Idoxifene, a novel selective estrogen receptor modulator, is effective in a rat model of adjuvant-induced arthritis.
(33/1643)
Idoxifene, a selective estrogen receptor modulator, was evaluated in male and female rats with adjuvant-induced arthritis (AA). AA was induced in Lewis rats with Mycobacterium butyricum in paraffin oil injected into the base of the tail, and the animals were treated with idoxifene prophylactically (days 0-21) or therapeutically (days 10-21). Efficacy was determined by measurements of paw inflammation, bone mineral content, and bone mineral density (BMD) with dual X-ray absorptiometry and by histological evaluation. Serum interleukin-6 levels were measured as a marker of the anti-inflammatory effects of the compound. Estrogen was included for comparison and was administered at 5 mg/kg, three times a week s.c. Prophylactic treatment of male AA rats with idoxifene at 10, 3, and 1 mg/kg and estrogen at 5 mg/kg significantly inhibited paw inflammation. There was improved joint integrity measured by BMD and reduced serum interleukin-6 levels in animals treated with 10 mg/kg/day idoxifene. Idoxifene and estrogen were as effective for AA in female Lewis rats as in male rats, significantly inhibiting paw inflammation and improving BMD. Histological evaluation of the tibiotarsal joints of female rats treated with 10 mg/kg showed protection of bone, cartilage, and soft tissue. Therapeutic treatment with either idoxifene or estrogen (starting on day 10 of disease) of male and female Lewis rats also was effective in reducing paw inflammation in these animals, although the effect was much less than that observed with the prophylactic dosing protocol. (+info)
Change of footwear insulation at various sweating rates.
(34/1643)
Moisture inside the footwear can considerably affect the thermal insulation. In this study with a thermal foot model there was simulated three sweat rates (3, 5 and 10 g/h). Five types of footwear with various insulation levels (dry insulation from 0.19 to 0.50 m2. K/W) were tested. The footwear insulation reduction was calculated for 1.5 hour period. The reduction in insulation was related to sweating rate and initial insulation. The footwear with high insulation lost even in percentile more insulation than thin boots under the same conditions (9-19% at 3 g/h, 13-27% at 5 g/h and 19-36% at 10 g/h). A relationship between insulation decrease and sweating rate was established. An 8-hour sweating test (5 g/h) and a test for determining evaporative heat, losses were carried out in addition. The insulation reduction during the first 1.5 hours of the 8-hour test answered for more than half of the total reduction. (+info)
Coincident development of sesamoid bones and clues to their evolution.
(35/1643)
Sesamoid bones form within tendons in regions that wrap around bony prominences. They are common in humans but variable in number. Sesamoid development is mediated epigenetically by local mechanical forces associated with skeletal geometry, posture, and muscular activity. In this article we review the literature on sesamoids and explore the question of genetic control of sesamoid development. Examination of radiographs of 112 people demonstrated that the relatively infrequent appearances of the fabella (in the lateral gastrocnemius tendon of the knee) and os peroneum (in the peroneus longus tendon of the foot) are related within individuals (P < 0.01). This finding suggests that the tendency to form sesamoids may be linked to intrinsic genetic factors. Evolutionary character analyses suggest that the formation of these sesamoids in humans may be a consequence of phylogeny. These observations indicate that variations of intrinsic factors may interact with extrinsic mechanobiological factors to influence sesamoid development and evolution. (+info)
Coordinated ground forces exerted by buttocks and feet are adequately programmed for weight transfer during sit-to-stand.
