Effect of Acute and Chronic Physical Exercise on Patients with Periodic Leg Movements

ESTEVES, A. M., M. T. DE MELLO, M. PRADELLA-HALLINAN, and S. TUFIK. Effect of Acute and Chronic Physical Exercise on Patients with Periodic Leg Movements. Med. Sci. Sports Exerc., Vol. 41, No. 1,. pp. 237-242, 2009. Purpose: Nonpharmacological interventions may lead to an improvement in sleep quality. The objective of our study was to evaluate the effects of acute intensive exercise and chronic exercise on sleep patterns in patients with periodic leg movements (PLM). Methods: The study involved acute and chronic exercise. The acute intensive exercise group consisted of 22 volunteers who underwent a maximum effort test and a polysomnography (PSG) on the same night. The chronic exercise group included. 11 patients who performed 72 physical training sessions undergoing three PSG studies on the night of sessions 1, 36, and 72. Blood samples were collected from both acute and chronic groups for beta-endorphin dosage. Results: Our results showed that both forms of physical exercise lowered PLM levels. The acute physical exercise increased sleep efficiency, rapid eye movement (REM) sleep, and reduced wake after sleep onset, whereas the chronic physical exercise increased sleep efficiency, REM sleep, and reduced sleep latency. We also found a significant negative correlation between beta-endorphin release after acute intensive exercise and PLM levels (r = -0.63). Conclusion: Physical exercise may improve sleep patterns and reduce PLM levels. The correlation between beta-endorphin release after acute intensive exercise and PLM levels might be associated with the impact physical exercise has on the opiodergic system. We suggest that physical exercise may be a useful nonpharmacological treatment for PLM.

The Stability of the Blood Oxygenation Level-Dependent Functional MRI Response to Motor Tasks Is Altered in Patients With Chronic Ischemic Stroke

Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)

Precise Insertion of Orthodontic Miniscrews with a Stereolithographic Surgical Guide Based on Cone Beam Computed Tomography Data: A Pilot Study

Purpose: Orthodontic miniscrews are commonly used to achieve absolute anchorage during tooth movement. One of the most frequent complications is screw loss as a result of root contact. Increased precision during the process of miniscrew insertion would help prevent screw loss and potential root damage, improving treatment outcomes. Stereo lithographic surgical guides have been commonly used for prosthetic implants to increase the precision of insertion. The objective of this paper was to describe the use of a stereolithographic surgical guide suitable for one-component orthodontic miniscrews based on cone beam computed tomography (CBCT) data and to evaluate implant placement accuracy. Materials and Methods: Acrylic splints were adapted to the dental arches of four patients, and six radiopaque reference points were filled with gutta-percha. The patients were submitted to CBCT while they wore the occlusal splint. Another series of images was captured with the splint alone. After superimposition and segmentation, miniscrew insertion was simulated using planning software that allowed the user to check the implant position in all planes and in three dimensions. In a rapid-prototyping machine, a stereolithographic guide was fabricated with metallic sleeves located at the insertion points to allow for three-dimensional control of the pilot bur. The surgical guide was worn during surgery. After implant insertion, each patient was submitted to CBCT a second time to verify the implant position and the accuracy of the placement of the miniscrews. Results: The average differences between the planned and inserted positions for the ten miniscrews were 0.86 mm at the coronal end, 0.71 mm at the center, and 0.87 mm at the apical tip. The average angular discrepancy was 1.76 degrees. Conclusions: The use of stereolithographic surgical guides based on CBCT data allows for accurate orthodontic mini screw insertion without damaging neighboring anatomic structures. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:860-865

Effect of diabetes on orthodontic tooth movement in a mouse model

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.

Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: Possible association with progressive or stable nature of the lesions

Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) are expressed in apical periodontitis, suggesting a role for these molecules during lesion development. However, the profiles of RANKL/OPG expression in periapical lesions remain unknown. In this study we investigated the patterns of RANKL and OPG mRNA expression by real-time polymerase chain reaction in human periapical granulomas (N = 44) and compared them with sites presenting characteristic bone resorbing activity: healthy (n = 14) and orthodontically stretched and compressed periodontal ligament (n = 26), healthy gingiva (n = 24), chronic gingivitis (n = 32), and chronic periodontitis (n = 34) samples. Both RANKL and OPG mRNA expression was higher in periapical granulomas when compared with healthy periodontal ligament. Distinct patterns of RANKL and OPG expression ratio were found in the granulomas and in different physiologic and pathologic conditions, with characteristic bone resorption activity potentially being indicative of the stable or progressive nature of the lesions. Lesions with radiographic image smaller than 5 mm showed higher RANKL/OPG expression than images greater than 5 mm. Periapical granulomas presented heterogeneous patterns of RANKL and OPG expression, ranging from samples with RANKL/OPG ratio similar to that seen in sites with minimal or absent bone resorption to samples with RANKL/OPG expression pattern comparable with active bone resorption sites.

Effects of the pendulum appliance, cervical headgear, and 2 premolar extractions followed by fixed appliances in patients with Class II malocclusion

Introduction: In this retrospective study, we compared the cephalometric effects, the dental-arch changes, and the efficiency of Class II treatment with the pendulum appliance, cervical headgear, or extraction of 2 maxillary premolars, all associated with fixed appliance therapy. Methods: The sample of 82 patients with Class II malocclusion was divided into 3 groups: group 1 patients (n = 22; treatment time, 3.8 years) were treated with the pendulum appliance and fixed orthodontic appliances. Group 2 patients (n = 30; treatment time, 3.2 years) were treated with cervical headgear followed by fixed appliances; group 3 patients (n = 30; treatment time, 2.1 years) were treated with 2 maxillary premolar extractions and fixed appliances. The average starting ages of the groups ranged from 13.2 to 13.8 years. Data were obtained from serial cephalometric measurements and dental casts. The dental casts were analyzed with the treatment priority index. The treatment efficiency index was also used. Results: The 3 treatment protocols produced similar cephalometric effects, especially skeletally. Comparisons among the 2 distalizing appliances (pendulum and cervical headgear) and extraction of 2 maxillary premolars for Class II treatment showed changes primarily in the maxillary dentoalveolar component and dental relationships. The facial profile was similar after treatment, except for slightly more retrusion of the upper lip in the extraction patients. The treatment priority index demonstrated that occlusal outcomes also were similar among the groups. The treatment efficiency index had higher values for the extraction group. Conclusions: The effects of treatment with the pendulum appliance or cervical headgear and extraction of 2 maxillary premolars associated with fixed appliances were similar from both occlusal and cephalometric standpoints. Class II treatment with extraction of maxillary teeth was more efficient because of the shorter treatment time. Differences in maxillary incisor retraction should be noted, but these differences might have been due to greater maxillary dentoalveolar protrusion in the extraction group before treatment. (Am J Orthod Dentofacial Orthop 2009;136:833-42)

Comparative efficiency of Class II malocclusion treatment with the pendulum appliance or two maxillary premolar extractions and edgewire appliances

The objective of this study was to compare, on study models and initial cephalograms, the efficiency of Class II malocclusion treatment with the pendulum appliance, and with two maxillary premolar extraction protocol. The sample consisted of 48 treated Class II malocclusion patients: group 1 comprised 22 patients (7 males, 15 females) treated with the pendulum appliance, with an initial mean age of 14.44 years and group 2, 26 patients (14 males, 12 females) treated with two maxillary premolar extractions at an initial mean age of 13.66 years. To compare the efficiency of each treatment protocol, the occlusal outcomes were evaluated on dental casts using the Peer Assessment Rating (PAR) Index and the treatment time (TT) of each group was calculated on clinical charts. The degree of treatment efficiency was calculated as the ratio between the percentage of occlusal improvement, evaluated through the PAR index, and TT. Statistical analysis was undertaken by means of t-tests. The findings demonstrated that the two maxillary premolar extraction protocol provided the occlusal outcomes in a shorter time (group 1: 45.7 months, group 2: 23.01 months) and, therefore, demonstrated greater treatment efficiency than the pendulum appliance.

