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H Rose

Publications and source records attributed to H Rose.

At least 55 records · Page 3Linked to original sources

Fatty acid transfer across the myocardial capillary wall.

Interstitial transudate of isolated isometrically working perfused rat hearts was analyzed to investigate fatty acid (FA) release and transfer across the capillary wall. Unsaturated FA were released under certain conditions. Lowering medium FA (16:0) with constant or varying FA/A-ratio (A: albumin) decreased interstitial FA-concentration down to 17% of arterial FA-concentration. This was accompanied by reduced uptake-rate. Transcapillary diffusion-resistance, unless markedly altering, cannot be responsible for this observation. Calculated diffusion-rates of FA and FA* protein-complexes in the endothelial cytoplasm and interstitium indicate that FA-transfer takes place almost exclusively bound to carrier-proteins. The apparent permeability surface-area-values of FA for transendothelial FA-transfer are three orders of magnitude higher than those for sucrose; diffusion-coefficients for FA across the endothelium are close to those in water, excluding substantial diffusion-barrier of the capillary wall. Dissociation-rate-constants calculated from experimental data are in the range of those reported for FA* albumin-complexes in vitro. Thus the observed transcapillary FA-gradients are apparently due to the limited dissociation-rate of the FA*albumin-complex in the intravascular space.

Animals↗

Alanine and hyperosmolarity are responsible for the stimulation of cardiomyocyte glucose transport by samples containing a glucose tolerance factor.

Low-molecular-weight, cationic samples, that were previously reported to contain a glucose tolerance factor, were obtained by partial purification from yeast extract. These samples increased the rate of glucose transport in isolated cardiomyocytes 2.0- to 2.5-fold. A further purification by gel filtration led to the separation of two active components that were identified as (i) L-alanine and (ii) an elevated osmolarity. Moreover, the effect of partially purified fractions (before gel filtration) (i) was decreased upon alanine depletion with alanine dehydrogenase and (ii) was mimicked by the additive action of alanine and of a hyperosmolar medium. These findings indicate that the effect of this partially purified material is not accounted for by a putative glucose tolerance factor. Interestingly, alanine elicited its effect at concentrations that correspond to physiological plasma values, which suggests that this amino acid might be involved in the regulation of glucose transport in cardiomyocytes. Furthermore, the effect of alanine was prevented by DL-cycloserine (1 mM) or aminooxyacetate (1 mM), but not by cycloheximide (35 microM), indicating that (a) transamination reaction(s), but not protein synthesis, is required.

Adipose Tissue↗

Negative inotropic effects of the new class I antiarrhythmic agents berlafenone and alprafenone on electrically stimulated isolated cardiomyocytes.

Isolated cardiac myocytes from adult rats were used in a stimulation chamber to investigate the negative inotropic effects of propafenone and the new compounds berlafenone (1-2'-biphenyloxy)-3-tert-butylamino-propanol-2-hydrochloride, GK 23 G; CAS 18965-97-4) and alprafenone (1-(4-methylphenyl)-3-[3'-(2-hydroxy-3-tert-pentylaminopropoxy)-4'- methoxyphenyl]-1-propanonhydrochloride, AH 141; CAS 124316-02-5). This chamber is part of a new device that allows the simultaneous evaluation of mechanics and of the energetics of electrically induced contractions of the myocytes. 1. The contractile behaviour of attaches myocytes was analysed by an image processing system using digitized frames of a CCD camera. 2. The metabolic demand for excitation-contraction coupling was calculated from the drop in oxygen tension (registered by a Clark electrode) caused by suspended myocytes when stimulated in the presence of the contraction inhibiting agent 2,3-butanedione monoxime in the stimulation chamber. 3. The apparent refractory period was evaluated by pacing the myocytes with increasing stimulation rates and determining the frequency at which failure of single contractions occurred. All 3 agents produced a reduction in contraction amplitude of the electrically stimulated myocytes with a similar dose-response relationship (IC50 approx. 10 mumol/l). 4 mumol/l berlafenone reduced the contraction amplitude to 62% of control. Under these conditions the energy expenditure of the contracting cells for excitation and excitation-contraction coupling (ion-cycling) was also reduced (77 +/- 17% of control). Since most of this energy is used for Ca2+ (greater than 80%) it may be concluded that a reduced Ca2+ release causes the negative inotropic action of berlafenone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Highly insulin-responsive isolated rat heart muscle cells yielded by a modified isolation method.

