Increasing Recovery Time Research Articles

Increasing Recovery Time Between Injuries Improves Cognitive Outcome After Repetitive Mild Concussive Brain Injuries in Mice

Although previous evidence suggests that the cognitive effects of concussions are cumulative, the effect of time interval between repeat concussions is largely unknown. To determine the effect of time interval between repeat concussions on the cognitive function of mice. We used a weight-drop model of concussion to subject anesthetized mice to 1, 3, 5, or 10 concussions, each a day apart. Additional mice were subjected to 5 concussions at varying time intervals: daily, weekly, and monthly. Morris water maze performance was measured 24 hours, 1 month, and 1 year after final injury. After 1 concussion, injured and sham-injured mice performed similarly in the Morris water maze. As the number of concussions increased, injured mice performed worse than sham-injured mice. Mice sustaining 5 concussions either 1 day or 1 week apart performed worse than sham-injured mice. When 5 concussions were delivered at 1-month time intervals, no difference in Morris water maze performance was observed between injured and sham-injured mice. After a 1-month recovery period, mice that sustained 5 concussions at daily and weekly time intervals continued to perform worse than sham-injured mice. One year after the final injury, mice sustaining 5 concussions at a daily time interval still performed worse than sham-injured mice. When delivered within a period of vulnerability, the cognitive effects of multiple concussions are cumulative, persistent, and may be permanent. Increasing the time interval between concussions attenuates the effects on cognition. When multiple concussions are sustained by mice daily, the effects on cognition are long term.

Effect of sevoflurane versus propofol-based anesthesia on the hemodynamic response and recovery characteristics in patients undergoing microlaryngeal surgery

Background:This randomized study was conducted to compare the hemodynamic changes and emergence characteristics of sevoflurane versus propofol anesthesia for microlaryngeal surgery.Methods:Forty adult patients undergoing microlaryngoscopy were randomly allocated into two groups. In propofol group, anesthesia was induced with 2-3 mg/kg propofol and maintained with propofol infusion 50-200 μg/kg/h. In sevoflurane group induction was carried out with 5-8% sevoflurane and maintained with sevoflurane in nitrous oxide and oxygen. The propofol and sevoflurane concentrations were adjusted to maintain the bispectral index of 40-60. All patients received fentanyl 2 μg/kg before induction and succinylcholine 2 mg/kg to facilitate tracheal intubation. The hemodynamic changes during induction and suspension laryngoscopy were compared. In addition, the emergence time, time to extubation, and recovery were assessed.Results:The changes in heart rate were comparable. The mean arterial pressure was significantly lower after induction and higher at insertion of operating laryngoscope in propofol group as compared to sevoflurane group. More patients in propofol group had episodes of hypotension and hypertension than sevoflurane group. The emergence time, extubation times, and recovery time were similar in both groups.Conclusion:We found that sevoflurane showed advantage over propofol in respect of intraoperative cardiovascular stability without increasing recovery time.

Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose–response relationship

BackgroundSugammadex shows a dose–response relationship for reversal of neuromuscular block (NMB) during propofol anaesthesia. Sevoflurane, unlike propofol, can prolong the effect of neuromuscular blocking agents (NMBAs), increasing recovery time. This open-label, randomized, dose-finding trial explored sugammadex dose–response relationships, safety, and pharmacokinetics when administered for reversal of moderate rocuronium- or vecuronium-induced NMB during sevoflurane maintenance anaesthesia. MethodsAfter anaesthesia induction with propofol, adult patients were randomized to receive single-dose rocuronium 0.9 mg kg−1 or vecuronium 0.1 mg kg−1, with maintenance doses as needed. Anaesthesia was maintained with sevoflurane. NMB was monitored using acceleromyography. After the last dose of NMBA, at reappearance of T2, single-dose sugammadex 0.5, 1.0, 2.0, or 4.0 mg kg−1 or placebo was administered. The primary efficacy variable was time from the start of sugammadex administration to recovery of T4/T1 ratio to 0.9. Safety assessments were performed throughout. ResultsThe per-protocol population comprised 93 patients (rocuronium, n=46; vecuronium, n=47). A statistically significant dose–response relationship was demonstrated for mean recovery times of T4/T1 ratio to 0.9 with increasing sugammadex dose with both NMBAs: rocuronium, 96.3 min (placebo) to 1.5 min (sugammadex 4.0 mg kg−1); vecuronium, 79.0 min (placebo) to 3.0 min (sugammadex 4.0 mg kg−1). Plasma sugammadex concentrations indicated linear pharmacokinetics, independent of NMBA administered. No study drug-related serious adverse events occurred. Evidence of reoccurrence of block was reported in seven patients [sugammadex 0.5 mg kg−1 (suboptimal dose), n=6; 2.0 mg kg−1, n=1]. ConclusionsDuring sevoflurane maintenance anaesthesia, sugammadex provides well-tolerated, effective, dose-dependent reversal of moderate rocuronium- and vecuronium-induced NMB.

