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Functional recovery from sciatic nerve crush lesion in the rat correlates with individual differences in responses to chronic intermittent stress.

The aim of the present study was to monitor the influence of chronic stress on functional recovery from a sciatic nerve crush lesion in the rat. Male Wistar rats underwent standard unilateral sciatic nerve crush. Subsequently, chronic stress was induced during the recovery phase using a daily 30 min shock box session where rats received three electric footshocks each session (0.5 sec, 1 mA). Reduced body weight gain, adrenal gland hypertrophy, and thymus involution indicated that the stress rats were chronically stressed. Evaluation of sensorimotor function revealed significant differences in recovery between control and stress groups. Correlational analysis of individual stress rats indicated that recovery of the walking pattern was negatively correlated with adrenal gland and medulla enlargement, thymus involution, and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone 45 min following the final stress session. In control rats, the index of sciatic nerve function (SF index, expressed as the difference between the injured paw and the intact contralateral paw as a percentage) was significantly correlated with adrenal medulla weight only. The present study reveals that chronic intermittent footshock stress impedes sensorimotor recovery following a sciatic nerve crush lesion and that the consequences of chronic intermittent stress are individually determined. We suggest that the quality of functional locomotor recovery after nerve crush lesion is related to the adaptive capacity or coping style of the individual rat.

Adaptation, Physiological↗

The role of augmented breaths (sighs) in bronchial asthma attacks.

The study is based on plethysmographic, neurophysiological and respiratory mass-spectrographic records established during anaphylactic or histamine-induced bronchial asthma attacks in guinea-pigs. The frequency of occurrence of the augmented breaths (sighs) is correlated with the intensity of the lung deflation reflex (tachypnoea) which arises during the attack. In the acute phase of the asthma attack, the sighs increase in number and reinforce the uneven ventilation which underlies stimulation of the pulmonary deflation receptors. The sigh becomes an essential component of the vicious circle of uneven ventilation and vagal lung deflation reflex induced. This circle is broken in the recovery phase of the asthma attack, during which the sighs decrease in number, as the conditions underlying their occurrence subside; they now lessen the uneven ventilation and by reopening closed lung units promote a return to normal conditions in lung mechanics. It is concluded that augmented breaths, like the asthmatic tachypnoea, are caused by uneven ventilation resulting in pulmonary self-compression and in turn stimulation of the pulmonary deflation (irritant) endings. Some factors which possibly contribute to the elicitation of augmented breaths are discussed.

Animals↗

Effects of induced hyperventilation on electrodermal response habituation to agoraphobia-relevant stimuli.

The role of hyperventilation in the aetiology of anxiety disorders was investigated in an analogue study. It was hypothesised that induced hyperventilation would alter subsequent subjective and physiological responses to visually presented agoraphobic material. Three groups (N = 16) of students were used and each was divided into two sub-groups which were presented with slides of either potentially agoraphobic or neutral content. During the first phase of the experiment, subjects were exposed to 10 slides whilst their breathing rate was manipulated. Group FB was instructed to hyperventilate by asking the subjects to breathe fast and deeply, Group SB was instructed to breathe at a slow rate and Group NB breathed normally. After a recovery phase, subjects were re-exposed to the same visual stimuli as used in the first phase of the experiment. Measures of skin conductance response amplitude were obtained for each stimulus in the series. In addition, heart rate and respiration were monitored, and subjective measures of somatic and affective states were obtained. Subjects also rated the pleasantness of the stimuli. The hyperventilation instructions resulted in delayed electrodermal habituation relative to the other groups. This finding could not be accounted for in terms of group differences in either physiological or subjective 'arousal'.

Adult↗

Ca2+ regulation in the presynaptic terminals of goldfish retinal bipolar cells.

1. To investigate regulation of the intracellular free Ca2+ concentration ([Ca2+]i) in presynaptic terminals, the Ca2+ current (ICa) and [Ca2+]i in axon terminals were simultaneously monitored in acutely dissociated retinal bipolar cells under whole-cell voltage clamp. 2. The recovery phase of the Ca2+ transient, which was evoked by activation of ICa, became slower when the Na(+)-Ca2+ exchanger was suppressed by removing extracellular Na+. 3. Inhibition of the plasma membrane Ca2+ pump produced by raising extracellular pH to 8.4 increased the basal [Ca2+]i and caused incomplete recovery from the Ca2+ transient. These effects were not observed in orthovanadate-loaded bipolar cells. 4. The Ca2+ transient was not significantly affected by ryanodine, caffeine, thapsigargin, Ruthenium Red or FCCP. Internal Ca2+ stores may not participate in shaping the Ca2+ transient. 5. The ratio of the peak amplitude of the Ca2+ transient to the total amount of Ca2+ influx became smaller as the size of the Ca2+ influx increased. This action was not affected by blockage of Ca2+ transporters in the plasma membrane, or by reduction of the rate of Ca2+ influx. The peak amplitude of the Ca2+ transient seemed to be determined by Ca2+ buffering substances with a positive co-operativity.

