甲氧苄氨嘧啶—PVP共沉淀物的研究

本工作用差示扫描量热法(DSC)研究甲氧苄氨嘧啶与PVP溶剂法制备的共沉淀物,表明已不存在甲氧苄氨嘧啶晶体。用x射线衍射法研究了1:12共沉淀物,证明无甲氧苄氨嘧啶的晶体衍射峰。经分光光度法测定结果,1:12共沉淀物比原药的溶解度大28.3倍。     

A central mechanism of acute baroreflex resetting in the conscious dog

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses.

A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.     

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.     

Validity and reliability of the Bengali version of the Hepatitis Quality of Life Questionnaire

Purpose  

Hepatitis B virus (HBV) is endemic in Bangladesh, and the quality of life (QoL) of these patients remains unknown as there is no instrument available in the native language. In this study, we translated the 56-item Hepatitis Quality of Life Questionnaire (HQLQ) into Bengali and evaluated its validity and reliability.     

应用前列腺素E1注射治疗勃起功能障碍8年经验

目的观察前列腺素E1(PGE1)注射治疗勃起功能障碍(ED)的长期疗效、副作用及预后。方法使用PGE1行阴茎海绵体注射,阴茎硬度检查仪(Rigiscan)连续记录1h,并根据观察结果,调查PGE1注射剂量,确定每例患者合适的注射量,掌握注射方法后回家自行注射。共筛选出ED患者410例,随访患者阴茎勃起情况、药量调整和副作用。结果410例ED患者中,心理性139例,静脉性83例,动脉性36例,神经性78例,混合性74例。对治疗满意的患者有256例(62.44%),其中21例(5.1%)在使用PGE15次后停用,并能达到满意的性生活而治愈。293例(71.46%)患者自述注射时有胀痛感。171例(43.17%)因疼痛(105例)、操作不便(25例)、副作用顾虑(37例)和其他原因(4例)而于6个月后放弃治疗。204例(49.76%)患者使用时间已超过1年,24例(5.85%)患者使用时间已超过5年,7例(1.7%)使用已有8年。未发现阴茎异常勃起和阴茎海绵体纤维化。注射损伤阴茎表面血管致瘀斑者有20例。有27例患者失访。结论PGE1是治疗ED的一种安全有效的药物,可以长期使用。其最常见的副作用是阴茎疼痛。Rigiscan能帮助确定PGE1的注射剂量。