Comparison of the Effect of Intrathecal Administration of Clonidine and Yohimbine on the Locomotion of Intact and Spinal Cats

2001 ◽  
Vol 85 (6) ◽  
pp. 2516-2536 ◽  
Author(s):  
Nathalie Giroux ◽  
Tomás A. Reader ◽  
Serge Rossignol
Keyword(s):  
Acid Methyl Ester ◽  
Intrathecal Administration ◽  
Cycle Duration ◽  
Descending Pathways ◽  
Step Cycle ◽  
Locomotor Pattern ◽  
Before And After ◽  
Spontaneous Expression ◽  
High Doses ◽  
Treadmill Locomotion

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate “fictive” locomotion in immobilized acutely spinalized cats and α2-noradrenergic agonists, such as 2,6,-dichloro- N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the α2 agonist, clonidine, and the antagonist (16α, 17α)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L3–L4before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50–150 μg/100 μl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800–1600 μg/100 μl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 μg/100 μl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

A comparison of treadmill locomotion in adult cats before and after spinal transection

1996 ◽  
Vol 76 (1) ◽  
pp. 471-491 ◽  
Author(s):  
M. Belanger ◽  
T. Drew ◽  
J. Provencher ◽  
S. Rossignol
Keyword(s):  
Muscular Activity ◽  
Swing Phase ◽  
Cycle Duration ◽  
Electromyographic Activity ◽  
Step Cycle ◽  
Initial Portion ◽  
Emg Amplitude ◽  
Flexor Muscles ◽  
Before And After ◽  
Treadmill Locomotion

1. The aim of this study was to document the kinematics and the electromyographic activity recorded from several muscles during treadmill locomotion in the same cat (N = 4), before and after spinalization by using a chronic implantation method. Because identical experimental and control conditions were used, it was possible to establish similarities and differences in the timing and amplitude of the muscular activity and kinematics under the intact and spinal conditions in the same animal. The data presented in this paper were collected when the cats had fully recuperated a stable locomotor pattern, walking at a constant speed of approximately 0.4 m/s. 2. The adult spinal cats retained many of the general locomotor features and electromyographic (EMG) characteristics seen before transection. However, there were also important differences. 3. There was a reduction in the step length that was principally due to the forward placement of the paw at the onset of the stance. Similarly, there was a decrease in the step cycle duration which was attributed to a reduction of both the stance and swing phases. 4. The overall angular excursions of the hip, knee, and ankle were generally similar, although joints were sometimes more flexed at all phases of the step cycle. In contrast, the overall excursions of the metatarsophalangeal joints was much greater in all four cats after spinalization due to a paw drag during the initial portion of the swing phase that exaggerated the plantarflexion. 5. There was an increase in the EMG amplitude of the flexor muscles at two of three joints (i.e., hip, knee, and ankle) in each cat after spinalization. The change in the EMG amplitude of the extensors did not appear to be as consistent as that observed in the flexor muscles. When looking at each cat individually, the postspinalization extensor activity decreased at two of three joints in two cats, whereas the opposite was true for the other two cats. 6. There was a delay in the onset of the knee flexor (semitendinosus) activity while the ankle dorsiflexor (tibialis anterior) activity started earlier with respect to the beginning of the swing phase. The onset of hip flexors was somewhat more variable. This change in the timing of flexor activity was most probably responsible for the paw drag at the onset of the swing phase. 7. The present results reveal that despite the few differences, the spinal cord and the hindlimbs afferents are capable of generating very good locomotor patterns with almost normal kinematics and EMG characteristics.

Effects of Red Nucleus Microstimulation on the Locomotor Pattern and Timing in the Intact Cat: A Comparison With the Motor Cortex

1999 ◽  
Vol 81 (5) ◽  
pp. 2297-2315 ◽  
Author(s):  
Marie-Josée Rho ◽  
Sylvain Lavoie ◽  
Trevor Drew
Keyword(s):  
Motor Cortex ◽  
Red Nucleus ◽  
Emg Activity ◽  
Cycle Duration ◽  
Step Cycle ◽  
Rubrospinal Tract ◽  
Locomotor Pattern ◽  
Train Duration ◽  
Flexor Muscles ◽  
Cathodal Current

