Clinical features of acute retinal necrosis at Hokkaido University Hospital

PURPOSE: To study clinical features of acute retinal necrosis (ARN) at Hokkaido University Hospital. METHODS: Twenty-one eyes of 19 patients with ARN (10 male and 9 female patients) who were treated at Hokkaido University Hospital between 1992 and 2006 were retrospectively examined from clinical records. RESULTS: The average age of the patients was 53.4 years (range, 13 to 91 years). 17 cases were unilateral and 2 were bilateral. The pathogenic virus was herpes simplex virus-1 (HSV-1) in 2 patients, and varicella-zoster virus (VZV) in 17 patients. Clinical severity was assessed from spreading speed and area of the retinal exudation, and 5 eyes were judged as fulminant cases (4 VZV eyes, 1 HSV eye), 6 eyes as severe cases (6 VZV eyes), and 10 eyes as mild cases (9 VZV eyes, 1 HSV eye). The range of retinal exudation was 1 to 2 quadrants in 7 eyes, 3 to 4 quadrants in 3 eyes, and increased to all quadrants in 11 eyes. Retinal detachment (RD) was observed in 8 eyes (38%), and the final visual acuity was less than 0.1 in 9 eyes (43%). CONCLUSIONS: The leading cause of ARN at Hokkaido University Hospital was VZV, and no HSV-2 ARN was seen. Compared with other areas in Japan, ARN at Hokkaido University Hospital seems to show less frequent RD, but the same prognosis for final visual acuity.     

Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion

BACKGROUND: We investigated the relationship between the retinal thickness and electroretinogram (ERG) components in patients with central retinal artery occlusion (CRAO). METHODS: The optical coherence tomographic (OCT) images and ERGs of the nine patients (six men and three women; mean age, 61.8 years) were retrospectively analyzed. The thickness of the inner and outer retinal layers at 1 and 2 mm nasal and temporal to the fovea was measured in the horizontally scanned OCT images. The ratio of the inner layer thickness/sensory retinal thickness (IT/ST ratio) was calculated. The amplitudes of the a- and b-waves of the mixed rod-cone ERGs and the photopic negative response (PhNR) of the photopic ERGs were analyzed. The ratio of the amplitude of each component in the affected eye to that of the healthy fellow eye (a/f ratio) was calculated. RESULTS: In the chronic phase (1 to 8 months after onset, eight eyes), the inner layer was significantly thinner than that in the acute phase (P = 0.0147, 0.0076, 0.002, and 0.0003 for 2 mm nasal, 1 mm nasal, 1 mm temporal, and 2 mm temporal respectively, within 5 days of onset, six eyes), while the thickness of outer layer was not significantly changed. The ERGs were recorded 6.4 +/- 1.5 days after the onset of CRAO. The median of the a/f ratio was 0.84 in the a-wave, 0.56 in the b-wave, and 0.27 in the PhNR. The IT/ST in the chronic phase was positively correlated with the a/f ratio of the amplitude of the PhNR. CONCLUSIONS: Measurement of retinal thickness by OCT can be useful for monitoring the changes following CRAO. The correlation between the retinal thickness, especially inner layer thickness, and the ERG components was determined, suggesting that the PhNR in the acute phase might be a good indicator for predicting the thinning of the damaged retina in the chronic phase.     

Pyrroloquinolones and pyrazoloquinolones as potential antibacterial agents. Synthesis and antibacterial activity

Diethyl 1-cyclopropyl-5,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3,6-dicarboxylate 4 as a key-intermediate was synthesized via the Dieckmann reaction. The reaction of 4 with nucleophiles proceeded regioselectively at C-5. Facile cyclization between the C-5 and C-6 side chains of the resulting products gave novel pyrroloquinolones 10 and 12 and pyrazoloquinolones 15. They were converted into a series of cyclic amino-substituted pyrroloquinolones 17–21 and pyrazoloquinolones 22–24, and their in vitro antibacterial activities were tested. 1H-Pyrrolo[2,3-f]quinolone 17a and 2H-pyrrolo[3,4-f]quinolone 21a exhibited a potent in vitro antibacterial activity.     

A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40–89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04–1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29–0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04–2.53) and in men (HR 2.00, 95 % CI 1.04–3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.     

