[Insufficient help to victims of violence].
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Crime Victims↗
Biomedical subjects
L Bang
Publications and source records attributed to L Bang.
Nitroglycerin-mediated vasorelaxation is modulated by endothelial calcium-activated potassium channels.
OBJECTIVE: Recent in vitro data suggest, large conductance calcium-activated K+ channels (BKCa) modulate the vascular response to nitric oxide (NO). The in vivo implications and the characteristics of this interaction are not clear. This study firstly investigates whether modulation of BKCa affects the vascular response to nitroglycerin (NTG)-derived NO in vivo and in the isolated heart and secondly examines the influence of endothelial BKCa on NTG-mediated vasodilation in vitro. METHODS: The hypotensive effect of NTG was measured in conscious, chronically catheterized rats during i.v. infusions of iberiotoxin (IbTX, a selective inhibitor of BKCa) or placebo. Similarly, NTG-induced flow-changes in the isolated perfused rat heart were examined before and after IbTX treatment (0.1 microM). Concentration-relaxation curves to NTG in the presence of various K+ channel modulating agents were performed in vitro on porcine coronary arteries with and without intact endothelium. RESULTS: I.v. infusion of IbTX reduced the in vivo hypotensive effect of NTG by 55% (before IbTX: 32.0 +/- 3.0 mmHg, vs. after IbTX: 14.5 +/- 3.2 mmHg, P < 0.05) and nearly abolished NTG-induced increase in coronary flow in the isolated perfused heart (P < 0.05). In vitro, this effect depended on an intact endothelium (endothelium intact segments; NTG: pD2 = 5.8 +/- 0.1, Emax = 97.6 +/- 3.2% vs. NTG + IbTX: pD2 = 4.9 +/- 0.2, Emax = 49.7 +/- 6.2%, P < 0.05; endothelium denuded segments; NTG: pD2 = 6.9 +/- 0.1, Emax = 104.0 +/- 1.4% vs. NTG + IbTX: pD2 = 6.7 +/- 0.1, Emax = 100 +/- 1.2%, P > 0.05). CONCLUSION: The results suggest, that modulation of endothelial BKCa significantly affects NTG-induced vasorelaxation in vitro, in the isolated perfused heart and in vivo.
Animals↗
Vascular smooth muscle contraction is an independent regulator of endothelial nitric oxide production.
This investigation was conducted to determine whether endothelial nitric oxide (NO) production is regulated by vascular smooth muscle contraction. Unperfused ring segments of rat aorta and mesenteric artery were studied using isometric tension recording (n = 6-8 in all experiments). Following a reference contraction to K+ 80 mM (100%), arteries were left either unstimulated or stimulated by different concentrations of K+ or prostaglandin F2alpha (PGF2alpha) to induce different levels of vascular precontraction. N(G)-nitro-L-arginine methyl ester (L-NAME 0.1-300 microM) or NS 2028 (0.03-3 microM), which is a new specific inhibitor of the NO-sensitive guanylate cyclase, was then added at increasing concentrations to evaluate endothelial NO production. L-NAME and NS 2028 produced a concentration-dependent vasoconstrictor response which was progressively enhanced with increasing levels of precontraction. For L-NAME, this amounted in aorta to (% of reference contraction): 35+/-1% and 105 +/- 4% (precontraction by K(+) 20 and 30 mM) and 22+/-1%, 89+/-1%, 138+/-1% and 146+/-2% (precontraction by PGF2alpha 0.5, 1, 2 and 3 microM). A similar coupling was found in the mesenteric artery. A precontraction as little as 2% was enough to trigger a vasoconstrictor response to L-NAME. In contrast, L-NAME and NS 2028 had no effect in non-contracted arteries, not even when passive mechanical stretch was increased by 100%. The results suggest (i) that endothelial NO formation is progressively increased with increasing vascular tone, and (ii) that vascular isometric contraction per se stimulates endothelial NO formation. It is concluded, that active vascular smooth muscle contraction is an independent regulator of endothelial NO production.
