Feminism, relativism, and the philosophy of science: an overview.
Explore the source record for details and available documents.
Female↗
Biomedical subjects
D G Allen
Publications and source records attributed to D G Allen.
Diphenylamine-2-carboxylate (DPC) reduces calcium influx in a mouse mandibular cell line (ST885).
Non-selective cation channels are found in many diverse cell types and have been proposed as a potential entry path for Ca2+. ST885 cells contain large numbers of these channels which are active in the resting cell. We have used Fura-2 to monitor changes in intracellular free Ca2+ ([Ca2+]i) in response to step changes in extracellular Ca2+ ([Ca2+]o). We found that DPC, a blocker of the non-selective cation channel in these cells, caused a reduction of approximately 50% in the rate of rise in [Ca2+]i following a step increase in [Ca2+]o. Since our experiments demonstrate that this phenomenon is not due to DPC blockade of Cl- channels, the Na+/Ca2+ exchanger or cyclooxygenase, we conclude that it is attributable to a direct effect of DPC on the non-selective cation channel. It thus appears that the non-selective cation channel is a significant pathway for basal Ca2+ entry in these cells.
Animals↗
Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers.
Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline.
Animals↗
Feminist nursing research without gender.
This theoretic article examines the potential for different types of nursing research to reinforce or undermine gender categories that historically have served to limit some women and marginalize others. Feminist research that gathers or analyzes information in the form of a male/female or man/woman dichotomy risks reproducing social relations damaging to women. Other approaches to dispersing or deconstructing gender dichotomies are discussed, and a series of questions about feminist nursing research is raised.
Female↗
Okadaic acid, a protein phosphatase inhibitor, increases the calcium transients in isolated ferret ventricular muscle.
Okadaic acid is a protein phosphatase inhibitor which has been found to produce a marked positive inotropic effect in isolated cardiac muscle. Using aequorin-injected ferret papillary muscles, we demonstrate that the increase in tension seen with okadaic acid is accompanied by a simultaneous increase in the amplitude of the calcium transients. By comparison with the effects of changing the extracellular calcium concentration, it is shown that the increase in calcium transient amplitude can account for the inotropic effect of okadaic acid.
Animals↗
Changes in tetanic and resting [Ca2+]i during fatigue and recovery of single muscle fibres from Xenopus laevis.
1. Single muscle fibres were dissected from the toe muscles of Xenopus laevis and microinjected with Fura-2 to measure myoplasmic calcium concentration ([Ca2+]i). Injected fibres were illuminated at 340 and 380 nm and the ratio of the resulting fluorescence at 505 nm (the Fura-2 ratio) was taken as a measure of [Ca2+]i. Fibres were fatigued at 21 degrees C by repeated tetani until developed tension had fallen to 50% of control. 2. Tetanic tension declined monotonically during fatiguing stimulation, whereas the tetanic Fura-2 ratio first increased and then declined. At the 10th tetanus, tension was 87% of control whereas the Fura-2 ratio was 106% of control. At the end of fatiguing stimulation, where tension was around 50% of control, the tetanic Fura-2 ratio was reduced to 71%. The rate of decline of both tension and the Fura-2 ratio after a tetanus slowed during fatigue. During recovery, the tension and the tetanic Fura-2 ratio recovered in parallel. 3. The resting Fura-2 ratio increased throughout fatigue reaching 237% of control when tension had declined to 50%. There was a rapid phase of recovery, complete within 1 min, by which time the resting Fura-2 ratio was 198% of control. Subsequent recovery was slower and took 20-30 min to reach a stable level which was 121% of control. 4. The resting Fura-2 ratio towards the end of fatiguing stimulation was greater than the tetanic Fura-2 ratio in the early part of recovery although there was no detectable increase of resting tension during fatiguing stimulation. This observation suggests that the Ca2+ sensitivity of the contractile proteins was reduced at the end of fatiguing stimulation. 5. Plots of the tetanic tension against tetanic Fura-2 ratios throughout fatiguing stimulation and recovery also suggested that Ca2+ sensitivity was reduced during fatiguing stimulation when compared to recovery. 6. The increases in resting [Ca2+]i caused by raised [K+]o (from 2.5 to 10 mM) and/or by application of 15% CO2 were much less than those produced by fatiguing stimulation. Much of the elevated [Ca2+]i in fatigue could be reversed by application of dantrolene (25 microM). 7. The results suggest that both reduced tetanic [Ca2+]i and reduced Ca2+ sensitivity contribute to the decline of tension during fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Cellular mechanisms of fatigue in skeletal muscle.
