The action of capsaicin (CAP) on the total Ca2+ current was examined in internally perfused voltage-clamped dorsal root ganglion (DRG) neurones of guinea pigs. CAP changed the total Ca2+ current in about 50% of the investigated DRG neurones ("CAP-sensitive" neurones) in the following way: (I) a transient increase of the current amplitude at potentials between -35 mV and about -10 mV was accompanied by a shift of the current-voltage relation towards negative potentials by 5-8 mV; (II) the current inactivation was accelerated at potentials positive to about -35 mV; and (III) the current activation of Ca2+ currents (time to peak values) was also accelerated. Separated low voltage-activated (T-type) currents at potentials negative to about -35 mV were either not affected or reduced. It remains undecided whether CAP increases T-type currents in a particular potential range or activates an N-type current. External application of 50 microM Ni2+ blocks the effect of CAP, but does not affect the acceleration of the high voltage-activated (L-type) current inactivation induced by menthol. This appears to exclude a CAP effect on L-type current inactivation. "CAP sensitive" and "CAP insensitive" neurones could be discriminated by their different Ca2+ currents: the former demonstrate both fast and slow inactivating currents while the latter have only L-type currents. The observed changes of fast-inactivating Ca2+ currents may be related to the specific action of CAP on peptidergic sensory neurones.

Animals↗

PubMedDate not supplied

Hypothyroid-like effect of amiodarone in the ventricular myocardium of the rat.

Due to the similar electrophysiological effects of amiodarone and hypothyroidism in the myocardium, the induction of a local hypothyroid state has been proposed as the mechanism of action of amiodarone. To examine this hypothesis we have studied the influence of amiodarone on the distribution of ventricular isomyosins--a sensitive parameter of the thyroid state in the rat heart--and the effects of amiodarone on 3,5,3'-triiodothyronine (T3) myocardial nuclear receptor binding in vivo. Amiodarone induced a dosage-dependent redistribution of isomyosins similar to hypothyroidism, while simultaneously inducing a low T3 syndrome at the higher dose level. In hypothyroid rats, which were pretreated with amiodarone, substitution of T3 (2 micrograms/100 g) led to a complete reversal of the myosin pattern not differing from control hypothyroid rats which were only given T3; the effect of T3 (0.5 microgram/100 g) was however partially inhibited by amiodarone. Nuclear receptor binding of T3 determined in hypothyroid rats in vivo was unaffected by amiodarone. We conclude that amiodarone induces a hypothyroid-like state in the ventricular myocardium of rats by inhibiting the action of T3--an effect which cannot be attributed to an antagonism at the T3 nuclear receptor level.

Amiodarone↗

PubMedDate not supplied

N alpha-arylsulfonyl-omega-(4-amidinophenyl)-alpha-aminoalkylcarboxylic acid amides--novel selective inhibitors of thrombin.

Explore the source record for details and available documents.

Amidines↗

PubMedDate not supplied

Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women.

The human vagina is known to be heavily innervated by vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. In the present study we have examined the effect of VIP (900 pmol x kg-1 x h-1, IV during 30 min) on vaginal lubrication and blood flow in fourteen normal non-pregnant women. Vaginal blood flow was measured by the heat clearance technique and the vaginal lubrication quantified by the weight gain of preweighed filter papers placed on the surface of the vaginal wall for 30 min. Arterial blood pressure, pulse frequency and the concentration of VIP in peripheral blood were monitored. VIP (median concentrations of 200-300 pmol x l-1) induced a significant increase in vaginal blood flow accompanied by a 100% increase in vaginal lubrication (from 27 mg/cm2 to 53 mg/cm2). The VIP infusion lead to a significant increase in pulse frequency and a significant fall in diastolic arterial blood pressure. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication.

Adult↗

PubMedDate not supplied

Lack of effect of long-term glutathione administration on aflatoxin B1-induced hepatoma in male rats.

