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1.
Phys Rev E ; 107(6-2): 065005, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37464639

ABSTRACT

In some parameter and solution regimes, a minimally coupled nonrelativistic quantum particle in one dimension is isomorphic to a much heavier, vibrating, very thin Euler-Bernoulli rod in three dimensions with ratio of bending modulus to linear density (ℏ/2m)^{2}. For m=m_{e}, this quantity is comparable to that of a microtubule. Axial forces and torques applied to the rod play the role of scalar and vector potentials, respectively, and rod inextensibility plays the role of normalization. We show how an uncertainty principle ΔxΔp_{x}≳ℏ governs transverse deformations propagating down the inextensible, force and torque-free rod, and how orbital angular momentum quantized in units of ℏ or ℏ/2 (depending on calculation method) emerges when the force and torque-free inextensible rod is formed into a ring. For torqued rings with large wave numbers, a "twist quantum" appears that is somewhat analogous to the magnetic flux quantum. These and other results are obtained from a purely classical treatment of the rod, i.e., without quantizing any classical fields.

2.
Aust Health Rev ; 45(6): 696-703, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34856118

ABSTRACT

Objective This study examined the content and impact of a new digital communication medium, called a VIDCAST, implemented at a large hospital and health service when the COVID-19 pandemic was announced, and the key concerns held by staff at the time when the health service was preparing for the COVID-19 pandemic to arrive in this health service. Methods A mixed-methods approach was used. Thematic analysis of 20 transcripts of daily VIDCASTS broadcast between 30 March and 24 April 2020 was undertaken, in addition to descriptive analysis of feedback from an anonymous online survey. Results Survey feedback from 322 staff indicated almost universal satisfaction with this new communication method. The VIDCASTS provided a new COVID-safe method for the Executive to connect to staff at a time of uncertainty. Thematic analysis of the content of the VIDCASTS revealed three themes: 'Accurate Information', 'Reassurance and Support' and 'Innovation'. The Executive was able to reassure staff about what the organisation was doing to safeguard the health and wellbeing of all, and enabled an effective response to the pandemic. Conclusions The digital communication channel of VIDCASTS, rapidly operationalised at a major Australian hospital and health service in March 2020, provided important information and support for staff as it prepared for the anticipated COVID-19 surge. What is known about the topic? When the COVID-19 pandemic began, traditional face-to-face staff meetings were disrupted and many hospitals and their staff were left scrambling for information, and for reassurance about their safety, as they prepared to receive increasing numbers of COVID-19 patients. What does this paper add? The implementation of a digital communication tool was able to address many of the concerns raised by hospital staff in other geographic locations dealing with surging COVID-19 cases and underpinned a globally leading COVID-19 response. What are the implications for practitioners? New digitised communication methods provided an effective vehicle to inform and support staff in the early stages of pandemic preparation.


Subject(s)
COVID-19 , Pandemics , Australia/epidemiology , Communication , Humans , Pandemics/prevention & control , SARS-CoV-2
3.
Soft Matter ; 16(18): 4389-4406, 2020 May 14.
Article in English | MEDLINE | ID: mdl-32249282

ABSTRACT

Both animal and plant tissue exhibit a nonlinear rheological phenomenon known as compression stiffening, or an increase in moduli with increasing uniaxial compressive strain. Does such a phenomenon exist in single cells, which are the building blocks of tissues? One expects an individual cell to compression soften since the semiflexible biopolymer-based cytoskeletal network maintains the mechanical integrity of the cell and in vitro semiflexible biopolymer networks typically compression soften. To the contrary, we find that mouse embryonic fibroblasts (mEFs) compression stiffen under uniaxial compression via atomic force microscopy studies. To understand this finding, we uncover several potential mechanisms for compression stiffening. First, we study a single semiflexible polymer loop modeling the actomyosin cortex enclosing a viscous medium modeled as an incompressible fluid. Second, we study a two-dimensional semiflexible polymer/fiber network interspersed with area-conserving loops, which are a proxy for vesicles and fluid-based organelles. Third, we study two-dimensional fiber networks with angular-constraining crosslinks, i.e. semiflexible loops on the mesh scale. In the latter two cases, the loops act as geometric constraints on the fiber network to help stiffen it via increased angular interactions. We find that the single semiflexible polymer loop model agrees well with the experimental cell compression stiffening finding until approximately 35% compressive strain after which bulk fiber network effects may contribute. We also find for the fiber network with area-conserving loops model that the stress-strain curves are sensitive to the packing fraction and size distribution of the area-conserving loops, thereby creating a mechanical fingerprint across different cell types. Finally, we make comparisons between this model and experiments on fibrin networks interlaced with beads as well as discuss implications for single cell compression stiffening at the tissue scale.


