Search PubMed⌕ Search

Biomedical subjects

J R Lopez

Publications and source records attributed to J R Lopez.

15 recordsLinked to original sources
PubMed1992

Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia.

Malignant hyperthermia (MH) is a genetic disease characterized by hypermetabolism in skeletal muscle following a triggering stimulus and can be reversed or pretreated with dantrolene sodium. The myoplasmic free [Ca2+] was measured, using Ca2+ selective microelectrodes in vivo in the superficial fibers of the sartorius muscle of eight MH-susceptible and eight control subjects. Both groups received continuous epidural anesthesia with chloroprocaine 3%. In both the control and MH muscle fibers, the myoplasmic free [Ca2+] was measured before and after the intravenous administration of a cumulative dantrolene dose of 0.5, 1.5, and 2.5 mg/kg. The mean resting myoplasmic free [Ca2+] was 0.112 +/- 0.004 microM (mean +/- SEM n = 32) in the control and 0.485 +/- 0.022 microM (n = 33) in the MH subjects. In the MH subjects, dantrolene induced a dose-dependent reduction in myoplasmic free [Ca2+]. The 0.5-mg/kg dose reduced it to 0.326 +/- 0.017 microM (n = 22), the 1.5-mg/kg dose to 0.233 +/- 0.015 microM (n = 25), and the 2.5-mg/kg dose to 0.092 +/- 0.008 microM (n = 26). In controls, dantrolene also reduced resting myoplasmic free [Ca2+] but to a lesser extent. The 0.5-mg/kg dose reduced it to 0.096 +/- 0.004 microM (n = 22), the 1.5-mg/kg dose to 0.077 +/- 0.003 microM (n = 23), and the 2.5-mg/kg dose to 0.068 +/- 0.002 microM (n = 27). The results of the study extend our previous findings in humans and swine and demonstrate that it is possible to measure myoplasmic free [Ca2+] in vivo in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1992

Transdermal fentanyl.

OBJECTIVE: To review the use of transdermal fentanyl for the treatment of moderate to severe chronic pain. The article provides background on the pharmacology and pharmacokinetics of the drug, as well as the properties of the transdermal system. In addition, clinical trials, adverse effects, and therapeutic considerations and recommendations are presented. DATA SOURCES: Clinical trials, review articles, and reference texts. STUDY SELECTION: Comparative clinical trials involving the use of transdermal fentanyl on postoperative and chronic pain patients. DATA EXTRACTION: Data from clinical human trials published in the English language were reviewed. Trials were assessed by sample size, opioid dosage regimen, and therapeutic outcome. DATA SYNTHESIS: Transdermal fentanyl was found to be effective in the control of chronic and postoperative pain. In one trial the overall patient satisfaction with pain control was 79 percent for the transdermal fentanyl group and 44 percent for the placebo group. In another trial, the amount of additional parenteral morphine was significantly lower for the group receiving transdermal fentanyl than for the placebo group (49.9 +/- 4.9 vs. 77.0 +/- 6.3 mg, respectively, p < 0.01). The most common adverse effects recorded were nausea (45-85 percent), pruritus (14-60 percent), and sedation (40-59 percent). The cost of analgesic therapy with this delivery system is higher than that of parenteral opioid analgesia, but less than patient-controlled analgesia. CONCLUSIONS: The transdermal fentanyl formulation offers some minor advantages over other forms of conventional pain management. Results of early clinical trials are promising, but more studies are needed to evaluate its long-term effectiveness and adverse effects. Specifically, comparisons with standard parenteral and patient-controlled opioid analgesia in chronic malignant and nonmalignant pain are necessary for adequate evaluation of transdermal fentanyl.

Administration, Cutaneous↗
PubMed1991

Inositol 1,4,5-trisphosphate increases myoplasmic [Ca2+] in isolated muscle fibers. Depolarization enhances its effects.

Inositol 1,4,5-trisphosphate (InsP3) has been proposed as an intracellular messenger which mobilizes calcium from the sarcoplasmic reticulum, during excitation-contraction coupling in skeletal muscle. We have measured the myoplasmic free calcium concentration ([Ca2+]i) by means of calcium selective microelectrodes in intact fibers isolated from Leptodactylus insularis microinjected with InsP3. In muscle fibers bathed in normal Ringer, the mean resting [Ca2+]i was 0.11 +/- 0.01 microM (M +/- SEM, n = 30). The microinjection of 0.3, 0.5 and 1 microM InsP3 induced transient increments in the [Ca2+]i to 0.35 +/- 0.02 microM (n = 9), to 0.53 +/- 0.03 microM (n = 11) and 0.94 +/- 0.06 microM (n = 10) respectively. Microinjection of 0.3, 0.5 and 1 microM InsP3 in muscle fibers incubated in low Ca2+ solution induced increments in [Ca2+]i similar to those observed in fibers bathed with normal Ringer. The microinjection of 0.3, 0.5 and 1 microM InsP3 in muscle fibers partially depolarized with 10 mM [K+]o induced transient enhancements of the resting [Ca2+]i that were greater than the transients observed in the normally polarized muscle. In partially depolarized fibers microinjected with 0.3, 0.5 and 1 microM InsP3, the [Ca2+]i was changed to 1.45 +/- 0.14 microM (n = 20), to 3.37 +/- 0.34 microM (n = 7) and to 7.43 +/- 0.70 microM (n = 6) respectively. In all partially depolarized fibers these increments in [Ca2+]i were associated with local contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine.

