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At least 73 records · Page 4Linked to original sources
PubMed1998

[Valproic acid relieved marked rigidity in three patients with end-stage parkinsonism].

We applied valproic acid (VPA) on the rigidity of three parkinsonian patients, two with Parkinson disease and one with striatonigral degeneration. They were all at Hoehn and Yahr's stage V and showed marked rigidity. In these patients, effect of L-DOPA had become limited or increasing the dosage of L-DOPA was difficult because of its side effects. Parkinsonian symptoms were assessed by using motor score of Unified Parkinson's Disease Rating Scale. The degree of rigidity in these three patients was markedly decreased with 300-600 mg/day of VPA. The blood level of VPA ranged from 24.8 to 66.5 micrograms/ml, which was relatively low compared with the effective blood level as an anti-epileptic agent. Parkinsonian symptoms other than rigidity, and the increased deep tendon reflexes which were present in the patient with striatonigral degeneration were not affected by VPA. Reduction of L-DOPA intensified rigidity again which had been under control. Trials of VPA on parkinsonism have been reported from two groups (Price PA, et al. 1978; Nutt J, et al. 1979), neither of which has observed any benefit of VPA. The difference of their results and ours seems to depend on the stage of patients; their patients had mild to moderate symptoms, whereas ours were in the end stage with marked rigidity. Since the effect of VPA upon parkinsonism is limited to rigidity, the end-stage patients whose care is difficult due to severe rigidity may obtain the best benefit of VPA. VPA is considered to take effect by activating gamma-aminobutyric acid (GABA) system. Because GABA is a common inhibitory neurotransmitter distributed in the wide areas of the central nervous system, it is difficult to locate the action site of VPA with regard to the amelioration of rigidity. The stretch reflex loop in the spinal cord does not seem to be the action site because no change was noted in deep tendon reflex. GABAergic striatal efferent neurons do not seem to be the sole action site either, because parkinsonian symptoms were not affected except for rigidity. The vestibular nucleus which receives strong GABAergic afferents from cerebellar Purkinje cells is an efficient tonus regulator. Since suppression of the function of the nucleus is known to reduce rigidity, it is at least a candidate for the action site of VPA. But there is no direct evidence for this matter. The exact action site of VPA remains to be elucidated.

Aged↗
PubMedDate not supplied

Kinetics of interleukin-2 induced changes in rigidity of human natural killer cells.

The success of adoptive immunotherapy is dependent in part on the successful delivery of effector cells to the tumor and the expression of cellular activities, such as adhesion, extravasation, and cytotoxic activity of the effector cells in the tumor. The structural rigidity of the effector cell is an important determinant of these functions. The present study was designed to quantify the changes in cellular rigidity and cytotoxic activity of human natural killer (NK) cells in the presence or absence of interleukin-2 (IL-2). Micropipet aspiration was used to measure the resistance of NK cells to an imposed external deformation. Homogeneous suspensions of NK cells were activated with 1000 U/mL of recombinant IL-2 in vitro and tested for cellular rigidity from 0 to 96 h post stimulation. The IL-2 activated cells increased their rigidity within 24 h and maintained it at this level for 96 h. Prolonged incubation of cells in IL-2 (14 d) resulted in a consistently high rigidity, which was further increased on starvation of the cells from IL-2. The increased rigidity of these cells was maintained throughout 96 h of IL-2 deprivation, although significant relaxation of rigidity was observed between 48 and 96 h. The relaxation of rigidity was associated with an increase in the number of nonviable cells. Reintroduction of IL-2 for 24 h to a culture of NK cells depleted of IL-2 for 48 h did not restore the cells to the pre-depletion level of rigidity. Cytotoxic activity of the activated NK cells following removal of IL-2 decreased to about 60% of the control activity within 24 h and continued through 72 h post-deprivation. These findings suggest that the initial activation of human NK cells by IL-2 will produce a relatively rapid increase in rigidity that may cause entrapment of these cells in small capillaries in vivo and that removal of IL-2 will produce an additional increase in rigidity, which is associated with decreased functional activity.