Subject(s)
Fibrin/metabolism , Fibroblasts , Models, Theoretical , Rheology , Actomyosin/metabolism , Animals , Mice , Microscopy, Atomic Force , Polymers
4.
Phys Rev E ; 99(5-1): 052413, 2019 May.
Article in English | MEDLINE | ID: mdl-31212528

ABSTRACT

Compression stiffening, or an increase in shear modulus with increasing compressive strain, has been observed in recent rheometry experiments on brain, liver, and fat tissues. Here we extend the known types of biomaterials exhibiting this phenomenon to include agarose gel and fruit flesh. The data reveal a linear relationship between shear storage modulus and uniaxial prestress, even up to 40% strain in some cases. We focus on this less-familiar linear relationship to show that two different results from classic elasticity theory can account for the phenomenon of linear compression stiffening. One result is due to Barron and Klein, extended here to the relevant geometry and prestresses; the other is due to Birch. For incompressible materials, there are no adjustable parameters in either theory. Which one applies to a given situation is a matter of reference state, suggesting that the reference state is determined by the tendency of the material to develop, or not develop, axial stress (in excess of the applied prestress) when subjected to torsion at constant axial strain. Our experiments and analysis also strengthen the notion that seemingly distinct animal and plant tissues can have mechanically similar behavior at the quantitative level under certain conditions.


Subject(s)
Compressive Strength , Elasticity , Models, Biological , Biomechanical Phenomena , Fruit , Mangifera
5.
Phys Rev X ; 8(4)2018.
Article in English | MEDLINE | ID: mdl-31448179

ABSTRACT

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out of phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2D morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluidlike film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential." Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bioinspired applications, and address how our model is and is not unique to the developing nervous system.

6.
Transfus Med ; 27(4): 268-274, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28661030

ABSTRACT

OBJECTIVES: To study the effect of red blood cell (RBC) storage duration on long-term mortality in patients undergoing cardiac intervention. BACKGROUND: RBCs undergo numerous structural and functional changes during storage. Observational studies have assessed the association between RBC storage duration and patient outcomes with conflicting results. METHODS: Between January 2006 and December 2014, 82 408 patients underwent coronary angiography. Of these, 1856 patients received one to four RBC units within 30 days after this procedure. Patients were allocated according to length of RBC storage duration: short-term (≤11 days), intermediate (IM)-term (12-23 days) and long-term (≥24 days). The study endpoints were 30-day and long-term all-cause mortality. RESULTS: A total of 4168 RBC units were given to 1856 patients. The mean RBC storage duration was 8.5 ± 2.1, 17.7 ± 3.4 and 29.9 ± 3.4 days in the short-term, IM-term and long-term storage groups, respectively. There was no difference in baseline characteristics between the groups. The long-term storage group received significantly more units (2.4 ± 1.0 units) as compared to the short-term (2.0 ± 1.0 units; P < 0.001) and IM-term storage group (2.2 ± 1.0 units; P < 0.01). In the survival analysis, there was no significant difference in all-cause mortality between the groups (log-rank: 0.509 for 30-days mortality; 0.493 for 5-year mortality). Additional stratified analysis demonstrated no association between RBC storage duration and long-term mortality. CONCLUSION: This study did not find an association between RBC storage duration and 30-days or long-term mortality in patients undergoing cardiac intervention.


Subject(s)
Blood Preservation/adverse effects , Coronary Angiography/mortality , Erythrocyte Transfusion/mortality , Erythrocytes , Aged , Aged, 80 and over , Denmark , Female , Follow-Up Studies , Humans , Male , Middle Aged , Registries , Retrospective Studies , Time Factors
7.
Clin Res Cardiol ; 106(7): 525-532, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28168513