(36/1643)
The purpose of this study was to test the hypothesis whether weight transfer during sit-to-stand (STS) is the result of coordinated ground forces exerted by buttocks and feet before seat-off. Whole-body kinematics and three-dimensional ground forces from left and right buttock as well as from left and right foot were recorded for seven adults during STS. We defined a preparatory phase from onset of the first detectable anterior/posterior (A/P) force to seat-off (buttock forces fell to 0) and a rising phase from seat-off to the decrease of center of mass (CoM) vertical velocity to zero. STS was induced by an increase of vertical and backward directed ground forces exerted by the buttocks that significantly preceded the onset of any trunk movement. All ground forces peaked before or around the moment of seat-off, whereas all kinematic variables, except trunk forward rotation and hip flexion, peaked after seat-off, during or after the rising phase. The present study suggests that the weight transfer from sit to stand is induced by ground forces exerted by buttocks and feet before seat-off, i.e., during the preparatory phase. The buttocks generate the isometric "rising forces," e.g., the propulsive impulse for the forward acceleration of the body, while the feet apply adequate damping control before seat-off. This indicates that the rising movement is a result of these coordinated forces, targeted to match the subject's weight and support base distance between buttocks and feet. The single peaked, bell-shaped profiles peaking before seat-off, were seen beneath buttocks for the "rising drive," i.e., between the time of peak backward directed force and seat-off, as well as beneath the feet for the "damping drive," i.e., from onset to the peak of forward-directed force and for CoM A/P velocity. This suggests that both beginning and end of the weight transfer process are programmed before seat-off. The peak deceleration of A/P CoM took place shortly ( approximately 100 ms) after CoM peak velocity, resulting in a well controlled CoM deceleration before seat-off. In contrast to the view of other authors, this suggests that body equilibrium is controlled during weight transfer. (+info)
Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ.
(37/1643)
The effect of intrathecal nocistatin on formalin-induced pain in mice was investigated and compared with that of nociceptin/orphanin FQ (Noc/OFQ) to get information on the functional relationship between nocistatin and Noc/OFQ in the spinal cord. Subcutaneous injection of formalin into the hindpaw induced biphasic pain behaviors. Nocistatin, 1 pg, given intrathecally 1 min before 2% formalin injection, significantly attenuated the first phase of the formalin-induced pain. Also, 10 to 1000 pg of nocistatin, given 10 min after formalin injection, significantly inhibited the second phase of the formalin test. Naloxone, 5 mg/kg i.p., failed to antagonize inhibitory effects of nocistatin on either phase of the formalin-induced pain, indicating that analgesic effects of nocistatin were unrelated to the classic opioid system. At 1 to 100 pg, Noc/OFQ exerted no influence on either phase of the 2% formalin-induced pain. However, at 1% formalin, Noc/OFQ significantly aggravated the second phase at 10 pg but not the first phase at 1 to 1000 pg. This aggravating effect of Noc/OFQ was completely reversed by 10 pg of nocistatin. At 0.3 and 1 microg, Noc/OFQ, but not nocistatin, significantly inhibited both phases of the 2% formalin-induced pain. Suppressive effects of 1 microg of Noc/OFQ on the formalin-induced pain were not affected by 1 microg of nocistatin. These results suggest that Noc/OFQ might be involved in the second phase of the mouse formalin test and that, under such pathophysiological conditions, nocistatin could exhibit antagonism against Noc/OFQ at the spinal level. (+info)
Interaction between tumor necrosis factor microsatellite polymorphisms and the HLA-DRB1 shared epitope in rheumatoid arthritis: influence on disease outcome.