Cell Size↗
PubMed1998

Nocturnal penile tumescence and rigidity monitoring in young potent volunteers: reproducibility, evaluation criteria and the effect of sexual intercourse.

PURPOSE: We studied the reproducibility of nocturnal penile tumescence, rigidity evaluation criteria and the possible effects of sexual intercourse in young, healthy, potent male volunteers. MATERIALS AND METHODS: We recruited 12 male medical students 21 to 24 years old into the study. A disorder-free medical history, availability of a sexual partner and normal erectile function were the inclusion criteria. All subjects completed 3 sessions of 3 nights of recording using the RigiScan* device with at least a 3-day interval between recordings. During the last 3-night recording subjects were asked to have sexual intercourse at least once. Analysis of the recordings was focused on the best erectile event as well as on rigidity and tumescence activity units normalized per hour. RESULTS: The subjects completed 36, 3-night recordings. Of the total of 108 sessions 18 occurred after sexual intercourse. We analyzed 562 erectile episodes. All 3-night recordings included at least 1 episode of rigidity at the penile tip greater than 60% and more than 10 minutes in duration. Sexual intercourse did not significantly affect nocturnal penile tumescence and rigidity. When rigidity and tumescence activity unit values were normalized by the hour and expressed as mean values of the 3-night sessions, documented values became reproducible. CONCLUSIONS: At least 2 consecutive nights of recording are necessary to evaluate nocturnal penile tumescence and rigidity recordings. Nocturnal penile tumescence and rigidity with at least 1 erectile episode of tip penile rigidity greater than 60% and 10 minutes in duration may be associated with potency. Mean rigidity and tumescence activity unit values per hour of a recording may be used as objective parameters to measure overall erectile activity. In addition, sexual intercourse seems to decrease nocturnal penile tumescence and rigidity measurements, although not statistically significant. We anticipate that application of these criteria for nocturnal penile tumescence and rigidity evaluation will improve the diagnostic validity of the test. Future research will determine whether these criteria are too strict for the evaluation of aging men.

Adult↗
PubMed1975

Etonitazine-induced rigidity and its antagonism by centrally acting muscle relaxants.

Some narcotic drugs have been reported to produce increases in muscle tone in rats. In our laboratory we have found that etonitazine produces a 'lead-pipe' rigidity of the trunk and limb musculature. The reported studies were conducted to characterize etonitazine-induced rigidity more fully, to compare the degree of rigidity with that produced by morphine, codeine and methadone, and to assess the sensitivity of this rigidity to centrally acting muscle relaxants. Of the 4 narcotics tested, etonitazine was far more potent than methadone or morphine for producing rigidity; codeine did not produce peak rigidity comparable to the other 3 narcotics. Etonitazine-induced rigidity occurs at a supraspinal level since the effect was prevented by spinal transsection. Etonitazine-induced rigidity was prevented by the narcotic antagonists cyclazocine, pentazocine and naloxone but not by the serotonin depletor, p-chlorophenylalanine. Etonitazine-induced rigidity was antagonized by centrally acting muscle relaxants, including diazepam, methocarbamol, carisoprodol and zoxazolamine; in agreement with their relative clinical muscle relaxant potencies, diazepam is the most potent antagonist of etonitazine-induced rigidity.

Analgesics, Opioid↗
PubMed2002

Discrimination of morphine- and haloperidol-induced muscular rigidity and akinesia/catalepsy in simple tests in rats.