ABSTRACT

BACKGROUND: The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before acute CMR assessment compared to CMR-participants in a previously published double-blinded, placebo-controlled all-comer trial with CMR outcome as the primary endpoint. METHODS: Baseline characteristics and composite endpoint of all-cause mortality, heart failure and re-infarction after 30 days and 5 years of follow-up were assessed and compared between CMR-drop-outs and CMR-participants using the trial screening log and the Eastern Danish Heart Registry. RESULTS: The drop-out rate from acute CMR was 28% (n = 92). These patients had a significantly worse clinical risk profile upon admission as evaluated by the TIMI-risk score (3.7 (± 2.1) vs 4.0 (± 2.6), p = 0.043) and by left ventricular ejection fraction (43 (± 9) vs. 47 (± 10), p = 0.029). CMR drop-outs had a higher incidence of known hypertension (39% vs. 35%, p = 0.043), known diabetes (14% vs. 7%, p = 0.025), known cardiac disease (11% vs. 3%, p = 0.013) and known renal function disease (5% vs. 0%, p = 0.007). However, the 30-day and 5-years composite endpoint rate was not significantly higher among the CMR drop-out ((HR 1.43 (95%-CI 0.5; 3.97) (p = 0.5)) and (HR 1.31 (95%-CI 0.84; 2.05) (p = 0.24)). CONCLUSION: CMR-drop-outs had a higher incidence of cardiovascular risk factors at baseline, a worse clinical risk profile upon admission. However, no significant difference was observed in the clinical endpoints between the groups.


Subject(s)
Coronary Artery Bypass/methods , Endpoint Determination/methods , Magnetic Resonance Imaging, Cine/methods , Risk Assessment/methods , ST Elevation Myocardial Infarction/diagnosis , Thrombolytic Therapy/methods , Cause of Death/trends , Denmark/epidemiology , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Risk Factors , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Selection Bias , Survival Rate/trends , Time Factors , Ventricular Function, Left/physiology
9.
Int J Cardiol ; 146(3): 395-8, 2011 Feb 03.
Article in English | MEDLINE | ID: mdl-19700209

ABSTRACT

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Ventricular Function, Left , Humans , Myocardial Contraction , Postoperative Complications/prevention & control
10.
Appl Ergon ; 33(6): 533-40, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12507337

ABSTRACT

Industrial interventions that focus on increased productivity may impair the ergonomics, on a workstation or individual level. This paper presents a method that characterises work time consumption and physical work load of manual work, using video recordings synchronised with physiological measurements of, e.g. muscular activity, and postures. The underlying idea was that it is possible to amalgamate technical and human aspects resulting in a synergetic evaluation. The method was developed through two case studies within the Swedish automotive industry, where manual materials handling was studied. A methodological result was that the synchronising procedure was sufficiently precise to allow work activities to be assigned significantly different levels of physical work load. These different levels may be used to predict physical work load in the design and change of production systems. It was concluded that the method is accurate enough to be a useful tool in industrial interventions.


Subject(s)
Task Performance and Analysis , Video Recording/methods , Work/physiology , Automobiles , Electromyography/instrumentation , Electromyography/methods , Ergonomics/instrumentation , Humans , Industry , Sweden
11.
J Endocrinol ; 170(1): 147-55, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11431147

ABSTRACT

The effects of in vivo treatment with estrogen and progesterone on isoproterenol-induced uterine relaxation and beta(2)-adrenoceptor (beta(2)AR) mRNA production in non-pregnant rat myometrium were investigated. Whether homologous myometrial desensitization of beta(2)AR function was dependent on or modulated by the two steroids was also examined. Estrogen treatment alone or in combination with progesterone reduced maximal relaxation (E(max)) of isolated uterine strips subsequently challenged with isoproterenol whereas progesterone alone had no effect on this parameter. The reduction was accompanied by an enhanced beta(2)AR mRNA concentration. The concentration of isoproterenol giving half-maximal relaxing response (EC(50)) increased following estrogen treatment and this effect was curbed by progesterone. Isoproterenol had no effect on beta(2)AR transcription irrespective of the steroid regimes employed. E(max) of isolated uterine strips was reduced following prolonged in vivo treatment with isoproterenol but the effect was found only when estrogen alone was administered concomitantly. Finally, in vivo treatment with isoproterenol increased EC(50) of uterine strips subsequently stimulated with isoproterenol in vitro. This effect was independent of steroid treatment. We conclude that homologous desensitization of beta(2)AR function in non-pregnant rat myometrium in terms of sensitivity (EC(50)) is independent of sex steroids but in terms of maximal response (E(max)) occurs only in the presence of estrogen. We speculate whether progesterone withdrawal in connection with the well-known estrogen dominance at rat parturition may strengthen the desensitization induced by beta(2)AR activation and thus contribute to the transformation of the uterus from a quiescent to a highly contractile organ.