(38/1643)
OBJECTIVE: To investigate whether interactions between tumor necrosis factor (TNF) microsatellite polymorphisms and the HLA-DRB1 shared epitope (SE) are associated with disease severity in rheumatoid arthritis (RA), and to determine if such associations are the same in male and female patients. METHODS: Genotyping for the TNFa microsatellite and HLA-DRB1 was carried out on 157 RA patients with established disease (duration >5 years). Disease severity measures included radiographic damage (the Larsen method), functional assessment by the Health Assessment Questionnaire, history of joint surgery, and global appraisal of outcome by means of a visual analog scale score. The association of severity measures with TNFa microsatellite polymorphisms stratified by SE status, and the interaction between TNFa and the SE, were investigated using stratified analyses and multiple or logistic regression analyses. RESULTS: No significant associations were observed between any single TNFa microsatellite polymorphism and disease severity, although preliminary evidence for an interaction between TNFa6 and TNFa11 was obtained. In the presence of the SE, a significantly worse outcome was associated with individuals carrying TNFa6, and a significant interaction (P = 0.04-0.006) was found between these alleles for all the outcome measures examined except history of joint surgery. In the absence of the SE, the TNFa6 allele was associated with significantly better outcome scores. When examined by sex, significant associations between the TNFa6/SE haplotype and disease outcome measures were found only in females. No statistically significant interactions were found in males, although the TNFa6/SE haplotype was still associated with the worst outcome scores. CONCLUSION: The association of the SE with disease severity in RA is influenced by an interaction with the TNFa6 microsatellite polymorphism. This interaction appears to be acting predominantly in female patients, although the trend is similar in the smaller percentage of males carrying the TNFa6/SE haplotype. (+info)
Postural synergies associated with a stepping task.
(39/1643)
BACKGROUND AND PURPOSE: Synergistic relationships among multiple muscle components are thought to exist to simplify control of posture and movement. The purpose of this study was to examine the extent to which children, young adults, and older adults exhibit consistent sequences of postural muscle activation when lifting the right foot onto a step from a standing position. SUBJECTS: Twenty subjects without known impairments of the neuromuscular system (10 male, 10 female) in each of 3 age groups--children (8-12 years), young adults (25-35 years), and older adults (65-73 years)--participated. METHODS: A pressure switch taped to the subject's right foot was used to determine movement onset and offset. Latencies of muscle activation were determined using surface electromyography. A preferred postural synergy was defined as the sequence of postural muscle activation observed during the majority of trials for each subject. RESULTS: Mean movement times did not differ among age groups. Although the left tibialis anterior (TA) muscle was the first of the postural muscles activated in 93% of the trials, subjects displayed considerable variability in the subsequent order of postural muscle activation. Across subjects, a total of 14 different preferred postural synergies were observed. Age groups did not differ in the number of different synergies. CONCLUSION AND DISCUSSION: Early TA activation may reflect biomechanical constraints of the stepping task, producing forward displacement of the center of mass over the changing base of support. The fact that subjects of all ages were quite variable in the specific sequences of muscles activated subsequent to the TA suggests that, for this type of task, therapists should not focus their interventions on facilitating execution of particular synergy patterns. (+info)
Local anaesthetic effect of topical amethocaine gel in neonates: randomised controlled trial.
(40/1643)
AIM: To assess the efficacy of amethocaine as a topical local anaesthetic in neonates. METHODS: A randomised, double blind controlled trial compared 4% amethocaine gel (Ametop) with placebo in 60 healthy neonates (29 to 42 weeks of gestation) in the first week after birth. Either 1.5 g 4% w/w amethocaine (gel) or 1.5 g placebo gel were applied to the dorsum of one foot. No gel was applied to the other foot. Each foot was occluded and left for one hour. Local anaesthesia was then assessed by eliciting the cutaneous withdrawal reflex in response to stimulation with a series of graded nylon filaments (von Frey hairs). The reflex was first elicited from the control and then the treated foot. The difference in filament thickness and deforming weight required to elicit the reflex was recorded. RESULTS: In infants treated with amethocaine, 17 of 31 (54. 8%) showed evidence of local anaesthetic action compared with five of 29 (17.2%) in the placebo group (p=0.003). The mean difference in deforming weight required to elicit the reflex was 18.8 g in the amethocaine group compared with 3.9 g in the placebo group (p=0.02). The apparent local anaesthetic action of the placebo can be explained by habituation to repeated stimulation. CONCLUSIONS: It is concluded that topical amethocaine gel has a local anaesthetic action on neonatal skin which merits further investigation. An effective and safe surface local anaesthetic would be valuable for the relief of procedure related pain in neonates. (+info)