Specific 5-hydroxylation of piperlongumine by Beauveria bassiana ATCC 7159.

A new hydroxylated derivative was efficiently prepared by transforming the natural anti-cancer product, piperlongumine, with Beauveria bassiana ATCC 7159. Its structure was determined to be 5-hydroxylpiperlongumine on the basis of the spectroscopic data. The absolute configuration at C-5 was established as R by Mosher's method.

Magnetic resonance mapping demonstrates benefits of VEGF-induced myocardial angiogenesis.

Coronary occlusive disease is the leading cause of death in industrial nations and affects one in four adults. Although heart attacks are caused by occlusion of a coronary artery, some patients have occlusions without infarction because they have sufficient collateral vessels providing an alternate pathway for blood supply. Vascular endothelial growth factor (VEGF) is an angiogenic peptide that can stimulate collateral vessel development in the ischaemic myocardium. We used magnetic resonance imaging (MRI) and image processing to identify and quantify non-invasively the benefits related to VEGF infusion on collateral development in the heart. This was accomplished as a placebo-controlled study in the porcine model of chronic ischaemia that most closely mimics the human pathophysiology of progressive coronary occlusion. Image series converted to a space-time map demonstrated that with treatment the ischaemic zone was smaller and the contrast arrival delay was less, which resulted in better ejection fraction and regional wall thickening. These findings demonstrate in a manner applicable to humans, that VEGF improves collateral blood supply, resulting in improved cardiac global and regional function after and in spite of coronary artery occlusion.

Cardiogenic shock induced by cocaine in swine with normal coronary arteries.

OBJECTIVE: The aim was to test the hypothesis that acute intravenous cocaine administration can cause coronary microvascular constriction culminating in myocardial ischaemia and cardiogenic shock. METHODS: Systemic haemodynamic variables and coronary blood flow were measured in 14 Yorkshire swine at baseline and following intravenous administration of 1, 3, and 10 mg.kg-1 of cocaine. Epicardial coronary artery diameter was measured from coronary arteriograms and coronary flow velocity was recorded with a Doppler flow wire. RESULTS: Cocaine produced a decrease in mean arterial pressure (65%), cardiac output (80%), and stroke volume (80%), and an increase in pulmonary artery diastolic pressure (60%). Although coronary blood flow decreased by 70%, epicardial coronary cross sectional area decreased by only 37-45%. Pretreatment with prazosin did not abolish the decrease in coronary blood flow. After administration of 10 mg.kg-1 of cocaine, five of 14 animals developed myocardial ischaemia and cardiogenic shock, culminating in ventricular fibrillation and death. CONCLUSIONS: In anaesthetised Yorkshire swine, cumulative intravenous doses of cocaine caused a significant reduction in coronary blood flow resulting in myocardial ischaemia, which cannot be attributed to epicardial vasoconstriction alone. This suggest that cocaine-induced coronary ischaemia may result from microvascular constriction, which is only partially prevented by alpha 1 blockade. In addition, direct toxic effects of cocaine on the myocardium may also contribute to the development of cardiogenic shock.

Extent of myocardial collateralization: determination with three-dimensional elastic-subtraction spiral CT.

RATIONALE AND OBJECTIVES: This study was undertaken to develop a standard that can be used to assess new high-resolution collateral zone imaging methods. MATERIALS AND METHODS: The authors performed ex vivo helical CT in seven pig hearts after microsphere studies of blood flow and coronary angiography. They compared the zones of collateralization depicted at CT and at microsphere studies. RESULTS: The extent of the collateral zone at CT, computed by using elastic subtraction, correlated well with the coronary blood flow distribution determined with microsphere analysis (r = .95). The root-mean-square error was 6.5%, which indicates good agreement. CONCLUSION: Accurate assessment of collateralization extent has become an important goal because of the discovery of agents that stimulate the growth of coronary collateral vessels. The precision of elastic-subtraction CT and its validation with respect to the blood flow distribution at microsphere analysis indicate that elastic-subtraction CT can serve as a standard for the measurement of collateralization extent.

Endoscopic surveillance practice for Barrett' s oesophagus in Scotland and early experience in implementing local guidelines.

Management of columnar lined oesophagus (CLO; Barrett s oesophagus) is controversial. We prospectively audited surveillance practices in Scotland and prospectively assessed the impact of introducing local guidelines for Barrett s surveillance in Edinburgh. Most respondents were gastroenterologists. The majority take random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80 patients underwent surveillance. The guideline protocol was not followed in 30 (37.5%) patients. Follow up of patients without dysplasia generally conformed to the guidelines. Follow up of patients with low grade dysplasia was highly variable while management of those with high grade dysplasia followed the guidelines. Overall we found a wide variability in the management and surveillance of CLO. Early experience suggests that implementation of guidelines is helpful but there is still variation in practice.

Noninvasive comprehensive characterization of renal artery stenosis by combination of STAR angiography and EPISTAR perfusion imaging.

In a small fraction of patients with hypertension, the cause is stenosis of the renal artery. To date, there is no established noninvasive screening technique available to identify this population, for whom treatment with a surgical procedure or percutaneous transluminal angioplasty is often possible. In this study, the sensitivity and specificity of STAR angiography and EPISTAR perfusion imaging in characterizing renal artery stenosis were evaluated in an animal model. Qualitatively, STAR provided projection angiograms that were comparably sensitive to x-ray angiograms but obtained noninvasively. The sensitivity for detecting the stenosis was 100%. The specificity varied according to the definition of the threshold for significance, which varied 78-94%, depending on whether > 70% or > 50% diameter reduction was considered. Improvements in specificity will depend upon use of shorter echo times and higher spatial resolution. Our preliminary data indicate that EPISTAR provides sensitivity and specificity of 100% for characterizing stenosis with diameter reductions of > 70%.