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Biomedical subjects

J Heller

Publications and source records attributed to J Heller.

At least 163 records · Page 9Linked to original sources
PubMed1990

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog.

Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt-1.day-1, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 micrograms.kgbodywt-1.min-1) or nifedipine (NIF, 0.3 microgram.kgbodywt-1.min-1). Neither drug changed the mean arterial pressure. Apart from the natriuresis and diuresis, which were significantly greater with NIF than with VER, the response to both drugs was similar. Increases in renal blood flow (RBF; 17% with VER, 20% with NIF), glomerular filtration rate (GFR; VER: 34%; NIF: 39%) and filtration fraction (VER: 12%; NIF: 14%) were observed; similar values were obtained at the single nephron level. Pressure in glomerular capillaries, measured directly after ablation of a thin layer of cortex corticis, was increased by 11% with VER and 10% with NIF; no changes in proximal tubular and peritubular capillary pressure were seen. The glomerular ultrafiltration coefficient (Kf) did not change with either drug. Total arteriolar resistance was decreased (VER: 20%; NIF: 15%) due to a decrease in afferent resistance (VER: 31%; NIF: 27%) with no corresponding change in efferent resistance. The cause of the lack of responsiveness of the efferent arteriole remains unclear. In conclusion, in acute experiments with intrarenal administration, both drugs increase RBF and GFR by a preferential afferent dilatory mechanism without any change in Kf.

Animals↗
PubMed1990

Controlled drug release from bioerodible hydrophobic ointments.

A new type of poly (ortho ester) was prepared by the condensation of a triol and an alkyl ortho ester. The condensation produces polymers that are viscous pastes at r.t. even though molecular weights in excess of 50,000 dalton can be produced. Such materials are useful as bioerodible drug delivery devices because rate of release of an incorporated therapeutic agent can be controlled by the addition of small amounts of acidic excipients to the polymer. A significant advantage of these materials is that therapeutic agents can be incorporated by simple mixing at r.t. without the use of solvents.

Biodegradation, Environmental↗
PubMed1990

Development of poly(ortho esters): a historical overview.

At the present time, three poly(ortho ester) systems have been described. The first one was developed at the Alza Corporation and is prepared by the transesterification reaction between a diol and diethoxytetrahydrofuran. It is currently marketed under the trade name of Alzamer. A second poly(ortho ester) system, developed at SRI International, is prepared by the addition of polyols to the diketene acetal 3,9 bis (ethylidene 2,4,8,10 tetraoxaspiro [5,5] undecane). A third poly (ortho ester) system, also developed at SRI International, is prepared by a transesterification reaction between a triol and an ortho ester, followed by self-condensation of the reaction product. Major utility of poly(ortho esters) as bioerodible drug delivery devices resides in their acid sensitivity which allows preparation of devices with lifetimes ranging from hours to many months by using acidic or basic excipients physically incorporated into the matrix.

Biodegradation, Environmental↗
PubMed1990

Development of enzymatically degradable protective coatings for use in triggered drug delivery systems: derivatized starch hydrogels.

Starch is a common polysaccharide which consists of glucopyranose residues in an alpha-D-(1-4) linkage that yields D-glucose upon hydrolysis. Saturated aqueous solutions of soluble starch are easily reacted in the presence of glycidyl methacrylate to produce methacrylate grafted starch. Grafted starch solutions were polymerized to produce hydrogels, with and without the addition of an unsaturated acid. The grafted starch solutions and the resulting hydrogels are both shown to be degraded by the enzyme alpha-amylase. These acidic hydrogels are potentially useful as enzymatically degradable protective coatings in self-regulated drug delivery system applications. The pH of an acidic starch hydrogel required by this self-regulated drug delivery system does indicate that an adequately acidic hydrogel can be produced.

Amylases↗
PubMed1990

Kinetics of red cell Na+ and K+ transport in Prague hypertensive rats.

Kinetics of ouabain-sensitive, furosemide-sensitive (FS), bumetanide-sensitive (BS) and -resistant Na+ and K+ transport were studied in erythrocytes of Prague hypertensive rats (PHR) and Prague normotensive rats (PNR). Maximal transport rates (Vmax) and apparent affinities for either intracellular Na+ or extracellular K+ (replaced by Rb+) were determined in red cells in which Na+ content varied around the physiological range and that were incubated in Na+ media. No major differences between PHR and PNR were disclosed in the kinetics of ion transport mediated by the Na(+)-K+ pump or BS inward Na(+)-K+ cotransport. FS Rb+ uptake was higher (due to a greater Vmax) in red cells of PHR as compared to PNR. In cells with a lowered Na+ content this elevation of FS Rb+ uptake was largely due to an augmented K(+)-Cl- cotransport which exhibits a low affinity for Rb+o and is blocked by 1 mM furosemide but not by 10 microM bumetanide. Red cells of PHR and PNR strains did not differ in either Na+ or Rb+ leaks. A slight increase of red cell Na+ content in PHR was evaluated in terms of the pump-leak concept. The present study did not reveal any obvious kinetic abnormalities of red cell cation transport the presence of which in tissues involved in blood pressure regulation would favor the development or the maintenance of genetic hypertension in PHR.