The present study was conducted to establish a simple method for measuring muscular rigidity in rats, which could be used for screening and is able to discriminate between rigidity and akinesia/catalepsy. Therefore, we treated rats with morphine (30 mg/kg i.p.), since large doses of morphine lead to muscular rigidity and akinesia. We measured muscular rigidity with a new method by determining the resistance of the hindlimb to passive flexion in the 'balance test' and also checked haloperidol (3 mg/kg i.p.) treated rats for muscular rigidity. Furthermore, catalepsy was also tested after administration of each of these drugs. Then, the influence of D(1)-like and D(2)-like dopamine receptor stimulation on muscular rigidity and catalepsy was studied. Therefore, the partial D(1) agonist SKF 38393 (3 and 8 mg/kg s.c.), the D(2)/D(1) agonist pergolide (0.25 and 0.5 mg/kg i.p.) and the dopamine precursor L-DOPA (50 and 100 mg/kg i.p.) were administered up to 30 min before muscular rigidity was measured in morphine-treated rats. The results showed that morphine, but not haloperidol led to muscular rigidity, whereas both drugs led to positive scores in the catalepsy test. The dopaminergic drugs partly antagonized the morphine-induced muscular rigidity in the doses applied, but not the catalepsy. Apparently, rigidity, akinesia/catalepsy produced by morphine can be discriminated from that produced by haloperidol in simple and quick tests.

Analgesics, Opioid↗
PubMed1986

Physiology of alfentanil-induced rigidity.

The authors investigated the hemodynamic, metabolic, electroencephalographic (EEG), and electromyographic (EMG) characteristics of narcotic-induced rigidity during induction of anesthesia with alfentanil (175 micrograms/kg) in 10 patients. Thiopental (4 mg/kg) was administered to a ten-patient control group. Rigidity was quantified in eight muscle groups (sternocleidomastoid, deltoid, biceps, forearm flexors, intercostal, rectus abdominus, vastus medialis/lateralis, and gastrocnemius). Marked rigidity was observed in all muscle groups in all patients receiving alfentanil and in none receiving thiopental. Central venous pressure increased with onset of rigidity, while mean arterial pressure and cardiac index remained unchanged. Manual ventilation was extremely difficult during alfentanil-induced rigidity. Arterial oxygen tension decreased more rapidly during rigidity than during the same time interval in the control group, while patients experiencing rigidity were more acidotic, as reflected by greater increases in base deficit. The EEG demonstrated an anesthetic state without seizure activity. The immediate increase in central venous pressure with the onset of rigidity, along with occasional simultaneous parallel variations in central venous pressure and the EMG, strongly suggest a mechanical mechanism for the change in central venous pressure. The metabolic changes during rigidity may be partly related to the absence of the normal cardiovascular reflexes that are reported to occur during voluntary isometric muscle contractions. A neurochemical mechanism of narcotic-induced rigidity is briefly reviewed.

Alfentanil↗
PubMed1998

Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity.

OBJECTIVE: To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis. METHODS: Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment. RESULTS: This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, ususphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound. CONCLUSIONS: The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.

Adult↗
PubMed1982

Effects of striatal and pallidal lesions and intrapallidal GABA and opiate drugs on tremorine-induced rigidity in the rat.

Tremorine-induced hindlimb rigidity was prevented by the neurotoxin kainic acid in one neostriatum. A unilateral globus pallidus (GP) electrolesion reduced the tone of the contralateral leg (CL) and differentially modified tremorine rigidity. The ipsilateral leg rigidity was reduced and the CL rigidity was increased. Resting tone and tremorine-induced rigidity were measured in CL after injection in one GP of drugs that modify pallidal GABA function. The GABA drugs tested in GP had no consistent effects on resting limb tone. By contrast, baclofen and muscimol, agonists for GABA receptors, both prevented tremorine rigidity, whereas the antagonists bicuculline and picrotoxin increased rigidity. Opiate receptor agonists in GP did not effect tone of rigidity but naltrexone prevented rigidity in CL leg. The findings suggest a close involvement of GP in mediating cholinergic limb rigidity.

Animals↗
PubMed1997

Domains of neuronal microtubule-associated proteins and flexural rigidity of microtubules.

