Objectively measured physical activity is associated with dorsolateral prefrontal cortex volume in older adults.

BACKGROUND: Epidemiological studies suggest physical activity (PA) can slow or prevent both cognitive decline and age-related atrophy in frontal and hippocampal gray matter volumes. However, much of this evidence is based on self-reported measures of PA. METHODS: PA was measured objectively with a SenseWear™ Armband to examine the cross-sectional associations between the duration of light, moderate and vigorous intensity PA with gray matter volume in the dorsolateral prefrontal cortex (DLPFC) and hippocampus in 167 (female: 43%) cognitively healthy older adults aged 73 to 78. RESULTS: The duration of objective moderate to vigorous intensity physical activity (MVPA) was associated with a greater volume of the right DLPFC (ߠ​= â€‹0.16; p â€‹= â€‹0.04). In addition, objective moderate-intensity PA alone was also associated with greater volume of the left (ߠ​= â€‹0.17; p â€‹= â€‹0.03) and right (ߠ​= â€‹0.19; p â€‹= â€‹0.01) DLPFC after controlling for covariates and adjustment for multiple comparisons. In contrast, there were no significant associations between light- or vigorous-intensity PA and gray matter volumes (all p â€‹> â€‹0.05). No associations between PA and cognitive performance were detected, and self-reported PA was not associated with any of the outcomes investigated. CONCLUSIONS: These findings suggest that an intensity-dependent relationship may exist, whereby a greater duration of MVPA, perhaps driven by moderate-intensity PA, is associated with preserved gray matter volume in frontal regions of the brain. Future research should investigate the mechanisms of this dose-effect and determine whether greater brain volumes associated with objective PA convey protective effects against cognitive decline.

Can the intensity of physical activity be accurately measured in older adults using questionnaires?

OBJECTIVES: This study assessed the accuracy of two questionnaires for measuring the duration of physical activity (PA) by intensity compared to an objective measure in older adults. DESIGN: Cross-sectional observation METHODS: A total of 169 (female=43.8%) participants aged 73-78 years (mean: 75.1 y; SD: 1.3) wore a SenseWear™ Armband (SWA) for seven-days and reported the duration of PA by intensity with a Physical Activity Recall (PAR) questionnaire and the Active Australia Survey (AAS). In addition, the duration of moderate-to-vigorous-PA (MVPA) and overall active time, weighted for intensity (Total PA; MET: min/week) was assessed. Univariate general linear models were used to compare the questionnaire and SWA measures of PA while controlling for age, sex and education. RESULTS: The PAR was associated with SWA moderate intensity PA (b=0.19; 95% CI 0.03-0.35), MVPA (b=0.19; 95% CI 0.02-0.37) and Total PA (b=0.33; 95% CI 0.11-0.55). Although significant correlations were present, the models explained a small proportion of the variance in the SWA variables. The AAS was not associated with the SWA for any PA outcome. There was also significant under-reporting of PA duration for both questionnaires in comparison to the SWA. CONCLUSIONS: The PAR questionnaire may be suitable for determining the effect of greater levels of PA on health outcomes. However, neither questionnaire can be considered valid in determining the duration of PA divided by intensity. In addition, questionnaire and objectively measured PA are not equivalent and absolute measures of PA derived from questionnaires should be interpreted with caution.

Cognition in breast cancer survivors: A pilot study of interval and continuous exercise.

OBJECTIVES: The current study investigated the effects of two exercise interventions on cognitive function amongst breast cancer survivors. DESIGN: Pilot randomised-controlled trial. METHODS: Seventeen female cancer survivors (mean: 62.9±7.8years) were randomised into three groups: high-intensity interval training (HIIT, n=6); moderate-intensity continuous training (MOD, n=5); or wait-list control (CON, n=6). The HIIT and MOD groups exercised on a cycle ergometer 3days/week for 12-weeks. Primary outcomes were cognitive function assessments utilising CogState. Secondary outcomes were resting middle cerebral artery blood flow velocity, cerebrovascular reactivity and aerobic fitness (VO2peak). Data were analysed with General Linear Mixed Models and Cohen's d effect sizes were calculated. RESULTS: All 17 participants who were randomised were available for follow-up analysis and adherence was similar for HIIT and MOD (78.7±13.2% vs 79.4±12.0%; p=0.93). Although there were no significant differences in the cognitive and cerebrovascular outcomes, HIIT produced moderate to large positive effects in comparison to MOD and CON for outcomes including episodic memory, working memory, executive function, cerebral blood flow and cerebrovascular reactivity. HIIT significantly increased VO2peak by 19.3% (d=1.28) and MOD had a non-significant 5.6% (d=0.72) increase, compared to CON which had a 2.6% decrease. CONCLUSIONS: This study provides preliminary evidence that HIIT may be an effective exercise intervention to improve cognitive performance, cerebrovascular function and aerobic fitness in breast cancer survivors. Considering the sample size is small, these results should be confirmed through larger clinical trials.

