うつ症状が室温低値と血圧高値の関連に及ぼす影響

Objectives: Cold exposure accounts for more than 7% of all-cause mortality worldwide, and cold-induced blood pressure (BP) elevation and consequent cardiovascular events are partially responsible. For prevention, it is important to identify risk factors for exaggerated temperature-sensitivity of BP but this is not fully understood. This study investigated whether depressive symptoms affect the relationship between indoor temperature and BP. Methods: We conducted a cross-sectional analysis of 1076 community-based individuals who were at least 60 years of age. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale at a cutoff point of 4/5. We performed ambulatory BP monitoring and indoor temperature measurement on two consecutive days during the cold season in Nara, Japan. Results: When using daytime SBP as a dependent variable, multilevel linear regression analyses showed that lower daytime indoor temperature was significantly associated with higher daytime SBP in the depressive group (n = 216, β = -0.804, P < 0.001) but not in the nondepressive group (n = 860, β = -0.173, P = 0.120); moreover, a significant interaction between depression and daytime indoor temperature was observed (P = 0.014). These relationships were independent of potential confounders including age, gender, BMI, medications, and physical activity. Similar results were obtained for morning SBP, nocturnal SBP dipping, and morning BP surge. Conclusion: The results suggest that depressive participants are more likely to have cold-induced BP elevation than nondepressive participants. Further longitudinal studies are warranted to determine whether people with depressive symptoms are at a high risk for cold-related cardiovascular events.博士（医学）・甲第859号・令和5年3月15

Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined. CASE PRESENTATION: A 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN. CONCLUSION: Combination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection

Broader autism phenotype as a risk factor for postpartum depression: Hamamatsu Birth Cohort (HBC) Study

AbstractThe broader autism phenotype (BAP), which refers to the expression of behavioral and cognitive propensities that are milder but qualitatively similar to those defining autism spectrum disorder, can play a crucial role in postpartum depression (PPD). We investigated whether pregnant women's BAP would increase the risk for PPD, using a representative birth cohort in Japan. Pregnant women were enrolled in the Hamamatsu Birth Cohort (HBC) Study during their mid-gestation (N=841) and were followed up until 3 months after delivery. BAP was measured mainly during the 2nd trimester of the pregnancy by using the Broader Phenotype Autism Symptoms Scale. Participants scoring 9 points or higher on the Edinburgh Postnatal Depression Scale at least once during the first 3 months after childbirth were diagnosed with PPD. Among participants, 128 (15.2%) women were found to have PPD. Multiple logistic regression analyses showed that BAP were associated with PPD (OR=1.19, 95% CI [1.07–1.31]), even after controlling for other potential confounders. In addition, the association was not moderated by history of depression and/or anxiety disorders, including concurrent depressive and anxiety symptoms during pregnancy. The findings suggest that pregnant women with BAP have an elevated risk for PPD

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan

Abstract Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. Methods A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Findings Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US$1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US$22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US$67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Conclusion Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF

Effects of Tridocosahexaenoyl-Glycerol Emulsion on Proteinuria in Rats with Nephrotoxic Serum Nephritis

Background: Docosahexaenoic acid (DHA) is one of the n–3 polyunsaturated fatty acids and an important component of cell membrane phospholipids (PL). Nephrotoxic serum (NTS) nephritis was a worldwide model of the Goodpasture syndrome. We investigated the effects of tridocosahexaenoyl-glycerol (DHA-TG) emulsion on proteinuria in rats with NTS nephritis. Methods: Sixteen male Wistar rats weighing approximately 200 g were used. Twelve rats were treated with NTS via the tail vein and divided into 3 groups (groups A, B, and C). Another 4 rats treated with saline served as controls (group D). DHA-TG and soybean oil emulsions were intraperitoneally administered to the rats in groups A and B, respectively, 24 h prior to NTS injection, and 0, 1, 2, 3, 4, and 5 days after the injection. Saline was administered to the rats in groups C and D in the same manner. All rats were sacrificed on day 6 to obtain plasma and kidney samples. Analyses of urinary protein levels and fatty acid composition of plasma and kidney as well as histological examination of the kidneys were performed. Results: Urinary protein levels in group A were significantly lower than those in group C (35.0 ± 13.3 vs. 79.2 ± 11.8 mg/day on day 5, means ± SE, p Conclusions: These results suggest that the DHA-TG emulsion may have beneficial effects on NTS nephritis in the rat

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

Background: A single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been associated with increased risk of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the relationship between the EGF SNP genotype and the development and prognosis of HCC, in a Japanese population. Methods: Restriction fragment-length polymorphism was used to determine the presence of the EGF SNP genotype in 498 patients, including 208 patients with HCC. The level of EGF messenger ribonucleic acid (mRNA) expression in cancerous tissues was measured by quantitative reverse transcription polymerase chain reaction. The correlation between the EGF SNP genotype and prognosis was statistically analyzed in the patients with HCC. Results: The proportion of the A/A, A/G, and G/G genotypes were 5.3%, 42.8%, and 51.9%, respectively, in the patients with HCC, whereas in those without HCC, they were 8.6%, 35.9%, and 55.5%, respectively, revealing that the odds ratio (OR) of developing HCC was higher in patients with a G allele (OR =1.94, P=0.080 for A/G patients and OR =1.52, P=0.261 for G/G patients, as compared with A/A patients). In particular, when the analysis was limited to the 363 patients with hepatitis C, the OR for developing HCC was 3.54 (P=0.014) for A/G patients and was 2.85 (P=0.042) for G/G patients, as compared with A/A patients. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.033). No statistically significant differences were observed between the EGF SNP genotype and diseasefree or overall survival. Conclusion: The EGF SNP genotype might be associated with a risk for the development of HCC in Japanese patients but not with prognosis. Of note, the association is significantly stronger in patients with hepatitis C, which is the main risk factor for HCC in Japan

Genetic Association Analysis of NOS1 and Methamphetamine-Induced Psychosis Among Japanese

The neuronal nitric oxide synthase gene (NOS1) is located at 12q24, a susceptibility region for schizophrenia, and produces nitric oxide (NO). NO has been reported to play important roles as a gaseous neurotransmitter in brain. NO is a second messenger for the N-methyl-D aspartate (NMDA) receptor and is related to the dopaminergic system. Because the symptomatology of methamphetamine (METH) use disorder patients with psychosis is similar to that of patients with schizophrenia, NOS1 is a good candidate gene for METH-induced psychosis. Therefore, we conducted a case-control association study between NOS1 and METH-induced psychosis with Japanese subjects (183 with METH-induced psychosis patients and 519 controls). We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs6490121, rs2682826) in NOS1 from previous reports. Written informed consent was obtained from each subject. This study was approved by the Ethics Committee at Fujita Health University School of Medicine and each participating institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA). No significant association was found between NOS1 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS1 might not contribute to the risk of METH-induced psychosis in the Japanese population