The effect of long-term GSH administration on aflatoxin B1 (AFB1)-induced carcinogenesis in the livers of male Wistar II rats was evaluated. No significant effect of an 11 months period of reduced glutathione (GSH) administration was observed concerning both the survival curve and the incidence of liver tumors. Liver tissues of all animals were bearing tumors or nodular lesions 24 months after AFB1 treatment, regardless of GSH treatment. The capacity of the GSH conjugation system was elevated in the liver tissue of AFB1-treated animals both by an increase of GSH content and an increase of the specific activities of several GSH S-transferase isoenzymes. Likewise the specific activities of GSH related enzymes as GSSG reductase and gamma-glutamyltransferase (gamma-GT) and the activity of the GSH independent detoxication system NAD(P)H:quinone oxidoreductase were increased in the AFB1-treated livers, there was no significant effect of GSH treatment. These results demonstrate that long-term GSH treatment has no effect on the survival of AFB1-pretreated male rats on the incidence of liver tumors and on the activities of drug metabolizing systems. The hepatic detoxication capacity 24 months after AFB1 treatment is elevated.

Aflatoxin B1↗

PubMedDate not supplied

Clinical case definitions for malaria: clinical malaria associated with very low parasite densities in African infants.

In areas endemic for Plasmodium falciparum, clinical malaria is believed to be less common in infants than in older children, but specific case definitions have rarely been determined for this age group. As malaria case definitions are known to be both age- and site-specific, assessment of the risk of disease in infancy requires the development of appropriate diagnostic criteria. In southern Ghana, 154 children were recruited at birth and monitored for fever and malaria infection until 2 years of age. Logistic regression was used to model fever risk as a continuous function of parasite density to determine case definitions for the diagnosis of clinical malaria, and to determine age- and season-specific estimates of the fraction of fevers attributable to malaria (AF); 2360 observations were made on 154 children. For fevers defined by a measured temperature > or = 37.5 degrees C, the estimated population AF was 44% (95% confidence interval 34-53). Estimates of AF varied with age and season. For infants, AF was 51% during the wet season and 22% during the dry season; for children over one year of age, AF was 89% during the wet season and 36% during the dry season. The estimated parasite density threshold for initiation of a febrile episode was 100 parasites per microL of blood in infants, compared with 3500 parasites per microL for children over one year of age. Using these case definitions, the incidence of clinical malaria was estimated at 0.09 cases per child-year at risk for children less than 6 months of age, 0.40 for children aged 6-11 months, and 0.69 for children aged 12-23 months. Of 66 cases of clinical malaria, only 3 were observed in children under 5 months of age. We concluded that, although most fevers in infants are not due to malaria, infant clinical malaria may occur at extremely low parasite densities. This may be indicative of a lack of anti-disease immunity in this age group. In southern Ghana, an infant with axillary temperature > or = 37.5 degrees C and parasitaemia > or = 100/microL should be considered to have clinical malaria. Nevertheless, the incidence of clinical malaria is very low in children under 6 months of age, confirming that they are significantly protected from clinical malaria compared to older children.

Age Factors↗

PubMedDate not supplied

A community hospital's effort to expedite treatment for patients with chest pain.

OBJECTIVE: The purpose of this study was to determine treatment times at a community hospital that does not receive prehospital electrocardiogram (ECG) transmission and to determine the effect of time to first hospital ECG on overall door-to-drug time. DESIGN: Descriptive. SETTING: 238-bed Regional Medical Center in Burlington, North Carolina. SAMPLE: One hundred four patients with a final diagnosis of acute myocardial infarction were included in this 16-month study. RESULTS: A median door-to-ECG time of 5 minutes was within the American College of Cardiology/American Heart Association recommendation of 10 minutes. Shorter treatment times to obtain the first ECG and initiate thrombolytic therapy were associated with younger patients and those arriving by ambulance. CONCLUSIONS: While efficiency in obtaining a first hospital ECG on patients with suspected acute myocardial infarctions was achieved, this did not result in low door-to-drug times. Further streamlining of protocol and the exploration of prehospital initiatives may result in a significant reduction in door-to-drug times.

Chest Pain↗

PubMedDate not supplied

Hemodynamic effects of nicorandil, isosorbide dinitrate, and dihydralazine in healthy volunteers.