Comparison of Body Composition Assessment Methods in Professional Urban Firefighters.

Given the importance of body composition in maintaining optimal physical and functional capacities, the use of appropriate, field-based assessment tools should be a priority to assist in maintaining the occupational safety of firefighters and the community. For ease, body mass index has often been used to assess these changes. However, it is limited in its accuracy. The purposes of this study were twofold: (a) to compare the validity of different measures of body composition against dual-energy X-ray absorptiometry (DXA) in urban firefighters and (b) to assess these measures in their ability to provide meaningful interpretation of criteria-driven categories of adiposity. A total of 64 male firefighters (age = 44.0 ± 9.5 years) underwent full anthropometric profiling (predictor equations used to determine body fat percentage [BF%]), bioelectrical impedance analysis (BIA), and DXA assessments. Participants' body mass index was calculated, and BF% and lean mass were determined along with criteria-driven categorizations of adiposity. Anthropometric (skinfolds) predictor equations (e.g., mean bias = -4.4% for BF%) were typically closer to DXA measures, compared with BIA (9.4% for BF%). However, when determining categories of criteria-driven adiposity, BIA (42.9% overweight or obese) provided closer estimates to the DXA-determined distribution (44.6%) than anthropometric-based measures (up to 40%). Body mass index appears an inappropriate measure for accurately determining categories of adiposity with 64.1% classified as overweight or obese. Given the logistical constraints of anthropometric profiling, and the closeness of BIA to DXA in adiposity categories, BIA may be a suitable alternative to DXA for assessing body composition in professional urban firefighters.

Compression garments and cerebral blood flow: Influence on cognitive and exercise performance.

This study aimed to describe the effect of compression garments on middle cerebral artery blood flow velocity (MCAv) in relation to cognitive and exercise performance whilst cycling. In a randomised-controlled-cross-over design, 15 well-trained male cyclists were recruited to participate in three identical trials wearing loose fitting shorts (control), low-grade, or medium-grade compression garments. The protocol involved four 8 min increments of cycling at 30%, 50%, 70%, and 85% maximal power output and a 4 km time-trial. Participants undertook a cognitive Stroop task at baseline and at the midpoint of each increment. MCAv was monitored with Transcranial Doppler Ultrasonography. Mean arterial pressure (MAP) and partial pressure of end-tidal CO2 (PetCO2) were measured throughout. MCAv, MAP, PetCO2, and reaction time of the complex Stroop task were influenced by exercise intensity, but not compression garments. Compression garments significantly affected cognitive accuracy in the complex Stroop task such that low-grade compression appeared to enhance cognitive accuracy in comparison to the control condition at the highest intensity (p = .010). Time-trial performance did not differ between the control (338.0 ± 17.3 s), low-grade (338.7 ± 18.7 s), or medium-grade (342.2 ± 19.3 s) conditions (p = .114). Compression garments did not affect MCAv during exercise or time-trial performance, but compression may be beneficial for improved cognitive accuracy during high-intensity exercise. Further research is required to elucidate the potential impact on cognitive performance.

Middle cerebral artery blood flow velocity during a 4 km cycling time trial.

