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Biomedical subjects

A Frey

Publications and source records attributed to A Frey.

At least 73 records · Page 4Linked to original sources
PubMed1991

[ST-segment depressions correlate in patients with hypertensive heart disease with spontaneous changes in blood pressure].

In 15 patients with essential hypertension, anginal pain, and angiographically excluded coronary artery disease 24-h monitoring of the ST-segment and blood pressure was performed. 26 episodes with ST-segment depressions 0400.1 mV were recorded in 11/15 patients. In 10/26 episodes with ST-segment depressions blood pressure was elevated above 150/95 mm Hg or by more than 20% as compared to three successive measurements before the ST-segment depressions. Heart rate was increased by more than 20% in 20/26 ST-segment depressions. During 9 periods with ST-segment depressions angina pectoris was reported; in addition 27 anginal attacks without ST-segment depressions were observed. A significant, positive correlation between the diastolic (p less than 0.005) and systolic (p less than 0.02) blood pressure and the extent of the ST-segment depression was observed. These correlations imply a patho-physiological meaning of ST-segment depressions in hypertensive patients.

Angina Pectoris↗
PubMed1990

Origin and distribution of enteric neurones in Xenopus.

In Xenopus, we investigated the origin of enteric neurones and their distribution in relation to the extracellular matrix (ECM) components, fibronectin (FN) and tenascin (TN). Enteric neurone precursor cells originate from the anterior trunk neural crest (NC). They migrate along the ventromedial NC pathway (between somites and neural tube/notochord) into the primitive gut (via the dorsal mesentery/lateral plate mesoderm) where they differentiate into enteric neurones. NC cells were identified during their migration and in the gut using the X. laevis - X. borealis nuclear marker system. The neuronal character of NC cells in the gut could be demonstrated immunohistochemically with a monoclonal antibody against the HNK-1 epitope. This antibody is superior to N-CAM and neurofilament antibodies which proved insufficient in Xenopus. In early tadpoles (stage 45), enteric neurones occurred frequently in the mesenchymal lining of the oesophagus, either singly or in groups of two to three cells. In more distal portions of the digestive tract, enteric neurones were rarely found. In metamorphosing tadpoles (stage 62/63), enteric neurones were scattered singly beneath the mucosa, or formed small aggregates between the inner and outer muscle layer throughout the length of the digestive tract. The neurones occurred in positions corresponding to the myenteric and submucosal plexus of higher vertebrates. The distribution of enteric neurones was studied in relation to fibronectin (FN) and tenascin (TN), glycoproteins of the ECM, which support (FN) and inhibit (TN) amphibian NC cell migration. Using immunohistochemistry, FN was found during NC cell migration in ECM spaces along the ventromedial pathway, and in the gut between the mucosa and the muscle layers, where it would be able to support adhesion and migration of NC cells. TN, in contrast, appeared much later than FN, both in the dorsal trunk and also ventrally, in the gut. In older tadpoles, TN was present in the mesenchyme and muscle layers of the digestive tract, where it might have an inhibiting influence on the migration of enteric neurones within the gut wall.

Animals↗
PubMed1990

The mesophase of parenteral fat emulsion is both substrate and inhibitor of lipoprotein lipase and hepatic lipase.

Six 10% and 20% parenteral fat emulsions were separated by centrifugation into two fractions: (1) a supernatant containing the bulk of triacylglycerols (Tg) as fat particles stabilized by phospholipids (PL); and (2) an infranatant, called mesophase, consisting essentially of PL (one third of the original PL in the 10% formula, one sixth in the 20% formula, in the case of emulsions containing 12 g PL.L-1) and small amounts of Tg and free sterols, probably in the form of liposomes. The lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the Tg-rich lipoprotein clearance, hydrolyze both types of particles, although Tg-fat particles are their preferred substrate. Inactivated serum (providing apo C-II) is needed to ensure the maximum LPL hydrolysis rate of both types of particles. It partially inhibits the HL activity on the mesophase. Substrate of the lipolytic enzymes, the mesophase, is also an inhibitor of their activity, the inhibition being directly proportional to the amount of PL contained in the mesophase. This inhibition is of uncompetitive type. For LPL, it seems that the mesophase acts on a site distinct from that of the apo C-II binding site. These results partly explain the low PL clearance after a fat emulsion infusion. But in particular, they help to explain the lower clearance of a 10% emulsion (larger PL excess) compared with a 20% emulsion (with the same amount of Tg, but less PL excess).