Microtubules are flexible polymers whose mechanical properties are an important factor in the determination of cell architecture and function. It has been proposed that the two most prominent neuronal microtubule-associated proteins (MAPs), tau and MAP2, whose microtubule binding regions are largely homologous, make an important contribution to the formation and maintenance of neuronal processes, putatively by increasing the rigidity of microtubules. Using optical tweezers to manipulate single microtubules, we have measured their flexural rigidity in the presence of various constructs of tau and MAP2c. The results show a three- or fourfold increase of microtubule rigidity in the presence of wild-type tau or MAP2c, respectively. Unexpectedly, even low concentrations of MAPs promote a substantial increase in microtubule rigidity. Thus at approximately 20% saturation with full-length tau, a microtubule exhibits >80% of the rigidity observed at near saturating concentrations. Several different constructs of tau or MAP2 were used to determine the relative contribution of certain subdomains in the microtubule-binding region. All constructs tested increase microtubule rigidity, albeit to different extents. Thus, the repeat domains alone increase microtubule rigidity only marginally, whereas the domains flanking the repeats make a significant contribution. Overall, there is an excellent correlation between the strength of binding of a MAP construct to microtubules (as represented by its dissociation constant Kd) and the increase in microtubule rigidity. These findings demonstrate that neuronal MAPs as well as constructs derived from them increase microtubule rigidity, and that the changes in rigidity observed with different constructs correlate well with other biochemical and physiological parameters.

Adsorption↗
PubMed1984

Static and dynamic rigidities of normal and sickle erythrocytes. Major influence of cell hemoglobin concentration.

Static and dynamic deformabilities of erythrocytes are important determinants of microcirculatory blood flow. To determine the influence of increased cellular hemoglobin concentration on these properties, we quantitated static and dynamic deformabilities of isolated subpopulations of oxygenated normal and sickle erythrocytes with defined cell densities using micromechanical manipulations of individual cells. The rheological properties measured to characterize static deformability were membrane extensional rigidity and bending rigidity. To characterize dynamic deformability of the cells, we measured the time constants for rapid elastic recovery from extensional and bending deformations. The extensional rigidity of sickle cells increased with increasing cell hemoglobin concentration while that of normal cells was independent of the state of cell hydration. Moreover, sickle cells were found to exhibit inelastic behavior at much lower cell hemoglobin concentrations than normal cells. In contrast, the dynamic rigidity of both normal and sickle cells was increased to the same extent at elevated hemoglobin concentrations. Moreover, this increase in dynamic rigidity with increasing cellular dehydration was much more pronounced than that seen for static rigidity. Both the increased static and dynamic rigidities of the dehydrated sickle cells could be greatly improved by hydrating the cells. This suggests that increased bulk hemoglobin concentration, which is perhaps inordinately increased adjacent to the membrane, plays a major role in regulating the rigidity of sickle cells. In addition, irreversible membrane changes also appear to accompany cell dehydration in vivo, resulting in increased membrane shear rigidity and plastic flow. We expect that the marked increases in rigidity of dehydrated sickle cells observed here may have a major influence on the dynamics of their circulation in the microvasculature.

Anemia, Sickle Cell↗
PubMed2005

Rigidity sensing at the leading edge through alphavbeta3 integrins and RPTPalpha.

Cells require optimal substrate stiffness for normal function and differentiation. The mechanisms for sensing matrix rigidity and durotaxis, however, are not clear. Here we showed that control, Shp2-/-, integrin beta1-/-, and talin1-/- cell lines all spread to a threefold greater area on fibronectin (FN)-coated rigid polyacrylamide surfaces than soft. In contrast, RPTPalpha-/- cells spread to the same area irrespective of rigidity on FN surfaces but spread 3x greater on rigid collagen IV-coated surfaces than soft. RPTPalpha and alphavbeta3 integrins were shown previously to be colocalized at leading edges and antibodies to alphavbeta3 blocked FN rigidity sensing. When FN beads were held with a rigid laser trap at the leading edge, stronger bonds to the cytoskeleton formed than when held with a soft trap; whereas back from the leading edge and in RPTPalpha-/- cells, weaker bonds were formed with both rigid and soft laser traps. From the rigidity of the trap, we calculate that a force of 10 pN generated in 1 s is sufficient to activate the rigidity response. We suggest that RPTPalpha and alphavbeta3 at the leading edge are critical elements for sensing FN matrix rigidity possibly through SFK activation at the edge and downstream signaling.

