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Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using Intralipid and Encapsin as perfusates.

This study was conducted to compare the ability of two potential microdialysis perfusates to enhance the recovery of SB-265123, a lipophilic, highly protein-bound compound, both in vitro and in vivo. Initial in vitro experiments established that the recovery of SB-265123 by microdialysis using normal saline as a perfusate was poor (1.7%). Different concentrations of Intralipid and Encapsin also were evaluated in an identical in vitro setting, to determine enhancement of recovery. In vitro recovery was enhanced to approximately 24 and 65% with 5 and 20% Intralipid, and to approximately 59 and 62% with 5 and 20% Encapsin, respectively. A rat in vivo study was conducted with 20% Encapsin to confirm the in vitro observations. In the in vivo study, 75-80% recovery of free SB-265123 was achieved using 20% Encapsin as a perfusate. The results from this study indicate that for SB-265123, a lipophilic, highly protein-bound molecule, Encapsin is an efficient recovery enhancer in vitro. The results from this investigation further demonstrate that a recovery enhancer may be useful for in vivo applications, even with a compound that is highly bound to plasma protein.

2-Hydroxypropyl-beta-cyclodextrin↗

Resting 12-lead electrocardiogram as a reliable predictor of functional recovery after recanalization of chronic total coronary occlusions.

BACKGROUND: A major goal of revascularization is the recovery of left ventricular (LV) function. Nuclear imaging techniques are widely used for detecting recovery of function with a good sensitivity, but only moderate specificity. Predictors of recovery in chronic total coronary occlusions (CTO) are not investigated. HYPOTHESIS: The 12-lead-resting electrocardiogram (ECG) is a predictor of LV recovery after successful recanalization of CTO. METHODS: Successful recanalization of CTO was performed in 127 patients. Of these, 62 patients, who constitute the study group, had impaired regional wall motion prior to recanalization. The 12-lead resting ECG was evaluated for Q-wave areas and parameters of QT dispersion. Impairment of regional wall motion was evaluated by LV angiogram at baseline and at follow-up. RESULTS: Angiographic follow-up after 5 +/- 1.4 months documented reocclusion in eight patients. Complete follow-up with a patent coronary artery and an ECG without bundle-branch block was available in 43 patients. Wall motion severity index (WMSI) improved from -2.92 +/- 0.28 to -1.34 +/- 0.61 (p < 0.001) in patients without Q waves, whereas it was unchanged in patients with Q waves (-3.01 +/- 0.30 and -2.81 +/- 0.32). Absence of Q waves at baseline predicted recovery of regional wall motion with 89% sensitivity and 67% specificity. Positive predictive value for recovery was 68% in patients without Q waves, but only 11% in patients with Q waves. In multivariate analysis, only absence of Q waves predicted improvement in WMSI (p = 0.01). CONCLUSIONS: In patients with recanalization of CTO, recovery of regional wall motion is reliably predicted by analysis of the resting 12-lead ECG for pathologic Q waves.

Coronary Angiography↗

Lactic acid inhibition of gap junctional intercellular communication in in vitro astrocytes as measured by fluorescence recovery after laser photobleaching.

Lactic acid can permeate plasma membranes, causing intracellular acidosis. Gap junctions are sensitive to pHi and can be reversibly uncoupled by weak acids. In this study, dye coupling between in vitro astrocytes, presumably mediated by gap junctions, was measured in the absence and presence of lactic acid. Fluorescence recovery after laser photobleaching (gap-FRAP analysis) was used to measure dye coupling. Astrocytes bathed in Eagle's minimum essential medium (EMEM) with lactic acid, pHo 5.5-6, showed no difference in their dye coupling (mean recovery of fluorescence 30%) when compared to control astrocytes (mean recovery of fluorescence 26%). However, 24 mM lactic acid in EMEM, pHo 4.5, decreased dye coupling (mean recovery of fluorescence 2.0%). This effect occurred within 5 min of treatment. When lactic acid-EMEM, pH 4.5, was removed from astrocytes after 30 min and the cells were incubated in EMEM for 24 hr, decreased coupling was not reversed (mean recovery 4.0%). When lactic acid-treated astrocytes were incubated in EMEM for 48 hr, the mean recovery of fluorescence increased to 15% (i.e., 42% of the recovery seen in controls). These observations suggest that brief exposure to high concentrations of lactic acid can have immediate and long-lasting effects on glial gap junctional communication. Under pathological circumstances, such a sequence could be initiated, and this might impair astrocytic control of the central nervous system microenvironment mediated by spatial buffering.

