[Primary care health professionals counsel more male then female smokers].
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Adult↗
Biomedical subjects
J L Alvarez
Publications and source records attributed to J L Alvarez.
Cardiac cellular actions of hydrochlorothiazide.
In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.
Action Potentials↗
Homeopathy in Cuban epidemic neuropathy: an open clinical trial.
In an outbreak of epidemic neuropathy (EN) in Cuba (1992-1993), most patients were improved by vitamin therapy. In subjects with residual symptoms, alternative treatments including homeopathy were suggested to ameliorate optic and peripheral signs of the disease. An open clinical pilot trial was conducted on 31 patients with long standing symptoms of optic (OPTI group, n=15) or peripheral EN (PERI group, n=16). During the trial, OPTI and PERI patients continued the same treatment that they received before. Carboneum sulphuratum and Tabacum in homeopathic dilutions were administered for 30 days. These medicines are specific to optic EN, but not closely linked with peripheral EN. Clinical status was evaluated by neurological and ophthalmologic tests at diagnosis (Ddiag), 7 days before homeopathic treatment (D0) and 90 days after (D90). From D0 to D90, the percentages of improvement were 73.3% for the OPTI form and 12.5% for the PERI form. The percentage of improved OPTI patients was significantly higher after the homeopathic treatment vs the period between Ddiag and D0 for optical EN (P<0.01), but not for PERI subjects (P>0.05). In the OPTI group, colour vision, visual acuity and visual field improved after homeopathic treatment (P<0.001), these parameters did not change between Ddiag and D90 (P>0.05). Carboneum sulphuratum and Tabacum showed a reasonable effectiveness in optical EN, but were not effective in PERI EN.
Cuba↗
Late post-myocardial infarction induces a tetrodotoxin-resistant Na(+)Current in rat cardiomyocytes.
Left ventricular remodeling after myocardial infarction is accompanied by electrical abnormalities that might predispose to rhythm disturbances. To get insight into the ionic mechanisms involved, we studied myocytes isolated from four different regions of the rat ventricles, 4-6 months after ligation of the left coronary artery. Using the whole-cell patch-clamp technique, we never observed T-type Ca(2+)current in both diseased and control hearts. In contrast, in 41 out of 78 cells isolated from 16 post-myocardial infarcted rats, analysed in the presence of 30 m m Na(+)ions, we found a tetrodotoxin (TTX)-resistant Na(+)current with quite variable amplitude in every investigated region. Albeit being resistant to 100 microM TTX, this Na(+)-dependent current was highly sensitive to lidocaine since 3 microM lidocaine induced about 65% tonic block. It was also inhibited by 5 microM nifedipine and 2 m m Co(2+), but was insensitive to 100 microM Ni(2+). The TTX-resistant Na(+)channel availability was shifted rightward by 25-30 mV with respect to TTX-sensitive Na(+)current; therefore, a large "window current" might flow in the voltage range from -70 to -20 mV. In conclusion, in late post-myocardial infarction, a Na(+)current with specific kinetics and pharmacology may provide inward charges in a critical range of membrane voltages that are able to alter action potential time course and trigger ventricular arrhythmia. These apparent new characteristics of the Na(+)channel might result in part from environmental changes during heart remodeling.
Animals↗
Modulation of voltage-dependent facilitation of the T-type calcium current by sodium ion in isolated frog atrial cells.
Sodium ions have been reported to alter the permeation properties of L- and N-type Ca2+ channels. Here in frog atrial cardiomyocytes under whole-cell patch-clamp conditions, we have examined the effects of lowering the external Na+ concentration on the amplitude of T-type Ca2+ current, ICaT, and on the relief of its steady-state inactivation by large depolarizing prepulses, ICaT facilitation. A partial reduction in Na+ ion concentration did not significantly alter ICaT amplitude elicited at -50 mV. However, after a large depolarization, low- Na+ solutions enhanced the relief of inactivation and induced ICaT facilitation. This facilitation occurred independently of the divalent charge carrier, high intracellular Ca2+ buffering or the intracellular Na+ content. Its effects were additional to the beta-adrenergic effects mediated by a decrease of Gi/o-protein inhibitory tone. In Ca2+-free solution the very large T-type current, then carried by Na+ ions, showed only a weak relief of inactivation. In conclusion, ICaT facilitation--which, as previously reported, is modulated by the transient voltage-dependent relief of Gi-protein inhibitory tone--is further enhanced in a low-Na+ solution. In Ca2+-free solution, relief of inactivation due to re-openings dependent on the divalent charge carrier is improbable. It thus appears that for a short while after a large depolarization, external Na+ compete with Ca2+ ions on permeation-controlling sites, so as to modulate channel re-openings and thus the amplitude of voltage-facilitated ICaT independently of the control exerted by the inhibitory G-protein.