Prolonged activation of skeletal muscle leads to a decline of force production known as fatigue. In this review we outline the ionic and metabolic changes that occur in muscle during prolonged activity and focus on how these changes might lead to reduced force. We discuss two distinct types of fatigue: fatigue due to continuous high-frequency stimulation and fatigue due to repeated tetanic stimulation. The causes of force decline are considered under three categories: 1) reduced Ca2+ release from the sarcoplasmic reticulum, 2) reduced myofibrillar Ca2+ sensitivity, and 3) reduced maximum Ca(2+)-activated tension. Reduced Ca2+ release can be due to impaired action potential propagation in the T tubules, and this is a principal cause of the tension decline with continuous tetanic stimulation. Another type of failing Ca2+ release, which is homogeneous across the fibers, is prominent with repeated tetanic stimulation; the underlying mechanisms of this reduction are not fully understood, although several possibilities emerge. Changes in intracellular metabolites, particularly increased concentration of Pi and reduced pH, lead to reduced Ca2+ sensitivity and reduced maximum tension, which make an important contribution to the force decline, especially with repeated tetanic stimulation.
Actin Cytoskeleton↗
EMD 53998 sensitizes the contractile proteins to calcium in intact ferret ventricular muscle.
EMD 53998 (a thiadiazinone) is an inotropic drug that produces a pronounced increase in the Ca2+ sensitivity of the contractile proteins in skinned cardiac fibers. The present study was undertaken to determine whether this effect on Ca2+ sensitivity could explain the increase in tension observed in intact ventricular muscle. The experiments were performed on isolated ferret papillary muscles that had been microinjected with aequorin to measure the intracellular Ca2+ concentration. Force and intracellular Ca2+ concentration were monitored before, during, and after application of EMD 53998. EMD 53998 (5 microM) increased developed tension by 230%; aequorin light transients increased by only 85%, and this increase was reduced and became insignificant in the presence of agents that prevent catecholamine release. When a similar increase in developed tension was produced by elevation of extracellular calcium, the aequorin light transients increased by 240%. Thus, EMD 53998 produces a substantial Ca2+ sensitization in intact ventricular muscle, and this can explain most of its inotropic effect. In addition, EMD 53998 caused a small prolongation of the time course of contraction and a small reduction of the time course of the aequorin light transient. A computer model is described that shows that both these effects can be explained by the effect of EMD 53998 on Ca2+ sensitivity. At much higher concentrations, EMD 53998 also caused an increase in resting tension. EMD 53998 is the first agent for which much of the inotropic effect in intact cardiac muscle can be accounted for by increased Ca2+ sensitivity of the contractile proteins. Inotropic agents with this mechanism of action cause increased force production with much less increase in the intracellular Ca2+ transients than conventional agents and, therefore, increase the energy efficiency of the myocardium and are less likely to cause Ca(2+)-activated arrhythmias.
Animals↗
Mechanisms of acute ischemic contractile failure of the heart. Role of intracellular calcium.
Explore the source record for details and available documents.
Animals↗
The effects of 2,3-butanedione monoxime on initial heat, tension, and aequorin light output of ferret papillary muscles.
At low concentrations (up to 5 mM) the compound 2,3-butanedione monoxime (BDM) was found to reduce twitch tension and initial heat production in isolated papillary muscles without significantly affecting the size of the intracellular Ca2+ transient measured with aequorin luminescence. Higher concentrations of BDM caused further inhibition of twitch tension and heat production with a fall in the size of the Ca2+ transient. The size of the aequorin transient was 50% of the control value at 15 mM BDM while twitch tension was negligible. These results suggest that BDM selectively inhibits Ca2+ activated force in cardiac muscle at low concentrations with additional effects on intra-cellular calcium at concentrations above 5 mM.
Aequorin↗
Spatial gradients of intracellular calcium in skeletal muscle during fatigue.
We have measured the distribution of intracellular calcium concentration in isolated single muscle fibres from Xenopus laevis using the fluorescent calcium indicator fura-2 with digital imaging fluorescence microscopy. Under control conditions, resting and tetanic calcium were uniform throughout a fibre. When fatigue was produced using a prolonged, high-frequency tetanus, the distribution of calcium within muscle fibres became non-uniform, with greater levels near the outer parts of a fibre than near the centre. This non-uniform distribution of calcium was rapidly abolished by lowering the stimulation frequency. When fatigue was produced using a series of repeated intermittent tetani, tetanic calcium showed an initial small increase, followed by a decrease as stimulation was continued. The distribution of calcium remained uniform under these conditions. Calcium distribution was also uniform during recovery from intermittent tetanic stimulation. Although fibres varied considerably in their fatigue resistance, the time for tension to fall to 50% was correlated with the reduction in tetanic calcium seen at this time. These results indicate that there are at least two patterns of reduced calcium release that can contribute to the development of fatigue. The appearance of a calcium gradient is consistent with impaired t-tubular conduction, while a uniform reduction of calcium is likely to be due to the action of metabolic factors on systems controlling calcium homeostasis within the cell.