Subject(s)
Estradiol/pharmacology , Myometrium/metabolism , Progesterone/pharmacology , RNA, Messenger/analysis , Receptors, Adrenergic, beta-3/genetics , Uterine Contraction/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , Data Interpretation, Statistical , Female , In Vitro Techniques , Inhibitory Concentration 50 , Isoproterenol/pharmacology , Myometrium/drug effects , Rats , Rats, Wistar , Receptors, Adrenergic, beta-3/metabolism , Reverse Transcriptase Polymerase Chain Reaction
12.
J Endocrinol ; 169(1): 33-41, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11250644

ABSTRACT

The objectives of the present study were to investigate the effects of the reproductive steroids oestradiol and progesterone on myometrial levels of cyclooxygenase-2 (COX-2) mRNA and PGF(2alpha) induced myometrial contractility and to study whether the effect of beta(2)-adrenoceptor stimulation by isoproterenol on the myometrium alters these parameters. Oestrogen treatment of ovariectomized rats increased myometrial COX-2 mRNA whereas PGF(2alpha) receptor (PGF(2alpha)-R) mRNA was unchanged following this treatment and maximal contractility (E(max)) of isolated uterine strips challenged with PGF(2alpha) was unaltered. Progesterone treatment alone decreased COX-2 mRNA in comparison with values obtained from oestrogen-treated animals, and in combination with oestrogen the enhancing effect of progesterone on COX-2 mRNA was curbed. EC(50) of uterine strips challenged with PGF(2alpha) increased following oestrogen treatment whereas this parameter was substantially decreased following progesterone treatment. When oestrogen was combined with isoproterenol infusion mRNA values of both COX-2 and PGF(2alpha)-R were reduced. Finally, when isoproterenol infusions were given in combination with both oestrogen and progesterone, PGF(2alpha)-R mRNA and E(max )were enhanced as compared with similar rats not having received isoproterenol. We conclude that oestrogen increases COX-2 mRNA production and subsequent prostaglandin synthesis in non-pregnant rat myometrium. We further conclude that in the oestrogen-dominated rat myometrium the relaxing effect of beta(2)-adrenoceptor stimulation involves attenuation of both prostaglandin synthesis and PGF(2alpha)-R expression. We finally conclude that in the presence of both oestrogen and progesterone this effect of beta(2)-adrenoceptor stimulation is restrained.


Subject(s)
Estradiol/pharmacology , Isoenzymes/biosynthesis , Myometrium/metabolism , Progesterone/pharmacology , Prostaglandin-Endoperoxide Synthases/biosynthesis , Uterine Contraction/drug effects , Adrenergic beta-Agonists/pharmacology , Analysis of Variance , Animals , Cyclooxygenase 2 , Dinoprost/pharmacology , Dose-Response Relationship, Drug , Female , In Vitro Techniques , Isoenzymes/genetics , Isoproterenol/pharmacology , Myometrium/drug effects , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/analysis , Rats , Rats, Wistar , Receptors, Prostaglandin/genetics , Receptors, Prostaglandin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Stimulation, Chemical
13.
Biol Reprod ; 63(5): 1443-9, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11058550

ABSTRACT

In the present study we have shown that the genetic expression of prostaglandin (PG)F(2alpha) receptor (R) and cyclooxygenase (COX)-2 increases in laboring rat myometrium. This finding was associated with a relatively weak contractile in vitro response (E:(max)) of isolated uterine strips when challenged with PGF(2alpha). Five days postpartum PGF(2alpha)-R mRNA values exceeded those during labor while COX-2 mRNA was reduced to preparturient values. Maximal contractility of isolated strips stimulated with PGF(2alpha) at this time was enhanced and E:C(50) decreased. Oxytocin treatment of estrogen-primed nonpregnant rats down-regulated uterine contractile responsiveness to PGF(2alpha), leaving mRNA values for this receptor unchanged, whereas oxytocin receptor blockade with atosiban (an oxytocin receptor antagonist) left E:(max) unaltered. In contrast, atosiban treatment of pregnant rats resulted in a 2.5-fold increase in E:(max) and a considerably reduced EC(50) during labor when compared to untreated delivering rats. The increased contractile ability was associated with a threefold increase in PGF(2alpha)-R mRNA production, indicating that the regulation by atosiban of the PGF(2alpha)-induced response is exerted at the genetic level. Based on the present data we suggest that 1) PGF(2alpha)-R stimulation may not primarily exert a contracting role in the normally delivering myometrium, and 2) the presence of the PGF(2alpha)-R system in rat myometrium may explain the apparent functional redundancy of the oxytocinergic system during the process of birth in animals lacking oxytocin or where the oxytocin receptor is blocked. In this context PGF(2alpha) receptor stimulation may, in the absence of oxytocin receptor stimulation, exert the contractile forces needed for proper propulsion of the fetus.