Animals↗
PubMed1990

Chronic benzodiazepine administration: effects in vivo and in vitro.

Chronic benzodiazepine administration is associated with neurochemical alterations in the GABAergic system, as determined in a variety of animal models and tissue culture systems. In animals, effects of chronic benzodiazepine agonists on receptor binding are uncertain, but several studies indicate a decrease in GABA-dependent chloride uptake. In contrast, limited data indicate that chloride uptake is increased after chronic antagonist administration, and results of inverse agonist administration are uncertain. Most animal studies are limited by lack of attention to drug choice and to pharmacokinetic variables, and by failure to determined delivered drug concentrations. More limited data in tissue culture systems are conflicting with regard to effects on benzodiazepine binding, but recent studies indicate that GABA-dependent chloride uptake may be decreased after chronic agonist exposure, and increased after chronic antagonist and inverse agonist administration. Data from these systems may complement results obtained in intact animals, and cultures may allow more detailed examination of the kinetics and specificity of drug effects.

Animals↗
PubMed1990

Ion transport in erythrocytes of Prague hypertensive rat.

The Prague hypertensive rat is a unique strain exhibiting genetic hypertension in which a hypertensive line (PHR) was bred in parallel with a normotensive one (Prague normotensive rat--PNR) from the same parental pair. Sodium efflux from Na(+)-loaded erythrocytes into Mg2(+)-sucrose medium was measured in these two strains as well as in spontaneously hypertensive rats (Okamoto-Aoki, SHR) and in normotensive outbred Wistar rats. Kinetic parameters--maximal velocity and apparent dissociation constant (reflecting the affinity for internal sodium)--were calculated. It was found that PHR as well as SHR had a higher Na+ leak and a decreased activity of the ouabain-sensitive Na+ transport as compared to Wistar rats. Furosemide-sensitive Na+ transport was substantially lower in erythrocytes of both hypertensive strains (PHR and SHR) than in the respective normotensive strains (PNR and Wistar).

Animals↗
PubMed1989

[Noninvasive determination of the anaerobic threshold in middle-age men].

The "anaerobic threshold" was estimated non-invasively in two groups of untrained middle-aged men (Mean age 31.4 +/- 4.8 and 51.8 +/- 5.4 years) simultaneously from minute volume dependence on oxygen consumption or CO2 output, and by means of pulse rate kinetics estimation, both at a growing intensity of exertion. The values of selected function variables (VO2, pulse rate and performance in pedalling) at "threshold" level showed no significant difference in either estimation in both absolute and relative quantities (expressed in per cent of maximum values). Very close relationships were found between the values of selected function parameters at "anaerobic threshold" level estimated with the above two methods (p less than 0.005 in all cases). The two methods of "anaerobic threshold" estimation are interchangeable under the following conditions: the initial intensity of exercise at about 50% VO2 max level, the duration of each degree of exertion ranges between 30 and 150 seconds, the differences in the intensity of exercise between different degrees are roughly 4 to 6 pulses/min, and the total number of the degrees of exercise is 5 to 8. Estimations of pulse rate kinetics with the intensity of exercise rising can be utilized for the determination of the "anaerobic threshold" even in persons of advanced age both under laboratory and under field conditions.

Adult↗
PubMed1989

[Non-invasive determination of the "anaerobic threshold" using heart rate kinetics].

The functional parameters at the level of the "anaerobic threshold" (ANT) are used very frequently to characterize aerobic functions of the organism. For estimation of the ANT most frequently changes of the LA blood concentration in relation to an increasing load are used. The LA concentration depends to a considerable extent on the state of glycogen reserves in muscles which may change as a result of physical loads and as a result of dietary intervention. Ventilation parameters and values of the GR are practically independent on glycogen reserves. For the evaluation of mutual relationships between parameters at the level of the ventilation ANT and the level of ANT assessed by means of changes of the HR, both ANT values were assessed in a group of trained endurance runners on a treadmill and in a group of untrained young men on a bicycle ergometer. For practical use both ANT estimations can be considered identical, assuming that when using the HR for assessment of ANT we implement the following conditions: 1. The initial intensity of the load is at the level of 50 VO2max. or lower. 2. The duration of different grades of the load is 30-150 s. 3. Differences in the intensity of the load between different grades are 4-6 strokes. 4. The total number of loads varies between 7 and 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Transdermal delivery of levonorgestrel. IV: Evaluation of membranes.