Animals↗
Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction.
OBJECTIVE: Deleterious electrical abnormalities evolve during myocardial infarction. The goal of this study was to analyse current changes during the late decompensated phase of heart disease induced by coronary ligation and to compare them in various heart regions. METHODS: Young rats were submitted to left coronary ligature. After 4-6 months, cells were enzymatically dissociated and isolated from the upper part basal region of the left ventricle, as well as from the septum, apex and the right ventricle before being studied under whole-cell patch-clamp. RESULTS: Basal L-type Ca2+ current, ICaL elicited at +10 mV did not exhibit regional dependence neither in control nor after post-myocardial infarction (PMI). ICaL showed both a significantly reduced peak amplitude (17.1 +/- 2.8 pA/pF versus 9.9 +/- 1.4 pA/pF in seven control and seven PMI hearts, n = 32 and 40, respectively) and a slower inactivation, such that the amount of inward charges during a 200 ms-depolarizing pulse was nearly unchanged. beta-Adrenergic stimulation was less effective in increasing ICaL in PMI cells but it slowed inactivation further. Significant differences in the K+ currents were observed. A regional distribution was seen for Ito only, with the largest amplitude in the right ventricle (in pA/pF: 23.1 +/- 2.4, 18.2 +/- 3.9, 14.8 +/- 2.4, 8.3 +/- 1.7 in the right ventricle, apex, septum and left ventricle, respectively n = 8, 7, 8 and 9). This was also true in failing heart cells despite Ito being halved in each of the four regions (in pA/pF: 12.2 +/- 2.5, 11.2 +/- 1.9, 5.1 +/- 1.0 and 4.8 +/- 1.0, respectively n = 12, 12, 11 and 13). IK1 was also significantly reduced by 20% in the PMI cells. Two-way analyses of variance demonstrated the absence of interaction between the topographical origin of the cells and the physiological state of the rats. The alpha 1-adrenergic agonist, methoxamine significantly reduced Ito and IK1 to the same extent in both sham and PMI cells, by about 35% and 20% respectively. CONCLUSIONS: Long-term left coronary occlusion induces significant alterations in both Ca2+ and K+ currents that occur with similar amplitude in both ventricles. They include a marked reduction in Ito amplitude as well as a slowing of ICaL inactivation. Both factors could contribute to the disturbances in cellular electrical behaviour and the occurrence of arrhythmias in the post-myocardial infarcted heart.
Action Potentials↗
Characteristics of Ca2+ channel blockade by oxodipine and elgodipine in rat cardiomyocytes.
The two novel dihydropyridines, oxodipine and elgodipine greatly depressed the KCl-induced contraction of rabbit aorta and decreased the cardiac force of contraction of rat ventricular strips with lower potency. Both compounds markedly shortened cardiac action potentials. In rat cultured neonatal ventricular myocytes, oxodipine and elgodipine decreased the L-type Ca2+ current (I(CaL)) with IC50 of 0.24 and 0.33 microM respectively while oxodipine was slightly more potent on the T-type Ca2+ current (I(CaT)) than elgodipine (IC50 = 0.41 vs. 2.18 microM). Both compounds were less potent in inhibiting I(CaL) of adult cardiomyocytes. Oxodipine exhibited mostly a tonic block of both currents while elgodipine induced mainly a use-dependent block. Oxodipine and elgodipine increased by at least one order of magnitude their inhibitory potency on I(CaT) and I(CaL) when the cells were partially depolarized. We conclude that the mechanisms of inhibition of Ca2+ channels by these two dihydropyridines are different and suggest that the underlying mechanism of vascular selectivity is the voltage-dependent block of I(CaL), with the use-dependent inhibition of Ca2+ currents by elgodipine further contributing to this selectivity.
