BACKGROUND: Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries. METHODS: A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95^th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93), CONCLUSIONS This study represents the first comprehensive exposure assessment for DON, T2/HT2, and ZEN in Japanese adults using human biomonitoring methods. These data provide valuable information for a better understanding of mycotoxin exposure in Japan.
Humans ; Zearalenone/urine* ; Japan ; Male ; Female ; Trichothecenes/urine* ; T-2 Toxin/urine* ; Biological Monitoring ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Young Adult ; Mycotoxins/urine* ; Environmental Exposure/analysis* ; East Asian People

BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

BACKGROUND: Although serum carotene may contribute to dementia prevention, there is a lack of longitudinal evidence for early cognitive decline before dementia symptoms. The aim of this study was to examine whether serum carotene levels were associated with annually evaluated cognitive trajectories among the Japanese general population. METHODS: Among 581 baseline participants, 199 individuals (83 males; mean age [min, max], 62.7 [39, 90] years) who underwent cognitive assessments more than twice after baseline were analyzed. "Attention" levels were assessed using one- and three-target Digit Cancellation Tests (D-CAT1 and D-CAT3). "General cognitive ability" was assessed by the short version of Mini-Mental State Examination (SMMSE). Serum carotenes (α-carotene, β-carotene and lycopene) were measured by high-performance liquid chromatography. After the measurements, we calculated total carotene levels by summing up the levels of all measured carotene. Carotene levels were categorized into three groups for analysis (low: 0%-25%, middle: 25%-75%, and high: 75%-100%). A linear mixed model was used to estimate the slope of the D-CAT score trajectory and to compare it between three categories. RESULTS: Compared with the middle carotene group, decline of attention was faster in the D-CAT1 for low β-carotene (β = -3.48, p = 0.035), lycopene (β = -3.10, p = 0.062), and total carotene (β = -4.75, p = 0.003), but not for α-carotene (β = -2.60, p = 0.111). For the D-CAT3, decline of attention was faster in the group of low lycopene (β = -3.17, p = 0.002) and total carotene (β = -2.17, p = 0.037) compared with the middle carotene group, while no clear association for α-carotene (β = -0.67, p = 0.521) and β-carotene (β = -0.64, p = 0.639). There were no clear associations between serum carotene and the SMMSE score. CONCLUSIONS These findings suggest low levels of serum lycopene are associated with a decline of attention in the setting of the general population.
Humans ; Male ; Carotenoids/blood* ; Female ; Longitudinal Studies ; Middle Aged ; Japan ; Aged ; Adult ; Aged, 80 and over ; Attention ; Lycopene ; East Asian People

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for diagnosing mediastinal lymph node lesions. Cell blocks prepared from the needle washing fluid and flow cytometry of tissue samples are helpful in making the diagnosis, but the combination of both examinations is not routinely performed. A 77-year-old woman with fever, dyspnea, and anorexia was admitted to our hospital. Computed tomography showed enlarged mediastinal lymph nodes with calcification and left ureteral calculus; however, no focus of infection was identified. We suspected lymph node tuberculosis or malignant lymphoma, and EBUS-TBNA was performed to evaluate the mediastinal lymph node lesions. Because a cell block prepared from the needle rinse fluid was suspicious for malignant lymphoma, we changed the puncture needle from 22 G to 19 G and performed a second EBUS-TBNA. Diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of flow cytometry of the EBUS-TBNA samples. Here we report this case of DLBCL in which mediastinal lymph node tuberculosis was suspected and cell block preparation and flow cytometry using EBUS-TBNA specimens were useful for the diagnosis.

Carpal tunnel syndrome is a common orthopedic disease. Western medicine treatments for carpal tunnel syndrome include conservative drug treatments, temporary external fixations, and operative treatments. Cases of patients being treated with Kampo medicine have been reported. The patient was an 80-year-old woman, who visited our clinic because of numbness in her right hand. She was diagnosed with carpal tunnel syndrome. She was administrated with a Kampo medicine, keishito. After 7 days, her symptoms were relieved, and after 14 days her symptoms had resolved. We could not find any reports showing that keishito was effective in treating carpal tunnel syndrome. We believe that her symptoms of carpal tunnel syndrome were caused by eiefuwa (nutrient-defense disharmony) and were successfully treated with keishito.

