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Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications., (© 2024 John Wiley & Sons Ltd.)

Purpose: Vascular endothelial growth factor (VEGF) inhibitors are widely used in chemotherapy for non-small lung cancer (NSCLC). The purpose of the current study was to examine the impact of background cardiovascular risk factors on VEGF inhibitor-related adverse vascular events (VEGF-related AVEs) in patients with NSCLC who also had comorbidities., Methods: We conducted a retrospective study of 118 NSCLC patients treated with bevacizumab or ramucirumab from April 2010 to December 2022. We compared baseline cardiovascular risk factors with VEGF-related AVEs., Results: VEGF-related AVEs and discontinuation due to VEGF-related AVEs were reported in 54 patients and 21 patients, respectively. VEGF-related AVEs were significantly more common with male sex, smoking history, history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Discontinuation due to VEGF-related AVEs was significantly more common in patients with history of hypertension or chronic kidney disease. VEGF-related AVEs were significantly more common in patients with ≥ 3 cardiovascular risk factors than patients with < 3. Discontinuation due to VEGF-related AVEs was significantly more common in patients with ≥ 4 cardiovascular risk factors than patients with < 4. Multivariate analysis demonstrated that male sex, hypertension, and ≥ 6 cycles of VEGF inhibitors were each associated with VEGF-related AVEs and hypertension was associated with discontinuation due to VEGF-related AVEs., Conclusion: Our study demonstrated that history of hypertension was independently associated with increased risk of both VEGF-related AVEs and discontinuation due to VEGF-related AVEs. In conclusion, we need to be aware of VEGF-related AVEs when using VEGF inhibitors for patients with ≥ 3 cardiovascular risk factors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hexanoyl-lysine (HEL), 8-hydroxy-2'deoxyguanosine (8-OHdG), and dityrosine (DT) have served as potential biomarkers for detecting oxidative modified lipids, DNA, and proteins in biological samples, respectively. Whether regular higher levels of consumption of vegetables/fruit (V/F) would decrease oxidative modification of these biomolecules in the body remain unelucidated. To examine the association of regular V/F consumption with the generation of these reactive oxygen species-induced biomarkers, this study evaluated V/F consumption in a school-based sample of teenaged girls (mean age 15.6 ± 1.7 years, n = 103), and quantified the formation of oxidative stress biomarkers in their urine. Only 19.4% and 23.3% of participants reported that they consumed the recommended daily amount of vegetables and fruits, respectively. Individuals who consumed lower levels of fruit (<100g/day) or vegetables (<250g/day) had significantly higher HEL excretion in their urine than those who consumed higher levels of fruit (≥100g/day) ( p < 0.05) or vegetables (≥250g/day) ( p = 0.057). The results of a multiple regression analysis showed that vegetable consumption was an important inhibiting factor of early lipid peroxidation measured as HEL in urine, independent of various confounders (β = - 0.332, p < 0.05). The findings suggest that relatively higher consumption of vegetables would help in the prevention of early lipid peroxidation in adolescents., Competing Interests: The authors declare no conflict of interest.

ABSTARCT Purpose : To investigate ocular manifestations in patients positive for serum anti-neutrophil cytoplasmic antibodies (ANCAs) in Japan. Methods : The clinical records of patients who had ocular manifestations and who were serum ANCA positive between 2011-2017 at Tokyo Medical and Dental University Hospital were retrospectively reviewed. Results : Eighteen patients were identified to be positive for serum ANCA and had ocular manifestations, including optic nerve involvement (50%), scleritis (27.8%), iritis (27.8%), retinal vasculitis (16.7%), oculomotor disorder (16.7%), and peripheral ulcerative keratitis (11.1%). Six patients had ANCA-associated vasculitis (AAV), including 5 patients with granulomatosis with polyangiitis and 1 patient with microscopic polyangiitis. Most patients with optic nerve involvement were myeloperoxidase-ANCA positive. Contrastingly, most patients with anterior segment involvement were proteinase-3-ANCA positive. Conclusion : Ocular manifestations were observed in some patients positive for serum ANCAs. Serum ANCA evaluation is useful for identifying the etiology of ocular inflammation and for diagnosing AAV, a life-threatening disease.

Introduction: We aimed to investigate the effect of orally ingested collagen peptides (CPs) on skin condition and elucidate their mechanism of action., Methods: A randomized, placebo-controlled, double-blind trial was conducted in 99 healthy Japanese women, aged 35-50 years. The subjects were randomized into 3 groups (33 subjects/group) to receive 1 or 5 g of CP or placebo once daily for 12 weeks. Skin water content, transepidermal water loss (TEWL), skin elasticity, and skin thickness were evaluated before treatment and after 4, 8, and 12 weeks of treatment. The level of natural moisturizing factor (NMF) constituents in the stratum corneum (SC) was quantified before treatment and after 12 weeks of treatment., Results: Oral ingestion of CP increased the water content in the SC and epidermis and decreased TEWL. Furthermore, the NMF level in the SC was increased. However, skin elasticity and skin thickness remained unchanged., Conclusions: The improvement in skin water content following the oral ingestion of CP can be attributed to an increase in the level of NMF in the SC., Trial Registration: UMIN000030375 (retrospectively registered)., (© 2021 S. Karger AG, Basel.)