Animals↗

Increased myeloperoxidase index and large unstained cell values can predict the neutropenia phase of cancer patients treated with standard dose chemotherapy.

OBJECTIVE: The objective of this study was to better understand neutropenia induced by standard dose chemotherapy and to verify if there are any hematological parameters for defining the phase and possibly the duration of neutropenia. METHODS: The kinetics of large unstained cells (LUCs) and lymphocytes was evaluated in 324 blood counts of 56 chemotherapy cycles through the use of a Technicon H2 or an ADVIA 120 hematology analyzer. Blood samples collected during the neutropenia phase were also studied by flow cytometry using a large panel of monoclonal antibodies. Parametric and nonparametric statistics were employed to compare the different variables analyzed. A linear regression between each variable before and after nadir and a simple linear correlation among the same variables in the neutropenic and recovery phase were performed. RESULTS: The percentage of LUCs reaches the higher value at nadir and the difference between the mean value of prenadir and nadir is statistically significant (P <.01). The number of LUCs increases during the pre and postnadir phase. Lymphocytes number appears stable in the prenadir phase. The MPXI index increases in the prenadir phase and falls at nadir and this difference is statistically significant(P <.01). LUCs are correlated with blasts and CD34+ cells in the pre and postnadir phase, with CD3+/CD4+ cells in the prenadir phase, and with CD2+/CD56+ in the postnadir phase. CONCLUSIONS: Our data have shown that the estimation of both percentage of LUCs and MPXI can predict the neutropenia phase and orient for its duration. The lymphocyte number may be regarded as a parameter of risk of fever after day 5 of chemotherapy and the number of blood CD34+ cells may be predicted by LUC count.

Adult↗

Naturally occurring serum antiidiotypic antibody against antiliver-specific membrane lipoprotein in patients with hepatitis.

Studies were undertaken to evaluate whether antiidiotypic antibody against antiliver-specific membrane lipoprotein is related to the disease activity of patients with hepatitis. Sera from normal individuals, patients with viral hepatitis and medical staffs were depleted of antiliver-specific membrane lipoprotein antibody by absorbing with liver-specific membrane lipoprotein-bearing cell line SK-Hep-1. Anti-antiliver-specific membrane lipoprotein was detected by binding activity to antihuman liver-specific membrane lipoprotein monoclonal antibody using solid-phase radioimmunoassay and by inhibitory activity for binding of antiliver-specific membrane lipoprotein monoclonal antibody to SK-Hep-1 using competitive radioimmunoassay. The results obtained by the two assays were equivalent for detecting anti-antiliver-specific membrane lipoprotein. Sera from patients with acute viral hepatitis during recovery phase (n = 6) and chronic persistent hepatitis (n = 12), respectively, showed significantly increased anti-antiliver-specific membrane lipoprotein activity (p less than 0.01) when compared to those from normal individuals (n = 10), whereas sera from patients with chronic active liver disease (n = 12) did not reveal significantly different values from controls. Sera from the medical staff (n = 11) who had contact with hepatitis patients also demonstrated increased anti-antiliver-specific membrane lipoprotein activity (p less than 0.05). Inhibitory activity of anti-antiliver-specific membrane lipoprotein in the serum appeared localized within the F(ab')2 fragments of immunoglobulin G fraction by competitive radioimmunoassay. The specificity of the inhibitory activity of the serum was confirmed by its inability to block unrelated antigen-antibody reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗

Neurotensin-like immunoreactivity (NTLI) concentration in the cerebrospinal fluid of children and its alteration in a febrile aseptic meningitis.

Neurotensin-like immunoreactivity (NTLI) concentrations in the cerebrospinal fluid (CSF) of normal children and patients with febrile aseptic meningitis, aged 7 months to 15 years, were studied. The NTLI concentrations in CSF of 27 children with normal CSF findings were 160.1 +/- 54.6 pg/ml (mean +/- S.D.). The NTLI concentration in CSF of 26 patients in an acute phase of aseptic meningitis was 110.6 +/- 51.1 pg/ml which was significantly (P less than 0.01) lower than the controls. These patients had a mean temperature of 101.4 +/- 1.5 degrees F which remained elevated for an average of 3.5 days. The NTLI concentrations in CSF of 23 patients in a recovery phase (after blood and CSF findings became normal with no fever) were 166.5 +/- 57.8 pg/ml, which did not differ significantly from the normal. There were no statistical correlations between the NTLI concentration in CSF and the protein concentration or total cell count in CSF. These results suggest that NTLI concentration changes during a febrile aseptic meningitis and that it may be associated with thermoregulation.