Animals↗
Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels.
The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed contractions induced by K+ (20 mM) compared with K+ (80 mM). In addition, concentration-relaxation curves for hydralazine (pD2 = 5.38 +/- 0.06; Emax = 85.9 +/- 3.6%) were shifted 10-fold to the right by the BK(Ca) blockers tetraethylammonium (1 mM) and iberiotoxin (0.1 microM). In contrast, nimodipine (a Ca2+-entry blocker), relaxed contractions induced by K+ (20 mM) and K+ (80 mM) equally and nimodipine-induced relaxations were neither antagonized by tetraethylammonium nor by iberiotoxin. In isolated perfused rat hearts, hydralazine (1 microM) increased coronary flow by 28.8 +/- 2.7%. Iberiotoxin (0.1 microM) suppressed this response by 82% (P < 0.05). In conscious, chronically catheterized rats the hypotensive response to hydralazine (0.6 mg kg(-1) min(-1)) was significantly reduced by 41% during infusion of iberiotoxin (0.1 mg kg(-1)). It is concluded, that opening of BK(Ca) takes part in the mechanism whereby hydralazine produces vasodilation.
Animals↗
Characterization of NS 2028 as a specific inhibitor of soluble guanylyl cyclase.
1 The haeme-containing soluble guanylyl cyclase (alpha1beta1-heterodimer) is a major intracellular receptor and effector for nitric oxide (NO) and carbon monoxide (CO) and mediates many of their biological actions by increasing cyclic GMP. We have synthesized new oxadiazolo-benz-oxazins and have assessed their inhibitory actions on guanylyl cyclase activity in vitro, on the formation of cyclic GMP in cultured cells and on the NO-dependent relaxation of vascular and non-vascular smooth muscle. 2 Soluble guanylyl cyclase, purified to homogeneity from bovine lung, was inhibited by 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS 2028) in a concentration-dependent and irreversible manner (IC50 30 nM for basal and 200 nM for NO-stimulated enzyme activity). Evaluation of the inhibition kinetics according to Kitz & Wilson yielded a value of 8 nM for Ki, the equilibrium constant describing the initial reversible reaction between inhibitor and enzyme, and 0.2 min(-1) for the rate constant k3 of the subsequent irreversible inhibition. Inhibition was accompanied by a shift in the soret absorption maximum of the enzyme's haem cofactor from 430 to 390 nm. 3 S-nitroso-glutathione-enhanced soluble guanylyl cyclase activity in homogenates of mouse cerebellum was inhibited by NS 2028 (IC50 17 nM) and by 17 structural analogues in a similar manner, albeit with different potency, depending on the type of substitution at positions 1, 7 and 8 of the benzoxazin structure. Small electronegative ligands such as Br and Cl at position 7 or 8 increased and substitution of the oxygen at position 1 by -S-,- NH- or -CH2- decreased the inhibition. 4 In tissue slices prepared from mouse cerebellum, neuronal NO synthase-dependent activation of soluble guanylyl cyclase by the glutamate receptor agonist N-methyl-D-aspartate was inhibited by NS 2028 (IC50 20 nM) and by two of its analogues. Similarly, 3-morpholino-sydnonimine (SIN-1)-elicited formation of cyclic GMP in human cultured umbilical vein endothelial cells was inhibited by NS 2028 (IC50 30 nM). 5 In prostaglandin F2alpha-constricted, endothelium-intact porcine coronary arteries NS 2028 elicited a concentration-dependent increase (65%) in contractile tone (EC50 170 nM), which was abolished by removal of the endothelium. NS 2028 (1 microM) suppressed the relaxant response to nitroglycerin from 88.3+/-2.1 to 26.8+/-6.4% and induced a 9 fold rightward shift (EC50 15 microM) of the concentration-relaxation response curve to nitroglycerin. It abolished the relaxation to sodium nitroprusside (1 microM), but did not affect the vasorelaxation to the KATP channel opener cromakalim. Approximately 50% of the relaxant response to sodium nitroprusside was recovered after 2 h washout of NS 2028. 6 In phenylephrine-preconstricted, endothelium-denuded aorta of the rabbit NS 2028 (1 microM) did not affect relaxant responses to atrial natriuretic factor, an activator of particulate guanylyl cyclase, or forskolin, an activator of adenylyl cyclase. 7 NO-dependent relaxant responses in non-vascular smooth muscle were also inhibited by NS 2028. The nitroglycerin-induced relaxation of guinea-pig trachea preconstricted by histamine was fully inhibited by NS 2028 (1 microM), whereas the relaxations to terbutaline, theophylline and vasoactive intestinal polypeptide (VIP) were not affected. The relaxant responses to electrical field stimulation of non-adrenergic, non-cholinergic nerves in the same tissue were attenuated by 50% in the presence of NS 2028 (1 microM). 8 NS 2028 and its analogues, one of which is the previously characterized 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), appear to be potent and specific inhibitors of soluble guanylyl cyclase present in various cell types. Oxidation and/or a change in the coordination of the haeme-iron of guanylyl cyclase is a likely inhibitory mechanism.