Effects of short-term acetaminophen and celecoxib treatment on orthodontic tooth movement and neuronal activation in rat

Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for pain relief in orthodontics, but clinical studies reported that they may reduce tooth movement (TM). By other side, TM seems to activate brain structures related to nociception, but the effects of NSAIDs in this activation have not been studied yet. We analyzed the effect of short-term treatment with acetaminophen or celecoxib in the separation of rat upper incisors, as well as in neuronal activation of the spinal trigeminal nucleus, following tooth movement. Thirty rats (400-420 g) were pretreated through oral gavage (1 ml/dose)with acetaminophen (200 mg/kg), celecoxib (50 mg/kg) or vehicle (carboxymethylcellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance for TM. In controls, this appliance was immediately removed after its introduction. Rats received ground food, and every 12 h, one of the drugs or vehicle. After 48 h, they were anesthetized, maxilla was radiographed, and were perfused with 4% paraformaldehyde. Brains were further processed for Fos immunohistochemistry. TM induced incisor distalization (p < 0.05) and neuronal activation of the spinal trigeminal nucleus. Treatment with both drugs did not affect tooth movement, but reduced c-fos expression in the caudalis subnucleus. No changes in c-fos expression were seen in the oralis and interpolaris subnuclei. We conclude that neither celecoxib nor acetaminophen seems to affect tooth movement, when used for 2 days, but both drugs are able to reduce the activation of brain structures related to nociception. Short-term treatment with celecoxib, thus, may be a therapeutic alternative to acetaminophen when the latter is contra indicated. (C) 2009 Elsevier Inc. All rights reserved.

Persistent Impairment of Testicular Histology and Sperm Motility in Adult Rats Treated with Cisplatin at Peri-Puberty

Cisplatin is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. This study evaluated the effects of peri-pubertal cisplatin administration on several reproductive end-points and the reversibility of these effects in adulthood. Peri-pubertal Wistar male rats (45 days old) were divided into two groups: control (saline 0.9%) and cisplatin (1 mg/kg/day, 5 days/week, for 3 weeks, i.p.). The study was conducted in two steps and evaluations were performed at ages of 66 (post-pubertal age) and 140 (adult age) days on: (i) organ weights, serum gonadotropins and testosterone levels, sperm counts, motility and morphology, testicular histomorphometry, spermatogenesis kinetics, Sertoli cell number and in situ detection of apoptotic germ cells and (ii) sexual behaviour, fertility and intratesticular testosterone. At the end of cisplatin therapy, rats showed reductions in sperm production and reserves, sperm with progressive movement, tubular diameter, intratesticular testosterone and fertility potential, but increased numbers of TUNEL-positive seminiferous tubules, immotile sperm and pre-implantation losses compared with control. Moreover, cisplatin-treated post-pubertal rats displayed impaired testicular histopathology and sexual behaviour. Serum gonadotropins and testosterone levels, sperm morphology, spermatogenesis kinetics and Sertoli cell number were comparable between experimental groups at both ages. Alterations found in post-puberty were recovered at adulthood, except for sperm motility and damage to testicular histology. The persistence of these cisplatin effects, despite the unaltered fertility after natural mating in rats, may have implications for reproductive function of young boys undergoing cancer therapy, given the lower reproductive efficiency in human beings compared with rats.

Cervical mobilisation: concurrent effects on pain, sympathetic nervous system activity and motor activity

Recent findings that spinal manual therapy (SMT) produces concurrent hypoalgesic and sympathoexcitatory effects have led to the proposal that SMT may exert its initial effects by activating descending inhibitory pathways from the dorsal periaqueductal gray area of the midbrain (dPAG). In addition to hypoalgesic and sympathoexcitatory effects, stimulation of the dPAG in animals has been shown to hal e a facilitatory effect on motor activity. This study sought to further investigate the proposal regarding SMT and the FAG by including a test of motor function in addition to the variables previously investigated, Using a condition randomised, placebo-controlled, double blind, repeated measures design, 30 subjects with mid to lon er cervical spine pain of insidious onset participated in the study. The results indicated that the cervical mobilisation technique produced a hypoalgesic effect as revealed by increased pressure pain thresholds on the side of treatment (P = 0.0001) and decreased resting visual analogue scale scores (P = 0.049). The treatment technique also produced a sympathoexcitatory effect with an increase in skin conductance (P < 0.002) and a decrease in skin temperature (P = < 0.02). There was a decrease in superficial neck flexor muscle activity (P < 0.0002) at the lower levels of a staged cranio-cervical flexion test. This could imply facilitation of the deep neck flexor muscles with a decreased need for co-activation of the superficial neck flexors, The combination of all findings,would support the proposal that SMT may, at least initially, exert part of its influence via activation of the PAG, (C) 2000 Harcourt Publishers Ltd.