Effect of synaptic plasticity on sensory coding and steady-state filtering properties in the electric sense

Our modeling study examines short-term plasticity at the synapse between afferents from electroreceptors and pyramidal cells in the electrosensory lateral lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus. It focusses on steady-state filtering and coherence-based coding properties. While developed for electroreception, our study exposes general functional features for different mixtures of depression and facilitation. Our computational model, constrained by the available in vivo and in vitro data, consists of a synapse onto a deterministic leaky integrate-and-fire (LIF) neuron. The synapse is either depressing ( D), facilitating ( F) or both ( FD), and is driven by a sinusoidally or randomly modulated Poisson process. Due to nonlinearity, numerically computed input–output transfer functions are used to determine the filtering properties. The gain of the response at each sinusoidally modulated frequency is computed by dividing the fitted amplitudes of the input and output cycle histograms of the LIF models. While filtering is always low-pass for F alone, D alone exhibits a gain resonance (non-monotonicity) at a frequency that decreases with increasing recovery time constant of synaptic depression ( τ d ). This resonance is mitigated by the presence of F. For D, F and FD, coherence improves as the synaptic conductance time constant ( τ g ) increases, yet the mutual information per spike decreases. The information per spike for D and F follows opposite trends as their respective time constants increase. The broadband but non-monotonic gain and coherence functions seen in vivo suggest that D and perhaps FD dynamics are involved at this synapse. Our results further predict that the likely synaptic configuration is a slower τ g , e.g. via a mixture of AMPA and NMDA synapses, and a relatively smaller synaptic facilitation time constant ( τ f ) and larger τ d (with τ f smaller than τ d and τ g ). These results are compatible with known physiology.

Responses of Daphnia magna to pulsed exposures of arsenic

Research on the toxicity of arsenic has focused on sublethal effects that do not provide sufficient information for risk estimation. While most studies have focused on organism response to constant arsenic exposures, organisms in nature are exposed to fluctuating As concentrations. Consequently, results obtained from standardized bioassays with constant exposures may not adequately characterize risk to indigenous biota. This research was designed to characterize the response of Daphnia magna to fluctuating arsenic exposures during 21-day experiments. At concentrations > or =3000 microg/L As, 21-day pulsed exposure mortality increased as a function of exposure concentration and duration. In addition, 21-day pulsed exposure mortality increased with increasing recovery time. Pulsed As exposure did not affect the growth of D. magna over 21 days. Twenty-one day accumulative reproduction of D. magna was only affected by pulsed exposures of high As concentration and long durations.

Hardening capacity in the Drosophila melanogaster species group is constrained by basal thermotolerance

Summary To determine the relationship between basal thermotolerance and hardening capacity across related taxa, these traits were quantified for eight Drosophila species: D. melanogaster, D. simulans, D. sechellia and D. yakuba of the melanogaster subgroup and D. auraria, D. vulcana, D. serrata and D. birchii of the montium subgroup. The effects of pretreatment temperature and recovery time between pretreatment and heat shock on thermotolerance were also assessed. For any given species, all elevated temperature pretreatments (31 °C, 33 °C and 35 °C) equally increased thermotolerance. For any given species, increasing recovery time between pretreatment and heat shock increased thermotolerance, though this effect may be related to factors other than hardening. Basal thermotolerance and absolute hardening capacity (pretreated thermotolerance minus basal thermotolerance) varied considerably among the species, and was not phylogenetically clustered. Though unmodified and phylogenetically corrected correlations indicated a relationship between basal thermotolerance and absolute hardening capacity, this result was largely due to the presence of one species, the highly thermotolerant D. melanogaster. Relative hardening capacity (absolute hardening capacity divided by basal thermotolerance) was fixed for all species at approximately 0·25.