Subject(s)
Dinoprost/pharmacology , Myometrium/drug effects , Oxytocics/pharmacology , Receptors, Oxytocin/antagonists & inhibitors , Animals , Cyclooxygenase 2 , Female , In Vitro Techniques , Isoenzymes/biosynthesis , Isoenzymes/genetics , Prostaglandin-Endoperoxide Synthases/biosynthesis , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/biosynthesis , Rats , Receptors, Oxytocin/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tocolytic Agents/pharmacology , Uterine Contraction/drug effects , Vasotocin/analogs & derivatives , Vasotocin/pharmacology
15.
Appl Ergon ; 30(5): 443-53, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10484280

ABSTRACT

The aim was to evaluate the prevailing ergonomic conditions in a parallelized flow, long cycle time, assembly system. The evaluation focused on physical exposure, psychosocial factors and work-related musculoskeletal symptoms. A random sample of 67 assembly operators was included in a cross-sectional study mainly based on questionnaires. Hand/wrist symptoms were common and related to work exposure with hand-held powered tools. In general, the self-reported physical exposure showed only a few significant associations with musculoskeletal symptoms. This may in part be explained by the ergonomic conditions generally being good, with a relatively low duration of 'combined' extreme work postures. Significant associations were found between the psychosocial work environment and musculoskeletal symptoms.


Subject(s)
Attitude to Health , Automobiles , Ergonomics , Musculoskeletal Diseases/etiology , Occupational Diseases/etiology , Adult , Cross-Sectional Studies , Evaluation Studies as Topic , Female , Hand/physiopathology , Humans , Low Back Pain/etiology , Male , Musculoskeletal Diseases/psychology , Neck Pain/etiology , Occupational Diseases/psychology , Occupational Exposure , Posture/physiology , Prevalence , Risk Factors , Sex Factors , Shoulder Pain/etiology , Surveys and Questionnaires , Time Factors , Workload , Workplace , Wrist/physiopathology
16.
J Endocrinol ; 161(3): 403-11, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10333543

ABSTRACT

The objective of the present study was to further elucidate our previous observation that beta2-adrenoceptor activation induces oxytocin receptor (OTR) expression in rat myometrium. We wanted to investigate whether the mechanism behind this effect was under the influence of gonadal steroids. Ovariectomized non-pregnant rats were treated with estrogen, progesterone or a combination of both for 3 days. Some rats were concomitantly treated with isoproterenol. Estrogen treatment increased both OTR mRNA production and maximal binding of [3H]-oxytocin to isolated myometrial plasma membranes, but it did not affect contractility of isolated uterine strips challenged with oxytocin. When the estrogen regimen was combined with isoproterenol treatment, an augmented maximal contractile response (Emax) to oxytocin was observed although no further increase in OTR mRNA and binding was seen. Progesterone treatment did not in itself alter OTR mRNA, OTR binding or Emax. However, OTRs were induced at the level of gene expression when progesterone was supplemented with isoproterenol infusion. Finally, progesterone suppressed the effect of estrogen on OTR mRNA production and binding when the two compounds were administered together. However, when isoproterenol treatment was added this effect was abolished and Emax was enhanced more than that seen following treatment with estrogen alone. These data suggest that beta2-adrenoceptor activation represents an important regulator of OTR expression/function in estrogen- and progesterone-dominated rat myometrium.