Depressed serum selenoprotein P: possible new predicator of increased risk for cerebrovascular events

Selenium protection against cellular damage by oxygen radicals is accomplished through selenoproteins. Thus, selenium protection during the development of stroke, an oxidative stress–related disease, may not be appropriately reflected in the total serum selenium concentration. Therefore, we hypothesized that serum selenoproteins should also be measured to understand the relationship between selenium status and oxidative stress. To establish whether stroke is associated with changes in serum selenoprotein levels, a population-based, nested case-control study was performed. The subjects were recruited from 1632 residents older than 40 years who had completed health examinations in 1992. Blood samples collected from 30 controls and 30 initial stroke victims between 1992 and 1994 were analyzed for total serum selenium and selenium-containing protein distribution. Selenium-containing proteins were separated using 2 high-performance liquid chromatography columns in tandem and detected by inductively coupled plasma–mass spectrometry. The mean serum selenium concentration was lower in the patients who had a stroke than in the controls (105.2 vs 116.5 μg/L). Selenium contents in glutathione peroxidase and albumin did not show any significant difference; however, selenoprotein P was significantly lower in the stroke cases than in the controls (54.5 vs 63.0 μg/L, P = .006). Results from multivariate logistic regression analysis showed that reduced serum level of selenoprotein P was associated with a higher risk of stroke (odds ratio = 0.28; 95% confidence interval, 0.10-0.85).     

Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats

There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. It has been reported that both the AMPK and angiotensin-II acts as a negative regulator for each protein. It has been well proven that the MAPK cascade could be modulated by the presence of angiotensin-II. Moreover, studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation. Therefore, we speculate and tried to demonstrate that the modulation of AT-R/MAPK pathway through AMPK might play crucial roles for the pathogenesis of diabetic cardiomyopathy, using the transgenic (Spontaneous Diabetic Torii-SDT) rats. We performed Western blot analysis for the measurement of myocardial AT-R, AMPK and MAPK cascades-related protein expressions, p67-phox and caspase-12. In addition, we employed dihydroethidium (DHE), Azan Mallory and hemotoxylin eosin (HE) staining methods to demonstrate the superoxide radical production, fibrosis and hypertrophy, respectively. The protein expressions, such as AT-1R, p-ERK1/2, p67-phox and caspase-12 were found to be significantly increased and conversely, the Ang-(1-7) mas R, Tak1, LKB1 and p-AMPKα1, p-p38 MAPK and p-JNK protein expressions were found to be considerably decreased in the SDT rats, in comparison to the normal rats. The DHE, Azan Mallory and HE stainings also revealed that the SDT rats have more superoxide radical production, fibrosis and hypertrophy, respectively than the normal rats. Taken together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy.     

Brain Microstructure and Impulsivity Differ between Current and Past Methamphetamine Users

Methamphetamine (Meth) use disorder continues to be highly prevalent worldwide. Meth users have higher impulsivity and brain abnormalities that may be different between current and past Meth users. The current study assessed impulsivity and depressive symptoms in 94 participants (27 current Meth users, 32 past Meth users and 35 non-drug user controls). Additionally, brain microstructure was assessed using diffusion tensor imaging (DTI); fractional anisotropy (FA) and mean diffusivity (MD) were assessed in the striatum, and FA, MD, radial and axial diffusivity were quantified in five white matter structures using DtiStudio.Across the three subject groups, current users had the highest self-reported impulsivity scores, while both Meth user groups had larger striatal structures than the controls. Past Meth users had the highest FA and lowest MD in the striatum, which is likely due to greater magnetic susceptibility from higher iron content and greater dendritic spine density. In white matter tracts, current Meth users had higher AD than past users, indicating greater water diffusion along the axons, and suggesting inflammation with axonal swelling. In contrast, past users had the lowest AD, indicating more restricted diffusion, which might have resulted from reactive gliosis. Although current Meth users had greater impulsivity than past users, the brain microstructural abnormalities showed differences that may reflect different stages of neuroinflammation or iron-induced neurodegeneration. Combining current and past Meth users may lead to greater variability in studies of Meth users. Longitudinal studies are needed to further evaluate the relationship between recency of Meth use and brain microstructure.     

A novel antimetabolite: TAS-102 for metastatic colorectal cancer

TAS-102 is a new oral anti-tumor drug, composed of a thymidine-based nucleoside analog (trifluridine: FTD) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride: TPI). TAS-102 has been shown to significantly improve overall survival and progression-free survival in patients with refractory metastatic colorectal cancer (mCRC) in placebo-controlled randomized phase II and III trials. The current review summarizes mechanisms of action, pharmacokinetics/dynamics and preclinical and clinical data of TAS-102 in colorectal cancer. TAS-102 is a new salvage-line treatment option for patients with mCRC. TAS-102 is well tolerated and has great potential in future clinical drug combination therapies.     

Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

相似文献