PURPOSE: This study sought to describe middle cerebral artery blood flow velocity (MCAv) during a 4 km cycling time trial, and relate it to different pacing strategies adopted by participants. METHODS: After familiarisation and a standardised exercise protocol, 15 male trained cyclists rode a 4 km time trial on a cycling ergometer. MCAv was assessed via transcranial Doppler ultrasound in the right hemisphere at resting baseline, and throughout the time trial. Mean arterial pressure, end-tidal partial pressure of carbon dioxide (PetCO2) and heart rate were assessed alongside MCAv. Plasma lactate was assessed post time trial. Data were compared depending upon whether participants completed the time trial with a positive (first half faster than the last) or negative pacing profile although there was no difference in the time to completion with either pacing strategy (positive 344 ± 23 s, negative 334 ± 14 s; p = 0.394). RESULTS: Lower mean MCAv (positive pacing -7.6 ± 14.2%, negative pacing +21.2 ± 15.0% compared to resting baseline measures; p = 0.004) and lower PetCO2 (significant interaction p < 0.001) towards the end of the time trial were observed with positive compared to negative pacing. Heart rate and lactate did not differ between pacing strategies. CONCLUSIONS: Changes in MCAv appear to depend on the pacing strategy adopted, with a positive pacing strategy likely to contribute to a hyperventilatory drop in PetCO2 and subsequent reduction in MCAv. Although lower cerebral blood flow cannot be directly linked to an inability to raise or maintain power output during the closing stages of the time trial, this potential contributor to fatigue is worth further investigation.

The Relationship Between Subjective Falls-Risk Assessment Tools and Functional, Health-Related, and Body Composition Characteristics.

We sought to explore the relationship between two subjective falls-risk assessment tools (Falls Efficacy Scale-International [FES-I] and Activities-Specific Balance Confidence [ABC] Scale) and functional, health-related, and body composition characteristics. A total of 245 community-dwelling people aged 60 to 88 years underwent assessments for subjective falls risk (using the FES-I and ABC Scale), health-related (cognitive; Short-Form Health Survey [SF-12]), functional (physical activity and physical function), and body composition characteristics (measured by dual X-ray absorptiometry). The FES-I and ABC Scale are strongly correlated with each other for females and males ( r = -.70, p < .001; r = -.65, p < .001), respectively. There are substantial differences between males and females when they self-assess their risk of falling as well as what characteristics contribute to explaining these self-assessments. Females are potentially more self-aware of their functional, body composition and health-related characteristics to better estimate their own risk of falling. FES-I correlates better with functional, body composition, and health-related characteristics, and thus may be more appropriate for use than the ABC in community-dwelling older adults.

Electronic Cigarette Exposure: Calls to Wisconsin Poison Control Centers, 2010­2015.

BACKGROUND: E-cigarettes are battery-powered devices that deliver nicotine and flavorings by aerosol and have been marketed in the United States since 2007. Because e-cigarettes have increased in popularity, toxicity potential from device misuse and malfunction also has increased. National data indicate that during 2010­2014, exposure calls to US poison control centers increased only 0.3% for conventional cigarette exposures, whereas calls increased 41.7% for e-cigarette exposures. METHODS: We characterized cigarette and e-cigarette exposure calls to the Wisconsin Poison Center January 1, 2010 through October 10, 2015. We compared cigarette and e-cigarette exposure calls by exposure year, demographic characteristics, caller site, exposure site, exposure route, exposure reason, medical outcome, management site, and level of care at a health care facility. RESULTS: During January 2010 to October 2015, a total of 98 e-cigarette exposure calls were reported, and annual exposure calls increased approximately 17-fold, from 2 to 35. During the same period, 671 single-exposure cigarette calls with stable annual call volumes were reported. E-cigarette exposure calls were associated with children aged ≤5 years (57/98, 58.2%) and adults aged ≥20 years (30/98, 30.6%). Cigarette exposure calls predominated among children aged ≤5 years (643/671, 95.8%). CONCLUSION: The frequency of e-cigarette exposure calls to the Wisconsin Poison Center has increased and is highest among children aged ≤5 years and adults. Strategies are warranted to prevent future poisonings from these devices, including nicotine warning labels and public advisories to keep e-cigarettes away from children.

The effect of high and low exercise intensity periods on a simple memory recognition test.

