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.     

PR35THE INCIDENCE OF NON‐MELANOMA SKIN CANCER IN NEW ZEALAND

Background It is estimated that skin cancers cost $33 million per annum to the New Zealand healthcare system. Basal cell carcinoma and squamous cell carcinoma are the commonest types of non melanoma skin cancers (NMSCs). Anecdotal evidence indicates that there has been a doubling in the incidence of NMSCs in New Zealand over the last decade. Because of the high incidence mandatory reporting of NMSCs to the National Cancer Registry is not required. This lack of accurate data has led to poor health care policies and strategies including funding and workforce planning. Aims The aims of this study are to (1) present the latest statistics on NMSCs in New Zealand, including the incidence across different regions over the last decade, patient demographics, anatomic distribution of NMSCs, incidence and sites of metastasis, and disease‐specific survival; to (2) the histopathology of NMSCs, including surgical margins, histologic grade, and perineural, lymphatic, and vascular invasion; and (3) the relative role of different faculties treating NMSCs. Method This project has been approved by the multi‐centre ethics committee. A retrospective review was conducted from patients’ histology records from public and private pathology laboratories within defined catchment areas. Criterion for analysis is a confirmed diagnosis of NMSC treated surgically. A Microsoft Access database is created that will facilitate subsequent data retrieval and analysis. Results and Conclusion It is hoped that this up‐to‐date data will form the framework for the development of sound and sustainable healthcare policies of management of NMSCs including management strategies and workforce planning, and research direction on this common disease.     

Correlates of lifetime suicide attempts among individuals with affective disorders in a Chinese rural community.

The aim of this study was to compare the demographic and clinical characteristics of individuals with affective disorders who had attempted suicide at some time in their lives and those who had not made a suicide attempt. In a Chinese rural community, individuals with suicide attempt (N = 30) and those without suicide attempt (N = 166) were assessed with Present State Examination (PSE). Attempters had a significantly higher level of family economic status, higher rate of lifetime depressed mood and hopelessness, and delusions than nonattempters. The logistic regression models also indicated that depressed mood and hopelessness were the most important predictors of suicide attempts. No significant difference in treatment condition was found between attempters and non-attempters. Early identification and interventions focusing on reducing depressed mood, hopelessness, and controlling psychotic symptoms may be helpful in reducing the risk of suicide attempts among individuals with affective disorders residing in the community.     

PR01“A PICTURE SPEAKS A THOUSAND WORDS”– THE USE OF DIGITAL PHOTOGRAPHY AND THE INTERNET IN MONITORING FREE TISSUE TRANSFER

Purpose Post operative monitoring is crucial for the success of microsurgical free tissue transfer. Sophisticated and expensive methods are available for monitoring. We propose a novel technique using digital photography and the internet as a reliable and cost effective method to monitor free tissue transfers. Methods 163 micro‐vascular procedures were monitored using this technique over 8 months. Serial photographs taken to show flap color. Capillary refill time, pin prick‐ bleed time and color and hand held Doppler signal was recorded in the movie mode of a standard 5 mega pixel camera with duration of 15 seconds. Data was sent to the surgeon at regular intervals and or as deemed necessary. Results Analysis of the 67 cases is presented. 5 re‐explorations were done. The early diagnosis of venous congestion was possible using this technique. Timely intervention contributed to the success of the re‐explorations and these flaps could be salvaged. The file size of images was in the range of 1 MB–6 MB. The file size of an entire set of images ranged about 7 MB–9 MB. These were sent across the ADSL internet lines. Conclusion The use of the digital images and the internet allow reconstructive surgeons to have a reliable picture of the state of their free tissue transfers. This permits decrease in observer error and saves valuable time which otherwise needs to be spent to verify situations of doubt and offers an ideal solution to the logistic problem of having to visit the patient in case of doubt.     

阿米替林合并认知疗法治疗精神分裂症后抑郁的对照研究

目的　评价阿米替林合并认知疗法对精神分裂症后抑郁的治疗效果。方法　将符合CCMD 3诊断标准的 86例精神分裂症后抑郁患者随机分为治疗组和对照组 ,治疗组给予阿米替林合并认知治疗 ,对照组织给予阿米替林治疗 ,疗程 12周。采用汉密尔顿抑郁量表 (HAMD)、简明精神病量表(BPRS)、阴性症状量表 (SANS)评定临床疗效 ,采用副反应量表 (TESS)评定副反应。结果　在治疗的 4、8、12周末 ,HAMD评分治疗组优于对照组 ,显效率分别为 83 95 %和 6 1 90 % (u =5 .83,P <0 0 5 )。结论　阿米替林与认知治疗组结合治疗精神分裂症后抑郁疗效好于单用阿米替林治疗。     

输尿管上段结石的微创手术治疗

目的：探讨输尿管上段结石的治疗方法。方法：回顾性分析输尿管镜下气压弹道碎石(URSL），后腹腔镜输尿管切开取石(RLU)、经皮肾穿刺取石(PCNL)治疗输尿管上段结石患者的临床资料。其中URSL组25例，RLU组20例。PCNL组9例。结果：URSL组碎石成功18例；7例不成功，其中3例改为开放手术，1例改为后腹腔镜取石。2例行ESWL术，1例仅留置双J管。术后1个月拔管后自行排出。2例并发输尿管穿孔。RLU组取石成功18例，2例滑入肾内，经配合输尿管镜和腹腔镜直视下经皮肾穿刺取石成功，术后15例有伤口漏尿。PCNL组成功9例，无并发症。结论：USRL创伤小。术后恢复快。是治疗输尿管上段结石的较为满意的治疗方法。PCNL创伤小，取石成功率高，在结石靠近肾盂、儿童输尿管上段结石并同侧肾结石和结石以下输尿管狭窄时应优先考虑。但技术难度较大。RLU可作为URSL不成功后的辅助治疗方法。     

In vitro reversal MDR of human carcinoma cell line by an antisense oligodeoxynucleotide-doxorubicin conjugate.

A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo.