The lived experience of women subjected to domestic violence and abuse.

The number of incidents of domestic violence appears to be continually on the increase. Domestic violence and repeated victimisation and offending can even give rise to fatality. Evaluation of the quality of service delivery and understanding of domestic violence by community members and health care workers show poor results with some people still clinging to myths coming from cultural beliefs. The goal of this article is to explore and describe the lived experience of women subjected to domestic violence and abuse; and to make recommendations for nursing practice, nursing education and nursing research to support women who were subjected to domestic violence and abuse, in facilitating their mental health and optimising their ability to terminate the abusive situation. The framework of the Theory for Health Promotion in Nursing (Rand Afrikaans University, 2000) was used. A qualitative, explorative, descriptive and contextual research design and in-depth, semi-structured, qualitative research interviews were used. Guba's model of trustworthiness (Poggenpoel, 1998: 348-350) was applied. Guba's model for trustworthiness was used (Poggenpoel, 1998: 348-350) Data analysis was done according to Tesch's method (Poggenpoel, 1998: 343-352). The target population of this study was white women in Middelburg, Mpumalanga Province, that experienced abuse for at least the last year and were still married to or in the process of divorcing the abuser. The researcher used a sample of nine participants of which one was involved in the pilot study.

Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review.

Doxorubicin, a very potent and often used anti-cancer drug, has a wide spectrum of biological activity. Classic studies have demonstrated that doxorubicin and other members of the anthracycline family intercalate with DNA and partially uncoil the double-stranded helix. Doxorubicin has a high affinity for cell nuclei: as much as 60% of the total intracellular amount of doxorubicin is found in the nucleus. Once binding to DNA occurs, several consequences may ensue. The binding of anthracyclines to DNA inhibits DNA polymerase and nucleic acid synthesis. In addition, anthracyclines are known to stabilize the otherwise cleavable complex between DNA and homodimeric topoisomerase II enzyme subunits, resulting in the formation of protein-linked DNA double strand breaks. In tumor cells, these anthracycline-induced perturbations are believed to result in a final common pathway of endonucleolytic DNA fragmentation known as apoptosis. Because proliferation is an important determinant of tumor growth, interference with the genome is regarded as the primary cause of the anti-tumor action of doxorubicin. Intercalation with DNA may not be important in the cardiotoxicity associated with doxorubicin therapy (see next section), because cardiac cell proliferation in humans stops after 2 months of age. This review is focussed on the effects of doxorubicin on mechanical performance in skinned cardiac trabeculae after acute and chronic administration of doxorubicin. We look especially at the mechanical performance and the molecular changes observed and related to mechanical performance.

The length dependency of calcium activated contractions in the femoral artery smooth muscle studied with different methods of skinning.

The relationship between the calcium concentration and the isometric tension obtained with different techniques of skinning provides information on the biochemical events of contraction in vascular smooth muscle. Muscle preparations of the rabbit femoral artery were skinned with triton X-100, saponin, beta-escin and alpha-toxin and the relationship between the calcium concentration and isometric tension was determined at different preparation lengths. We determined the calcium sensitivity as a function of muscle length with different techniques of skinning. At a pCa of 6.0, triton X-100 skinned smooth muscle of the femoral artery generated 50% of the maximal tension. In alpha-toxin skinned preparations, this calcium sensitivity was shifted to a pCa of 5.6. The sensitivity of the saponin and 3-escin skinned preparations were in between those of the triton X-100 and the alpha-toxin skinned preparations. The cooperativity of the regulation of contraction varied among the differently skinned preparations between 3 (alpha-toxin) and 6 (triton X-100). The relationships between the calcium concentration and the isometric tension of the differently skinned preparations up to the optimal length for tension generation did not exhibit any length dependency. The length tension relationship, obtained from the maximal response at the highest calcium concentration is in line with that from other studies. The presence of intracellular proteins and membranes affects the regulation of contraction in smooth muscle of the femoral artery.

Doxorubicin impairs crossbridge turnover kinetics in skinned cardiac trabeculae after acute and chronic treatment.

