Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

多发性肌炎的动物模型及雷公藤多甙对其疗效的研究

目的　寻找一种多发性肌炎的良好动物模型及其有效的治疗药物。　　方法　给动物注射同种大鼠的肌匀浆 ,观察其活动状态 ;通过肌肉组织染色及ELISA法 ,研究肌肉的病理学变化 ,同时给动物喂服雷公藤多甙观察药物疗效。　　结果　部分动物表现肌无力和肌萎缩 ,大多数肌肉组织学检查示肌纤维炎性变 ;免疫组化检查可见肌膜、肌内膜和肌束膜中有IgG沉积。动物服雷公藤多甙后肌肉病变明显减轻 ,其疗效与强的松相似。　　结论　用同种大鼠肌匀浆免疫动物可诱导出多发性肌炎的动物模型 ;雷公藤多甙能有效地治疗多发性肌炎。     

An etiological study on fulminant viral hepatitis]

Viral markers were studied in 79 cases of viral hepatitis with hepatic failure. The results were shown as follows: 8 cases were positive for anti-HAV IgM (10.12%); 76 cases positive for HBsAg or anti-HBc IgM (96.20%) and 41 cases positive for anti-HCV antibodies (51.89%). Among those with anti-HCV positive, 35 cases were co-infected with HBV, 5 cases with HAV and/or HCV, only one was infected with HCV alone 2 cases were HD-Ag positive (2.52%) and one not identified (1.27%). With the reference of clinical findings, patients co-infected with HBV/HCV or anti-HBc IgM positive were more critical and usually entail higher mortality. In cases with HCV co-infections, the positive HBV replication markers seems to be reduced. Hepatic failure without HBV replicative markers had a high rate of hepatic coma as well as poor outcome.     

The use of the facial translocation technique in the management of tumors of the paranasal sinuses and skull base.

OBJECTIVE: We sought to assess the efficacy of facial translocation in the management of tumors of the skull base and paranasal sinuses. STUDY DESIGN AND SETTING: From July 1993 to December 1999, 75 patients, aged 3 to 102 years old, underwent facial translocation. Thirty-three (44%) patients also underwent a combined neurosurgical procedure. Nineteen (25%) had previous surgery. These patients were followed up to 6 years. RESULTS: There were 21 benign and 54 malignant tumors. There were no perioperative deaths. The morbidity rate was 31%. Of the 54 patients with malignant tumors, the actuarial 3-year survival rate was 59%, whereas the local control rate was 54%. CONCLUSION: The facial translocation technique offers favorable exposure of the critical zones of the anterior and middle cranial base, thus facilitating extensive resection and reconstruction. SIGNIFICANCE: This study demonstrates that facial translocation is one of the best surgical approaches to the skull base.     

Coronary permeability and left ventricular function following thrombolytic therapy

We study 40 patients, 55 +/- 7 years old with acute myocardial infarction treated early by thrombolytic therapy (20 STK and 20 rt-PA). All patients were angiographically studied in the following conditions: 1) baseline, before initiating therapy. 2) Three hours after treatment. 3) Twenty four hours later. 4) Before discharge. The infarct related artery was patent 24 hours after treatment in 31 patients (78%); five of them were patent before treatment, and we observed an early reperfusion in 20 patients (57%) and late reperfusion in 6 patients (17%). The number of patients with angiographic evidence of intraluminal thrombus decreased progressively through conditions while the grade TIMI of coronary perfusion increased in the absence of reocclusion. Final regional wall motion of infarct related myocardial zones and their degree of recovery were significantly higher in recanalized patients, as compared with non-reperfused patients. Similarly, left ventricular functional recovery was higher in patients with antegrade of collateral flow to the infarct area, as compared with totally occluded patients.     

Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.

Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P < 0.001) and 17.3 +/- 6.9% (P < 0.001) at 2 and 7 d, respectively. Quantitative estimates of neuronal loss at 7 d (2.3 +/- 7.7% reduction; P = 0.58, not significant) demonstrate that the NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.     

Hand hygiene and glove use behavior in an Italian hospital.

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.