Freshly isolated adipocytes or cardiac myocytes appear to be subject to unspecific stimulation during isolation and subsequent handling, e.g. with respect to glucose transport. We have developed a modified procedure that yields rat cardiomyocytes with a very low basal, i.e. non stimulated hexose uptake rate (ca. 3 pmol * s-1 * mg protein-1 at 1 mM sugar), as compared to data reported by others. This low value correlates with the reported oxygen consumption of non-beating, isolated rat hearts, when these are perfused with glucose as the only substrate. The basal rate of glucose uptake in our quiescent cardiomyocytes is slightly lower than the value measured by others in beating rat hearts in vivo. Insulin (10 nM) stimulates 2-deoxy-D-glucose uptake 8- to 20-fold and 3-O-methyl-D-glucose uptake 14- to 20-fold, as compared to control. This insulin effect is markedly larger than that usually observed in isolated cardiomyocytes, but it is similar in magnitude to the stimulation of glucose transport reported for isolated, perfused rat hearts. In these cells, new stimulatory effects on the glucose transport, e.g. that of sulfhydryl reagents like phenylarsine oxide, become apparent. We conclude that the cardiomyocytes obtained by this modified method exhibit a basal glucose transport rate that is close to physiological values. These cells represent a new highly responsive model to detect and to investigate the effects of glucose transport stimulators (insulin, contraction etc.).

3-O-Methylglucose↗

Simultaneous measurement of contraction and oxygen consumption in cardiac myocytes.

A setup has been developed that simultaneously measures the mechanics and the energetics of electrically induced contractions at physiological frequencies of isolated cardiac myocytes. The core of the setup is a self-manufactured stimulation chamber in which most of the myocytes are in suspension while some are attached to a plastic cover slip prepared from culture Petri dishes. The analysis of the contractile behavior of the attached myocytes is based on an image-processing system with digitized frames of a charge-coupled device camera. Thirty-six frames illuminated by a stroboscope are taken at increasing time intervals between stimulus and flash (snap), allowing one to resolve the contraction cycle with a very high time resolution (down to 1 ms). The number of pixels that differ between each of these frames and a "reference" frame of the cells in the relaxed state (slack cell length) are used to quantify the contractions. An oxygen electrode in the chamber registers the drop of oxygen tension resulting from the consumption by the myocytes, which exhibit a strictly aerobic metabolism. The resulting data are also stored and analyzed in an IBM-AT-compatible computer.

Animals↗

Possible involvement of alanine and pyruvate in the regulation of glucose transport in heart muscle cells.

In isolated rat heart muscle cells, addition of L-alanine (1.5 mmol/l) or of L-valine (3 mmol/l) resulted in either a ca 1.5- or 1.3-fold increase in glucose transport, resp. half-maximal stimulation was observed in the presence of L-alanine, but not of L-valine, within a physiological plasmatic range of concentrations. D-Alanine (1.5 mmol/l) was ineffective and the stimulating effect of L-alanine could be prevented by an excess of L-serine (15-30 mmol/l). L-Alanine produced an increase in 3-O-methyl-D-glucose transport Vmax (from 44.6 to 81.5 pmol.s-1.mg protein-1) without affecting the Km (12.2 in control vs 12.8 mmol/l in alanine-treated cells). Pyruvate (1.5 mmol/l) inhibited glucose transport by 20% and prevented the stimulating action of L-alanine (1.5 mmol/l). These results suggest that the effect of L-alanine in cardiac myocytes occurs through the interaction with an intracellular site and that both alanine and pyruvate may play a role in the regulation of glucose transport in these cells.

Alanine↗

Sarcolemmal fatty acid transfer in isolated cardiomyocytes governed by albumin/membrane-lipid partition.