Effects of red nucleus microstimulation on the locomotor pattern and timing in the intact cat: a comparison with the motor cortex. To determine the extent to which the rubrospinal tract is capable of modifying locomotion in the intact cat, we applied microstimulation (cathodal current, 330 Hz; pulse duration 0.2 ms; maximal current, 25 μA) to the red nucleus during locomotion. The stimuli were applied either as short trains (33 ms) of impulses to determine the capacity of the rubrospinal tract to modify the level of electromyographic (EMG) activity in different flexors and extensors at different phases of the step cycle or as long trains (200 ms) of pulses to determine the effect of the red nucleus on cycle timing. Stimuli were also applied with the cat at rest (33-ms train). This latter stimulation evoked short-latency (average = 11.8–19.0 ms) facilitatory responses in all of the physiological flexor muscles of the forelimb that were recorded; facilitatory responses were also common in the elbow extensor, lateral head of triceps but were rare in the physiological wrist and digit extensor, palmaris longus. Responses were still evoked in most muscles when the current was decreased to near threshold (3–10 μA). Stimulation during locomotion with the short trains of stimuli evoked shorter-latency (average = 6.0–12.5 ms) facilitatory responses in flexor muscles during the swing phase of locomotion and, except in the case of the extensor digitorum communis, evoked substantially smaller responses in stance. The same stimuli also evoked facilitatory responses in the extensor muscles during swing and produced more complex effects involving both facilitation and suppression in stance. Increasing the duration of the train to 200 ms modified the amplitude and duration of the EMG activity of both flexors and extensors but had little significant effect on the cycle duration. In contrast, whereas stimulation of the motor cortex with short trains of stimuli during locomotion had very similar effects to that of the red nucleus, increasing the train duration to 200 ms frequently produced a marked reset of the step cycle by curtailing stance and initiating a new period of swing. The results suggest that whereas both the motor cortex and the red nucleus have access to the interneuronal circuits responsible for controlling the structure of the EMG activity in the step cycle, only the motor cortex has access to the circuits responsible for controlling cycle timing.

Dynamic Sensorimotor Interactions in Locomotion

2006 ◽  
Vol 86 (1) ◽  
pp. 89-154 ◽  
Author(s):  
Serge Rossignol ◽  
Réjean Dubuc ◽  
Jean-Pierre Gossard
Keyword(s):  
Dependent Manner ◽  
Dynamic Adjustment ◽  
Descending Pathways ◽  
Step Cycle ◽  
Dynamic Interactions ◽  
Feedback Mechanisms ◽  
Foot Placement ◽  
Locomotor Pattern ◽  
Central Program ◽  
Sensorimotor Interactions

Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigger, stop, and steer locomotion. The feedback originates from muscles and skin afferents as well as from special senses (vision, audition, vestibular) and dynamically adapts the locomotor pattern to the requirements of the environment. The dynamic interactions are ensured by modulating transmission in locomotor pathways in a state- and phase-dependent manner. For instance, proprioceptive inputs from extensors can, during stance, adjust the timing and amplitude of muscle activities of the limbs to the speed of locomotion but be silenced during the opposite phase of the cycle. Similarly, skin afferents participate predominantly in the correction of limb and foot placement during stance on uneven terrain, but skin stimuli can evoke different types of responses depending on when they occur within the step cycle. Similarly, stimulation of descending pathways may affect the locomotor pattern in only certain phases of the step cycle. Section ii reviews dynamic sensorimotor interactions mainly through spinal pathways. Section iii describes how similar sensory inputs from the spinal or supraspinal levels can modify locomotion through descending pathways. The sensorimotor interactions occur obviously at several levels of the nervous system. Section iv summarizes presynaptic, interneuronal, and motoneuronal mechanisms that are common at these various levels. Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.

Early Locomotor Training With Clonidine in Spinal Cats

1998 ◽  
Vol 79 (1) ◽  
pp. 392-409 ◽  
Author(s):  
Connie Chau ◽  
Hugues Barbeau ◽  
Serge Rossignol
Keyword(s):  
Locomotor Activity ◽  
Daily Injection ◽  
Emg Activity ◽  
Locomotor Training ◽  
Step Cycle ◽  
Locomotor Pattern ◽  
Video Images ◽  
Weight Support ◽  
Ankle Joints ◽  
Before And After