Animals↗
Coronary vasorelaxant effect of levosimendan, a new inodilator with calcium-sensitizing properties.
We examined the action of levosimendan, a new Ca2+-sensitizing inodilator, on isolated porcine coronary arteries. Vessel rings were studied in isometric myographs. Arterial cyclic adenosine monophosphate (cAMP) levels were determined by radioimmunoassay. Levosimendan (10(-7)-10(-3) M) completely relaxed arteries preconstricted by prostaglandin F2alpha (PGF2alpha) with a pD2 (-logEC50) value of 3.99 +/- 0.05 (n = 6-9 in all experiments). Pretreatment with levosimendan also prevented contraction induced by PGF2alpha. The vasorelaxation produced by levosimendan (10(-7)-10(-3) M) was not attenuated by removal of the endothelium. Levosimendan (10(-7)-10(-3) M) relaxed contractions induced by 30 mM K+ as well as 80 mM K+, whereas the K+ channel opener levcromakalim selectively relaxed contraction induced by 30 mM K+. Neither the cyclooxygenase inhibitor indomethacin nor the beta-adrenoceptor blocker propranolol influenced levosimendan-induced vasorelaxation. The Ca2+-entry blocker isradipine failed to relax arteries precontracted by endothelin-1 in Ca2+-free/EGTA medium. However, levosimendan (10(-7)-3 x 10(-3) M) completely relaxed endothelin-1-induced contractions in this medium. Levosimendan potentiated the relaxant effect of a cAMP-stimulating drug, isoprenaline, but also that of nitroglycerin and isradipine. At a maximal effective concentration, it increased arterial tissue contents of cAMP twofold. In conclusion, levosimendan produces coronary vasorelaxation by a mechanism that seems to be endothelium independent and not mediated by K+ channel opening, Ca2+-entry blockade, release of cyclooxygenase products, or beta-adrenoceptor stimulation. Accumulation of cAMP may possibly participate in vasorelaxation at high concentrations of levosimendan, but a cAMP-independent mechanism seems to be involved at lower concentrations.
Animals↗
[Violence--a challenge for health policy and an obligation for forensic medicine].
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Adult↗
Total number of particles in a bounded region estimated directly with the nucleator: granulosa cell number in ovarian follicles.
OBJECTIVE: Our objective was to evaluate the precision of the "nucleator" with regard to estimation of the number of granulosa cells in individual follicles and the average number of granulosa cells per follicle in a group of follicles. STUDY DESIGN: Nine murine ovarian follicles embedded in plastic were oriented isotropically with the "orientator" by Mattfeldt, cut into 20 microns serial sections, and stained with hematoxylin. In each follicle the number of granulosa cells was estimated in two ways, both unbiased: (1) with the nucleator principle in the section that contains the nucleolus of the oocyte and (2) in the complete set of follicle sections with the "fractionator" principle. Estimates with the fractionator were interpreted as "true" values. Therefore the precision (CE) of the nucleator estimates could be calculated. RESULTS AND CONCLUSION: The nucleator provides precise estimates of the number of granulosa cells in one complete follicle: CE = 0.12. The amount of effort is minimal, because estimation is based on roughly 50 granulosa cells. The precision of the procedure with regard to estimation of the average number of granulosa cells in a group of follicles depends mainly on the biologic variation (CVbiol = 0.71).
