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Thiopurines exert harmful effects on spermatogenesis in Nudt15R138C knock-in mice
No full textBackground:
The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15R138C knock-in mice.
Methods:
The male Nudt15R138C knock-in mice (9-12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition.
Results:
After MP treatment for 4 weeks, Nudt15R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15+/+ mice and Nudt15+/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15R138C/R138C mice compared to Nudt15+/+ and Nudt15+/R138C mice. Apoptotic cells were significantly increased in Nudt15R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15+/R138C mice, but not Nudt15+/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15+/R138C and Nudt15+/+ mice after 12-week MP treatment.
Conclusions:
Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes.journal articl
RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy.（最新研究の報告）
Get PDFapplication/pdfOthersJournal of Biological Chemistry. 2023 Mar;299(3):102993.
DOI: 10.1016/j.jbc.2023.102993othe
Dietary Factors, Dietary Patterns, and Cardiovascular Disease Risk in Representative Japanese Cohorts: NIPPON DATA80/90
Get PDFapplication/pdfDiet is one of the most important factors affecting healthy life expectancy through the onset of cardiovascular disease (CVD) risk as well as various chronic diseases. Because dietary habits and disease structure differ depending on the country, region, and/or race, evidence from each population is required. NIPPON DATA80/90 is a long-term cohort study of a representative Japanese population that participated in national nutrition surveys. Among the many findings of this cohort study, a dietary pattern with higher intake of fruits, vegetables, fish (n-3 polyunsaturated fatty acids), and dietary fiber and lower intake of salt as well as sodium-to-potassium ratio was found to be associated with a lower risk of CVD mortality. The results from our cohort study would be useful for effectively preventing CVD. This article reviews the published studies from the NIPPON DATA80/90 to highlight the significant findings that may be used to develop risk prevention strategies for CVD.Journal Articlejournal articl
キョダイ ジョウコウ ダイドウミャクリュウ ニヨリ ハイドウミャク ガ アッパイサレ ウシン フゼン オ テイシタ 1レイ
Get PDF症例は67歳男性。1週間前からの動悸と呼吸苦を主訴に前医を受診した。経胸壁心臓超音波検査で著明な右心負荷（右房右室間圧格差81 mmHg）と重度の三尖弁閉鎖不全症を指摘され、原因精査のために行われた造影CT検査で最大径100 mmの上行大動脈瘤を指摘された。巨大な上行大動脈瘤が主肺動脈を圧排し、右心不全を引き起こしていると考えられた。同日当院に転院搬送され、緊急手術を施行された。体外循環を確立した後に、人工血管を用いた上行大動脈置換と自己心膜パッチを用いた主肺動脈の瘻孔部の閉鎖を行った。術後経過は良好で、術後11日目に独歩で自宅退院した。術後1835日目の外来でも良好な経過を確認されている。今回の症例は、巨大な上行大動脈瘤により肺動脈が圧排されて高度狭窄を来し、右心不全を呈したと考えられる。早期の外科治療で救命し得た１例を経験したので報告する。A 67-year-old man was admitted to his previous hospital because of heart palpitations and dyspnea. Transthoracic echocardiography showed right ventricular overload with tricuspid regurgitant pressure gradient of 80 mmHg and severe tricuspid regurgitation. In addition, contrast-enhanced computed tomography showed a pulmonary artery occlusion due to an ascending aortic aneurysm of which maximum diameter is 100 mm. He was therefore transferred to our hospital for undergoing emergency surgery. At operation, the ascending aortic aneurysm covered and invaded the main pulmonary artery. The ascending aorta was replaced using a vascular prosthesis and the defect hole of the main pulmonary artery was repaired with a patch of autologous pericardium. The postoperative period was uneventful, and he was discharged 11 days after the operation. At an 1853-day-follow-up visit, he was found to be asymptomatic with no activity limitations.departmental bulletin pape
Dietary diversity modification through school-based nutrition education among Bangladeshi adolescent girls : A cluster randomized controlled trial
Get PDFapplication/pdfObjective:
To measure the efficacy of school-based nutrition education on dietary diversity of the adolescent girls in Bangladesh.Methods:
A matched, pair-cluster randomized controlled trial was conducted from July 2019 to September 2020. Randomization was done to select intervention and control schools. There were 300 participants (150 in the intervention and 150 in the control arm) at baseline. We randomly selected our study participants (adolescent girls) from grades six, seven, and eight of each school. Our intervention components included parents' meetings, eight nutrition education sessions, and the distribution of information, education, and communication materials. An hour-long nutrition education session was provided using audio-visual techniques in a class of intervention school once a week by trained staffs of icddr,b for two months. Data on dietary diversity, anthropometry, socio-economic and morbidity status, a complete menstrual history, and haemoglobin status of adolescent girls were collected at recruitment and after five months of intervention. We calculated the mean dietary diversity score of adolescent girls at baseline and at the endline. As the dietary diversity score was incomparable between the control and intervention arm at baseline, we performed the difference-in-difference analysis to assess the effect of the intervention.Results:
Mean age of the adolescent girls was 12.31 years and 12.49 years in the control and intervention arms respectively. Percentages of consumption of organ meat, vitamin A-rich fruits and vegetables, legumes, nuts, and seeds were higher in the intervention arm than in the control arm at the end-line. The mean dietary diversity score remained unchanged in the control arm at 5.55 (95% CI: 5.34-5.76) at baseline and 5.32 (95% CI: 5.11-5.54) at the endline. After the intervention, mean dietary diversity increased from 4.89 (95% CI: 4.67-5.10) at baseline to this mean was 5.66 (95% CI: 5.43-5.88) at the endline. Result from the difference-in-difference analysis revealed that the mean dietary diversity was likely to increase by 1 unit due to intervention.Conclusion:
The shorter duration of the intervention in our study could not show whether it could change the behavior of adolescent girls in increasing dietary diversity through school-based nutrition education, but it showed a pathway for increasing dietary diversity at school. We recommend including more clusters and other food environment elements in retesting to increase precision and acceptability.Trial registration:
This study was registered with ClinicalTrials.gov, trial registration no: NCT04116593. https://clinicaltrials.gov/ct2/show/NCT04116593.Journal Articlejournal articl
Response to a letter to the editor related to Graefe's Arch Clin Exp Ophthalmol. 2023 April; 261(4):951-957. "Blood neutrophil-to-lymphocyte ratio as a risk factor in the treatment of retinopathy of prematurity"
No full textJournal Articlejournal articl
Clopidogrel Use in CYP2C19 Loss-of-Function Carriers With High Bleeding Risk After Percutaneous Coronary Intervention.
Get PDFBackground:
It is not known whether clopidogrel use in cytochrome P450 (CYP) 2C19 loss-of-function (LOF) carriers with high bleeding risk (HBR) contributes to adverse outcomes after percutaneous coronary intervention (PCI).Methods and Results: This retrospective observational study included 618 consecutive patients with available CYP2C19 polymorphism information who underwent PCI between September 2014 and August 2021. Patients with HBR (319 [52%] met the Academic Research Consortium definition) were divided into 2 groups according to P2Y12inhibitor action, namely decreased (i.e., clopidogrel in CYP2C19 LOF carriers) and retained (i.e., clopidogrel in CYP2C19 LOF non-carriers or prasugrel regardless of CYP2C19 polymorphisms), and clinical outcomes at 1 year were compared using inverse probability-weighted Cox proportional hazard regression. The primary ischemic outcome (a composite of cardiovascular death, myocardial infarction, or ischemic stroke) was significantly higher in the decreased than retained group (10.2% vs. 3.0%; adjusted hazard ratio [aHR] 2.78; 95% confidence interval [CI] 1.40-5.52; P=0.004). The primary bleeding outcome (Bleeding Academic Research Consortium 3 or 5) did not differ significantly between the decreased and retained groups (3.4% vs. 6.9%, respectively; aHR 0.48; 95% CI 0.22-1.01; P=0.054). There were no interactions between the treatment groups and HBR status in primary ischemic and bleeding outcomes.