Animals↗
PubMed1990

Synthesis of apolipoprotein A-1 in pig brain microvascular endothelial cells.

In an approach toward the identification of hitherto unknown proteins involved in the function of the blood-brain barrier, we constructed a pig brain microvessel-derived cDNA library that is enriched in blood-brain barrier specific sequences by means of subtractive cloning. Sequence analysis of selected clones revealed that one of the cDNAs encoded porcine apolipoprotein (apo) A-1. The identity of apo A-1 mRNA was further confirmed by in vitro translation of RNA from brain microvascular endothelial cells and subsequent immunoprecipitation with an antibody against human apo A-1. We further investigated the expression of apo A-1 mRNA in several tissues and in endothelial cells of the pig. It is shown that cultured brain microvascular endothelial cells provide an in vitro model to study the expression and function of apo A-1 in the microvasculature of the brain.

Amino Acid Sequence↗
PubMed1990

Gram-negative bacteria sepsis in the rat and tissue lipolytic activity on LCT and MCT/LCT-based commercial parenteral emulsions.

The aim of this study was to evaluate the effect of a gram-negative bacteria sepsis on the activity of the enzymes lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the clearance of circulating triacylglycerol-rich fat particles. Fasting rats were intravenously injected with NaCl9 g.l-1, live or heat-killed Pseudomonas aeruginosa bacteria. After 18 h the animals were killed. When compared to controls, the 2 treated groups showed an increase in body temperature, cholesterolemia, triglyceridemia and a decrease in ketonemia, proteinemia, albuminemia and in the in vitro activity of diaphragm, heart and adipose tissue LPL and of HL. The decrease in the enzyme activities occurred independent of the type of emulsion used as in vitro substrate, whether it was based on long-chain triglycerides or on medium- and long-chain triglycerides, but in any case the activity was lower with the first than with the second type of fat emulsion.

Animals↗
PubMed1990

Long-chain versus medium and long-chain triglyceride-based fat emulsion in parental nutrition of severe head trauma patients.

In order to assess the metabolic value of medium-chain triglycerides (MCT) in severely stressed intensive care unit patients, two fat emulsions containing either long-chain triglycerides (LCT), or a mixture of 50% MCT and 50% LCT were compared in 24 head trauma patients over a 10 day period. Variations of serum triglyceride, non-esterified fatty acid, glycerol and phospholipid concentrations remained comparable after both lipid infusions. Bilirubin, alkaline phosphatase and transaminase plasma levels were altered in both groups without any significant differences or clinical consequences. Cumulative nitrogen balance remained negative (-10 g N. day-1 i.e. -100 g N. 10 days-1) and comparable in both groups. However, thyroxin-binding prealbumin concentrations increased significantly in patients receiving the MCT/LCT mixture. It is concluded that MCT might have a beneficial effect on visceral protein metabolism after trauma.

Blood Proteins↗
PubMed1989

Cloning and expression of gamma-glutamyl transpeptidase from isolated porcine brain capillaries.