Unprecedented oxidation of a biologically active aroylhydrazone chelator catalysed by iron(III): serendipitous identification of diacylhydrazine ligands with high iron chelation efficacy

Ligands of the 2-pyridylcarbaldehyde isonicotinoylhydrazone class show high iron (Fe) sequestering efficacy and have potential as agents for the treatment of Fe overload disease. We have investigated the mechanisms responsible for their high activity. X-ray crystallography studies show that the tridentate chelate 2-pyridylcarbaldehyde isonicotinoylhydrazone undergoes an unexpected oxidation to isonicotinoyl(picolinoyl)hydrazine when complexed with Fe-III. In contrast, in the absence of Fel the parent hydrazone is not oxidized in aerobic aqueous solution. To examine whether the diacylhydrazine could be responsible for the biological effects of 2-pyridylcarbaldehyde isonicotinoylhydrazone, their Fe chelation efficacy was compared. In contrast to its parent hydrazone, the diacylhydrazine showed little Fe chelation activity. Potentiometric titrations suggested that this might be because the diacylhydrazine was charged at physiological pH, hindering its access across membranes to intracellular Fe pools. In contrast, the Fe complex of this diacylhydrazine was charge neutral, which may allow facile movement through membranes. These data allow a model of Fe chelation for this compound to be proposed: the parent aroylhydrazone diffuses through cell membranes to bind Fe and is subsequently oxidized to the diacylhydrazine complex which then diffuses from the cell. Other diacylhydrazine analogues that were charge neutral at physiological pH demonstrated high Fe chelation efficacy. Thus, for this class of ligands, the charge of the chelator appears to be an important factor for determining their ability to access intracellular Fe. The results of this study are significant for understanding the biological activity of 2-pyridylcarbaldehyde isonicotinoylhydrazone and for the design of novel diacylhydrazine chelators for clinical use.

Clinically significant drug interactions with agents specific for migraine attacks

The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-MT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When egopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.

The preparation of reach to grasp movements in adults with Down syndrome

The aim of this study was to determine the extent to which adults with Down syndrome (DS) are able to utilise advance information to prepare reach to grasp movements. The study comprised ten adults with DS; ten children matched to an individual in the group with DS on the basis of their intellectual ability, and twelve adult controls. The participants used their right hand to reach out and grasp illuminated perspex blocks. Four target blocks were positioned on a table surface, two to each side of the midsagittal plane. In the complete precue condition, participants were provided with information specifying the location of the target. In the partial precue condition, participants were given advance information indicating the location of the object relative to the midsagittal plane (left or right). In the null condition, advance information concerning the position of the target object was entirely ambiguous. It was found that both reaction times and movement times were greater for the participants with DS than for the adults without DS. The reaction times exhibited by individuals with DS in the complete precue condition were lower than those observed in the null condition, indicating that they had utilised advance information to prepare their movements. In the group with DS, when advance information specified only the location of the target object relative to the midline, reaction times were equivalent to those obtained when ambiguous information was given. In contrast, the adults without DS exhibited reaction times that were lower in both the complete and partial precue conditions when compared to the null condition. The pattern of results exhibited by the children was similar to that of the adults without DS. The movement times exhibited by all groups were not influenced by the precue condition. In summary, our findings indicate that individuals with DS are able to use advance information if it specifies precisely the location of the target object in order to prepare a reach to grasp movement. The group with DS were unable, however, to obtain the normal advantage of advance information specifying only one dimension of the movement goal (i.e., the position of an object relative to the body midline). (C) 2001 Elsevier Science B.V. All rights reserved.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.