The mechanism of transfer of long chain fatty acids across the myocardial sarcolemmal membrane was investigated in isolated, calcium-resistant, rat cardiomyocytes. The initial rate of 14C-palmitate uptake was determined at constant and increasing palmitate/albumin ratios. The latter condition led to a saturable dependence of uptake rate on palmitate concentration. At a constant palmitate/albumin ratio however, there was an almost constant rate of uptake even though the absolute concentration of palmitate increased. The enhanced metabolic rate resulting from electrically induced contractions of the myocytes decreased the apparent Km of uptake from 62 to 23 microM. Thirty seconds after administration, there was no further increase in the [14C]palmitate content of the myocytes. Moreover, from experiments using ghost membrane vesicles the concentration of palmitate in membranes increased almost linearly with increasing palmitate/albumin ratios. This concentration remained virtually constant if vesicles were pre-treated with diamide. Our results do not support the concept of an albumin receptor-mediated uptake but rather suggest that fatty acids are incorporated into cardiomyocytes by a simple diffusion process which is not rate-limiting. The rate of uptake is influenced both by the metabolic rate and by the concentration of fatty acids in the membranes. The rate-limiting step of fatty acid uptake is probably either the formation of acyl-CoA catalyzed by the membrane associated acyl-CoA synthetase, or the transfer of fatty acid carnitine esters across the mitochondrial matrix membrane.

Albumins↗

Modifications in proximal tubular function induced by nitrendipine in a rat model of acute ischemic renal failure.

Calcium channel blockers have been reported to preserve renal function when given prophylactically in animal models of acute renal failure (ARF), but the mechanism by which this effect occurs is unknown. We report that nitrendipine (NTR) ameliorates the decline in endogenous creatinine clearance when administered before to clamp-induced ischemia in rats (NTR + clamp, 0.21 +/- 0.06 ml/min; clamp alone, 0.13 +/- 0.04 ml/min, p less than 0.05). To determine whether this protective effect involves the proximal tubule, we compared the uptake of phosphate by brush border membrane (BBM) vesicles in NTR-pretreated ARF rats and in ARF rats pretreated with vehicle alone. A comparison of vehicle-pretreated/sham-operated and vehicle-pretreated/ARF rats served as a control. The initial uphill phase of Na+ gradient-dependent phosphate transport was significantly greater in NTR/ARF rats as compared with vehicle/ARF rats. Pretreatment with NTR did not affect BBM transport of D-glucose or proline. We conclude that NTR has a modest protective effect on overall renal function, and that preservation of proximal tubular function is probably part of this effect.

Acute Kidney Injury↗

Reliability measures in distorting body-image.

This study is the first to make a direct comparison between the distorting mirror and the distorting videocamera with the same group of nonclinical subjects. It also establishes the internal consistency, the test-retest reliability and the convergent validity of both techniques. Analysis indicates, as with other studies, that perceived image is consistently over-estimated and ideal image is consistently under-estimated by both techniques. With the distorting mirror, the frontal orientation is repeatable over four days and with the video the profile is the more reliable orientation. A comparison between profile and frontal orientations on any single test occasion (internal consistency) indicates that the results correlate well so either orientation is acceptable for experimental purposes. The extent to which both techniques were measuring the same aspect (convergent validity) was more marked for the ideal image. A researcher using the distorting mirror can be confident that the ideal image is reliable over time using either orientation but that the perceived image requires a frontal orientation. The frontal or profile orientation is acceptable for the ideal image using the distorting video, but the profile orientation is advisable if one wishes a reliable perceived image. The researcher should also be cautious in assuming that both techniques are measuring an identical body-image construct.

Anorexia Nervosa↗

Effect of nitrendipine in a rat model of ischemic acute renal failure.

An increase in intracellular calcium has been identified as an etiologic factor in acute renal failure (ARF) and blockade of slow calcium channels has been successful in its amelioration. Diuretics may also prevent or mitigate the effects of renal ischemia. We examined the actions of a new calcium channel blocker, nitrendipine (NTR), given intravenously to rats prior to bilateral clamping of the renal pedicle for 45-60 min. Four groups of rats were studied. Group I: Rats given the vehicle only and subjected to sham surgery had a creatinine clearance (Ccr) of .93 +/- .05 ml/min (n = 20). Group II: Rats given NTR (1 or 3 mg/kg) and subjected to sham surgery had a Ccr of .65 +/- .03 ml/min (n = 17). Group III: The infusion of the vehicle alone 10-15 min before clamping resulted in a Ccr of .12 +/- .02 ml/min (n = 23, p less than .001 vs. group I). Group IV: Rats given NTR and then clamped had a Ccr of .30 +/- .04 ml/min (n = 31, p less than .001 vs. group III, p less than .001 vs. group II). Higher doses of NTR did not improve the results. We concluded that NTR partially protects against ARF, but NTR lowered Ccr compared to control rats (p less than .001, group I vs. group II).

