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*

Mouthwash is used to support brushing because it is distributed throughout the oral cavity. In this study, we examined the efficacy of a mixture of three hot water extracts (from Hordeum vulgare L, Apocynum venetum L, and Brasenia schreberi J. F. Gmel) for the purpose of developing an effective mouthwash. The mixture suppressed enhanced tumor necrosis factor α and matrix metalloproteinase 3 gene expression by Porphyromonas gingivalis lipopolysaccharide stimulation in human gingival fibroblasts. Furthermore, human studies using a mouthwash containing the plant extracts (MW) improved gingival index and bleeding on probing in the gum, and reduced the concentration of methyl mercaptan, which causes bad breath, in the mouth. These findings suggest that continued use of MW has positive effects on gingival inflammation and halitosis, and is useful for maintaining oral health.

Advances in information and communication technology (ICT)-especially, the spread of social networking services (SNSs)-have facilitated the dissemination of information and an explosion of health information lacking scientific evidence. Therefore, we believe that community pharmacies are the most suitable bases for distributing health information. In 2019, we launched the health support pharmacy “Toyonaka Model” in collaboration with the pharmaceutical association, municipal government, and university. Touch-panel digital signage (DS) was used for real-time distribution of ever-changing information and a rapid grasp of pharmacy users’ responses to various types of information. Between September 2019 and August 2021, one DS was installed in a pharmacy in each of Toyonaka City’s seven areas along with 14 questions on the usefulness of the delivered information. Respondents answered the 14 questions by a tablet or questionnaire; touch logs for DS were collected. When a pharmacy user consulted with a pharmacist about information delivered via DS, the contents were recorded and described by the pharmacist on a 4-point scale (e.g., “inquiry only,” “went through to execution”). From the 850 completed questionnaires and 61,565 touches, 88.7% of the respondents indicated that the information was useful, and 90.0% expressed interest in receiving more health information in the future. Thus, health information provided by DS may be useful to pharmacy users, as demonstrated by 113 cases in which the pharmacist was consulted regarding such information. In 62 of these cases, there were indications that the DS information might have influenced users’ behavior and intended actions.

Tumor lysis syndrome (TLS) is a metabolic disorder that is caused by acute lysis of massive tumor cells. We report a case with opioids-related severe respiratory depression induced by TLS. A 39-year-old man received chemotherapy for mycosis fungoides. Two hours after administration of chemotherapeutic agents, his renal function worsened, and he was diagnosed with TLS by laboratory and clinical findings. Moreover, he showed severe respiratory depression and pinpoint pupils, and become drowsy. These symptoms were attributed to oxycodone that had been administered to treat his tumor-related cutaneous pain, and were improved by injection of anti-opioids agent naloxone. In this case, we consider that the clearance of oxycodone was disrupted by renal dysfunction caused by TLS, leading to enhancement of the effects of oxycodone.

Effects of three plant extracts (Hordeum vulgare L., Apocynum Venetum L., Brasenia schreberi J.F.G mel.) on human gingival fibroblasts were examined. As a result, we observed the promoting effect of the extract of Hordeum vulgare L. and the extract of Apocynum Venetum L. respectively on FGF2 and FGF7 production. Moreover, the mixture of the three plant extracts showed the effect of improving the changes in type I collagen gene expression and matrix metalloproteinase 1 gene expression by LPS addition. Next, a dentifrice containing the three plant extracts was subjected to human efficacy trials. We measured periodontal pocket depth, attachment level, bleeding on probing and saliva TNFα as an indicator of periodontal disease. The results suggest that the dentifrice formulated with the three plant extracts were effective for the improvement of periodontal disease.

　　A major cause of pulmonary thromboembolism (PTE) is deep venous thrombosis (DVT). We report here a case of DVT in a 31-year-old woman during week 29 of her second pregnancy. At week 29, the patient noticed swelling of the left leg and pain in the groin after sitting. At almost week 30, walking became difficult due to pain and she was referred to hospital. Computed tomography (CT) revealed a thrombus from the left common iliac vein to the femoral vein and multiple thrombi in the right pulmonary artery. Blood testing showed elevated D-dimer (3.4μg/ml). Continuous intravenous unfractionated heparin was administered, and the dose was increased due to decreased activated partial thromboplastin time control. Despite conservative therapy for DVT, the thrombi showed no change since admission. At almost week 37, a temporary inferior vena cava filter (t-IVCF) was placed to prevent pulmonary thromboembolism, and she had an uneventful delivery of a baby by Caesarean section. Warfarin was administered postpartum. The t-IVCF was removed 4 days after delivery, and the patient was discharged 10 days after delivery. Within the field of obstetrics, the need for IVCF insertion should be considered on an individual case basis and should not be viewed as a standard option.