A few studies in Japan have demonstrated positive attitudes, self-efficacy, social support, and perceived barrier were associated with fruit and vegetable (F&V) intake in adults; however, limited evidence addresses the association of psychosocial factors with F&V intake in adolescents. A cross-sectional study through a questionnaire survey was conducted at junior and senior high schools, and 933 students completed the questionnaire. Data were analyzed by X 2 test and Student t -test. The findings demonstrated 2.7% of participants were aware of the current recommendations for vegetable and 2.0% for fruit. Only 4% and 8.1% of participants reported they consumed recommended amount of vegetables and fruits. In comparison with males, females showed higher scores of attitude ( p < 0.01), responsibility ( p < 0.01), and social support ( p < 0.01). The barriers to vegetable intake were "I'm eating enough now", "not always available when eating away from home"; the barriers to fruit intake were "don't have a habit of having 100% juice or fruit in the morning", and "cost too much". The findings suggest the change of adolescents' knowledge about what they should eat is needed in boosting F&V consumption. The development of an intervention program for adolescents needs to target socio-environmental factors such as family support, and nutritional education for early healthy habit formation.

A few studies indicate exposure to forests may alleviate oxidative stress in the body. However, more evidence is needed to support this potentiality. The purpose of the current study aimed at examining whether there is any difference in urinary levels of oxidatively modified proteins or lipids-dityrosine (DT) and hexanoyl-lysine (HEL), respectively, after a forest or urban walk. The study was performed on 29 university students who took part in forest walks (Shinjo Village) in Okayama Prefecture of Japan and on 42 university students who took part in urban walks in the downtown area of Okayama City. Urine samples before and after the walks were analyzed for DT and HEL excretion. Air phytoncides during the walks were also measured. We found a decreased tendency in urinary DT and HEL ( p < 0.05) in most participants after the forest walks, but not after the urban walks. We further found the total levels of air phytoncides in the forest field were 1.50 times higher compared with those in the urban field. This study suggests the possibility that regular immersion in a forest environment might contribute toward weakening of the oxidative modifications of proteins or lipids in the body., Competing Interests: The authors declare no conflicts of interest.

In this study, we examined the effect of ingestion of lingonberry and amla fruit extract (LAE) on several human skin conditions. To conduct a randomized, double-blinded, placebo-controlled study, we randomly divided 99 healthy female subjects into three groups; the first group received a drink containing 25 mg of lingonberry extract and 30 mg of amla fruit extract; the second group received a drink containing double the volume of extracts received by the first group; and the third group received a placebo drink. Each participant drank 50 mL of their assigned drink once daily for 12 weeks. The primary endpoint was skin elasticity, and the secondary endpoints included skin thickness, stratum corneum water content, and degree of wrinkles around the eyes. After 12 weeks of LAE drink intake, skin elasticity showed significant, dose-dependent improvements (P < 0.01). Skin thickness, stratum corneum water content, and the degree of wrinkles also significantly improved (P < 0.001) in a dose-dependent manner. The improvements in skin elasticity and thickness, as well as in the stratum corneum water content and the degree of wrinkles, observed upon oral intake of LAE indicate that LAE may be considered a candidate anti-aging agent for preventing skin weakening., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Some studies have shown that exposure to forests has positive effects on human health, although the mechanisms underlying the health benefits of a forest environment have not been elucidated yet. The current study was aimed at examining how the levels of urinary hydrogen peroxide (H₂O₂) and 8-hydroxy-2'deoxyguanosine (8-OHdG) change after a forest or urban walk in healthy subjects. Twenty-eight volunteers (19 men and 9 women) participated in the study. The forest walks were carried out in a forest in Okayama Prefecture, Japan, and the urban walks (15 men and 7 women) were carried out in the downtown area of Okayama city, each for two hours. Spot urine samples were collected before the walk, the next day and one week after the forest or urban walk. Compared with pre-forest walk levels, urinary H₂O₂ ( p < 0.1) and 8-OHdG ( p < 0.1) concentrations significantly decreased in the participants the day after the forest walk; furthermore, urinary 8-OHdG remained at a low level even at one week after the forest walk ( p < 0.05). However, there were no significant changes in the concentrations of these oxidative biomarkers after the urban walk. These findings suggest the possibility that exposure to forests may alleviate oxidative stress in the body.

Purpose: To investigate a clinical survey of uveitis in Tokyo Medical and Dental University Hospital., Subjects and Methods: The clinical records of patients with uveitis who were treated from October 1998 to December 2001 and from January 2007 to December 2011 were reviewed. The clinical results of both periods were compared., Results: A total number of 455 patients (707 eyes) and 1091 patients (1716 eyes) were analyzed in this survey. The mean age of the first period was 45.4, and of the second 50.3 years old. The incidences of sarcoidosis (11.0%, 13.7%) and Vogt-Koyanagi-Harada disease (5.7%, 5.9%) were virtually unchanged in the two series. However, the incidence of Behçet's disease was higher in the first period (10.6%) than in the second (5.8%). The frequency of herpetic iritis (1.8%, 4.7%) and intraocular lymphoma (0.4%, 2.6%)showed apparent increase. Unclassified uveitis decreased from 55.6% to 47.5%., Conclusions: The etiologies of uveitis have changed with the progress of diagnostic techniques and the establishment of new disease concepts.

Purpose: To compare the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), or cytomegalovirus (CMV)., Methods: The medical records were reviewed of 46 patients whose diagnoses were based on their clinical characteristics [e.g., unilateral involvement, presence of keratic precipitates (KPs), and elevation of intraocular pressure (IOP)] and on PCR detection of herpes virus DNA in the aqueous humor. The demographics, chief complaints, and clinical characteristics of the three types of herpetic AU were compared., Results: Of the 46 patients with AU, eight had HSV-AU, 20 had VZV-AU, and 18 had CMV-AU. HSV-AU and VZV-AU shared common features, i.e., a relatively acute disease process and the presence of large KPs. Among the three groups of patients, the characteristic features of those with VZV-AU were severe intraocular inflammation, as shown by severe aqueous flare, highest viral load in the aqueous humor, and presence of segmental iris atrophy. In comparison, patients with CMV-AU had the mildest intraocular inflammation, lowest corneal endothelial cell density, and highest IOP., Conclusions: Although the AU caused by each of the three types of herpes viruses has a number of common features, each disease also has distinct features that should facilitate an accurate diagnosis.

