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Biomedical subjects

D G Allen

Publications and source records attributed to D G Allen.

At least 217 records · Page 12Linked to original sources

Treatment of rhesus monkeys (Macaca mulatta) with intrauterine devices loaded with levonorgestrel.

The effects of levonorgestrel-loaded plastic intrauterine devices on endometrial morphology were investigated in 15 rhesus monkeys for 14 weeks. The devices were designed to release 25 microgram of the hormone per day and were inserted in the uterus by hysterotomy. Control animals were sham operated or received inert placebo devices. With the levonorgestrel-releasing devices, widespread changes in endometrial morphology were seen. These changes included atrophy of the endometrial mucosal and glandular epithelium and decidualization of the endometrial stroma. With the inert placebo control devices, only minor changes in endometrial morphology were observed.

Animals↗

Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings loaded with levonorgestrel.

The effects of levonorgestrel-releasing intravaginal rings were investigated in 15 rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either three or ten times the human dose level of the hormone. Untreated placebo rings were used as a control. The devices were well retained. After insertion of the vaginal rings, a dose-related decrease in vaginal bleeding was observed. The vaginal microbial flora were assessed qualitatively and semi-quantitatively and although all groups including controls showed some changes in microbial populations, by the end of the study nearly all animals returned to a normal balanced microflora. Terminal studies showed that, at the high dose level, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular epithelium had occurred. A dose-related increase in mucus within the lumen of the endocervical canal was observed. Focal or diffuse atrophy of the vaginal mucosal epithelium was seen in the majority of levonorgestrel-treated animals.

Animals↗

Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings impregnated with either progesterone or norethisterone.

The effects of both progesterone- and norethisterone-loaded intravaginal rings were investigated in twenty-five rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either the human dosage level of the hormone or ten times this level. Untreated placebo rings were used for control purposes. The devices were well retained. With the exception of increased plasma fibrinogen levels in animals treated with norethisterone, no marked differences in either local or systemic toxicity between the progesterone and norethisterone intravaginal rings were apparent. Following insertion of the hormone-treated intravaginal rings, a dose-related decrease in vaginal bleeding was recorded. The vaginal microbial flora were assessed qualitatively and semiquantitatively and all groups including the placebo controls showed a changes in mcirobial populations. Terminal studies indicated that at high dose levels, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular endometrial epithelium had occurred. An increase in cervical mucus was observed within the lumen of the endocervical canal in a proportion of hormone-treated animals. In the vagina, a dose-related focal or diffuse atrophy of the mucosal epithelium was found.

Animals↗

Calcium transients in aequorin-injected frog cardiac muscle.

The Ca2+ -sensitive bioluminescent protein aequorin was microinjected into cells of frog atrial trabeculae to study intracellular calcium transients associated with excitation-contraction coupling. The amplitude of the aequorin signal increased with extracellular Ca2+ concentration and stimulus frequency, but decreased with stretch. Isoprenaline and acetylstrophanthidin both increased the amplitude, but had strikingly different effects on the time course of the signal.

Action Potentials↗

Aequorin luminescence: relation of light emission to calcium concentration--a calcium-independent component.

Light emission from the calcium-sensitive bioluminescent protein aequorin was measured at calcium ion concentrations of 10(-9) to 10(-2) molar. At very low Ca2+ concentations, light emission is independent of calcium ion concentration. The maximum slope of the log-log plot of light as a function of calcium ion concentration is about 2.5. The complete relation is well described by a two-state model involving three calcium-binding sites.

Aequorin↗

On the relationship between action potential duration and tension in cat papillary muscle.

Tension and action potentials have been measured simultaneously from isolated cat papillary muscles. Two groups of experiments are described. In the first group, the external conditions under which the muscle contracted were changed. Specifically, stimulation rate, extra-cellular [Ca++], extracellular [Na++] were altered, and adrenaline was added to the bathing fluid. A tendency for given levels of tension to be accompanied by action potentials of constant duration is demonstrated under some of these conditions. In the second group of experiments, tension and action potentials were recorded following some change in external conditions; specifically, after a long rest, after a change in muscle length, and after the muscle had been set up in the experimental apparatus (the 'running-in' period). In the period that followed each of these interventions, peak tension increased substantially over at least several minutes but all external conditions (for example, temperature, muscle length, stimulation rate, and composition of the bathing fluid) remained constant. In each of these three situations tension increased but in one case the action potential duration increased, in another it decreased, and in the third it was unchanged. It is concluded that change in action potential durations do not necessarily make an important contribution to the changes in tension of papillary muscles.

Action Potentials↗

Studies of the contractility of mammalian myocardium at low rates of stimulation.

1. Measurements have been made of tension development in papillary muscles isolated from the right ventricles of young cats. In some cases membrane potentials have also been recorded, using micro electrodes. 2. Regular contractions at a stimulation rate of 20 min(-1) (the 'standard' rate used in this study) had the following characteristics (30 degrees C): peak tension developed, about 43mN mm(-2); time to peak tension and time to 80% repolarization of the cell membrane, about 400 ms. 3. The corresponding figures for the first contraction after a rest of several minutes (rested state contraction) were: tension developed, about 4mN mm(-2); time to peak tension and time to 80% repolarization of the cell membrane, about 560 ms. Sometimes there was also an early peak in the mechanical response, about 250 ms after stimulation. 4. The time course with which tension development declined when the muscle was allowed to rest was examined under various conditions. It was found to decline more slowly when the muscle was potentiated by raising the bathing Ca2+ concentration and by stimulation at rates above 20 min(-1). 5. Tension development in rested state contractions was found to depend on the Ca2+ and Na+ concentrations in the bathing solution. The full effect of a change in either could be produced by exposing the resting muscle to the altered ionic conditions. 6. These experimental findings have been interpreted in terms of a simple model of the calcium movements involved in excitation-contraction coupling in the myocardial cell.

Action Potentials↗

Preponderance of postsystolic period in the positive inotropic effects of increases in (Ca++).

If the frequency of stimulation of isolated kitten right ventricular papillary muscles is progressively reduced, the size of contractions decreases until a frequency is reached (rested state rate) where further reduction produces no change (rested state contraction, Koch-Weser and Blinks, 1963). At 30 degrees C and 2.25 mM Ca++, the rested state rate was about one per 2-5 min, the peak tension of 0.2-0.6 g/mm2 was about 5-15% of the tension of 20/min beats, and times to peak tension and 80% repolarization about doubled. Sudden calcium increases in the perfusion fluid, [Ca++]p, from 2.25 to 6.75 mM were produced at random during intervals between rested state contractions, and time and amplitude of peak isometric tension, max +/- dT/dt of subsequent beats were studied. The greatest positive inotropic response of the initial beats following increments in [Ca++]p resulted when [Ca++]p was increased immediately after a rested state contraction: as the postsystolic interval before the [Ca++]p increment was increased, the positive inotropic effects decreased approximately exponentially, attaining a plateau level in about 30 sec. This plateau was then maintained until the period prior to the initial test beat in high calcium was less than the approximately 2-min diffusion equilibrium time between [Ca++]p and the interior of the fiber.

Animals↗