Nanoscale Hydrophobic Recovery: A Chemical Force Microscopy Study of UV/Ozone-Treated Cross-Linked Poly(dimethylsiloxane)

Chemical force microscopy (CFM) in water was used to map the surface hydrophobicity of UV/ozone-treated poly(dimethylsiloxane) (PDMS; Sylgard 184) as a function of the storage/recovery time. In addition to CFM pull-off force mapping, we applied indentation mapping to probe the changes in the normalized modulus. These experiments were complemented by results on surface properties assessed on the micrometer scale by X-ray photoelectron spectroscopy and water contact-angle measurements. Exposure times of < or = 30 min resulted in laterally homogeneously oxidized surfaces, which are characterized by an increased modulus and a high segmental mobility of PDMS. As detected on a sub-50-nm level, the subsequent "hydrophobic recovery" was characterized by a gradual increase in the pull-off forces and a decrease in the normalized modulus, approaching the values of unexposed PDMS after 8-50 days. Lateral imaging on briefly exposed PDMS showed the appearance of liquid PDMS in the form of droplets with an increasing recovery time. Longer exposure times (60 min) led to the formation of a hydrophilic silica-like surface layer. Under these conditions, a gradual surface reconstruction within the silica-like layer occurred with time after exposure, where a hydrophilic SiOx-enriched phase formed < 100-nm-sized domains, surrounded by a more hydrophobic matrix with lower normalized modulus. These results provide new insights into the lateral homogeneity of oxidized PDMS with a resolution in the sub-50-nm range.

The felid purr: A healing mechanism?

A current hypothesis suggests the purr indicates contentment, however, cats purr when they are severely injured or frightened. Forty-four felids were recorded including cheetahs, ocelots, pumas, domestic cats, and servals. A Sony TCD-D8 Digital Audio Recorder (DAT) and Statham Radio microphones recorded the purrs. FFTs and spectrographs were performed using National Instrument’s Polynesia. An accelerometer was also used to measure domestic cat purrs. Every felid in the study generated strong frequencies between 25 and 150 Hz. Purr frequencies correspond to vibrational/electrical frequencies used in treatment for bone growth/fractures, pain, edema, muscle growth/strain, joint flexibility, dyspnea, and wounds. Domestic cats, servals, ocelots, and pumas produce fundamental, dominant, or strong frequencies at exactly 25 Hz and 50 Hz, the two low frequencies that best promote bone growth/fracture healing [Chen et al., Zhong. Wai Ke Za Zhi. 32, 217–219 (1994)]. These four species have a strong harmonic exactly at, or within 2 Hz of 100 Hz, a frequency used therapeutically for pain, edema, wounds, and dyspnea. An internal healing mechanism would be advantageous, increasing recovery time and keeping muscles and bone strong when sedentary. [Published with permission from the New Zealand Veterinary Journal; work supported by Endevco.]

