Reactive oxygen species mediate compensatory glomerular hypertrophy in rat uninephrectomized kidney

Hyperfiltration in glomeruli is the most common pathway to progressive renal dysfunction. Moreover, reduction of renal mass by unilateral nephrectomy results in an immediate increase in glomerular flow to the remnant kidney, followed by compensatory glomerular hypertrophy. Reactive oxygen species (ROS) are involved in renal hypertrophic responses; however, the role of ROS in compensatory glomerular hypertrophy remains unclear. Therefore, this role was investigated in the present study. Wistar rats were randomly placed into two groups: uninephrectomized rats (Nx) and uninephrectomized rats treated with tempol (Nx + TP). The glomerular volume increased in the Nx 1 week after surgery, but was significantly suppressed in the Nx + TP. Levels of phospho-Akt and phospho-ribosomal protein S6, which are critical for cell growth and hypertrophy, were markedly increased in the glomeruli of the Nx, while tempol treatment almost abolished the activation of these proteins. These results suggest that ROS have important roles in compensatory hypertrophy in glomeruli. M. Ozeki and H. Nagasu have contributed equally to this study.     

氟伐他汀对2型糖尿病合并高胆固醇血症患者的抗氧化作用

目的调查氟伐他汀对2型糖尿病合并高胆固醇血症患者体内氧化压力的影响以及与降脂作用的相关性。方法糖尿病合并高脂血症患者41例，男21例，女20例，平均年龄（56．7±6．0）岁，均在日本弘前大学附属医院收集。每晚服用20mg氟伐他汀，于用药前及用药后4、8、12周分别测定血浆中低密度脂蛋白（LDL），LDL size、LHPO、TBARS的动态变化。结果血浆LHPO，TBARS、LDL—C在用药的第8周（分别为19．4±8．1 vs43.3±13．1nmol／mg LDLpm；5．33±0．97vs8．83±1．11nmol／mL；125±9vs157±12mg／dL，P〈0．05）和12周（分别为14．4±5．1vs43．3±13．1nmol／mg LDLpro；2．3±0．3vs8．83±1．11nmol／mL；131±5vs157±12mg／dL，P〈0．05）明显降低，LDL size无统计学差异。结论氟伐他汀能够显著降低患者血中的LHPO、TBARS、LDL，表明对2型糖尿病合并高脂血症患者有抗氧化作用．且与其抗血脂的作用相关．     

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

Recent research has focused on the effects of ambient particulate pollution and much evidence has indicated that particulate pollution is associated with the onset of asthma and allergy; however, the effect of diesel exhaust particles (DEP) on the development of allergen-induced airway remodeling has not been fully investigated in vivo. In the present study, we examined the effects of DEP on Dermatophagoides farinae allergens (Der f)–induced asthma-like phenotypes in mice. Mice were administered i.t. 8 times with Der f. DEP were injected i.t. with Der f 4 times throughout the experiment or twice at the sensitization period. In both cases, DEP aggravated Der f–induced increases in airway responsiveness to acetylcholine, the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), serum Der f–specific IgG1 levels, Th2 cytokines and transforming growth factor-β 1 levels in BALF, and amount of hydroxyproline in the right lungs. Furthermore, goblet cell hyperplasia and subepithelial fibrosis were also markedly aggravated. These findings indicate that DEP can potentiate airway remodeling induced by repeated allergen challenge as well as Th2-drived airway hyperresponsiveness, eosinophilic inflammation, and IgG1 production and that DEP can exhibit adjuvant activity for airway remodeling, probably due to the enhancement of allergen sensitization and/or of Th2 polarizing pathways.     

A case of gallbladder adenoma with wide base]

A 65-year-old man was referred for a gallbladder elevated lesion. Abdominal US showed a hypoechoic tumor with wide base at the gallbladder body. The maximum velocity of the gallbladder wall blood flow was 20 cm/s. The outermost hyperechoic layer was irregular, but not disrupted on EUS images. We diagnosed the lesion as gallbladder carcinoma with the depth of subserosa. Cholecystectomy was performed and the tumor was diagnosed as tubular adenoma of the gallbladder. The p53 immumostaining was negative. A gallbladder adenoma with wide base is rare, here we report this case with the several considerations.     