Crossbridge dynamics underlying the acute and chronic inotropic effects of doxorubicin (Dox) were studied by application of releasing length steps (amplitude, 0.5-10%) to skinned cardiac trabeculae. Acute incubation of trabeculae with 20 microM Dox for 30 min resulted in a decrease of the velocity of unloaded shortening (V(0), from 9.3 +/- 1.1 to 7.7 +/- 0.7 microm/s, P <.05) and in an increase of the rate of force redevelopment (tau(r), from 56 +/- 4 to 65 +/- 3 ms, P <.05) in response to step amplitudes ranging from 5 to 10%. In contrast, chronic Dox treatment in rats (2 mg/kg/week for 4 weeks) significantly impaired trabecular crossbridge dynamics after step releases of 0.5%. This was reflected by an increase of all time constants describing tension recovery: tau(1), from 10 +/- 1 to 14 +/- 1 ms; tau(2), from 65 +/- 6 to 82 +/- 6 ms; tau(3), from 92 +/- 7 to 293 +/- 67 ms; P <.05. In addition, V(0) was decreased (from 8.6 +/- 0.6 to 6.8 +/- 0.3 microm/s, P <.05) and tau(r) was increased (from 67 +/- 4 to 89 +/- 3 ms; P <.05) in the slack-test. We found that chronic Dox treatment resulted in a shift from the "high ATPase" alpha-myosin heavy chain (MHC) isoform toward the "low-ATPase" beta-MHC isoform in the ventricles (control: alpha-MHC 79 +/- 2% and beta-MHC 21 +/- 2%; Dox-treated: alpha-MHC 53 +/- 2% and beta-MHC 47 +/- 2%; P <.05). The present results show that acute Dox incubation affects the detachment rate of crossbridges, which leads to a delayed relaxation and an arrest of crossbridges in strongly bound states. In contrast, chronic Dox treatment leads to an impairment of both the attachment and detachment rates in the crossbridge cycle, which may be explained by an altered MHC isoform composition in ventricular myocardium. Interfering with Dox-induced alterations of crossbridge kinetics may provide a new strategy to prevent Dox-associated cardiotoxicity.

Electrophoretic Deposition: A Quantitative Model for Particle Deposition and Binder Formation from Alcohol-Based Suspensions.

We investigated electrophoretic deposition from a suspension containing positively charged particles, isopropanol, water, and Mg(NO(3))(2), with the aim of describing the deposition rates of the particles and Mg(OH)(2), which is formed due to chemical reactions at the electrode, in terms of quantitative models. LaB(6) particles were used as a model system. The particle layer is consolidated by simultaneous precipitation of Mg(OH)(2) which acts as a binder to hold the particles together. The Mg(OH)(2) content was determined solely by the amount of charge passed through the cell. Quantitative precipitation of all OH(-) formed at the electrode was observed, except at very low current. The occurrence of a minimum current was ascribed to a threshold for Mg(OH)(2) deposition. The same minimum current was observed for particle deposition. In combination with results using NaNO(3), where no adherent layer was formed, this illustrates that Mg(OH)(2) binder is necessary for consolidation. Once the minimum current was exceeded, it was found that all particles that migrate to the electrode under the influence of the electric field contribute to the formation of the layer, i.e., the "sticking coefficient" for the particles equals 1.0. The applicability of the particle and Mg(OH)(2) deposition models was tested by variation of the Mg(NO(3))(2) concentration, pH, and water content. Copyright 2000 Academic Press.

A preliminary evaluation of a sheep blowfly trap in the Western Cape.

An insecticide-free sheep blowfly trapping system, utilising a synthetic lure, was evaluated at 4 localities in the Western Cape. Control sites, where no suppression was practised, were identified for each locality. The blowfly population was monitored for 48 hours monthly at each of the localities. Five to 7 suppression traps at the respective localities were identified for this purpose. Three to 10 traps were set monthly for monitoring in the control areas. Trapping resulted in the suppression (P < 0.01) of the Lucilia population at Caledon, where a large area of approximately 50 km2 was trapped. The suppression area of all the localities was < or =850 ha. At Elsenburg, blowfly numbers were low. There was a strong suggestion of a general reduction in the Lucilia numbers at this locality. Trapping failed to reduce Lucilia numbers at Tygerhoek and Langgewens. Lack of control over the influx of Lucilia from adjacent sheep-producing areas probably contributed to this result. The observed response at Elsenburg was probably due to its situation in a predominantly wine-growing area. Most of the blowflies recovered from the control traps during the month with the highest yield at the respective localities belonged to the genus Lucilia. The results obtained at Caledon and published reports suggest that large-scale trapping of Lucilia spp. may play a role in an integrated pest management system for blowflies.