Adolescent↗

Administration of Flk2/Flt3 ligand induces expansion of human high-proliferative potential colony-forming cells in the SCID-hu mouse.

The effects of Flk2/Flt3 ligand (FL) administration on human hematopoiesis were investigated using SCID-hu mice transplanted with human fetal bone fragments. Treatment with recombinant human FL induced significant increases in the frequencies of the high-proliferative potential colony-forming cells and low-proliferative potential colony-forming cells in steady-state human bone marrow. FL also promoted the expansion of high-proliferative potential colony-forming cells and low-proliferative potential colony-forming cells in the human bone marrow during the recovery phase after irradiation, which was evident in increases in the frequencies as well as in the absolute numbers of colony-forming cells. Furthermore, higher percentages of CD33+ CD15- cells were found in the marrows treated with FL as compared to that of controls, indicating that FL hastened the recovery of at least some aspect of myelopoiesis after irradiation. These results indicate that FL induces the expansion of primitive hematopoietic progenitor cells in vivo and, therefore, may be useful in treating patients to promote an early hematopoietic recovery after cytoablative therapies.

Animals↗

Peripheral neural correlates of cutaneous anaesthesia induced by skin cooling in man.

The effect of local skin cooling on the behavior of low- and high-threshold mechanoreceptive afferents innervating glabrous and non-glabrous skin was studied in microneurographic recordings on awake human subjects. Cooling with ice or ethyl chloride to a skin surface temperature below 10 degrees C caused a reduction of receptor sensitivity in 49 out of 52 studied low-threshold afferents. This effect was reversible upon warning but some reduction often persisted for a few minutes after normal skin temperature had been reached. The subjects' sensations of application and removal of von Frey hair stimuli were more resistant than had reappeared before the sensation of sustained pressure. This could be explained by shorter recovery times for fast than for slowly adapting units and by a relative preservation of the dynamic responses of the slowly adapting units. During the recovery phase some low-threshold mechanoreceptive afferents exhibited a transient 'spontaneous' discharge in the absence of external mechanical stimulation. The suppression of afferent C-fibre responses to needle strokes was more pronounced and long-lasting than the effect on A-fibre responses and largely paralleled the recovery of sensation of pain. It is concluded that the local anaesthetic effect of skin cooling is to a large extent explicable in terms of receptor desensitization although other mechanisms may contribute.

Adult↗

Vestibulo-tactile interactions regarding motion perception and eye movements in yaw.

This paper shows that tactile stimulation can override vestibular information regarding spinning sensations and eye movements. However, we conclude that the current data do not support the hypothesis that tactile stimulation controls eye movements directly. To this end, twenty-four subjects were passively disoriented by an abrupt stop after an increase in yaw velocity, about an Earth vertical axis, up to 120 degrees /s. Immediately thereafter, they had to actively maintain a stationary position despite a disturbance signal. Subjects wore a tactile display vest with 48 miniature vibrators, applied in different combinations with visual and vestibular stimuli. Their performance was quantified by RMS body velocity during self-control. Fast eye movement phases were analyzed by counting samples exceeding a velocity limit, slow phases by a novel method applying a first order model. Without tactile and visual information, subjects returned to a previous level of angular motion. Tactile stimulation decreased RMS self velocity considerably, though less than vision. No differences were observed between conditions in which the vest was active during the recovery phase only or during the disorienting phase as well. All effects of tactile stimulation found on the eye movement parameters could be explained by the vestibular stimulus.

Adult↗

Motility and mechanosensitivity of macrocilia in the ctenophore Beroë.

Mechanical activation of the microtubule sliding mechanism in cilia and flagella by local passive bending has been postulated to be essential for the initiation and propagation of bending waves along the axoneme. In addition, responsiveness of cilia to hydrodynamic forces imposed externally by their neighbours is thought to be responsible for metachronal coordination of ciliary activity, as well as for synchronal beating of component cilia within compound ciliary organelles. Direct tests of the mechanosensitivity of motile cilia are limited, but generally support these views. It remains problematical, however, whether mechanical interaction between cilia operates continuously during both the effective and recovery phases of the asymmetrical beat cycle. Moreover, the directional sensitivity and temporal responsiveness of motile cilia to mechanical stimuli have been explored in only a few cases. Finally, the continuous nature of the ciliary beat cycle has hindered investigation of the 'switch point hypothesis' in which doublet sliding is assumed to be activated sequentially on the two halves of the axoneme to produce bends in opposite directions. Here we report that macrocilia on the ctenophore Beroë beat discontinuously with separate effective and recovery strokes, resulting in 'split-cycle' waves of metachronal coordination. This new pattern of ciliary beating is used to investigate the motile responses of cilia to controlled mechanical stimuli during each phase of the beat cycle.