Chau, Connie, Hugues Barbeau, and Serge Rossignol. Early locomotor training with clonidine in spinal cats. J. Neurophysiol. 79: 392–409, 1998. Clonidine, a noradrenergic alpha-2 agonist, can initiate locomotion early after spinalization in cats. Because this effect lasts 4–6 h, we have injected clonidine daily, intraperitoneally or intrathecally, and intensively trained five spinal cats to perform hindlimb walking on a treadmill starting at day 3 and continuing until 10 days posttransection. Each day, clonidine was injected to induce locomotor activity and cats were trained to walk with as much weight support as possible and at different speeds during multiple (1–5) locomotor training sessions, each lasting from 10 to 20 min, until the effects of clonidine wore off. Electromyographic (EMG) activity synchronized to video images of the hindlimbs were recorded before and after each clonidine injection. The results showed, first, a day-to-day change of the locomotor pattern induced by clonidine from the 3rd to the 11th day including an increase in the duration of the step cycle, an increase in the duration of extensor EMG activity, and an increase in total angular excursion of the hip, knee, and ankle joints. Second, after 6–11 days of this regimen, there was an emergence of a coordinated locomotor pattern with weight support of the hindquarters that was visible even before that day's clonidine injection. The results suggested that daily injection of clonidine followed by early and daily interactive locomotor training can enhance the recovery of locomotion in spinal cats.

Recovery of Locomotion After Ventral and Ventrolateral Spinal Lesions in the Cat. II. Effects of Noradrenergic and Serotoninergic Drugs

1999 ◽  
Vol 81 (4) ◽  
pp. 1513-1530 ◽  
Author(s):  
Edna Brustein ◽  
Serge Rossignol
Keyword(s):  
Spinal Cord Injuries ◽  
Recovery Period ◽  
Early Period ◽  
Cycle Duration ◽  
Locomotor Performance ◽  
Lateral Stability ◽  
Descending Pathways ◽  
Step Cycle ◽  
Spinal Lesions ◽  
Spinal Lesion

Recovery of locomotion after ventral and ventrolateral spinal lesions in the cat. II. Effects of noradrenergic and serotoninergic drugs. The effects of serotoninergic and noradrenergic drugs (applied intrathecally) on treadmill locomotion were evaluated in two adult cats subjected to a ventral and ventrolateral spinal lesion (T13). Despite the extensive spinal lesion, severely damaging important descending pathways such as the reticulo- and vestibulospinal tracts, both cats recovered quadrupedal voluntary locomotion. As detailed in a previous paper, the locomotor recovery occurred in three stages defined as early period, when the animal could not walk with its hindlimbs, recovery period, when progressive improvement occurred, and plateau period,when a more stable locomotor performance was observed. At this latter stage, the cats suffered from postural and locomotor deficits, such as poor lateral stability, irregular stepping of the hindlimbs, and inconsistent homolateral fore- and hindlimb coupling. The present study aimed at evaluating the potential of serotoninergic and/or noradrenergic drugs to improve the locomotor abilities in the early and late stages. Both cats were implanted chronically with an intrathecal cannula and electromyographic (EMG) electrodes, which allowed determination, under similar recording conditions, of the locomotor performance pre- and postlesion and comparisons of the effects of different drugs. EMG and kinematic analyses showed that norepinephrine (NE) injected in early and plateau periods improved the regularity of the hindlimb stepping and stabilized the interlimb coupling, permitting to maintain constant locomotion for longer periods of time. Methoxamine, the α1-agonist (tested only at the plateau period), had similar effects. In contrast, the α2-agonist, clonidine, deteriorated walking. Serotoninergic drugs, such as the neurotransmitter itself, serotonin ( 5HT), the precursor 5-hydroxytryptophan ( 5HTP), and the agonist quipazine improved the locomotion by increasing regularity of the hindlimb stepping and by increasing the step cycle duration. In contrast, the 5HT1A agonist 8-hydroxy-dipropylaminotetralin ( DPAT) caused foot drag in one of the cats, resulting in frequent stumbling. Injection of combination of methoxamine and quipazine resulted in maintained, regular stepping with smooth movements and good lateral stability. Our results show that the effects of drugs can be integrated to the residual voluntary locomotion and improve some of its postural aspects. However, this work shows clearly that the effects of drugs (such as clonidine) may depend on whether or not the spinal lesion is complete. In a clinical context, this may suggest that different classes of drugs could be used in patients with different types of spinal cord injuries. Possible mechanisms underlying the effect of noradrenergic and serotoninergic drugs on the locomotion after partial spinal lesions are discussed.