The effect of length on the sensitivity to phenylephrine and calcium in intact and skinned vascular smooth muscle.

The length dependency of the sensitivity to activators of the smooth muscle of different blood vessels is not yet fully understood. Muscle preparations of the aorta, the femoral artery and the portal vein of the rabbit were investigated for the length dependency of the sensitivity to phenylephrine and calcium in both intact and triton X-100 skinned preparations. For intact smooth muscles we found that at increased preparation length, the sensitivity of contraction was increased. The femoral artery showed the largest effect and the portal vein the smallest. In the skinned preparations of the three preparations the calcium sensitivity was not dependent on the preparation length. We conclude that the changes of the sensitivity in intact preparations are not caused by changes of the calcium sensitivity of the contractile proteins.

Force generation and shift of mass between myosin and actin in skinned striated muscle fibres at low calcium concentrations.

Skinned muscle fibres from the gracilis muscle of the rabbit were used to record small angle X-ray diffraction spectra under various contractile conditions. The intracellular calcium concentration, expressed as pCa, was varied between 8.0 and 5.74. Equatorial diffraction spectra were fitted by a function consisting of five Gaussian curves and a hyperbola to separate the (1.0), (1.1), (2.0), (2.1) and Z-line diffraction peaks. The hyperbola was used to correct for residual scattering in the preparation. The ratio between the intensities of the (1.1) and (1.0) peaks was defined as the relative transfer of mass between myosin and actin, due to crossbridge formation after activation by calcium. The relation between the ratio and the relative force of the fibre (normalized to the force at pCa 5.74 and sarcomere length 2.0 microns) was linear. At high pCa (from pCa 6.34 to 8.0) no active force was observed, while the ratio still decreased. Sarcomere length was recorded by laser diffraction. The laser diffraction patterns did not show changes in sarcomere length due to activation in the high pCa range (between 8.0 and 6.34). From these results the conclusion is drawn that crossbridge movement occurs even at subthreshold calcium concentrations in the cell, when no active force is exerted. Since no force is generated this movement may be related to crossbridges in the weakly bound state.

Impairment of the actin-myosin interaction in permeabilized cardiac trabeculae after chronic doxorubicin treatment.

The development of chronic cardiotoxicity in cancer patients treated with doxorubicin (DOX) and other anthracycline antineoplastic agents is a major dose-limiting factor. In a previous study, we demonstrated an acute effect of anthracyclines on the actin-myosin contractile system. Here, we report chronic effects of DOX both on the contractile system and on the function of the sarcoplasmic reticulum (SR). Male Wistar rats were treated with DOX (2 mg/kg, i.v., once a week for 4 weeks), whereas control rats received equal volumes of saline. Right ventricular trabeculae were isolated and skinned by exposure to Triton X-100 or saponin at 1, 2, 4, and 6 weeks after the final DOX administration. The maximal tension of trabeculae was similar between DOX-treated and control animals at 1 week posttreatment. At 2, 4, and 6 weeks posttreatment, the maximal tension of trabeculae of DOX-treated animals was significantly decreased by 27, 32, and 37%, respectively (P < 0.01). The rigor tension in trabeculae of DOX-treated animals was similar at 1 week posttreatment but significantly decreased at 2, 4, and 6 weeks posttreatment (by 25, 25, and 37%, respectively; P < 0.01). The ratio between rigor tension and maximal tension was significantly higher in DOX-treated groups as compared to controls (0.39 +/- 0.01 and 0.36 +/- 0.01; P < 0.05). Calcium sensitivity of DOX-treated preparations was significantly decreased as compared to controls (5.59 +/- 0.02 and 5.65 +/- 0.01; P < 0.05), whereas no effects were found on the cooperativity of the regulatory proteins, as measured by the Hill coefficient. The calcium release function of the SR, measured by caffeine (25 mM) stimulation in saponin-skinned trabeculae, was the same in DOX-treated and control groups at all posttreatment periods. The results of the present study show that long-term DOX treatment causes substantial impairment of the cross-bridge interaction in skinned trabeculae, which is reflected by a progressive attenuation of the contractile performance. The function of the SR, however, remains unaffected by DOX treatment in our preparations. The direct effect of chronic DOX treatment on the actin-myosin system provides an additional mechanism through which anthracyclines exert their cardiotoxic effects and may facilitate the development of cardioprotective strategies.

