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Motor Effects (motor + effects)
Selected AbstractsWould the elderly be better off if they were given more placebos?GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2010E Paul Cherniack Placebos are useful in the medical care of the elderly, although the exact definition of a "placebo" or "placebo effect" is difficult to define precisely. They have an important role as control treatments in research trials, but a non-specific "placebo effect" may also be beneficial part of many physician,patient interactions. Physicians also give them deliberately according to several studies worldwide to satisfy patient demands or because they believe in a "placebo effect" among other reasons. A significant placebo effect has been observed among older patients in clinical trials of antidepressants (12,15%), and in treatments of Parkinson's disease (16%). Placebos activate serotonergic pathways in the brain used by antidepressants. In Parkinson's disease, the administration of a placebo stimulates dopamine release in the dorsal (resulting in motor effects) and ventral striatum (which influences expectation of reward). Much of our understanding of the placebo effect comes from studies of placebo analgesia which is influenced by conditioning, expectation, meaning and context of the treatment for the patient, and patient,physician interaction. It is anatomically medicated by brain opioid pathways. Response to "sham" acupuncture in osteoarthritis may be an example of its use in the elderly. Placebos have often been considered a deception and thus unethical. On the other hand, some physicians and ethicists have suggested conditions for appropriate uses for placebos. A placebo might offer the theoretical advantage of an inexpensive treatment that would not cause adverse drug reactions or interactions with other medications, potentially avoiding complications of polypharmacy. [source] Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR3IGF-I on rat isolated ileum following abdominal irradiationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2000R Fraser Abstract Background and Aims: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. Methods: Intestinal motor activity was recorded from 6,8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system. Results: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals. Conclusions: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis. [source] Effect of estradiol on striatal dopamine activity of female hemiparkinsonian monkeysJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2009Marc Morissette Abstract A higher prevalence and incidence of Parkinson's disease is observed in men, and beneficial motor effects of estrogens are observed in parkinsonian women. In rodents, an effect of estradiol on dopamine systems is documented, whereas much less is known in monkeys. Enkephalin was shown to exert a compensatory modulatory effect on the denervated dopamine nigrostriatal pathway in monkeys and in humans. Moreover in rodents, striatal preproenkephalin mRNA is increased by estrogen treatment. Hence, we investigated the responsiveness of striatal dopamine to estradiol in long-term ovariectomized monkeys bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic parkinsonian postmenopausal women. Seven ovariectomized female monkeys received a unilateral MPTP lesion; 4 years after ovariectomy, three received 1-month treatment with 17,-estradiol and the others received vehicle. The lesioned striata showed extensive denervation in all monkeys as measured with dopamine and metabolite concentrations assayed by high-performance liquid chromatography and by autoradiography of the dopamine transporter. The lesioned and intact striata of estradiol-treated monkeys had increased 3-methoxytyramine, and lesioned putamen increased dopamine concentrations compared with vehicle-treated monkeys. Estradiol treatment increased the dopamine transporter in subregions of the intact caudate and putamen compared with the intact striata of vehicle-treated monkeys, but not in the lesioned striata. Preproenkephalin mRNA levels measured by in situ hybridization were increased in the lesioned striata of vehicle treated monkeys and were not further enhanced in estradiol-treated monkeys. These results show that long after ovariectomy, modeling postmenopausal hormonal conditions, brain dopamine metabolism, and transporter are still responsive to estradiol. © 2008 Wiley-Liss, Inc. [source] Genetic polymorphism of catechol- O -methyltransferase and levodopa pharmacokinetic,pharmacodynamic pattern in patients with Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2005Manuela