It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium [( Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]i and [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]i and [Mg2+]i were determined by means of ion-selective microelectrodes. The resting [Ca2+]i in normal muscle fibers was 0.11 +/- 0.01 microM (mean +/- SEM), whereas in the MH muscles the resting [Ca2+]i was 0.36 +/- 0.01 microM. In neither group was the resting [Ca2+]i modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]i associated with the syndrome from 7.29 +/- 0.43 microM in untreated animals to 0.84 +/- 0.03 microM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+]i were not different in control and MH-susceptible muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of calcium "antagonists" on vertebrate skeletal muscle cells.

Clinically potent skeletal muscle relaxants are used primarily for their effects on the central nervous system. But they also have direct effects on muscle contraction that possibly involve Ca2+ channels. We compared the effects of dantrolene, an agent known to have a direct action on vertebrate skeletal muscle, with other substances used as (1) relaxants and (2) antagonists of Ca-dependent excitation-contraction coupling. Isolated intact frog muscle cells were injected with the photoprotein aequorin, and membrane potential changes, intracellular Ca2+ transients, and contractile force were measured. Dantrolene (10(-8) to 10(-5) M) decreased the amplitude of Ca2+ transients, did not affect their rates of decay, and reduced contractile force. We also used an integrated digital-imaging system to record microscopic changes, namely, active shortening in myofibrils and changes in striation spacing. Dantrolene did not increase the time between contraction in myofibrils near the surface compared with myofibrils near the center of a cell. Hence dantrolene does not suppress Ca2+ transients by disturbing current flow in the transverse tubular system. Each of the following actually increased Ca2+ transients and contractile force evoked by action potentials: baclofen (10(-7) to 10(-5) M) less than flordipine (10(-6) M) less than meprobamate (10(-7) to 10(-3) M) less than chlordiazepoxide (10(-5) X 10(-4) M) less than procaine (10(-5) to 5 X 10(-4] less than GABA (10(-5) M) less than D-600 (10(-6) M) less than nylidrin (10(-5) M)--in order of increasing potency. Ca2+ channels in the sarcoplasmic reticulum of intact skeletal muscle are evidently inhibited by dantrolene but not by Ca2+ antagonists.

Animals↗
PubMed1988

Laboratory oviposition, fecundity and egg hatching ability of colonized Anopheles albimanus from southwestern Mexico.

Fecundity, oviposition patterns and egg hatching characteristics were studied in two colonies of Anopheles albimanus isolated from the Pacific coast of southern Mexico. Fecundity was inversely proportional to the cage space available to the female and was influenced by the bloodmeal source, feeding method and previous feeding history. The length of the gonotrophic cycle decreased with succeeding experience from a mean 6.6 in the first to 2.6 days for the fifth cycle. Oviposition timing was also dependent on availability of oviposition substrate. Hatching success of eggs increased significantly when the oviposition site was witheld until 48 hr post-bloodmeal.

Animals↗
PubMed1987

Dantrolene prevents the malignant hyperthermic syndrome by reducing free intracellular calcium concentration in skeletal muscle of susceptible swine.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered when susceptible subjects are exposed to volatile anesthetic agents and/or depolarizing muscle relaxants. We have used Ca2+ selective microelectrodes to measure in vivo the intracellular free [Ca2+] in skeletal muscle of MH susceptible swine before and after the administration of dantrolene. We have investigated the effectiveness of this muscle relaxant in preventing clinical MH and the relationship between the resting intracellular free [Ca2+] and the probability of inducing the MH syndrome. The resting intracellular free [Ca2+] was 0.41 +/- 0.01 microM (M +/- SEM), which agrees with our previous measurements in susceptible swine. The administration of 0.5, 1, 2, 2.5 and 3 mg/Kg Dantrolene, reduced the intracellular free [Ca2+] to 0.31, 0.21, 0.09, 0.08, 0.08 microM respectively. The 0.5 mg/Kg dose induced a moderate decrease of [Ca2+]i and failed to prevent the MH syndrome after exposure to halothane (2%). The 1 mg/Kg dose produced a further reduction in [Ca2+]i and was sufficient to prevent the clinical syndrome in 2 out of 3 animals. The 2.5 mg/Kg dose was uniformly protective in all animals. These results suggest that the mechanism by which dantrolene protects susceptible animals exposed to triggering agents is by reducing the intracellular free [Ca2+] in skeletal muscle.

Anesthetics↗
PubMed1987

Changes in intracellular ionized Ca concentration associated with muscle fiber type transformation.

Since increased muscle activity, which results in fast-slow fiber transformation, is associated with increases in sarcoplasmic Ca2+ concentration ([Ca2+]i), it seemed of interest to study the level of [Ca2+] after cessation of stimulation in fibers of the extensor digitorum longus muscle chronically stimulated (8 Hz). [Ca2+]i was measured in individual fibers with a Ca2+-sensitive electrode after subtracting the membrane potential, measured simultaneously from the potential of the Ca2+ electrode. During the first 14 days of stimulation, [Ca2+]i increased from approximately 0.1 to 0.5 microM and declined in approximately 3 wk to a value slightly higher than the initial one. The rise and decline of [Ca2+]i was preceded by a transient increase in total calcium. If stimulation was terminated after 7-8 wk when an essentially complete fast-to-slow transformation had taken place, a subsequent rest period led to a reverse slow-to-fast transformation, which was also preceded by a transient increase of [Ca2+]i reaching a peak at day 5 of rest. Unstimulated fast and slow fibers and fully transformed fibers do not differ in their [Ca2+] levels; thus it appears that the transformation process itself is accompanied, particularly in its earlier stages, by elevated [Ca2+]i levels. Elucidation of the relation between changes in Ca2+ and changes in gene expression will require further work.

Adenosine Triphosphatases↗