Routine droperidol pre-medication improves sedation for ERCP

Background: Pre-medication with droperidol has been used to improve sedation during endoscopy, especially in patients with a history of alcohol or narcotic abuse. We studied whether routine use of droperidol pre-endoscopic retrograde cholangiopancreatography (ERCP) could improve patient and physician satisfaction with sedation. Methods: Sixty-seven patients undergoing routine ERCP were enrolled in this double-blind placebo-controlled study. Patients were given either parenteral normal saline solution or 5 mg of droperidol 15 minutes before the procedure. After the ERCP, several parameters of procedural sedation were scored on an ordinal scale by the endoscopist, the endoscopy nurse, and the recovered patient. In addition, a follow-up telephone call was made to the patient after 24 hours. Results: The mean procedural room time was similar in the two groups. Nearly 25% less meperidine and diazepam was used in the droperidol-treated patients, making the overall medication cost similar in both groups. The mean recovery room time was 113 minutes for the placebo group and 106 minutes for the droperidol group. Droperidol premedication significantly decreased post-procedure nausea and vomiting, reduced gagging at intubation, and decreased retching during the procedure. Droperidol also improved physician (p = 0.001), nurse (p = 0.001), and patient (p = 0.0001) impressions of overall sedation and decreased the need for physical restraint during the procedure. Droperidol significantly increased the number of patients with no memory of the procedure. Conclusion: Droperidol improved overall patient, physician, and nurse satisfaction with sedation during ERCP. It also reduced post-ERCP nausea and vomiting without increasing recovery time or medication cost. Droperidol is recommended for routine pre-ERCP sedation. (Gastrointest Endosc 2000;52:362–6).

Heat shock and 5-azacytidine inhibit nitric oxide synthesis and tumor necrosis factor-alpha secretion in activated macrophages.

To elucidate the role of stress response during macrophage activation, the effects of heat shock and the amino acid analog, 5-azacytidine on nitric oxide (NO) production, tumor necrosis factor-alpha (TNF-alpha) secretion, and heat shock protein (HSP) synthesis have been studied in murine peritoneal macrophages (C57BL/6). Heat shock (1 hr at 43 degrees C) or 5-azacytidine markedly inhibited the release of NO into the medium from interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS)-stimulated macrophages. Although heat shock significantly decreased TNF-alpha secretion only at the initiation stage of macrophage stimulation, 5-azacytidine treatment resulted in a more prolonged reduction in the secretion of TNF-alpha. When heat-shocked cells were stimulated with IFN-gamma plus LPS under normal culture conditions at 37 degrees C, the heat shock-induced inhibition of NO release reversed progressively with increasing recovery time. Although the total amount of cellular HSP72 measured by Western blot increased time-dependently over 7 hr, newly synthesized HSP72 measured by [35S]methionine incorporation was evident only after 1 and 3 hr of recovery time after heat shock treatment. At these time points, the lowest nitrite accumulation and TNF-alpha secretion into the medium was evident. It is concluded that signaling pathways related to newly synthesized HSP such as HSP72 are implicated in the down regulation of NO synthesis and TNF-alpha secretion in macrophages.

Arc restrikes yielding back-commutations in the contact gap of low voltage interrupters

Arc commutation from the arc chute back into the contact gap of a low voltage circuit-breaker caused by a high arc voltage pulse due to arc splitting was investigated in a model interrupter with the aid of a synthetic test method. In the experiment a well defined time after the arc left the contacts a high voltage ramp was applied across the contact gap. The criterion considered was the breakdown value of the voltage. Recovery time (in the range of 500 μs to 2 ms), geometry and materials of contacts (Cu, Ag/C, Ag/Ni, Ag/MeO) and walls (nongassing and gassing) were varied. Increasing recovery time increased the breakdown voltage significantly due to the decrease of the temperature in the contact area. The minimum breakdown value corresponded to the instantaneous reignition voltage. An increase of the wall distance caused an insignificant increase of the breakdown voltage due to the decrease of field distortion. Gassing wall materials caused slightly higher breakdown voltages than nongassing walls. Increasing contact gap from 2 mm to 4 mm increased the breakdown voltage. No influence was observed at lower (1.5 mm) and at higher contact gaps up to 7 mm. The influence of the contact material was generally little; Cu contacts yielded insubstantially lower breakdown voltages than the other contact materials investigated.

Anatomical regeneration and behavioral recovery following crush injury of the trigeminal root in lamprey