Animals↗

Contractile recovery from acidosis in toad ventricle is independent of intracellular pH and relies upon Ca2+ influx.

Hypercapnic acidosis produces a negative inotropic effect on myocardial contractility followed by a partial recovery that occurs in spite of the persistent extracellular acidosis. The underlying mechanisms of this recovery are far from understood, especially in those species in which excitation-contraction coupling differs from that of the mammalian heart. The main goal of the present experiments was to obtain a better understanding of these mechanisms in the toad heart. Hypercapnic acidosis, induced by switching from a bicarbonate-buffered solution equilibrated with 5% CO2 to the same solution equilibrated with 12% CO2, evoked a decrease in contractility followed by a recovery that reached values higher than controls after 30 min of continued acidosis. This contractile pattern was associated with an initial decrease in intracellular pH (pHi) that recovered to control values in spite of the persistent extracellular acidosis. Blockade of the Na+/H+ exchanger (NHE) with cariporide (5 micromol l-1) produced a complete inhibition of pHi restitution, without affecting the mechanical recovery. Hypercapnic acidosis also produced a gradual increase of diastolic and peak Ca2+i transient values, which occurred immediately after the acidosis was settled and persisted during the mechanical recovery phase. Inhibition of Ca2+ influx through the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R (1 micromol l-1 for myocytes and 20 micromol l-1 for ventricular strips), or of L-type Ca2+ channels by nifedipine (0.5 micromol l-1), completely abolished the mechanical recovery. Acidosis also produced an increase in the action potential duration. This prolongation persisted throughout the acidosis period. Our results show that in toad ventricular myocardium, acidosis produces a decrease in contractility, due to a decrease in Ca2+ myofilament responsiveness, followed by a contractile recovery, which is independent of pHi recovery and relies on an increase in the influx of Ca2+. The results further indicate that both the reverse mode NCX and the L-type Ca2+ channels, appear to be involved in the increase in intracellular Ca2+ concentration that mediates the contractile recovery from acidosis.

Acidosis↗

Functional and metabolic effects of uridine and UTP on the skeletal muscle of the rat submitted to exercise.

Twenty millimolar and 2 mM uridine triphosphate and 2 mM uridine were injected intra-arterially into rat leg muscles during a 20 min period of intense exercise and during the recovery phase (20 min). Administration of 20 mM uridine triphosphate during exercise, provoked a complete depression of muscle contractility. On the contrary, supply of 2 mM uridine triphosphate or 20 mM uridine induced a reduction in the decrease of muscular developed tension during the exercise period of time and favoured functional recovery. This positive effect of pyrimidine compounds on muscular functional parameters did not seem to be correlated with metabolic effects. Indeed, 2 mM uridine supply did not modify the evolution of intramuscular glycogen and lactate concentrations and made worsened the adenine nucleotide degradation induced by exercise.

Animals↗

Use of peripheral blood stem cells to accelerate hemopoietic recovery following autologous bone marrow transplantation.

Twenty-one patients with high risk non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Nine out of 21 patients received in addition to bone marrow (BM) cells also peripheral blood (PB) cells collected by leucapheresis performed in the recovery phase after high-doses of either cyclophosphamide or etoposide (7 patients), or after ara-C (2 patient). All patients receiving BM + PB cells had ABMT as salvage therapy following extensive relapse or progression of their disease. The addition of PB cells to BM cells allowed a significantly faster recovery after ABMT. Median time to reach WBC greater than 1,000/microL was 14 days versus 20.5 days for patients receiving BM only. Furthermore, a reduced requirement of supportive care and a shorter period of isolation was observed. These results confirm that PB cells combined with BM cells allow a prompt hematopoietic reconstitution after myeloablation. In addition, the data demonstrate the efficacy of PB cells collected after various cytotoxic drugs, even in patients previously exposed to cytoreductive regimens.

Adolescent↗

[Prediction of bone marrow function by the appearance rate of RNA-rich reticulocytes during the chemotherapy for hematologic malignancy].