Animals↗

Functional regeneration and recovery of locomotor activity in spinally transected lamprey.

Spinally transected lamprey recovery locomotor function within 3-6 weeks, and recovery is due, in part, to functional regeneration of neural pathways in the central nervous system (CNS). Our data demonstrate for the first time in the lamprey that descending axons arising from brainstem command neurons can functionally regenerate and restore locomotor initiation below a healed spinal transection site. Immediately after behavioral recovery (3-6 weeks) the locomotor pattern was incomplete but returned to normal during the remainder of the recovery period (6-40 weeks). Initially, the extent of regeneration of descending axons was limited but increased to at least 30-50 mm at recovery times of 24-40 weeks. Regenerated giant Muller axons do not contribute significantly to recovery of locomotor function; rather, regenerated axons of smaller reticulospinal neurons appear to restore locomotor initiation. The restoration of locomotor coordination across a spinal lesion is dependent on two mechanisms: regeneration of spinal coordinating neurons and mechanosensory inputs. Comparisons are made to spinal cord regeneration in other lower vertebrates and to the relative lack of CNS regeneration and behavioral recovery in higher vertebrates.

Animals↗

MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment.

The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1-treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline-treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1-treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

Latent variable modelling of recovery trajectories: sexual function following radical prostatectomy.

As treatments improve and survival time lengthens, the course of recovery and long-term quality of life (QoL) is of greater interest. The application of latent class growth models to longitudinal QoL data provides unique insights into recovery that are not evident with marginal analyses. We examine this approach in the context of a large population-based observational study. This is the first attempt to characterize individuals' recovery over time following prostate cancer surgery, and to determine factors associated with varying recovery experiences of prostate cancer patients. Four major patterns emerged that illustrate typical patterns of recovery following radical prostatectomy. Given a man's baseline data, this method produces estimates of the probability of belonging to each recovery class. The method is presented as a useful tool for identifying hypotheses associated with recovery and potential antecedents of importance.

Erectile Dysfunction↗

Recovery of MC-LR in fish liver tissue.

Cyanotoxins, particularly microcystins (MCs), have been shown to be a hazard to human health. MCs accumulate in aquatic organisms probably as a result of irreversible binding to liver protein phosphatases. The aim of this study was to describe the recovery of MC from fish liver using various detection methods, with MC-LR as the representative congener. These findings are discussed in conjunction with the current procedures and limit values used for human risk assessment. Following incubation of liver homogenates with various MC-LR concentrations, the homogenates were extracted by a water/methanol/butanol mixture via different treatments and subsequently analyzed via the colorimetric protein phosphatase inhibition assay (cPPA), HPLC, and anti-Adda ELISA. Detection via cPPA appeared to yield the highest recovery of MC-LR, although the presence of unspecific background may have resulted in overestimation of the true recovery. The recoveries determined via HPLC and anti-Adda ELISA were comparable to each other. The limits of detection were 0.01-2.4 microg MC-LR/g liver tissue, depending on the method used. Maximum MC-LR recovery from samples incubated with 10 and 100 microg MC-LR/g ranged between 44% and 101%. Recovery from samples incubated with 1 microg MC-LR/g liver tissue was below 3%. Lower recovery is assumed to result from irreversible, covalent MC protein binding, as confirmed by Western blotting of liver homogenates with anti-Adda immunoprobing. The results demonstrate that further investigation of and improvement in routinely applied MC methods for fish tissue and/or food analyses are needed for a reliable risk assessment.