Modeling the impact of COPD on the brain

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p ≤ 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.     

Firing of putative cholinergic neurons and micturition center neurons in the rat laterodorsal tegmentum during distention and contraction of urinary bladder

The relation between unit activity in the laterodorsal tegmental (LDT) area and the state of the urinary bladder was examined in urethane-anesthetized rats. Neurons in the LDT area can be classified into two populations: broad-spike (possibly cholinergic) and brief-spike (non-cholinergic). When the rats showed cortical electroencephalographic activity with large amplitude lower frequency, indicative of deep anesthesia, more than 40% of the broad-spike neurons was excited and about 10% was inhibited by infusion of saline into the bladder. The response was followed by decrease in amplitude and slight increase in frequency of the cortical activity, i.e., lightening of anesthesia. During light anesthesia, excitation was observed only in less than 10% of the units, while 17% was inhibited. In the brief-spike neurons, a similar proportion (about 20%) was excited and less than 10% was inhibited by the distention during either state of anesthesia. About 10% of the broad-spike neurons in the LDT area and 30% of the brief-spike neurons examined were discharged prior to the bladder contraction. Such neurons of the brief-spike category were encountered frequently outside of the central gray; lateral, caudal and ventral to the main mass of cholinergic neurons in the LDT area. These results suggest the possible involvement of the broad-spike (cholinergic) neurons in the elevation of vigilance level caused by bladder distention. The brief-spike (non-cholinergic) neurons firing with relation to bladder contraction may be part of the micturition reflex center.     

Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules.

The salient histopathologic features of low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include complex glandular structures and morules with biotin-rich optically clear nuclei. Interestingly, these characteristic features are shared by the cribriform-morular variant of papillary thyroid carcinoma, whose morphology is identical to that of familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore, the single reported case of lung cancer associated with FAP was L-FLAC/WDFA. These observations lead us to hypothesize that up-regulation of the Wnt signaling pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11 cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high-grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta-catenin. All cases of L-FLAC/WDFA showed predominantly aberrant nuclear/cytoplasmic expression, especially in budding glands and morules, whereas six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic expression restricted to the distal branching airway epithelium. Mutational analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA showed a point mutation at codon 34 and codon 37 in two cases, respectively. The present study indicates that up-regulating disturbances in the Wnt signaling pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L-FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that of the developing fetal lung airway. With the expression pattern of beta-catenin as a marker, most cases of H-FLAC as well as CAC appear to have different oncogenic pathways from cases of L-FLAC/WDFA. The present study together with other available data also suggests that abnormal up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors with morular formation from a variety of anatomic sites.     

Senescence marker protein 30 is up‐regulated in kainate‐induced hippocampal damage through ERK‐mediated astrocytosis

Senescence maker protein 30 (SMP30) is decreased in an androgen‐independent manner in kidney and liver with age. However, regulation of SMP30 expression in the brain has not been examined in aging and neurodegenerative diseases. To investigate SMP30 expression in the brain, we utilized aging and kainate (KA)‐induced neurodegenerative disease models. Interestingly, expression of SMP30 was unlikely to decrease in the aged brain, but total levels of SMP30 protein were increased at 4 weeks after KA injury. Increased glial fibrillary acidic protein (GFAP) with elevated SMP30 expression was observed at the same time post‐KA, indicating that regulation of SMP30 expression in the brain may be associated with astrocytosis. We confirmed that KA induced GFAP expression with increased SMP30 in rat astrocyte cells. Moreover, we found that ERK1/2 activation was involved in the up‐regulation of SMP30 in astrocytes. Our results suggest that elevated SMP30 in activated astrocytes plays an important supportive role after brain damage. © 2009 Wiley‐Liss, Inc.