In this randomized, double-blind, crossover, single-dose study with 12 healthy subjects, we determined the hemodynamic changes and their time kinetics after administration of the mononitrate nicorandil (60 mg s.l.) and compared these effects with changes after administration of isosorbide dinitrate (ISDN; 20 mg s.l.), dihydralazine (10 mg i.v.), and placebo. Mechanocardiography, electrical impedance cardiography, and M-mode echocardiography measured drug effects. Dihydralazine increased heart rate, systolic pressure, and ventricular ejection time, and it decreased peripheral resistance, diastolic pressure, preejection period, end-systolic diameter and wall stress; these changes indicate an intense, pure afterload reduction. ISDN decreased systolic pressure, peripheral resistance, end-diastolic and systolic diameters and wall stress, shortened the ejection time, and prolonged the preejection period. The responses suggest ISDN causes a notable preload reduction accompanied by some afterload reduction. Nicorandil's effects were similar to those of ISDN in that the reductions in preload were equal, although the afterload reduction was more intense. Nicorandil's effects reached significance within 10 min, reached a maximum by 60 min, and had not vanished at 4 h. A drug with this profile and time kinetics should be tested further in situations requiring pre- and afterload reductions.

Adult↗

PubMedDate not supplied

Model-based estimation of cardiovascular repolarization features: ischaemia detection and PTCA monitoring.

The ST-T segment of the surface ECG reflects cardiac repolarization, and is quite sensitive to a number of pathological conditions, particularly ischaemia. ST-T changes generally affect the entire waveshape, and are inadequately characterized by single features such as depression of the ST segment at one particular point. Metrics which represent overall waveshape should provide more sensitive indicators of ST-T wave abnormalities, particularly when they are subtle, intermittent or periodic. This study discusses a Karhunen-Loève transform (KLT) technique for the analysis of the ST-T waveform. The KL technique was used to analyse the ST-T complexes in the ESC ST-T database. KL coefficients were plotted as a function of time, and were effective in detection of transient ischaemic episodes. Twenty per cent of the records showed bursts of periodic ischaemia suggesting local vascular instability. A comparison between kl and ST depression series has shown the KL technique as more appropriate to the study of ST-T complex variations. Using the kl series, an ischaemia detector has been developed based on a resampled, filtered, and differentiated KL series. This technique demonstrates a sensitivity of 65% and a specificity of 54%. These low values can be due to shifts of the electrical axis which are detected as ischaemic changes, real ischaemic episodes that were not annotated with the protocol used at the European ST-T database, or erroneous detections. An increase in sensitivity can be obtained at the expense of a decrease in the positive predictive value and thus becomes a useful technique for previous scanning of the ECG record and subsequent review by the expert. The technique has also been used to monitor patients during a PTCA process, demonstrating that this technique allows us to monitor PTCA-induced ischaemia. A detailed analysis has shown that in some cases a repetitive oscillatory behaviour appears, lasting for a period of around 20 s, and highly related to the oscillatory behaviour of the HR. In other cases, transient changes in KL series with salves behaviour associated with the injection of contrast are shown on the ST-T waveform. We conclude that the KL-based analysis of the ST-T segment is a robust and sensitive technique, with considerable advantages over single feature measures in characterizing the subtle waveform changes which may be of importance in clinical risk detection.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Renal artery occlusion model in dogs for the evaluation of thrombolytic agents.

The purpose of this study was to develop a model of renal artery occlusion and to investigate the effects of various thrombolytic agents on an acute occlusion of the renal artery with respect to ischemic tolerance of renal parenchyma. In order to do this, a thrombosis model in dogs (n = 36) was established and a total of 72 dorsal renal arteries occluded using autologous clot material. For the in vitro preparing of a clot, autologous blood (20 mL) was withdrawn and 100 U thrombin immediately added. Then 1 mL of the clot material was injected into the dorsal branch of the exposed renal artery. The dogs were divided into 8 groups (2 control groups, 6 therapy groups with local and systemic thrombolytic therapy). Thrombolysis was performed using urokinase, single-chain urokinase, and recombinant tissue-plasminogen activator. In all cases the clot preparation technique allowed complete and stable occlusion of the renal arteries. Local and systemic application of the thrombolytic agents, however, resulted in complete recanalization of the clot material in all study groups. Recombinant tissue-plasminogen activator turned out to be the most effective agent in terms of recanalization time. The technique described allowed effective and reproducible artery occlusion for in vivo experimental work to study comparatively thrombolytic agents with respect to fibrin specificity, lytic efficacy, and side effects.

Animals↗