Animals↗

Methods to assess the development and recovery of locomotor function after spinal cord injury in rats.

The ability to assess recovery of function after spinal cord injury is a very important part of spinal cord injury research. Recent progress has been made in a number of avenues of treatment designed to ameliorate the consequences of spinal cord injury and enhance recovery of function. This potential for intervention to modify the sequellae of spinal cord injury requires stringent criteria for methods used to evaluate the effects of injury and subsequent recovery of function. Methods which rely on composite ratings of an animal's overall performance, while appropriate for screening groups of animals with spinal cord injury, are not sufficient to demonstrate whether a particular treatment has had a specific effect on motor function or the degree to which function is affected. We have designed a series of sensitive quantitative methods to assess the recovery of locomotor function in rats. The methods examine specific reflex responses and specific components of motor behavior and are sensitive to subtle differences in the pattern of locomotion and individual limb movements. Several of the tests can be used to assess the development of locomotor function as well as the mature response. Postural reflex testing and locomotor function under conditions of graded difficulty are examined and the motor capacity of individual limbs is assessed. Animals are trained to cross runways, to walk on a treadmill, and to climb onto a platform. The animals' performance is videotaped for subsequent quantitative analysis. The pattern of overground and treadmill locomotion is also examined by footprint analysis. Spinal cord injury alters an animal's reflex responses and deficits are evident in locomotor function. Examples are given of the quantitative measurements obtained from analysis of the animals' performance on each of the tests. No single test is sufficient to assess recovery of function after spinal cord injury. Rather, a combination of tests, each examining particular components of normal and recovered motor function, is required. The methods used to assess recovery of locomotor function are specific, are sensitive, and allow individual limb movements to be isolated. Such specific methods allow one to begin to address the mechanisms underlying recovery of function following spinal cord injury.

Animals↗

The recovery of postural reflexes and locomotion following low thoracic hemisection in adult cats involves compensation by undamaged primary afferent pathways.

Spinal hemisection in the adult cat results in motor impairments followed by substantial recovery of function (16, 20, 39, 53). The present study was undertaken to assess the contribution of undamaged ipsilateral segmental and contralateral descending systems to recovery of motor function. Quantitative behavioral methods were used to examine monopedal reflex and bipedal locomotor functions after thoracic hemisection. Different facets of motor behavior recover at different times. The recovery of monopedal postural reflexes precedes the recovery of more complex motor behavior. Since the reflexes tested are initiated by segmental afferent input and show recovery and normal motor patterns during locomotion, as defined by kinematic analysis show recovery, it is likely that dorsal root input compensates for the loss of descending input to one side of the spinal cord. Quantitative immunocytochemical methods for visualizing the central projections of dorsal root fibers (monoclonal antibody RAT-102; 49) and the descending serotoninergic pathway were used to examine the response of these pathways to hemisection. Hemisection results in a permanent decrease in the density of serotoninergic projections and a permanent increase in dorsal root projections in the spinal cord. The increased density of RAT-102 may represent an increase in the projection of dorsal root fibers and provide the increased input necessary to mediate enhanced reflex control. A transient increase in GAP-43 in the dorsal horn ipsilateral to the hemisection suggests that the increased density of RAT-102 immunoreactivity is associated with growth. Taken together, our results suggest that sprouting of primary afferents within the spinal cord is one mechanism underlying the recovery of function after hemisection.

Adaptation, Physiological↗

Chromosome segregation in crane-fly spermatocytes: cold treatment and cold recovery induce anaphase lag.

