Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Angiotensin I conversion and coronary constriction by angiotensin II in ischemic and hypoxic isolated rat hearts.

Dose-response curves of angiotensin I (AI, 1.0-1000.0 pmol) and angiotensin II (AII, 1.25-1250.00 pmol) were obtained in isolated rat hearts subjected to control conditions, mild hypoxia (PO2 = 145 mm Hg), reoxygenation, ischemic (perfusion pressure = 35 mm Hg) and reperfusion. Both AI and AII caused dose-dependent coronary flow (CF) of 26 +/- 3 and 27 +/- 2%, respectively. The effects of both AI and AII were substantially attenuated during hypoxia, but were fully restored upon reoxygenation. During ischemia, the effect of AII was unaltered while the effect of AI was enhanced compared to the control (P less than 0.05). This enhancement was reversible on reperfusion. Cardiac conversion of AI, calculated from ED50 values for AI and AII, was significantly increased during ischemia (P less than 0.05). Infusion of saralasin (0.5-5.0 micrograms/min) did not increase CF in any of the groups. We conclude that (1) the coronary vasoconstrictive effect of AII is preserved in ischemia but attenuated in hypoxia and (2) cardiac conversion of AI to AII is enhanced in hearts injured by ischemia.     

Synthesis of CCK-8 Tetrapeptide Fragment by Enzymatic Method

Cholecystokinin (CCK )isa polypeptidehor monecontaining 33aminoacidsresiduewithgastroin testinal,biliarandbrainactivities Itiswidelydis tributedinthevertebratecentralnervoussystem ,anditcanstimulateextensivelytheliberationofinsulinandglucagonfromtheLangerhansislets GreateffortshavebeendevotedtothesynthesisofCCK 8,itsderivativesandanalogues Amongthedifferentmethods ,theenzymaticmethodisthemosteffectiveonewithmanyadvantagesoverconventionalchemicalmethodologies :enzymespecificitysuppress essid…     

Experimental and clinical possibilities of MR spectroscopy of the heart

MR-spectroscopy of the heart is a relatively new technique for the study of various aspects of cardiac metabolism. The majority of results has so far been obtained with the isolated perfused heart. Here, 31P-MR spectroscopy can be employed to measure high-energy phosphate metabolism and intracellular pH repeatedly and non-invasively. Using a technique called saturation transfer, velocities of enzymatic reactions, such as the creatine kinase reaction, can be measured. Intra- and extracellular Na+ and K+ concentrations can be registered with 23Na- and 39K-MR in conjunction with shift reagent. 13C-MR can be used to tackle carbohydrate metabolism. In-situ-R-spectroscopy allows determination of high-energy phosphates in intact large mammals. Clinical applications of MR-spectroscopy remain to be defined; preliminary results indicate high diagnostic and prognostic potential for patients with coronary artery disease and congestive heart failure.     

Determination of bone mineral density by dual x-ray absorptiometry in patients with uncemented total hip arthroplasty.

Bone remodeling is an expected sequela with total hip arthroplasty (THA). Although there are several methods of estimating bone response in THA patients from radiographs, there are no accurate and generally accepted methods for quantitative determinations in vivo. In this study, we describe an application of dual x-ray absorptiometry (DXA) for measuring bone mineral content and bone mineral density in the proximal femur following THA. DXA is a noninvasive technique with minimal radiation exposure (< 5 mrem). Various aspects of measurement error (accuracy and reliability) of this application of DXA were determined in a series of studies reported here. Accuracy error (how similar are the measured and actual values) was < 1% determined in bone phantoms of four densities. Precision error (how reproducible are the measurements) was also < 1% at all four densities in the phantoms and was only slightly elevated (0.9-1.5%) in repeated measurements of implanted cadaver femora. Precision error in vivo, determined both from multiple replicates on five patients and from duplicate scans on 30 patients, was further elevated but remained < 5%. Contributions to precision error, rotation of the leg, and interoperator variability were assessed; none was found to elevate precision error appreciably. We suggest that DXA is a feasible method for quantifying bone response following THA, and will allow discrimination of small changes (> 5%) not previously measurable.