Endothelial and smooth muscle properties of coronary and mesenteric resistance arteries in spontaneously hypertensive rats compared to WKY rats

Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D₁₀₀) were determined and vessels were set up to a normalized internal diameter (0.9 D₁₀₀). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells.     

表小檗碱对α受体的作用

表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择     

Hepatic fibrosis in fetal alcohol syndrome. Pathologic similarities to adult alcoholic liver disease

The light- and electron-microscopic changes in a biopsy of the liver obtained at age 17 mo from a child with fetal alcohol syndrome were studied. At the time of biopsy, hepatomegaly and raised serum transaminases were present as well as neurologic and growth defects and the typical facial anomalies seen in this syndrome. Light microscopy of the liver biopsy specimen revealed parenchymal fat with portal and perisinusoidal fibrosis. Ultrastructurally, perisinusoidal spaces contained deposits of intermediate-size and large collagen fibers, myofibroblasts and occasional Ito cells, and subendothelial basement membrane-like material. These changes resemble those seen in adult human and baboon alcoholic liver disease and suggest that hepatic fibrosis in fetal alcohol syndrome has a similar pathogenesis.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Investigating the role of heparin sulfate proteoglycans in hereditary multiple exostoses (HME) tumourigenesis

Introduction Heparin sulfate (HS) has long been implicated in the bone deformity hereditary multiple exostoses (HME), and it is now clear that HME is associated with mutations in the HS biosynthetic genes EXT1 and EXT2. Interestingly, HME is also associated with an increased risk of chondro‐ and osteo‐sarcomas. Methods and results Preliminary analysis of GAG samples purified from fibroblasts of both HME and isolated non‐HME exostoses patients reveal a dramatic shift in the ratio of CS : HS, with the HME and isolated cases having a much higher proportion of CS relative to normal controls. This is true in the case of both shed and cell surface material but is far more extreme in the latter, with the HS reducing from approximately 45% in the controls to less than 10% in HME patients. Initial analysis also reveals shortened chain length within these samples; indeed they often have two populations of chains present. Simple analysis of the total disaccharide composition of these samples demonstrates no significant differences against controls. However, detailed analysis of the subpopulations of chains (as determined by chain length) within these samples as well as cartilaginous samples from exostoses patients may provide further insight into the changes that occur within the biosynthetic pathway following disrupted EXT function. We are also carrying out immunocytochemistry with a variety of HS‐specific antibodies with the aim to further investigate normal HS structure and localization. This is being carried out on human primary chondrocytes isolated from normal patients and also adult mesenchymal stem cells as they undergo differentiation into chondrocytes. HS has been identified in both these cell types, and it is hoped that the manipulation of these cells through RNAi of different enzymes of the HS biosynthetic pathway will provide a suitable model for studying what changes may occur in cellular HS structures over the initial differentiation process in the growth plate. Discussion Together, these investigations should provide a good model to allow us to determine the role of HS in chondrocyte differentiation and maturation in both normal and diseased states.     

FS13.5Occupational contact dermatitis: printer worker's viewpoints

Introduction:  Occupational contact dermatitis (OCD) is very common in the printing industry due to contact with chemicals, paper, and wet work. It can be avoided by adequate protective measures, but the effectiveness of intervention depends heavily on the employer's and employee's awareness of this health risk.
Objectives:  The study aimed to collect information on the knowledge, attitudes and beliefs of print workers about the risk of OCD and methods of prevention.
Methods:  A series of focus groups were held with print workers, health and safety officers and managers to discuss their awareness of dermal risk factors, risk behaviour at work, attitudes to health and safety and options on possible preventive measures. A number of companies were also visited to observe, overtly and covertly, the normal work practices.
Results:  OCD was not perceived to be either a major problem or a health and safety priority. There was general agreement about the processes and work practices that could cause skin problems. However, work practices varied considerably and did not always reflect this awareness. There was general concern about the type and availability of personal protective equipment, especially gloves and after‐work skin cream. The provision of an occupational health service was generally felt to be inadequate, and no company had a policy in place that specifically addressed skin care.
Conclusions:  These findings highlight the urgency to intensify health and safety education on skin care within the printing industry. Recommendations were developed for the evaluation of a series of risk reduction strategies.