Contin PharmD Abstract We explored the potential effect of catechol- O -methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson's disease (PD). We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half-life, and the area under the plasma concentration,time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect,time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low-activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate-activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high-activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic,pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic,pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society [source] Tolterodine causes measurable restoration of urethral sensation in women with urge urinary incontinence,,NEUROUROLOGY AND URODYNAMICS, Issue 4 2010Kimberly Kenton Abstract Introduction & Hypothesis Determine if treatment of urge incontinence with tolterodine results in changes in bladder and/or urethral sensation using Current Perception Threshold (CPT) testing. Methods Women with ,1 incontinence episode on 7-day diary were treated with 4 mg of long-acting tolterodine for 2-months. At baseline and 2-months, participants had CPT testing of the urethral and bladder at 3 frequencies 2000, 250, and 5 Hz. Baseline and post-treatment measures were compared using Wilcoxon Signed Rank Test. Results Seventeen women underwent baseline CPT testing. Four discontinued medication due to side effects and did not have repeated testing. Urethral CPT at 250 Hz was lower after treatment (median 1.3 [Interquartile range .69--2.1] and .75 [.45--1.2], p,=,.003) and at 5 Hz trended toward a significant decrease (1.1 [1--1.9] and .84 [.32--1.1], p,=,.06). Conclusions Urethral sensitivity improves after 2-months of tolterodine, suggesting it may restore urethral sensory nerves in addition to known motor effects. Neurourol. Urodynam. 29:555,557, 2010. © 2009 Wiley-Liss, Inc. [source] Anaesthesia and saccadic eye movementsANAESTHESIA, Issue 9 2000O. A. Khan During the last 10 years, there has been a vast increase in day-case surgery under general anaesthesia, but this has not been accompanied by research into the residual cognitive and motor effects during recovery from anaesthesia. Part of the explanation for this phenomenon is the lack of a suitable biophysical monitor of anaesthetic sedation. This review discusses one of the most commonly used of these biophysical monitors , namely saccadic eye movements. In particular, the efficacy of peak saccadic velocity as a monitor of sedation will be evaluated. In addition, the physiology and pharmacology of saccadic eye movements will be discussed within the context of developing other parameters of saccadic eye movements as novel biophysical monitors of anaesthetic sedation. [source] Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labourBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 3 2006BA Houtzager Objective, To compare the long-term psychosocial and motor effects on children exposed in utero to nifedipine or ritodrine for the management of preterm labour. Design, Randomised controlled trial. Setting, Multicentre study in two university and one primary hospital in the Netherlands. Population, In the original trial, 185 women were randomised to either nifedipine (n= 95) or ritodrine (n= 90). Of the 185 liveborn children, 171 survived (92%), and of these 102 (61%) were followed up at age 9,12 years. Methods, Age-specific questionnaires were administered to the parent and teacher. Additional data were obtained from medical records. Main outcome measures, Questionnaires were used to assess the child's behavioural,emotional problems, quality of life (QoL), motor functioning, parenting distress and the child's education. Results, Of the 171 eligible families, 102 (61%) agreed to participate and completed the questionnaires. Response was equal in the ritodrine group (n= 54 of 83 surviving children, 65%) compared with the nifedipine group (n= 48 of 88 surviving children, 55%). After controlling for differing perinatal characteristics at birth, no significant differences between the groups were detected with respect to long-term behaviour,emotional outcome, QoL, education, motor functioning or parenting distress. Psychosocial outcome was slightly better in the nifedipine group. Conclusions, The results do not support any differential postnatal effect of the tocolytic agents ritodrine or nifedipine on the child's long-term psychosocial and motor functioning. The slightly better outcome of children randomised in the nifedipine group is most likely due