Purpose: To evaluate the subfoveal choroidal thickness (SCT) at the convalescent stage of Vogt-Koyanagi-Harada disease and to investigate the correlations among SCT, the presence of the sunset glow fundus, and size of the peripapillary atrophy (PPA)., Methods: The medical records of consecutive patients with Vogt-Koyanagi-Harada disease without active intraocular inflammation were reviewed, and one eye was randomly chosen for analyses. The disease duration was more than 3 years. Enhanced depth imaging optical coherence tomography was performed to measure SCT. The area of PPA was measured using the PDT/MPS software. Sunset glow fundi were classified into two groups according to the degree of depigmentation., Results: Nineteen eyes with Vogt-Koyanagi-Harada disease were studied. The mean SCT of 12 eyes with severe sunset glow fundus was 144 ± 72 μm which was thinner than that of the 7 eyes with no or mild depigmentation (P = 0.0057). The SCT was inversely correlated with the disease duration (P = 0.048) and the PPA area (P = 0.0002). The PPA area was positively correlated with the disease duration (P = 0.007)., Conclusion: The thinner choroid and larger PPA areas were correlated with the degree of depigmentation or disease duration and might be caused by latent choroidal inflammation in the convalescent stage of Vogt-Koyanagi-Harada disease.

Conclusion: The long-term follow-up study revealed a good audiovestibular prognosis in our patients with Vogt-Koyanagi-Harada disease (VKH) after adequate treatment., Objectives: To evaluate the audiovestibular findings and long-term prognosis of patients with VKH., Methods: A total of 82 ears in 41 patients (9 males and 32 females, aged 18-78 years) with VKH were examined in the audiovestibular study. Of the 41 patients, 16 patients with follow-up periods of more than 12 months (13-158 months) were included in the long-term follow-up study. Audiovestibular examinations included pure-tone audiometry; positional, positioning, and spontaneous nystagmus tests; and a caloric test., Results: Among the 41 patients, 28 (68%) complained of auditory symptoms at the initial visit and 28 (68%) showed sensorineural hearing loss (SNHL). Of the 24 patients who underwent nystagmus tests, only 3 (13%) presented with vestibular symptoms whereas 11 (46%) had nystagmus. Among 32 ears in 16 patients enrolled in the long-term follow-up study, 19 ears showed SNHL at the initial visit. The SNHL returned to normal in 14 ears (74%) and remained minimal in severity in the other 5 ears (26%) at the last visit. None of the patients showed persistent or repetitive vestibular symptoms.

Purpose: To investigate the clinical course of Behçet's uveitis patients following discontinuation of infliximab therapy., Methods: This retrospective chart review study examined Behçet's disease patients who received infliximab treatment between 2000 and 2012. Medical records of patients whose infliximab treatment was discontinued were reviewed, with special focus on the frequency of uveitis attacks in the period before initiation, during treatment and after cessation of the infliximab therapy. Mean visual acuities were evaluated for each treatment period., Results: Out of the 43 patients treated with infliximab at our uveitis clinic, ten were discontinued due to adverse events or inefficiency. Data for seven patients followed for more than 12 months before initiation and after cessation of infliximab were analyzed. Frequency of acute uveitis attacks was 7.43 per 12 months before initiation of infliximab, 2.86 during treatment and 0.57 after cessation. A statistically higher frequency of uveitis attacks was observed before initiation of infliximab compared to during (p < 0.05) and after cessation of treatment (p < 0.05). There was no statistical significance observed between the period during treatment and after cessation (p = 0.29). The mean logMAR was 0.79 at baseline, 0.68 during treatment, and 0.88 at 12 months after cessation. These differences were not statistically significant., Conclusions: A satisfactory clinical course with well-controlled ocular inflammation was found after discontinuation of infliximab therapy in Behçet's uveitis patients. These results suggest that a safe, pre-planned discontinuation of infliximab therapy can be performed in patients with Behçet's uveitis.

Instant and precise control of phosphorescent emission can be performed by ultrasound-induced gelation of organic liquids with chiral, clothespin-shaped trans-bis(salicylaldiminato)Pt(II) complexes, anti-1. Nonemissive solutions of racemic, short-linked anti-1a (n = 5) and optically pure, long-linked anti-1c (n = 7) in organic liquids are transformed immediately into stable phosphorescent gels upon brief irradiation of low-power ultrasound. Emission from the gels can be controlled by sonication time, linker length, and optical activity of the complexes. Several experimental results indicated that structure-dependent homo- and heterochiral aggregations and ultrasound-control of the aggregate morphology are key factors for emission enhancement.

The release of perylene from octadecylsilyl (ODS)-silica gel into water using a nonionic surfactant was kinetically studied by single microparticle injection and absorption microspectroscopy techniques. The release of perylene from the porous microparticles significantly depended on the surfactant concentration. The release rate constant was inversely proportional to the microparticle radius; the rate-determining step was the process at the spherical microparticle surface. The mechanism is discussed in terms of the solubilization of perylene at the microparticle surface by the micelle., (2011 © The Japan Society for Analytical Chemistry)

Purpose: Optic disc neovascularization (NVD) in patients with Behçet's uveoretinitis is a relatively uncommon but severe complication that lacks standardized treatments. We report 2 cases of Behçet's uveoretinitis that achieved partial regression of NVD after infliximab therapy., Methods: Intravenous infliximab infusions were administrated to 2 immunosuppressive therapy-resistant Behçet's uveoretinitis patients with severe NVD accompanied by vitreous hemorrhage (both eyes in case 1 and the left eye in case 2 ). Best-corrected visual acuity, funduscopic findings, and fluorescein angiography were evaluated before and after the treatments., Results: After being switched to infliximab therapy, NVD in both cases stopped developing and regressed partially, as confirmed by fluorescein angiography and resolution of vitreous hemorrhage, which led to an improvement of the best-corrected visual acuity., Conclusions: Results suggest that infliximab administration might be an effective treatment in NVD patients with Behçet's uveoretinitis.