Conclusions:
Among patients with HBR, clopidogrel use in CYP2C19 LOF carriers was significantly associated with increased ischemic events after PCI.journal articl
Development of new bioabsorbable implants with de novo adipogenesis
Get PDFPoly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.journal articl
Bone marrow-derived mononuclear cells ameliorate neurological function in chronic cerebral infarction model mice via improvement of cerebral blood flow
Get PDFBackground aims:
Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their outcomes have not been fully satisfactory. In particular, the development of regenerative therapies for chronic ischemic stroke is greatly needed. Herein intracerebral administration of bone marrow-derived mononuclear cells (BM-MNCs) was assessed as a potential treatment for chronic ischemic stroke using a severe combined immunodeficiency mouse model characterized by minimal vascular variation unrelated to immunodeficiency.
Methods:
A reproducible model of permanent middle cerebral artery occlusion was prepared, and intracerebral BM-MNC transplantation was performed 14 days after stroke induction in the infarcted brain.
Results:
Sensorimotor behavioral function and cerebral blood flow were significantly improved upon treatment with BM-MNCs compared to control medium injection. The transplanted cells exhibited characteristics of the vascular endothelium and microglia/macrophages. Significant angiogenesis and suppression of astrogliosis and microgliosis were observed in the affected brain. Messenger RNA expression analysis showed significant increases in anti-inflammatory cytokines, A2 astrocyte/anti-inflammatory microglia markers and vascular endothelial markers such as vascular endothelial growth factor and significant decreases in pro-inflammatory cytokines and A1 astrocyte/pro-inflammatory microglia markers following BM-MNC transplantation.
Conclusions:
These results suggest that intracerebral administration of BM-MNCs should be considered an effective cell therapy for chronic stroke.journal articl
Combined Therapeutic Plasma Exchange and Continuous Renal Replacement Therapy in Children With Dengue-Associated Acute Liver Failure and Shock Syndrome: Single-Center Cohort From Vietnam
Get PDFObjectives:
Pediatric acute liver failure (PALF) is a fatal complication in patients with severe dengue. To date, clinical data on the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for managing dengue-associated PALF concomitant with shock syndrome are limited.
Design:
Retrospective cohort study (January 2013 to June 2022).
Patients:
Thirty-four children.
Setting:
PICU of tertiary Children's Hospital No. 2 in Vietnam.
Interventions:
We assessed a before-versus-after practice change at our center of using combined TPE and CRRT (2018 to 2022) versus CRRT alone (2013 to 2017) in managing children with dengue-associated acute liver failure and shock syndrome. Clinical and laboratory data were reviewed from PICU admission, before and 24 h after CRRT and TPE treatments. The main study outcomes were 28-day in-hospital mortality, hemodynamics, clinical hepatoencephalopathy, and liver function normalization.
Measurements and main results:
A total of 34 children with a median age of 10 years (interquartile range: 7-11 yr) underwent standard-volume TPE and/or CRRT treatments. Combined TPE and CRRT ( n = 19), versus CRRT alone ( n = 15), was associated with lower proportion of mortality 7 of 19 (37%) versus 13 of 15 (87%), difference 50% (95% CI, 22-78; p < 0.01). Use of combined TPE and CRRT was associated with substantial advancements in clinical hepatoencephalopathy, liver transaminases, coagulation profiles, and blood lactate and ammonia levels (all p values < 0.001).
Conclusions:
In our experience of children with dengue-associated PALF and shock syndrome, combined use of TPE and CRRT, versus CRRT alone, is associated with better outcomes. Such combination intervention was associated with normalization of liver function, neurological status, and biochemistry. In our center we continue to use combined TPE and CRRT rather than CRRT alone.journal articl