Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats

The present study was undertaken to examine the effects of the ACE (angiotensin converting enzyme) inhibitor imidapril, on the brain, when administered after the onset of stroke in a stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Learning deficits and induced lesions in the brain as well as in the kidneys and heart were investigated in detail. SHRSP were divided into two groups with or without salt loading at the age of 4 weeks. The salt loading was performed for 7-9 weeks to increase the incidence of stroke. Within 24 h after the first observation of stroke, animals were subsequently treated with 5 mg/kg imidapril orally once a day or the vehicle for up to the age of 27 weeks. Imidapril attenuated progression of neurological abnormalities such as irritability, hyperkinesia and motor dysfunction, and increased survival rate. In three-panel runway testing, learning deficits did not develop significantly in the imidapril-treated group, and was comparable to that in the non-salt-loaded/non-stroke group. Imidapril reduced oedema formation in the cortex, hippocampus and striatum, and also suppressed lesion formation in the kidneys and heart. Imidapril thus suppressed progression of neurological deficits with loss of learning ability following onset of stroke, and also suppressed formation of oedema in the brain and decreased the number of lesions in other organs. Imidapril-induced reduction of cerebrovascular damage, which presumably occurs in the brain after stroke, may account for the inhibitory effects of imidapril on lesion formation and learning impairment.     

Midterm results of the Synergy cementless tapered stem: stress shielding and bone quality

Background  Tapered femoral stems have been shown to produce less thigh pain and stress shielding than other cement-less stem designs. The purpose of this study was to examine the performance of this type of femoral stem in Japanese patients. Methods  A series of 40 total hip arthroplasties with a Synergy tapered femoral component were performed in 33 patients between March 1999 and February 2001 at our institution. Three hips (in three patients) were lost to follow-up, so 37 hips in 30 patients were followed for an average of 70 months. The patients’ average age at the time of surgery was 59 years (range 43–80 years). Clinical evaluation included the Japanese Orthopaedic Association (JOA) Hip Score and the incidence of thigh pain. Preoperative radiographic examination included the cortical index and Dorr’s bone type. Postoperative radiographic examination included evaluation of biological fixation, spot welds, cortical hypertrophy, and stress shielding. Results  The average JOA Hip Score improved significantly from 35 preoperatively to 91 postoperatively. No patient suffered thigh pain. All femoral components were classified as bony stable. Spot welds and cortical hypertrophy were commonly found in the middle to the distal portion of the component. Severe (third and fourth degree) stress shielding was observed in 24.3% of the cases. A low cortical index, a Dorr type C femur, and a large stem size were associated with severe stress shielding. Conclusions  The midterm clinical results with the Synergy femoral component were satisfactory for Japanese patients. Although severe stress shielding was frequently observed in patients with poor bone quality, stem stability was not affected. Extent of grit blasting and stem length may be factors causing severe stress shielding in Japanese patients with poor bone quality. In conclusion, poor bone quality is a less favorable indication for the cementless tapered stem.     

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.     

Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B

Autosomal forms of Emery-Dreifuss muscular dystrophy (AD-/AR-EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are caused by mutations in the gene encoding A-type lamins (LMNA). A-type lamins are major components of nuclear lamina and known to have important roles in maintaining nuclear integrity. LMNA mutations are also suggested to cause reduced myogenic differentiation potentials, implying that satellite cell nuclei in AD-EDMD/LGMD1B are likewise affected. We examined nuclear changes of skeletal muscles including satellite cells from four patients with AD-EDMD/LGMD1B by light and electron microscopy. We found that 92.5 ± 5.0% of myonuclei had structural abnormalities, including shape irregularity and/or chromatin disorganization, and the presence of peri-/intranuclear vacuoles. Chromatin changes were also observed in 50% of the satellite cell nuclei. Increased number of Pax7-positive nuclei, but fewer number of MyoD-positive nuclei were seen on immunohistochemical analyses, suggesting functional alteration of satellite cells in addition to the nuclear morphological changes in AD-EDMD/LGMD1B.     

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.     

Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31.

Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31.     

Drug treatment of patients with insomnia and excessive daytime sleepiness: pharmacokinetic considerations.

Insomnia and excessive daytime sleepiness (EDS) are frequently observed conditions in the general public. A national survey in the USA in 1979 indicated that 35% of American adults experience insomnia in the course of a year. The prevalence of EDS varies depending on the survey (0.3 to 13.3%), but a recent study stated that 2.4% of individuals reported that they continually fell asleep at work. These problems are often long term and negatively affect the individuals' quality of life. People with these sleep problems often have difficulties maintaining high levels of productivity at work or pursuing their daily activities; individuals with insomnia lack the feeling of being rested or refreshed in the morning and EDS is unavoidable in most cases. Behavioural therapy has been shown to be effective for many people affected with insomnia and EDS. However, pharmacological treatments using hypnosedatives and central nervous system (CNS) stimulants are usually necessary, and effective, for those with more severe cases. These compounds have thus been widely prescribed in clinical practice (e.g., 2.6% of all adults surveyed used medically prescribed hypnosedatives and 4.5% used over-the-counter drugs to promote sleep). The onset and duration of action of these hypnosedatives and CNS stimulant drugs are important factors to be considered when prescribing these compounds. These factors primarily depend on physicochemical properties (lipid solubility and protein binding), as well as the pharmacokinetic profile (absorption, distribution, elimination and clearance) of the compounds. Significant differences in profile exist amongst hypnosedatives and CNS stimulants, and these differences may account for the observed variations in clinical action and adverse effects during and after treatment. In this review, we will introduce recently obtained knowledge of the pharmacokinetics of hypnosedatives and CNS stimulants and their applications for patients affected with insomnia and EDS.