Anaphase lagging of autosomes was observed in 6.1 +/- 5.4% of the primary spermatocytes in untreated larvae of the crane fly, Nephrotoma suturalis. Lagging was induced by exposure of larvae to 6 degrees C and during recovery at 22 degrees C from exposure to 0.2, 2, and 6 degrees C. The incidence of anaphase lag was maximal at 80 to 90 min of recovery. Induced lagging was observed at that recovery time after exposures of only 2.5 h to 2 or 0.2 degrees C, but its incidence increased with longer exposures. As many as 85% of the cells in anaphase contained autosomal laggards after 61 h at 2 degrees C and 80 to 90 min of recovery. At 2 degrees C, cells reached the prophase-prometaphase transition, but spindles did not appear to form. Those cells proceeded through prometaphase during recovery, reaching mid-anaphase after 80 to 90 min of recovery. Chromosomes that lagged at anaphase during recovery from 2 degrees C were observed in living cells to be half-bivalents derived from bivalents that congressed to the metaphase plate. One or both half-bivalents of any bivalent could lag. In some cells, one half-spindle had more half-bivalents than the other. Cells with autosomal laggards often did not cleave, and in uncleaved cells the second division employed spindles having two, three, or four poles. The basis of induced lagging might be a lapse in spindle attachment or motive force application at the start of anaphase or a failure of chromosomes to achieve proper orientation before the onset of anaphase.

Animals↗

The recovery of tension in transients during steady lengthening of frog muscle fibres.

The tension transients following step length changes imposed on tetanized muscle fibres during the steady phase of force response to lengthening were determined at different velocities. At low velocities the early partial recovery after a step was smaller and slower than under isometric conditions, while the speed of the final total recovery was faster. The degree of depression of the early recovery and the speed of the final recovery increased with the lengthening velocity. At a given lengthening velocity the speed of the total recovery depended on size and direction of the steps, increasing from the region of the larger releases to that of the larger stretches. The changes in the early partial recovery are explained qualitatively by the theory of Huxley and Simmons (1971), while the changes in the speed of the final recovery are explained by assuming that detachment of cross-bridges is negligible until a certain range of cross-bridge strain is reached, and then increases rapidly. It is also necessary to assume that cross-bridges detached in this way re-attach much more rapidly than when they detach on completion of their cycle during shortening.

Animals↗

Comparison of posttransfusion recoveries achieved with either fresh or stored platelet concentrates.

The effectiveness of platelet concentrate transfusion depends on such variables as blood bag material, donor--recipient compatibility, and time elapsed between donation and transfusion. To study the latter a corrected thrombocyte increment for recovery in the recipients was evaluated with 108 platelet transfusions in 31 patients. In 83 treatment programs, the mean recovery at the one-hour post-transfusion time point was 8.6 X 10(9) platelets/l with fresh platelets and 5.9 X 10(9) platelets/l with stored platelets. Significantly better recovery was achieved with freshly prepared platelet over the total of platelet concentrates stored for up to 96 hours; however, if the recoveries in different patient groups given stored platelets were considered separately in terms of storage times of up to 48 h or 48-96 h, the good recovery with fresh platelets was significantly better only when compared to the older (p = 0.034) but not to the younger group of stored platelets. In patients with signs indicating enhanced platelet destruction (fever, splenomegaly, disseminated intravascular coagulation) the transfusion with fresh platelet concentrates gave a significantly better recovery compared to stored platelet concentrates (p = 0.028), whereas in the absence of such signs the recovery produced by fresh concentrates was not significantly higher than with stored concentrates. These findings may be relevant for the logistics in blood banking.

Adult↗

31P-nuclear magnetic resonance spectroscopy study of the time course of energy metabolism during exercise and recovery.