Action Potentials↗
Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine.
The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro-5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for cycleanine and nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The results suggest that cycleanine can act as a potent vascular selective Ca-antagonist.
Alkaloids↗
Effects of a toxin from the mucus of the Caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes.
The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5-1 mg/ml it increased the L-type Ca current (ICaL) by 25-50%. This increase in ICaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1-10 mg/ml). In this concentration range, Bainh markedly (approximately 75%) increased the inward-going rectifier current, IKI. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.
Action Potentials↗
When is a lower limit of detection low enough?
In cleanup operations and environmental surveillance efforts, a level of concern usually specifies a concentration limit for a particular radionuclide above which some action may be warranted. It is critical that the analytical method selected for measurements has a detection limit well below the action level. This is to guarantee that the technique used provides precise assessment at the level of concern. Sample analysis made with good precision is one of the major steps for obtaining quality data that allow a sound decision on whether the nuclide concentration is in compliance. This paper examines how the magnitude of the detection limit of an analysis method affects the precision of a measurement at the action level. With the established relationship, the detection limit that would achieve a pre-set precision for measurements at a level of concern can be quantitatively determined. The desired detection capability thus serves as a guide for selecting the appropriate measurement system.
Environment↗
Data quality objectives for surface-soil cleanup operation using in situ gamma spectrometry for concentration measurements.
In situ gamma spectrometry is an efficient method for monitoring the progress of cleanup activities for radioactive contaminants in surface soil and for evaluating the attainment of cleanup standards. However, desired data precision and accuracy must be specified for such a detection system prior to the operation to ensure that the level of uncertainty associated with the concentration measurements is acceptable. A method for developing data quality objectives is described in this paper for in situ gamma spectrometry to achieve numerical goals for data precision and accuracy for cleanup operations. Concentration measurement for a radionuclide at its cleanup level must have a precision commensurate with the importance of cleanup decisions. The 95% lower limit of detection of the system is suggested to be about one tenth the expected system response at the cleanup level. The count time required to achieve the preferred 95% lower limit of detection, and hence the desired precision, can then be determined. The accuracy error arises from the overall calibration factor, which relates the detector responses (e.g., count rate) to physical quantities of interest (e.g., radionuclide soil concentration). The major source of error for the calibration factor using in situ gamma spectrometry is the misidentification of the type of the depth profile of radionuclide concentration in soil. If surrogate radionuclides are used, such as 241Am for plutonium, the variation in the concentration ratio would be another significant source of error. Soil sampling programs performed prior to a cleanup operation will greatly reduce the accuracy error for an in situ detection system, and the analysis of system errors may determine the degree of sampling required. The planning of such a program is discussed in the study. Uncertainty analysis using a Latin Hypercube sampling technique for the calibration factor is also demonstrated. The quantitative result of the uncertainty analysis is useful for determining a nuclide's maximum peak count rate using gamma spectrum that ensures the attainment of the cleanup standard for that nuclide with a pre-specified confidence level (e.g., 95%). The cleanup operation of 239,240Pu in surface soil in the safety shot areas at the Nevada Test Site serves as an example to illustrate the data quality objectives development.
Americium↗
Facilitation of T-type calcium current in bullfrog atrial cells: voltage-dependent relief of a G protein inhibitory tone.