In order to understand the mechanisms regulating the blood-brain barrier we isolated a cDNA clone for gamma-glutamyl transpeptidase from purified porcine brain capillaries by cross-species DNA hybridization using a DNA fragment from a rat kidney cDNA clone. The sequence of the porcine gamma-glutamyl transpeptidase cDNA shows 84% identity in the coding region to the sequence of human placenta gamma-glutamyl transpeptidase cDNA. The derived protein sequences of the human and porcine gamma-glutamyl transpeptidase are 98% similar. Alignment of the porcine and the published rat gamma-glutamyl transpeptidase cDNA sequences revealed an average identity of 79%, except for a small region of 194 base pairs containing a high number of mismatches. After four nucleotide changes within this region of the published rat cDNA sequence, which correct two frame shifts, the derived protein sequences of the rat and the porcine gamma-glutamyl transpeptidase show 97% similarity. The corrected sequence, which includes a region of 65 amino acids, contains additional N-glycosylation sites as well as a hydrophobic protein domain that might represent a second membrane-spanning domain. Tissue-specific expression and diversity of the gamma-glutamyl transpeptidase mRNA transcripts in various porcine and human tissues were analysed by Northern blot hybridization. The 2.2-kb transcript of brain gamma-glutamyl transpeptidase is mainly expressed in the endothelial cells of brain microvessels, in agreement with previous data that showed the brain protein being localized within the blood-brain barrier.

Amino Acid Sequence↗
PubMed1989

Activities of lipoprotein lipase and hepatic lipase on long- and medium-chain triglyceride emulsions used in parenteral nutrition.

Prolonged parenteral nutrition frequently includes lipid emulsions. This report investigates how emulsions containing triacylglycerols of different molecular weight affect the rate of clearance in vivo and the activity in vitro of the two enzymes responsible for this clearance: diaphragm lipoprotein lipase (LPL) and hepatic endothelial lipase (HL). Whatever their molecular weight, the triacylglycerols of the emulsions were hydrolyzed by LPL and HL. However, the reaction was faster with medium-chain triglycerides (MCT) than with long-chain triglycerides (LCT). To be active, LPL required the presence of serum (apolipoprotein CII); for maximum activity less serum was required for MCT than for LCT. In the case of HL, serum inhibited the effect on LCT but not on MCT. However, hydrolysis of emulsified triacylglycerols by LPL and HL required the presence of albumin as a transporter of the fatty acids released. Less albumin was needed for maximum activity with MCT than with LCT. In vivo, although MCT emulsions were eliminated more rapidly than LCT emulsions, the former resulted in a greater increase in plasma concentrations of triacylglycerols and free glycerol than did the latter. This is explained by the fact that MCT provides about 1.8 times more triacylglycerol molecules than the LCT. In vitro, LPL and HL hydrolyzed structured lipids (randomly esterified triacylglycerols of medium- and long-chain fatty acids) slightly less rapidly than they did control lipids, but there was no comparable difference in the blood lipid parameters examined in vivo. Because the MCT emulsions are cleared rapidly, their fatty acids are rapidly made available to the various tissues where they are oxidized.

3-Hydroxybutyric Acid↗
PubMed1989

Clinical and experimental effects of medium-chain-triglyceride-based fat emulsions--a review.

Although total parenteral nutrition usually includes lipids, traditional long-chain triglyceride (LCT) emulsions do not fulfil the energy-providing role allotted to them. The special properties of medium-chain triglycerides (MCTs) and fatty acids led to replacement of part of the infused LCTs by MCTs. The present review shows that: 1. MCT/LCT emulsions are as safe and as well tolerated as the traditional emulsions, and contain enough essential fatty acids to meet patients' needs. 2. Relative to LCT emulsions, MCT/LCT emulsions exhibit a number of differences: * More rapid clearance from the circulation. Lipoprotein lipase and hepatic lipase hydrolyse them preferentially. * Decreased liability to be deposited as fat, in adipose tissue and liver. They do not overload the reticula-endothelial system, which may better preserve its capacity to phagocytose bacteria. * More rapid and complete oxidation, Faster energy provision for all tissues, even though a small part is dissipated in a clinical non-relevant thermogenesis and by o-oxidation. They are ketogenic if infused alone. * Concomitant administration of glucose does not influence their clearance rate, only slightly decreases their oxidation rate, but prevents the acceleration of ketogenesis. Two other properties of MCT/LCT emulsions are probable, though not confirmed: * exchanges of lipids between artificial fat particles and plasma lipoproteins may be less with these emulsions than with LCTs, though it is not yet known what effect diminished disturbance of lipoprotein homeostasis has on the organism. * The nitrogen-sparing effect of a TPN regimen containing MCTs/LCTs seems better than a regimen providing LCTs only.