Animals↗
PubMed1991

Brain sites mediating opiate-induced muscle rigidity in the rat: methylnaloxonium mapping study.

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a hydrophilic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced muscle rigidity in the rat. To extend these observations and to explore further the regions important for opiate-induced rigidity, rats were implanted with chronic guide cannulae aimed at discrete brain sites with an emphasis on the region from the periaqueductal grey (PAG) to the RPn. Each animal was pretreated by a blinded observer with an intracerebral injection of MN (125 ng total dose) or saline, and electromyographic (EMG) activity was recorded from the gastrocnemius muscle. Alfentanil (ALF; 500 micrograms/kg) was then administered subcutaneously and the magnitude of tonic EMG activity was assessed as a measure of hindlimb rigidity. The administration of MN into the pontine raphe nucleus (RPn) and also into the more lateral nucleus reticularis tegmenti pontis significantly attenuated ALF rigidity compared with saline-pretreated controls. Within the midbrain, MN selectively reversed rigidity when injected into the periaqueductal grey (PAG). The dorsal PAG appeared to be a more important site than the ventral PAG. There was no significant effect on ALF rigidity of MN injections into brain regions between the ventral PAG and the RPn while MN injections into the deep layers of the superior colliculus, lateral to the dorsal PAG, partially attenuated ALF rigidity. In contrast, rigidity was not consistently reversed after MN injections into the basal ganglia, the dorsal superior colliculus, or the region of the decussation of the dorsal tegmentum. This study provides strong evidence that nuclei of the reticular formation, specifically the PAG, raphe pontis, and reticularis tegmenti pontis that are known to play a role in other opioid-mediated behaviors, are important in opiate-induced muscle rigidity in the rat. These results could have implications for the prevention of this undesirable effect of high-dose opiate administration.

Alfentanil↗
PubMed1986

On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats.

The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.

Animals↗
PubMed1983

Effects of lesions in some basal ganglia nuclei and efferent projections on tremorine-induced limb rigidity in rats.

A mechanical apparatus was used to measure in rats the effects of some unilateral basal ganglia lesions on the hind-limb rigidity produced by the cholinomimetic compound, tremorine. A globus pallidus lesion reduced the resting tone and greatly increased rigidity in the contralateral leg. Lesions in the entopeduncular, subthalamic, and accumbens nuclei had no effects on rigidity, although the entopeduncular nucleus lesion reduced resting limb tone. The role of the globus pallidus in rigidity is significant in relation to work in which striatal lesions abolished tremorine-induced rigidity. Some brain regions that receive basal ganglia efferent fibers received a lesion unilaterally. Lesions in the substantia nigra, red nucleus, or pedunculopontine nucleus had no effect on tremorine-induced rigidity. A habenular lesion significantly reduced rigidity in both hind legs. Very pronounced reductions in rigidity occurred after midbrain lesions involving the central periaqueductal grey region and the superior colliculus. The basal ganglia output pathways that may mediate tremorine rigidity are discussed, together with the possibility that the superior colliculus, which has many muscarinic receptors, may be influenced directly by tremorine.

Animals↗
PubMedDate not supplied

The effects of thiopental sodium on fentanyl-induced muscle rigidity in a human model.