PURPOSE: The purpose of this study was to investigate the effect of variable intensities on a simple memory recognition task during exercise. METHODS: Twenty active participants took part in initial testing, a familiarization trial and then four 60 min cycling interventions in a randomized order. Interventions consisted of no exercise (control), constant exercise at 90% ventilatory threshold (constant) and 2 trials that initially mimicked the constant trial, but then included periods of high (∼90% VO 2 peak ) and low intensities (∼50% VO 2 peak ). Cardiorespiratory measures and capillary blood samples were taken throughout. A short tablet-based cognitive task was completed prior to and during (50 and 55 min into exercise) each intervention. RESULTS: The exercise conditions facilitated response time (p = 0.009), although the extent of this effect was not as strong in the variable exercise conditions (p = 0.011-0.089). High intensity exercise periods resulted in some cognitive regression back towards control trial performance. Elevations in cardiorespiratory measures and periods of hypocapnia could not explain changes in cognitive performance. CONCLUSION: Changes in cognitive performance with variations in exercise intensity are likely to have implications for sport and occupational settings. The timing of cognitive tests to exercise intensity changes as well as use of short cognitive assessments will be important for future work.

The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis.

BACKGROUND: Free radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, which allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking. OBJECTIVE OF REVIEW: To investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction. TYPE OF REVIEW: Systematic review and multicentre, individual patient data meta-analysis. SEARCH STRATEGY: MEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of 'anticoagulants' and 'free flap reconstruction'. EVALUATION METHOD: Studies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta-analysis. RESULTS: Five studies were of adequate quality, and data from four studies (80%) were available for meta-analysis, describing 759 FRFF procedures. Anticoagulants used were as follows: aspirin (12%), low molecular weight dextran (18.3%), unfractioned heparin (28.1%), low molecular weight heparin (49%) and prostaglandin-E1 (2.1%). Thirty-one per cent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap-related complications. CONCLUSIONS: The studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap-related complications. In addition, some anticoagulants may cause systemic complications.

Association between Physical Functionality and Falls Risk in Community-Living Older Adults.

Ageing-related declines in physiological attributes, such as muscle strength, can bring with them an increased risk of falls and subsequently greater risk of losing independence. These declines have substantial impact on an individual's functional ability. However, the precise relationship between falls risk and physical functionality has not been evaluated. The aims of this study were to determine the association between falls risk and physical functionality using objective measures and to create an appropriate model to explain variance in falls risk. Thirty-two independently living adults aged 65-92 years completed the FallScreen, the Continuous-Scale Physical Functional Performance 10 (CS-PFP10) tests, and the 12-Item Short-Form Health Survey (SF-12). The relationships between falls risk, physical functionality, and age were investigated using correlational and multiple hierarchical regression analyses. Overall, total physical functionality accounted for 24% of variance in an individual's falls risk while age explained a further 13%. The oldest-old age group had significantly greater falls risk and significantly lower physical functional performance. Mean scores for all measures showed that there were substantial (but not significant) differences between males and females. While increasing age is the strongest single predictor of increasing falls risk, poorer physical functionality was strongly, independently related to greater falls risk.

Breast cancer local recurrence after breast reconstruction.

The primary aim of surgery in breast cancer is to achieve local control of disease. Secondly, improving quality of life and patient satisfaction is of utmost importance. While the positive effect of postmastectomy reconstruction on the psychological well-being of women with breast cancer has been demonstrated, evidence-based data on its oncological safety remain sparse. There is concern that the presence of autologous tissue or an implant may mask locoregional recurrence. Furthermore, there is little agreement on the appropriateness of routine radiological surveillance of these patients as well as on the surgical treatment of locoregional recurrence. We attempt to review the impact of breast reconstruction on the incidence and detection of locoregional recurrence and discuss treatment options.

Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells.

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), two closely related peptides, initiate their biological responses through their interaction with calcitonin receptor-like receptor (CRLR). The CRLR receptor phenotype can be determined by coexpression of CRLR with one of the three-receptor activity modifying proteins (RAMPs). In this report, we characterized the pharmacological properties of the human or porcine CRLR with individual RAMPs transiently expressed in human embryonic kidney cell line (HEK-293). Characterization of RAMP1/human or porcine CRLR combination by radioligand binding ([125I] halphaCGRP) and functional assay (activation of adenylyl cyclase) revealed the properties of CGRP receptor. Similarly characterization of RAMP2/human or porcine CRLR and RAMP3/human or porcine CRLR combination by radioligand binding ([125I] rADM) and functional assay (activation of adenylyl cyclase) revealed the properties of ADM (22-52) sensitive-ADM receptor. In addition, porcine CRLR/RAMP2 or 3 combination displayed specific high affinity [125I] halphaCGRP binding also. Also, co-transfection of porcine CRLR with RAMPs provided higher expression level of the receptor than the human counterpart. Thus the present study along with earlier studies strongly support the role of RAMPs in the functional expression of specific CRLRs.