　　We have developed a new surgical procedure for uterine prolapse of round ligament suspension to the psoas minor tendon by the use of a laparoscope. Here, we describe the new technique and report the outcome of surgery in three cases.　　Operative procedure: The fundus of the uterus is lifted back up to its natural position by fixing the round ligament of the uterus to the psoas minor tendon after incising the peritoneum covering psoas. It is important to use the tendon as a stronger reattachment site in addition to the psoas major muscle. The round ligament is tacked to the tendon by a 2-0 nonabsorbable suture on bilateral sides. The second suture may be added if the uterus is not appropriately lifted up by the first suture. The retroperioneum is closed by a continuous 3-0 absorbable suture after fixation.　　Cases: Two patients with severe uterine prolapse and one patient with a mild condition went through the operation safely and have experienced no recurrence for 10 to 24 months. One severely ill patient complained about post -operative right inguinal pain early and another with the severe condition complained that something felt wrong with the right thigh.　　We propose the operation of laparoscopic round ligament psoas minor tendon-hitching as a safe and effective surgical treatment for uterine prolapse.

　　We researched intrauterine fetal death (IUFD) after 22 weeks of gestation from 2009 to 2014 in our departments. During this period, there were 6236 childbirths and 35 cases (0.56%) resulted in IUFD. We researched the background and causes of IUFD in these 35 cases. The median age was 34 years and advanced maternal age accounted for 48.6% of cases, while elderly primipara accounted for 20%. There were 5 cases (14.3%) of pregnancy after fertility treatment. The median gestational age when IUFD was recognized was 30 weeks, but the gestational age in 4 cases was unclear because of lack of antenatal check-ups. The main risk factors for IUFD were maternal age over 35 (0.95% to 0.40%) and lack of antenatal check-ups (3.7% to 0.5%). The major causes of IUFD were umbilical cord abnormalities (n=10) and placental abruption (n=8), but IUFD of unknown etiology accounted for about 30% of cases. We should better inform mothers about the importance of antenatal check-ups and manage pregnancies carefully for those who have risk factors for IUFD. Furthermore, we should increase research into the causes of stillbirths.

  Recently, the relevance of Helicobacter pyroli (H. pylori) infection to atrophic gastritis and gastric cancer in has been elucidated. Therefore, to diagnose H. pylori infection is important for suspecting the existence of those diseases of the stomach. We investigated the relationships of the H. pylori IgG antibody to H. pylori infection, atrophic gastritisor various stomach lesions to understand the significance and usefulness of evaluating the antibody level in the annual multiphasic health check-up participants. The subjects in this study were 148 people (male: 93, female: 55, average age: 56.4) in Toride city, which is located in the suburb of Tokyo. They had visited our hospital for medical checkups. Eighty-seven subjects underwent upper gastric endoscopy and 55 (63%) tested positive for H. pylori IgG antibody and H. pylori infection was confirmed in 41 (75%). Although 32 subjects tested negative for the antibody, 8 cases (25%) was diagnosed with H. pylori infection. The frequencies of positive antibody in atrophic gastritis, erosion and ulcer, fundic gland polyp, hyperplastic foveolar polyp, adenoma and malignancy were 17%, 70%, 61%, 77%, 31%, 62%, 0% and 100%, respectively. On the other hand of 80 subjects were who underwent barium X-ray examination, 44 tested positive for the antibody (55%). The frequency of positive antibody in no lesion, depressed lesion, elevated lesion and malignant lesion were 61%, 59%, 36% and 100%, respectively. Taken together, H. pylori antibody was a good marker for H. pylori infection and the positive antibody indicated high frequencies of atrophic gastritis and malignancy. Therefore, advices to have participants who have a positive antibody should be strongly an endscopic examination stomach lesions.