Animals↗
Lithium stimulates the first meiotic division in mouse oocytes.
Cumulus enclosed oocytes, cumulus enclosed oocytes denuded of their cumulus and cumulus free oocytes from 21 day old unstimulated mice were cultured for 18 hours in control medium supplemented with lithium chloride, dbcAMP and forskolin at various concentrations. In control medium 66% of the cumulus enclosed oocytes, 93% of the denuded oocytes, and 94% of the cumulus free oocytes resumed meiosis (germinal vesicle breakdown), whereas the levels of polar body formation were 27%, 12% and 39%, respectively. In the presence of lithium significantly more cumulus enclosed oocytes and cumulus free oocytes resumed meiosis and formed a polar body, whereas lithium had no effect on the denuded oocytes. Forskolin and dbcAMP stimulated resumption of meiosis and cumulus expansion in the cumulus enclosed oocytes and inhibited resumption of meiosis in the cumulus free oocytes. Lithium more or less eliminated this inhibitory effect of both forskolin and dbcAMP in the cumulus free oocytes. The results indicate (i) that activation of the cAMP second messenger path in the cumulus cells induces them to synthesize a meiosis inducing substance(s) which stimulates the oocyte to resume meiosis, and (ii) that other second messenger systems than the cAMP pathway, e.g. the phosphatidylinositol cycle, are involved in resumption of meiosis and polar body formation. We conclude that lithium enhances the capability of mouse oocytes for resumption of meiosis and polar body formation.
Animals↗
Who consults for rape? Sociodemographic characteristics of rape victims attending a medical rape trauma service at the Emergency Hospital in Oslo.
OBJECTIVE: To consider the number of victims of rape and attempted rape in a city (Oslo) who sought treatment when medical help had been made available. To examine the sociodemographic characteristics of the patient group that applied for help. DESIGN: Prospective study. SETTING: A rape trauma service (RTS) established at the Emergency Hospital in Oslo. The service is free, open around the clock, and independent of police notification. PARTICIPANTS: All patients attending RTS from 1 January to 31 December. RESULTS: 164 women and four men applied for medical treatment in 1987, four times as many as in 1985, before RTS was started. Their ages varied between 14 and 89 years, with a median of 27 years. Women aged 14-39 years were significantly over-represented in relation to the general female population of Oslo. Married women were significantly under-represented among the female patients, both married women raped by their spouses and married women raped by other men. 45 patients stated that they had been sexually assaulted on a previous occasion without reporting the incident or applying for help. CONCLUSION: Compared with the police an available medical service for rape victims reached four times as many rape victims as in 1985, from a larger share of the population.
Adolescent↗
Rape victims--assaults, injuries and treatment at a medical rape trauma service at Oslo Emergency Hospital.
OBJECTIVE: To describe assaults, injuries, and treatment in the 168 patients who attended the medical rape trauma service in 1987. To give an impression of the medico-legal documentation that is required. DESIGN: Prospective study. SETTING: A rape trauma service (RTS) established at the Emergency Hospital in Oslo. The service is free, open around the clock, and independent of police notification. RTS has standardized the medico-legal report used for rape victims. PARTICIPANTS: All patients attending RTS from 1 January to 31 December. RESULTS: Eighty-two (49%) patients reported the incident to the police. Two-thirds of the patients were assaulted by strangers, one-fifth by two or more assailants, and 16 were subjected to attempted rape. Weapons were used in 50 of the assaults. Eighty-one patients had physical injuries requiring documentation but no special treatment. Fourteen patients were infected with sexually transmitted diseases, three patients became pregnant. Seventy-eight patients returned for a medical follow-up. As many as 128 patients (76%) needed care from all parts of the emergency medical and psycho-social services. CONCLUSION: RTS shows that primary health service can be responsible for the treatment of rape victims and for the medico-legal documentation of rape trauma.
