Aging is not equal across memory systems.

The present experiments compared the effects of aging on learning several hippocampus- and striatum-sensitive tasks in young (3-4 month) and old (24-28 month) male Fischer-344 rats. Across three sets of tasks, aging was accompanied not only by deficits on hippocampal tasks but also by maintained or even enhanced abilities on striatal tasks. On two novel object recognition tasks, rats showed impaired performance on a hippocampal object location task but enhanced performance on a striatal object replacement task. On a dual solution task, young rats predominately used hippocampal solutions and old rats used striatal solutions. In addition, on two maze tasks optimally solved using either hippocampus-sensitive place or striatum-sensitive response strategies, relative to young rats, old rats had impaired learning on the place version but equivalent learning on the response version. Because glucose treatments can reverse deficits in learning and memory across many tasks and contexts, levels of available glucose in the brain may have particular importance in cognitive aging observed across tasks and memory systems. During place learning, training-related rises in extracellular glucose levels were attenuated in the hippocampus of old rats compared to young rats. In contrast, glucose levels in the striatum increased comparably in young and old rats trained on either the place or response task. These extracellular brain glucose responses to training paralleled the impairment in hippocampus-sensitive learning and the sparing of striatum-sensitive learning seen as rats age, suggesting a link between age-related changes in learning and metabolic substrate availability in these brain regions.

The prognostic use of right heart catheterization data in patients with advanced heart failure: how relevant are invasive procedures in the risk stratification of advanced heart failure in the era of neurohormones?

BACKGROUND: Right heart catheterization long has been a routine investigation in advanced heart failure, and its measurements have been linked variably to prognosis. However, in the modern era, newer potential markers of prognosis are coming to light. This study reconsiders the use of right heart catheterization data and compares their use to that of N-terminal pro-brain natriuretic peptide (NT-proBNP), a neurohormone linked with prognosis in chronic heart failure. METHODS: We assessed prospectively the prognostic potential of baseline right heart catheterization data in 97 consecutive patients with advanced heart failure referred to the Scottish Cardiopulmonary Transplant Unit for consideration of cardiac transplantation. Patients underwent baseline routine investigation, including right heart catheterization and blood draws for NT-proBNP analysis. Patients were observed for a median of 370 days. RESULTS: The primary end-point of all-cause mortality was reached in 17 patients (17.5%), and the secondary end-point of all-cause mortality or urgent cardiac transplantation was reached in 21 (21.6%) patients. Univariate predictors of all-cause mortality included pulmonary artery systolic pressure (PASP), pulmonary artery wedge pressure (PAWP), and NT-proBNP concentration greater than their median values. Univariate predictors of the secondary end-point included right atrial pressure, PASP, PAWP, and NT-proBNP concentration greater than their median values, and left ventricular ejection fraction, cardiac output, and cardiac index less than their median values. In multivariate analyses, however, only NT-proBNP concentration remained an independent predictor of all-cause mortality. Both NT-proBNP concentration and PAWP were independent predictors of all-cause mortality and of the need for urgent cardiac transplantation. CONCLUSION: Baseline data from routine right heart catheterization are of limited prognostic use in advanced heart failure. A baseline NT-proBNP concentration is a superior, non-invasive method of risk stratification in this era of measuring neurohormones.

N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure.

AIMS: The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2 and the HFSS. METHODS AND RESULTS: We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (chi2=6.03, P=0.01) and the combined endpoint of all cause mortality or urgent CTx (chi2 =12.68, P=0.0004). LVEF, VO2 and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study. CONCLUSION: A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2 or HFSS.

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method.

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.

The use of FT-IR for the determination of stratum corneum hydration in vitro and in vivo.

Measurement of the water content of stratum corneum plays an important role in physiological and therapeutic inquiries in dermatology. There are many techniques available for non-invasive determination of skin hydration such as measurement of electrical, mechanical, thermal and spectroscopic properties of the skin. Most techniques, however, suffer from the fact that they do not employ a direct measurement of water content rather a property caused by skin hydration. Recently, Potts et al., (Arch. Derm. Res. 277, 489-495, 1985) developed an FT-IR method for the determination of water content of the skin both in vitro and in vivo. The method employed attenuated total reflectance infrared (ATR-IR) to measure a weak O-H stretch formed by the presence of water at 2100 cm-1. This absorbance is distant from interferences due to skin and most topically applied substances and therefore may be used in the quantitation of skin water content (hydration). This report describes the use of this technique in an investigation into the effect of occlusion on the water content of the skin. Method development and validation employing an in vitro system is also discussed.

Comparison of the metabolism of chylomicrons and chylomicron remnants by the perfused liver.

1. The hepatic metabolism of chylomicrons and chylomicron remnants was compared after adding approximately equal numbers of each lipoprotein particle to the perfusate of isolated livers. 2. At least 40% of the added remnants were metabolized by the liver compared with less than 3% for chylomicrons. 3. There was significantly more net removal of labelled remnants than of chylomicrons by the liver. 4. A greater proportion of labelled cholesterol than of labelled triacylglycerol fatty acids was transferred to the liver from each lipoprotein. 5. Cholesteryl esters of remnants were hydrolysed to triacylglycerol fatty lipoprotein. 5. Cholesteryl esters of remnants were hydrolysed to triacylglycerol fatty acids of remnants were oxidized to CO2 more extensively than those of chylomicrons. 6. There was greater oxidation of remnant glycerolipic [(1(-14)C]oleate than of glycerolipid [1(-14)C]palmitate. 7. A large fraction of the fatty acids of remnants, but not of chylomicrons, was transferred to phospholipids, which were released by the liver in a lipoprotein of relative density less than 1.006. 8. Label from remnants, but not from chylomicrons, was found in lipoproteins of relative density greater than 1.006, which were not released during perfusion but could be flushed out from the liver at the end of perfusion.

Carotid sinus syndrome: new surgical considerations.

1. Direct surgical denervation of the carotid sinus would appear to offer the best long-term results for carotid sinus syncope. 2. Carotid sinus denervation should be done under temporary cardiac pacing for safety and for completeness of denervation. 3. Arteriography is indicated to eliminate those cases of cerebral vascular insufficiency that might mimic carotid sinus syndrome. Credit must be given to Dr. R. Hughes, Clearfield, Pa., who recognized this diagnosis and referred the patient for therapy.