In normal larval lamprey, bilateral application of horseradish peroxidase (HRP) to the dorsal part of the anterior oral hood labeled subpopulations of trigeminal components on both sides of the brain; peripherally projecting motoneurons, medullary dorsal cells (sensory), and spinal dorsal cells (sensory), as well as centrally projecting afferents in the trigeminal descending tracts. Following unilateral crush injury of the right trigeminal root, HRP labeling of sensory and motor trigeminal components on the right side gradually increased with increasing recovery time, between 2 weeks and 12 weeks postcrush (PC). Axons of trigeminal motoneurons appeared to exhibit robust regeneration, whereas restoration of projections in the descending trigeminal tract ipsilateral to the injury was incomplete. Control experiments indicated that motor and sensory axons from the intact side of the oral hood did not sprout across the midline to the denervated side. Several results suggested that regenerated trigeminal sensory fibers made synapses with brain neurons that have direct or indirect inputs to reticulospinal (RS) neurons. Following a unilateral crush injury of the right trigeminal root, escape behavior in response to stimulation of the right side of the oral hood gradually returned to normal. Muscle recordings at various recovery times confirmed that anatomical regeneration of trigeminal sensory axons was functional. In addition, at 8 or 12 weeks PC, brief stimulation of the oral hood ipsilateral or contralateral to the crush injury elicited synaptic responses in RS neurons on either side of the brain, similar to that in normal animals. In the lamprey, compensatory mechanisms probably allow recovery of behavioral function despite incomplete regeneration of trigeminal sensory axons within the central nervous system.

Alterations in the biorheological features of some soft tissues after limb lengthening

The aim of this study was to investigate the effects of a surgical limb lengthening procedure on the biorheological features of some lengthened soft tissues. In this procedure external fixators were applied to goats' right radius to stretch the tissues. The right forelegs of goats were lengthened by 2, 4 cm, respectively. After lengthening ceased, the goats were examined after different periods of time. The lengthened median nerves, arteries and veins were harvested and used to study their biorheological features. Tensile strength of lengthened and control specimens were measured and their stress relaxation features and stress-strain relationships were studied. Results showed that at the beginning of recovery, the stress-strain curves, relaxation curves and tensile strengths of the lengthened specimens began to deviate from those of their controls. However, with increasing recovery time, the curves and tensile strength of the lengthened specimens reverted to those of their controls. All the tissues studied exhibited the same behavior.

An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells.

Tumor cells exposed to a growth stress such as low pH, glucose starvation and hypoxia have been shown to exhibit a transient increase in experimental metastatic potential, particularly when allowed to recover under normal growth conditions for a period of 24-48 h. In this study we examined whether this increase in metastatic ability could be explained by changes in the expression of a number of different metastasis-associated genes, when the cells were exposed to similar conditions (24-48 h exposure to the stress condition followed by 0-48 h recovery under normal growth conditions). Although the cell lines used (KHT fibrosarcoma, SCC VII squamous cell carcinoma, and B16F1 melanoma) demonstrated altered metastatic ability after the treatment, no overall temporal correlation between changes in the mRNA levels for cathepsin B, cathepsin L, nm23, TIMP-1, osteopontin, or VEGF and metastatic ability in the three cell lines was observed. The production of gelatinase A (72 kDa collagenase) and gelatinase B (92 kDa collagenase) was also measured by gelatin zymography. There was an increase in production of these enzymes with increasing recovery time, but it did not parallel changes in metastatic potential. Although these results suggest that the products of most of the genes studied may not be involved in the transient metastatic changes, further studies are required to establish whether changes in protein levels track with changes in mRNA levels for these genes.

Anthropogenic Disturbance of Caribbean Mangrove Ecosystems: Past Impacts, Present Trends, and Future Predictions

We review historical, current, and projected future impacts of four classes of anthropogenic disturbance-extraction, pollution, reclamation, and changing climate-on Caribbean mangrove ecosystems (mangal). These disturbances occur, respectively, at increasing spatial and temporal scales, and require increasing recovery time. Small-scale selective extraction has little system-wide effect, but regeneration is slow even on single hectare clear-cuts due to rapid soil acidification. Petroleum is the primary pollutant of Caribbean mangal, and results in tree defoliation, stand death, and loss of associated sessile and mobile animal species. Hydrocarbons persist in mangrove sediments for decades, and are correlated with increasing seedling mutation rates. Chemical, industrial, and urban wastes are associated with increased heavy metal content of seedlings, stand die-back, reduced system-wide species richness, and higher incidence of Vibrio spp. (shellfish poisoning). Mangal has been reclaimed for urbanization, industrialization, and increasingly, for tourism. Overall, the region is losing mangrove forests at 1 percent per yr, although the rate is much faster on the Caribbean mainland (- 1.7% yr-1) than it is on the islands (=0.2% yr-1). The region's fisheries are declining at a similar rate, as most commercial shellfish and finfish use mangal for nurseries and/or refugia. Few Caribbean states have legislation or enforcement capabilities to protect or manage mangal, although at least 11 international treaties and conventions could be applied to conserve or sustainably use these forests. These treaties may protect riverine and basin mangal, but are likely to be moot with respect to fringing mangal, which may vanish as a consequence of global climate change. Growth enhancements of mangroves resulting from increasing atmospheric CO2 probably will not compensate for negative effects of concomitant rises in regional sea level.