Journal Article↗
PubMed1989

Fat emulsion particle size: influence on the clearance rate and the tissue lipolytic activity.

In lipid emulsions for parenteral use the mean particle diameter of the droplets in the 20% emulsions is larger than in the 10% emulsions. In long-chain triglyceride emulsions it is greater than in medium-chain triglyceride emulsions. As the particle diameter decreases, the total interfacial area increases, as does the lipoprotein lipase (LPL) and hepatic lipase (HL) activity. For a given quantity of triglycerides and phospholipids the lipolytic activity is proportional to the total interfacial area. A doubling of the phospholipid concentration is accompanied by a small reduction in the activity of both enzymes. In going from long-chain to medium-chain triglycerides, there is an acceleration in the clearance rate of infused lipid. For a similar emulsion, the clearance rate decreases as the particle size decreases. It seems plausible that the larger the mean droplet diameter, the greater the participation of the reticuloendothelial system in the clearance.

Animals↗
PubMed1989

Correlations between ST-segment depressions in patients with arterial hypertension and changes in arterial blood pressure and the heart rate.

In 10 treated hypertensives without coronary heart disease we carried out 24-h monitoring of the ST-segment and blood pressure. Twenty-four periods with ST-segment depressions of greater than 0.1 mV were recorded in nine of 10 patients. In nine of 24 periods with ST-segment depressions blood pressure was elevated. The heart rate was increased in 20 of 24 ST-segment depressions. During nine periods with ST-segment depressions angina pectoris was reported, and 27 anginal attacks without ST-segment depressions were observed. These results indicate that only 38% of ST-segment depressions in hypertensive heart disease are paralleled by increases in blood pressure, but 83% are paralleled by increases in the heart rate (P less than 0.001), which shows a better correlation with ST-segment depressions than blood pressure.

Angina Pectoris↗
PubMed1989

cDNA cloning and sequence analysis of the glucose transporter from porcine blood-brain barrier.

A porcine brain microvessel-derived cDNA library enriched in blood-brain-barrier-specific sequences was constructed by a subtractive cloning procedure. Two cDNA clones from this library were found to encode a glucose transport protein. These clones were used to isolate a nearly full length cDNA from a representative brain microvessel library. Analysis of the amino-acid sequence deduced from the cDNA sequence revealed 97% identity with the human HepG2 glucose carrier. Amino-acid substitutions appear to be clustered in certain regions of the polypeptide. The nucleotide sequences of the 3'-noncoding regions close to the putative polyadenylation sites are highly conserved in glucose transporter mRNAs of different species. The expression of this mRNA has been investigated in various tissues and shown to be decreased in primary cultures of brain microvascular endothelial cells.

Amino Acid Sequence↗
PubMed1988

Prolonged submaximal exercise and L-carnitine in humans.

Changes in the main physiological parameters and circulating indicators of carbohydrate, protein, lipid (and ketone body) metabolism were measured in ten exercising subjects before L-carnitine (L-carn) loading, after 4 weeks of daily loading with 2 g L-carn, and 6-8 weeks after terminating L-carn administration. Measurements were made on venous blood samples collected during each experiment at fixed time intervals over an initial rest of 45 min, 60 min bicycle exercise performed near 50% VO2max and 120 min recovery. Free and total plasma carnitine levels reached a plateau corresponding to an average rise of 25% for both fractions, 9-10 days after the beginning of the L-carn diet. These levels returned to their initial values 6-8 weeks after cessation of the supply. Generally L-carn supplementation did not significantly modify the physiological parameters and circulating metabolites. No distinct increase of the relative participation of endogenous lipids in the fuel supply of prolonged submaximal exercise was observed. In normal human subjects the increased demand for fatty acid oxidation resulting from exercise seems to be adequately supported by endogenous levels of carnitine.

Adult↗
PubMed1988

Medium-chain triglycerides in parenteral nutrition in the newborn: a short-term clinical trial.