Simplifying microvascular head and neck reconstruction: a rational approach to donor site selection.

The purpose of this study was to review the authors' 13-year experience with free tissue transfer for head and neck oncology patients. This study was a retrospective review of 728 free flaps performed in 698 patients. Recipient sites were subdivided by region into the mandible (N = 253), mid face/orbit (N = 190), hypopharynx (N = 134), oral cavity (N = 104), skull base (N = 36), and scalp (N = 11). The overall free flap success rate was 98.6%. Seventy-nine flaps (10.9%) were reexplored for vascular compromise. Ten flaps (1.4%) were lost in their entirety. The overall complication rate was 17.5%. Four donor sites (forearm, fibula, rectus, and jejunum) were used for 92% of the patients. The results of the study confirm the efficacy of free tissue transfer in the reconstruction of oncological head and neck defects. In this series the free forearm, fibula, rectus, and jejunum flaps have become the workhorse donor sites for the vast majority of defects.

Management of radiated reoperative wounds of the cervicothoracic spine: the role of the trapezius turnover flap.

Reoperation for malignant disease of the cervicothoracic spine can lead to compromised wound healing secondary to poor tissue quality from previous operations, heavily irradiated beds, and concomitant steroid therapy. Other complicating factors include exposed dura and spinal implants. Introducing well-vascularized soft tissue to obliterate dead space is critical to reliable wound healing. The purpose of this study was to determine the efficacy of the trapezius turnover flap in the management of these complex wounds. This study is a retrospective review of all patients undergoing trapezius muscle turnover flaps for closure of complex cervicothoracic wounds after spinal operations for metastatic or primary tumors. Six patients (3 male/3 female) were operated over an 18-month period (mean patient age, 43 years). Primary pathologies included radiation-induced peripheral nerve sheath tumor (N = 2), chondrosarcoma (N = 1), nonsmall-cell lung cancer (N = 1), paraganglioma (N = 1), and spindle cell sarcoma (N = 1). Trapezius muscle turnover flaps were unilateral and based on the transverse cervical artery in every patient. Indication for flap closure included inability to perform primary layered closure (N = 3), open wound with infection (N = 2), and exposed hardware (N = 1). All patients had previous operations of the cervicothoracic spine (mean, 5.8 months; range 2-9 months) for malignant disease and prior radiation therapy. Exposed dura was present in all patients, and 2 patients had dural repairs with bovine pericardial patches. Spinal stabilization hardware was present in 4 patients. All patients underwent perioperative treatment with systemic corticosteroids. All flaps survived, and primary wound healing was achieved in each patient. The only wound complication was a malignant pleural effusion communicating with the back wound, which was controlled with a closed suction drain. All wounds remained healed during the follow-up period. Four patients died from progression of disease within 10 months of surgery. The trapezius turnover flap has been used successfully when local tissue conditions prevent primary closure, or in the setting of open, infected wounds with exposed dura and hardware. The ease of flap elevation and minimal donor site morbidity make it a useful, single-stage reconstructive option in these difficult wounds.

Reconstruction of the hypopharynx and cervical esophagus.

Hypopharynx and cervical esophageal defects are challenging problems for the reconstructive surgeon. Prior surgery and radiation therapy contribute to the difficulty in managing these patients. The surgeon must possess a reconstructive algorithm that varies depending on the defect, available donor sites, and his or her experience. The free jejunal flap is the flap used for most of these defects. The radial forearm flap is reserved for partial defects measuring less than 50% of the circumference of the pharynx. The gastric pull-up is used when an intrathoracic esophagectomy is necessary. The pectoralis flap is reserved for situations when external coverage is necessary in addition to hypopharyngeal reconstruction or when a free-tissue transfer is not appropriate. Reconstruction can offer most patients successful swallowing while minimizing complications.

Evaluation of a combined calcium sodium alginate and bio-occlusive membrane dressing in the management of split-thickness skin graft donor sites.