Subject(s)
Adrenergic beta-Agonists/pharmacology , Isoproterenol/pharmacology , Myometrium/metabolism , Receptors, Oxytocin/metabolism , Animals , Estradiol/pharmacology , Female , Gene Expression/drug effects , In Vitro Techniques , Myometrium/drug effects , Ovariectomy , Oxytocin/metabolism , Progesterone/pharmacology , Protein Binding/drug effects , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Statistics, Nonparametric , Uterine Contraction/drug effects
17.
Biol Reprod ; 60(2): 322-9, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9915997

ABSTRACT

It has been proposed that the rise in myometrial oxytocin receptor (OTR) concentrations at term triggers parturition. In the present study, we have shown that in vivo infusion of the beta2-adrenoceptor (beta2AR) antagonist ICI-118.551 in late pregnant rats prevents the rise in myometrial OTR binding normally seen during delivery. A reduced contractile responsiveness of uterine strips isolated from rats in labor when challenged with oxytocin (OT) and a slight shortening of gestation accompanied this effect. OTR mRNA levels were, however, unaltered after the treatment, suggesting that the effect of beta2AR blockade on myometrial OTR was posttranscriptional or due to influences on extra-myometrial tissue. Infusion of the OTR antagonist atosiban down-regulated OTR binding sites in the parturient myometrium and resulted in an impaired contractile response to OT without affecting gestational length. OTR gene expression did not change, as seen from unchanged OTR mRNA values. Neither atosiban nor ICI-118.551 infusions alone changed fetal mortality. A significant increase in the incidence of fetal deaths was found, however, when rats were treated with a combination of atosiban and ICI-118.551. This treatment also down-regulated myometrial OTR and weakened the contractile response to OT, but it did not change gestational length. We conclude that the timing and onset of a normal parturition as well as a favorable outcome seem to be independent of a rise in OTR. This fact cannot exclude the possibility that an increase in OTR is of importance in the genesis of preterm labor. We suggest that beta2 stimulation up-regulates OTR during delivery. This effect may partly be responsible for the tachyphylaxis seen after the use of beta2 agonists to control preterm labor. We further suggest that OTR stimulation up-regulates OTR during labor. The OTR down-regulation seen after atosiban treatment adds to the direct relaxing effect of atosiban on the myometrium. In view of this, atosiban may prove to be a more useful tocolytic than the traditionally used beta2 agonists.


Subject(s)
Adrenergic beta-2 Receptor Antagonists , Adrenergic beta-Antagonists/pharmacology , Myometrium/metabolism , Receptors, Oxytocin/antagonists & inhibitors , Receptors, Oxytocin/metabolism , Animals , Cell Membrane/metabolism , Female , Fetal Death/chemically induced , Gestational Age , Hormone Antagonists/pharmacology , Oxytocin/metabolism , Oxytocin/pharmacology , Pregnancy , Pregnancy Outcome , Propanolamines/adverse effects , Propanolamines/pharmacology , RNA, Messenger/metabolism , Rats , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/physiology , Receptors, Oxytocin/genetics , Uterine Contraction/drug effects , Vasotocin/adverse effects , Vasotocin/analogs & derivatives , Vasotocin/pharmacology
18.
Am J Physiol ; 275(6): R1833-42, 1998 12.
Article in English | MEDLINE | ID: mdl-9843872

ABSTRACT

The hypothesis that renal sodium handling is controlled by changes in plasma sodium concentration was tested in seated volunteers. A standard salt load (3.08 mmol/kg body wt over 120 min) was administered as 0.9% saline (Isot) or as 5% saline (Hypr) after 4 days of constant sodium intake of 75 (LoNa+) or 300 mmol/day (HiNa+). Hypr increased plasma sodium by approximately 4 mmol/l but increased plasma volume and central venous pressure significantly less than Isot irrespective of diet. After LoNa+, Hypr induced a smaller increase in sodium excretion than Isot (48 +/- 8 vs. 110 +/- 17 micromol/min). However, after HiNa+ the corresponding natriureses were identical (135 +/- 33 vs. 139 +/- 39 micromol/min), despite significant difference between the increases in central venous pressure. Decreases in plasma ANG II concentrations of 23-52% were inversely related to sodium excretion. Mean arterial pressure, plasma oxytocin and atrial natriuretic peptide concentrations, and urinary excretion rates of endothelin-1 and urodilatin remained unchanged. The results indicate that an increase in plasma sodium may contribute to the natriuresis of salt loading when salt intake is high, supporting the hypothesis that osmostimulated natriuresis is dependent on sodium balance in normal seated humans.