Percentage of RNA-rich (High fluorescence Ratio, HFR), RNA-middle (Middle Fluorescence Ratio, MFR) and RNA-low (Low Fluorescence Ratio, LFR) reticulocytes was estimated by Sysmex R-1000 reticulocyte counter during the chemotherapy of 27 cases with acute leukemia and malignant lymphoma (36 courses). In the beginning of marrow suppression, HFR and/or MFR were decreased faster than LFR, neutrophils or platelets in 14 courses (38.9%). Simultaneous decrease of HFR, MFR and other blood cells were observed in 57.2%. In the recovery phase of bone marrow, faster increase of HFR and/or MFR was noted in 52.8% and simultaneous increase of these reticulocytes with other blood cells was observed in 9 courses (25%). Appearance rate of RNA-rich younger reticulocytes is a sensitive parameter for the prediction of bone marrow suppression and recovery during the chemotherapy for hematologic malignancy.

Adolescent↗

Seizure susceptibility during recovery from hypercapnia in neonatal dogs.

Seizure susceptibility during recovery from hypercapnia was investigated in seven anesthetized neonatal dogs; 13, 20, or 30% CO2 gas was administered for 30 min through a ventilator to result in three levels of hypercapnia in which measured PaCO2 values were approximately 70, 100, and 140 mm Hg. Thereafter, the animals were allowed to recover for 45 min; during this recovery phase, electrocorticography was performed. In five of seven dogs, approximately 1.5 Hz slow irregular spike and wave bursts appeared at 6 min after abrupt withdrawal from hypercapnia and lasted several minutes. This seizure activity was followed by a brief period of electrical suppression. This phenomenon was most often observed during the recovery from moderate hypercapnia and between the PaCO2 values of 100 and 50 mm Hg. When seizure activities appeared in the electrocorticogram, arterial blood pressure increased -40 mm Hg from the preseizure level. These results suggest that neonatal seizures may occur during recovery from hypercapnia.

Acidosis↗

Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia.

The objective of this work was to study the role of mannose-binding lectin (MBL) and C-reactive protein (CRP) in pneumococcal pneumonia, to determine whether MBL acts as an acute-phase reactant and whether the severity of the disease correlates with MBL levels. The study comprised 100 patients with pneumococcal pneumonia. The pneumonia severity score was calculated and graded into a risk class of mortality (Fine scale). The MBL genotypes and the levels of MBL and CRP at the acute and recovery phases were determined. Fifty patients with the wild-type MBL genotype showed higher MBL levels in each phase (P < 0.001) and an increased risk to developing bacteraemia, odds ratio (OR) 2.74, 95% confidence interval (CI) 1.01-7.52) (P = 0.02), but this did not correlate with the pneumonia severity class. CRP levels in the acute phase, 79.53 mg/l [standard deviation (s.d.) 106.93], were higher in the subjects with positive blood cultures (P = 0.003), and remained higher [20.12 mg/l (s.d. 31.90)] in the group of patients with an underlying disease (P = 0.01). No correlation was observed between the levels of MBL and CRP in each phase, or with the pneumonia severity score. We cannot conclude that MBL acts uniformly as an acute-phase reactant in pneumococcal pneumonia. MBL levels do not correlate well with the severity of the pneumonia. The risk of developing bacteraemia could be enhanced in individuals with the wild-type MBL genotype.

Acute-Phase Reaction↗

Augmented sympathetic tone alters muscle metabolism with exercise: lack of evidence for functional sympatholysis.

It is unclear whether sympathetic tone opposes dilator influences in exercising skeletal muscle. We examined high levels of sympathetic tone, evoked by lower body negative pressure (LBNP, -60 mmHg) on intramuscular pH and phosphocreatine (PCr) levels (31P-nuclear magnetic resonance spectroscopy) during graded rhythmic handgrip (30 contractions/min; approximately 17, 34, 52 and 69% maximal voluntary contraction). Exercise was performed with LBNP and without LBNP (Control). At the end of exercise, LBNP caused lower levels of muscle pH (6.59 +/- 0.09) compared with Control (6.78 +/- 0.05; P < 0.05). PCr recovery, an index of mitochondrial respiration, was less during the recovery phase of the LBNP trial. Exercise mean arterial pressure was not altered by LBNP. The protocols were repeated with measurements of forearm blood flow velocity and deep venous samples (active forearm) of hemoglobin (Hb) saturation, pH, and lactate. With LBNP, mean blood velocity was reduced at rest, during exercise, and during recovery compared with Control (P < 0.05). Also, venous Hb saturation and pH levels during exercise and recovery were lower with LBNP and lactate was higher compared with Control (P < 0.05). We conclude that LBNP enhanced sympathetic tone and reduced oxygen transport. At high workloads, there was a greater reliance on nonoxidative metabolism. In other words, sympatholysis did not occur.

Adult↗