Intraocular pressure and visual field changes in normal-tension glaucoma patients treated using either unoprostone or latanoprost: a prospective comparative study

13301甲第4642号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：Clinical Ophthalmology 11 pp.1617-1624 2017. Dovepress. 共著者：Daisuke Takemoto, Tomomi Higashide, Yoshiaki Saito, Shinji Ohkubo, Sachiko Udagawa, Hisashi Takeda, Kazuhisa Sugiyam

Sesamin catechol glucuronides exert anti-inflammatory effects by suppressing IFN-β and iNOS expression through the deconjugation in macrophage-like J774.1 cells

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced NO production in mouse macrophage-like J774.1 cells and found that a mono-catechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol- O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation

Simultaneous Evaluation of Three-Dimensional Lip Kinetics and Tongue Pressure during Swallowing

Objectives: The purpose of this study was to evaluate the amount of lip movement and simultaneous tongue pressure changes on an artificial palatal plate during swallowing. Methods: Subjects were 9 healthy males (25.4 ± 2.1 years of age). Three-dimensional lip movement was measured by a wireless optoelectronic system, and tongue pressure was simultaneously recorded by a sensor sheet attached to the incisive papilla of an artificial palatal plate. Reflective markers were attached to the right and left corners of the mouth to measure the distance between them. All subjects were instructed to swallow 5 mL and 20 mL samples of water at will. The maximum change of distance between the corners of mouth, the maximum tongue pressure, and the time interval between the two maxima (lip-tongue interval) were calculated. Wilcoxon’s test was used to detect significant differences in these measurements between the two volumes. Results: Maximum tongue pressure did not differ significantly between swallowed volumes. The maximum change of distance between the corners of mouth was larger and the lip-tongue interval was significantly shorter with the larger volume. Conclusions: We suggest that swallowing a larger volume is accomplished by larger lip movement rather than larger tongue movement. These results indicate that lip movement during swallowing can be evaluated objectively

Risk of Drug-Induced Accidents and Injuries in Elderly Patients Treated with Specific Drugs Rather than Polypharmacy : Analyses of the Japanese Adverse Drug Event Report Database

One of the reasons the health care system requires long-term nursing care for elderly patients is the risk of falls and fractures. In this study, we sought to identify risk factors for drug-induced falls and fractures in elderly patients in Japan. Risk factors for drug-induced falls and fractures in the elderly were analyzed by searching for the Standardised Medical Dictionary for Regulatory Activities （MedDRA） query （SMQ） “accidents/injuries” in the Japanese Adverse Drug Event Report database （JADER）, as this SMQ was the most well suited for evaluating data on falls and fractures. For elderly patients in Japan, the risk factors for drug-induced accidents/injuries include age ≥ 70 years old, female sex, and treatment with specific drugs, but not polypharmacy. Among the risk factors with the 10 highest reporting odds ratios （RORs） were treatment with: anti-osteoporosis agents such as bisphosphonates （e.g., minodronic acid）, eldecalcitol and bazedoxifene; dementia therapeutic agents such as rivastigmine and memantine; antiparkinsonian agents such as entacapone and pramipexole; and neuropathic pain relievers such as pregabalin. Although various geriatric syndromes were generally caused by polypharmacy, it has been posited that individual medications such as those mentioned above have a more significant association with drug-induced accidents and injuries in the elderly than polypharmacy. These drugs should be used cautiously while considering drug interruption, dose reductions, and switching to alternative therapies with lower risks. An association between accidents/injuries and drugs targeting the central nervous system （such as hypnotics, sedatives, anxiolytics, and antidepressants） has previously been reported. However, in the present study, no elevated risks in association with triazolam, zopiclone, flunitrazepam, diazepam, rilmazafone, estazolam, etizolam, or paroxetine were detected. Using RORs for risk detection for drugs in the JADER database is accessible and useful, and enables sensitive risk detection

Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

慢性炎症「肉芽腫」における好中球の新しい炎症制御系の解明 --M2マクロファージの新たな誘導メカニズム解明--. 京都大学プレスリリース. 2023-02-17.In search of inflammatory Achilles heel. 京都大学プレスリリース. 2023-03-10.Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas

Iodine-125 Seed Implantation (Permanent Brachytherapy) for Clinically Localized Prostate Cancer

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatment’s effi cacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classifi ed as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of diffi culty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the fi rst month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and eff ective for localized prostate cancer within short-term follow up.</p

Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19–deficient mice

Tight junction (TJ)–like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19–deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological “sealing” function of Schwann cells

Healthy Campus Trial: a multiphase optimization strategy (MOST) fully factorial trial to optimize the smartphone cognitive behavioral therapy (CBT) app for mental health promotion among university students: study protocol for a randomized controlled trial.

BACKGROUND: Youth in general and college life in particular are characterized by new educational, vocational, and interpersonal challenges, opportunities, and substantial stress. It is estimated that 30-50% of university students meet criteria for some mental disorder, especially depression, in any given year. The university has traditionally provided many channels to promote students' mental health, but until now only a minority have sought such help, possibly owing to lack of time and/or to stigma related to mental illness. Smartphone-delivered cognitive behavioral therapy (CBT) shows promise for its accessibility and effectiveness. However, its most effective components and for whom it is more (or less) effective are not known. METHODS/DESIGN: Based on the multiphase optimization strategy framework, this study is a parallel-group, multicenter, open, fully factorial trial examining five smartphone-delivered CBT components (self-monitoring, cognitive restructuring, behavioral activation, assertion training, and problem solving) among university students with elevated distress, defined as scoring 5 or more on the Patient Health Questionnaire-9 (PHQ-9). The primary outcome is change in PHQ-9 scores from baseline to week 8. We will estimate specific efficacy of the five components and their interactions through the mixed-effects repeated-measures analysis and propose the most effective and efficacious combinations of components. Effect modification by selected baseline characteristics will be examined in exploratory analyses. DISCUSSION: The highly efficient experimental design will allow identification of the most effective components and the most efficient combinations thereof among the five components of smartphone CBT for university students. Pragmatically, the findings will help make the most efficacious CBT package accessible to a large number of distressed university students at reduced cost; theoretically, they will shed light on the underlying mechanisms of CBT and help further advance CBT for depression. TRIAL REGISTRATION: UMIN, CTR-000031307 . Registered on February 14, 2018

Lack of a surface layer in Tannerella forsythia mutants deficient in the type IX secretion system

Tannerella forsythia, a Gram-negative anaerobic bacterium, is an important pathogen in periodontal disease. This bacterium possesses genes encoding all known components of the type IX secretion system (T9SS). T. forsythia mutants deficient in genes orthologous to the T9SS-encoding genes porK, porT and sov were constructed. All porK, porT and sov single mutants lacked the surface layer (S-layer) and expressed less-glycosylated versions of the S-layer glycoproteins TfsA and TfsB. In addition, these mutants exhibited decreased haemagglutination and increased biofilm formation. Comparison of the proteins secreted by the porK and WT strains revealed that the secretion of several proteins containing C-terminal domain (CTD)-like sequences is dependent on the porK gene. These results indicate that the T9SS is functional in T. forsythia and contributes to the translocation of CTD proteins to the cell surface or into the extracellular milieu

MCPH1 regulates chromosome condensation and shaping as a composite modulator of condensin II

MCPH1, a protein linked to primary microcephaly, directly modulates condensin II to regulate chromosome condensation and shape