Stimulation of the Parapyramidal Region of the Neonatal Rat Brain Stem Produces Locomotor-Like Activity Involving Spinal 5-HT7 and 5-HT2A Receptors

2005 ◽  
Vol 94 (2) ◽  
pp. 1392-1404 ◽  
Author(s):  
Jun Liu ◽  
Larry M. Jordan
Keyword(s):  
Brain Stem ◽  
Pattern Generator ◽  
Neonatal Rat ◽  
Cycle Duration ◽  
Receptor Antagonists ◽  
Step Cycle ◽  
Output Stage ◽  
Discrete Population ◽  
First Time ◽  
Neonatal Rat Brain

Locomotion can be induced in rodents by direct application 5-hydroxytryptamine (5-HT) onto the spinal cord. Previous studies suggest important roles for 5-HT7 and 5-HT2A receptors in the locomotor effects of 5-HT. Here we show for the first time that activation of a discrete population of 5-HT neurons in the rodent brain stem produces locomotion and that the evoked locomotion requires 5-HT7 and 5-HT2A receptors. Cells localized in the parapyramidal region (PPR) of the mid-medulla produced locomotor-like activity as a result of either electrical or chemical stimulation, and PPR-evoked locomotor-like activity was blocked by antagonists to 5-HT2A and 5-HT7 receptors located on separate populations of neurons concentrated in different rostro-caudal regions. 5-HT7 receptor antagonists blocked locomotor-like activity when applied above the L3 segment; 5-HT2A receptor antagonists blocked locomotor-like activity only when applied below the L2 segment. 5-HT7 receptor antagonists decreased step cycle duration, consistent with an action on neurons involved in the rhythm-generating function of the central pattern generator (CPG) for locomotion. 5-HT2A antagonists reduced the amplitude of ventral root activity with only small effects on step cycle duration, suggesting an action directly on cells involved in the output stage of the pattern generator for locomotion, including motoneurons and premotor cells. Experiments with selective antagonists show that dopaminergic (D1, D2) and noradrenergic (α1, α2) receptors are not critical for PPR-evoked locomotor-like activity.

Dose-response effects of atropine on pancreatic response to secretin before and after truncal vagotomy

1985 ◽  
Vol 248 (5) ◽  
pp. G532-G538
Author(s):  
M. V. Singer ◽  
W. Niebel ◽  
K. H. Uhde ◽  
D. Hoffmeister ◽  
H. Goebell
Keyword(s):  
Heart Rate ◽  
Atropine Sulfate ◽  
Truncal Vagotomy ◽  
Before And After ◽  
Pancreatic Fistulas ◽  
Effective Doses ◽  
High Doses ◽  
Protein Output ◽  
Higher Doses ◽  
Intravenous Atropine

In dogs with gastric and pancreatic fistulas, we studied the effect of intravenous atropine in doses ranging from 0.9 to 58 nmol X kg-1 X h-1 on the pancreatic secretory response to secretin before and after truncal vagotomy. Truncal vagotomy did not alter the incremental bicarbonate response to secretin. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine sulfate significantly decreased the bicarbonate response to low doses (5.2 and 10.3 pmol X kg-1 X h-1) of secretin but had no significant effect on responses to high doses (20.5 and 41 pmol X kg-1 X h-1). The inhibitory potency of the effective doses of atropine did not differ significantly. Secretin did not stimulate pancreatic protein output above basal. Truncal vagotomy reduced protein output basally and during secretin by about 50%. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine significantly decreased protein output basally and during secretin. Secretin and truncal vagotomy did not alter basal heart rate. Only the three highest doses (14, 29, and 58 nmol X kg-1 X h-1) of atropine significantly increased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Persistence of hyperprolactinemia after treatment of primary hypothyroidism and withdrawal of long term use of estrogen: are the tuberoinfundibular dopaminergic neurons permanently lesioned?

2005 ◽  
Vol 49 (3) ◽  
pp. 468-472 ◽  
Author(s):  
Luiz Augusto Casulari ◽  
Fábio Celotti ◽  
Luciana A. Naves ◽  
Lucília Domingues ◽  
Carla Papadia
Keyword(s):  
Dopaminergic Neurons ◽  
Hormone Replacement ◽  
Hormonal Contraceptive ◽  
Primary Hypothyroidism ◽  
Trh Test ◽  
Pituitary Mass ◽  
Thyroid Hormone Replacement ◽  
Before And After ◽  
High Doses

Long term use of high doses of estrogen and the presence of chronic hyperprolactinemia may, at least in the rat, provoke lesions in the tuberoinfundibular dopaminergic (TIDA) neurons responsible for the control of prolactin (Prl) secretion. This occurrence, which is not yet well documented in humans, may have taken place in a patient on chronic oral hormonal contraceptive (OC) treatment who was seen for primary hypothyroidism, hyperprolactinemia and a pituitary mass. After thyroid hormone replacement, OC withdrawn and bromocriptine treatment, this patient could not maintain normal Prl levels, unless continuously treated with a dopaminergic agonist even when MRI was indicative of a normal situation. Function of TIDA neurons was investigated by TRH test (200µg IV) performed before and after treatment with 25mg carbidopa plus 250mg L-dopa every 4 hours for one day. Basal TSH was normal (3.9µU/mL) whereas basal Prl was high (67.5 ng/mL); both TSH and Prl levels appropriately increased after TRH: peaks 31.8µU/mL and 157.8 ng/mL, respectively. After treatment with carbidopa/L-dopa, basal TSH (1.6µU/mL) and Prl (34ng/mL) decreased and the response to TRH was partially blocked (10.3µU/mL and 61ng/mL, respectively). In spite of a normal response, we discuss the possibility that the persistence of hyperprolactinemia is due to lesion of the TIDA neurons produced by the long term use of high doses of estrogens and by the presence of chronic hyperprolactinemia.