A series of experiments were performed to evaluate the flux of levonorgestrel (LN), ethyl acetate (EtAc), and ethanol (EtOH) through excised rat skin, through a variety of synthetic membranes and through membranes supported on rat skin. Using a donor phase of EtAc:EtOH (7:3) containing excess solid LN, the flux of LN through rat skin was approximately 1.0 microgramc/cm2.h. The normalized fluxes of LN, EtAc, and EtOH through ethylene vinyl acetate (EVAc) copolymers of varying vinyl acetate (VAc) content (12 to 25%) were 1.3 to 3.1 x 10(-8), 2.6 to 6.8 x 10(-4), and 4.8 to 9.9 x 10(-5) g.cm/cm2.h, respectively. Permeability experiments were also performed with the EVAc membranes supported on rat skin. By selecting the VAc content and thickness of the EVAc membranes, it was possible to control the delivery of enhancer (EtAc:EtOH) through rat skin (membrane-rate control) or to let the skin control the overall delivery of enhancer.

Acetates↗
PubMed1989

Ventilatory threshold and mechanical efficiency in endurance runners.

In order to evaluate changes in parameters at the ventilatory threshold (VT) and in mechanical efficiency (ME) during training in the years 1982 and 1983 we tested seven top-class endurance runners on a treadmill. The VT and ME were assessed during their training period (January 1982 and 1983) and during their competitive period (March and July 1982). The maximal functional variables were almost constant during the training year, the maximal change in VO2max being about 5%. Similarly, VO2 at the VT was almost constant; the maximal change in VO2 at VT was also about 5%. Substantially greater changes, about 10%, were recorded in the velocity of running at the VT, at which the maximum was attained in July (18.9 +/- 0.8 km.h-1 or 5.25 +/- 0.22 m.s-1); this value was significantly higher than values assessed during the remaining tests. The greatest change, about 23%, during the training year was found in ME, for which the maximum was attained in July (35.7% +/- 2.1%). This was not significantly different from the value recorded in March (34.5% +/- 3.3%), but both values were significantly higher than those recorded during the training period. We can therefore conclude that in highly trained endurance runners the times needed to attain the optimal conditions for sports performance differ from the point of view of special speed training and from the point of view of mechanical-metabolic readiness.

Adult↗
PubMed1989

Energy cost of running in similarly trained men and women.

The energy demand of running on a treadmill was studied in different groups of trained athletes of both sexes. We have not found any significant differences in the net energy cost (C) during running (expressed in J.kg-1.m-1) between similarly trained groups of men and women. For men and women respectively in adult middle distance runners C = 3.57 +/- 0.15 and 3.65 +/- 0.20, in adult long-distance runners C = 3.63 +/- 0.18 and 3.70 +/- 0.21, in adult canoeists C = 3.82 +/- 0.34 and 3.80 +/- 0.24, in young middle-distance runners C = 3.84 +/- 0.18 and 3.78 +/- 0.26 and in young long-distance runners C = 3.85 +/- 0.12 and 3.80 +/- 0.24. This similarity may be explained by the similar training states of both sexes, resulting from the intense training which did not differ in its relative intensity and frequency between the groups of men and women. A negative relationship was found between the energy cost of running and maximal oxygen uptake (VO2max) expressed relative to body weight (for men r = -0.471, p less than 0.001; for women r = -0.589, p less than 0.001). In contrast, no significant relationship was found in either sex between the energy cost of running and VO2max. We conclude therefore that differences in sports performance between similarly trained men and women are related to differences in VO2max.kg-1. The evaluation of C as an additional characteristic during laboratory tests may help us to ascertain, along with other parameters, not only the effectiveness of the training procedure, but also to evaluate the technique performed.

Adolescent↗
PubMed1989

Transdermal delivery of levonorgestrel. V. Preparation of devices and evaluation in vitro.

Transdermal devices were prepared and evaluated for their ability to codeliver levonorgestrel and the permeation enhancers ethyl acetate and ethanol in vitro. The 24-hr devices were prepared with membranes composed of ethylene vinyl acetate (EVAc) copolymers. The vinyl acetate (VAc) content of the membranes (50 +/- 10 or 100 +/- 10 microns thick) was varied from 12 to 25% to give a range of permeabilities toward the enhancers. The reservoir used was ethyl acetate/ethanol (7:3, v/v; 0.5 ml) containing excess solid levonorgestrel and gelled with 2% hydroxypropyl cellulose. The higher VAc content membranes (18 and 25%) exhibited relatively high release rates of EtAc and EtOH leading to depletion of ethyl acetate and ethanol from the reservoir by the end of 24 hr. As a result, the transdermal flux of levonorgestrel, evaluated using rat skin, reached a maximum at about 8 hr and thereafter diminished to zero by 24 hr. The less permeable membranes (12 and 15% VAc content) led to a more sustained release of enhancers, but due to lower solvent delivery to the skin, levonorgestrel flux was substantially lower. There was a direct relationship between drug delivery through skin and the amount of solvent delivered until release of the enhancers had diminished. The potential use of ethyl acetate in transdermal drug delivery is also discussed.

Acetates↗