Effect of preconditioning on the viscoelastic response of primate patellar tendon

Current techniques for anterior cruciate ligament reconstruction with patellar tendon (PT) allow a measurable tension to be applied to the graft at the time of fixation. The viscoelastic nature of the PT, however, ensures that relaxation will cause the graft tension to decrease over time. To better understand this process, a primate model was used to evaluate acute viscoelastic relaxation in the PT. Thirty-five patella-patellar tendon-tibia (P-PT-T) complexes were harvested from normal primate knees (Cynomolgus monkeys), and were divided into five groups for mechanical comparison. Specimens were subjected to two 10-min relaxation tests separated by a 1-30-min unloaded interval. The first test provided baseline relaxation data as well as serving as preconditioning for the second test. Results indicate that preconditioning significantly reduces the tension lost in a graft due to viscoelastic relaxation. The effect of preconditioning is reduced with increasing recovery time (the time between preconditioning and the second relaxation test), but the effect is still significant after 30 min of unloading. No differences were observed in the relaxation behavior of specimens that were cyclicly or isometrically preconditioned, nor were differences observed between irradiated and nonirradiated specimens. These results suggest that preconditioning can reduce acute tension loss in a graft due to viscoelastic relaxation and that simple isometric preconditioning is just as effective as cyclic stretching.

Intravenous droperidol decreases nausea and vomiting after alfentanil anesthesia without increasing recovery time

The frequency rate of nausea and vomiting after an alfentanil-based anesthetic is high, with reported frequencies of 38% to 68%. This study was undertaken to evaluate the efficacy of low-dose and moderate-dose droperidol in decreasing the frequency of postoperative nausea and vomiting and to evaluate whether droperidol has any effect on .slowing recovery after a standard alfentanil-based anesthetic. Sixty normal adults who were scheduled to undergo short .surgical procedures requiring general anesthesia were assigned randomly in a double-blind manner to one of three groups of 20: (1) control—normal saline; (2) droperidol 10 μg/kg; or (3) droperidol 20 μg/kg. A standard alfentanil-based anesthetic was used, and the study drug was given immediately after induction of anesthesia. In the postanesthesia recovery room, all patients were evaluated according to the Aldrete score, noting the time to achieve a score of 10. Presence or absence and severity of nausea and vomiting were noted. To assess psychomotor recovery, a Trieger dot test was performed by every patient preoperatively, at the time of an Aldrete score of 10, and upon discharge from the recovery room. There was no statistical difference between the groups in age, sex, type of procedure, weight, total dose of alfentanil, or duration of anesthetic. The frequency of nausea and vomiting was significantly less ( p < 0.05) for the 20 μg/kg group (5%) than for the 10 μg/kg group (25%) or the control group (40%). A dose-response relationship zvas evident for the antiemetic effect of droperidol. An analog scale for severity of nausea and vomiting also demonstrated a dose response effect. The time to an Aldrete score o f 10 and the time to discharge from the recovery room were not statistically different between the groups. Trieger dot scores, used to evaluate recovery of psychomotor skills, did not demonstrate a statistical difference between the groups. The conclusions are that droperidol given during alfentanil-based anesthesia does prevent nausea and vomiting in a dose-dependent manner and has no apparent effect on recovery from anesthesia.

Effects of caffeine on calcium release from the sarcoplasmic reticulum in frog skeletal muscle fibres.