STUDY OBJECTIVE: To describe a safe human model in which to study the treatment of fentanyl-induced muscle rigidity and report on the efficacy of thiopental sodium for this purpose. DESIGN: Randomized, observer-blinded comparison of regimens. SETTING: Inpatient surgery at a university-affiliated teaching hospital. PATIENTS: Thirty patients scheduled for elective surgery in whom the administration of high-dose fentanyl was felt to be appropriate and who experienced severe muscle rigidity in the chest, abdomen, and upper extremities after the fentanyl was administered. INTERVENTIONS: One arm was isolated from circulation with a blood pressure (BP) cuff inflated to 100 mmHg above systolic blood pressure (SBP), after which fentanyl 25 to 50 micrograms/kg was administered intravenously (IV) at a rate of 1 mg/min in the contralateral arm. If severe muscle rigidity became apparent in three muscle groups (the chest, abdomen, and arms), patients were either (1) observed for 3.5 minutes without further intervention, (2) given thiopental sodium 1.5 mg/kg IV, followed 120 seconds later by succinylcholine 1 mg/kg IV, or (3) given succinylcholine 1 mg/kg IV, followed 120 seconds later by thiopental sodium 1.5 mg/kg IV. MEASUREMENTS AND MAIN RESULTS: A single observer, blinded to the technique, evaluated and recorded the degree of muscle rigidity present in the chest wall, abdomen, and upper extremities (one isolated from the circulation by a tourniquet) 90 seconds and 3.5 minutes after the onset of muscle rigidity in the control group and 90 seconds after the administration of either thiopental sodium or succinylcholine in the two experimental groups. The observer was the same individual in all instances. The muscle rigidity associated with the administration of high-dose fentanyl was clinically attenuated by the administration of thiopental sodium, especially in the extremities. Succinylcholine was more effective than thiopental sodium in producing muscle flaccidity in all muscle groups not isolated by a tourniquet. In no case did the muscle rigidity compromise our ability to oxygenate the patient adequately. CONCLUSIONS: Thiopental sodium does blunt the degree of muscle rigidity induced by high-dose fentanyl, though not as effectively as does succinylcholine. One can safely isolate an extremity prior to the administration of high-dose fentanyl and a muscle relaxant, intubate the trachea, and ventilate a patient, while retaining the ability to study the effect of centrally acting drugs on fentanyl-induced rigidity in the isolated extremity.

Fentanyl↗
PubMed1996

Role of central mu, delta-1, and kappa-1 opioid receptors in opioid-induced muscle rigidity in the rat.

BACKGROUND: Opioids appear to produce their physiologic effects by binding to at least three types of opioid receptors, the mu (mu), delta (delta), and kappa (kappa) receptors. Muscle rigidity occurs after administration of supra-analgesic doses of potent mu-preferring agonists like alfentanil. The role of different supraspinal opioid receptors in this rigidity has been addressed only recently. To elucidate the contribution of central mu, delta, and kappa receptors to muscle rigidity, the effects of intracerebroventricularly administered opioid receptor-selective agonists and antagonists on alfentanil-induced muscle rigidity were examined in rats. METHODS: Rats in which chronic intracerebroventricular cannulae had been implanted received an intracerebroventricular infusion of either saline or a mu (D-Ala2,N-Me-Phe4-Gly5-olenkephalin; DAMGO), delta(1) (D-Pen2,D-Pen5-enkephalin; DPDPE), or kappa(1) (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)- cyclohexyl)-benzene-acetamide methane sulfonate; U50,488H) opioid agonist. Ten minutes later, they received either saline or the mu-agonist alfentanil subcutaneously. Muscle rigidity was assessed using hindlimb electromyographic activity. Different groups of animals were pretreated with an intracerebroventricular infusion of either saline or a mu (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2; CTAP), delta (naltrindole), or kappa(1) (norbinaltorphimine) opioid antagonist before administration of either saline or a selective intracerebroventricular agonist. RESULTS: The mu agonist DAMGO alone dose-dependently induced muscle rigidity. This effect was antagonized by pretreatment with the mu-selective antagonist CTAP. Neither DPDPE nor U50,488H, when administered alone, affected muscle tone. However, both the delta(1) and kappa(1) agonists dose-dependently attenuated alfentanil-induced rigidity. This antagonism of alfentanil rigidity was abolished after pretreatment with the delta (naltrindole) and kappa(1) (nor-binaltorphimine) antagonists, respectively. CONCLUSIONS: The present data demonstrate that whereas systemic opiate-induced muscle rigidity is primarily due to the activation of central mu receptors, supraspinal delta(1) and kappa(1) receptors may attenuate this effect. This finding is consistent with previous demonstrations of functional interactions between different central opioid receptor populations in other opiate effects, and could have important pharmacotherapeutic implications.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