Adolescent↗
[Service for rape victims in Oslo].
The article presents the medical rape trauma service in Oslo, Norway. The rape trauma service was established in 1986 at the Emergency Hospital and serves all population in Oslo. The patient is offered a medical examination, a medico-legal documentation and evidence collection, crisis counselling, a stay at the observational ward, a victims lawyer, help to report to the police, a medical follow-up and a psycho-social follow-up. All treatment is free and the patient's choice. There is no obligation to report to the police. The number of rape victims being medically examined has increased four times compared to the average number of rape victims before the trauma service opened.
Crisis Intervention↗
[Expert witness in cases of rape].
The decision to try a rape case in court may depend on the medico-legal evidence documented by a doctor. Generally, doctors have little knowledge of expectations and requirements in court regarding testimony and expert opinion. In 1990, the Norwegian Directorate of Health recommended that victims of rape and violence all over the country--independent of police notification--be offered a medical and a medico-legal examination and follow-up. The Oslo Emergency Hospital has practised this health service for six years. The article describes the Oslo routine as a basis for doctors with little or no knowledge of the subject. Rape trauma, a variant of post-traumatic stress disturbance, manifests over time as physical, psychological and social reactions which influence the patient's health. The doctor must therefore follow the patient over time in order to apply this diagnosis. Rape trauma may be unknown to the court; a reason why the doctor should inform the prosecutor if it is decided that the case is to be tried in court. In order to document rape trauma as evidence the doctor must be called as an expert medical witness and not as an ordinary witness.
Expert Testimony↗
Smooth muscle relaxation and inhibition of responses to pinacidil and cromakalim induced by phentolamine in guinea-pig isolated trachea.
A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation when the tone was induced by histamine, carbachol, 30 mM K+ or 124 mM K+. Relaxant EC50 values ranged from 8 to 50 microM with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F2 alpha (PGF2 alpha) or leukotriene C4 (LTC4). At a concentration of 100 microM the alpha 2-adrenoceptor blocker, yohimbine, produced minor inhibition of spasmogen-induced tone, whereas the alpha 1-adrenoceptor blocker prazosin (up to 10 microM) had no inhibitory effects in the trachealis. Propranolol (1 microM), prazosin (1 microM), yohimbine (100 microM), tetrodotoxin (3 microM), glibenclamide (10 microM), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100 microM), dipyridamole (3 microM) or methylene blue (100 microM) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF2 alpha or LTC4, phentolamine (1, 10 and 100 microM) antagonized the relaxant action of the K+ channel openers, pinacidil and cromakalim. The concentration-relaxation curves for pinacidil were shifted 30-fold to the right without change in the maximal effects, whereas the maximal cromakalim-induced relaxant responses were markedly suppressed by phentolamine.
Animals↗
Isradipine dynamics and pharmacokinetics in the isolated rabbit heart.
The cardiac effects of increasing concentrations of isradipine (racemic) from 1.64 pM to 232 nM were studied in isolated spontaneously beating rabbit hearts. Inhibitory responses with regard to contraction amplitude, contraction velocity and oxygen consumption exhibited a biphasic progressive course at increasing drug exposure. Computer derived inhibitory Emax-values of the second phase were 104, 103 and 87% (IC50: 7.1, 6.3 and 28.7 nM), respectively, whereas those of the initial phase were 24.7, 25.9 and 19.5% (IC50: 0.012, 0.038 and 0.026 nM). A progressive inhibition of frequency reached a maximum of only 21%. The ECG-derived PQ-interval showed a rapid increase (maximum 46%) at drug concentrations above 1 nM. Complete AV-block and ventricular asystolia occurred in half of the hearts at the second highest (99 nM) and in all except one at the highest concentration. SA-node activity was retained in 9 of 10 hearts at the second highest and in 3 at the highest drug exposure. The QRS-and the frequency-corrected QT-interval did not increase significantly. Coronary flow-rate showed no initial increase, but a decrease to 70% of control at the highest concentration. Supplementary in vitro studies on rabbit coronary artery ring-preparations contracted with 124 mM K+ showed, however, an relaxant Emax-value for isradipine of about 100% and an inhibitory EC50-value of 0.63 nM with a 'Hill' coefficient of 1.1. At toxic concentrations isradipine showed a kinetic monophasic accumulation in the rabbit heart of about 44-fold with a half-time of 10.6 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Chronic health problems after rape].