1. Resting myoplasmic [Ca2+] and [Ca2+] transients (delta [Ca2+]) were monitored using Fura-2 fluorescence and Antipyrylazo III absorbance signals from voltage-clamped segments of cut frog skeletal muscle fibres in the presence and absence of 0.5 mM-caffeine. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from delta [Ca2+]. 2. delta [Ca2+] and Rrel were increased in caffeine for all pulses. The decline of delta [Ca2+] was slower after a given pulse in caffeine than without caffeine. Resting [Ca2+] was slightly elevated in caffeine. 3. The voltage dependence of the peak value of Rrel and of the steady level of Rrel at the end of a 60-120 ms pulse were both shifted towards more negative voltages in caffeine. For relatively small pulses the voltage at which a given release waveform was observed was also shifted to more negative voltages. 4. Intramembrane charge movements measured in the same fibres in which the above changes in Rrel were observed showed no significant changes in caffeine. 5. In caffeine calcium release continued for many milliseconds after the end of a short (10 ms) pulse. Continued release after a pulse was not observed without caffeine and was probably due to positive feedback of elevated [Ca2+] on calcium release resulting from calcium-induced calcium release in caffeine. 6. Intramembrane charge movements after short pulses showed no change in caffeine that could account for the continued calcium release after the pulse. 7. Continued release after short pulses in caffeine decreased as the pulse duration was increased and was absent for pulses of 60 ms or longer. Rrel also inactivated during such pulses. 8. Relatively large and long conditioning pulses in caffeine suppressed both the peak Rrel and the continued release after short pulses. Peak release and continued release after short pulses recovered in parallel with increasing recovery time following suppression by a conditioning pulse in caffeine. 9. These results indicate that in the presence of caffeine, charge movement and calcium-induced calcium release both contribute significantly to the activation of sarcoplasmic reticulum calcium release during fibre depolarization. Release activated by either mechanism appears to be inactivated by calcium-dependent inactivation. A significant contribution of calcium-induced calcium release during depolarization in the absence of caffeine is not ruled out by present observations.

Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast.

We have examined alterations in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using 31P nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to 60Co gamma-radiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol dm-3 glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol dm-3 2-deoxyglucose (2-DG), LHR was completely inhibited. NMR analyses were done on cells perfused in agarose threads and maintained under conditions similar to those in the survival studies. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. These observations suggest that either the production of ATP in irradiated cells is suppressed or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol dm-3 glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (Pi). In the absence of an external energy source, such as glucose, there was a slight increase in Pi. This suggests that polyP may be used as an alternative energy supply. When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in Pi with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage.

A Pharmacokinetic Explanation for Increasing Recovery Time Following Larger or Repeated Doses of Nondepolarizing Muscle Relaxants

The authors used pharmacokinetic and pharmacodynamic modeling to explain the time course of neuromuscular blockade following single or multiple doses of three nondepolarizing muscle relaxants. Published and unpublished pharmacokinetic and pharmacodynamic data for 13 normal subjects were used to simulate the duration of neuromuscular blockade (time from administration of the muscle relaxant to 25% recovery of control twitch tension) following six successive doses of atracurium (150-400 micrograms/kg initially, followed by 100 micrograms/kg), vecuronium, or pancuronium (30-80 micrograms/kg initially, followed by 20 micrograms/kg). With atracurium, duration of action was similar for the second and sixth doses, regardless of the initial dose. With vecuronium (initial doses of 30-80 micrograms/kg) and pancuronium (initial doses of 30-60 micrograms/kg), duration of action was longer after the sixth dose than after the second; with larger initial doses of pancuronium (70 and 80 micrograms/kg), duration of action was similar following the second and sixth doses. The authors also determined two recovery times (time for twitch tension to recover from 5-25% and from 25-75% of control value) for varying single doses of atracurium, vecuronium, or pancuronium. When the dose of atracurium was increased from 200 to 400 micrograms/kg, neither recovery time increased. When the dose of vecuronium was increased from 40 to 80 micrograms/kg, 5-25% recovery time increased from 6.0 +/- 2.5 min to 8.8 +/- 4.0 min (mean +/- SD) and 25-75% recovery time increased from 8.7 +/- 4.3 min to 12.6 +/- 4.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)