We report a case of qi-deficiency fever that was successfully treated with hochuekkito. A 26-year-old woman presented to our clinic with a complaint of pain of her fingers. Clinical findings revealed no evidence of rheumatoid arthritis. Since she wanted treatment for the recent mild fever, additional examination was performed. Infection, malignant tumor, and collagen disease were ruled out as probable cause of the fever. Clinically, she was diagnosed with qi-deficiency fever. After treatment with hochuekkito, her body temperature normalized, indicating that treatment with hochuekkito was effective. Hochuekkito was originally prescribed for treatment of qi deficiency due to yin fire ; however, it is currently used for treatment of other diseases. In this report, we described a case using hochuekkito.

In daily medical examinations of orthopedic surgery, treatment for chronic pain is sometimes needed. We report a case of chronic pain developed after an open fracture 15 years ago and successfully treated with sokeikakketsuto. A 35­-year-­old man unfortunately sustained an open fracture in his right lower leg in a traffic accident at his age of 20 years. He underwent 12­-13 surgeries for osteosynthesis, post-­operative focal infection, and leg extension. Subsequently, he developed periodic pain in his right ankle joint. He consulted our clinic because of the severe pain; although non-­steroidal anti-­inflammatory drugs were ineffective, sokeikakketsuto was dramatically effective. To treat chronic pain after an old fracture, sokeikakketsuto may be considered as a choice of treatment.

Crowned dens syndrome (CDS) is a pseudogout of the cervical vertebra, which shows calcification around the dens of the axis. We report a case of CDS that was successfully treated with daiobotampito and shimotsuto. An 83-year-old woman visited our clinic because of neck pain. She was diagnosed with CDS and was initially administered daiobotampito and eppikajutsuto. Her neck pain improved slightly, but recurred. She was then administered daiobotampito and shimotsuto, after which her neck pain disappeared. We considered that daiobotampito and shimotsuto were effective for this prolonged illness based on persistent stasis and blood deficiency according to her treatment course and laboratory findings.

Painful orthopedic diseases are sometimes aggravated because of weather changes ; this is referred to as meteorological pain. We report two cases of great occipital neuralgia (GON) due to traffic accident in patients whose pain was aggravated by weather changes. Case 1 involved a 41-year-old woman who developed lumbago and cervical pain following a traffic accident. Two months after the accident, she had irregular occipital pain. Three months after the accident, a great typhoon occurred, and she suffered from severe occipital pain since that morning. She was diagnosed with GON as meteorological pain and was administered goreisan ; her occipital pain then improved. Case 2 involved a 31-year-old woman who developed cervical pain following a traffic accident. Three months after the accident, she experienced severe occipital pain due to weather changes. She was diagnosed with GON as meteorological pain and was administered goreisan ; her occipital pain then improved. Goreisan is dramatically effective for GON as meteorological pain caused by cervical sprain.

A 74-year-old woman presented to our clinic with a history of vascular-and stent-graft insertion for aortic dissection developed a tendency to bleed from a palmar wound due to chronic disseminated intravascular coagulation (DIC). Initially, she sustained the palmar wound due to a fall. On the second day after the injury, she experienced continuous bleeding and consulted the orthopedic department of a general hospital, where her dressing was changed. On the third day after injury, she sought consultation at our clinic. The clot and wound remained intact even 12 days after the injury. Therefore, the clot was removed and the bleeding was stopped surgically. On the same day, 5 hours after the surgical treatment, the patient presented to our clinic because of continuous bleeding. She was then administered kyukikyogaito and kamikihito to stop the bleeding. Her laboratory findings revealed thrombocytopenia, and additional inspection was performed. The bleeding stopped on the next day. On the third day after administration, the bleeding remained controlled and an additional inspection revealed DIC. In the cardiology hospital, the cause of tendency to bleed of chronic DIC was pointed out as being due to a leakage at the end of the stent-graft. Kampo medicine was thought to be useful for temporal hemostasis for bleeding due to chronic DIC.