Purpose: Indocyanine green angiography (IA) is a highly sensitive method to evaluate choroidal inflammatory lesions. We present standardized IA findings of initial acute Vogt-Koyanagi-Harada (VKH) disease in Japanese patients before therapeutical intervention., Methods: Medical records of patients with VKH disease at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital were retrospectively analyzed. We analyzed six IA signs: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal vessels, disc hyperfluorescence, and diffuse late choroidal hyperfluorescence., Results: Ten patients from the two hospitals were studied. The most constant findings present in all eyes were early hyperfluorescent stromal vessels, HDDs, and either fuzzy or lost pattern of large stromal vessels. Disc hyperfluorescence was present in 18 eyes. Choroidal perfusion inhomogeneity was seen in six patients, and diffuse late choroidal hyperfluorescence was seen to a certain degree in all eyes., Conclusions: Four of the analyzed signs, including early hyperfluorescent stromal vessels, HDDs, fuzzy or lost pattern of large stromal vessels, and disc hyperfluorescence were consistent findings in Japanese VKH patients. Because the primary lesion is situated in the choroid, IA is the method of choice to monitor disease activity in VKH disease.

Aim: The aim of the study was to investigate the correlation between the clinical manifestation and the cytomegalovirus (CMV) viral load in the aqueous humour of patients with CMV anterior uveitis., Methods: Seven patients with CMV-associated iridocyclitis and four patients with CMV-associated corneal endotheliitis were enrolled. Presence of CMV, but not other human herpes viruses, was confirmed by multiplex polymerase chain reaction (PCR). Viral load was measured using real-time PCR. Clinical manifestations were examined using a slit-lamp microscope and ophthalmoscope, applanation tonometer and specular microscope., Results: All 11 patients had unilateral recurrent anterior uveitis with high intraocular pressure and mutton fat keratic precipitates with pigmentation. Stromal oedema of the cornea was found in CMV-associated endotheliitis, but not in CMV-associated iridocyclitis patients. A significant corneal endothelium cell loss was recorded in all 11 patients with CMV-associated endotheliitis and iridocyclitis patients. High viral loads of CMV were detected in the aqueous humour of all 11 patients. A significant association was found between the corneal endothelial cell loss intensity and CMV viral load in the aqueous humour., Conclusion: There is a significant correlation between the CMV viral load and corneal endothelial cell loss in both CMV-associated iridocyclitis and corneal endotheliitis.

Purpose: To evaluate the correlation between changes in the susceptibility of bacteria and mutations in the quinolone-resistance determining region (QRDR) after 3 weeks of continuous fluoroquinolone instillation., Setting: Miyata Eye Hospital, Miyazaki, Japan., Methods: In this prospective randomized study, gatifloxacin 0.3% eyedrops or levofloxacin 0.5% eyedrops were administered for 1 week before cataract surgery and for 2 weeks after surgery. Samples were collected from the conjunctival sac before instillation of the antibiotic agent and 14 days after surgery. Susceptibility to the fluoroquinolones and gene mutations in the QRDR of the isolated Staphylococcus epidermidis were analyzed., Results: The detection rate of S. epidermidis was 27% in the gatifloxacin group (n=79 eyes) and 21% in the levofloxacin group (n=73 eyes) before instillation of the antibiotic and 6% and 19%, respectively, 14 days postoperatively. The susceptibility rates of S. epidermidis strains to levofloxacin were statistically significantly lower after instillation than before antibiotic instillation, and the number of gene mutations in the QRDR was statistically significantly higher after instillation. There was no difference in the gatifloxacin group between before and after antibiotic instillation. In the 9 eyes in which S. epidermidis was detected in samples taken before and after antibiotic instillation, most strains were genetically different from each other between the 2 time points., Conclusions: Three-week continuous instillation of levofloxacin affected the indigenous bacterial flora in the conjunctival sac, suggesting possible induction of microbial substitution to fluoroquinolone-resistant S. epidermidis. However, there was no change with gatifloxacin.

Purpose: To investigate a clinical survey of uveitis in southern Kyushu of Japan, where human T-lymphotropic virus type 1 (HTLV-1) and toxoplasmosis is highly endemic., Methods: The clinical records of patients with uveitis between 1975 and 2007 at Miyata Eye Hospital were reviewed., Results: A total number of 1338 patients (2012 eyes), consisting of 526 men and 812 women with mean age of 50.5 years old, were analyzed. The most common clinical entity was HTLV-1 uveitis (17.1%), followed by Vogt-Koyanagi-Harada disease (9.9%), sarcoidosis (7.2%), toxoplasmosis (7.1%), Behçet's disease (4.3%) and others. Unclassified uveitis comprised 41.1% in the series. Anterior uveitis was seen in 30.8%, intermediate uveitis in 17.3%, posterior uveitis in 9.3%, and pan-uveitis in 42.6%., Conclusions: HTLV-1 uveitis and toxoplasmosis were the major clinical entities in southern Kyushu of Japan. This relates to the high seroprevalence of the infectious agents in this region of Japan.

Purpose: This study compared the post-cataract surgery anti-inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling., Methods: Seventy-two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty-five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time-points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery., Results: There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone., Conclusions: There were no significant differences in anti-inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery.