Multiscale modeling of macromolecular conformational changes combining concepts from rigidity and elastic network theory.

The development of a two-step approach for multiscale modeling of macromolecular conformational changes is based on recent developments in rigidity and elastic network theory. In the first step, static properties of the macromolecule are determined by decomposing the molecule into rigid clusters by using the graph-theoretical approach FIRST and an all-atom representation of the protein. In this way, rigid clusters are not limited to consist of residues adjacent in sequence or secondary structure elements as in previous studies. Furthermore, flexible links between rigid clusters are identified and can be modeled as such subsequently. In the second step, dynamical properties of the molecule are revealed by the rotations-translations of blocks approach (RTB) using an elastic network model representation of the coarse-grained protein. In this step, only rigid body motions are allowed for rigid clusters, whereas links between them are treated as fully flexible. The approach was tested on a data set of 10 proteins that showed conformational changes on ligand binding. For efficiency, coarse-graining the protein results in a remarkable reduction of memory requirements and computational times by factors of 9 and 27 on average and up to 25 and 125, respectively. For accuracy, directions and magnitudes of motions predicted by our approach agree well with experimentally determined ones, despite embracing in extreme cases >50% of the protein into one rigid cluster. In fact, the results of our method are in general comparable with when no or a uniform coarse-graining is applied; and the results are superior if the movement is dominated by loop or fragment motions. This finding indicates that explicitly distinguishing between flexible and rigid regions is advantageous when using a simplified protein representation in the second step. Finally, motions of atoms in rigid clusters are also well predicted by our approach, which points to the need to consider mobile protein regions in addition to flexible ones when modeling correlated motions.

Elasticity↗
PubMed1996

Stability of maxilla downgrafting after rigid or wire fixation.

PURPOSE: This article compares the long-term outcomes of rigid internal fixation with wire fixation. PATIENTS AND METHODS: In this retrospective study, nine cases of vertical midface augmentation in which rigid fixation was used were compared with 11 cases with wire fixation. One surgeon completed all cases for the rigid fixation group, and another surgeon completed the cases in the wire fixation group. RESULTS: Follow-up was 16 +/- 11 months for the rigid fixation group and 20 +/- 12 months for the wire fixation group. Inferior movement at the anterior portion of the maxilla was 7.0 +/- 2.9 mm with rigid fixation and 4.5 +/- 3.6 mm with wire fixation (P < .05). Postsurgical superior movement (relapse) was 0.4 +/- 0.4 mm with rigid fixation and 2.4 +/- 2.4 mm with wire fixation (P < .01). Inferior movement at the posterior maxilla was 3.1 +/- 0.2 mm with rigid fixation and 2.8 +/- 2.3 mm with wire fixation. Postsurgical superior movement (relapse) was 0.8 +/- 0.4 mm with rigid fixation and 0.5 +/- 2.3 mm with wire fixation, which was not significantly different. CONCLUSION: This comparison showed downgrafting of the maxilla using autogenous bone harvested from the iliac crest and rigid internal fixation to be a predictable and stable procedure.

Adolescent↗