In order to study the effects of infusions of medium-chain triglycerides (MCTs) in newborns (2 to 4 weeks old), we administered these fats to patients requiring short-term (48 h) parenteral nutrition. The regimens provided glucose (10 g.kg-1 B.W..24 h), amino acids (1 g.kg-1 B.W..24 h), and, between 8.00 a.m. and 8.00 p.m. of each day, a 10% fat emulsion (1.5 g triglycerides.kg-1 B.W.). The one group (n = 10) received an emulsion containing long-chain triglycerides (LCTs), while the other group (n = 12) was given an MCT/LCT emulsion. No adverse reaction related to either emulsion occurred. Plasma Na, K, Ca and Cl levels and the capillary gasometry did not change during the trials. Plasma triglycerides, non-esterified fatty acids, and free glycerol were increased immediately at the end of the lipid infusion. Concerning triglycerides and non-esterified fatty acids, the increase was greater with the MCT/LCT emulsion than with the LCT emulsion but all values returned to normal within 12 h after the end of the fat infusion. The blood ketone body concentrations did not change and there was no ketonuria. Under our conditions, the MCT/LCT emulsion maintained the plasma glucose and urea levels better than the LCT emulsion.

Female↗
PubMed1988

Carnitine supplementation and fat emulsion clearance and utilization.

The aim of the present work is to learn if intravenous administration of L-carnitine accelerates the clearance of a lipid emulsion. Intravenous fat tolerance tests have been done on rats (0.4 g triacylglycerols.kg-1 B.W.). Measurement of the light scattering index of the plasma permitted determination of the exogenous lipid concentration and thus allowed to represent the clearance curve of the infused emulsion. It was found that prior administration of L-carnitine (110, 160 or 560 mg.kg-1 B.W.) does not modify the clearance rate either of a long chain triglyceride emulsion or of a medium chain triglyceride based emulsion. The observed clearance in L-carnitine deficient animals, resulting either from intraperitoneal injections of D-carnitine (3 g.kg-1 B.W. for four days) or from a 6-months long diet of suboptimal amounts of precursor amino acids and vitamins for carnitine biosynthesis, was not reduced relative to the clearance in corresponding control animals. Also, the in vitro activities of the two enzymes involved in the clearance of the infused lipids, lipoprotein lipase (diaphragm and adipose tissue) and hepatic endothelial lipase, were unmodified by the L-carnitine.

Animals↗
PubMed1988

Ambulatory monitoring of the ST segment, using direct-recording Holter systems.

Direct-recording ambulatory electrocardiographic monitoring systems may produce serious errors not only because of their restricted bandwidth, but even more because of the "half-wavelength-to-head-contact effect." This article describes an easy measurement procedure and a mathematic model of the storage medium. The frequency response is calculated by way of five data from a single measurement. Some errors of typical recorders are discussed with the help of synthesized electrocardiographs. Measurements by six different recorders are listed.

Ambulatory Care↗
PubMed1987

Mechanically induced ventricular extrasystoles in the isolated perfused guinea-pig heart. A model to study cardiac arrhythmia and to differentiate antiarrhythmic drugs.

Pressure pulses applied to an isolated perfused guinea-pig heart via underwater hydrodynamic pressure waves during early diastole induce ventricular extrasystoles (VES). Intensity of pulse pressure and number of VES in relation to number of stimuli show a narrow and reproducible relation following a sigmoid function. Thus we were able to establish a pressure dose-response function between hydrodynamic peak pressure and percentage of VES-responses to mechanical stimulation. In overriding the natural heart rate a ventricular rhythm can be maintained for several hours. In the hypoxic or anoxic heart repetitive automatism can be induced by pulse pressure stimulus. In severe ischemia ventricular fibrillation may occur. In this model differentiation between various classes of antiarrhythmic drugs seems possible in setting up pressure dose-response curves for different concentrations of these drugs. The inhibition of VES is limited to class I antiarrhythmic drugs (quinidine, lidocaine) while specific Ca-antagonists (class IV) are ineffective, thus showing that induction of VES is mediated by a Na channel-dependent process. Preliminary data show that these results can be extended to in situ experiments using an external mechanical stimulator.

Animals↗