Introduction: Ocular penetration of newer fluoroquinolones (FQs) has not been fully investigated in humans, especially in regard to conjunctival tissue penetration. The aim of our study was to evaluate the conjunctival permeability of 3 FQs, which do not contain benzalkonium chloride, using excised pterygium tissue., Methods: Patients undergoing pterygium surgery received a single application of one of the following: 0.5% moxifloxacin (MFLX), 0.3% gatifloxacin (GFLX), or 0.5% levofloxacin (LVFX). Samples of conjunctival tissue were collected 10, 30, or 45 min following administration of the study drug. Each sample was analyzed by high-performance liquid chromatography, and drug concentrations were measured over time., Results: Conjunctival concentration of all 3 FQs was highest 10 minutes after instillation, then gradually decreased. At all time points, MFLX showed the highest conjunctival concentrations among the 3 drugs. Mean MFLX concentrations were 116.7 +/- 28.9, 19.0 +/- 6.3, and 15.9 +/- 4.7 microg/g at 10, 30, and 45 min, respectively, and were statistically greater than GFLX or LVFX concentrations at 10 and 45 min., Conclusions: All tested FQs achieved peak concentrations within 10 min following administration. Initial peak concentrations of MFLX were greater than either GFLX or LVFX, and concentrations of MFLX remained highest among the 3 FQs throughout the 45-min time window.

Aim: To investigative whether clinical manifestations of anterior uveitis are associated with the viral load of varicella zoster virus (VZV) in the aqueous humor in patients with herpes zoster ophthalmicus (HZO) and zoster sine herpete (ZSH)., Methods: After informed consent was given, an aliquot of aqueous humor was collected from patients with VZV anterior uveitis (n = 8). Genomic DNA of the human herpes viruses was measured in the aqueous humor by two PCR assays: a qualitative multiplex PCR and a quantitative real-time PCR., Results: All patients had unilateral acute anterior uveitis with high intraocular pressure, mutton fat keratic precipitates with some pigmentation, and trabecular meshwork pigmentation. Multiplex PCR demonstrated VZV genomic DNA in all of the samples, but not in other human herpes virus samples (human simplex virus types 1 and 2, Epstein-Barr virus, cytomegalovirus and human herpes virus types 6, 7 and 8). Real-time PCR revealed a high copy number of VZV DNA in the aqueous humor. After the initial onset of anterior uveitis, iris atrophy and distorted pupil with paralytic mydriasis developed. The intensity of iris atrophy and pupil distortion, but not ocular hypertension, correlated with the viral load of VZV in the aqueous humor., Conclusion: VZV viral load in the aqueous humor correlated significantly with damage to the iris (iris atrophy and pupil distortion) in patients with HZO and ZSH.

Purpose: To evaluate the importance of early cerebrospinal fluid (CSF)-guided diagnosis and early high-dose corticosteroid therapy on the complications and visual prognosis of Vogt-Koyanagi-Harada (VKH) disease., Patients and Methods: Charts from patients with VKH disease who had been seen at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital between 1994 and 2002 were retrospectively reviewed. The patients were classified into two groups. The first group (group A) consisted of patients who had received a full work-up including CSF examination and corticosteroid pulse therapy at the acute ophthalmic stage of disease. The second group (group B) consisted of patients who were referred to us by local ophthalmologists long after the disease onset, had not had a CSF examination and had been treated with low-dose systemic corticosteroids or topical corticosteroid therapy. The ocular complications, systemic complications and visual prognosis were compared between the two groups., Results: Twenty-two patients were included in group A and ten patients in group B. The initial diagnosis at the acute ophthalmic stage had been VKH disease in all patients of group A, while, in group B, the diagnosis was idiopathic uveitis in six patients (60%) initially. Frequency of recurrent uveitis and integumentary symptoms were significantly lower in group A. Intensity of sunset glow fundus was significantly more severe in group B. All eyes in group A obtained a final visual acuity of 0.8 or better, whereas 11 eyes (55%) in group B were below this level., Conclusions: The results indicate that early diagnosis, helped by CSF examination and early high-dose corticosteroid therapy, decreased the complication rate and improved the visual prognosis.

Zinc pyrithione (ZnPT) or copper pyrithione (CuPT) have been effectively used as ship-antifouling agents, as an alternative to organotin compounds. Because of their instability in light and a lack of suitable analytical procedures, there is little data on their residue levels in environmental matrices. It is possible to investigate the fate of such compounds by toxicity alteration with certain treatments. The purpose of this study was to evaluate the degradation of pyrithiones through toxicity reduction by near ultraviolet (UV-A) irradiation. Metal pyrithiones dissolved in acetonitrile were irradiated with a UV-A lamp for 0, 0.5, 1, and 2 h, and were subjected to UV spectral measurement and toxicity evaluation using both sea urchin and freshwater rotifer bioassays. For the bioassays, photolyzed samples were dissolved in dimethyl sulfoxide after evaporation of the acetonitrile. The changes in UV spectra of photolyzed ZnPT or CuPT showed a time-dependent degradation, and the UV spectra at 2 h irradiation suggested substantial decomposition. Toxicities of ZnPT and CuPT were 12 and 5 microg/L as 24 h LC50 to the survival of rotifers and 10(-6) ng/L and 2.3 ng/L as 27 h EC50 to normal pluteus formation, respectively. By evaporation of the acetonitrile, the EC50 of ZnPT was 2.2 ng/L, which was the same as that of CuPT. The EC50s of ZnPT or CuPT for both species increased with longer irradiation times. Photolyzed ZnPT or CuPT demonstrated substantial degradation in the UV spectra, but possessed marked toxicity, which is probably due to toxic degradation products. One reason why photolyzed CuPT was toxic to rotifers was explained by the high toxicity of copper ions formed by UV-A irradiation., (Copyright 2006 Wiley Periodicals, Inc.)