Subject(s)
Diet, Sodium-Restricted , Kidney/physiology , Natriuresis/physiology , Water-Electrolyte Balance/physiology , Adult , Blood Volume/drug effects , Blood Volume/physiology , Central Venous Pressure/drug effects , Central Venous Pressure/physiology , Humans , Male , Natriuresis/drug effects , Saline Solution, Hypertonic/pharmacology , Sodium/blood , Sodium Chloride/pharmacology
19.
Eur J Pharmacol ; 355(2-3): 203-10, 1998 Aug 21.
Article in English | MEDLINE | ID: mdl-9760035

ABSTRACT

Metabolites of the analogue 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin (carbetocin) following incubation with a rat kidney homogenate were isolated and their pharmacodynamic properties investigated. Apart from the parent compound two metabolites were identified namely desGlyNH2-carbetocin (carbetocin metabolite I) and desLeuGlyNH2-carbetocin (carbetocin metabolite II). Both carbetocin, carbetocin metabolite I and carbetocin metabolite II displayed binding affinities to the myometrial oxytocin receptor of a similar magnitude as oxytocin. Carbetocin was found to have agonistic properties on isolated myometrial strips and it was found to exert this effect through generation of inositol phosphates, as is the case for oxytocin. However, maximal contractile effect of carbetocin was approximately 50% lower than that of oxytocin (2.70 +/- 0.12 g compared to 5.22 +/- 0.26 g) and EC50 was approximately ten times higher (48.0 +/- 8.20 nM compared to 5.62 +/- 1.22 nM). Neither carbetocin metabolite I nor carbetocin metabolite II were able to contract isolated myometrial tissue. All three compounds displayed antagonistic properties against oxytocin in vitro, with carbetocin being the strongest inhibitor (pA2 = 8.21) and carbetocin metabolite II (pA2 = 8.01) being stronger than carbetocin metabolite I (pA2 = 7.81). These results indicate that carbetocin is a partial agonist/antagonist to the oxytocin receptor while the two metabolites carbetocin metabolite I and carbetocin metabolite II are pure antagonists. All three analogues bound to the myometrial vasopressin V1 receptor, albeit with much lower affinities than to the oxytocin receptor. Carbetocin metabolite II showed the weakest binding affinity of 33.7 +/- 7.34 nM compared to 7.24 +/- 0.29 nM for carbetocin and 9.89 + 2.80 nM for carbetocin metabolite I. Only carbetocin bound to the renal vasopressin V2 receptor though the binding affinity was very low (61.3 +/- 14.6 nM).


Subject(s)
Kidney/metabolism , Myometrium/drug effects , Oxytocics/metabolism , Oxytocin/analogs & derivatives , Receptors, Oxytocin/metabolism , Receptors, Vasopressin/metabolism , Animals , Female , Myometrium/physiology , Oxytocics/pharmacology , Oxytocin/metabolism , Oxytocin/pharmacology , Rats , Rats, Wistar
20.
Scand J Work Environ Health ; 24(2): 125-9, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9630060

ABSTRACT

OBJECTIVE: This study describes a new technique for measuring skin exposure to cutting fluids and evaluates the variability of skin exposure among machine operators performing cyclic (repetitive) work. METHODS: The technique is based on video recording and subsequent analysis of the video tape by means of computer-synchronized video equipment. The time intervals at which the machine operator's hand was exposed to fluid were registered, and the total wet time of the skin was calculated by assuming different evaporation times for the fluid. The exposure of 12 operators with different work methods was analyzed in 6 different workshops, which included a range of machine types, from highly automated metal cutting machines (ie, actual cutting and chip removal machines) requiring operator supervision to conventional metal cutting machines, where the operator was required to maneuver the machine and manually exchange products. RESULTS: The relative wet time varied between 0% and 100%. A significant association between short cycle time and high relative wet time was noted. However, there was no relationship between the degree of automatization of the metal cutting machines and wet time. CONCLUSIONS: The study shows that skin exposure to cutting fluids can vary considerably between machine operators involved in manufacturing processes using different types of metal cutting machines. The machine type was not associated with dermal wetness. The technique appears to give objective information about dermal wetness.


Subject(s)
Dermatitis, Contact/etiology , Dermatitis, Irritant , Dermatitis, Irritant/etiology , Dermatitis, Occupational/etiology , Metals/adverse effects , Occupational Exposure/adverse effects , Adult , Dermatitis, Contact/epidemiology , Dermatitis, Irritant/epidemiology , Dermatitis, Occupational/epidemiology , Fungicides, Industrial/adverse effects , Humans , Industrial Oils/adverse effects , Male , Middle Aged , Risk Factors , Solutions , Videotape Recording , Water/adverse effects
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