Animals↗
Abnormal uterine bleeding and cancer of the genital tract.
All patients in Tasmania admitted to hospital for investigation of abnormal uterine bleeding in 1987 and 1988 were studied. A total of 4,318 patients were investigated. Four of 539 (0.7%) patients with intermenstrual or postcoital bleeding and 31 of 538 (5.8%) patients with postmenopausal bleeding were found to have endometrial cancer. Of the 3,421 patients investigated for 'heavy' periods (menorrhagia) there was no case of endometrial cancer. The detection rate of endometrial cancer on dilatation and curettage before the menopause is extremely low. Patients presenting with menorrhagia should not be treated surgically in the first instance unless an obvious organic cause is present.
Adult↗
The curriculum revolution: radical re-visioning of nursing education.
Explore the source record for details and available documents.
Authoritarianism↗
Pharmacokinetics of phenobarbital in the cat following multiple oral administration.
Phenobarbital was administered orally to seven healthy cats at a dose of 5 mg/kg once a day for 21 days. Serum phenobarbital concentrations were determined using a commercial immunoassay technique. A one-compartment model was used to describe the final elimination curve. The elimination half-life (t1/2 b) after the final day of treatment was 43.3 +/- 2.92 h. The large apparent volume of distribution of 695.0 +/- 43.9 mL/kg suggests that the drug was widely distributed within the body. The t1/2 b following multiple oral administration was significantly shorter than previously reported for a single oral dose of phenobarbital in the cat. Analysis of pharmacokinetic results after days 1 and 21 of treatment suggested that the elimination kinetics of phenobarbital did not change significantly with multiple oral administration. It appears that differences in elimination kinetics can exist between populations of cats. These differences emphasize the need for individual monitoring of cats receiving phenobarbital.
Administration, Oral↗
Critical social theory and nursing education.
Explore the source record for details and available documents.
Curriculum↗
Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration.
Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.
Administration, Oral↗
Effects of pimobendan, a novel inotropic agent, on intracellular calcium and tension in isolated ferret ventricular muscle.
1. In this study we have investigated the effects of a novel inotropic agent, pimobendan (UDCG 115-BS), on skinned and intact ventricular muscle from ferrets. 2. Pimobendan (20 or 100 mumol/l) increased tension at a given free [Ca2+] when applied to skinned ventricular muscle, i.e. it increased the Ca2+ sensitivity of the myofibrils. 3. Tension and intracellular free Ca2+ [( Ca2+]i) were measured simultaneously in intact papillary muscles using the aequorin technique. When 25 mumol/l pimobendan was added to the superfusing solution, a slowly developing positive ionotropic effect was produced, which was accompanied by an increase in the size of the systolic rise in [Ca2+]i (Ca2+ transients) with a similar time course. 4. In order to determine whether pimobendan increased the Ca2+ sensitivity of myofibrils in an intact papillary muscle, we compared the increase in Ca2+ transients and tension observed in response to changes in extracellular [Ca2+] with those observed in response to pimobendan. The result of this comparison was that in intact muscle pimobendan caused no apparent increase in myofibrillar Ca2+ sensitivity. 5. Pimobendan caused an abbreviation of the time course of the Ca2+ transients, but the twitch was slightly prolonged. 6. When isoprenaline was added to the superfusing solution, a positive inotropic effect was produced, which was accompanied by a marked increase in the size of the Ca2+ transients. Isoprenaline caused an abbreviation of the time course of both the Ca2+ transients and the twitch. When the Ca2+ sensitivity of the intact myofibrils was determined as described above, isoprenaline caused a desensitization. Pimobendan produced a sensitization when compared with isoprenaline. 7. These results are consistent with the hypothesis that pimobendan produces an inotropic effect in isolated cardiac muscle which is mediated both by an increase in Ca2+ sensitivity and by an increase in adenosine 3':5'-cyclic monophosphate due to its phosphodiesterase-inhibiting activity. Such a combination of activities may be particularly advantageous for an inotropic agent.
Aequorin↗