Purpose: Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells., Methods: Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14;18) translocation correlated with prognosis., Results: Forty of 72 (55%) PIOL patients expressed the bcl-2 t(14;18) translocation at the major breakpoint region. Fifteen of 68 (22%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14;18) translocations and survival or relapse. However, patients with the translocation were significantly younger., Conclusions: PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease.

Background: The relationship between abdominal visceral fat accumulation and lacunar infarcts has not been previously investigated in Japanese men., Methods and Results: The subjects were 637 middle-aged (40-64 years) and 222 elderly (65-79 years) men who participated in a health checkup program from 1999 to 2003. The association between lacunar infarcts identified by magnetic resonance imaging and cardiovascular risk factors, including abdominal visceral fat accumulation evaluated by computed tomography, was examined. The prevalence of lacunar infarcts was 4.9%. Hypertension was associated with lacunar infarcts among both the middle-aged men [age-adjusted odds ratio (OR)=2.9 (95% confidence interval (CI): 1.1-7.8)] and the elderly men [OR=5.1 (95%CI: 1.4-19.0)]. Abdominal visceral fat accumulation was slightly associated with lacunar infarcts among middle-aged men, but not among elderly men: OR in the highest (>or=117 cm(2)) vs lowest (or=143 cm(2)) was still slightly associated with lacunar infarcts after adjustment for age, hypertension, drinking and smoking among middle-aged men [OR=2.7 (95%CI: 0.8-9.1)]., Conclusions: This cross-sectional study suggests that abdominal visceral fat accumulation is a possible risk factor of lacunar infarcts, in addition to hypertension, in middle-aged Japanese men.

Purpose: To determine whether a definite diagnosis of malignant lymphoma can be made from paraffin-embedded archived orbital specimens by gene rearrangement analysis using microdissection and polymerase chain reaction (PCR)., Methods: Specimens from four patients with histopathologically diagnosed orbital malignant lymphoma were examined. The malignant cells were microdissected off the paraffin-embedded specimens. DNA was extracted from the cells, and the immunoglobulin heavy chain ( IgH) gene was amplified by PCR. Gene rearrangements were detected by using primers for the third framework (FR3A), the second framework (FR2A), and the complementary determining region 3 (CDR3). Translocation of the B-cell lymphoma/leukemia-2 ( bcl-2) gene was also examined., Results: Malignant cells were present on the slides of the paraffin-embedded specimens of three of four cases. The specimens from these three cases showed IgH rearrangements for FR3A, FR2A, and CDR3. A bcl-2-associated translocation was also detected in one case., Conclusions: Gene rearrangement analysis is applicable to paraffin-embedded archived orbital specimens to confirm a diagnosis of malignant lymphoma. The advantage of this method is that only a small specimen is needed because the detection sensitivity is high.

Objective: The significance of abdominal visceral fat accumulation was evaluated in Japanese men with impaired glucose tolerance (IGT)., Research Design and Methods: The IGT subjects (n = 123) were aged 55 +/- 9 years with a BMI of 24 +/- 3 kg/m(2). The 148 control subjects with normal glucose tolerance (NGT) were matched for age and BMI. IGT and NGT were classified according to the 1985 World Health Organization criteria. Abdominal fat distribution was analyzed by computed tomography at umbilical level. Plasma lipid, glucose, and insulin concentrations and blood pressure (BP) were measured., Results: In subjects with IGT, the average visceral fat area (VFA) was significantly greater than in subjects with NGT. Fasting insulin, the sum of insulin concentrations during an oral glucose tolerance test, insulin resistance according to a homeostasis model assessment for insulin resistance (HOMA-IR), systolic BP, and serum triglyceride were significantly higher, whereas the DeltaI(30-0)/DeltaG(30-0) was significantly lower, in subjects with IGT. Subjects with IGT and NGT were then divided into three subgroups according to the number of risk factors they possessed (dyslipidemia, hypertension, neither, or both). In both IGT and NGT subjects, BMI, VFA, subcutaneous fat area, fasting insulin, HOMA-IR, and insulin secretion of the homeostasis model assessment were significantly higher in the double-risk factor subgroup than in the no-risk factor subgroup, and VFA was a potent and independent variable in association with the presence of a double risk factor., Conclusions: Visceral fat accumulation is a major contributor for multiple risk factor clustering in Japanese men with IGT and NGT.

We have applied a reconstructive operation to patients with injury of the lateral ligament in the ankle joint using an artificial ligament made of polyester (Leeds-Keio) since 1985. The operation was performed on 451 feet of 436 patients. Average follow-up period was 5 years and 8 months. Talar tilt and anterior drawer translation before and after the operation were improved from 16 degrees to 4 degrees and from 11 mm to 4 mm, respectively. In this study, which has followed the same patients over an extended period, there were no cases with a decrease in the range of motion of the joint, with further development of osteoarthritis, or with a poorer result than those observed in our earlier study, which reported a short-term follow-up of the same patients. It may therefore be concluded that this reconstructive procedure of the lateral ligament of the ankle joint, using the artificial ligament, is also excellent after long-term follow-up.

N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a precursor of the synthetic sweetener aspartame, was synthesized, using thermolysin immobilized onto Amberlite XAD-7, both in ethyl acetate and in tert-amyl alcohol. The initial rates for synthesis of Z-AspPheOMe in the organic solvents were predicted on the basis of a model proposed for an aqueous/organic biphasic reaction and compared with the experimentally observed substrate concentration dependencies. The experimental synthetic rates using the enzyme immobilized at a high enzyme concentration were lower than the calculated ones over a wide range of the substrate concentration. It was suggested as a reason for this discrepancy that the enzyme molecules form compact aggregates and those existing inside the aggregates cannot be utilized for reaction. The experimental results with the enzyme immobilized at a low concentration in ethyl acetate coincided well with the calculated ones. On the other hand, when tert-amyl alcohol was used, the experimental results were different in tendency irrespective of the amount of enzyme loaded, probably due to the fact that a distinct water phase does not exist around the enzyme aggregates inside the support.