This study evaluated the time courses of intracellular pH and the metabolism of phosphocreatine (PCr) and inorganic phosphate (Pi) at the onset of four exercise intensities and recoveries. Non-invasive evaluation of continuous changes in phosphorus metabolites has become possible using 31P-nuclear magnetic resonance spectroscopy (31P-MRS). After measurements at rest, six healthy male subjects performed 4 min of femoral flexion exercise at intensities of 0 ("loadless"), 10, 20 and 30 kg.m.min-1 in a 2.1 T superconducting magnet with a 67-cm bore. Measurements were continuously made during 5 min of recovery. During a series of rest-exercise-recovery procedures, 31P-MRS were accumulated using 32 scans-spectrum-1 requiring 12.8 s each. At the onset of exercise, PCr decreased exponentially with a time constant of 27-32 s regardless of the exercise intensity. The time constant PCr resynthesis during recovery was about 27-40 s. The PCr kinetics were independent of exercise intensity. There were similar Pi kinetics at the onset of all types of exercise, while those of Pi recovery became significantly longer at the higher exercise intensities (P < 0.05). Furthermore, the intracellular pH indicated temporary alkalosis just at the onset of exercise, probably due to absorption of hydrogen ions by PCr hydrolysis, and then decrease at a point about 40%-50% of the pre-exercise PCr. The pH recovery time was longer than that for the Pi or PCr kinetics. By using a more efficient resolution system it was possible to obtain the phosphorus kinetics during exercise and to follow PCr resynthesis within the first few minutes of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Haematological recovery following high-dose cyclophosphamide with autologous bone marrow transplantation.

A total of 31 patients with previously untreated small-cell carcinoma of the lung were treated with very-high-dose cyclophosphamide, using autologous bone marrow transplantation (ABMT) to assist haematological recovery. The period of neutropenia was shorter with 40 mg/kg cyclophosphamide x 4 (7 patients) than when the dose of cyclophosphamide was increased to 50 mg/kg x 4 (11 patients), despite ABMT 2 days after chemotherapy in each group. In all, 13 patients were treated with 50 mg/kg cyclophosphamide x 4, with infusion of bone marrow delayed to day 4, 6 or 8 after chemotherapy to determine the contribution of ABMT to haematological recovery. The period of neutropaenia was increased when marrow was returned 6 days following chemotherapy, confirming that ABMT contributed to haematological recovery after this schedule of treatment. A total of 11 patients had a second cycle of 50 mg/kg cyclophosphamide x 4 after recovery from the first cycle of high-dose chemotherapy. The period of myelosuppression was greater with the second cycle of chemotherapy, although ABMT was carried out during both cycles. The results show that ABMT contributes to haematological recovery when the dose of cyclophosphamide is high enough to produce prolonged hypoplasia. The increased myelosuppression observed after a second high-dose treatment in spite of ABMT suggests either that both transplanted and endogenous marrow activity contribute to recovery of myelopoiesis or that there is residual damage to marrow stroma after the first cycle of treatment. The data indicate the necessity of carefully assessing the role of ABMT in haematological recovery with high-dose chemotherapy regimens.

Blood↗

The effects of psychological factors and physical trauma on recovery from oral surgery.

This study evaluated the effects of several psychological factors on postsurgical recovery while controlling for and also evaluating the effects of the physical trauma induced by the surgery. Subjects were 38 patients (18 males and 20 females) who were scheduled to have four third molars surgically removed. The psychological factors measured included anxiety and expectations about recovery, trait anxiety, coping behaviors, and health locus of control. Surgical trauma was rated after surgery, and the following aspects of recovery were monitored: postoperative pain, interference with normal function, swelling, and healing. Poorer postoperative recovery was significantly predicted by each of the psychological variables and by higher levels of surgical trauma. In addition, the effects of the psychological variables on recovery were shown to be largely independent of the trauma effects. The data suggest that (a) future studies which give patients more positive expectations and reduce their anxiety about recovery may improve their recovery and (b) the types of patients most in need of preoperative psychological support would be those who have higher trait anxiety, vigilant coping behaviors, or an internal locus of control.

Adolescent↗

A study of lactate metabolism without tracer during passive and active postexercise recovery in humans.

