Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Plasma catecholamines and lipoproteins in chronic psychological stress.

Changes in plasma catecholamines, lipoproteins and dietary intake were examined in 13 medical students during a 3-month period prior to their examinations, and in 12 controls. In the medical students mean +/- s.e.(mean) plasma cholesterol increased over the study period (3.98 +/- 0.16 v. 4.26 +/- 0.16 mmol/l, P less than 0.05) and this was reflected by a rise in low-density lipoprotein cholesterol (2.53 +/- 0.15 v. 2.71 +/- 0.17 mmol/l, P less than 0.05). Both supine adrenaline (0.45 +/- 0.05 v. 0.70 +/- 0.07 nmol/l, P less than 0.01) and noradrenaline (2.74 +/- 0.18 v. 3.40 +/- 0.31 nmol/l, P less than 0.05) increased over this period. Apart from a decline in the modest alcohol consumption (9.1 +/- 3.45 v. 2.6 +/- 1.4 g/day, P less than 0.02) there was no change in dietary intake in the medical students. There were no significant changes in plasma catecholamines, lipoproteins or dietary intake in control subjects over the study period. Changes in catecholamines and lipoproteins occurring in association with chronic psychological stress may contribute to the increased coronary heart disease mortality associated with Type A behaviour and stressful life events.     

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models

Summary Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models — the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL₂ cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group, HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.     

Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia

We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride <2.1 mmol l⁻¹; haemoglobin HbA_1c 5.5%±0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride >2.1 mmol 1⁻¹; HbA_1c 8.8%±0.9%); nondiabetic subjects with serum triglycerides <2.1 mmoll⁻¹; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride>2.1 mmol l⁻¹). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d<1.006 g ml⁻¹). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%–15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic control subjects whose levels decreased after 2 h (P<0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic patients (P<0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled diabetic and non-diabetic subjects.     

Abnormalities in apo B-containing lipoproteins in diabetes and atherosclerosis

Atherosclerosis is the major cause of death in patients with diabetes. Low-density lipoprotein (LDL) being the most important cholesterol-carrying lipoprotein has been studied extensively in both diabetes and non-diabetes. This paper reviews the literature but also focuses on the precursors of LDL and in particular the postprandial apo B-containing lipoproteins. Abnormalities in the postprandial lipoproteins and alteration in chylomicron assembly and clearance are discussed and the evidence presented suggesting the importance of dysregulation of these lipoproteins in atherosclerotic progression. The relationship between chylomicron production in the intestine and hepatic release of very low-density lipoproteins (VLDL) is explored, as is the interrelationship between clearance rates of these lipoproteins. The size of LDL influences its atherogenicity. VLDL composition and size in relation to its influence on LDL is discussed. The effect of diet on the composition of lipoproteins and the relationship between fatty acid composition and clearance is reviewed. Evidence that diabetic control beneficially alters lipoprotein composition is presented suggesting how improved diabetic control may reduce atherosclerosis. The review concludes with a discussion on the effect of the apo B-containing lipoproteins and their modification through glycation and oxidation on macrophage and endothelial function.     

Protective effect of flavonoids against red blood cell hemolysis by free radicals

BACKGROUND:

Flavonoids are polyphenolic substances with antioxidant properties, and they are found in different vegetables and fruits. Epidemiological studies have shown that the consumption of flavonoids reduces the prevalence of cardiovascular diseases. The use of synthetic antioxidants, however, has been limited because of their toxicity. Therefore, medical researchers have intensified their quest to find natural antioxidants.

OBJECTIVES:

To investigate the effect of several pure flavonoids, such as kaempferol, quercetin, morin and rutin, on red blood cell hemolysis and evaluate their -SH capacity as an indicator of membrane protection.

METHODS:

The rate of hemolysis and cell membrane -SH capacity were determined by spectrophotometry. Red blood cell peroxidation was induced using 2,2′-azo-bis-(2-amidinopropane) dihydrochloride. The effect of each flavonoid on hemolysis was examined at three concentrations (0.5 μg/mL, 5 μg/mL and 10 μg/mL), however, only the greatest concentration (10 μg/mL) of each flavonoid was used to study the effect on -SH groups.

RESULTS:

In all cases, the antioxidant activity was dose-dependent. Rutin showed the highest inhibitory effect on hemolysis among flavonoids (42.5%). The protective effect of kaempferol, rutin and morin against -SH group oxidation measured 7.7%, 23.3% and 26.4%, respectively.

CONCLUSIONS:

Results showed that flavonoids and flavonoid-containing plants can be used as natural antioxidants for the treatment and prevention of disease conditions, the pathogenesis of which is mediated by lipid peroxidation.     

Outcome of major cardiac injuries at a Canadian trauma center

Background  

Canadian trauma units have relatively little experience with major cardiac trauma (disruption of a cardiac chamber) so injury outcome may not be comparable to that reported from other countries. We compared our outcomes to those of other centers.