to more favourable perinatal outcomes in this group. These results merit further investigation in a larger group of survivors. [source] Role of NK1 and NK2 receptors in mouse gastric mechanical activityBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2006Flavia Mulè The aim of the present study was to examine the role of NK1 and NK2 receptors in the control of mechanical activity of mouse stomach. In this view, the motor effects induced by NK1 and NK2 receptor agonists and antagonists were analyzed, measuring motility as intraluminal pressure changes in mouse-isolated stomach preparations. In parallel, immunohistochemical studies were performed to identify the location of NK1 and NK2 receptors on myenteric neurons and smooth muscle cells. Substance P (SP) induced biphasic effects: a contraction followed by relaxation; neurokinin A (NKA) and [, -Ala8]-NKA(4,10), selective agonist of NK2 receptors, evoked concentration-dependent contractions, whereas [Sar9, Met(O2)11]-SP, selective agonist of NK1 receptors, induced concentration-dependent relaxation. SR48968, NK2 receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation. SR140333, NK1 receptor antagonist, did not modify the spontaneous activity and antagonized the relaxant response to tachykinins, failing to affect the contractile effects. The relaxation to SP or to [Sar9, Met(O2)11]-SP was abolished by tetrodotoxin (TTX) and significantly reduced by N -nitro- L -arginine methyl ester (L -NAME). NK2 -immunoreactivity (NK2 -IR) was seen at the level of the smooth muscle cells of both circular and longitudinal muscle layers. NK1 -immunoreactive (NK1 -IR) neurons were seen in the myenteric ganglia and NK1/nNOS double labeling revealed that some neurons were both NK1 -IR and nNOS-IR. These results suggest that, in mouse stomach, NK1 receptors, causing relaxant responses, are present on nitrergic inhibitory myenteric neurons, whereas NK2 receptors, mediating contractile responses, are present at muscular level. British Journal of Pharmacology (2006) 147, 430,436. doi:10.1038/sj.bjp.0706645 [source] A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injuryBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2004Wei-Ping Wu Nitric oxide (NO) participates, at least in part, to the establishment and maintenance of pain after nerve injury. Therefore, drugs that target the NO/cGMP signaling pathway are of interest for the treatment of human neuropathic pain. Various compounds endowed with NO-releasing properties modulate the expression and function of inducible nitric oxide synthase (iNOS), the key enzyme responsible for sustained NO production under pathological conditions including neuropathic pain. With this background, we synthesized a new chemical entity, [1-(aminomethyl)cyclohexane acetic acid 3-(nitroxymethyl)phenyl ester] NCX8001, which has a NO-releasing moiety bound to gabapentin, a drug currently used for the clinical management of neuropathic pain. We examined the pharmacological profile of this drug with respect to its NO-releasing properties in vitro as well as to its efficacy in treating neuropathic pain conditions (allodynia) consequent to experimental sciatic nerve or spinal cord injuries. NCX8001 (1,30 ,M) released physiologically relevant concentrations of NO as it induced a concentration-dependent activation of soluble guanylyl cyclase (EC50=5.6 ,M) and produced consistent vasorelaxant effects in noradrenaline-precontracted rabbit aortic rings (IC50=1.4 ,M). NCX8001, but not gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide-induced overexpression and function of iNOS in RAW264.7 macrophages cell line. Furthermore, NCX8001 also inhibited the release of tumor necrosis factor alpha (TNF,) from stimulated RAW264.7 cells. NCX8001 (28,280 ,mol kg,1, i.p.) reduced the allodynic responses of spinal cord injured rats in a dose-dependent fashion while lacking sedative or motor effects. In contrast, gabapentin (170,580 ,mol kg,1, i.p.) resulted less effective and elicited marked side effects. NCX8001 alleviated the allodynia-like responses of rats to innocuous mechanical or cold stimulation following lesion of the sciatic nerve. This effect was not shared by equimolar doses of gabapentin. Potentially due to the slow releasing kinetics of NO, NCX8001 alleviated pain-like behaviors in two rat models of neuropathic pain in a fashion that is superior to its parent counterpart gabapentin. This new gabapentin derivative, whose mechanism deserves to be explored further, offers new hopes to the treatment of human neuropathic pain. British Journal of Pharmacology (2004) 141, 65,74. doi:10.1038/sj.bjp.0705596 [source] | ||||||||||