Influence of purinoceptors' agonists and antagonists on opossum internal anal sphincter

1988 ◽  
Vol 255 (3) ◽  
pp. G389-G394 ◽  
Author(s):  
S. Rattan ◽  
R. Shah
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Inhibitory Effect ◽  
Inhibitory Response ◽  
Rectal Balloon ◽  
Balloon Distension ◽  
Before And After ◽  
High Doses ◽  
Alpha Chloralose ◽  
Dose Dependent

Studies were performed in alpha-chloralose-anesthetized and pancuronium-treated opossums. Resting internal anal sphincter pressures (IASP) were monitored using low-compliant continuously perfused catheters. P1 and P2 purinoceptor agonists, adenosine and ATP, respectively, administered close intra-arterially, caused dose-dependent decreases in the IASP. The inhibitory effect of these agonists on the IASP was tetrodotoxin resistant. Rectal balloon distension (RD) (which mimics the rectoanal inhibitory reflex) caused volume-dependent IAS relaxation. Electrical stimulation of the sacral nerve (SNS) also produced frequency-dependent decreases in IASP. The inhibitory response to adenosine (P1 purinoceptor agonist), ATP (P2 purinoceptor agonist), RD, and SNS on the internal anal sphincter (IAS) was examined before and after 8-phenyltheophylline (P1 purinoceptor antagonist) and alpha,beta-methylene ATP (P2 purinoceptor antagonist that irreversibly binds and desensitizes P2 purinoceptor). P1 and P2 purinoceptor antagonists produced selective antagonism of the inhibitory responses on the IAS of their respective agonists only. Furthermore, high doses of adenosine and ATP produced desensitization and block of their own actions only. The purinoceptors' antagonists, and the desensitization of purinoceptors by high doses of adenosine and ATP, failed to modify the fall in IASP in response to RD or SNS. From these studies we conclude that distinct inhibitory P1 and P2 purinoceptors are present on the IAS smooth muscle. However, these inhibitory purinoceptors may not be responsible for the rectoanal reflex-mediated IAS relaxation.

A role for NMDA receptors in posthypoxic frequency decline in the rat

1998 ◽  
Vol 274 (6) ◽  
pp. R1546-R1555 ◽  
Author(s):  
Sharon K. Coles ◽  
Paul Ernsberger ◽  
Thomas E. Dick
Keyword(s):  
Nmda Receptors ◽  
Receptor Activation ◽  
Respiratory Pattern ◽  
Breathing Frequency ◽  
Respiratory Response ◽  
Arterial Blood ◽  
Before And After ◽  
High Doses ◽  
The Brain ◽  
Nmda Receptor Activation

Posthypoxic frequency decline (PHFD) refers to the undershoot in respiratory frequency that follows brief hypoxic exposures. Lateral pontine neurons are required for PHFD. The neurotransmitters involved in the circuit that activate and/or are released by these pontine neurons regulating PHFD are unknown. We hypothesized that N-methyl-d-aspartate (NMDA) receptors are required for PHFD, because of the similarity in respiratory pattern after blocking lateral pontine activity or NMDA receptors. Furthermore, we hypothesized that the location of these NMDA receptors could be visualized by optimizing binding affinity with spermidine. In vagotomized, anesthetized rats ( n = 16), cardiorespiratory responses to hypoxia (8% O2, 30–90 s) were recorded before and after dizocilpine (10 μg-1 mg/kg iv), and NMDA receptors were mapped with [3H]dizocilpine ( n = 6). Dizocilpine elicited a dose-related effect on PHFD, blocking PHFD at high doses. Resting arterial blood pressure and breathing frequency decreased with high doses of dizocilpine, but the respiratory response to hypoxia remained intact. Our novel anatomical data indicate that NMDA receptors were widespread but distributed differentially in the brain stem. We conclude that NMDA receptors are located in pontine and medullary respiratory-related regions and that PHFD requires NMDA-receptor activation.

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