The optimal treatment of the split-thickness skin graft (STSG) donor site remains an unresolved issue. This study was conducted to evaluate the combined use of calcium sodium alginate and a bio-occlusive membrane dressing in the management of STSG donor sites. This study was a prospective evaluation of all patients requiring an STSG over a 6-month period ending October 1998. There were 57 patients with a mean age of 61 years. All skin grafts were harvested with an electric dermatome from the anterior thigh and were 0.012 to 0.016 inches thick. Donor sites were dressed with calcium sodium alginate followed by a bio-occlusive dressing. Postoperatively, the skin graft donor site dressing was removed and replaced. The mean skin graft area was 114 cm2. The first dressing change occurred, on average, 3 days postoperatively. All dressings were taken down and the wounds reevaluated 7 days postoperatively. Fifty-two patients (91%) had achieved complete reepithelialization by this time. Five patients (9%) required an additional dressing. All wounds were healed completely by postoperative day 10. Donor site discomfort was minimal and limited to the time of dressing change. There were no wound-related complications. The average cost of dressing supplies was $48.00 per patient and $23.00 per dressing. This method of managing STSG donor sites allowed for unimpeded reepithelialization without wound complication. The bio-occlusive dressing eliminated the pain typically associated with fine mesh gauze dressings. The absorptive property of the calcium sodium alginate eliminated the problem of seroma formation and leakage seen routinely with the use of a bio-occlusive dressing alone. These results confirm that this technique is both efficacious and cost-effective.

Correction of scapular winging by supraclavicular neurolysis of the long thoracic nerve.

Injury to the long thoracic nerve results in winging of the scapula. When there is no known direct site of injury to this nerve, the traditional treatment consists of bracing the shoulder and, if recovery of function does not occur, then carrying out a muscle transfer to reconstitute the forces required to bring the scapula into appropriate position with respect to the thorax. The present report describes four patients in whom a site of compression of the long thoracic nerve within the scalene muscles proved to be the site of compression. A supraclavicular neurolysis of the long thoracic nerve resulted in correction of the winged scapula in all four of these patients.

Pharmacology of SB-273779, a nonpeptide calcitonin gene-related peptide 1 receptor antagonist.

Calcitonin gene-related peptide (CGRP), a potent vasodilatory and cardiotonic peptide, has a potential role for CGRP in diverse physiologic and pathophysiologic situations such as congestive heart failure, diabetes, migraine, and neurogenic inflammation. Although a peptide CGRP receptor antagonist, CGRP(8-37,) is available, its utility presents significant limitations for these indications. Here, we describe the properties of SB-(+)-273779 [N-methyl-N-(2-methylphenyl)-3-nitro-4-(2-thiazolylsulfinyl)nitrobenzanilide], a selective nonpeptide antagonist of CGRP(1) receptor. SB-(+)-273779 inhibited (125)I-labeled CGRP binding to SK-N-MC (human neuroblastoma cells) and human cloned CGRP(1) receptor with K(i) values of 310 +/- 40 and 250 +/-15 nM, respectively. SB-(+)-273779 also inhibited CGRP (3 nM)-activated adenylyl cyclase in these systems with IC(50) values of 390 +/-10 nM (in SK-N-MC) and 210 +/-16 nM (recombinant human CGRP receptors). Prolonged treatment (>30 min) of SK-N-MC cells with SB-(+)-273779 followed by extensive washing resulted in reduction in maximum CGRP-mediated adenylyl cyclase activity, suggesting that this compound has irreversible binding characteristics. In addition, SB-(+)-273779 antagonized CGRP-mediated 1) stimulation of intracellular Ca(2+) in recombinant CGRP receptors in HEK-293 cells, 2) inhibition of insulin-stimulated [(14)C]deoxyglucose uptake in L6 cells, 3) vasodilation in rat pulmonary artery, and 4) decrease in blood pressure in anesthetized rats. SB-(+)-273779 tested at 3 microM had no significant affinity for calcitonin, endothelin, angiotensin II, and alpha-adrenergic receptors under standard ligand binding assays. SB-(+)-273779 also did not inhibit forskolin and pituitary adenylate cyclase-activating polypeptide. These results suggest that SB-(+)-273779 is a valuable tool for studying CGRP-mediated functional responses in complex biological systems.