The initial kinetics for the syntheses of N-(benzyloxycarbonyl)-L-alanyl-L-phenylalanine methyl ester (ZAPM) and N-(benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (ZDPM) in an aqueous/organic biphasic system, using free thermolysin were elucidated, both experimentally and theoretically. As model organic solvents, ethyl acetate and tert-amyl alcohol were used. The substrate concentration dependencies of the initial rate of syntheses for ZAPM and ZDPM observed in the biphasic system were well simulated using the overall partition coefficients of the substrates and product taking into consideration the effect of the formation of ion-pair complexes between the acid and amine components of the substrate, the initial rate equations determined in an aqueous buffer saturated with the organic solvent, and the pH dependence of the rate constant. The equilibrium yield for the synthesis of ZDPM was also in good agreement with the calculated result using the overall partition coefficients and equilibrium constant measured in the aqueous buffer.

Various factors affecting the stability of thermolysin immobilized by cross-linking with glutaraldehyde were elucidated, particularly in the water-immiscible organic solvents such as ethyl acetate and tert-amyl alcohol. The main reason for enzyme inactivation in water-immiscible organic solvents was found to be autolysis in the water phase, which may surround the enzyme immobilized inside the support. By contrast, in water-miscible organic solvents thermal denaturation was the predominant cause of enzyme inactivation. Courses of inactivation were expressed by second-order kinetics in the initial stage, after which inactivation proceeded at a slower rate. The extent of autolysis was found to strongly depend on the kind of organic solvent, the water content, and type of support and these dependencies were explained by the difference in the amount and state of water inside the support. Thermolysin was immobilized onto Amberlite XAD-7 as a compact aggregate inside the support which may increase the stability of the enzyme. Finally, it was shown that the stability of the immobilized enzyme could be correlated with the logP value for water-miscible organic solvents and with the solubility of water for water-immiscible organic solvents.

The overall partition coefficients of the acid and amine components of amino acid derivatives, the substrates for proteinase-catalyzed synthesis of oligopeptide precursors, in an aqueous/organic biphasic system were studied both experimentally and theoretically. In a single-component system containing either an acid or amine component, the overall partition coefficient was well expressed by a model using the acid dissociation constant and partition coefficients for the non-ionized and ionized forms of the component. The overall partition coefficient in a binary-component system containing both acid and amine components was well simulated by the model when the formation of ion-pair complexes in the organic solvent phase was taken into consideration in addition to the partitioning of the non-ionized and ionized forms of the components. The formation of ion-pair complexes in the organic solvent phase was indicated by an analysis using Fourier transform infrared ray spectroscopy (FT-IR). In addition to the partition equilibrium, the aqueous-phase pH change after partitioning could be predicted by the model.

The authors presented a case report of a seven-year-old male with eight submerged primary molars and a primary lateral incisor. Two major treatment modalities, tooth extraction and observation, were reported. In this case we applied the two alternative modalities and observed the patient for five years. The permanent successors were in the process of almost normal eruption after the extraction of the submerged primary teeth; no eruption and more severe submerging were observed, however, in the permanent successors of the submerged primary teeth that were not extracted. These results suggest that submerged or impacted primary teeth should be extracted immediately when they are moderately or severely submerged.

We report a case of spontaneous haemothorax in a 19 year old boy with an exostosis of the left second rib. It may have been caused by nontraumatic rupture of markedly dilated pleural vessels, as a result of long-standing friction between the exostosis and the pleura. This is the first report of spontaneous haemothorax, without penetrative injury to the pleura or the diaphragm, in a patient with hereditary multiple exostosis.

Systems for overexpression and purification of active alpha, beta and gamma subunits of Escherichia coli H(+)-ATPase were established. The alpha and beta subunits recovered as soluble form were purified by hydroxyapatite column chromatography. Since the gamma subunit was overexpressed as the insoluble form, this subunit was purified by polyacrylamide gel-electrophoresis containing sodium dodecyl sulfate. By subsequent denaturation of this subunit with guanidine hydrochloride and renaturation, the active gamma subunit for reconstitution of the F1-ATPase activity with the purified alpha and beta subunit was obtained. The delta and epsilon subunits which were fused to the carboxy terminus of glutathione S-transferase (GST) were overproduced and purified by affinity chromatography. These fused proteins (delta-GST and epsilon-GST) were incubated with the purified alpha, beta and gamma subunits and applied to affinity chromatography. The alpha beta gamma delta-GST and alpha beta gamma epsilon-GST complex were eluted specifically by addition of glutathione and exhibited high and low ATPase activity, respectively, with a subunit stoichiometry similar to that in the native F1-ATPase, indicating that active complexes could be reconstituted with the fused proteins. These results suggested that the amino-terminal ends of the delta and epsilon subunits are not involved in formation of the active complex. The fused epsilon-GST bound the gamma subunit strongly, and the alpha subunit weakly. The delta-GST bound the gamma subunit significantly, and the alpha and beta subunits very weakly.

A variant alkaline phosphatase (ALP), with heat-sensitivity characteristics similar to that of the bone type, was found in the serum of a patient suffering from lung cancer. In disc polyacrylamide gel electrophoretic studies most of this enzyme had migrated to the region corresponding to liver ALP, with the remainder affecting bone ALP. Like kidney ALP, this ALP was markedly inhibited by 0.5 mmol/l L-cysteine. The K(m) of this ALP for p-nitrophenylphosphate was 0.39 mmol/l, similar to that of kidney ALP. The sugar moiety of this enzyme bore greater resemblance to that of kidney ALP than liver or bone ALP. However, immunoprecipitation of this particular ALP was strong with a monoclonal antibody against liver ALP and moderate with an antibody against bone ALP.