The effect of actin filament compliance on the interpretation of the elastic properties of skeletal muscle fibres.

Recently, X-ray diffraction studies provided direct evidence for an appreciable length change in the actin filament upon activation. This finding has profound implications on the interpretation of the elastic properties of skeletal muscle fibre. In this study we determined the compliance of the actin filament during activation, using the data obtained previously from quick stretch and release experiments on skeletal muscle fibres of the frog. The effects of filament compliance are demonstrated clearly in the elastic properties of partially activated fibres. The low-frequency elasticity increases linearly with tension, reflecting an increase in the number of force-producing cross-bridges. At higher frequencies, this linearity is lost. In this study we describe the data consistently in terms of a cross-bridge stiffness increasing linearly with tension and a constant Young's modulus for the actin filament of 44 MN m-2. This corresponds to a compliance of 23 pm microns-1 per kN m-2 tension developed. Using this value for the actin filament Young's modulus, its contribution to the elastic properties of skeletal muscle fibre of the frog is considered in rigor and relaxation. The filament compliance hardly affects the overall elasticity of the muscle fibre in relaxation. In contrast, it contributes to a large extent to the overall elasticity in rigor. Taking account of the filament compliance, we find that the Young's modulus in rigor exhibits an increase from 14 MN m-2 at frequencies below 500 Hz to 55 MN m-2 above 40 kHz.

Anthracyclines enhance tension development in cardiac muscle by direct interaction with the contractile system.

Anthracyclines are highly effective anticancer agents which induce a well described but incompletely understood cardiac toxicity. In this study, a direct action of several anthracyclines on the force generating mechanism of heart muscle preparations is described. To allow discrimination between membrane related effects and a direct action of anthracyclines on the actin-myosin contractile system, both inner and outer membranes of cardiac fibres were permeabilized. All anthracyclines tested in this study [doxorubicin (Dox), epirubicin, daunorubicin and idarubicin] showed positive inotropic actions. Dox and epirubicin, which are considered the most cardiotoxic drugs of the anthracycline family, significantly increased the maximal calcium activated tension by 33% (n = 8, P < 0.01) and by 26% (n = 8, P < 0.01) respectively. Daunorubicin and idarubicin increased the maximal tension by 12% and 9% respectively (P = n.s.). Other chemotherapeutic drugs (Taxol and 5-FU) had no effect on maximal tension. To elucidate the mechanism behind this Dox-induced increase in maximal tension, calcium sensitivity curves were measured and rigor experiments were performed. A small but significant increase in pCa50 value (+0.14 +/- 0.03, P < 0.05) was observed only after incubation with 20 microM Dox. Dox acted during the transition to force generating cross-bridges as reflected by the significant increase in rigor tension (12%, P < 0.05) after preincubation of cardiac fibres with Dox. Cycling of cross-bridges is a prerequisite for Dox to increase tension because no effect on tension was seen after Dox was added to fibres in an established rigor. In summary, anthracyclines increased the maximal tension in cardiac muscle fibres by direct interaction with the actin-myosin cross-bridges. Changes in calcium sensitivity are unlikely to contribute to the observed increase in maximal tension. The rise in tension as is seen in this experimental set-up may contribute to destruction of the contractile machinery of cardiac muscle. In agreement with this hypothesis is the observation that the more cardiotoxic anthracyclines induced the largest increase in maximal tension of the cardiac fibres.

Strain dependence of the elastic properties of force-producing cross-bridges in rigor skeletal muscle.