Acute Kidney Injury↗

[Modification of radiogenic leukopenia].

In our investigations on rats was proofed the qualification of substances 2-Cyanoethyl Urea (CEH), Thymus-Extract and Lithium-carbonate for a potential reducing or shortening of the leucocyte-depression after whole-body irradiation. Intravenous applications of 2-Cyanoethyl Urea in Wistar rats showed no effect not only in the increase of leucocytes but also in variation in portions of leucocytes. In our investigations we could not influence radiogenic phase of leucopenia by application of CEH after 7 Gy whole-body irradiation. Intramuscular injections of thymus extract don't influence the number of leucocytes in peripheral blood in irradiated Wistar rats. The differential blood-count was uninfluenced. Increase in concentration of thymus extract and also higher frequency of the applications effect no changes in blood-count. Leucocyte depression after whole-body irradiation was independent of the application modus of thymus extract. Lithium-carbonate shows a significant increase of leucocytes in peripheral blood in dependence of dosage and frequency of application. After whole-body irradiation with 7 Gy under lithium therapy it was shown that on day 6th after irradiation leucocyte number was significantly higher than in controls. Radiogenic leucopenia phase was reduced significantly by lithium.

Aerosols↗

Electrically stimulated cardiomyocytes: evaluation of shortening, oxygen consumption and tracer uptake.

Progress in the utilisation of the model "isolated cardiac myocytes" was achieved by designing a special stimulation chamber. This chamber allows eliciting of contraction of suspended myocytes by electrical stimulation. Oxygen consumption was thereby linearly enhanced dependent on the rate of stimulation. Different extent of shortening was observed indicating different inotropic state. Considering the myocytes to behave as a spring (with small delta L) a correlate to work performed was obtained which allowed evaluation of changes in ATP/O-ratios. Uptake of 3-O-methyl-D-glucose was dependent on the mechanical and therefore metabolic activity of the cells. The results show that transfer of glucose across the myocardial sarcolemma is adapted to the metabolic demand by affinity variation and not by recruitment of the transporters.

3-O-Methylglucose↗

Contraction and metabolic activity of electrically stimulated cardiac myocytes from adult rats.

An experimental setup has been developed, which allows electrical stimulation of cardiac myocytes and simultaneous measurement of oxygen consumption, lactate production, extent of shortening and of substrate uptake. In resting cells and in cells stimulated with 120 to 480/min the oxygen consumption ranged from 25 to 100 microliter/min X gww, with a linear relationship between rate of stimulation and oxygen consumption (VO2). When using 5 mM glucose plus 2 mM pyruvate or 10 mM lactate as substrates, isoproterenol (8 X 10(-8) M) augmented contraction and VO2 at all rates of stimulation. Assuming Hook's law for passive elastic behavior for the contracting myocytes over the length change observed, a good correlation exists between the degree of cell shortening calculated from VO2 per beat and the degree of contraction measured. This correlation can be used as a measure of the economy of O2 utilization.

Animals↗

[Effect of 2-cyanoethylurea, thymus extract and lithium carbonate on the leukocyte count in peripheral blood following whole body irradiation].

In our investigations the qualification of the substances 2-cyanoethyl urea, thymus extract and lithium carbonate was tested for a potential reducing or shortening of the leukocyte-depression in rats after whole-body irradiation. Intravenous applications of 2-cyanoethyl urea and intramuscular injections of thymus extract showed no effect in Wistar rats not only in increase of leukocyte number of peripheral blood, but also in variation of leukocyte portion in differential blood-count. Leukocytes depression appearing in consequence of whole-body irradiation was independent of cyanoethyl urea applications and of thymus extract, too. Lithium carbonate shows a significant increase of leukocytes in peripheral blood in dependence of dosage and frequency of applications. After whole-body irradiation with 7 Gy under lithium therapy, it was shown that on day 6 after irradiation leukocyte number was significantly higher than in controls. Radiogenic leukopenia phase was reduced significantly by lithium.

Animals↗

[Estrogen receptor status of breast cancer patients].

Reported in this paper are studies conducted into oestrogen receptor levels of 103 patients with mammary carcinoma, with the dextran-carbon method being used. The findings thus recorded are discussed for their clinical relevance. Recorded were correlations between quantitative oestrogen receptor levels, on the one hand, and menopausal status, grading, histological typing, and tumour size, on the other.

Adenocarcinoma↗