Tracers have been used extensively to study lactate metabolism in humans during rest and exercise. Nevertheless, quantification of in vivo lactate kinetics as measured by lactate tracers remains controversial and new data are necessary to clarify the issue. The present study has developed a simple kinetic model which does not require labelled molecules and which yields proportional and quantitative information on lactate metabolism in humans during postexercise recovery performed at different levels of intensity. Five subjects took part in six experiments each of which began with the same strenuous exercise (StrEx; 1 min, 385 W, 110 rpm). The StrEx of each session was followed by a different intensity of recovery: passive recovery (PR) and active recoveries (AR) with power outputs of 60, 90, 120, 150 and 180 W, respectively. Blood lactate concentration was measured prior to and immediately after StrEX and regularly during the 1st h of recovery. Oxygen uptake (VO2) was measured every 30 s during the whole session. The results showed that the disappearance rate constant (ke) increases abruptly from PR [0.080 (SEM 0.004) min-1] to moderate AR [60 W: 0.189 (SEM 0.039) min-1] and decreases slowly during more intense AR [180 W: 0.125 (SEM 0.027) min-1]. The lactate apparent clearance (Cl.F-1) was calculated from the area under the lactate concentration-time curve. The Cl.F-1 increased 1.81 (SEM 0.17) fold from PR to moderate AR (60 W) and only 1.31 (SEM 0.14) from PR to the most intense AR (180 W). Using the model, the apparent lactate production (F"K0) was also calculated. The F"K0 increased regularly following a slightly curvilinear function of VO2 and was 2.61 (SEM 0.53) fold greater during the most intense AR (180 W) than during PR. Because of the lack of data concerning the size of apparent lactate distribution volume (Vd), the apparent turnover rate (Rbl) has been presented here related to Vd. The Rbl.Vd-1 increased also following a slightly curvilinear function of VO2. The Rbl.Vd-1 was 85.90 (SEM 14.42) mumol.min-1.l-1 during PR and reached 314.09 (SEM 153.95) mumol.min-1.l-1 during the most intense AR (180 W). In conclusion the model presented here does not require labelled molecules and firstly makes it possible to follow the proportional change of apparent lactate clearance and apparent lactate production during active postexercise recovery in comparison with passive recovery conditions and secondly to estimate the blood lactate turnover.

Adult↗

Pyritinol facilitates the recovery of cortical cholinergic deficits caused by nucleus basalis lesions.

The effect of a nootropic, Pyritinol, on the recovery of cortical cholinergic deficits induced by injury of the nucleus basalis has been tested on two groups of unilateral quisqualic acid nbM-lesioned rats. The first group had a 30 nmol lesion producing a cortical cholinergic impairment at 21 days, with a spontaneous recovery at 45 days. The second group had a 50 nmol lesion that produced a deeper cholinergic deficit, which did not recover at 45 days. Pyritinol enhanced the recovery in the 30 nmol group of animals on the 21st day after surgery. The recovery was measured as an increase in the activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and the high affinity choline uptake system, and the histochemical densities of the cortical AChE network and the M2 receptor. Histochemical analysis of the nbM enabled cortical recovery to be related to the number of surviving neurons and also to their hypertrophy and AChE-ChAT hyperactivity. Pyritinol enhanced recovery in 30 nmol lesioned animals but in the other group, with a lower number of surviving neurons and a lower ability of the cells to become hypertrophic, the drug was unable to promote cortical recovery.

Animals↗

Measuring immediate recovery from general anaesthesia using a scoring system.

The study describes the design and testing of a scoring system to measure immediate recovery from anaesthesia. The scoring system which measures the patient's cognitive, motor haemodynamic and respiratory recovery, was applied in 1,626 patients. The score was measured at five minutes intervals and the results were plotted on recovery graphs for each patient. The analysis shows that patients who had received automatic ventilation during their anaesthetic were likely to arrive in the recovery room with a score of 14 or 15 (the top score), while other patients were likely to arrive with lower scores and progressed in their recovery at 0.9 (SD 0.6) score units per minute. Multivariate analysis confirms that the anaesthetist's decision to employ automatic or spontaneous ventilation is the most important single factor in determining the rate of increase of the recovery score. It is suggested that this scoring system, which fits well with the clinical appreciation of the case, is a useful tool in the hands of the recovery nurse.

Anesthesia, General↗