Stretch and release experiments carried out on skinned single fibers of frog skeletal muscle under rigor conditions indicate that the elastic properties of the fiber depend on strain. For modulation frequencies below 1000 Hz, the results show an increase in Young's modulus of 20% upon a stretch of 1 nm/half-sarcomere. Remarkably, the strain dependence of Young's modulus decreases at higher frequencies to about 10% upon a 1-nm/half-sarcomere stretch at a modulation frequency of 10 kHz. This suggests that the cause of the effect is less straightforward than originally believed: a simple slackening of the filaments would result in an equally large strain dependence at all frequencies, whereas strain-dependent properties of the actin filaments should show up most clearly at higher frequencies. We believe that the reduction of the strain dependence points to transitions of the cross-bridges between distinct force-producing states. This is consistent with the earlier observation that Young's modulus in rigor increases toward higher frequencies.

Direct recording of EDP-EDV relationship in isolated rat left ventricle: effect of diastolic crossbridge formation.

OBJECTIVE: The aim was to investigate whether the end diastolic pressure-end diastolic volume (EDP-EDV) relationship of the left ventricle can be influenced by calcium dependent elements, especially at low values of end diastolic pressure. METHODS: Isolated rat hearts were perfused in a modified Langendorff perfusion system. The EDP-EDV relationship of the left ventricle was investigated. Pressure was recorded with a microtip pressure catheter and volume with a microconductance catheter. Crossbridge cycling was affected by adding calcium antagonists (verapamil, diltiazem, nifedipine at 2.10(-7) M) or by adding the Mg-ATPase blocker BDM (2,3-butanedione-2-monoxime, 10(-3) M) to the perfusate. RESULTS: The above had a negative inotropic effect in systole. At EDP = 0 after stimulation the active isovolumetric pressure was zero. In diastole, BDM shifted the EDP-EDV relationship to slightly smaller EDVs. A decrease of about 5% in the EDV was found at lower EDP values. Ca2+ antagonists increased the EDV up to 40-80% at low EDP values. At higher EDP values only a small increase of EDV (about 10%) was found after verapamil perfusion. The results obtained are interpreted in terms of a three step crossbridge model. CONCLUSIONS: At low EDP, diastolic volume is dependent upon weakly bound crossbridges as a function of the [Ca2+] in the cardiac cell.

A fluorescence depolarization study of the orientational distribution of crossbridges in muscle fibres.

A fluorescence depolarization study of the orientational distribution of crossbridges in dye-labelled muscle fibres is presented. The characterization of this distribution is important since the rotation of crossbridges is a key element in the theory of muscle contraction. In this study we exploited the advantages of angle-resolved experiments to characterize the principal features of the orientational distribution of the crossbridges in the muscle fibre. The directions of the transition dipole moments in the frame of the dye and the orientation and motion of the dye relative to the crossbridge determined previously were explicitly incorporated into the analysis of the experimental data. This afforded the unequivocal determination of all the second and fourth rank order parameters. Moreover, this additional information provided discrimination between different models for the orientational behaviour of the crossbridges. Our results indicate that no change of orientation takes place upon a transition from rigor to relaxation. The experiments, however, do no rule out a conformational change of the myosin S1 during the transition.

Application of angle-resolved fluorescence depolarization in muscle research.

Angle-resolved fluorescence depolarization (AFD) experiments have been used for over a decade in studies of fluorescent molecules in macroscopically aligned systems such as lipid bilayers and stretched polymer films. The importance of this technique lies in the fact that it affords the determination of both the second- and the fourth-rank order parameters of the orientational distribution of the probe molecules in the sample. Here we apply the technique to the study of the orientational distribution of crossbridges in muscle fibers. This orientational distribution is particularly relevant in muscle research, as crossbridge rotation is commonly regarded to be the driving mechanism in force development. An unfortunate consequence of the fact that the crossbridges have an average orientation of approximately 45(o) relative to the fiber axis is that the values of the second-rank order parameter [Symbol: see text]P 2[Symbol: see text] of the crossbridge distribution are close to 0. Therefore, knowledge of [Symbol: see text]P 4[Symbol: see text] is essential for a reliable reconstruction of the form of the distribution function. AFD of dyelabeled muscle was measured under rigor and relaxation conditions. The results indicate that no significant changes in depolarization take place upon a transition from the rigor to the relaxed state in the muscle and seem not to support the rotating crossbridge model, which postulates a clear change of orientation of the crossbridges.

