peripheral edema. Her rhabdomyolysis resolved with normalization of serum sodium levels during administration of sodium chloride. However, her anorexia and fatigue remained unresolved. After reducing the amount of sodium chloride administered, the patient still had hyponatremia. Detailed endocrinological examinations indicated IAD; her hyponatremia was associated with inappropriately high plasma arginine vasopressin levels. The patient received corticosteroid replacement therapy, which resolved her anorexia, fatigue, excessive arginine vasopressin, and hyponatremia. CONCLUSIONS This case highlights the importance of considering the possibility of central AI in patients with hyponatremia and excessive arginine vasopressin levels. In addition, rhabdomyolysis associated with hyponatremia can be an important manifestation of IAD.

Metabolomics analysis elucidates unique influences on purine / pyrimidine metabolism by xanthine oxidoreductase inhibitors in a rat model of renal ischemia-reperfusion injury.

BACKGROUND: Clinically applied as anti-gout drugs, xanthine oxidoreductase (XOR) inhibitors, especially the potent, selective, non-purine-analog XOR inhibitors febuxostat and topiroxostat, exert organ-protective effects. We tested the hypothesis that preservation of tissue concentrations of high-energy phosphates, such as ATP and ADP, contributes to organ-protective effects through CE-TOFMS metabolomics. METHODS: Rats were subjected to 30 min of renal ischemia-reperfusion (I/R) injury 60 min after oral administration of 10 mg/kg febuxostat, 10 mg/kg topiroxostat, 50 mg/kg allopurinol, or vehicle. RESULTS: In non-purine-analog XOR inhibitor-treated groups, renal concentrations of high-energy phosphates were greater before and after I/R injury, and renal adenine compounds were less depleted by I/R injury than in the vehicle and allopurinol groups. These findings were well in accordance with the proposed hypothesis that the recomposition of high-energy phosphates is promoted by non-purine-analog XOR inhibitors via the salvage pathway through blockade of hypoxanthine catabolism, whereas non-specific inhibitory effects of allopurinol on purine/pyrimidine enzymes impede this re-synthesis process. CONCLUSIONS: This metabolic approach shed light on the physiology of the organ-protective effects of XOR inhibitors.

Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as the Predominant Manifestation of Adrenal Insufficiency.

A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after the initiation of corticosteroid replacement therapy. To our knowledge, this is the first reported case of adrenal insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should consider reversible non-parkinsonian bradykinesia associated with frontal lobe dysfunction as an unusual manifestation of adrenal insufficiency.

Postoperative changes in neutrophil-to-lymphocyte ratio and platelet count: A simple prognostic predictor for adult-to-adult living donor liver transplantation.

BACKGROUND/OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) is a simple index that represents systemic inflammatory change. The number of platelets is also known to reflect both post-transplant graft regeneration and dysfunction. Thus, we aimed to investigate the usefulness of NLR and platelet number in predicting the clinical course after adult-to-adult living donor liver transplantation (AA-LDLT) in the acute postoperative period in recipients. METHODS: Between January 1999 and December 2013, 61 patients underwent their first AA-LDLT at our institute. We retrospectively analyzed their clinical data, including NLR and number of platelets, until postoperative day 14, and evaluated their ability to predict prognosis after AA-LDLT. RESULTS: The optimal cutoff values of postoperative maximum NLR and maximum platelets to predict prognosis were 50 and 80 × 103/µL, respectively. The 1- and 5-year survival rates were 87.5% and 79.1% in the normal maximum NLR group, respectively, and 46.2% for both in the high maximum NLR group (p = 0.0033). The 1- and 5-year survival rates, respectively, were 90.9% and 84.1% in the high maximum platelets group and 47.1% and 41.2% in the low maximum platelets group (p < 0.0001). In multivariate analysis, maximum NLR ≥ 50 and maximum platelets < 80 × 103/µL were independently associated with 1-year mortality. CONCLUSION: A high NLR and a low platelet count during acute postoperative period might correlate with poor prognosis after AA-LDLT.

Development of a novel chronic kidney disease mouse model to evaluate the progression of hyperphosphatemia and associated mineral bone disease.

Medial arterial calcification (MAC) and renal osteodystrophy are complications of mineral bone disease (MBD) associated with chronic kidney disease (CKD). Our aim was to develop a novel mouse model to investigate the clinical course of CKD-MBD. Eight-week-old C57BL/6 J male mice were assigned to the following groups: the control group, fed a standard chow for 6 or 12 weeks; the CKD-normal phosphorus (NP) group, fed a chow containing 0.2% adenine, with normal (0.8%) phosphorus, for 6 or 12 weeks; and the CKD-high phosphorus (HP) group, fed 6 weeks with the 0.2% adenine/0.8% phosphorus diet, followed by a chow with 1.8% phosphorus for 2 weeks, 4 weeks or 6 weeks. Serum phosphorus was significantly increased in the CKD-HP group, and associated with MAC formation; the volume of calcification increased with longer exposure to the high phosphorus feed. MAC was associated with upregulated expression of runt-related transcription factor 2, alkaline phosphatase, and osteopontin, indicative of osteoblastic trans-differentiation of vascular smooth muscle cells. A significant mineral density depletion of cortical bone was observed. We describe the feasibility of developing a model of CKD-MBD and provide findings of a direct association between elevated serum phosphorus and the formation of MAC and renal osteodystrophy.