1. The properties of the low-threshold calcium current, ICa,T, were investigated in bullfrog isolated atrial cardiomyocytes using the whole-cell, patch-clamp technique under control conditions and during beta-adrenergic stimulation. 2. The intracellular application of GTP gamma S or adenosine-5'-O-3-thiotriphosphate (ATP gamma S), poorly hydrolysable analogues of GTP and ATP, respectively, barely affected ICa,T amplitude in control conditions. beta-Adrenergic stimulation effects were more marked in the presence of ATP gamma S. 3. The intracellular application of GDP beta S and ADP reduced ICa,T amplitude. In cells pretreated with pertussis toxin, ICa,T amplitude was significantly increased. In both conditions, the addition of isoprenaline was without effect. 4. Under both control and beta-adrenergic-stimulated conditions, a conditioning prepulse to +70 mV did not fully inactivate ICa,T; rather ICa,T facilitation often occurred after beta-adrenergic stimulation. 5. In GTP gamma S- and ATP gamma S-dialysed cells, ICa,T facilitation was generally observed after a prepulse; it was larger in the ATP gamma S dialysis. Facilitation was sustained but ended immediately upon cessation of conditioning prepulses. After beta-adrenergic stimulation, facilitation was more marked in GTP gamma S- than in ATP gamma S-dialysed cells. 6. ICa,T facilitation was prevented by the intracellular application of GDP beta S and by pertussis toxin pretreatment. 7. ICa,T facilitation developed markedly in the presence of intracellular cyclic AMP. This effect was prevented by pertussis toxin pretreatment of the cells. 8. It is thus proposed that ICa,T is under a double antagonistic control by both a Gs and a Gi protein. Furthermore, the double-pulse-induced facilitation of ICa,T results from a voltage-dependent relief of the Gi protein inhibitory tone. Such an effect is increased by protein kinase A-dependent phosphorylation, presumably of the Gi protein.
Animals↗
Effects of physical exercise on some parameters of bone metabolism in postmenopausal women.
This study was performed on 19 postmenopausal female volunteers in a period of five months of moderate physical exercise in order to examine beneficial changes in muscle strength and flexibility as well as changes in sex hormone binding globulin (SHBG) and other parameters related to bone metabolism. While SHBG decreased significantly (from 56.0 +/- 20.0 to 43.9 +/- 16.1 nM, P = 0.009) phosphorus and urea increased (from 2.8 +/- 0.4 to 4.0 +/- 0.5 mg/dl, P = 0.00006 and from 32.1 +/- 9.4 to 42.3 +/- 11.0 mg/dl, P = 0.03, respectively). These changes were accompanied by significant increases in muscle strength and flexibility. Other parameters such as alkaline phosphatase and calcium did not change significantly during the study. Plasma levels of SHBG were negatively correlated with phosphorus. As higher SHBG has been related to increased bone loss in older women, we conclude that moderate physical activity is an effective means to preserve bone loss in postmenopausal women.
Alkaline Phosphatase↗
[A descriptive clinical study of a type of arthritis in beekeepers of the Badajoz area of La Siberia Extremeña].
BACKGROUND: The appearance of episodes of arthritis has been detected in beekeepers in the Siberia Extremadura (Spain) related to working with the hives. This present work describes the clinical features of such arthritic syndrome. METHODS: Sixty cases were selected at random from a previous epidemiological study to undergo a clinical protocol that included, anamnesis, physical signs, haematological, biochemical and immunological analyses, and radiological exploration of hands, wrists, feet, and pelvis. RESULTS: The picture is characterized by episodes of oligoarthritis associated with bee-stings in the affected joints or nearby. The most frequent radiologic lesions are pinched articular lines, sclerosis, and the presence of geodes. Analytically, there was frequent eosinophilia, abnormalities in haemostasis tests, and a rise in serum alkaline phosphatase. CONCLUSIONS: An acute inflammatory oligoarthritis of unknown cause has been described which affects the hands asymmetrically, and which is found in beekeepers in relation to their work with the hives. It occasionally involves into a chronic localized arthropathy capable of provoking ankylosis and permanent articular disability.
Acute Disease↗
Predictive factors of Mycobacterium tuberculosis infection and pulmonary tuberculosis in prisoners.