Ca2+ channel antagonists enhance tension in skinned skeletal and heart muscle fibres.

Striated muscle fibres, both skeletal and cardiac of different species including human, skinned by freeze-drying, were activated in solutions strongly buffered for Ca2+. The single fibres were immersed in solutions with different [Ca2+]. Sarcomere length was set and controlled by laser diffraction. Fibre type was determined by Sr2+ activation. The relation between the negative logarithm of the Ca2+ concentration and the normalized tension, the Ca2+ sensitivity curve, was investigated. The effect on the contractile machinery of three different Ca2+ channel antagonists (verapamil, diltiazem and nifedipine) in a therapeutic concentration (10(-6) M) was investigated. The possible effects on the Ca2+ sensitivity curve were quantified by: (1) the change in maximal tension developed at pCa2+ = 4.4; (2) the change in pCa2+ value at which 50% of the tension induced at pCa2+ = 4.4; (3) the steepness of the Ca2+ sensitivity curve in this point. The three drugs tested, at a therapeutic concentration of 1 microM, all enhanced maximal induced tension by respectively 25, 20 and 7%. The sarcomere length dependency of the effect proved to be dependent upon the drug, but also slightly on fibre type (skeletal or cardiac), or on species. It is concluded that the drug influences the cooperativity of the two different types of binding sites on troponin-C (low- and high-affinity sites). Tension enhancement was due to increased stiffness of the actin-myosin interaction site.

Tetragonal deformation of the hexagonal myofilament matrix in single skinned skeletal muscle fibres owing to change in sarcomere length.

Single skinned skeletal muscle fibres were immersed in solutions containing two different levels of activator calcium (pCa: 4.4; 6.0). Sarcomere length was varied from 1.6 to 3.5 microns and recorded by laser diffraction. Slack length was 2.0 microns. Small-angle equatorial X-ray diffraction patterns of relaxed and activated fibres at different sarcomere lengths were recorded using synchrotron radiation. The position and amplitude of the diffraction peaks were calculated from the spectra based on the hexagonal arrangement of the myofilament matrix, relating the position of the (1.0)- and (1.1)-diffraction peaks in this model by square root of 3. The diffraction peaks were fitted by five Gaussian functions (1.0, 1.1, 2.0, 2.1 and Z-line) and residual background was corrected by means of a hyperbola. The coupling of the position of the (1.0)- and (1.1)-peak was expressed as a factor: FAC = [d(1.0)/d(1.1)]/square root 3. In the relaxed state this coupling factor decreased at increasing sarcomere length (0.9880 +/- 0.002 at 2.0 microns; 0.900 +/- 0.01 at 3.5 microns). The coupling factor tends toward the one that will be obtained from the squared structure of actin filaments near the Z-discs. At shorter sarcomere lengths a decrease of the coupling factor has also been seen (0.9600 +/- 0.005 at 1.6 microns), giving rise to an increased uniform deformation of the hexagonal matrix, when sarcomere length is changed from slack length. From these experiments we conclude that a change in sarcomere length (from slack length) increases the deformation of the actin-myosin matrix to a tetragonal lattice.

Doxorubicin interacts directly with skinned single skeletal muscle fibres.

The effect of doxorubicin, a highly effective anticancer agent, on the contractile apparatus of skinned single muscle fibres was tested in a concentration of 1 microM. Sarcomere length was set and held at 2 microns. Doxorubicin induced an increase in tension dependent on the Ca2+ concentration and time of incubation. The rise was up to 25% at [Ca2+] 40 microM. A parallel, small but significant shift of the calcium sensitivity curve, the relation between normalized tension and the negative logarithm of [Ca2+], the pCa, was observed. The results of this study suggest a direct interaction of doxorubicin with the actin myosin structure, possibly by an effect on myosin-ATP activity.