N-(benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester, a precursor of the synthetic sweetener, aspartame, was synthesized from N-(benzyloxycarbonyl)-L-aspartic acid and L-phenylalanine methyl ester with an immobilized thermolysin (EC 3.4.24.4) in the mixed organic solvent system of tert-amyl alcohol and ethyl acetate. A mixed solvent consisting of tert-amyl alcohol and ethyl acetate at a ratio of 33:67 (v/v) was found to be the most suitable with respect to synthetic rate and stability of the immobilized enzyme. The reaction continued to proceed quite successfully in a column reactor at 40 degrees C and at a space velocity of 3.6 h(-1) with a yield of 99%, using 40 mM Z-Asp and 200 mM PheOMe dissolved in the mixed solvent as the substrate. (c) 1995 John Wiley & Sons, Inc.

N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a precursor of the synthetic sweetner asparatame, was synthesized from N-(benzyloxycarbolyl)-L-aspartic acid (Z-Asp) and L-phenylalanine methyl ester (PheOMe) with an immobilized thermolysin in various organic solvents. We found that in tert-amyl alcohol containing a small amount of water the immobilized enzyme showed a high activity comparble to that in ethyl acetate with quite a high stability. The immobilized enzyme was fully stable up to 70 degrees C in tert-amyl alcohol in the absence of the subatrate, and up to 50 degrees C in the presence of the substrate. The high stability in the presence of the substrate was found due to the fact that the release of calcium ions, the stabilizing factor of thermolysin, is suppressed.The substrate concentration dependence of the initial synthetic rate with the immobilized enzyme was quite different from that with the free enzyme in the biphasic system, in contrast to that in ethyl acetate. Finally, Z-AspPheOMe was continuously synthesized in a column reactor using 200 mM PheOMe and 120 mM Z-Asp as the substrate for over 300 h at 45 degrees C and a space velocity of 1 h(-1) without any loss of acivity. (c) 1994 John Wiley & Sons, Inc.

N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a precursor of the aspartame, and N-(benzyloxycarbonyl)-L-phenylalanyl-Lphenylalanine methyl ester (Z-PhePheOMe) were synthesized from the respective amino acid derivatives with an immobilized thermolysin (EC 3.4.24.4) in ethyl acetate. Various factors affecting the synthesis of these dipeptide precursors were clarified. The initial synthetic rate was the highest at the water content of 3.5% for both reactions. The substrate concentration dependencies of the initial synthetic rate of Z-AspkPheOMe and Z-PhePheOMe with the immobilized enzyme in ethyl acetate were different from those in an aqueous buffer solution saturated with ethyl acetate but similar to those in the aqueous/organic biphasic system using the free enzyme. Particularly, the initial synthetic rate of Z-AspPhOMe increased in order higher than first order with respect to the concentration of L-phenylalanine methyl ester (PheOMe), whereas it decreased sharply with the concentration of N-(benzyloxycarbonyl)-L-aspartic acid (Z-Asp). Such kinetic behavior could be explained by regarding the inside of the immobilized enzyme as being a biphasic mode composed from the organic phase and aqueous phase where the enzymatic reaction takes place. The reaction in the aqueous/organic biphasic system using the free enzyme could be simulated by taking into consideration the partition of the substrate and the initial rate of synthesis in the aqueous buffer saturated with ethyl acetate. Based on this analysis, the rate of reaction with the immobilized enzyme in ethyl acetate could also be predicted. Z-AsPheOMe and Z-PhePheOMe were synthesized by the fed-batch method where the acid component of the substrate was intermittently added during the course of reaction and by the batch method. In the synthesis of Z-AspPheOMe, the synthetic rate and maximum yield of reaction as well as the stability of the immobilized enzyme were higher in the fed-batch reaction than those in the batch reaction. In the synthesis of Z-PhePheOMe, the results obtained by both methods were similar. (c) 1994 John Wiley & Sons, Inc.

A survey of the frequency of various kinds of foods, dietary habits, life style, and health status was performed on 2,049 men aged from 40 to 59 living in an urban area who were participants in a "human dock" medical checkup. The relationships between these factors and health status were studied in order to identify a particular life style associated with good health status. The instrument utilized in this survey was a special form of a structured questionnaire. The results are summarized below. 1. The frequency of various kinds of foods were correlated with the kind of breakfast eaten, dietary habits, physical exercise habits, daily physical activity, smoking, and occupation. The strongest correlation to frequency of various kinds of foods was found to be with the kind of breakfast eaten and dietary habits. 2. Dietary habits were also correlated to various aspects of life style: smoking, drinking, the frequency of various kinds of foods, kind of breakfast eaten, daily physical activity, sleeping hours, habits related to physical exercise, and the frequency of meals eaten away from home. Dietary habits correlated most closely with the frequency of various kinds of foods and daily physical activity. The frequency of various kinds of food and dietary habits were found to correlate with various aspects of life style, and those subjects with good overall life styles were also found to have desirable dietary life styles. The correlation of desirable dietary habits, food intake and a suitable life style with good health status was confirmed by the results of clinical blood tests used as an index of health status.(ABSTRACT TRUNCATED AT 250 WORDS)

An autopsy case of bronchiolo-alveolar adenocarcinoma in the lung is reported. The patient is a 70-year-old male who complained of severe cough with 500-600 ml watery sputum a day, loss of weight. and general fatigue. Autopsy revealed numerous whitish tumors in various sizes with multiple cysts in both lungs, with no metastasis being found in any other organs. Histological findings identified the tumor as a bronchiolo-alveolar adenocarcinoma originating from the lungs. Electron-microscopic findings showed that the tumor cells were covered by prominent microvilli, and contained abundant irregularly-shaped cytoplasmic vacuoles suggestive of mucin.