BACKGROUND: Tuberculosis currently represents a serious problem in prison populations. METHODS: With the aim of studying the predictive factors for, and the prevalence of, Mycobacterium tuberculosis infection and pulmonary tuberculosis in a Spanish prison, all those admitted during 1991 and 1992 were included (N = 1314). The tuberculin skin test, HIV serology, chest X-ray and bacteriological examination of sputum were carried out. Statistical analysis was done by univariant tests, stratified analysis and logistic regression. RESULTS: The prevalence of M. tuberculosis infection was 55.5% (95% confidence interval [CI] 52.5-58.5). An association was found with sex, imprisonment more than once, HIV infection and age. The co-infection rate (tuberculosis plus HIV) was 9.2%. Logistic regression showed a greater risk with age (4.4% per year), time spent in prison and for males. The prevalence of pulmonary tuberculosis was 1.26% and an association was found with M. tuberculosis infection, HIV infection (odds ratio [OR] = 13.7), intravenous drug users (OR = 17.2) and imprisonment more than once (OR = 7.3). Logistic regression showed an association with HIV co-infection (OR = 20.2). CONCLUSIONS: The prevalence of M. tuberculosis infection and pulmonary tuberculosis is high when compared with similar studies. The influence of age, time spent in prison and co-infection with HIV is relevant to recommendations for specific tuberculosis prevention programmes in correctional facilities.
Acquired Immunodeficiency Syndrome↗
Design of an airborne plutonium survey program for personnel protection.
Various options were considered for surveying and real-time monitoring for airborne plutonium for optimum protection of personnel. Placement of samplers, dilution factors, and analysis time were considered in the strategy for achieving regulatory compliance and maintaining internal dose as low as reasonably achievable (ALARA). It was found that protection was relatively insensitive to placement as was sensitivity of detection. It was also found that maximum protection was obtained with few detectors and increasing the number of detectors above the optimum value did not appreciably increase the information about a release nor did it aid in locating the release. It was determined that the best protection was obtained with alarming monitors if the detection sensitivity was sufficiently low. Integrating samplers requiring laboratory analysis can be more sensitive than alarming monitors, but the lack of timeliness limits the amount of protection. The integrating samplers can be used effectively to monitor engineering controls. Personal air samplers also offer little protection but can be very effective in analyzing exposure by craft and job type.
Air Pollutants, Radioactive↗
Gastric perforation due to ventriculo-peritoneal shunt.
Gastric perforation is a complication that can arise from ventriculo-peritoneal (VP) shunting. Careful examination of a newborn girl admitted to our department revealed several neurological problems. A VP shunt was inserted under direct visualization, leaving 20 cm of the catheter in the peritoneal cavity. The infant was discharged 6 days after surgery and readmitted 4 months later due to increasing head circumference and severe malnutrition. Physical examination revealed a soft abdomen, normal peristalsis, and no signs of peritoneal irritation. The patient was submitted to exploratory surgery, which showed that the catheter had penetrated about 6 cm into the stomach. The VP shunt was removed and replaced by a left ventriculo-atrial system. The patient evolved well and was discharged 5 days later. Probable causes of the perforation are discussed in this paper.
Female↗
Effects of tetrandrine on Ca(2+)- and Na(+)-currents of single bullfrog cardiomyocytes.
Tetrandrine is a natural alkaloid classified as a calcium antagonist. However, its precise actions on Ca(2+)-currents in cardiac cells have not been fully characterized. In the present study, we have investigated the mechanism of action of tetrandrine on the Ca(2+)-currents of single bullfrog cardiac cells, using the patch-clamp technique. Tetrandrine slightly increased ICaL from negative holding potentials (-100 mV) at low concentrations (10 nM-1 microM) and inhibited it at higher concentrations. At depolarized holding potentials (-50 mV) only an enhanced inhibition was seen. Tetrandrine blockade of the L-type Ca(2+)-current (ICaL) was mostly tonic. This is similar to ICaL blockade by nifedipine but not by verapamil, the latter being mostly use-dependent. Use-dependent effects of tetrandrine and nifedipine were evident at high rates. Availability curves were shifted leftwards (10-12 mV) by tetrandrine (10 microM) and nifedipine (1 microM). The T-type Ca(2+)-current (ICaT), although less sensitive, was decreased by both agents in a voltage-independent way. Tetrandrine (10-30 microM) but not nifedipine (1-10 microM), depressed the Na(+)-current (INa) in tonic, use- and voltage-dependent manners. We conclude that tetrandrine and nifedipine share some common actions on cardiac Ca(2+)-channels, while showing differences in their actions on Na(+)-channels. The depression of INa by tetrandrine suggests it could be effective on supraventricular tachycardias.
Alkaloids↗