A questionnaire examination was conducted of a sample of 168 well-educated women who suffered rape on average 13 years ago. A retrospective survey was made of acute and chronic symptoms. Physical symptoms were reported by 44% of the sample, mental symptoms by 98% and social symptoms by 79%. 11% have attempted suicide, and 19% report excessive use of alcohol and/or medicines. The symptoms are of a category which, when presented to doctors, might be diagnosed as "unspecified symptoms". Only 17 women (10%) sought treatment immediately after the rape. Half of these were referred by the police. Three of these women felt that their needs were met by the health services. As a result of their experience of untreated rape trauma, six out of ten women in the sample would now seek specified treatment if raped again.
Adult↗
Effects of pinacidil and other cyanoguanidine derivatives on guinea-pig isolated trachea, aorta and pulmonary artery.
The effects of pinacidil and four other cyanoguanidine derivatives (P 1060, P 1106, P 1787, P 1890) were evaluated on guinea-pig isolated trachea, aorta and pulmonary artery. All compounds were effective smooth muscle relaxants. Concentration-relaxation curves and corresponding EC50 and Emax values were determined in preparations contracted by histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. Pinacidil relaxed trachea by 100% and vascular tissues by 70%. P 1060 and P 1106 also produced complete tracheal relaxation, but had a lower maximal effect of 40% in vascular smooth muscle. P 1787 and P 1890 relaxed all three types of tissues by 100%. The order of potency of the drugs was P 1106 greater than P 1060 greater than pinacidil greater than P 1890 greater than P 1787. Pinacidil, P 1060 and P 1106 were more potent on pulmonary artery than on aortic preparations. Based on the effects of the drugs on 30 mM K(+)- and 124 mM K(+)-induced contractions and the ability of glibenclamide to antagonize the drugs, P 1060 and P 1106 appeared to be pure K+ channel openers whereas pinacidil seemed to operate by additional mechanisms. P 1787 and P 1890 relaxed smooth muscle by a mechanism other than opening of K+ channels.
Animals↗
Cardiac uptake kinetics and possible dynamic effects of a new cerebral antiischaemic compound FG 9202 (NBQX) studied in the isolated rabbit heart.
Accumulation of the putative drug FG 9202 in isolated rabbit hearts showed monophasic exponential kinetics with a half-life of only 0.59 min. The disposition showed a three-phasic exponential time course with half-lives of 0.34, 1.51 and 15.8 min, respectively, which was interpreted as three-compartment kinetics. FG 9202 accumulated only about 3 times in the myocardium at steady-state with 51, 32 and 17% referable to a superficial and two deeper myocardial drug pools. The drug did not significantly affect contraction amplitude or velocity of contraction at increasing concentrations up to 40.6 micrograms.ml-1 (119 microM). Heart beating frequency decreased slightly but only significantly at some of the higher concentrations. Neither dromotropic, bathmotropic nor ischaemic ECG-effects were observed. Coronary flow-rate and myocardial oxygen consumption decreased at the highest drug concentrations. Myocardial efficiency expressed as the ratio of contractile parameters to oxygen consumption showed a minor but insignificant increase at the highest drug-exposure levels. Our findings indicate that FG 9202 is not potentially toxic to the isolated, spontaneously beating rabbit heart in vitro.
Animals↗